Wang X

General

Full name : Wang Xiaohai

First name : Xiaohai

Mail : Merck & Co., Inc. West Point PA 19486

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Country : USA

Email : xiaohai_wang@merck.com

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References (482)

Title : COP-22 Alleviates D-Galactose-Induced Brain Aging by Attenuating Oxidative Stress, Inflammation, and Apoptosis in Mice - Ma_2024_Mol.Neurobiol__
Author(s) : Ma Y , Wang X , Li X , Chen X , Teng Z , Yang J , Liu G
Ref : Molecular Neurobiology , : , 2024
Abstract : Aging is a natural and inevitable process of organisms. With the intensification of population aging, research on aging has become a hot topic of global attention. The most obvious manifestation of human aging is the aging of brain function, which has been linked to the development of neurodegenerative diseases. In this study, COP-22, a mono-carbonyl curcumin derivative, was evaluated for its anti-aging ability, especially its ability to resist brain aging induced by D-galactose (D-gal) in mice. For brain protection, COP-22 could resist D-gal-induced oxidative stress by increasing the activity of antioxidative defense enzymes and enhancing antioxidant capacity in the brain tissue; COP-22 could improve the dysfunction of the cholinergic system by decreasing the increased activity of acetylcholinesterase and increasing the reduced content of acetylcholine induced by D-gal; and COP-22 could protect nerve cells of the brain. Further, western blot was used to determine related proteins of the brain. We found that COP-22 could effectively protect against brain injury (SIRT1, p53, p21, and p16) by inhibiting oxidative stress (Nrf2 and HO-1), inflammation (IL-6 and TNF-alpha), and apoptosis (Bax and caspase-3) in D-gal-induced aging mice. Additionally, COP-22 demonstrated the ability to reduce oxidative stress in serum and liver caused by D-gal, as well as relieve the damages in the liver and kidney induced by D-gal. These results indicated that COP-22 had potential anti-aging activity and could be used in the therapy of aging and aging-associated diseases like Alzheimer disease.
ESTHER : Ma_2024_Mol.Neurobiol__
PubMedSearch : Ma_2024_Mol.Neurobiol__
PubMedID: 38347285

Title : Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate Mofetil - Xie_2024_J.Microbiol.Biotechnol_34_249
Author(s) : Xie Q , Cao Z , You W , Cai X , Shen M , Yin Z , Jiang Y , Wang X , Ye S
Ref : J Microbiol Biotechnol , 34 :249 , 2024
Abstract : New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
ESTHER : Xie_2024_J.Microbiol.Biotechnol_34_249
PubMedSearch : Xie_2024_J.Microbiol.Biotechnol_34_249
PubMedID: 38419324

Title : A new plant-esterase inhibition based electrochemical sensor with signal amplification by MoS(2)@N-CDs for chlorpyrifos detection - Chen_2024_RSC.Adv_14_10703
Author(s) : Chen J , Ji C , Wang X , Tian Y , Tao H
Ref : RSC Adv , 14 :10703 , 2024
Abstract : Chlorpyrifos (CPF) is the most common pesticide entering the food chain and posing a threat to human health. This study presents a new electrochemical biosensor based on molybdenum disulfide nanosheets and nitrogen-doped carbon dot nanocomposite (MoS(2)@N-CDs) and kidney bean esterase (KdBE), and it is shown to achieve accurate detection of CPF. MoS(2)@N-CDs were prepared by a facile solvothermal method and characterized by electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical characterization confirmed that MoS(2)@N-CDs facilitated electron transfer and increased the electroactive surface area of the electrode, thereby improved the sensing performance of the electrode. The oxidation peak current of 1-naphthol, which was produced by the hydrolysis of 1-naphthyl acetate catalyzed by KdBE, was adopted as the signal of the sensor. CPF can suppress KdBE activity and consequently cause a decrease in the sensing signal. The experimental results show that the variation of sensing signal is a reliable index to evaluate the CPF level. Under the optimized conditions, the developed enzyme sensor showed superior CPF assay performance with a linear detection range as wide as 0.01-500 microg L(-1) and LOD as low as 3.5 x 10(-3) microg L(-1) (S/N = 3). The inter- and intra-batch RSDs for electrode testing were 4.02% and 2.69%, respectively. Moreover, the developed biosensor also showed good stability and anti-interference. The spiked recoveries of CPF in oilseed rape and cabbage ranged from 98.09% to 106.01% with low relative standard deviation (RSD) (<5.23%), suggesting that the sensor is a promising tool to enable simple, low-cost but highly sensitive large-scale screening of CPF residues in food.
ESTHER : Chen_2024_RSC.Adv_14_10703
PubMedSearch : Chen_2024_RSC.Adv_14_10703
PubMedID: 38567337

Title : Comparison Study of Two Fumonisin-Degrading Enzymes for Detoxification in Piglets - Wang_2024_Toxins.(Basel)_16_3
Author(s) : Wang Z , Lv Z , Czabany T , Nagl V , Krska R , Wang X , Han B , Tao H , Liu J , Wang J
Ref : Toxins (Basel) , 16 :3 , 2024
Abstract : Fumonisins (FBs), particularly fumonisin B1 (FB1) and fumonisin B2 (FB2) produced mainly by Fusarium verticillioide and Fusarium proliferatum, are common contaminants in animal feed and pose a serious threat to both animal and human health. The use of microbial enzymes to efficiently and specifically convert fumonisins into non-toxic or low-toxic metabolites has emerged as the most promising approach. However, most of the available enzymes have only been evaluated in vitro and lack systematic evaluation in vivo. In this study, the detoxification efficacy of two carboxylesterases, FumD (FUMzyme((a))) and FumDSB, was evaluated comparatively in piglets. The results show that feeding piglets 4.4 mg/kg FBs-contaminated diets for 32 days did not significantly affect the average daily gain, organ indices, and immunoglobulins of the piglets. However, a significant reduction (21.2%) in anti-inflammatory cytokine interleukin-4 was observed in the FBs group, and supplementation with FUMzyme((a)) and FumDSB significantly increased interleukin-4 by 62.1% and 28.0%, respectively. In addition, FBs-contaminated diets resulted in a 3-fold increase in the serum sphinganine/sphingosine (Sa/So) ratio, which is a specific biomarker that has been used to accurately reflect fumonisin levels. The serum Sa/So ratio was significantly reduced by 48.8% after the addition of FUMzyme((a)), and was insignificantly reduced by 8.2% in the FumDSB group. These results suggested that FUMzyme was more effective than FumDSB in mitigating FBs toxicity in piglets by down-regulating the Sa/So ratio.
ESTHER : Wang_2024_Toxins.(Basel)_16_3
PubMedSearch : Wang_2024_Toxins.(Basel)_16_3
PubMedID: 38276527
Gene_locus related to this paper: sphmc-FumD , 9sphn-a0a101vlk1

Title : Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function - Shi_2024_Clin.Pharmacokinet__
Author(s) : Shi D , Chen L , Li G , Wu N , Zhang F , Wang X , Mu N , Chen X , Yang X , Lu J , Lu Y , Wang M , Zhang D
Ref : Clinical Pharmacokinetics , : , 2024
Abstract : OBJECTIVE: HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function. METHODS: This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9). Safety was evaluated throughout the study, and the pharmacodynamic effects were assessed on the basis of a DPP-4 inhibition rate. RESULTS: HSK7653 exposure levels including the maximum plasma concentration (C(max)), area under the plasma concentration-time curve from zero to last time of quantifiable concentration (AUC(0-t)), and area under the plasma concentration-time curve from zero to infinity (AUC(0-inf)) showed no significant differences related to the severity of renal impairment. Renal clearance (CL(R)) showed a certain downtrend along with the severity of renal impairment. The CL(R) of the group with severe renal impairment and the group with end-stage renal disease were basically similar. The DPP-4 inhibition rate-time curve graph was similar among the renal function groups. All groups had favorable safety, and no serious adverse events occurred. CONCLUSIONS: HSK7653 is a potent oral DPP-4 inhibitor with a long plasma half-life, supporting a dosing regimen of once every 2 weeks. Impaired renal function does not appear to impact the pharmacokinetic and pharmacodynamic properties of HSK7653 after a single administration in Chinese subjects. HSK7653 is also well tolerated without an increase in adverse events with increasing renal impairment. These results indicate that dose adjustment of HSK7653 may not be required in patients with renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05497297.
ESTHER : Shi_2024_Clin.Pharmacokinet__
PubMedSearch : Shi_2024_Clin.Pharmacokinet__
PubMedID: 38184489

Title : Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers - Wang_2024_Clin.Pharmacol.Drug.Dev__
Author(s) : Wang X , Liu H , Cui C , Niu X , Li H , Niu S , Yan P , Wu N , Li F , Wu Q , Chen K , Hu B , Liu D
Ref : Clin Pharmacol Drug Dev , : , 2024
Abstract : Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (deltaQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (deltadeltaQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (C(max)) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.
ESTHER : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedSearch : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedID: 38757550

Title : Design, synthesis, and evaluation of dual-target inhibitors for the treatment of Alzheimer's disease - Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
Author(s) : Zhai J , Hao C , Wang X , Cao Y , Pan Y , Zhou M , Sun J , Li C
Ref : Arch Pharm (Weinheim) , :e2300693 , 2024
Abstract : Abeta(1-42) and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC(50) = 0.05 +/- 0.02 microM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Abeta(1-42) and protect nerve cells, and it can also penetrate the blood-brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl(3) -induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.
ESTHER : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedSearch : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedID: 38332316

Title : Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR - Xu_2024_Xenobiotica__1
Author(s) : Xu X , Taha R , Chu C , Xiao L , Wang T , Wang X , Huang X , Jiang Z , Sun L
Ref : Xenobiotica , :1 , 2024
Abstract : Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerative colitis, and indirubin is used for the treatment of chronic myelogenous leukaemia. However, IN and indirubin have adverse reactions, such as abdominal pain, diarrhoea, and intussusception, and their specific mechanism is unclear.The purpose of our research was to determine the specific mechanism underlying the adverse effects of IN and indirubin. By tracking the modifications in guinea pigs after the intragastric administration of indirubin for 28 days.The results demonstrate that indirubin could accelerate bowel movements and decrease intestinal acetylcholinesterase (AchE) expression. Experiments with NCM460 cells revealed that indirubin significantly reduced the expression of AchE, and the AchE levels were increased after the silencing of AhR and re-exposure to indirubin.This study showed that the inhibition of AchE expression by indirubin plays a key role in the occurrence of adverse reactions to indirubin and that the underlying mechanism is related to AhR-mediated AchE downregulation.
ESTHER : Xu_2024_Xenobiotica__1
PubMedSearch : Xu_2024_Xenobiotica__1
PubMedID: 38164702

Title : New Near-Infrared Fluorescence Imaging Platform with Large Stokes Shift for Carboxylesterase 2 Detection in Thyroid Cancer and Inflammatory Diseases Diagnosis - Wang_2024_Anal.Chem__
Author(s) : Wang X , Gao J , Fan C , Gao Y , Yang X , Chen L
Ref : Analytical Chemistry , : , 2024
Abstract : Development of new near-infrared fluorophores is one of the eternal themes in the field of biosensing and biological imaging. In this work, we constructed a novel fluorophore platform MOR by replacing methylindole of hemicyanine fluorophore (CyR) with benzoxazole to acquire better fluorescence characteristics. Based on the platform, a near infrared (NIR) fluorescent probe MOR-CES2 was synthesized for the specific "off-on" response to carboxylesterase 2 (CES2). The probe exhibited excellent properties including near-infrared emission (735 nm), large Stokes shift (105 nm), high sensitivity (LOD, 0.3 ng/mL), and rapid response (15 min). The successful application of MOR-CES2 in biological imaging of CES2 in mice with thyroid cancer and inflammatory bowel disease demonstrated that the probe could identify cancer cells and tissues and sensitively respond to inflammation. The results proved the potency of MOR-CES2 as an efficient imaging tool to assist in the surgical resection of CES2-related tumors.
ESTHER : Wang_2024_Anal.Chem__
PubMedSearch : Wang_2024_Anal.Chem__
PubMedID: 38372636

Title : Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea - Wang_2024_J.Agric.Food.Chem__
Author(s) : Wang Q , Wang X , Cai D , Yu J , Chen X , Niu W , Wang S , Liu X , Zhou D , Yin F , Wang T , Shi X , Wu Z , Zhang J , Hao J , Liu P
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.
ESTHER : Wang_2024_J.Agric.Food.Chem__
PubMedSearch : Wang_2024_J.Agric.Food.Chem__
PubMedID: 38226868 || 38634420

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior - Wang_2024_Neurosci.Bull__
Author(s) : Wang X , Lin D , Jiang J , Liu Y , Dong X , Fan J , Gong L , Shen W , Zeng L , Xu T , Jiang K , Connor SA , Xie Y
Ref : Neurosci Bull , : , 2024
Abstract : Synapse organizers are essential for the development, transmission, and plasticity of synapses. Acting as rare synapse suppressors, the MAM domain containing glycosylphosphatidylinositol anchor (MDGA) proteins contributes to synapse organization by inhibiting the formation of the synaptogenic neuroligin-neurexin complex. A previous analysis of MDGA2 mice lacking a single copy of Mdga2 revealed upregulated glutamatergic synapses and behaviors consistent with autism. However, MDGA2 is expressed in diverse cell types and is localized to both excitatory and inhibitory synapses. Differentiating the network versus cell-specific effects of MDGA2 loss-of-function requires a cell-type and brain region-selective strategy. To address this, we generated mice harboring a conditional knockout of Mdga2 restricted to CA1 pyramidal neurons. Here we report that MDGA2 suppresses the density and function of excitatory synapses selectively on pyramidal neurons in the mature hippocampus. Conditional deletion of Mdga2 in CA1 pyramidal neurons of adult mice upregulated miniature and spontaneous excitatory postsynaptic potentials, vesicular glutamate transporter 1 intensity, and neuronal excitability. These effects were limited to glutamatergic synapses as no changes were detected in miniature and spontaneous inhibitory postsynaptic potential properties or vesicular GABA transporter intensity. Functionally, evoked basal synaptic transmission and AMPAR receptor currents were enhanced at glutamatergic inputs. At a behavioral level, memory appeared to be compromised in Mdga2 cKO mice as both novel object recognition and contextual fear conditioning performance were impaired, consistent with deficits in long-term potentiation in the CA3-CA1 pathway. Social affiliation, a behavioral analog of social deficits in autism, was similarly compromised. These results demonstrate that MDGA2 confines the properties of excitatory synapses to CA1 neurons in mature hippocampal circuits, thereby optimizing this network for plasticity, cognition, and social behaviors.
ESTHER : Wang_2024_Neurosci.Bull__
PubMedSearch : Wang_2024_Neurosci.Bull__
PubMedID: 38321347

Title : Comparison of Flavonoid Content, Antioxidant Potential, Acetylcholinesterase Inhibition Activity and Volatile Components Based on HS-SPME-GC-MS of Different Parts from Matteuccia struthiopteris (L.) Todaro - Wang_2024_Molecules_29_
Author(s) : Wang QY , Gao Y , Yao JN , Zhou L , Chen HP , Liu JK , Wang X , Guo J , Zang S , Liu B , Wu Y
Ref : Molecules , 29 : , 2024
Abstract : Matteuccia struthiopteris is one of the most globally consumed edible ferns and widely used in folk medicine. Reports mainly focus on young fronds and the rhizome which are common edible medicinal parts. However, there are few detailed reports on other parts. Therefore, the volatile components of different parts based on HS-SPME-GC-MS were identified, and total flavonoid contents, antioxidant activities and acetylcholinesterase inhibitory activities were compared in order to reveal the difference of volatile components and potential medicinal value of different parts. The results showed that total flavonoid contents, antioxidant activities and volatile components of different parts were obviously different. The crozier exhibited the strongest antioxidant activities, but only underground parts exhibited a dose-dependent inhibition potential against AChE. Common volatile compounds were furfural and 2-furancarboxaldehyde, 5-methyl-. In addition, it was found that some volatile components from adventitious root, trophophyll, sporophyll and petiole were important ingredients in food, cosmetics, industrial manufacturing and pharmaceutical applications.
ESTHER : Wang_2024_Molecules_29_
PubMedSearch : Wang_2024_Molecules_29_
PubMedID: 38338359 || 38474653

Title : Comparative study on the enzymatic degradation of phenolic esters: The HPLC-UV quantification of tyrosol and gallic acid liberated from tyrosol acyl esters and alkyl gallates by hydrolytic enzymes - Wang_2024_Food.Chem_442_138529
Author(s) : Wang X , Wang Q , Cai D , Yu J , Chen X , Guo X , Tong P , Liu X , Yin F , Zhou D
Ref : Food Chem , 442 :138529 , 2024
Abstract : HPLC-UV analysis was used to evaluate the enzymatic degradation characteristics of tyrosol acyl esters (TYr-Es) and alkyl gallates (A-GAs). Among various hydrolytic enzymes, TYr-Es can be hydrolyzed by pancrelipase, while A-GAs cannot be hydrolyzed by pancrelipase. Interestingly, carboxylesterase-1b (CES-1b), carboxylesterase-1c (CES-1c) and carboxylesterase-2 (CES-2) are able to hydrolyze TYr-Es and A-GAs, and thus to liberate tyrosol (TYr) and gallic acid (GA). By contrast, the degrees of hydrolysis (DHs) of TYr-Es and A-GAs by CES-1b and CES-1c were significantly higher than those by CES-2. Meanwhile, the DHs of TYr-Es were much higher than those of A-GAs. Especially, the DHs firstly increased and then decreased with the increasing alkyl chain length. Besides, DHs positively correlated with the unsaturation degree at the same chain length. Through regulating carbon length, unsaturation degree and the ester bond structure, controlled-release of phenolic compounds and fatty acids (or fatty alcohols) from phenolic esters will be easily achieved.
ESTHER : Wang_2024_Food.Chem_442_138529
PubMedSearch : Wang_2024_Food.Chem_442_138529
PubMedID: 38271912

Title : A general model for predicting enzyme functions based on enzymatic reactions - Qian_2024_J.Cheminform_16_38
Author(s) : Qian W , Wang X , Kang Y , Pan P , Hou T , Hsieh CY
Ref : J Cheminform , 16 :38 , 2024
Abstract : Accurate prediction of the enzyme comission (EC) numbers for chemical reactions is essential for the understanding and manipulation of enzyme functions, biocatalytic processes and biosynthetic planning. A number of machine leanring (ML)-based models have been developed to classify enzymatic reactions, showing great advantages over costly and long-winded experimental verifications. However, the prediction accuracy for most available models trained on the records of chemical reactions without specifying the enzymatic catalysts is rather limited. In this study, we introduced BEC-Pred, a BERT-based multiclassification model, for predicting EC numbers associated with reactions. Leveraging transfer learning, our approach achieves precise forecasting across a wide variety of Enzyme Commission (EC) numbers solely through analysis of the SMILES sequences of substrates and products. BEC-Pred model outperformed other sequence and graph-based ML methods, attaining a higher accuracy of 91.6%, surpassing them by 5.5%, and exhibiting superior F1 scores with improvements of 6.6% and 6.0%, respectively. The enhanced performance highlights the potential of BEC-Pred to serve as a reliable foundational tool to accelerate the cutting-edge research in synthetic biology and drug metabolism. Moreover, we discussed a few examples on how BEC-Pred could accurately predict the enzymatic classification for the Novozym 435-induced hydrolysis and lipase efficient catalytic synthesis. We anticipate that BEC-Pred will have a positive impact on the progression of enzymatic research.
ESTHER : Qian_2024_J.Cheminform_16_38
PubMedSearch : Qian_2024_J.Cheminform_16_38
PubMedID: 38556873

Title : Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane - Xing_2024_Eur.J.Med.Chem_268_116289
Author(s) : Xing S , Tang X , Wang L , Wang J , Lv B , Wang X , Guo C , Zhao Y , Feng F , Liu W , Chen Y , Sun H
Ref : Eur Journal of Medicinal Chemistry , 268 :116289 , 2024
Abstract : Most recently, worldwide interest in butyrylcholinesterase (BChE) as a potential target for treating Alzheimer's disease (AD) has increased. In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 microM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC(0-inf) = 1729.95 ng/mL*h, upgraded by 2.6 times) and oral bioavailability (F(po) = 48.18%, upgraded by 2 times). S16-1029 also displayed weak or no inhibition against Cytochrome P450 (CYP450) and human ether a-go-go related gene (hERG) potassium channel. In vivo experiments on tissue distribution revealed that S16-1029 could cross the blood-brain barrier (BBB) and reach the central nervous system (CNS). In vivo cognitive improvement efficacy and good in vitro target inhibitory activity (eqBChE IC(50) = 11.35 +/- 4.84 nM, hBChE IC(50) = 48.1 +/- 11.4 nM) were also assured. The neuroprotective effects against several AD pathology characteristics allowed S16-1029 to successfully protect the CNS of progressed AD patients. According to the findings of this study, altering molecular planarity might be a viable strategy for improving the drug-like property of CNS-treating drugs.
ESTHER : Xing_2024_Eur.J.Med.Chem_268_116289
PubMedSearch : Xing_2024_Eur.J.Med.Chem_268_116289
PubMedID: 38452730

Title : Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules - Yang_2024_Elife_13_
Author(s) : Yang L , Zhang J , Liu S , Zhang Y , Wang L , Wang X , Wang S , Li K , Wei M , Zhang C
Ref : Elife , 13 : , 2024
Abstract : Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to providing a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In olfactory bulb, the SYT1-tdTomato signals are highly enriched in glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.
ESTHER : Yang_2024_Elife_13_
PubMedSearch : Yang_2024_Elife_13_
PubMedID: 38450720

Title : Preparation of functional oils rich in phytosterol esters and diacylglycerols by enzymatic transesterification - Shi_2024_Food.Chem_448_139100
Author(s) : Shi W , Li H , Fu Y , Tang X , Yu J , Wang X
Ref : Food Chem , 448 :139100 , 2024
Abstract : Phytosterol esters (PEs) and diacylglycerols (DAGs) have various health benefits in humans. In this study, PEs and DAGs were synthesized by lipase-catalyzed transesterification between a natural oil and phytosterols. First, commercial lipases were screened for transesterification and were further verified using multiple-ligand molecular docking. AYS "Amano" (a lipase from Candida rugosa) was found to be the optimum lipase. Subsequently, the enzymatic transesterification conditions were optimized. The optimized conditions were determined to be a 1:2 M ratio of phytosterols to oil, 100 mmol/L phytosterols, and 9 % AYS "Amano", and 50 degreesC for 24 h in 20 mL n-hexane. Under these conditions, over 70 % of phytosterols were converted to PEs. In this study, an efficient enzymatic process was developed to produce value-added functional oils rich in PEs and DAGs, with PEs content <= 31.6 %, DAGs content <= 11.2 %, acid value >= 0.91 mg KOH/g, and peroxide value >= 2.38 mmol/kg.
ESTHER : Shi_2024_Food.Chem_448_139100
PubMedSearch : Shi_2024_Food.Chem_448_139100
PubMedID: 38552457

Title : Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients - Zhang_2024_BMC.Cardiovasc.Disord_24_251
Author(s) : Zhang S , Wang J , Chen S , Zhang Y , He R , Wang X , Ding F , Hu W , Dai Y , Lu L , Zhang R , Ni J , Chen Q
Ref : BMC Cardiovasc Disord , 24 :251 , 2024
Abstract : BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.
ESTHER : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedSearch : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedID: 38745157

Title : Aerobic exercise-induced decrease of chemerin improved glucose and lipid metabolism and fatty liver of diabetes mice through key metabolism enzymes and proteins - Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
Author(s) : Lin X , Qu J , Yin L , Wang R , Wang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159409 , 2023
Abstract : Our previous studies have implicated an important role of adipokine chemerin in exercise-induced improvements of glycolipid metabolism and fatty liver in diabetes rat, but the underlying mechanisms remain unknown. This study first used an exogenous chemerin supplement to clarify the roles of decreased chemerin in exercised diabetes mice and possible mechanisms of glucose and lipid metabolism key enzymes and proteins [such as adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 4 (GLUT4)]. In addition, two kinds of adipose-specific chemerin knockout mice were generated to demonstrate the regulation of chemerin on glucose and lipid metabolism enzymes and proteins. We found that in diabetes mice, exercise-induced improvements of glucose and lipid metabolism and fatty liver, and exercise-induced increases of ATGL, LPL, and GLUT4 in liver, gastrocnemius and fat were reversed by exogenous chemerin. Furthermore, in chemerin knockdown mice, chemerin(-/-)adiponectin mice had lower body fat mass, improved blood glucose and lipid, and no fatty liver; while chemerin(-/-)fabp4 mice had hyperlipemia and unchanged body fat mass. Peroxisome proliferator-activated receptor gamma (PPARgamma), ATGL, LPL, GLUT4 and PEPCK in the liver and gastrocnemius had improve changes in chemerin(-/-).adiponectin mice while deteriorated alterations in chemerin(-/-).fabp4 mice, although PPARgamma, ATGL, LPL, and GLUT4 increased in the fat of two kinds of chemerin(-/-) mice. CONCLUSIONS: Decreased chemerin exerts an important role in exercise-induced improvements of glucose and lipid metabolism and fatty liver in diabetes mice, which was likely to be through PPARgamma mediating elevations of ATGL, LPL and GLUT4 in peripheral metabolic organs.
ESTHER : Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
PubMedSearch : Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
PubMedID: 37871796

Title : Visualization of production and remediation of acetaminophen-induced liver injury by a carboxylesterase-2 enzyme-activatable near-infrared fluorescent probe - Yang_2023_Talanta_269_125418
Author(s) : Yang B , Ding X , Zhang Z , Li J , Fan S , Lai J , Su R , Wang X , Wang B
Ref : Talanta , 269 :125418 , 2023
Abstract : Acetaminophen (APAP) overdose, also known as APAP poisoning, may directly result in hepatic injury, acute liver failure and even death. Nowadays, APAP-induced liver injury (AILI) has become an urgent public health issue in the developing world so the early accurate diagnosis and the revelation of underlying molecular mechanism of AILI are of great significance. As a major detoxifying organ, liver is responsible for metabolizing chemical substances, in which human carboxylesterase-2 (CES2) is present. Hence, we chose CES2 as an effective biomarker for evaluating AILI. By developing a CES2-activatable and water-soluble fluorescent probe PFQ-E with superior affinity (K(m) = 5.9 microM), great sensitivity (limit of detection = 1.05 ng/mL), near-infrared emission (655 nm) and large Stokes shift (135 nm), activity and distribution of CES2 in cells were determined or imaged effectively. More importantly, the APAP-induced hepatotoxicity and the underlying molecular mechanism of pathogenesis of AILI were investigated by measuring the "light-up" response of PFQ-E towards endogenous CES2 in vivo for the first time. Based on the superior performance of the probe PFQ-E for sensing CES2, we believe that it has broad potential in clinical diagnosis and therapy response evaluation of AILI.
ESTHER : Yang_2023_Talanta_269_125418
PubMedSearch : Yang_2023_Talanta_269_125418
PubMedID: 37988783

Title : Corner Engineering: Tailoring Enzymes for Enhanced Resistance and Thermostability in Deep Eutectic Solvents - Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
Author(s) : Wang X , Sheng Y , Cui H , Qiao J , Song Y , Li X , Huang H
Ref : Angew Chem Int Ed Engl , :e202315125 , 2023
Abstract : Deep eutectic solvents (DESs), heralded for their synthesis simplicity, economic viability, and reduced volatility and flammability, have found increasing application in biocatalysis. However, challenges persist due to a frequent diminution in enzyme activity and stability. Herein, we developed a general protein engineering strategy, termed corner engineering, to acquire DES-resistant and thermostable enzymes via precisely tailoring of the transition region in enzyme structure. Employing Bacillus subtilis lipase A (BSLA) as a model, we delineated the engineering process, yielding five multi-DESs resistant variants with highly improved thermostability, such as K889E/N89K exhibited up to a 10.0-fold catalytic efficiency (kcat/KM) increase in 30% (v/v) ChCl:acetamide and 4.1-fold in 95% (v/v) ChCl:ethylene glycol accompanying 6.7-fold thermal resistance improvement than wild type at ~50 degreesC. The generality of the optimized approach was validated by two extra industrial enzymes, endo-beta-1,4-glucanase PvCel5A (used for biofuel production) and esterase Bs2Est (plastics degradation). The molecular investigations revealed that increased water molecules at substrate binding sites and finetuned helix formation at the corner region are two dominant determinants governing elevated resistance and thermostability. This study, coupling corner engineering with obtained molecular insights, illuminates enzyme-DES interaction patterns and fosters the rational design of more DES-resistant and thermostable enzymes in biocatalysis and biotransformation.
ESTHER : Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
PubMedSearch : Wang_2023_Angew.Chem.Int.Ed.Engl__e202315125
PubMedID: 38010210
Gene_locus related to this paper: bacsu-lip , bacsu-pnbae

Title : APC and P53 mutations synergise to create a therapeutic vulnerability to NOTUM inhibition in advanced colorectal cancer - Tian_2023_Gut__
Author(s) : Tian Y , Wang X , Cramer Z , Rhoades J , Estep KN , Ma X , Adams-Tzivelekidis S , Katona BW , Johnson FB , Yu Z , Blanco MA , Lengner CJ , Li N
Ref : Gut , : , 2023
Abstract : OBJECTIVE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, with the majority of cases initiated by inactivation of the APC tumour suppressor. This results in the constitutive activation of canonical WNT pathway transcriptional effector -catenin, along with induction of WNT feedback inhibitors, including the extracellular palmitoleoyl-protein carboxylesterase NOTUM which antagonises WNT-FZD receptor-ligand interactions. Here, we sought to evaluate the effects of NOTUM activity on CRC as a function of driver mutation landscape. DESIGN: Mouse and human colon organoids engineered with combinations of CRC driver mutations were used for Notum genetic gain-of-function and loss-of-function studies. In vitro assays, in vivo endoscope-guided orthotopic organoid implantation assays and transcriptomic profiling were employed to characterise the effects of Notum activity. Small molecule inhibitors of Notum activity were used in preclinical therapeutic proof-of-principle studies targeting oncogenic Notum activity. RESULTS: NOTUM retains tumour suppressive activity in APC-null adenomas despite constitutive -catenin activity. Strikingly, on progression to adenocarcinoma with P53 loss, NOTUM becomes an obligate oncogene. These phenotypes are Wnt-independent, resulting from differential activity of NOTUM on glypican 1 and 4 in early-stage versus late-stage disease, respectively. Ultimately, preclinical mouse models and human organoid cultures demonstrate that pharmacological inhibition of NOTUM is highly effective in arresting primary adenocarcinoma growth and inhibiting metastatic colonisation of distal organs. CONCLUSIONS: Our findings that a single agent targeting the extracellular enzyme NOTUM is effective in treating highly aggressive, metastatic adenocarcinomas in preclinical mouse models and human organoids make NOTUM and its glypican targets therapeutic vulnerabilities in advanced CRC.
ESTHER : Tian_2023_Gut__
PubMedSearch : Tian_2023_Gut__
PubMedID: 37591698

Title : Soluble epoxide hydrolase deficiency promotes liver regeneration and ameliorates liver injury in mice by regulating angiocrine factors and angiogenesis - Deng_2023_Biochim.Biophys.Acta.Gen.Subj__130394
Author(s) : Deng W , Hu T , Xiong W , Jiang X , Cao Y , Li Z , Jiang H , Wang X
Ref : Biochimica & Biophysica Acta Gen Subj , :130394 , 2023
Abstract : BACKGROUND: Soluble epoxide hydrolase (sEH) is a key enzyme for the hydrolysis of epoxyeicosatrienoic acids (EETs) and has been implicated in the pathogenesis of hepatic inflammation, fibrosis, cancer, and nonalcoholic fatty liver disease. However, the role of sEH in liver regeneration and injury remains unclear. METHODS: This study used sEH-deficient (sEH(-/-)) mice and wild-type (WT) mice. Hepatocyte proliferation was assessed by immunohistochemical (IHC) staining for Ki67. Liver injury was evaluated by histological staining with hematoxylin and eosin (H&E), Masson's trichrome, and Sirius red, as well as IHC staining for alpha-SMA. Hepatic macrophage infiltration and angiogenesis were reflected by IHC staining for CD68 and CD31. Liver angiocrine levels were detected by ELISA. The mRNA levels of angiocrine or cell cycle-related genes were measured by quantitative real-time RT-PCR (qPCR). The protein levels of cell proliferation-related protein and phosphorylated signal transducer and activator of transcription 3 (STAT3) were detected by western blotting. RESULTS: sEH mRNA and protein levels were significantly upregulated in mice after 2/3 partial hepatectomy (PHx). Compared with WT mice, sEH(-/-) mice exhibited a higher liver/body weight ratio and more Ki67-positive cells on days 2 and 3 after PHx. The accelerated liver regeneration in sEH(-/-) mice was attributed to angiogenesis and endothelial-derived angiocrine (HGF) production. Subsequently, hepatic protein expression of cyclinD1 (CYCD1) and the downstream direct targets of the STAT3 pathway, such as c-fos, c-jun, and c-myc, were also suppressed post-PHx in sEH(-/-) compared to WT mice. Furthermore, sEH deficiency attenuated CCl(4)-induced acute liver injury and reduced fibrosis in both CCl(4) and bile duct ligation (BDL)-induced liver fibrosis rodent models. Compared with WT mice, sEH(-/-) mice had slightly decreased hepatic macrophage infiltration and angiogenesis. Meanwhile, sEH(-/-) BDL mice had more Ki67-positive cells in the liver than WT BDL mice. CONCLUSIONS: sEH deficiency alters the angiocrine profile of liver endothelial to accelerate hepatocyte proliferation and liver regeneration, and blunts acute liver injury and fibrosis by inhibiting inflammation and angiogenesis. sEH inhibition is a promising target for liver diseases to improve liver regeneration and damage.
ESTHER : Deng_2023_Biochim.Biophys.Acta.Gen.Subj__130394
PubMedSearch : Deng_2023_Biochim.Biophys.Acta.Gen.Subj__130394
PubMedID: 37315719

Title : Variation in the HSL Gene and Its Association with Carcass and Meat Quality Traits in Yak - Wang_2023_Animals.(Basel)_13_
Author(s) : Wang X , Qi Y , Zhu C , Zhou R , Ruo Z , Zhao Z , Liu X , Li S , Zhao F , Wang J , Hu J , Shi B
Ref : Animals (Basel) , 13 : , 2023
Abstract : Hormone-sensitive lipase (HSL) is involved in the breakdown of triacylglycerols in adipose tissue, which influences muscle tenderness and juiciness by affecting the intramuscular fat content (IMF). This study analyzed the association between different genotypes and haplotypes of the yak HSL gene and carcass and meat quality traits. We used hybridization pool sequencing to detect exon 2, exon 8, and intron 3 variants of the yak HSL gene and genotyped 525 Gannan yaks via KASP to analyze the effects of the HSL gene variants on the carcass and meat quality traits in yaks. According to the results, the HSL gene is highly expressed in yak adipose tissue. Three single nucleotide polymorphisms (SNPs) were identified, with 2 of them located in the coding region and one in the intron region. Variants in the 2 coding regions resulted in amino acid changes. The population had 3 genotypes of GG, AG, and AA, and individuals with the AA genotype had lower WBSF values (p < 0.05). The H3H3 haplotype combinations could improve meat tenderness by reducing the WBSF values and the cooking loss rate (CLR) (p < 0.05). H1H1 haplotype combinations were associated with the increased drip loss rate (DLR) (p < 0.05). The presence of the H1 haplotype was associated the increased CLR in yaks, while that of the H2 haplotype was associated with the decreased DLR in yaks (p < 0.05). These results demonstrated that the HSL gene may influence the meat quality traits in yaks by affecting the IMF content in muscle tissues. Consequently, the HSL gene can possibly be used as a biomarker for improving the meat quality traits in yaks in the future.
ESTHER : Wang_2023_Animals.(Basel)_13_
PubMedSearch : Wang_2023_Animals.(Basel)_13_
PubMedID: 38067071

Title : Enzymatic synthesis of branched chain fatty acid-enriched structured triacylglycerols via esterification with glycerol - Huang_2023_Food.Chem_429_136943
Author(s) : Huang Y , Li H , Wang Z , Fu Y , Chen Y , Wang X
Ref : Food Chem , 429 :136943 , 2023
Abstract : While branched-chain fatty acids (BCFA)-enriched triacylglycerols (TAG) has various health benefits, its preparation has not been reported. This study aimed to synthesize high-purity BCFA-enriched structured TAG. First, BCFA was enriched from lanolin through saponification, calcification, and urea complexation. Next, BCFA-enriched TAG was synthesized by enzymatic esterification of BCFA and glycerol. Then, lipases were screened by molecular docking and practical experiments, which suggested that Lipozyme 435 was the best lipase for esterification since it had the lowest binding energy. Structured TAG containing 92.23% BCFA was synthesized under conditions optimized by single-factor experiments. Furthermore, molecular distillation was adapted to remove excess fatty acids and small molecule impurities. Finally, high-purity BCFA-enriched structured lipid containing 70.26% TAG was obtained. Overall, this study successfully developed a method for synthesizing BCFA-enriched structured TAG, which holds great promise for applications in value-added foods.
ESTHER : Huang_2023_Food.Chem_429_136943
PubMedSearch : Huang_2023_Food.Chem_429_136943
PubMedID: 37517224

Title : Identification of metabolizing enzyme genes associated with xenobiotics and odorants in the predatory stink bug Arma custos based on transcriptome analysis - Li_2023_Heliyon_9_e18657
Author(s) : Li W , Zou J , Yang X , Yang M , Jiang P , Wang X , Huang C , He Y
Ref : Heliyon , 9 :e18657 , 2023
Abstract : The predatory stink bug, Arma custos, is a highly effective beneficial predator of crop pests. The lack of gene information related to xenobiotic detoxification and odorant degrading enzymes in the predator stink bugs to date has limited our ability for more in-depth studies of biological control. Hence, we conducted de novo assembly of the A. custos transcriptome from guts, antennae, and other tiussue samples of 5th instar larvae using Illumina sequencing technology. A total of 91, 50 and 23 genes of cytochrome P450 monooxygenases (CYPs), carboxyl/choline esterases (CCEs) and glutathione S-transferases (GSTs) genes were identified, respectively. Gene expansions of CYP3 and CYP4 clans and the hormone and pheromone processing CCE class were found in A. custos. Analysis of tissue-specific expression patterns showed that 37 CYPs, 14 CCEs and 8 GSTs were enriched in guts, and 6 CYPs, 5 CCEs and 2 GSTs were up-regulated in antennae, suggesting their potential roles on xenobiotics detoxification and ordorant degradation. Gene information data presented here could be useful for a deeper understanding of the ecology, physiology and behavior of this beneficial species and could be helpful to improve their bio-control efficiency.
ESTHER : Li_2023_Heliyon_9_e18657
PubMedSearch : Li_2023_Heliyon_9_e18657
PubMedID: 37576196

Title : The potential of hydroxytyrosol fatty acid esters to enhance oral bioavailabilities of hydroxytyrosol and fatty acids: Continuous and slow-release ability in small intestine and blood - Wang_2023_Food.Chem_422_136246
Author(s) : Wang X , Wang Q , Yu J , Guo X , Tong P , Yin F , Liu X , Zhou D
Ref : Food Chem , 422 :136246 , 2023
Abstract : HPLC-UV analysis in rat everted gut sac and in vitro simulated digestion models indicated that hydroxytyrosol fatty acid esters (HTy-Es) could be hydrolyzed by pancreatic lipase to slow-release of free fatty acids (FAs) and HTy. Meanwhile, the HTy-Es, the liberated FAs and the HTy could cross the membrane and were transported into blood circulation. HTy-Es were further hydrolyzed by carboxylesterase in in vitro rat plasma hydrolysis model, which also showed slow-release of FAs (C1-C4) and HTy. Especially, the rates of hydrolysis and transport initially increased and then decreased with the increasing alkyl chain length. Besides, the above rates of the HTy-Es with a straight chain were greater than those of its isomer with a branched chain. Therefore, the above-mentioned continuous and slow-release of FAs and HTy in small intestine and blood clearly demonstrated that HTy-Es would be an effective approach to enhance oral bioavailabilities of free fatty acids and hydroxytyrosol.
ESTHER : Wang_2023_Food.Chem_422_136246
PubMedSearch : Wang_2023_Food.Chem_422_136246
PubMedID: 37126954

Title : Influence of Five Drying Methods on Active Compound Contents and Bioactivities of Fresh Flowers from Syringa pubescens Turcz - Xu_2023_Molecules_28_
Author(s) : Xu W , Zhang J , Wu Y , Zhang Z , Wang X , Ma J
Ref : Molecules , 28 : , 2023
Abstract : The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against alpha-amylase, alpha-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC(50) values with 0.118 +/- 0.004 mg/mL for DPPH radical, 1.538 +/- 0.0972 for hydroxyl radical and 0.886 +/- 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H(2)O(2)-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1beta and TNF-alpha expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC(50) values of inhibitory activity on alpha-glucosidase and alpha-amylase from SHD sample were 2.516 +/- 0.024 and 0.734 +/- 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC(50) values of 3.443 +/- 0.060 and 1.732 +/- 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.
ESTHER : Xu_2023_Molecules_28_
PubMedSearch : Xu_2023_Molecules_28_
PubMedID: 38067533

Title : Ecotoxicological effects of soil lithium on earthworm Eisenia fetida: Lethality, bioaccumulation, biomarker responses, and histopathological changes - Xu_2023_Environ.Pollut__121748
Author(s) : Xu Z , Zhang Z , Wang X
Ref : Environ Pollut , :121748 , 2023
Abstract : Lithium is an emerging environmental contaminant in the current low-carbon economy, but little is known about its influences on soil invertebrates. In this work, earthworm Eisenia fetida was exposed to soils treated with different levels of lithium for 7 d, and multiple ecotoxicological parameters were evaluated. The results showed that mortality was dose-dependent and lithium's median lethal content (LC(50)) to earthworm was respectively 865.08, 361.01, 139.36, and 94.95 mg/kg after 1 d, 2 d, 4 d, and 7 d exposure. The bioaccumulation factor based on measured exogenous lithium content (BF(exog)) respectively reached 0.79, 1.01, 1.57, and 1.27 with the increasing lithium levels, suggesting that lithium accumulation was averagely 1.16-fold to the exogenous content, and 74.42%-81.19%, 14.54%-18.23%, and 2.26%-8.02% of the lithium in exposed earthworms were respectively retained in the cytosol, debris, and granule. Then, lithium stress stimulated the activity of superoxide dismutase, peroxidase, catalase, acetylcholinesterase, and glutathione S-transferase as well as the content of 8-hydroxy-2-deoxyguanosine and metallothionein, indicating the generation of oxidative damage, while the content of reactive oxygen species and malondialdehyde decreased. Finally, lithium introduced histopathological changes, including the degenerated seminal vesicle and muscle hyperplasia, as well as high or extreme nuclear DNA damage. This study confirmed the obvious bioaccumulation and toxic effects caused by soil lithium via ecotoxicological data, providing new theoretical insights into understanding the ecological risks of lithium to soil invertebrates.
ESTHER : Xu_2023_Environ.Pollut__121748
PubMedSearch : Xu_2023_Environ.Pollut__121748
PubMedID: 37127236

Title : Synthesis of EPA-enriched medium- and long-chain triacylglycerol by lipase-catalyzed transesterification: a novel strategy for clinical nutrition intervention - Wang_2023_J.Sci.Food.Agric__
Author(s) : Wang Y , Wei W , Liu R , Chang M , Jin Q , Wang X
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Eicosapentaenoic acid (EPA) has been recognized as a promising nutrient to improve the therapeutic efficacy of cancer patients. Nevertheless, there are certain limitations to the application of EPA due to its structural characteristics. To maximize the nutritive value of EPA, a type of medium- and long-chain triacylglycerol (MLCT) enriched with EPA was designed and synthesised via lipase-catalyzed transesterification of medium-chain triglyceride (MCT) and EPA-enriched fish oil (FO). RESULTS: The optimum synthesis conditions for EPA-enriched MLCT were Lipozyme RM as catalyst, substrate mass ratio (MCT/ EPA-enriched FO) 3:1, lipase loading 80 g kg(-1) , reaction temperature 60 degreesC, and reaction time 6 h. The content of MLCT was up to 80.79% after the transesterification reaction and the purification, and the content of MLCT containing EPA accounted for 70.21%. Furthermore, the distribution of EPA at the sn-2 position showed a significant increase in MLCT compared with original substrate, from 18.89% to 26.93%. Further, the in vitro digestion results demonstrated that MLCT had a significantly higher EPA bioaccessibility compared to the original substrate. CONCLUSION: The EPA-enriched MLCT has been developed, which may be a novel strategy for clinical nutrition intervention. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2023_J.Sci.Food.Agric__
PubMedSearch : Wang_2023_J.Sci.Food.Agric__
PubMedID: 36891643

Title : An ultrasensitive and selective near-infrared fluorescent probe for tracking carboxylesterases with large Stokes shift in living cells and mice - Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
Author(s) : Zhang W , Qi C , Wang X , Fu Z , Zhang J , Zhou Y , Wang Y
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 308 :123708 , 2023
Abstract : Carboxylesterases (CEs) play great role in CEs-related diseases and drug metabolism. Selectively monitoring its activity is important to explore its role in CEs-related diseases and drug combination. Herein, a new "turn-on" near-infrared (NIR) fluorescent probe (CHY-1) was reported with large Stokes shift (145 nm) for CEs detection. Dicyanoisophorone-based derivative was chosen as NIR fluorophore and 4-bromobutyrate was the identifying group. What's more, CHY-1 exhibited ultra-sensitivity (LOD - 9.2 x 10(-5) U/mL), high selectivity against Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE) and Chymotrypsin for CEs fluorescence detection under physiological pH and temperature. Furthermore, CHY-1 showed little effect on cell viability at high concentration and featured good optical imaging character for the slight change of CEs activity induced by 5-Fu (5-Fluorouridine, anti-tumor drug) and CEs inhibitor in living cells. Moreover, CHY-1 was also used to detect the activity and distribution of CEs in mice. Taken together, CHY-1 had widely applicable value in the diagnosis of CEs-related diseases and drug combination.
ESTHER : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedSearch : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedID: 38042124

Title : Targeted Absolute Protein Quantification Using SILAC Internal Standard and Full-Length Protein Calibrators (TAQSI) - Wang_2023_Methods.Mol.Biol_2603_269
Author(s) : Wang X , Shi J , Zhu HJ
Ref : Methods Mol Biol , 2603 :269 , 2023
Abstract : Mass spectrometry (MS)-based proteomics has been increasingly used for targeted absolute protein quantifications in both basic and clinical research. There is a great need to overcome some pitfalls of current MS-based targeted absolute protein quantification methods, such as high inter-assay variability and high cost associated with the use of synthesized isotopic peptides/proteins. Here we describe a targeted absolute protein quantification method utilizing SILAC internal standards and unlabeled full-length protein calibrators (TAQSI). The method has proven accurate, precise, reproducible, and cost-effective. Notably, the method is resistant to the variabilities caused by protein extraction and digestion. Moreover, it avoids measurement errors due to nonsynonymous mutations. This versatile method can be used for determining the absolute expressions of numerous proteins in various biological samples. As a proof-of-concept, this method was successfully applied to absolutely quantitate the protein expressions of carboxylesterase 1 (CES1) in human liver tissues.
ESTHER : Wang_2023_Methods.Mol.Biol_2603_269
PubMedSearch : Wang_2023_Methods.Mol.Biol_2603_269
PubMedID: 36370287

Title : Effects of natural products on functional constipation: analysis of active ingredient and mechanism - Zhou_2023_Naunyn.Schmiedebergs.Arch.Pharmacol__
Author(s) : Zhou P , Wang X , Sun M , Yan S
Ref : Naunyn Schmiedebergs Arch Pharmacol , : , 2023
Abstract : Constipation is a prevalent clinical ailment of the gastrointestinal system, yet its pathogenesis remains ambiguous. Despite the availability of numerous treatment modalities, they are insufficient in resolving the issue for patients. This work conducted a comprehensive review of the existing literature pertaining to the utilization of natural products for the treatment of constipation, with a focus on the efficacy of natural products in treating constipation, and to provide a comprehensive summary of their underlying mechanisms of action. Upon conducting a thorough review of the extant literature, we found that natural products can effectively treat constipation as modern synthetic drugs and compounded drugs with acetylcholinesterase (AChE) effects, rich in fiber and mucus, and the effects of increasing the tension of the ileum and gastrointestinal tract muscle, mediating signaling pathways, cytokine, excitability of the smooth muscle of the gastrointestinal tract, and regulating the homeostasis of intestinal flora. However, there is a wide variety of natural products, and there are still relatively few studies; the composition of natural products is complex, and the mechanism of action of natural products cannot be clarified. In the future, we need to further improve the detailed mechanism of natural products for the treatment of constipation.
ESTHER : Zhou_2023_Naunyn.Schmiedebergs.Arch.Pharmacol__
PubMedSearch : Zhou_2023_Naunyn.Schmiedebergs.Arch.Pharmacol__
PubMedID: 37870581

Title : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : Identifying Sex-Specific Serum Patterns of Alzheimer's Mice through Deep TMT Profiling and a Concentration-Dependent Concatenation Strategy - Dey_2023_J.Proteome.Res__
Author(s) : Dey KK , Yarbro JM , Liu D , Han X , Wang Z , Jiao Y , Wu Z , Yang S , Lee D , Dasgupta A , Yuan ZF , Wang X , Zhu L , Peng J
Ref : J Proteome Res , : , 2023
Abstract : Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting -5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.
ESTHER : Dey_2023_J.Proteome.Res__
PubMedSearch : Dey_2023_J.Proteome.Res__
PubMedID: 37910662

Title : Developing an adult stem cell derived microphysiological intestinal system for predicting oral prodrug bioconversion and permeability in humans - Sharma_2023_Lab.Chip__
Author(s) : Sharma A , Jin L , Wang X , Wang YT , Stresser DM
Ref : Lab Chip , : , 2023
Abstract : Microphysiological systems (MPS) incorporating human intestinal organoids have shown the potential to faithfully model intestinal biology with the promise to accelerate development of oral prodrugs. We hypothesized that an MPS model incorporating flow, shear stress, and vasculature could provide more reliable measures of prodrug bioconversion and permeability. Following construction of jejunal and duodenal organoid MPS derived from 3 donors, we determined the area under the concentration-time (AUC) curve for the active drug in the vascular channel and characterized the enzymology of prodrug bioconversion. Fosamprenavir underwent phosphatase mediated hydrolysis to amprenavir while dabigatran etexilate (DABE) exhibited proper CES2- and, as anticipated, not CES1-mediated de-esterification, followed by permeation of amprenavir to the vascular channel. When experiments were conducted in the presence of bio-converting enzyme inhibitors (orthovanadate for alkaline phosphatase; bis(p-nitrophenyl)phosphate for carboxylesterase), the AUC of the active drug decreased accordingly in the vascular channel. In addition to functional analysis, the MPS was characterized through imaging and proteomic analysis. Imaging revealed proper expression and localization of epithelial, endothelial, tight junction and catalytic enzyme markers. Global proteomic analysis was used to analyze the MPS model and 3 comparator sources: an organoid-based transwell model (which was also evaluated for function), Matrigel embedded organoids and finally jejunal and duodenal cadaver tissues collected from 3 donors. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) of global proteomic data demonstrated that all organoid-based models exhibited strong similarity and were distinct from tissues. Intestinal organoids in the MPS model exhibited strong similarity to human tissue for key epithelial markers via HCA. Quantitative proteomic analysis showed higher expression of key prodrug converting and drug metabolizing enzymes in MPS-derived organoids compared to tissues, organoids in Matrigel, and organoids on transwells. When comparing organoids from MPS and transwells, expression of intestinal alkaline phosphatase (ALPI), carboxylesterase (CES)2, cytochrome P450 3A4 (CYP3A4) and sucrase isomaltase (SI) was 2.97-, 1.2-, 11.3-, and 27.7-fold higher for duodenum and 7.7-, 4.6-, 18.1-, and 112.2-fold higher for jejunum organoids in MPS, respectively. The MPS approach can provide a more physiological system than enzymes, organoids, and organoids on transwells for pharmacokinetic analysis of prodrugs that account for 10% of all commercial medicines.
ESTHER : Sharma_2023_Lab.Chip__
PubMedSearch : Sharma_2023_Lab.Chip__
PubMedID: 38099395

Title : Combination of gold nanoclusters and silicon quantum dots for ratiometric fluorometry: One system, two mechanisms - Wang_2023_J.Pharm.Biomed.Anal_240_115940
Author(s) : Wang H , Lai J , Xu X , Yu W , Wang X
Ref : J Pharm Biomed Anal , 240 :115940 , 2023
Abstract : A ratiometric fluorometry based on silicon quantum dots (SiQDs) and gold nanoclusters (AuNCs) is constructed for detecting activity of butyrylcholinesterase (BChE) in human serum. By using thiobutyrylcholine iodide (BTCh) as the substrate of BChE-catalyzed hydrolysis reaction, variation of fluorescence emission from AuNCs is employed as an indicator of BChE activity since one of the hydrolysis products, thiocholine (TCh), would influence the aggregation state of AuNCs and consequently led to the change of fluorescence quantum efficiency of AuNCs. It is interesting that there are two mechanisms working for the fluorescence emission of aggregated AuNCs: aggregation-induced emission enhancement (AIEE) and aggregation-caused quenching (ACQ) with the presence of TCh at very low and higher concentration levels, respectively. Although both of these mechanisms can be utilized for sensing BChE, their opposite influence on the fluorescence emission of aggregated AuNCs should be worthy of attention, especially in the process of developing fluorescence methods for detecting trace targets by using AuNCs. In order to eliminate the fluctuation of fluorophotometer, SiQDs is chosen as the fluorophore to develop by ratiometric fluorescence methods in this work. Additionally, obvious aggregation of AuNCs induces significant decrease of inner filter effect (IFE) on the fluorescence emitted from SiQDs, while mild aggregation of AuNCs demonstrates little IFE. The linear ranges for detecting activity of BChE are 0.004 - 0.05 U/L and 0.5 - 20 U/L by ratiometric fluorometry based on the AIEE and ACQ, respectively. The very different responses originated from AIEE and ACQ of AuNCs would respectively make their own contributions to the determination of BChE activities at very low or high levels, which facilitate the developments of enhanced or quenched fluorescence methods. However, the detection of BChE activities at medium levels might suffer from the combination of AIEE and ACQ with ambiguous fractions. Therefore, it must be careful during the processes of developing and applying fluorescence methods based on the AIEE and ACQ of AuNCs, as well as the process of evaluating their analytical performance.
ESTHER : Wang_2023_J.Pharm.Biomed.Anal_240_115940
PubMedSearch : Wang_2023_J.Pharm.Biomed.Anal_240_115940
PubMedID: 38198882

Title : Development of a fluorescent sensor based on TPE-Fc and GSH-AuNCs for the detection of organophosphorus pesticide residues in vegetables - Wang_2023_Food.Chem_431_137067
Author(s) : Wang X , Yu H , Li Q , Tian Y , Gao X , Zhang W , Sun Z , Mou Y , Sun X , Guo Y , Li F
Ref : Food Chem , 431 :137067 , 2023
Abstract : A novel dual-signal fluorescent sensor was developed for detecting organophosphorus pesticides (OPs). It relies on the catalytic activities of acetylcholinesterase (AChE) and choline oxidase (ChOx) to generate hydrogen peroxide (H(2)O(2)) through the conversion of acetylcholine (ACh) to choline.H(2)O(2) then oxidizes ferrocene-modified tetraphenylethylene (TPE-Fc) to its oxidized state (TPE-Fc(+)), resulting in enhanced cyan fluorescence due to aggregation. Simultaneously, ferrocene oxidation generates hydroxyl radicals (OH), causing a decrease in orange fluorescence of glutathione-synthesized gold nanoclusters (GSH-AuNCs). The presence of OPs restricts AChE activity, reducing H(2)O(2) production. Increasing OPs concentration leads to decreased cyan fluorescence and increased orange fluorescence, enabling visual OPs detection. The sensor has a linear dynamic range of 10-2000 ng/mL with a detection limit of 2.05 ng/mL. Smartphone-based color identification and a WeChat mini program were utilized for rapid OPs analysis with successful outcomes.
ESTHER : Wang_2023_Food.Chem_431_137067
PubMedSearch : Wang_2023_Food.Chem_431_137067
PubMedID: 37579609

Title : Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy - Wang_2023_J.Pharm.Anal_13_776
Author(s) : Wang X , Zhang J , Zheng K , Du Q , Wang G , Huang J , Zhou Y , Li Y , Jin H , He J
Ref : J Pharm Anal , 13 :776 , 2023
Abstract : Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
ESTHER : Wang_2023_J.Pharm.Anal_13_776
PubMedSearch : Wang_2023_J.Pharm.Anal_13_776
PubMedID: 37577390

Title : Clinical characteristics and high risk factors of patients with Omicron variant strain infection in Hebei, China - Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
Author(s) : Wang L , Liu T , Yue H , Zhang J , Sheng Q , Wu L , Wang X , Zhang M , Wang J , Yu W
Ref : Front Cell Infect Microbiol , 13 :1294904 , 2023
Abstract : OBJECTIVE: The Omicron variant has a weaker pathogenicity compared to the Delta variant but is highly transmissible and elderly critically ill patients account for the majority. This study has significant implications for guiding clinical personalized treatment and effectively utilizing healthcare resources. METHODS: The study focuses on 157 patients infected with the novel coronavirus Omicron variant, from December, 2022, to February, 2023. The objective is to analyze the baseline data, test results, imaging findings and identify risk factors associated with severe illness. RESULTS: Among the 157 included patients, there were 55 cases in the non-severe group (all were moderate cases) and 102 cases in the severe group (including severe and critical cases). Infection with the Omicron variant exhibits significant differences between non-severe and severe cases (baseline data, blood routine, coagulation, inflammatory markers, cardiac, liver, kidney functions, Chest CT, VTE score, etc.). A multifactorial logistic regression analysis showed that neutrophil percentage >75%, eosinophil percentage <0.4%, D-dimer >0.55 mg/L, PCT >0.25 ng/mL, LDH >250 U/L, albumin <40 g/L, A/G ratio <1.2, cholinesterase<5100 U/L, uric acid >357 mole/L and blood calcium<2.11 mmol/L were the most likely independent risk factors for severe novel coronavirus infection. CONCLUSION: Advanced age, low oxygenation index, elevated neutrophil percentage, decreased eosinophil percentage, elevated PCT, elevated LDH, decreased albumin, decreased A/G ratio, elevated uric acid, decreased blood calcium, and elevated D-dimer are independent prognostic risk factors for non-severe patients progressing to severe illness. These factors should be closely monitored and actively treated to prevent or minimize the occurrence of severe illness.
ESTHER : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedSearch : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedID: 38145047

Title : Transcriptome reveals the toxicity difference of dimethyl disulfide by contact and fumigation on Meloidogyne incognita through calcium channel-mediated oxidative phosphorylation - Wang_2023_J.Hazard.Mater_460_132268
Author(s) : Wang Q , Wang X , Zhang D , Fang W , Li Y , Cao A , Yan D
Ref : J Hazard Mater , 460 :132268 , 2023
Abstract : The prevention and control of root-knot nematode disease has been posing a severe challenge worldwide. Fumigant dimethyl disulfide (DMDS) has excellent biological activity against nematodes. However, DMDS displays significant differences in contact and fumigation toxicity on nematodes. The specific regulatory mechanisms of DMDS on nematodes were investigated by characterizing the ultrastructure of nematodes, examining the physiological and biochemical indicators, and conducting transcriptome high-throughput sequencing. As indicated by the results, DMDS fumigation exhibited the biological activity of against M. incognita 121 times higher than DMDS contact. DMDS contact destroyed nematode body wall cells. Besides, DMDS fumigation destroyed the structure of pseudocoelom. DMDS treatment expedited the oxygen consumption of nematode while inhibiting acetylcholinesterase activity. As indicated by the analysis of vital signaling pathways based on transcriptome, DMDS based on the contact mode penetrated directly into the nematode through the body wall and subsequently affected calcium channels in the body wall and muscle, disrupting their structure; it serves as an uncoupling agent to interfere with ATP synthase. Moreover, DMDS based on the fumigation mode entered the body through the respiratory pathway of olfactory perception-oxygen exchange and subsequently affected calcium channels in the nerve; eventually, DMDS acted on complex IV or complex I.
ESTHER : Wang_2023_J.Hazard.Mater_460_132268
PubMedSearch : Wang_2023_J.Hazard.Mater_460_132268
PubMedID: 37619272

Title : Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation - Wang_2023_Small__e2305101
Author(s) : Wang X , Li Y , Hasrat K , Yang L , Qi Z
Ref : Small , :e2305101 , 2023
Abstract : Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8(+) T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8(+) T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-gamma, and immune memory effect also strengthen the defense against metastasis. The generation of O(2) catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.
ESTHER : Wang_2023_Small__e2305101
PubMedSearch : Wang_2023_Small__e2305101
PubMedID: 37635105

Title : Petrosamine Revisited. Experimental and Computational Investigation of Solvatochromism, Tautomerism and Free Energy Landscapes of a Pyridoacridinium Quaternary Salt - Gartshore_2023_Mar.Drugs_21_
Author(s) : Gartshore CJ , Wang X , Su Y , Molinski TF
Ref : Mar Drugs , 21 : , 2023
Abstract : Petrosamine (1)-a colored pyridoacridine alkaloid from the Belizean sponge, Petrosia sp., that is also a potent inhibitor of acetylcholine esterase (AChE)-was investigated by spectroscopic and computational methods. Analysis of the petrosamine-free energy landscapes, pK(a) and tautomerism, revealed an accurate electronic depiction of the molecular structure of 1 as the di-keto form, with a net charge of q = +1, rather than a dication (q = +2) under ambient conditions of isolation-purification. The pronounced solvatochromism (UV-vis) reported for 1, and related analogs were investigated in detail and is best explained by charge delocalization and stabilization of the ground state (HOMO) of 1 rather than an equilibrium of competing tautomers. Refinement of the molecular structure 1 by QM methods complements published computational docking studies to define the contact points in the enzyme active site that may improve the design of new AChE inhibitors based on the pyridoacridine alkaloid molecular skeleton.
ESTHER : Gartshore_2023_Mar.Drugs_21_
PubMedSearch : Gartshore_2023_Mar.Drugs_21_
PubMedID: 37623727

Title : Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats - Zeng_2023_Scand.J.Rheumatol__1
Author(s) : Zeng M , Issotina Zibrila A , Li X , Liu X , Wang X , Zeng Z , Wang Z , He Y , Meng L , Liu J
Ref : Scand J Rheumatol , :1 , 2023
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
ESTHER : Zeng_2023_Scand.J.Rheumatol__1
PubMedSearch : Zeng_2023_Scand.J.Rheumatol__1
PubMedID: 37339380

Title : Enzymatic enrichment of acylglycerols rich in n - 3 polyunsaturated fatty acids by selective methanolysis: Optimization and kinetic studies - Jiang_2023_J.Food.Sci__
Author(s) : Jiang C , Wang Z , Huang Y , Wang X , Chang M
Ref : J Food Sci , : , 2023
Abstract : n - 3 Polyunsaturated fatty acids (n - 3 PUFA) have special physiological effect, but their contents in natural oils may not meet the growing demand. Lipase-catalyzed selective methanolysis could be used to produce acylglycerols rich in n - 3 PUFA. To explore the kinetics of enzymatic methanolysis, factors affecting the reaction, including reaction system, water content, substrate molar ratio, temperature, lipase loading, and reaction time, were first investigated in the view of optimizing the reaction. Then the effects of triacylglycerol concentrations and methanol concentrations on initial reaction rate were studied. Finally, the key kinetic parameters of methanolysis were determined subsequently. The results showed that under optimal conditions, the n - 3 PUFA content in acylglycerols increased from 39.88% to 71.41%, and the n - 3 PUFA yield was 73.67%. The reaction followed a Ping-Pong Bi Bi mechanism with inhibition by methanol. The kinetic analysis indicated the lipase could selectively remove saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in acylglycerols. The inhibition constant of methanol to the n - 3 PUFA (K(iM) , 0.30 mmol/L) was lower than that to the SFA and MUFA (219.64 and 79.71 mmol/L). The combined effects of the fatty acid selectivity of Candida antarctica lipase A and methanol inhibition resulted in an enrichment of n - 3 PUFA in acylglycerols. Overall, the methanolysis reaction catalyzed by the lipase A is a prospective enrichment method. PRACTICAL APPLICATION: This study demonstrated that enzymatic selective methanolysis is a prospective enrichment method to produce acylglycerols rich in n - 3 PUFA. This method is highly efficient, environment-friendly, and simple. n - 3 PUFA concentrates have been widely applied in the food, health-care food, and pharmaceutical industries.
ESTHER : Jiang_2023_J.Food.Sci__
PubMedSearch : Jiang_2023_J.Food.Sci__
PubMedID: 37219384

Title : Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization - Zhang_2023_J.Neuroinflammation_20_6
Author(s) : Zhang H , Chen Y , Li F , Wu C , Cai W , Ye H , Su H , He M , Yang L , Wang X , Zhou K , Ni W
Ref : J Neuroinflammation , 20 :6 , 2023
Abstract : Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the blood-brain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the blood-brain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.
ESTHER : Zhang_2023_J.Neuroinflammation_20_6
PubMedSearch : Zhang_2023_J.Neuroinflammation_20_6
PubMedID: 36609266

Title : Effects of Chronic Roundup Exposure on Medaka Larvae - Killian_2023_J.Xenobiot_13_500
Author(s) : Killian D , Faheem M , Reh B , Wang X , Bhandari RK
Ref : J Xenobiot , 13 :500 , 2023
Abstract : The use of glyphosate-based herbicides is increasing yearly to keep up with the growing demands of the agriculture world. Although glyphosate-based herbicides target the enzymatic pathway in plants, the effects on the endocrine systems of vertebrate organisms, mainly fish, are widely unknown. Many studies with glyphosate used high-exposure concentrations (mg/L), and the effect of environmentally relevant or lower concentrations has not been clearly understood. Therefore, the present study examined the effects of very low, environmentally relevant, and high concentrations of glyphosate exposure on embryo development and the thyroid system of Japanese medaka (Oryzias latipes). The Hd-rR medaka embryos were exposed to Roundup containing 0.05, 0.5, 5, 10, and 20 mg/L glyphosate (glyphosate acid equivalent) from the 8 h post-fertilization stage through the 14-day post-fertilization stage. Phenotypes observed include delayed hatching, increased developmental deformities, abnormal growth, and embryo mortality. The lowest concentration of glyphosate (0.05 mg/L) and the highest concentration (20 mg/L) induced similar phenotypes in embryos and fry. A significant decrease in mRNA levels for acetylcholinesterase (ache) and thyroid hormone receptor alpha (thralpha) was found in the fry exposed to 0.05 mg/L and 20 mg/L glyphosate. The present results demonstrated that exposure to glyphosate formulation, at a concentration of 0.05 mg/L, can affect the early development of medaka larvae and the thyroid pathway, suggesting a link between thyroid functional changes and developmental alteration; they also showed that glyphosate can be toxic to fish at this concentration.
ESTHER : Killian_2023_J.Xenobiot_13_500
PubMedSearch : Killian_2023_J.Xenobiot_13_500
PubMedID: 37754844

Title : A caprylate esterase-activated fluorescent probe for sensitive and selective detection of Salmonella enteritidis - Zhang_2023_Anal.Bioanal.Chem_415_2163
Author(s) : Zhang H , Wang X , Xu Z , Ma J , Li ZL , Cheng WM , Jiang H
Ref : Anal Bioanal Chem , 415 :2163 , 2023
Abstract : Salmonella enteritidis is one of the most common foodborne pathogens. Many methods have been developed to detect Salmonella, but most of them are expensive, time-consuming, and complex in experimental procedures. Developing a rapid, specific, cost-effective, and sensitive detection method is still demanded. In this work, a practical detection method is presented using salicylaldazine caprylate as the fluorescent probe, which could be hydrolyzed by caprylate esterase liberated from Salmonella lysed by phage, to form strong fluorescent salicylaldazine. The Salmonella could be detected accurately with a low limit of detection of 6 CFU/mL and a broad concentration range of 10-10(6) CFU/mL. Moreover, this method was successfully used for the rapid detection of Salmonella in milk within 2 h through pre-enrichment by ampicillin-conjugated magnetic beads. The novel combination of fluorescent turn-on probe salicylaldazine caprylate and phage ensures this method has excellent sensitivity and selectivity.
ESTHER : Zhang_2023_Anal.Bioanal.Chem_415_2163
PubMedSearch : Zhang_2023_Anal.Bioanal.Chem_415_2163
PubMedID: 36869898

Title : Attack Site Density of a Highly-efficient PET Hydrolases - Li_2023_Protein.Pept.Lett__
Author(s) : Li Q , Liu W , Jing N , Yang K , Yao J , Wang X
Ref : Protein Pept Lett , : , 2023
Abstract : INTRODUCTION: Poly (ethylene terephthalate) (PET) is one of the most abundant polyester materials used in daily life and it is also one of the main culprits of environmental pollution. ICCG (F243I/D238C/S283C/Y127G) is enzyme with four modifications of leaf-branch compost cutinase (LCC) that display outstanding performance in hydrolyzing PET and hold a great potential in further applications. METHOD: Here, we used ICCG to degrade PET particles of various sizes and use the density of attack sites (attack) and kinetic parameters to evaluate the effect of particle size on enzyme degradation efficiency. We are surprised to observe that there is a certain relationship between Km and attack. In order to further confirm the relationship, we obtained three different enzymes (Y95K, M166S and H218S) by site-directed mutagenesis on the basis of ICCG. RESULT: The results confirmed that there was a negative correlation between Km and attack. In addition, we also found that increasing the affinity between the enzyme and the substrate does not necessarily lead to the increase of degradation rate. CONCLUSION: These findings show that the granulation of PET and the selection of appropriate particle size are helpful to improve its industrial application value. At the same time, additional protein engineering to increase ICCG performance is realistic, but it can't be limited to enhance the affinity between enzyme and substrate.
ESTHER : Li_2023_Protein.Pept.Lett__
PubMedSearch : Li_2023_Protein.Pept.Lett__
PubMedID: 37165591
Gene_locus related to this paper: 9bact-g9by57

Title : The screening for marine fungal strains with high potential in alkaloids production by in situ colony assay and LC-MS\/MS based secondary metabolic profiling - Lu_2023_Front.Microbiol_14_1144328
Author(s) : Lu T , Liu Y , Zhou L , Liao Q , Nie Y , Wang X , Lei X , Hong P , Feng Y , Hu X , Zhang Y
Ref : Front Microbiol , 14 :1144328 , 2023
Abstract : BACKGROUND: Alkaloids are the second primary class of secondary metabolites (SMs) from marine organisms, most of which have antioxidant, antitumor, antibacterial, anti-inflammatory, and other activities. However, the SMs obtained by traditional isolation strategies have drawbacks such as highly reduplication and weak bioactivity. Therefore, it is significantly important to establish an efficient strategy for screening strains and mining novel compounds. METHODS: In this study, we utilized in situ colony assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the strain with high potential in alkaloids production. The strain was identified by genetic marker genes and morphological analysis. The secondary metabolites from the strain were isolated by the combine use of vacuum liquid chromatography (VLC), ODS column chromatography, and Sephadex LH-20. Their structures were elucidated by 1D/2D NMR, HR-ESI-MS, and other spectroscopic technologies. Finally, these compounds bioactivity were assay, including anti-inflammatory and anti-beta aggregation. RESULTS: Eighteen marine fungi were preliminarily screened for alkaloids production by in situ colony assay using Dragendorff reagent as dye, and nine of them turned orange, which indicated abundant alkaloids. By thin-layer chromatography (TLC), LC-MS/MS, and multiple approaches assisted Feature-Based Molecular Networking (FBMN) analysis of fermentation extracts, a strain ACD-5 (Penicillium mallochii with GenBank accession number OM368350) from sea cucumber gut was selected for its diverse alkaloids profiles especially azaphilones. In bioassays, the crude extracts of ACD-5 in Czapek-dox broth and brown rice medium showed moderate antioxidant, acetylcholinesterase inhibitory, anti-neuroinflammatory, and anti-beta aggregation activities. Three chlorinated azaphilone alkaloids, compounds 1-3 (sclerotioramine, isochromophilone VI, and isochromophilone IX, respectively), were isolated from the fermentation products of ACD-5 in brown rice medium guided by bioactivities and mass spectrometry analysis. Compound 1 had shown remarkable anti-neuroinflammatory activity in liposaccharide induced BV-2 cells. CONCLUSION: In summary, in situ colony screening together with LC-MS/MS, multi-approach assisted FBMN can act as an efficient screening method for strains with potential in alkaloids production.
ESTHER : Lu_2023_Front.Microbiol_14_1144328
PubMedSearch : Lu_2023_Front.Microbiol_14_1144328
PubMedID: 37206330

Title : ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models - Chen_2023_J.Inflamm.Res_16_6361
Author(s) : Chen Y , Du H , Wang X , Li B , Chen X , Yang X , Zhao C , Zhao J
Ref : J Inflamm Res , 16 :6361 , 2023
Abstract : INTRODUCTION: The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM. METHODS: The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene. RESULTS: Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments. DISCUSSION: This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.
ESTHER : Chen_2023_J.Inflamm.Res_16_6361
PubMedSearch : Chen_2023_J.Inflamm.Res_16_6361
PubMedID: 38161353

Title : Responses and detoxification mechanisms of earthworm Amynthas hupeiensis to metal contaminated soils of North China - Liu_2023_Environ.Pollut__121584
Author(s) : Liu Y , Chen M , Mu X , Wang X , Zhang M , Yin Y , Wang K
Ref : Environ Pollut , :121584 , 2023
Abstract : Metal contamination is widespread, but only a few studies have evaluated the toxicological risks of metals (Cd, Cu, and Pb) in earthworms from farmlands in North China (Hebei province). Amynthas hupeiensis, the dominant species in the study area, was used to determine the responses and detoxification mechanisms of uncontaminated (CK), and low (LM)-, and high (HM)-metal-contaminated soils following 7-, 14-, and 28-days exposure. Metal toxicity in LM and HM soils inhibited the biomass of A. hupeiensis. The concentrations of Cd in A. hupeiensis bodies indicated accumulated Cd appeared to remain steady with prolonged exposure, while Cu/Pb increased significantly with soil levels. Bioaccumulation occurred in the order Cd > Pb > Cu in LM soil, and in the order Cd > Cu = Pb in HM soil, which was attributed to differences in available fractions between LM and HM soils. Physiological levels of biomarkers in A. hupeiensis were determined, including total protein (TP), glutathione (GSH), glutathione peroxidase (GPx), acetylcholinesterase (AChE), and malondialdehyde (MDA). Deviations in GSH, GPx, and AChE were considered to denote sensitive biomarkers using the IBRv2 index. Metabolomics data ((1)H nuclear magnetic resonance-based) revealed changes in metabolites following 28-days exposure to LM and HM soils. Differences in metabolism in A. hupeiensis following exposure to LM and HM were related to energy metabolism, amino acid biosynthesis, glycerophospholipid metabolism, inositol phosphate metabolism, and glutathione metabolism. Metal stress from LM and HM soils disturbed osmoregulation, resulting in oxidative stress, destruction of cell membranes and inflammation, and altered levels of amino acids required for energy by A. hupeiensis. These findings provide biochemical insights into the physiological and metabolic mechanisms underlying the ability of A. hupeiensis to resist metal stress, and for assessing the environmental risks of metal-contaminated soils in farmland in North China.
ESTHER : Liu_2023_Environ.Pollut__121584
PubMedSearch : Liu_2023_Environ.Pollut__121584
PubMedID: 37037277

Title : Hydrolysis and transport characteristics of tyrosol-SCFA esters in rat intestine and blood: Two-step release of tyrosol and SCFAs to enhance the beneficial effects - Wang_2023_Food.Chem_414_135710
Author(s) : Wang X , Wang Q , Hu Y , Yin F , Liu X , Zhou D
Ref : Food Chem , 414 :135710 , 2023
Abstract : The models of rat everted gut sac and hydrolysis by rat plasma were used to clarify the hydrolysis and transport characteristics of tyrosol-SCFA esters (TYr-SEs). HPLC-UV results indicated that TYr-SEs could be hydrolyzed by intestinal lipase, which showed sustained release of SCFAs and TYr. Meanwhile, TYr-SEs and the liberated SCFAs and TYr could cross the membrane and were transported into blood circulation. TYr-SEs were further hydrolyzed by carboxylesterase in plasma. Obviously, the hydrolysis of TYr-SEs in blood also showed sustained release of SCFAs and TYr. Especially, the rates of hydrolysis and transport correlated positively with the acyl chain lengths. Besides, the above rates of the TYr-SE with a straight chain were greater than those of its isomer with a branched chain. Therefore, the above-mentioned two-step release of SCFAs and TYr clearly demonstrated that TYr-SEs would be an effective approach to enhance the beneficial health effects of SCFAs and TYr.
ESTHER : Wang_2023_Food.Chem_414_135710
PubMedSearch : Wang_2023_Food.Chem_414_135710
PubMedID: 36821923

Title : Combination of two-photon fluorescent probes for carboxylesterase and ONOO(-) to visualize the transformation of nonalcoholic fatty liver to nonalcoholic steatohepatitis in liver orthotopic imaging - Jiao_2023_Talanta_270_125521
Author(s) : Jiao X , Wang Y , Zhang J , Wang X
Ref : Talanta , 270 :125521 , 2023
Abstract : As the most common cause of liver diseases, nonalcoholic fatty liver disease (NAFLD) can be classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). While NAFL is generally benign, the transition from NAFL to NASH is a cardinal feature of the non-benign liver disease that leads to cirrhosis and cancer, which indicates that tracking the transformation of NAFL to NASH timely is significant for precision management of liver diseases. Therefore, two fluorescent probes (CNFCl and DRNO) have been developed to visualize this pathological event. alpha-Fluorochloroacetamide and alpha-ketoamide was employed as the recognition site for carboxylesterase (CE) in CNFCl and peroxynitrite (ONOO(-)) in DRNO, respectively. CNFCl (lambda(em) = 445 nm) and DRNO (lambda(em) = 560 nm) showed high specificity and sensitivity towards CE and ONOO(-) respectively. By incubating with CE/ONOO(-) for 0.5 h respectively, both the emission intensity of CNFCl (linear range: 0-0.2 U/mL) and DRNO (linear range: 0-17.5 microM) displayed significant enhancement. As a result, the detection limit of CNFCl and DRNO for CE and ONOO(-) was calculated as 4.2 mU/L and 0.05 microM respectively. More importantly, the emission spectra of CNFCl and DRNO in the presence of CE and ONOO(-) respectively were cross-talk free under the two-photon excitation of 720 nm. This greatly facilitated the simultaneous detection of CE and ONOO(-) at distinctive channel, thus ensuring the high fidelity of the detection. These two probes were combined to image the fluctuation of CE and ONOO(-) during the conversion of NAFL to NASH in vitro and in vivo. It was found that while CE displayed a tendency to rise and then reduce during the transition from NAFL to NASH, ONOO(-) increased continuously, confirming that the combined imaging by CNFCl and DRNO might visualize the transformation of NAFL to NASH. The results provide robust visual tool to decipher the relationship between the stage of NAFLD and the level of CE/ONOO(-). We anticipate this study may open new avenues to distinguish NASH from NAFL, which may further promote the study of intracellular biological activities of CE and the development of NAFLD diagnostic methods.
ESTHER : Jiao_2023_Talanta_270_125521
PubMedSearch : Jiao_2023_Talanta_270_125521
PubMedID: 38091750

Title : Biological Degradation of Plastics and Microplastics: A Recent Perspective on Associated Mechanisms and Influencing Factors - Cai_2023_Microorganisms_11_
Author(s) : Cai Z , Li M , Zhu Z , Wang X , Huang Y , Li T , Gong H , Yan M
Ref : Microorganisms , 11 : , 2023
Abstract : Plastic and microplastic pollution has caused a great deal of ecological problems because of its persistence and potential adverse effects on human health. The degradation of plastics through biological processes is of great significance for ecological health, therefore, the feasibility of plastic degradation by microorganisms has attracted a lot of attention. This study comprises a preliminary discussion on the biodegradation mechanism and the advantages and roles of different bacterial enzymes, such as PET hydrolase and PCL-cutinase, in the degradation of different polymers, such as PET and PCL, respectively. With a particular focus on their modes of action and potential enzymatic mechanisms, this review sums up studies on the biological degradation of plastics and microplastics related to mechanisms and influencing factors, along with their enzymes in enhancing the degradation of synthetic plastics in the process. In addition, biodegradation of plastic is also affected by plastic additives and plasticizers. Plasticizers and additives in the composition of plastics can cause harmful impacts. To further improve the degradation efficiency of polymers, various pretreatments to improve the efficiency of biodegradation, which can cause a significant reduction in toxic plastic pollution, were also preliminarily discussed here. The existing research and data show a large number of microorganisms involved in plastic biodegradation, though their specific mechanisms have not been thoroughly explored yet. Therefore, there is a significant potential for employing various bacterial strains for efficient degradation of plastics to improve human health and safety.
ESTHER : Cai_2023_Microorganisms_11_
PubMedSearch : Cai_2023_Microorganisms_11_
PubMedID: 37512834

Title : In vitro plasma hydrolysis of phenolic esters and their absorption kinetics in rats: Controlled release of phenolic compounds and enhanced health benefits - Wang_2023_Food.Chem_435_137647
Author(s) : Wang X , Wang Q , Cai D , Yu J , Liu X , Yin F , Zhou D
Ref : Food Chem , 435 :137647 , 2023
Abstract : Phenolic esters are considered as promising functional food ingredients. However, their digestion, absorption and metabolism are still unclear. Tyrosol acyl esters (TYr-Es), hydroxytyrosol acyl esters (HTy-Es) and alkyl gallates (A-GAs) were hydrolyzed by carboxylesterase in plasma and exhibited slow release of polyphenols (phenolic acids). In vitro hydrolysis degrees initially increased and then decreased with the increasing carbon chain length (C2-C16). TYr-Es exhibited higher hydrolysis degrees compared to HTy-Es, and hydrolysis degrees of TYr-Es and HTy-Es were markedly higher than those of A-GAs. Due to the fast hydrolysis rates of TYr-Es and HTy-Es, they were undetectable in all rat plasma samples collected at several times within 24 h after administration. Whereas, A-GAs could be detected in rat plasmas and three absorption peaks were found in the pharmacokinetic profiles. Importantly, the T(1/2), MRT, AUC(0-), AUC(0-t) in octyl gallate group were longer (or stronger) than those in propyl gallate and dodecyl gallate groups.
ESTHER : Wang_2023_Food.Chem_435_137647
PubMedSearch : Wang_2023_Food.Chem_435_137647
PubMedID: 37804730

Title : A New Brominated Isocoumarin from the Marine Starfish-Associated Fungus Aspergillus sp. WXF1904 - Li_2023_Chem.Biodivers__e202301706
Author(s) : Li C , Lin X , Wang S , Guan D , Wang X , Yang B , Zhou X , Li J , Xiong B , Liu Y , Sun Y
Ref : Chem Biodivers , :e202301706 , 2023
Abstract : Based on the one strain many compounds strategy, a new brominated isocoumarin, 5-bromo-6,8-dihydroxy-3,7-dimethylisocoumarin (1), along with four new natural products, methyl 3-bromo-2,4-dihydroxy-6-methylbenzoate (2), methyl 2-bromo-4,6-dihydroxybenzoate (3), (E)-3-(3-bromo-4-hydroxyphenyl) acrylic acid (4) and 4-hydroxy-3-methyl-6-phenyl-2H-pyran-2-one (5), and four known compounds, methyl orsellinate (6), 4-hydroxy-3-methyl-6-(1-methyl-1-propenyl)-2H-pyran-2-one (7), pilobolusate (8) and cis-ferulic acid (9), were isolated from the ethyl acetate extract of the fungus Aspergillus sp. WXF1904 under the condition of adding bromine salt to the production medium. The structures of the new compounds were established by analysis of NMR and MS data. Compounds (1-9) were evaluated for inhibitory activity of acetylcholinesterase and pancreatic lipase, the new compound 1, known compounds 6 and 7 displayed weak inhibitory activity against acetylcholinesterase, compounds 257 and 8 showed weak inhibitory activity against pancreatic lipase.
ESTHER : Li_2023_Chem.Biodivers__e202301706
PubMedSearch : Li_2023_Chem.Biodivers__e202301706
PubMedID: 38079052

Title : Risk of resistance and the metabolic resistance mechanism of Laodelphax striatellus (Falln) to cyantraniliprole - Li_2023_Pestic.Biochem.Physiol_197_105685
Author(s) : Li Z , Wang X , Guo L , Yin T , Liu D , Liu S , You X , Xia X
Ref : Pestic Biochem Physiol , 197 :105685 , 2023
Abstract : Cyantraniliprole is a highly effective diamide insecticide used to control of Laodelphax striatellus (Fallen). This study aimed to assess the insecticide resistance risk of L. striatellus and its metabolic resistance mechanisms. After 25 continuous generations of selection, the resistance of L. striatellus to cyantraniliprole increased by 17.14-fold. The realistic heritability of resistance was 0.0751. After successive rearing for five generations without exposure to insecticides, the resistance ratio for the resistant strain of L. striatellus decreased by 3.47-fold, and the average resistance decline rate per generation was 0.0266. Cyantraniliprole-resistant strains did not exhibit cross-resistance to triflumezopyrim, pymetrozine, flonicamid, sulfoxaflor, dinotefuran, clothianidin, thiamethoxam, nitenpyram, or imidacloprid. Compared to those of the sensitive strain, the 2nd, 3rd, and 4th instars, nymphal stage durations, total preoviposition period, and average generation time of the resistant strain were markedly reduced. Furthermore, the activity of cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) were markedly increased. The upregulation of CYP419A1v2 expression was most evident among the P450 genes, with a 6.10-fold increase relative to that in the sensitive strain. The CarE gene LsCarE5 was significantly upregulated by 1.94-fold compared with that in the sensitive strain. With the continuous use of cyantraniliprole, L. striatellus may develop resistance to this insecticide. This resistance may be related to the increase in metabolic enzyme activities regulated by the overexpression of P450 and CarE genes.
ESTHER : Li_2023_Pestic.Biochem.Physiol_197_105685
PubMedSearch : Li_2023_Pestic.Biochem.Physiol_197_105685
PubMedID: 38072542

Title : A novel thermostable and salt-tolerant carboxylesterase involved in the initial aerobic degradation pathway for pyrethroids in Glycomyces salinus - Liu_2023_J.Hazard.Mater_451_131128
Author(s) : Liu Y , Tang S , Wang X , Tang X , Wu Q , Huang Z , Ding J
Ref : J Hazard Mater , 451 :131128 , 2023
Abstract : The long-term and excessive use of pyrethroid pesticides poses substantial health risks and ecosystem concerns. Several bacteria and fungi have been reported that could degrade pyrethroids. The ester-bond hydrolysis using hydrolases is the initial regulatory metabolic reaction of pyrethroids. However, the thoroughly biochemical characterization of hydrolases involved in this process is limited. Here, a novel carboxylesterase, designated as EstGS1 that could hydrolyze pyrethroid pesticides was characterized. EstGS1 showed low sequence identity (<27.03%) compared to other reported pyrethroid hydrolases and belonged to the hydroxynitrile lyase family that preferred short short-chain acyl esters (C2 to C8). EstGS1 displayed the maximal activity of 213.38 U/mg at 60 degreesC and pH 8.5 using pNPC2 as substrate, with K(m) and V(max) were 2.21 +/- 0.72 mM and 212.90 +/- 41.78 microM/min, respectively. EstGS1 is a halotolerant esterase and remains stable in 5.1 M NaCl. Based on molecular docking and mutational analysis, the catalytic triad of S(74)-D(181)-H(212) and three other substrate-binding residues I(108), S(159), and G(75) are critical for the enzymatic activity of EstGS1. Additionally, 61 and 40 mg/L of deltamethrin and lambda-cyhalothrin were hydrolyzed by 20 U of EstGS1 in 4 h. This work presents the first report on a pyrethroid pesticide hydrolase characterized from a halophilic actinobacteria.
ESTHER : Liu_2023_J.Hazard.Mater_451_131128
PubMedSearch : Liu_2023_J.Hazard.Mater_451_131128
PubMedID: 36893599
Gene_locus related to this paper: 9actn-EstGS1

Title : Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038 - Li_2023_Nat.Prod.Res__1
Author(s) : Li H , Long J , Wang X , She J , Liu Y , Li Y , Yang B
Ref : Nat Prod Res , :1 , 2023
Abstract : Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.
ESTHER : Li_2023_Nat.Prod.Res__1
PubMedSearch : Li_2023_Nat.Prod.Res__1
PubMedID: 37129009

Title : A potential novel biomarker: comprehensive analysis of prognostic value and immune implication of CES3 in colonic adenocarcinoma - He_2023_J.Cancer.Res.Clin.Oncol__
Author(s) : He L , Zhao C , Xu J , Li W , Lu Y , Gong Y , Gu D , Wang X , Guo F
Ref : J Cancer Research Clin Oncol , : , 2023
Abstract : PURPOSE: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. PATIENTS AND METHODS: The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. RESULTS: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CONCLUSION: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.
ESTHER : He_2023_J.Cancer.Res.Clin.Oncol__
PubMedSearch : He_2023_J.Cancer.Res.Clin.Oncol__
PubMedID: 37480527
Gene_locus related to this paper: human-CES3

Title : The protective effect of PL 1-3 on D-galactose-induced aging mice - Li_2023_Front.Pharmacol_14_1304801
Author(s) : Li P , Ma Y , Wang X , Li X , Yang J , Liu G
Ref : Front Pharmacol , 14 :1304801 , 2023
Abstract : The aging population has become an issue that cannot be ignored, and research on aging is receiving increasing attention. PL 1-3 possesses diverse pharmacological properties including anti-oxidative stress, inhibits inflammatory responses and anti-apoptosis. This study showed that PL 1-3 could protect mice, especially the brain, against the aging caused by D-galactose (D-gal). D-gal could cause oxidative stress, inflammation, apoptosis and tissue pathological injury and so on in aging mice. The treatment of PL 1-3 could increase the anti-oxidative stress ability in the serum, liver, kidney and brain of aging mice, via increasing the total antioxidant capacity and the levels of anti-oxidative defense enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and reducing the end product of lipid peroxidation (malondialdehyde). In the brain, in addition to the enhanced anti-oxidative stress via upregulating the level of the nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, PL 1-3 could improve the dysfunction of the cholinergic system via reducing the active of acetylcholinesterase so as to increase the level of acetylcholine, increase the anti-inflammatory and anti-apoptosis activities via downregulating the expressions of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha) and pro-apoptosis proteins (Bcl-2 associated X protein and Caspase-3) in the D-gal-induced aging mice, to enhance the anti-aging ability via upregulating the expression of sirtuin 1 and downregulating the expressions of p53, p21, and p16. Besides, PL 1-3 could reverse the liver, kidney and spleen damages induced by D-gal in aging mice. These results suggested that PL 1-3 may be developed as an anti-aging drug for the prevention and intervention of age-related diseases.
ESTHER : Li_2023_Front.Pharmacol_14_1304801
PubMedSearch : Li_2023_Front.Pharmacol_14_1304801
PubMedID: 38235117

Title : Ultrasensitivity Detecting AChE through "\;Covalent Assembly"\; and Signal Amplification Strategic Approaches and Applied to Screen Its Inhibitor - Zhao_2023_Anal.Chem__
Author(s) : Zhao Y , Shen A , Hao X , Li M , Hou L , Li Z , Duan R , Du M , Li X , Wang X , Zhao X , Yang Y
Ref : Analytical Chemistry , : , 2023
Abstract : An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.
ESTHER : Zhao_2023_Anal.Chem__
PubMedSearch : Zhao_2023_Anal.Chem__
PubMedID: 36812425

Title : The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation - Zhang_2023_Fish.Physiol.Biochem__
Author(s) : Zhang N , Wang X , Han Z , Gong Y , Huang X , Chen N , Li S
Ref : Fish Physiol Biochem , : , 2023
Abstract : To elucidate the underlying mechanism of the energy metabolism in largemouth bass (Micropterus salmoides), cultured fish (initial body weight: 77.57 +/- 0.75 g) in the present study were starved for 0 h, 12 h, 24 h, 48 h, 96 h and 192 h, respectively. The proximate composition analysis showed that short-term starvation induced a significant up-regulation in crude protein proportion in hepatic of cultured fish (P < 0.05). However, short-term starvation significantly decreased the hepatosomatic index and the viscerosomatic index of cultured fish (P < 0.05). The exact hepatic glycogen content in the group starved for 92 h presented remarkable decrease (P < 0.05). Meanwhile, compared with the weight change of lipid and protein (mg) in hepatic (y = 0.0007x(2) - 0.2827x + 49.402; y = 0.0013x(2) - 0.5666x + 165.31), the decreasing trend of weight in glycogen (mg) was more pronounced (y = 0.0032x(2) - 1.817x + 326.52), which suggested the preferential utilization of hepatic glycogen as energy substrates under short-term starvation. Gene expression analysis revealed that the starvation down-regulated the expression of insulin-like growth factor 1 and genes of TOR pathway, such as target of rapamycin (tor) and ribosomal protein S6 (s6) (P < 0.05). In addition, the starvation significantly enhanced expression of lipolysis-related genes, including hormone-sensitive lipase (hsl) and carnitine palmitoyl transferase I (cpt1), but down-regulated lipogenesis as indicated by the inhibited expression of fatty acids synthase (fas), acetyl-CoA carboxylase 1 (acc1) and acetyl-CoA carboxylase 2 (acc2) (P < 0.05). Starvation of 24 h up-regulated the expression of glycolysis genes, glucokinase (gk), phosphofructokinase liver type (pfkl) and pyruvate kinase (pk), and then their expression returned to the normal level. Meanwhile, the expression of gluconeogenesis genes, such as glucose-6-phosphatase catalytic subunit (g6pc), fructose-1,6-bisphosphatase-1 (fbp1) and phosphoenolpyruvate carboxy kinase (pepck), was significantly inhibited with the short-term starvation (P < 0.05). In conclusion, short-term starvation induced an overall decline in growth performance, but it could deplete the hepatic glycogen accumulation and mobilize glycogen for energy effectively.
ESTHER : Zhang_2023_Fish.Physiol.Biochem__
PubMedSearch : Zhang_2023_Fish.Physiol.Biochem__
PubMedID: 38108936

Title : Serum Cholinesterase, C-reactive Protein, Interleukin 6, and Procalcitonin Levels as Predictors of Mortality in Patients in the Intensive Care Unit - Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
Author(s) : Liu Q , Fan X , Cui W , Wang X , Zhang Z , Wang N , Qiao L
Ref : Turk J Anaesthesiol Reanim , 51 :408 , 2023
Abstract : OBJECTIVE: The prognostic utility of inflammatory markers in survival has been suggested in patients with cancer; however, evidence on their prognostic value in severely ill patients is very limited. We aimed to explore the prognostic value of cholinesterase (ChE), C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) in predicting mortality in patients from the intensive care unit (ICU). METHODS: Serum levels of ChE, CRP, IL-6 and PCT were measured in ICU patients from December 13(th), 2019 to June 28(th), 2022. We assessed the predictive power of ChE, CRP, IL-6, and PCT using the receiver operating characteristic (ROC) curves. Furthermore, we evaluated their diagnostic accuracy by comparing the areas under the ROC curve (AUCs) along with their corresponding 95% confidence intervals (CIs). The cut-off values were determined to dichotomise these biomarkers, which were then included in multivariable logistic regression models to examine their relationship with ICU mortality. RESULTS: Among 253 ICU patients included in the study, 66 (26%) died during the ICU stay. The AUCs to predict ICU mortality were 0.643 (95% CI, 0.566-0.719), 0.648 (95% CI, 0.633-0.735), 0.643 (95% CI, 0.563-0.723) and 0.735 (95% CI, 0.664-0.807) for ChE, CRP, IL-6 and PCT, respectively. After adjusting for age, sex and disease severity, lower ChE level (<3.668 x 10(3) U L(-1)) and higher levels of CRP (>10.546 mg dL(-1)), IL-6 (>986.245 pg mL(-1)) and PCT (>0.505 microg L(-1)) were associated with higher mortality risk, with odd ratios of 2.70 (95% CI, 1.32-5.54), 4.99 (95% CI, 2.41-10.38), 3.24 (95% CI, 1.54-6.78) and 3.67 (95% CI, 1.45-9.95), respectively. CONCLUSION: ChE, CRP, IL-6 and PCT were independent ICU mortality risk factors in severely ill patients. Elevated PCT levels exhibited better predictive value than the other three biomarkers that were evaluated.
ESTHER : Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
PubMedSearch : Liu_2023_Turk.J.Anaesthesiol.Reanim_51_408
PubMedID: 37876167

Title : Serum cholinesterase is associated with incident diabetic retinopathy: the Shanghai Nicheng cohort study - Yu_2023_Nutr.Metab.(Lond)_20_26
Author(s) : Yu R , Ye X , Wang X , Wu Q , Jia L , Dong K , Zhu Z , Bao Y , Hou X , Jia W
Ref : Nutr Metab (Lond) , 20 :26 , 2023
Abstract : BACKGROUND: Serum cholinesterase (ChE) is positively associated with incident diabetes and dyslipidemia. We aimed to investigate the relationship between ChE and the incidence of diabetic retinopathy (DR). METHODS: Based on a community-based cohort study followed for 4.6 years, 1133 participants aged 55-70 years with diabetes were analyzed. Fundus photographs were taken for each eye at both baseline and follow-up investigations. The presence and severity of DR were categorized into no DR, mild non-proliferative DR (NPDR), and referable DR (moderate NPDR or worse). Binary and multinomial logistic regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) between ChE and DR. RESULTS: Among the 1133 participants, 72 (6.4%) cases of DR occurred. The multivariable binary logistic regression showed that the highest tertile of ChE (<= 422 U/L) was associated with a 2.01-fold higher risk of incident DR (RR 2.01, 95%CI 1.01-4.00; P for trend < 0.05) than the lowest tertile (< 354 U/L). The multivariable binary and multinomial logistic regression showed that the risk of DR increased by 41% (RR 1.41, 95%CI 1.05-1.90), and the risk of incident referable DR was almost 2-fold higher than no DR (RR 1.99, 95%CI 1.24-3.18) with per 1-SD increase of log(e)-transformed ChE. Furthermore, multiplicative interactions were found between ChE and elderly participants (aged 60 and older; P for interaction = 0.003) and men (P for interaction = 0.044) on the risk of DR. CONCLUSIONS: In this study, ChE was associated with the incidence of DR, especially referable DR. ChE was a potential biomarker for predicting the incident DR.
ESTHER : Yu_2023_Nutr.Metab.(Lond)_20_26
PubMedSearch : Yu_2023_Nutr.Metab.(Lond)_20_26
PubMedID: 37138337

Title : Developmental Neurotoxicity of Trichlorfon in Zebrafish Larvae - Shi_2023_Int.J.Mol.Sci_24_
Author(s) : Shi Q , Yang H , Chen Y , Zheng N , Li X , Wang X , Ding W , Zhang B
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.
ESTHER : Shi_2023_Int.J.Mol.Sci_24_
PubMedSearch : Shi_2023_Int.J.Mol.Sci_24_
PubMedID: 37446277

Title : IL-33 Downregulates Hepatic Carboxylesterase 1 in Acute Liver Injury via Macrophage-derived Exosomal miR-27b-3p - Gao_2023_J.Clin.Transl.Hepatol_11_1130
Author(s) : Gao P , Li M , Lu J , Xiang D , Wang X , Xu Y , Zu Y , Guan X , Li G , Zhang C
Ref : J Clin Transl Hepatol , 11 :1130 , 2023
Abstract : BACKGROUND AND AIMS: We previously reported that carboxylesterase 1 (CES1) expression was suppressed following liver injury. The study aimed to explore the role of interleukin (IL)-33 in liver injury and examine the mechanism by which IL-33 regulates CES1. METHODS: IL-33 and CES1 levels were determined in the livers of patients and lipopolysaccharide (LPS)-, acetaminophen (APAP)-treated mice. We constructed IL-33 and ST2 knockout (KO) mice. ST2-enriched immune cells in livers were screened to identify the responsible cells. Macrophage-derived exosome (MDE) activity was tested by adding exosome inhibitors. Micro-RNAs (miRs) were extracted from control and IL-33-stimulated MDEs (IL-33-MDEs) and subjected miR sequencing (miR-Seq). Candidate miR was tested in vitro and in vivo and its binding of a target gene was assessed by luciferase reporter assays. Lentivirus-vector cellular transfection and transcript silencing were used to examine pathways mediating IL-33 suppression of miR-27b-3p. RESULTS: Patient liver IL-33 and CES1 expression levels were inversely correlated. CES1 downregulation in liver injury was rescued in both IL-33-deficient and ST2 KO mice. Macrophages were shown to be responsible for IL-33 effects. IL-33-MDEs reduced CES1 levels in hepatocytes. Exosomal miR-Seq and qRT-PCR demonstrated increased miR-27b-3p levels in IL-33-MDEs; miR-27b-3p was implicated in Nrf2 targeting. IL-33 inhibition of miR-27b-3p was found to be GATA3-dependent. CONCLUSIONS: IL-33-ST2-GATA3 pathway signaling increases miR-27b-3p content in MDEs, which upon being internalized by hepatocytes reduce CES1 expression by inhibiting Nrf2. The elucidation of this mechanism in this study contributes to a better understanding of CES1 dysregulation in liver injury.
ESTHER : Gao_2023_J.Clin.Transl.Hepatol_11_1130
PubMedSearch : Gao_2023_J.Clin.Transl.Hepatol_11_1130
PubMedID: 37577217

Title : In Vitro Gastrointestinal Digestion and Microbial Hydrolysis of Hydroxytyrosol-SCFA and Tyrosol-SCFA Acyl Esters: Controlled-Release of SCFAs and Polyphenols - Wang_2023_J.Agric.Food.Chem__
Author(s) : Wang X , Wang Q , Cai D , Guo X , Tong P , Yin F , Liu X , Zhou D
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : Phenolipids such as hydroxytyrosol-SCFA acyl esters (HTy-SEs) and tyrosol-SCFA acyl esters (TYr-SEs) with various alkyl chains lengths (C1-C4) and different isomers (branched-chain and straight-chain) were successfully synthesized. All esters were hydrolyzed by pancreatic lipase to produce polyphenols (HTy and TYr) and SCFAs (iso-butyric acid, acetic acid, propionic acid, and n-butyric acid). Moreover, HTy-SEs (and TYr-SEs) could also be hydrolyzed to free HTy (and TYr) and SCFAs by gut microbiota and Lactobacillus from mice feces. Especially, the hydrolysis rates showed positive correlation with the carbon skeleton length, and the hydrolysis degree (DH) of ester with a branched-chain fatty acid was weaker than that of ester with a straight-chain fatty acid. Besides, the DH values of TYr -SEs were significantly higher than those of HTy-SEs. Therefore, through regulating the structures of polyphenols, carbon skeleton lengths, and isomers, controlled-release of polyphenols and SCFAs from phenolipids will be easily achieved.
ESTHER : Wang_2023_J.Agric.Food.Chem__
PubMedSearch : Wang_2023_J.Agric.Food.Chem__
PubMedID: 37294303

Title : Design and construction of Carboxylesterase 2c Gene knockout Rats by CRISPR\/Cas9 - Liu_2023_Curr.Drug.Metab__
Author(s) : Liu J , Shang X , Yao B , Zhang Y , Huang S , Guo Y , Wang X
Ref : Curr Drug Metab , : , 2023
Abstract : BACKGROUND: Carboxylesterase 2 (CES2) is mainly distributed in the human liver and gut, and plays an active role in the metabolic activation of many prodrugs and lipid metabolism. Although CES2 is of great significance, there are still few animal models related to CES2. OBJECTIVES: This research aims to construct Ces2c gene knockout (KO) rats and further study the function of CES2. METHODS: CRISPR/Cas9 gene editing technology was used to target and cleave the rat Ces2c gene. Compensatory effects of major CES subtypes both in the liver and small intestine of KO rats were detected at mRNA levels. Meanwhile, diltiazem and aspirin were used as substrates to test the metabolic capacity of Ces2c in KO rats. RESULTS: This Ces2c KO rat model showed normal growth and breeding without off-target effects. The metabolic function of Ces2c KO rats was verified by the metabolic study of CES2 substrates in vitro. The results showed that the metabolic capacity of diltiazem in KO rats was weakened, while the metabolic ability of aspirin did not change significantly. In addition, the serum physiological indexes showed that the Ces2c deletion did not affect the liver function of rats. CONCLUSION: The Ces2c KO rat model was successfully constructed by CRISPR/Cas9 system. This rat model can not only be used as an important tool to study the drug metabolism mediated by Ces2, but also as an important animal model to study the physiological function of Ces2.
ESTHER : Liu_2023_Curr.Drug.Metab__
PubMedSearch : Liu_2023_Curr.Drug.Metab__
PubMedID: 36694315
Gene_locus related to this paper: ratno-pbcxe

Title : The Relationship between Intracarotid Plaque Neovascularization and Lp (a) and Lp-PLA2 in Elderly Patients with Carotid Plaque Stenosis - Sun_2022_Dis.Markers_2022_6154675
Author(s) : Sun C , Xi N , Sun Z , Zhang X , Wang X , Cao H , Jia X
Ref : Dis Markers , 2022 :6154675 , 2022
Abstract : The aim of this study was to investigate the relationship between carotid plaque neovascularization and lipoprotein (a) [Lp (a)], lipoprotein-associated phospholipase A2 (Lp-PLA2) in elderly patients with carotid plaque stenosis. One hundred elderly patients with carotid plaque stenosis diagnosed in our hospital from January 2020 to January 2022 were retrospectively analyzed and divided into stable (n = 62) and unstable (n = 38) groups according to whether the plaque was stable or not. Plasma Lp (a), Lp-PLA2, apoA, and apoB levels were measured; intraplaque angiogenesis (IPN) scores were examined by contrast-enhanced ultrasound (CEUS) to assess IPN grade in patients; and Pearson correlation was used to analyze the relationship between plasma Lp (a) and Lp-PLA2 levels and plaque characteristics and angiogenesis. The maximum thickness and total thickness of carotid plaque in the unstable group were significantly greater than those in the stable group (P < 0.05); the IPN grade was mainly grade III and IV in the unstable group and grade II in the stable group, and the IPN score was significantly higher in the unstable group than in the stable group (P < 0.05); there was no significant difference in the plasma apoA and apoB levels between the two groups (P > 0.05), and the plasma Lp (a) and Lp-PLA2 levels were significantly higher in the unstable group than in the stable group (P < 0.05); the neovascular grade, plasma Lp-PLA2, and Lp (a) levels were significantly increased (P < 0.05); the plasma Lp (a) and Lp-PLA2 levels were positively correlated with the maximum plaque thickness, total plaque thickness, degree of stenosis, and angiogenesis (P < 0.05). The plasma levels of Lp (a) and Lp-PLA2 are positively correlated with intraplaque angiogenesis, and their levels can reflect the stability of carotid plaques.
ESTHER : Sun_2022_Dis.Markers_2022_6154675
PubMedSearch : Sun_2022_Dis.Markers_2022_6154675
PubMedID: 35493296

Title : Display of a novel carboxylesterase CarCby on Escherichia coli cell surface for carbaryl pesticide bioremediation - Liu_2022_Microb.Cell.Fact_21_97
Author(s) : Liu Y , Wang X , Nong S , Bai Z , Han N , Wu Q , Huang Z , Ding J
Ref : Microb Cell Fact , 21 :97 , 2022
Abstract : BACKGROUND: Carbamate pesticides have been widely used in agricultural and forestry pest control. The large-scale use of carbamates has caused severe toxicity in various systems because of their toxic environmental residues. Carbaryl is a representative carbamate pesticide and hydrolase/carboxylesterase is the initial and critical enzyme for its degradation. Whole-cell biocatalysts have become a powerful tool for environmental bioremediation. Here, a whole cell biocatalyst was constructed by displaying a novel carboxylesterase/hydrolase on the surface of Escherichia coli cells for carbaryl bioremediation. RESULTS: The carCby gene, encoding a protein with carbaryl hydrolysis activity was cloned and characterized. Subsequently, CarCby was displayed on the outer membrane of E. coli BL21(DE3) cells using the N-terminus of ice nucleation protein as an anchor. The surface localization of CarCby was confirmed by SDS-PAGE and fluorescence microscopy. The optimal temperature and pH of the engineered E. coli cells were 30 degreesC and 7.5, respectively, using pNPC4 as a substrate. The whole cell biocatalyst exhibited better stability and maintained approximately 8-fold higher specific enzymatic activity than purified CarCby when incubated at 30 degreesC for 120 h. In addition, ~ 100% and 50% of the original activity was retained when incubated with the whole cell biocatalyst at 4 degC and 30 degreesC for 35 days, respectively. However, the purified CarCby lost almost 100% of its activity when incubated at 30 degreesC for 134 h or 37 degreesC for 96 h, respectively. Finally, approximately 30 mg/L of carbaryl was hydrolyzed by 200 U of the engineered E. coli cells in 12 h. CONCLUSIONS: Here, a carbaryl hydrolase-containing surface-displayed system was first constructed, and the whole cell biocatalyst displayed better stability and maintained its catalytic activity. This surface-displayed strategy provides a new solution for the cost-efficient bioremediation of carbaryl and could also have the potential to be used to treat other carbamates in environmental bioremediation.
ESTHER : Liu_2022_Microb.Cell.Fact_21_97
PubMedSearch : Liu_2022_Microb.Cell.Fact_21_97
PubMedID: 35643494
Gene_locus related to this paper: baca2-a7z924

Title : Novel Ce-based coordination polymer nanoparticles with excellent oxidase mimic activity applied for colorimetric assay to organophosphorus pesticides - Wang_2022_Food.Chem_397_133810
Author(s) : Wang J , Wang X , Wang M , Bian Q , Zhong J
Ref : Food Chem , 397 :133810 , 2022
Abstract : Cerium, as a lanthanide, has attracted considerable interest because of its excellent catalytic activity. Here, we propose a novel cerium-based coordination polymer nanoparticles named DPA-Ce-GMP, which have excellent oxidase-mimicking properties. Furthermore, a colorimetric probe that can act as an inhibitor to suppress the activity of acetylcholinesterase (AChE) was developed for detecting organophosphorus pesticides (OPs). DPA-Ce-GMP catalyzes colorless 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue color, and AChE catalyzes acetylthiocholine to produce thiocholine (TCh), which can weaken DPA-Ce-GMP-catalyzed TMB. After the addition of OPs, the enzymatic activity of AChE was inhibited to produce less amount of TCh, resulting in more DPA-Ce-GMP-catalyst oxidized TMB to show an increasing blue color. Dichlorvos, as the samples, with the limit of 0.024 microg/L. Overall, we believe that the colorimetric probe can be used for the rapid, low-cost, and large-scale field detection of OPs in food samples.
ESTHER : Wang_2022_Food.Chem_397_133810
PubMedSearch : Wang_2022_Food.Chem_397_133810
PubMedID: 35917788

Title : Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202 - Shao_2022_Molecules_27_
Author(s) : Shao S , Wang X , She J , Zhang H , Pang X , Lin X , Zhou X , Liu Y , Li Y , Yang B
Ref : Molecules , 27 : , 2022
Abstract : Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3-11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC(50) value of 1.31 microM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC(50) value of 2.32 microM.
ESTHER : Shao_2022_Molecules_27_
PubMedSearch : Shao_2022_Molecules_27_
PubMedID: 35335187

Title : The Therapeutic Effects of Seven Lycophyte Compounds on Cell Models of Alzheimer's Disease - Guo_2022_J.Alzheimers.Dis__
Author(s) : Guo Q , Cai Q , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : J Alzheimers Dis , : , 2022
Abstract : BACKGROUND: As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. To search for new analogs or derivatives of Hup-A, we produced five Lycophyte alkaloids and two analogues by chemical synthesis: Lyconadins A-E, H-R-NOB, and 2JY-OBZ4. OBJECTIVE: To systematically evaluated the therapeutic effects of the seven compounds on AD cell models. METHODS: We assessed the effects of the seven compounds on cell viability via CCK-8 kit and used HEK293-hTau cells and N2a-hAPP cells as AD cell models to evaluate their potential therapeutic effects. We examined their effects on cholinesterase activity by employing the mice primary neuron. RESULTS: All compounds did not affect cell viability; in addition, Lyconadin A and 2JY-OBZ4 particularly increased cell viability. Lyconadin D and Lyconadin E restored tau phosphorylation at Thr231, and H-R-NOB and 2JY-OBZ4 restored tau phosphorylation at Thr231 and Ser396 in GSK-3beta-transfected HEK293-hTau cells. 2JY-OBZ4 decreased the level of PP2Ac-pY307 and increased the level of PP2Ac-mL309, supporting that 2JY-OBZ4 may activate PP2A. Lyconadin B, Lyconadin D, Lyconadin E, H-R-NOB, and 2JY-OBZ4 increased sAbetaPPalpha level in N2a-hAPP cells. 2JY-OBZ4 decreased the levels of BACE1 and sAbetaPPbeta, thereby reduced Abeta production. Seven compounds exhibited weaker AChE activity inhibition efficiency than Hup-A. Among them, 2JY-OBZ4 showed the strongest AChE inhibition activity with an inhibition rate of 17% at 10microM. CONCLUSION: Among the seven lycophyte compounds, 2JY-OBZ4 showed the most expected effects on promoting cell viability, downregulating tau hyperphosphorylation, and Abeta production and inhibiting AChE in AD.
ESTHER : Guo_2022_J.Alzheimers.Dis__
PubMedSearch : Guo_2022_J.Alzheimers.Dis__
PubMedID: 36189599

Title : Novel small molecular compound 2JY-OBZ4 alleviates AD pathology in cell models via regulating multiple targets - Guo_2022_Aging.(Albany.NY)_14_
Author(s) : Guo Q , Wu G , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : Aging (Albany NY) , 14 : , 2022
Abstract : Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, characterized by cognitive deficits and memory dysfunction, which is clinically incurable so far. Novel small molecular compound 2JY-OBZ4 is one of structural analogue of Huperzine A (Hup-A), an anti-AD drug in China. In our previous work, 2JY-OBZ4 exhibited potent effects on tau hyperphosphorylation, Abeta production and acetylcholinesterase (AChE) activity. However, 2JY-OBZ4's anti-AD effects and the underlying molecular mechanisms remain unclear. We here reported that 2JY-OBZ4 resisted tau hyperphosphorylation at Thr181 and Ser396 sites in HEK293-hTau cells transfected with GSK-3beta, decreased tau phosphorylation via upregulating the activity of PP2A in HEK293-hTau cells and reduced Abeta production through regulating protein levels of APP cleavage enzymes in N2a-hAPP cells. Meanwhile, we found that 2JY-OBZ4 had no adverse effects on cell viability of mice primary neuron even at high concentration, and ameliorated synaptic loss induced by human oligomeric Abeta42. 2JY-OBZ4 had moderate AChE inhibitory activity with the half maximal inhibitory concentration (IC50) to be 39.48 microg/ml in vitro, which is more than two times higher than Hup-A. Together, 2JY-OBZ4 showed promising therapeutic effects in AD cell models through regulating multiple targets. The research provides a new candidate for the therapeutic development of AD.
ESTHER : Guo_2022_Aging.(Albany.NY)_14_
PubMedSearch : Guo_2022_Aging.(Albany.NY)_14_
PubMedID: 36227154

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida) - Li_2022_Environ.Toxicol.Pharmacol_97_104016
Author(s) : Li S , Yuan Y , Wang X , Cai L , Wang J , Zhao Y , Jiang L , Yang X
Ref : Environ Toxicol Pharmacol , 97 :104016 , 2022
Abstract : Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems.
ESTHER : Li_2022_Environ.Toxicol.Pharmacol_97_104016
PubMedSearch : Li_2022_Environ.Toxicol.Pharmacol_97_104016
PubMedID: 36435387

Title : A hemicyanine-based fluorescent probe for simultaneous imaging of Carboxylesterases and Histone deacetylases in hepatocellular carcinoma - Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
Author(s) : Shu Y , Huang C , Liu H , Hu F , Wen H , Liu J , Wang X , Shan C , Li W
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 281 :121529 , 2022
Abstract : Carboxylesterases (CESs) and Histone deacetylases (HDACs) are regarded as important signaling enzymes highly associated with the development and progression of multiple cancers, including hepatocellular carcinoma (HCC). In this work, a near-infrared (NIR) fluorescent probe named Lys-HXPI was designed and synthesized, which linked a hemicyanine dye and 6-acetamidohexanoic acid via an ester bond. Lys-HXPI displayed a remarkable increase with a NIR emission at 720 nm, a low detection limit (<10 nM) for HDAC1, HDAC 6, CES1 and CES2, as well as a high selectivity for the target enzymes over other relevant analytes. Furthermore, Lys-HXPI was used to image endogenous target enzymes in living cells, tumor-bearing nude mice and tissue slices. The ability of Lys-HXPI to simultaneous image CESs and HDACs was demonstrated with RT-qPCR and the confocal imaging in Hep G2 and MDA-MB-231. Taking advantage of NIR emission, the probe was also successfully applied to imaging Hep G2 tumor mice and tissue slices. Lys-HXPI is expected to be useful for the effective detecting of CESs and HDACs in complex biosystems.
ESTHER : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedSearch : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedID: 35797949

Title : Emerging role of carboxylesterases in nonalcoholic fatty liver disease - Liu_2022_Biochem.Pharmacol__115250
Author(s) : Liu J , Yao B , Gao L , Zhang Y , Huang S , Wang X
Ref : Biochemical Pharmacology , :115250 , 2022
Abstract : Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health problem. Carboxylesterases (CESs), as potential influencing factors of NAFLD, are very important to improve clinical outcomes. This review aims to deeply understand the role of CESs in the progression of NAFLD and proposes that CESs can be used as potential targets for NAFLD treatment. We first introduced CESs and analyzed the relationship between CESs and hepatic lipid metabolism and inflammation. Then, we further reviewed the regulation of nuclear receptors on CESs, including PXR, CAR, PPARalpha, HNF4alpha and FXR, which may influence the progression of NAFLD. Finally, we evaluated the advantages and disadvantages of existing NAFLD animal models and summarized the application of CES-related animal models in NAFLD research. In general, this review provides an overview of the relationship between CESs and NAFLD and discusses the role and potential value of CESs in the treatment and prevention of NAFLD.
ESTHER : Liu_2022_Biochem.Pharmacol__115250
PubMedSearch : Liu_2022_Biochem.Pharmacol__115250
PubMedID: 36130649

Title : Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis) - Tan_2022_Chemosphere__137594
Author(s) : Tan J , Liang C , Guo Y , Zou H , Ye J , Hou L , Wang X
Ref : Chemosphere , :137594 , 2022
Abstract : The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4.4-378.7 ng/L) for 60 days. The results showed that exposure to 378.7 ng/L GES caused a significant decrease in fish growth compared with the control and a marked reduction in the total distance traveled (50.6%) and swimming velocity (40.1-61.9%). The triiodothyronine (T3) levels were significantly increased by GES in a dose-dependent manner, whereas those of tetraiodothyronine (T4) were significantly decreased only at the G500 concentration. The acetylcholinesterase (AChE) activity was decreased significantly in the 4.42 ng/L GES treatments, but increased significantly at 378.67 ng/L. In the brain, a strong increase in the transcriptional levels of bdnf, trh, and dio2 was observed in fish after the 378.7 ng/L treatment. In addition, chronic exposure to GES caused colloid depletion with a concentration-dependent manner in the thyroid, and angiectasis, congestion, and vacuolar necrosis in the brain. These findings provide a better understanding of the effects of GES and associated underlying mechanisms in G. affinis.
ESTHER : Tan_2022_Chemosphere__137594
PubMedSearch : Tan_2022_Chemosphere__137594
PubMedID: 36538954

Title : A full-length transcriptome and gene expression analysis of three detoxification gene families in a predatory stink bug, Picromerus lewisi - Li_2022_Front.Physiol_13_1016582
Author(s) : Li W , Wang X , Jiang P , Yang M , Li Z , Huang C , He Y
Ref : Front Physiol , 13 :1016582 , 2022
Abstract : The predatory stink bug P. Lewisi shows potential for Integrated Pest Management programs for controlling Lepidoptera pest insects in crops and forests. The importance of this insect for biological control has stimulated several studies into its biology and ecology. However, P. lewisi has little genetic information available. In the present study, PacBio single-molecule real-time (SMRT) sequencing and Illumina RNA-seq sequencing technologies were used to reveal the full-length transcriptome profiling and tissue-specific expression patterns of P. lewisi. A total of 12,997 high-quality transcripts with an average length of 2,292 bp were obtained from different stages of P. lewisi using SMRT sequencing. Among these, 12,101 were successfully annotated in seven public databases. A total of 67 genes of cytochrome P450 monooxygenases, 43 carboxylesterase genes, and 18 glutathione S-transferase genes were identified, most of which were obtained with full-length ORFs. Then, tissue-specific expression patterns of 5th instar nymphs were analyzed using Illumina sequencing. Several candidate genes related to detoxification of insecticides and other xenobiotics as well as the degradation of odors, were identified in the guts and antennae of P. lewisi. The current study offered in-depth knowledge to understand the biology and ecology of this beneficial predator and related species.
ESTHER : Li_2022_Front.Physiol_13_1016582
PubMedSearch : Li_2022_Front.Physiol_13_1016582
PubMedID: 36299261

Title : Activation of GPR55 attenuates cognitive impairment, oxidative stress, neuroinflammation, and synaptic dysfunction in a streptozotocin-induced Alzheimer's mouse model - Xiang_2022_Pharmacol.Biochem.Behav__173340
Author(s) : Xiang X , Wang X , Wu Y , Hu J , Li Y , Jin S , Wu X
Ref : Pharmacol Biochem Behav , :173340 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cascading changes in cognition and behavior. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for the treatment of diabetes, but its function in AD is unclear. The objective of this study was to investigate the neuroprotective effects of O-1602, a GPR55 agonist, on the streptozotocin (STZ)-induced AD mouse model. A single intracerebroventricular (i.c.v.) injection of STZ into the brains of mice significantly induced cognitive impairment. In contrast, O-1602 (2.0 or 4.0 microg/mouse, i.c.v.) can improve the cognitive dysfunction caused by STZ in the Morris water maze (MWM) and novel object recognition (NOR) tests. Importantly, O-1602 treatment reversed STZ-induced GPR55 down-regulation, reduced the activity of beta-secretase 1 (BACE1) and the level of Abeta(1-42), and abolished the up-regulation of acetylcholinesterase (AChE) activity in the hippocampus and frontal cortex. Besides, O-1602 markedly suppressed STZ-induced oxidative stress, characterized by decreased malondialdehyde (MDA) level, and increased the levels of glutathione (GSH), superoxide dismutases (SOD), and catalase (CAT), as well as attenuated neuroinflammation as indicated by decreased series of pro-inflammatory cytokines and microglia activation. O-1602 treatment also ameliorated synaptic dysfunction by promoting the up-regulation of PSD-95 protein in the STZ-treated mice. Our results suggest that O-1602 has potent neuroprotective effects against STZ-induced neurotoxicity. Meanwhile, these findings suggest that GPR55 might be a novel and promising target for the treatment of AD.
ESTHER : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedSearch : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedID: 35090841

Title : Progress in enrichment of n-3 polyunsaturated fatty acid: a review - Xie_2022_Crit.Rev.Food.Sci.Nutr__1
Author(s) : Xie D , Chen Y , Yu J , Yang Z , Wang X
Ref : Crit Rev Food Sci Nutr , :1 , 2022
Abstract : n-3 Polyunsaturated fatty acids (n-3 PUFA) has been widely used in foods, and pharmaceutical products due to its beneficial effects. The content of n-3 PUFA in natural oils is usually low, which decreases its added value. Thus, there is an increasing demand on the market for n-3 PUFA concentrates. This review firstly introduces the differences in bioavailability and oxidative stability between different types of PUFA concentrate (free fatty acid, ethyl ester and acylglycerol), and then provides a comprehensive discussion of different methods for enrichment of lipids with n-3 PUFA including physical-chemical methods and enzymatic methods. Lipases used for catalyzing esterification, transesterification and hydrolysis reactions play an important role in the production of highly enriched various types of n-3 PUFA concentrates. Lipase-catalyzed alcoholysis or hydrolysis reactions are the mostly employed method to prepare high-quality n-3 PUFA of structural acylglycerols. Although many important advantages offered by lipases in enrichment of n-3 PUFA, the high cost of enzyme limits its industrial-scale production. Further research should focus on looking for biological enzymes with extraordinary catalytic ability and clear selectivity. Other novel technologies such as protein engineering and immobilization may be needed to modify lipases to improve its selectivity, catalytic ability and reuse.
ESTHER : Xie_2022_Crit.Rev.Food.Sci.Nutr__1
PubMedSearch : Xie_2022_Crit.Rev.Food.Sci.Nutr__1
PubMedID: 35699651

Title : Moringa Oleifera Alleviates Abeta Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP\/PS1 Mice - Mahaman_2022_Nutrients_14_
Author(s) : Mahaman YAR , Feng J , Huang F , Salissou MTM , Wang J , Liu R , Zhang B , Li H , Zhu F , Wang X
Ref : Nutrients , 14 : , 2022
Abstract : Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Abeta and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Abeta burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.
ESTHER : Mahaman_2022_Nutrients_14_
PubMedSearch : Mahaman_2022_Nutrients_14_
PubMedID: 36296969

Title : Bioactivity-Guided Separation of Anti-Cholinesterase Alkaloids from Uncaria rhynchophlly (Miq.) Miq. Ex Havil Based on HSCCC Coupled with Molecular Docking - Yu_2022_Molecules_27_2013
Author(s) : Yu P , Chen Z , Liu Y , Gu Z , Wang X , Zhang Y , Ma Y , Dong M , Tian Z
Ref : Molecules , 27 :2013 , 2022
Abstract : As an important source of cholinesterase inhibitors, alkaloids in natural products have high potential value in terms of exerting pharmacological activities. In this study, a strategy for targeted preparation of cholinesterase inhibitors in Uncaria rhynchophlly (Miq.) Miq. ex Havil (UR) by high-speed counter-current chromatography was provided. In the method, a two-phase polar solvent system composed of ethyl acetate/n-butanol/water (1:4:5, v/v/v) was used, which isolated five alkaloids from the UR extract for the first time. All alkaloids were identified by HR-ESI-MS and NMR as 7-epi-javaniside (1), vincosamide (2), strictosamide (3), cadambine (4), and 3alpha-dihydrocadambine (5). The poorly resolved compounds 2 and 3 were separated by preparative HPLC (prep-HPLC). Among them, compounds 1, 4, and 5 were firstly obtained from UR. The purity of these plant isolates was 98.8%, 98.7%, 99.2%, 95.7%, and 98.5%, respectively. Compounds 1-5 exhibited an inhibitory effect on acetyl-cholinesterase and butyryl-cholinesterase with an IC(50) from 1.47 to 23.24 microg/mL and 1.01 to 18.24 microg/mL. Molecular docking and inhibitory activities indicated that compound 1 showed stronger inhibitory activity on acetyl-cholinesterase and butyryl-cholinesterase.
ESTHER : Yu_2022_Molecules_27_2013
PubMedSearch : Yu_2022_Molecules_27_2013
PubMedID: 35335376

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

Title : Development and validation of a LC-MS\/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice - Yuan_2022_Biomed.Chromatogr__e5380
Author(s) : Yuan M , Hu W , Feng Y , Tong Y , Wang X , Tan B , Xu H , Liu J
Ref : Biomedical Chromatography , :e5380 , 2022
Abstract : Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. RDV is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5'-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an ACQUITY HSS T(3) column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1000 ng/mL for RDV, 5-10000 ng/mL for both RM-442 and RN, respectively. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442, and RSD < 7.2% for RN) and accuracy (91.0%-106.3% for RDV, 92.5%-98.6% for RM-442, and 87.5%-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in blood of normal and diabetic nephropathy DBA/2J mice after intravenous injection of RDV 20 mg/kg. The AUC(0-t) of RN between the normal and diabetic nephropathy mice had significant difference (P < 0.01).
ESTHER : Yuan_2022_Biomed.Chromatogr__e5380
PubMedSearch : Yuan_2022_Biomed.Chromatogr__e5380
PubMedID: 35373846

Title : Preparation of 2-Arachidonoylglycerol by Enzymatic Alcoholysis: Effects of Solvent and Water Activity on Acyl Migration - Wang_2022_Foods_11_3213
Author(s) : Wang X , Liu K , Wang Y , Huang Z
Ref : Foods , 11 :3213 , 2022
Abstract : Enzymatic alcoholysis was performed in an organic medium to synthesize 2-monoacylglycerol (2-MAG) rich in arachidonic acid. The results showed that solvent type and water activity (a(w)) significantly affected the 2-MAG yield. Under the optimum conditions, 33.58% 2-MAG was produced in the crude product in t-butanol system. Highly pure 2-MAG was obtained after two-stage extraction using 85% ethanol aqueous solution and hexane at first stage and dichloromethane and water at second stage. Isolated 2-MAG was used as substrate to investigate the effect of solvent type and a(w) on 2-MAG acyl migration in a lipase-inactivated system. The results indicated that non-polar solvents accelerated the acyl migration of 2-MAG, whereas isomerization was inhibited in polar solvent systems. The a(w) exhibited the strongest inhibition effect on 2-MAG isomerization at 0.97, but also affected the hydrolysis of glycerides and lipase selectivity.
ESTHER : Wang_2022_Foods_11_3213
PubMedSearch : Wang_2022_Foods_11_3213
PubMedID: 37430962

Title : Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins - Liu_2022_J.Transl.Med_20_418
Author(s) : Liu X , Hua F , Yang D , Lin Y , Zhang L , Ying J , Sheng H , Wang X
Ref : J Transl Med , 20 :418 , 2022
Abstract : Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.
ESTHER : Liu_2022_J.Transl.Med_20_418
PubMedSearch : Liu_2022_J.Transl.Med_20_418
PubMedID: 36088343

Title : Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues - Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
Author(s) : Zhang X , Xu W , Xu R , Wang Z , Wang P , Peng K , Li M , Li J , Tan Y , Wang X , Pei H
Ref : Oxid Med Cell Longev , 2022 :4594956 , 2022
Abstract : Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection.
ESTHER : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedSearch : Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956
PubMedID: 35401929

Title : Recent advances of chemosensors for nerve agents - Wang_2022_Chem.Asian.J__
Author(s) : Wang X , Feng R , Fu T , Zhang J , Sun X
Ref : Chem Asian J , : , 2022
Abstract : Nerve agents are a branch of organophosphorus (OP) compounds that chemically cause irreversible inhibition of acetylcholinesterase, thereby failing the hydrolysis of acetylcholine, resulting in severe neurological disease and death in organisms. Thus, the unreasonable use of such compounds threatens public and national security, so it is a high demand to establish portable, low-cost, sensitive, and highly selective methods for their precise detection. In this review, we introduced the recent development of spectroscopy-based optical chemosensors that aimed for the detection of nerve agent, focusing on the progress made in the molecular design, sensing principle and applications. We also conclude this Review by highlighting the current challenges associated with the future development and outlook.
ESTHER : Wang_2022_Chem.Asian.J__
PubMedSearch : Wang_2022_Chem.Asian.J__
PubMedID: 35599234

Title : The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution - Yang_2022_Front.Neurol_13_900997
Author(s) : Yang X , Dang P , Liu W , Ma W , Ge X , Zhu K , Wang M , Huang X , Ding X , Wang X
Ref : Front Neurol , 13 :900997 , 2022
Abstract : BACKGROUND AND AIMS: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. MATERIALS AND METHODS: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. RESULTS: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). CONCLUSION: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE.
ESTHER : Yang_2022_Front.Neurol_13_900997
PubMedSearch : Yang_2022_Front.Neurol_13_900997
PubMedID: 36341087

Title : Identification of regulatory variants of carboxylesterase 1 (CES1): A proof-of-concept study for the application of the Allele-Specific Protein Expression (ASPE) assay in identifying cis-acting regulatory genetic polymorphisms - Her_2022_Proteomics__e2200176
Author(s) : Her L , Shi J , Wang X , He B , Smith L , Jiang H , Zhu HJ
Ref : Proteomics , :e2200176 , 2022
Abstract : It is challenging to study regulatory genetic variants as gene expression is affected by both genetic polymorphisms and non-genetic regulators. The mRNA allele-specific expression (ASE) assay has been increasingly used for the study of cis-acting regulatory variants because cis-acting variants affect gene expression in an allele-specific manner. However, poor correlations between mRNA and protein expressions were observed for many genes, highlighting the importance of studying gene expression regulation at the protein level. In the present study, we conducted a proof-of-concept study to utilize a recently developed allele-specific protein expression (ASPE) assay to identify the cis-acting regulatory variants of CES1 using a large set of human liver samples. The CES1 gene encodes for carboxylesterase 1 (CES1), the most abundant hepatic hydrolase in humans. Two cis-acting regulatory variants were found to be significantly associated with CES1 ASPE, CES1 protein expression, and its catalytic activity on enalapril hydrolysis in human livers. Compared to conventional gene expression-based approaches, ASPE demonstrated an improved statistical power to detect regulatory variants with small effect sizes since allelic protein expression ratios are less prone to the influence of non-genetic regulators (e.g., diseases and inducers). This study suggests that the ASPE approach is a powerful tool for identifying cis-regulatory variants. This article is protected by copyright. All rights reserved.
ESTHER : Her_2022_Proteomics__e2200176
PubMedSearch : Her_2022_Proteomics__e2200176
PubMedID: 36413357
Gene_locus related to this paper: human-CES1

Title : Role of epoxyeicosatrienoic acids in cardiovascular diseases and cardiotoxicity of drugs - Zhang_2022_Life.Sci_310_121122
Author(s) : Zhang Y , Gao L , Yao B , Huang S , Liu J , Liu Z , Wang X
Ref : Life Sciences , 310 :121122 , 2022
Abstract : Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs. Therefore, the regulation of CYP and sEH enzymes on EETs points out the direction for exploring EET-mediated cardiac protection. The metabolic pathway of EETs is not only an important target for the development of new drugs for CVD but also an important factor in preventing drug cardiotoxicity. The development and clinical application of sEH inhibitors and EETs analogues provide broad prospects for the treatment of CVD.
ESTHER : Zhang_2022_Life.Sci_310_121122
PubMedSearch : Zhang_2022_Life.Sci_310_121122
PubMedID: 36309225

Title : The protein conformational basis of isoflavone biosynthesis - Wang_2022_Commun.Biol_5_1249
Author(s) : Wang X , Pan H , Sagurthi S , Paris V , Zhuo C , Dixon RA
Ref : Commun Biol , 5 :1249 , 2022
Abstract : Isoflavonoids play important roles in plant defense and also exhibit a range of mammalian health-promoting activities. Their biosynthesis is initiated by two enzymes with unusual catalytic activities; 2-hydroxyisoflavanone synthase (2-HIS), a membrane-bound cytochrome P450 catalyzing a coupled aryl-ring migration and hydroxylation, and 2-hydroxyisoflavanone dehydratase (2-HID), a member of a large carboxylesterase family that paradoxically catalyzes dehydration of 2-hydroxyisoflavanones to isoflavone. Here we report the crystal structures of 2-HIS from Medicago truncatula and 2-HID from Pueraria lobata. The 2-HIS structure reveals a unique cytochrome P450 conformation and heme and substrate binding mode that facilitate the coupled aryl-ring migration and hydroxylation reactions. The 2-HID structure reveals the active site architecture and putative catalytic residues for the dual dehydratase and carboxylesterase activities. Mutagenesis studies revealed key residues involved in substrate binding and specificity. Understanding the structural basis of isoflavone biosynthesis will facilitate the engineering of new bioactive isoflavonoids.
ESTHER : Wang_2022_Commun.Biol_5_1249
PubMedSearch : Wang_2022_Commun.Biol_5_1249
PubMedID: 36376429
Gene_locus related to this paper: pueml-e9m5g1

Title : Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients - Zhou_2022_Aging.Clin.Exp.Res__
Author(s) : Zhou Q , Yu L , Yin C , Zhang Q , Wang X , Kang K , Shao D , Wang Q
Ref : Aging Clin Exp Res , : , 2022
Abstract : BACKGROUND: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA). METHODS: A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-alpha, IL-1beta, IL-6, and HMGB1) and brain damage factor S100beta. RESULTS: Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100beta after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-alpha between the two groups. CONCLUSION: The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity.
ESTHER : Zhou_2022_Aging.Clin.Exp.Res__
PubMedSearch : Zhou_2022_Aging.Clin.Exp.Res__
PubMedID: 35809206

Title : Polygoni multiflori radix extracts inhibit SARS-CoV-2 pseudovirus entry in HEK293T cells and zebrafish larvae - Wang_2022_Phytomedicine_102_154154
Author(s) : Wang X , Lin S , Tang RW , Lee HC , Chan HH , Choi SSA , Leung KW , Webb SE , Miller AL , Tsim KWK
Ref : Phytomedicine , 102 :154154 , 2022
Abstract : BACKGROUND: Globally, COVID-19 has caused millions of deaths and led to unprecedented socioeconomic damage. There is therefore, in addition to vaccination, an urgent need to develop complementary effective treatments and/or protective and preventative therapies against this deadly disease. METHODS: Here, a multi-component testing platform was established to screen a library of herbal extracts from traditional Chinese medicine (TCM), to identify potent herbal extracts/phytochemicals as possible therapeutics for COVID-19. We utilized assays for spike protein (S-protein) binding to angiotensin-converting enzyme II (ACE2); the enzymatic inhibition of 3CL protease; and entry of the SARS-CoV-2 pseudovirus into cultured HEK293T cells and zebrafish larvae. RESULTS: Over a thousand herbal extracts were screened and approximately 20 positive hits were identified. Among these, we found that the water and ethanol extracts of Polygoni Multiflori Radix (PMR) significantly inhibited S-protein binding to ACE2, 3CL protease activity, and viral entry into the cell and fish models. The water extract was more effective than the ethanol extract, with IC(50) values of 25 to 500 microg/ml. In addition, the polysaccharide-depleted fraction of the former, and epigallocatechin gallate (EGCG) which was found in both extracts, displayed significant antiviral activity. CONCLUSIONS: Our results indicate that the water and ethanol extracts of PMR have an inhibitory effect on SARS-CoV-2 pseudovirus host-cell entry. Furthermore, EGCG might be an active component of PMR, which blocks SARS-CoV-2 entry to cells. Taken together, our findings suggest that PMR might be considered as a potential treatment for COVID-19.
ESTHER : Wang_2022_Phytomedicine_102_154154
PubMedSearch : Wang_2022_Phytomedicine_102_154154
PubMedID: 35576740

Title : Emerging Mosquito Resistance to Piperonyl Butoxide-Synergized Pyrethroid Insecticide and Its Mechanism - Zhou_2022_J.Med.Entomol__
Author(s) : Zhou G , Li Y , Jeang B , Wang X , Cummings RF , Zhong D , Yan G
Ref : Journal of Medical Entomology , : , 2022
Abstract : Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito resistance after pre-exposure to PBO and subsequent enzymatic activity when exposed to PBO-synergized insecticides. We used Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of arboviruses and lymphatic filariasis, as a model to examine the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions pre- and post-PBO exposure. Mosquito eggs and larvae were collected from three cities in Orange County in July 2020 and reared in insectary, and F0 adults were used in this study. A JHB susceptible strain was used as a control. Mosquito mortalities and metabolic enzyme expressions were examined in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. Except for malathion, wild strain Cx quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality range 3.7 +/- 4.7% to 66.7 +/- 7.7%). Wild strain mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When wild strain mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compared to 0.02% for a susceptible strain. The knockdown resistance gene mutation (L1014F) rate was 62% in wild strain mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34% and GST by 11%, but had no impact on COE enzyme expression. Even with an optimal PBO concentration (7%) and exposure duration (3h), wild strain mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to the susceptible laboratory strain. These results further demonstrate other studies that PBO alone may not be enough to control highly pyrethroid-resistant mosquitoes due to multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored through a routine resistance management program for effective control of mosquitoes and the pathogens they transmit.
ESTHER : Zhou_2022_J.Med.Entomol__
PubMedSearch : Zhou_2022_J.Med.Entomol__
PubMedID: 35050361

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Enrichment of polystyrene microplastics induces histological damage, oxidative stress, Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus) - Wang_2022_Ecotoxicol.Environ.Saf_237_113540
Author(s) : Wang X , Jian S , Zhang S , Wu D , Wang J , Gao M , Sheng J , Hong Y
Ref : Ecotoxicology & Environmental Safety , 237 :113540 , 2022
Abstract : Polystyrene microplastics (PS-MPs, particle size<5 mm) cause great harm to aquatic organisms. However, their precise effects are not completely understood. In China, placing plastic film at the pond bottom has become an important loach aquaculture mode. In this mode, MPs will affect loach health. This study investigated the enrichment of PS-MPs and its effects on the growth, liver histomorphology, antioxidant enzymes, and Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus). The loach juveniles were raised at the concentration of 1000 microg/L fluorescent polystyrene microplastics (PS-MPs) with particle size of 0.5 microm or 5 microm for seven days, the results showed that fluorescent PS-MPs were found to be enriched in liver, intestine, and gill, and the enrichment amount was higher in liver than in gill and intestine (P < 0.05). Furthermore, the enrichment amount of different-sized PS-MPs was different in liver, gill, and intestine. The loach juveniles were cultured for 21 days in the water of the concentration of 100 or 1000 microg/L PS-MPs with particle size of 0.5 microm or 5 microm, the results showed that the survival rate, weight gain rate, and specific growth rate of loach juveniles were significantly reduced. The histological analysis revealed that PS-MPs caused liver damage. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and acetylcholinesterase (AChE) were decreased with the extended exposure to PS-MPs. Generally, the expressions of Nrf2 and Keap1 showed the similar change trend. From 7-14 day, the expression trend of oxidative stressed-related genes was not completely consistent with that of Nrf2 gene, but on day 21, the gene expression trend of oxidative stress-related SOD, CAT, and GSH-PX in the downstream of Keap1-Nrf2 signaling pathway was roughly consistent with that of Nrf2 gene. Basically, the change trends of these three gene expression were similar to those of their corresponding enzyme activities. This study provides theoretical basis for the toxicological effects of PS-MPs on freshwater fish.
ESTHER : Wang_2022_Ecotoxicol.Environ.Saf_237_113540
PubMedSearch : Wang_2022_Ecotoxicol.Environ.Saf_237_113540
PubMedID: 35453027

Title : Simultaneous Inhibitory Effects of All-Trans Astaxanthin on Acetylcholinesterase and Oxidative Stress - Wang_2022_Mar.Drugs_20_
Author(s) : Wang X , Zhang T , Chen X , Xu Y , Li Z , Yang Y , Du X , Jiang Z , Ni H
Ref : Mar Drugs , 20 : , 2022
Abstract : Alzheimers disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC(50) value) of 8.64 micromol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimers disease prevention.
ESTHER : Wang_2022_Mar.Drugs_20_
PubMedSearch : Wang_2022_Mar.Drugs_20_
PubMedID: 35447920

Title : Pisa syndrome in dementia with Lewy bodies: A Chinese multicenter study - Su_2022_Parkinsonism.Relat.Disord_103_50
Author(s) : Su Z , Liu S , Chen G , Gan J , Bao X , Zhu H , Wang X , Wu H , Ji Y
Ref : Parkinsonism Relat Disord , 103 :50 , 2022
Abstract : BACKGROUND: Pisa syndrome (PS) is rarely reported in Dementia with Lewy bodies (DLB). The aim of this article is to investigate the prevalence rate of PS and the correlation with clinical features evaluated in patients with DLB. METHODS: A total of 209 DLB patients were consecutively recruited and underwent standardized clinical evaluation in our multicenter study. The associations between PS and clinical factors were evaluated. RESULTS: The prevalence rate of PS in patients with DLB was 15.3%, which was higher in the moderate and severe stages than mild cognitive impairment and mild stages (81.2% vs. 18.8%). Patients with PS had a longer duration of disease (P = 0.020) and parkinsonism (P = 0.003), higher scores of NPI (P = 0.028), ADL (P = 0.002) and UPDRS part III (P < 0.001), lower scores of clock drawing test (P = 0.009), visuospatial/executive abilities (P = 0.018), attention (P = 0.020), language and praxis (P = 0.020), registration (P = 0.012), greater H&Y stage (P < 0.001), and higher proportion of cholinesterase inhibitors used (P = 0.044) than those without PS. Longer disease duration (OR = 1.166, P = 0.023), presence of parkinsonism (OR = 7.971, P = 0.007), moderate and severe dementia (OR = 3.215, P = 0.021) were associated with the presence of PS. Patients had a longer duration of PS (P = 0.014) and lower mean age of onset (P = 0.040) in the group with severe lateral trunk flexion. CONCLUSION: The development of PS may be associated with longer disease duration, the presence of parkinsonism and severe stages of dementia in DLB. Cholinesterase inhibitors may have a correlation with PS. The severity of lateral flexion is related to the duration of PS and mean age of onset.
ESTHER : Su_2022_Parkinsonism.Relat.Disord_103_50
PubMedSearch : Su_2022_Parkinsonism.Relat.Disord_103_50
PubMedID: 36041278

Title : Integrative assessment of biomarker responses in Mytilus galloprovincialis exposed to seawater acidification and copper ions - Qu_2022_Sci.Total.Environ_851_158146
Author(s) : Qu Y , Zhang T , Zhang R , Wang X , Zhang Q , Wang Q , Dong Z , Zhao J
Ref : Sci Total Environ , 851 :158146 , 2022
Abstract : The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 microg/L and 50 microg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered.
ESTHER : Qu_2022_Sci.Total.Environ_851_158146
PubMedSearch : Qu_2022_Sci.Total.Environ_851_158146
PubMedID: 35987231

Title : Development of a pH-Responsive, SO(4)(2-)-loaded Fe and N co-doped carbon quantum dots-based fluorescent method for highly sensitive detection of glyphosate - Peng_2022_Anal.Chim.Acta_1221_340110
Author(s) : Peng Z , Zeng M , Wu S , Yan Z , Rui J , Qiu P , Wang X
Ref : Anal Chim Acta , 1221 :340110 , 2022
Abstract : A novel sulfate-loaded iron-nitrogen co-doped carbon quantum dots (SO(4)(2-)-CQDs)-based fluorescent method was synthesized by the facile and environmentally friendly pyrolysis of persimmon frost (carbon source) and (NH(4))(2)Fe(SO(4))(2).6H(2)O. After SMMC-7721 cells were incubated with the SO(4)(2-)-CQDs for 24 h, more than 95% of the cells remained viable, even at a high concentration of the SO(4)(2-)-CQDs, indicating excellent biocompatibility and low toxicity. In addition, it was able to be taken up by the cells to emit their bright blue fluorescence after excitation at 365 nm, indicating suitable cell permeability. The SO(4)(2-)-CQDs also exhibited a unique response to changes in pH, which was applied in the detection of OPs by relying on the production of acetic acid from the hydrolysis of acetylcholine (ACh) by acetylcholinesterase (AChE), which decreased the pH and engendered an increase in the fluorescence of the SO(4)(2-)-CQDs; however, the inhibition of AChE by glyphosate resulted in little influence on fluorescence intensity due to the lack of acetic acid produced. This mechanism was the basis for the development of a sensitive assay for the detection of glyphosate. The resulting assay had a limit of detection of 0.066 ng/mL. Furthermore, the method was successfully applied for the precise and accurate monitoring of the concentration, distribution, and variation of glyphosate residues in chives and cultivated soil. Therefore, the proposed method was anticipated to provide a promising alternative for other detection methods to enable the reliable analysis of OPs in food products.
ESTHER : Peng_2022_Anal.Chim.Acta_1221_340110
PubMedSearch : Peng_2022_Anal.Chim.Acta_1221_340110
PubMedID: 35934352

Title : Tissue-specific accumulation, depuration, and effects of perfluorooctanoic acid on fish: Influences of aqueous pH and sex - Dong_2022_Sci.Total.Environ__160567
Author(s) : Dong H , Lu G , Wang X , Zhang P , Yang H , Yan Z , Liu J , Jiang R
Ref : Sci Total Environ , :160567 , 2022
Abstract : Perfluorooctanoic acid (PFOA) is widely distributed in nature, particularly in aquatic environments. Its bioaccumulation and toxicity in aquatic organisms can be affected by both the chemical status of PFOA in water and the physiology of the organism. However, research on the patterns of these effects is scarce. In this study, we investigated the influence of aqueous pH (pH 6, acidic; pH 7.5, neutral; pH 9, basic) and fish sex on PFOA uptake, clearance, and biochemical effects in crucian carp (C. auratus) using flow-through exposure. In the 17-d kinetic experiment, PFOA bioaccumulation adhered to a uniform first-order model in which PFOA uptake rates from water to blood and liver in acidic conditions were faster than those in other conditions, indicating possible acidic pH influence on PFOA uptake. PFOA clearance rates in these compartments of males were slower than in females, which was attributed to the notably stronger expression of Oat2 (organic anion transporter 2, responsible for reabsorption) in the kidneys of males. Similar responses were observed for peroxisome proliferation-related biomarkers at different pH levels and in different sexes. These biochemical responses were driven by the internal concentrations of PFOA. The inhibition acetylcholinesterase activity in the fish brain was closely linked to changes in P-glycoprotein content, demonstrating a protective relationship. Collectively, an aqueous pH lower than 7.5 might affect the uptake of PFOA by fish. The clearance discrepancies between the sexes highlight the importance of anion carriers for ionizable organic compounds in aquatic organisms.
ESTHER : Dong_2022_Sci.Total.Environ__160567
PubMedSearch : Dong_2022_Sci.Total.Environ__160567
PubMedID: 36455738

Title : Resistance selection of triflumezopyrim in Laodelphax striatellus (falln): Resistance risk, cross-resistance and metabolic mechanism - Wen_2022_Front.Physiol_13_1048208
Author(s) : Wen S , Liu C , Wang X , Wang Y , Wang J , Xia X
Ref : Front Physiol , 13 :1048208 , 2022
Abstract : The risk assessment and resistance mechanisms of insecticide resistance are critical for resistance management strategy before a new insecticide is widely used. Triflumezopyrim (TFM) is the first commercialized mesoionic insecticide, which can inhibit nicotinic acetylcholine receptor with high-performance against the small brown planthopper (SBPH), Laodelphax striatellus (Fallen). In our study, the resistance of SBPH to TFM increased 26.29-fold, and the actual heritability of resistance was 0.09 after 21 generations of continuous selection by TFM. After five generations of constant feeding under insecticide-free conditions from F(16) generation, the resistance level decreased 2.05-fold, and the average resistance decline rate per generation was 0.01, but there were no statistical decline. The TFM resistant strains had no cross-resistance to imidacloprid, nitenpyram, thiamethoxam, dinotefuran, flonicamid, pymetrozine, and chlorfenapyr. The third and fifth nymphal stage duration, pre-adult stage, adult preoviposition period, longevity, emergence rate, and hatchability of the resistant strain were significantly lower than those of the susceptible strain, while the female-male ratio was considerably increased. The fitness cost was 0.89. Further, cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) activities were markedly increased, but only the enzyme inhibitor piperonyl butoxide (PBO) had a significant synergistic effect on the resistant strain. The expression of CYP303A1, CYP4CE2, and CYP419A1v2 of P450 genes was significantly increased. SBPH has a certain risk of resistance to TFM with continuous application. The TFM resistance may be due to the increased activity of P450 enzyme regulated by the overexpression of P450 genes.
ESTHER : Wen_2022_Front.Physiol_13_1048208
PubMedSearch : Wen_2022_Front.Physiol_13_1048208
PubMedID: 36523557

Title : Acute thiamethoxam exposure induces hepatotoxicity and neurotoxicity in juvenile Chinese mitten crab (Eriocheir sinensis) - Yang_2022_Ecotoxicol.Environ.Saf_249_114399
Author(s) : Yang Y , Yu Q , Zhang C , Wang X , He L , Huang Y , Li E , Qin J , Chen L
Ref : Ecotoxicology & Environmental Safety , 249 :114399 , 2022
Abstract : The similar nervous system structure between crustaceans and insects and the high-water solubility of thiamethoxam can lead to the more severe toxicity of thiamethoxam to crustaceans. However, the effects of thiamethoxam on crustaceans are unclear. Therefore, a 96-h acute toxicity test was performed to explore the hepatotoxicity and neurotoxicity effects of thiamethoxam on Chinese mitten crab (Eriocheir sinensis) at concentrations 0 microg/L, 150 microg/L and 300 microg/L. The antioxidant and detoxification systems (including phases I and II) were significantly activated after exposure of juvenile crabs to thiamethoxam for 24sh in 300 microg/L group, whereas the toxic activation effect in 150 microg/L group was delayed. Moreover, a similar pattern was observed for the transcription levels of immune-related genes. Further analysis of inflammatory signaling pathway-related genes showed that thiamethoxam exposure with 300 microg/L for 24sh may induce a pro-inflammatory response through the NF-kappaB pathway. In contrast, the gene expression levels in 150 microg/L group were significantly upregulated compared with 0 microg/L group after 96sh. In addition, although the acute exposure of 150 microg/L thiamethoxam did not seem to induce significant neurotoxicity, the acetylcholinesterase activity was significantly decreased in 300 microg/L group after thiamethoxam exposure for 96sh. Correspondingly, thiamethoxam exposure with 300 microg/L for 24sh resulted in significantly downregulated transcriptional levels of synaptic transmission-related genes (e.g. dopamine-, gamma-aminobutyric acid- and serotonin-related receptors). Therefore, thiamethoxam may be harmful and cause potential toxic threats such as neurotoxicity and metabolic damage to crustaceans.
ESTHER : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedSearch : Yang_2022_Ecotoxicol.Environ.Saf_249_114399
PubMedID: 36508784

Title : Effects of short-term exposure to tralopyril on physiological indexes and endocrine function in turbot (Scophthalmus maximus) - Liu_2022_Aquat.Toxicol_245_106118
Author(s) : Liu B , Li P , He S , Xing S , Cao Z , Cao X , Wang X , Li ZH
Ref : Aquat Toxicol , 245 :106118 , 2022
Abstract : Tralopyril is an emerging marine antifouling agent with potential toxic effects on non-target aquatic organisms. To evaluate the toxicity of tralopyril, to turbot (Scophthalmus maximus), we assessed biomarkers, including oxidative stress, neurotoxicity, and osmotic homeostasis regulation enzymes, after a 7-day exposure to tralopyril (5 microg/L, 15 microg/L, 30 microg/L). Superoxide dismutase activity was significantly decreased at 30 microg/L, and Ca(2+)-Mg(2+)-ATPase activity in the gills was significantly increased at 15 microg/L and 30 microg/L. No statistically significant differences in the responses of acetylcholinesterase and nitric oxide were detected. In addition, 15 microg/L and 30 microg/L tralopyril induced hyperthyroidism, reflected by significantly increased of T3 levels. The expression levels of hypothalamus-pituitary-thyroid axis-related genes were also upregulated. The molecular docking results showed that the thyroid system disruption was not caused by competitive binding to the receptor. In addition, the integrated biomarker response index showed that 15 microg/L tralopyril had the greatest effect on turbot. In general, tralopyril caused oxidative damage, affected energy metabolism, and interfered with the endocrine system. These findings could provide reference data for assessing the ecological risk of tralopyril in marine environments.
ESTHER : Liu_2022_Aquat.Toxicol_245_106118
PubMedSearch : Liu_2022_Aquat.Toxicol_245_106118
PubMedID: 35176693

Title : Single-atom Ce-N-C nanozyme bioactive paper with a 3D-printed platform for rapid detection of organophosphorus and carbamate pesticide residues - Song_2022_Food.Chem_387_132896
Author(s) : Song G , Zhang J , Huang H , Wang X , He X , Luo Y , Li JC , Huang K , Cheng N
Ref : Food Chem , 387 :132896 , 2022
Abstract : Rapid detection of pesticide residues based on enzyme mimics has recently attracted much interest. However, most nanozymes have low activity. Herein, a "single-atom Ce-N-C nanozyme" (SACe-N-C nanozyme) was rationally devised and verified to mimic peroxidase (POD-like) with superior activity. Based on its high POD-like activities and cascaded catalytic reactions with acetylcholinesterase (AChE), we constructed a bioactive paper for the detection of pesticide residues, which offered a portable approach to monitor fruits and vegetables within 30 min. More importantly, a 3D printed platform was integrated on the basis of SACe-N-C bioactive paper to achieve on-site portable testing of omethoate, methamidophos, carbofuran, and carbosulfan, showing limits of detection (LODs) of 55.83, 71.51, 81.81, and 74.98 ng/mL, respectively. The recovery rates were 84.09-104.68%. This study provided new insight into the design of novel single-atom nanozymes for cascaded catalytic detection and other rapid detection applications with high efficiency and low cost.
ESTHER : Song_2022_Food.Chem_387_132896
PubMedSearch : Song_2022_Food.Chem_387_132896
PubMedID: 35421648

Title : Chlorophyll Inhibits the Digestion of Soybean Oil in Simulated Human Gastrointestinal System - Wang_2022_Nutrients_14_
Author(s) : Wang X , Li Y , Shen S , Yang Z , Zhang H , Zhang Y
Ref : Nutrients , 14 : , 2022
Abstract : Nowadays, much available processed and highly palatable food such as cream products and fried and convenient food, which usually showed a high energy density, had caused an increase in the intake of dietary lipids, further leading to significant growth in the prevalence of obesity. Chlorophyll, widespread in fruits and vegetables, was proven to have beneficial effects on alleviating obesity. This study investigated the effects of chlorophyll on the digestive characteristics of lipids under in vitro simulated adult and infant gastrointestinal systems. Chlorophyll decreased the release rate of free fatty acid (FFA) during in vitro adult and infant intestinal digestion by 69.2% and 60.0%, respectively. Meanwhile, after gastrointestinal digestion, chlorophyll changed the FFA composition of soybean oil emulsion and increased the particle size of oil droplets. Interestingly, with the addition of chlorophyll, the activity of pancreatic lipase was inhibited during digestion, which may be related to pheophytin (a derivative of chlorophyll after gastric digestion). Therefore, the results obtained from isothermal titration calorimetry and molecular docking further elucidated that pheophytin could bind to pancreatic lipase with a strong affinity of (4.38 +/- 0.76) x 10(7) M(-1) (K(a)), while the binding site was amino acid residue Trp253. The investigation not only explained why chlorophyll inhibited digestive enzyme activity to reduce lipids digestion but also provided exciting opportunities for developing novel chlorophyll-based healthy products for dietary application in preventing obesity.
ESTHER : Wang_2022_Nutrients_14_
PubMedSearch : Wang_2022_Nutrients_14_
PubMedID: 35565719

Title : Study on the toxic-mechanism of triclosan chronic exposure to zebrafish (Danio rerio) based on gut-brain axis - Wang_2022_Sci.Total.Environ__156936
Author(s) : Wang Y , Song J , Wang X , Qian Q , Wang H
Ref : Sci Total Environ , :156936 , 2022
Abstract : Triclosan (TCS), as a broad-spectrum bactericide, is extensively used in the fine chemical and textile industries. It is recognized as a new type of environmental endocrine disruptor with frequent detection and environmental pollution. However, the toxicity mechanism regarding neurodevelopment and neurobehavior remains unclear. This study is intended to explore the underlying toxic mechanism of TCS based on gut-brain axis. TCS-chronic exposure affected the development of zebrafish, induced feminization, obesity physical signs and abnormal organ index and caused neurobehavioral abnormalities by inhibiting both neurotransmitter acetylcholinesterase and dopamine activity, promoting brain neuron apoptosis and accelerating diencephalic lesions. Meanwhile, TCS-chronic exposure led to gut microbiota dysbiosis and decreased diversity, such as increased pathogenic bacteria and decreased probiotics in adult zebrafish gut, which caused many pathological damages, including partial shedding and ablation of intestinal villi, inflammatory infiltration, thinning of intestinal wall, and increased goblet cell in villus. Based on the communication between intestinal peripheral nerves and CNS, the above histopathological injuries and disorders were well underpinned and illustrated by the changes of biomarkers and the expression of related marker genes in the gut-brain axis. Additionally, short-chain fatty acids (SCFA), as the regulators of intestinal sympathetic nerve activation, are also secreting products of intestinal microflora and play a crucial role in regulating the balance of intestinal flora and protecting intestinal homeostasis. SCFA in low doses can effectively alleviate and rescue the toxic effects under TCS exposure, which evidenced that TCS exerted systemic toxic effects on the gut-brain axis by influencing the composition and diversity of gut flora in zebrafish, and fully demonstrated the interaction effect between intestine and brain. Hence, these findings contribute to the understanding, prevention, and diagnosis of endocrine disrupting diseases caused by environmental pollutants from the perspective of the gut-brain axis, and strengthening the early warning, management and control of TCS pollution.
ESTHER : Wang_2022_Sci.Total.Environ__156936
PubMedSearch : Wang_2022_Sci.Total.Environ__156936
PubMedID: 35772538

Title : A novel electrochemical sensing platform based on the esterase extracted from kidney bean for high-sensitivity determination of organophosphorus pesticides - Tao_2022_RSC.Adv_12_5265
Author(s) : Tao H , Liu F , Ji C , Wu Y , Wang X , Shi Q
Ref : RSC Adv , 12 :5265 , 2022
Abstract : Similar to acetylcholinesterase, the activity of plant-derived esterase can also be inhibited by organophosphorus pesticides. Therefore, an electrochemical sensing platform using kidney bean esterase as a new detection enzyme was proposed for the highly sensitive determination of organophosphorus pesticides. Purified kidney bean esterase was obtained by an efficient and economical aqueous two-phase extraction method. Carboxylated graphene/carbon nanotube composites (cCNTs-cGR) and Au nanoparticles were used to provide a biocompatible environment to immobilize kidney bean esterase and also accelerate electron transport between the analyte and the electrode surface. Due to the good synergistic electrocatalytic effects of these nanomaterials, the biosensor exhibited an amplified electrocatalytic response to the oxidation of alpha-naphthalenol, which makes the sensor more sensitive. Based on the inhibitory effect of trichlorfon on kidney bean esterase activity, high sensitivity and low-cost detection of trichlorfon was achieved. Under optimum conditions, the inhibition of trichlorfon is proportional to its concentration in the range of 5 to 150 ng L(-1) and 150 ng L(-1) to 700 ng L(-1) with an ultra-low detection limit of 3 ng L(-1). Moreover, the validity of the prepared biosensor was verified by analyzing several actual agricultural products (cabbage and rice) with satisfactory recoveries ranging from 94.05% to 106.76%, indicating that kidney bean esterase is a promising enzyme source for the analysis of organophosphorus pesticides in food samples.
ESTHER : Tao_2022_RSC.Adv_12_5265
PubMedSearch : Tao_2022_RSC.Adv_12_5265
PubMedID: 35425578

Title : Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour - Chen_2022_Phytochemistry_196_113089
Author(s) : Chen SQ , Jia J , Hu JY , Wu J , Sun WT , Zheng M , Wang X , Zhu KK , Jiang CS , Yang SP , Zhang J , Wang SB , Cai YS
Ref : Phytochemistry , 196 :113089 , 2022
Abstract : Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC(50) values of 2.61, 1.19, and 1.74 microM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 microg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC(50) of 20.06 microM) and alpha-glycosidase inhibitor (IC(50) of 17.18 microM), while tabernamine, ervahanine B, and ervadivaricatine B only showed alpha-glycosidase inhibitory activities with IC(50) values in the range of 0.95-4.61 microM.
ESTHER : Chen_2022_Phytochemistry_196_113089
PubMedSearch : Chen_2022_Phytochemistry_196_113089
PubMedID: 35074605

Title : Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer - Wang_2022_BMC.Cancer_22_635
Author(s) : Wang Y , Fang T , Yin X , Zhang L , Zhang X , Zhang D , Zhang Y , Wang X , Wang H , Xue Y
Ref : BMC Cancer , 22 :635 , 2022
Abstract : BACKGROUND: The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. METHODS: We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. RESULTS: Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. CONCLUSION: AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.
ESTHER : Wang_2022_BMC.Cancer_22_635
PubMedSearch : Wang_2022_BMC.Cancer_22_635
PubMedID: 35681154
Gene_locus related to this paper: human-AADAC

Title : Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer - Xu_2022_Ann.Transl.Med_10_169
Author(s) : Xu Y , Wang X , Chu Y , Li J , Wang W , Hu X , Zhou F , Zhang H , Zhou L , Kuai R , Jin Y , Yang D , Peng H
Ref : Ann Transl Med , 10 :169 , 2022
Abstract : BACKGROUND: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. METHODS: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). RESULTS: A total of 237 significantly differentially expressed genes (P(adj)<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. CONCLUSIONS: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
ESTHER : Xu_2022_Ann.Transl.Med_10_169
PubMedSearch : Xu_2022_Ann.Transl.Med_10_169
PubMedID: 35280417

Title : Kinetics, Thermodynamics and Mechanism of Enzymatic Degradation of Zearalenone in Degummed Corn Oil - Zhao_2022_Toxins.(Basel)_15_
Author(s) : Zhao C , Xie P , Jin J , Jin Q , Wang X
Ref : Toxins (Basel) , 15 : , 2022
Abstract : The kinetics and thermodynamics of the enzymatic degradation of zearalenone (ZEN) in degummed corn oil were investigated by analyzing the impacts of temperature, pH, ZEN hydrolase dosage and ZEN concentration on the initial reaction rate. The kinetic study found that the maximum reaction rate was 0.97 micromol x kg1 min1, the Michaelis constant (Km) was 11,476 micromol x kg1 and the Michaelis equation was V = 0.97[S]/(11,476 + [S]). The thermodynamic study showed that the activation energy (Ea) was 70.37 kJ.mol1, the activation enthalpy change of the reaction (deltaH) > 0, the free energy of activation (deltaG) > 0 and the activation entropy change (deltaS) < 0, indicating the reaction could not be spontaneous. The reaction mechanism of ZEN was studied by a hybrid quadrupole orbitrap mass spectrometer. It was found that ZEN first generated the intermediate G/L/D/W-ZEN+H2O, followed by generating the intermediate W-ZEN-H2O under the action of a degrading enzyme. Then, the lactone bond was opened to produce C18H24O6, and finally the decarboxylation product C17H24O4 formed automatically.
ESTHER : Zhao_2022_Toxins.(Basel)_15_
PubMedSearch : Zhao_2022_Toxins.(Basel)_15_
PubMedID: 36668839

Title : Removal of Zearalenone from Degummed Corn Oil by Hydrolase on a Batch-Refining Unit - Zhao_2022_Foods_11_
Author(s) : Zhao C , Xie P , Jin J , Jin Q , Wang X
Ref : Foods , 11 : , 2022
Abstract : The removal of zearalenone (ZEN) from degummed corn oil (DCO) using hydrolase on a batch-refining unit was studied. According to single-factor and response surface experiments, the optimum technological conditions for reaching the maximum degradation rate were a temperature of 39.01 degreesC, a pH of 8.08, a time of 3.9 h, and an enzyme dosage of 44.7 mg/kg, whereby the rate of ZEN degradation can reach 94.66%. Different effects on the removal of ZEN were observed at different initial ZEN contents under the optimal technological conditions, of which the decrease was rapid for high ZEN content and slow for low ZEN content.
ESTHER : Zhao_2022_Foods_11_
PubMedSearch : Zhao_2022_Foods_11_
PubMedID: 36496603

Title : Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-kB\/miR-155-5p\/eNOS\/NO\/IkB Cycle in Hypertensive Rats - Wang_2022_Antioxidants.(Basel)_11_
Author(s) : Wang X , Han W , Zhang Y , Zong Y , Tan N , Li L , Liu C , Liu L
Ref : Antioxidants (Basel) , 11 : , 2022
Abstract : Epoxyeicosatrienoic acids (EETs), angiogenic mediators degraded by soluble epoxide hydrolase (sEH), have been shown to exert beneficial effects on the cardiovascular system. The current study assessed the impact of increased EETs with an sEH inhibitor, t-AUCB, on two-kidney-one-clip (2K1C)-induced renovascular endothelial dysfunction, associated with hypertension, in rats. The hypertensive rats exhibited increased systolic blood pressure, reduced renal blood flow, impaired endothelium-dependent relaxation and eNOS phosphorylation in the renal arteries, elevated ROS production in the endothelium of the renal arteries, and decreased EET levels in plasma, the renal arteries, and endothelial cells; however, t-AUCB reversed all the deleterious effects. Moreover, we found that the stimulation of AMPK/UCP2 scavenged ROS and restored endothelial function in the renal arteries of hypertensive rats undergoing therapy with t-AUCB. In addition, we were the first to reveal the potential role of miR-155-5p in the occurrence and development of vascular endothelial dysfunction in hypertension. Importantly, t-AUCB recovered NO bioavailability by regulating the NF-kappaB/miR-155-5p/eNOS/NO/IkappaB cycle after the activation of AMPK/UCP2 and the subsequent inhibition of ROS in hypertensive rat renal artery endothelial cells. This study will provide evidence for this additional new mechanism, underlying the benefits of EETs and the related agents against hypertensive vasculopathy.
ESTHER : Wang_2022_Antioxidants.(Basel)_11_
PubMedSearch : Wang_2022_Antioxidants.(Basel)_11_
PubMedID: 35883863

Title : Silencing of MsD14 Resulted in Enhanced Forage Biomass through Increasing Shoot Branching in Alfalfa (Medicago sativa L.) - Ma_2022_Plants.(Basel)_11_
Author(s) : Ma L , Zhang Y , Wen H , Liu W , Zhou Y , Wang X
Ref : Plants (Basel) , 11 : , 2022
Abstract : Branching is one of the key determinants of plant architecture that dramatically affects crop yield. As alfalfa is the most important forage crop, understanding the genetic basis of branching in this plant can facilitate breeding for a high biomass yield. In this study, we characterized the strigolactone receptor gene MsD14 in alfalfa and demonstrated that MsD14 was predominantly expressed in flowers, roots, and seedpods. Furthermore, we found that MsD14 expression could significantly respond to strigolactone in alfalfa seedlings, and its protein was located in the nucleus, cytoplasm, and cytomembrane. Most importantly, transformation assays demonstrated that silencing of MsD14 in alfalfa resulted in increased shoot branching and forage biomass. Significantly, MsD14 could physically interact with AtMAX2 and MsMAX2 in the presence of strigolactone, suggesting a similarity between MsD14 and AtD14. Together, our results revealed the conserved D14-MAX2 module in alfalfa branching regulation and provided candidate genes for alfalfa high-yield molecular breeding.
ESTHER : Ma_2022_Plants.(Basel)_11_
PubMedSearch : Ma_2022_Plants.(Basel)_11_
PubMedID: 35406919

Title : Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities - Zang_2021_Molecules_26_
Author(s) : Zang Y , Liu K , Wang W , Li C , Ma J , Yang J , Chen X , Wang X , Zhang D
Ref : Molecules , 26 : , 2021
Abstract : The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC(50)) 1.63-4.62 microM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
ESTHER : Zang_2021_Molecules_26_
PubMedSearch : Zang_2021_Molecules_26_
PubMedID: 33671020

Title : Determination of methomyl in grain using deep eutectic solvent-based extraction combined with fluorescence-based enzyme inhibition assays - Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
Author(s) : Guo Y , Wang H , Chen Z , Jing X , Wang X
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 266 :120412 , 2021
Abstract : A deep eutectic solvent (DES)-based extraction method is established to facilitate the determination of methomyl in grain via enzyme inhibition fluorescence. The environmentally-friendly DES was synthesized from proline and ethylene glycol and used as a green replacement for traditional extraction solvents that are generally toxic. The DES was added to grain samples and vortex extraction of methomyl, the supernatant was then collected for fluorescence detection. Biomass carbon quantum dots (CQDs) synthesized from millet were used as fluorescent probes. Acetylcholinesterase catalyzes the hydrolysis of acetylthiocholine iodide to thiocholine. The positively-charged thiocholine interacts electrostatically with the negatively-charged quantum dots resulting in the quenching of their fluorescent emission. The pesticide extract solution blocks the enzyme activity and thus recovers the fluorescent from the quantum dots. The fluorescence response was correlated with the amount of methomyl residue in the grain over the range 0.01 to 5 mg kg(-1). The limit of detection was found to be 0.003 mg kg(-1), and the limit of quantification 0.01 mg kg(-1). Recoveries of 86.5% to 107.8% were obtained using real samples, including millet, rice, wheat, and barley, with a relative standard deviation of less than 3.8%. The method is efficient and convenient and has good application prospects for extracting and detecting pesticides in grain samples.
ESTHER : Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
PubMedSearch : Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
PubMedID: 34597870

Title : Effect of CES1 genetic variation on enalapril steady-state pharmacokinetics and pharmacodynamics in healthy subjects - Her_2021_Br.J.Clin.Pharmacol__
Author(s) : Her LH , Wang X , Shi J , Choi HJ , Jung SM , Smith LS , Wu AH , Bleske BE , Zhu HJ
Ref : British Journal of Clinical Pharmacology , : , 2021
Abstract : BACKGROUND AND OBJECTIVE: Enalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single-dose enalapril PK (10 mg); however, the results were inconclusive. A prospective, multi-dose, pharmacokinetics, and pharmacodynamics (PK/PD) study was conducted to determine the impact of the CES1 G143E variant on enalapril steady-state PK and PD in healthy volunteers. METHODS: Study participants were stratified to G143E non-carriers (n=15) and G143E carriers (n=6). All the carriers were G143E heterozygotes. Study subjects received enalapril 10 mg daily for seven consecutive days prior to a 72h PK/PD study. Plasma concentrations of enalapril and its active metabolite enalaprilat were quantified by an established LC-MS/MS method. RESULTS: The CES1 G143E carriers had 30.9% lower enalaprilat C(max) (P = 0.03) compared to the non-carriers (38.01 vs. 55.01 ng/mL). The carrier group had 27.5% lower AUC(0-) (P = 0.02) of plasma enalaprilat compared to the non-carriers (374.29 vs. 515.91 ng*hr/mL). The carriers also had a 32.3% lower enalaprilat-to-enalapril AUC(0-) ratio (P = 0.003) relative to the non-carriers. The average maximum reduction of systolic blood pressure in the non-carrier group was approximately 12.4% at the end of the study compared to the baseline (P = 0.001). No statistically significant blood pressure reduction was observed in the G143E carriers. CONCLUSIONS: The CES1 loss-of-function G143E variant significantly impaired enalapril activation and its systolic blood pressure-lowering effect in healthy volunteers.
ESTHER : Her_2021_Br.J.Clin.Pharmacol__
PubMedSearch : Her_2021_Br.J.Clin.Pharmacol__
PubMedID: 33963573

Title : Plasma carboxylesterase 1 predicts methylphenidate exposure: a proof-of-concept study using plasma protein biomarker for hepatic drug metabolism - Shi_2021_Clin.Pharmacol.Ther__
Author(s) : Shi J , Xiao J , Wang X , Jung SM , Bleske BE , Markowitz JS , Patrick KS , Zhu HJ
Ref : Clinical Pharmacology & Therapeutics , : , 2021
Abstract : Hepatic drug-metabolizing enzymes (DMEs) play critical roles in determining the pharmacokinetics and pharmacodynamics of numerous therapeutic agents. As such, noninvasive biomarkers capable of predicting DME expression in the liver have the potential to be used to personalize pharmacotherapy and improve drug treatment outcomes. In the present study, we quantified carboxylesterase 1 (CES1) protein concentrations in plasma samples collected during a methylphenidate (MPH) PK study. CES1 is a prominent hepatic enzyme responsible for the metabolism of many medications containing small ester moieties, including MPH. The results revealed a significant inverse correlation between plasma CES1 protein concentrations and the area under the concentration-time curves (AUCs) of plasma d-MPH (p = 0.014, r = -0.617). In addition, when plasma CES1 protein levels were normalized to the plasma concentrations of 24 liver-enriched proteins to account for potential interindividual differences in hepatic protein release rate, the correlation was further improved (p = 0.003, r = -0.703), suggesting that plasma CES1 protein could explain approximately 50% of the variability in d-MPH AUCs in the study participants. A physiologically based pharmacokinetic (PBPK) modeling simulation revealed that the CES1-based individualized dosing strategy might significantly reduce d-MPH exposure variability in pediatric patients relative to conventional fixed dosing trial and error regimens. This proof-of-concept study indicates that the plasma protein of a hepatic DME may serve as a biomarker for predicting its metabolic function and the pharmacokinetics of its substrate drugs.
ESTHER : Shi_2021_Clin.Pharmacol.Ther__
PubMedSearch : Shi_2021_Clin.Pharmacol.Ther__
PubMedID: 34743324

Title : Gender Disparities in Anti-dementia Medication Use among Older Adults: Health Equity Considerations and Management of Alzheimer's Disease and Related Dementias - Lu_2021_Front.Pharmacol_12_706762
Author(s) : Lu ZK , Xiong X , Wang X , Wu J
Ref : Front Pharmacol , 12 :706762 , 2021
Abstract : Objective: The prevalence of Alzheimer's disease and related dementias (ADRD) in women is higher than men. However, the knowledge of gender disparity in ADRD treatment is limited. Therefore, this study aimed to determine the gender disparities in the receipt of anti-dementia medications among Medicare beneficiaries with ADRD in the U.S. Methods: We used data from the Medicare Current Beneficiary Survey 2016. Anti-dementia medications included cholinesterase inhibitors (ChEIs; including rivastigmine, donepezil, and galantamine) and N-methyl-D-aspartate (NMDA) receptor antagonists (including memantine). Descriptive analysis and multivariate logistic regression models were implemented to determine the possible gender disparities in the receipt of anti-dementia medications. Subgroup analyses were conducted to identify gender disparities among beneficiaries with Alzheimer's disease (AD) and those with only AD-related dementias. Results: Descriptive analyses showed there were statistically significant differences in age, marital status, and Charlson comorbidities index (CCI) between Medicare beneficiaries who received and who did not receive anti-dementia medications. After controlling for covariates, we found that female Medicare beneficiaries with ADRD were 1.7 times more likely to receive anti-dementia medications compared to their male counterparts (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.19-2.45). Specifically, among Medicare beneficiaries with AD, females were 1.2 times more likely to receive anti-dementia medications (Odds Radio: 1.20; 95% confidence interval: 0.58-2.47), and among the Medicare beneficiaries with only AD-related dementias, females were 1.9 times more likely to receive anti-dementia medications (OR: 1.90; 95% CI: 1.23-2.95). Conclusion: Healthcare providers should be aware of gender disparities in receiving anti-dementia medications among patients with ADRD, and the need to plan programs of care to support both women and men. Future approaches to finding barriers of prescribing, receiving and, adhering to anti-dementia medications by gender should include differences in longevity, biology, cognition, social roles, and environment.
ESTHER : Lu_2021_Front.Pharmacol_12_706762
PubMedSearch : Lu_2021_Front.Pharmacol_12_706762
PubMedID: 34512340

Title : Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb - Wang_2021_Fitoterapia_156_105069
Author(s) : Wang X , Wang F , Wu J , Chen SQ , Jiang CS , Yang SP , Wang C , Cai YS
Ref : Fitoterapia , 156 :105069 , 2021
Abstract : Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and alpha-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and alpha-glucosidase.
ESTHER : Wang_2021_Fitoterapia_156_105069
PubMedSearch : Wang_2021_Fitoterapia_156_105069
PubMedID: 34743932

Title : Single-Nucleotide Polymorphisms Promote Dysregulation Activation by Essential Gene Mediated Bio-Molecular Interaction in Breast Cancer - Wang_2021_Front.Oncol_11_791943
Author(s) : Wang X , Zhao Z , Han X , Zhang Y , Li F , Li H
Ref : Front Oncol , 11 :791943 , 2021
Abstract : BACKGROUND: Breast cancer (BRCA) is a malignant tumor with a high mortality rate and poor prognosis in patients. However, understanding the molecular mechanism of breast cancer is still a challenge. MATERIALS AND METHODS: In this study, we constructed co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene-expression profiles and clinical data were integrated to detect breast cancer survival modules and the leading genes related to prognostic risk. Finally, we introduced machine learning algorithms to build a predictive model aiming to discover potential key biomarkers. RESULTS: A total of 42 prognostic modules for breast cancer were identified. The nomogram analysis showed that 42 modules had good risk assessment performance. Compared to clinical characteristics, the risk values carried by genes in these modules could be used to classify the high-risk and low-risk groups of patients. Further, we found that 16 genes with significant differential expressions and obvious bridging effects might be considered biological markers related to breast cancer. Single-nucleotide polymorphisms on the CYP24A1 transcript induced RNA structural heterogeneity, which affects the molecular regulation of BRCA. In addition, we found for the first time that ABHD11-AS1 was significantly highly expressed in breast cancer. CONCLUSION: We integrated clinical prognosis information, RNA sequencing data, and drug targets to construct a breast cancer-related risk module. Through bridging effect measurement and machine learning modeling, we evaluated the risk values of the genes in the modules and identified potential biomarkers for breast cancer. The protocol provides new insight into deciphering the molecular mechanism and theoretical basis of BRCA.
ESTHER : Wang_2021_Front.Oncol_11_791943
PubMedSearch : Wang_2021_Front.Oncol_11_791943
PubMedID: 34926308
Gene_locus related to this paper: human-ABHD11

Title : Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve - Wang_2021_J.Affect.Disord_292_565
Author(s) : Wang S , Ishima T , Qu Y , Shan J , Chang L , Wei Y , Zhang J , Pu Y , Fujita Y , Tan Y , Wang X , Ma L , Wan X , Hammock BD , Hashimoto K
Ref : J Affect Disord , 292 :565 , 2021
Abstract : BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice. METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed. RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium. LIMITATIONS: Detailed mechanisms are unclear. CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.
ESTHER : Wang_2021_J.Affect.Disord_292_565
PubMedSearch : Wang_2021_J.Affect.Disord_292_565
PubMedID: 34147969

Title : Osthole-Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer's Disease via Intranasal Administration - Song_2021_Oxid.Med.Cell.Longev_2021_8844455
Author(s) : Song Y , Wang X , Wang J , Hao Q , Hao J , Hou X
Ref : Oxid Med Cell Longev , 2021 :8844455 , 2021
Abstract : Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer's disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer's disease.
ESTHER : Song_2021_Oxid.Med.Cell.Longev_2021_8844455
PubMedSearch : Song_2021_Oxid.Med.Cell.Longev_2021_8844455
PubMedID: 33564364

Title : Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers - Wang_2021_Clin.Transl.Sci__
Author(s) : Wang X , Her L , Xiao J , Shi J , Wu AH , Bleske BE , Zhu HJ
Ref : Clin Transl Sci , : , 2021
Abstract : Trandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single-dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (C(max) ) and area under the curve from 0 to 72 h (AUC(0-72 h) ) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.
ESTHER : Wang_2021_Clin.Transl.Sci__
PubMedSearch : Wang_2021_Clin.Transl.Sci__
PubMedID: 33660934

Title : Application of deep eutectic solvent-based extraction coupled with an S-CQD fluorescent sensor for the determination of pirimicarb in cereals - Jing_2021_Food.Chem_370_131360
Author(s) : Jing X , Wu J , Wang H , Guo L , Zheng X , Wang X , Wang S
Ref : Food Chem , 370 :131360 , 2021
Abstract : A novel deep eutectic solvent-based extraction and sulfur-doped carbon quantum dots (S-CQDs) serving as fluorescence probes to detect pirimicarb in cereals were established. The deep eutectic solvent was synthesized using choline chloride and butanediol, achieving direct and efficient extraction of pirimicarb residue in the cereals. The fluorescence quenching of S-CQDs was caused by the electrostatic interaction between the negatively charged S-CQDs and positively charged thiocholine, which was the hydrolysate of acetylthiocholine. The fluorescence of S-CQDs was enhanced as the activity of acetylcholinesterase (AChE) was inhibited by pirimicarb, achieving the detection of pirimicarb in the cereal samples. The limit of detection (LOD) was 0.006 microg mL(-1). The recovery ranged from 96.6% to 108.2%. This extraction and detection method of pirimicarb based on an environmentally friendly DES and S-CQD fluorescent sensor maintains good stability and convenience, offering a promising strategy for extracting and testing harmful substances in food samples.
ESTHER : Jing_2021_Food.Chem_370_131360
PubMedSearch : Jing_2021_Food.Chem_370_131360
PubMedID: 34662796

Title : Degradation of epigallocatechin and epicatechin gallates by a novel tannase Tan(Hcw) from Herbaspirillum camelliae - Lei_2021_Microb.Cell.Fact_20_197
Author(s) : Lei J , Zhang Y , Ni X , Yu X , Wang X
Ref : Microb Cell Fact , 20 :197 , 2021
Abstract : BACKGROUND: Herbaspirillum camelliae is a gram-negative endophyte isolated from the tea plant. Both strains WT00C and WT00F were found to hydrolyze epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) to release gallic acid (GA) and display tannase activity. However, no tannase gene was annotated in the genome of H. camelliae WT00C. RESULTS: The 39 kDa protein, annotated as the prolyl oligopeptidase in the NCBI database, was finally identified as a novel tannase. Its gene was cloned, and the enzyme was expressed in E. coli and purified to homogeneity. Moreover, enzymatic characterizations of this novel tannase named Tan(Hcw) were studied. Tan(Hcw) was a secretary enzyme with a Sec/SPI signal peptide of 48 amino acids at the N-terminus, and it catalyzed the degradation of tannin, methyl gallate (MG), epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG). The optimal temperature and pH of Tan(Hcw) activities were 30 degreesC, pH 6.0 for MG and 40 degreesC, pH 7.0 for both EGCG and ECG. Na(+), K(+) Mn(2+) and Triton-X100, Tween80 increased the enzyme activity of Tan(Hcw), whereas Zn(2+), Mg(2+), Hg(2+), EMSO, EDTA and beta-mercaptoethanol inhibited enzyme activity. K(m), k(cat) and k(cat) /K(m) of Tan(Hcw) were 0.30 mM, 37.84 s(-1), 130.67 mM(-1) s(-1) for EGCG, 0.33 mM, 34.59 s(-1), 105.01 mM(-1) s(-1) for ECG and 0.82 mM, 14.64 s(-1), 18.17 mM(-1) s(-1) for MG, respectively. CONCLUSION: A novel tannase Tan(Hcw) from H. camelliae has been identified and characterized. The biological properties of Tan(Hcw) suggest that it plays a crucial role in the specific colonization of H. camelliae in tea plants. Discovery of the tannase Tan(Hcw) in this study gives us a reasonable explanation for the host specificity of H. camelliae. In addition, studying the characteristics of this enzyme offers the possibility of further defining its potential in industrial application.
ESTHER : Lei_2021_Microb.Cell.Fact_20_197
PubMedSearch : Lei_2021_Microb.Cell.Fact_20_197
PubMedID: 34641872
Gene_locus related to this paper: 9burk-TanHcw

Title : Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer's disease agents - Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
Author(s) : Yun Y , Miao Y , Sun X , Sun J , Wang X
Ref : J Enzyme Inhib Med Chem , 36 :1346 , 2021
Abstract : Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and beta-secretase inhibitory activity. The IC(50) value of compound 20 against acetylcholinesterase inhibition (0.086 +/- 0.01 micromol.L(-1)) is similar to donepezil (0.085 +/- 0.01 micromol.L(-1)) and is better than baicalein (0.404 +/- 0.04 micromol.L(-1)). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 +/- 0.03 micromol.L(-1)). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.
ESTHER : Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
PubMedSearch : Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
PubMedID: 34134572

Title : Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 Axis via a Positive NRF2-HO-1 Feedback Loop - Li_2021_Front.Oncol_11_679816
Author(s) : Li R , Zeng X , Yang M , Xu X , Feng J , Bao L , Xue B , Wang X , Huang Y
Ref : Front Oncol , 11 :679816 , 2021
Abstract : Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1.
ESTHER : Li_2021_Front.Oncol_11_679816
PubMedSearch : Li_2021_Front.Oncol_11_679816
PubMedID: 34123848

Title : Genome-Wide Identification of GDSL-Type Esterase\/Lipase Gene Family in Dasypyrum villosum L. Reveals That DvGELP53 Is Related to BSMV Infection - Zhang_2021_Int.J.Mol.Sci_22_
Author(s) : Zhang H , Zhang X , Zhao J , Sun L , Wang H , Zhu Y , Xiao J , Wang X
Ref : Int J Mol Sci , 22 : , 2021
Abstract : GDSL-type esterase/lipase proteins (GELPs) characterized by a conserved GDSL motif at their N-terminus belong to the lipid hydrolysis enzyme superfamily. In plants, GELPs play an important role in plant growth, development and stress response. The studies of the identification and characterization of the GELP gene family in Triticeae have not been reported. In this study, 193 DvGELPs were identified in Dasypyrum villosum and classified into 11 groups (clade A-K) by means of phylogenetic analysis. Most DvGELPs contain only one GDSL domain, only four DvGELPs contain other domains besides the GDSL domain. Gene structure analysis indicated 35.2% DvGELP genes have four introns and five exons. In the promoter regions of the identified DvGELPs, we detected 4502 putative cis-elements, which were associated with plant hormones, plant growth, environmental stress and light responsiveness. Expression profiling revealed 36, 44 and 17 DvGELPs were highly expressed in the spike, the root and the grain, respectively. Further investigation of a root-specific expressing GELP, DvGELP53, indicated it was induced by a variety of biotic and abiotic stresses. The knockdown of DvGELP53 inhibited long-distance movement of BSMV in the tissue of D. villosum. This research provides a genome-wide glimpse of the D. villosum GELP genes and hints at the participation of DvGELP53 in the interaction between virus and plants.
ESTHER : Zhang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Zhang_2021_Int.J.Mol.Sci_22_
PubMedID: 34830200

Title : Systematic Analysis and Biochemical Characterization of the Caffeoyl Shikimate Esterase Gene Family in Poplar - Wang_2021_Int.J.Mol.Sci_22_13366
Author(s) : Wang X , Chao N , Zhang A , Kang J , Jiang X , Gai Y
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Caffeoyl shikimate esterase (CSE) hydrolyzes caffeoyl shikimate into caffeate and shikimate in the phenylpropanoid pathway. In this study, we performed a systematic analysis of the CSE gene family and investigated the possible roles of CSE and CSE-like genes in Populus. We conducted a genome-wide analysis of the CSE gene family, including functional and phylogenetic analyses of CSE and CSE-like genes, using the poplar (Populus trichocarpa) genome. Eighteen CSE and CSE-like genes were identified in the Populus genome, and five phylogenetic groups were identified from phylogenetic analysis. CSEs in Group Ia, which were proposed as bona fide CSEs, have probably been lost in most monocots except Oryza sativa. Primary functional classification showed that PoptrCSE1 and PoptrCSE2 had putative function in lignin biosynthesis. In addition, PoptrCSE2, along with PoptrCSE12, might also respond to stress with a function in cell wall biosynthesis. Enzymatic assay of PoptoCSE1 (Populus tomentosa), -2 and -12 showed that PoptoCSE1 and -2 maintained CSE activity. PoptoCSE1 and 2 had similar biochemical properties, tissue expression patterns and subcellular localization. Most of the PoptrCSE-like genes are homologs of AtMAGL (monoacylglycerol lipase) genes in Arabidopsis and may function as MAG lipase in poplar. Our study provides a systematic understanding of this novel gene family and suggests the function of CSE in monolignol biosynthesis in Populus.
ESTHER : Wang_2021_Int.J.Mol.Sci_22_13366
PubMedSearch : Wang_2021_Int.J.Mol.Sci_22_13366
PubMedID: 34948162
Gene_locus related to this paper: poptr-CSE16 , poptr-CSE17 , popto-CSE14 , poptr-CSE6 , poptr-CSE12 , poptr-CSE8 , poptr-CSE5 , poptr-CSE1 , poptr-CSE3 , poptr-CSE15 , arath-F14G24.3 , poptr-b9gwn9 , poptr-b9hll5 , poptr-b9huf0 , poptr-b9n233

Title : Transcriptional regulation of carboxylesterase 1 (CES1) in human liver: role of the nuclear receptor NR1H3 (LXRalpha) and its splice isoforms - Collins_2021_Drug.Metab.Dispos__
Author(s) : Collins JM , Lu R , Wang X , Zhu HJ , Wang D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : Carboxylesterase 1 (CES1) is the predominant carboxylesterase in the human liver, involved in metabolism of both xenobiotics and endogenous substrates. Genetic or epigenetic factors that alter CES1 activity or expression are associated with changes in drug response, lipid, and glucose homeostasis. However, the transcriptional regulation of CES1 in the human liver remains uncertain. By applying both the random forest and Sobol's Sensitivity Indices (SSI) to analyze existing liver RNA expression microarray data (GSE9588), we identified NR1H3 (LXRalpha) as a key factor regulating constitutive CES1 expression. This model prediction was validated using siRNA knockdown and CRISPR-mediated transcriptional activation of NR1H3 in Huh7 and HepG2 cells. We found that NR1H3's activation of CES1 is splice isoform-specific, namely that increased expression of the NR1H3-211 isoform increased CES1 expression while NR1H3-201 did not. Also, in human liver samples, expression of NR1H3-211 and CES1 are correlated, while NR1H3-201 and CES1 are not. This trend also occurs during differentiation of induced pluripotent stem cells (iPSCs) to hepatocytes, where only expression of the NR1H3-211 isoform parallels expression of CES1 Moreover, we found that treatment with the NR1H3 agonist T0901317 in HepG2 cells had no effect on CES1 expression. Overall, our results demonstrate a key role of NR1H3 in maintaining the constitutive expression of CES1 in the human liver. Furthermore, our results support that the effect of NR1H3 is splice isoform-specific and appears to be ligand independent. Significance Statement Despite the central role of CES1 in metabolism of numerous medications, little is known about its transcriptional regulation. Here we identify NR1H3 as a key regulator of constitutive CES1 expression, and therefore is a potential target for future studies to understand inter-person variabilities in CES1 activity and drug metabolism.
ESTHER : Collins_2021_Drug.Metab.Dispos__
PubMedSearch : Collins_2021_Drug.Metab.Dispos__
PubMedID: 34697082
Gene_locus related to this paper: human-CES1

Title : Protective effects of pretreatment with Fe(2+), Cu(2+), and Rb(+) on phoxim poisoning in silkworm, Bombyx mori - Guo_2021_J.Trace.Elem.Med.Biol_68_126844
Author(s) : Guo J , Wang X , Wang W , Jia L , Guo W , Wu G
Ref : J Trace Elem Med Biol , 68 :126844 , 2021
Abstract : BACKGROUND: Phoxim is a widely used organophosphorus pesticide in agriculture. People are paying more and more attention to its toxicity. At present, there is no appropriate way to solve the phoxim poisoning of silkworm, which severely affected the development of sericulture. Fe(2+), Cu(2+), Rb(+) exerted their biological effects through various forms in vivo. METHODS: To evaluate the effect of Fe(2+)/Cu(2+)/Rb(+) on phoxim poisoning in silkworm, Bombyx mori were treated with fresh mulberry leaves soaked in 2.5 mg/L phoxim for 2 min with 50 mg/L FeCl(2), 150 mg/L CuCl(2), or 0.5 mg/L RbCl from 5 days of the fifth-instar silkworm. RESULTS: Fe(2+), Cu(2+), and Rb(+) pretreatments significantly inhibited the phoxim-induced reduction of survival rate and alleviated the phoxim-induced poisoning symptoms. The protective effects of Fe(2+), Cu(2+), and Rb(+) on phoxim poisoning might be due to their enhancement of superoxide dismutase (SOD), catalase (CAT), and carboxylesterase (CarE) in the hemolymph and fat body of silkworm. This enhancement might reduce reactive oxygen species (ROS) accumulation and oxidative stress (OS) caused by phoxim poisoning. Thereby it reduced the damage to silkworm tissues and cells. CONCLUSIONS: These results showed that Fe(2+), Cu(2+), and Rb(+) treatments protected the silkworm from phoxim poisoning by directly enhancing the activity of SOD, CAT, and CarE enzymes and reducing oxidative stress, but not dependent on the high expression of CYP genes. The use of Fe(2+), Cu(2+), and Rb(+) to enhance the activity of SOD, CAT, and CarE enzymes may be an underlying effective way to solve phoxim poisoning in the silkworm industry.
ESTHER : Guo_2021_J.Trace.Elem.Med.Biol_68_126844
PubMedSearch : Guo_2021_J.Trace.Elem.Med.Biol_68_126844
PubMedID: 34425455

Title : Contributions of Cathepsin A and Carboxylesterase 1 to the hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis - Li_2021_Drug.Metab.Dispos__
Author(s) : Li J , Shi J , Xiao J , Tran L , Wang X , Zhu HJ
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitro incubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH-dependent manner. At their physiological pH environment, the activity of CatA (pH 5.2) was approximately 1,000-fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200-fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis-(p-nitrophenyl) phosphate. Moreover, an in vitro study revealed that the CES1 variant G143E (rs71647871) is a loss-of-function variant for CES1-mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation. Significance Statement Contrary to the general perception that carboxylesterase 1 (CES1) is the major enzyme responsible for tenofovir alafenamide (TAF) hydrolysis in the human liver, the present study demonstrated that cathepsin A (CatA) may play a more significant role in TAF hepatic hydrolysis. Furthermore, the CES1 variant G143E (rs71647871) was found to be a loss-of-function variant for CES1-mediated TAF hydrolysis.
ESTHER : Li_2021_Drug.Metab.Dispos__
PubMedSearch : Li_2021_Drug.Metab.Dispos__
PubMedID: 34933885
Gene_locus related to this paper: human-CES1 , human-CTSA

Title : Whole-genome sequencing to detect mutations associated with resistance to insecticides and Bt proteins in Spodoptera frugiperda - Guan_2021_Insect.Sci_28_627
Author(s) : Guan F , Zhang J , Shen H , Wang X , Padovan A , Walsh TK , Tay WT , Gordon KHJ , James W , Czepak C , Otim MH , Kachigamba D , Wu Y
Ref : Insect Sci , 28 :627 , 2021
Abstract : The fall armyworm (FAW), Spodoptera frugiperda, is a major pest native to the Americas that has recently invaded the Old World. Point mutations in the target-site proteins acetylcholinesterase-1 (ace-1), voltage-gated sodium channel (VGSC) and ryanodine receptor (RyR) have been identified in S. frugiperda as major resistance mechanisms to organophosphate, pyrethroid and diamide insecticides respectively. Mutations in the adenosine triphosphate-binding cassette transporter C2 gene (ABCC2) have also been identified to confer resistance to Cry1F protein. In this study, we applied a whole-genome sequencing (WGS) approach to identify point mutations in the target-site genes in 150 FAW individuals collected from China, Malawi, Uganda and Brazil. This approach revealed three amino acid substitutions (A201S, G227A and F290V) of S. frugiperda ace-1, which are known to be associated with organophosphate resistance. The Brazilian population had all three ace-1 point mutations and the 227A allele (mean frequency = 0.54) was the most common. Populations from China, Malawi and Uganda harbored two of the three ace-1 point mutations (A201S and F290V) with the 290V allele (0.47-0.58) as the dominant allele. Point mutations in VGSC (T929I, L932F and L1014F) and RyR (I4790M and G4946E) were not detected in any of the 150 individuals. A novel 12-bp insertion mutation in exon 15 of the ABCC2 gene was identified in some of the Brazilian individuals but absent in the invasive populations. Our results not only demonstrate robustness of the WGS-based genomic approach for detection of resistance mutations, but also provide insights for improvement of resistance management tactics in S. frugiperda.
ESTHER : Guan_2021_Insect.Sci_28_627
PubMedSearch : Guan_2021_Insect.Sci_28_627
PubMedID: 32558234
Gene_locus related to this paper: spolt-ACHE2 , spolt-ACHE1

Title : Novel chrysin derivatives as hidden multifunctional agents for anti-Alzheimer's disease: design, synthesis and in vitro evaluation - Liu_2021_Eur.J.Pharm.Sci__105976
Author(s) : Liu C , Kou X , Wang X , Wu J , Yang A , Shen R
Ref : Eur J Pharm Sci , :105976 , 2021
Abstract : Alzheimer's disease (AD) is the most common type of dementia, the exact etiology of the disease has not been known yet. The use of single-target drugs limits the efficacy of drugs and has certain side effects. In this study, the 'hidden' multi-target strategy was used in combination with chrysin's metal chelating site and rivastigmine's anti-cholinesterase pharmacophore to form an ester, which improves the hydrophobicity and protects the phenolic hydroxyl group at the same time. Four derivatives (1-4) were synthesized as the hidden multifunctional agents for AD therapy. Most of the compounds displayed good activities of anti-cholinesterase, antioxidant, appropriate blood brain barrier (BBB) penetration and certain inhibitory activity of beta-amyloid (Abeta) aggregation. Compound 3 was demonstrated as the highest selective butyrylcholinesterase (BuChE) inhibitor and targeted both the catalytic active site (CAS) and the peripheral anion site (PAS). And it could be hydrolyzed by BuChE to release chrysin with good ability to chelate Cu(2+) and Fe(2+). At the same time, phenol fragment can exert its good antioxidant effect. Overall, these findings demonstrated that compound 3 might be considered as a potential hidden multifunctional candidate in the therapy of AD.
ESTHER : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedSearch : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedID: 34419572

Title : Behaviors and biochemical responses of macroinvertebrate Corbicula fluminea to polystyrene microplastics - Fu_2021_Sci.Total.Environ_813_152617
Author(s) : Fu L , Xi M , Nicholaus R , Wang Z , Wang X , Kong F , Yu Z
Ref : Sci Total Environ , 813 :152617 , 2021
Abstract : Microplastic, a well-documented emerging contaminant, is widespread in aquatic environments resulting from the production and fragmentation of large plastics items. The knowledge about the chronic toxic effects and behavioral toxicity of microplastics, particularly on freshwater benthic macroinvertebrates, is limited. In this study, adult Asian clams (Corbicula fluminea) were exposed to gradient microplastic solutions for 42 days to evaluate behavioral toxicity and chronic biotoxicity. The results showed that microplastics caused behavior toxicity, oxidative stress, and tissue damage in high-concentration treatments. Siphoning, breathing, and excretion was significantly inhibited (p < 0.05) at high-concentration treatments, suggesting that high-concentration microplastics induced behavioral toxicity in C. fluminea. Malondialdehyde content, superoxide dismutase, catalase, and glutathione reductase activities were significantly enhanced (p < 0.05) and the acetylcholinesterase was significantly inhibited (p < 0.05) throughout the exposure period in high-concentration treatments. Enzymes associated with energy supply were significantly higher at high-concentration microplastics treatments on D7 and D21. However, they recovered to a normal level on D42. The instability of the enzymes indicated that high-concentration microplastics induced oxidative stress and disorder in neurotransmission and energy supply. The gills of C. fluminea in treatments underwent cilia degeneration, which indicated that microplastics caused tissue damage in the gills. The analysis of integrated biomarker response values revealed that high-concentration microplastics led to long-term effects on the health of C. fluminea. In conclusion, continuous exposure to microplastics (10 mg L(-1)) would damage physical behavior and the antioxidant system of C. fluminea.
ESTHER : Fu_2021_Sci.Total.Environ_813_152617
PubMedSearch : Fu_2021_Sci.Total.Environ_813_152617
PubMedID: 34963588

Title : A dual-signal sensor for the analysis of parathion-methyl using silver nanoparticles modified with graphitic carbon nitride - Li_2021_J.Pharm.Anal_11_183
Author(s) : Li Y , Wan M , Yan G , Qiu P , Wang X
Ref : J Pharm Anal , 11 :183 , 2021
Abstract : A highly sensitive and selective method was developed for both UV-vis spectrophotometric and fluorimetric determination of organophosphorus pesticides (OPs). This method used silver nanoparticles (AgNPs) modified with graphitic carbon nitride (g-C(3)N(4)). The AgNPs reduced the fluorescence intensity of g-C(3)N(4). Acetylthiocholine (ATCh) could be catalytically hydrolyzed by acetylcholinesterase (AChE) to form thiocholine, which induces aggregation of the AgNPs. This aggregation led to the recovery of the blue fluorescence of g-C(3)N(4), with excitation/emission peaks at 310/460 nm. This fluorescence intensity could be reduced again in the presence of OPs because of the inhibitory effect of OPs on the activity of AChE. The degree of reduction was found to be proportional to the concentration of OPs, and the limit of fluorometric detection was 0.0324 microg/L (S/N = 3). In addition, the absorption of the g-C(3)N(4)/AgNPs at 390 nm decreased because of the aggregation of the AgNPs, but was recovered in presence of OPs because of the inhibition of enzyme activity by OPs. This method was successfully applied to the analysis of parathion-methyl in real samples.
ESTHER : Li_2021_J.Pharm.Anal_11_183
PubMedSearch : Li_2021_J.Pharm.Anal_11_183
PubMedID: 34012694

Title : Near-infrared fluorescent probe for evaluating the acetylcholinesterase effect in the aging process and dietary restriction via fluorescence imaging - He_2021_J.Mater.Chem.B__
Author(s) : He N , Yu L , Xu M , Huang Y , Wang X , Chen L , Yue S
Ref : J Mater Chem B , : , 2021
Abstract : Dietary restriction (DR), as a natural intervention, not only benefits the neuroendocrine system, but also has an antiaging action. Acetylcholinesterase (AChE) is one of the most important bioactive substances and plays a major part in choline changes in the aging process. Thus, we aim to evaluate the effect of DR on AChE in the brains of aging animals. In this study, we synthesize a NIR fluorescent probe BD-AChE for the real-time and in situ monitoring of AChE level changes in living cells and living mice, notably in brains. In situ visualization with BD-AChE verified a decrease in the AchE level in the brains of mice aging models. Evidently, the prepared probe has the excellent capability of measuring AChE variation in the brains of aging mice with DR via NIR fluorescence bioimaging, indicating that long-term DR can effectively affect AChE levels in the brain. The attenuation of AChE level in the brain of aging mice after DR could be helpful in infering the advantageous impact of DR on age-related neurodegenerative disease, as a better treatment alternative in the future.
ESTHER : He_2021_J.Mater.Chem.B__
PubMedSearch : He_2021_J.Mater.Chem.B__
PubMedID: 33666613

Title : Development and validation of an ultrasensitive LC-MS\/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial - Bai_2021_Biomed.Chromatogr_35_e4994
Author(s) : Bai H , Lu J , Cheng X , Liu L , Zhang W , Wei Y , Wang Y , Liu J , Ding J , Yu Q , Zhang Y , Chen G , Fan Y , Wang X
Ref : Biomedical Chromatography , 35 :e4994 , 2021
Abstract : This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C(18) analytical column (50x2.1mm, 5microm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.
ESTHER : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedSearch : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedID: 32986878

Title : Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy - Wang_2021_J.Nanobiotechnology_19_31
Author(s) : Wang K , Shang F , Chen D , Cao T , Wang X , Jiao J , He S , Liang X
Ref : J Nanobiotechnology , 19 :31 , 2021
Abstract : BACKGROUND: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. RESULTS: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. CONCLUSIONS: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.
ESTHER : Wang_2021_J.Nanobiotechnology_19_31
PubMedSearch : Wang_2021_J.Nanobiotechnology_19_31
PubMedID: 33482834

Title : Clinical Features and Prognosis in Chinese Patients With Dipeptidyl-Peptidase-Like Protein 6 Antibody-Associated Encephalitis - Miao_2021_Front.Neurol_12_817896
Author(s) : Miao A , Shi Y , Wang X , Ge J , Yu C
Ref : Front Neurol , 12 :817896 , 2021
Abstract : OBJECTIVES: Anti-dipeptidyl-peptidase-like protein 6 (anti-DPPX) encephalitis an extremely rare type of immune-mediated encephalitis. This study aimed to analyze the electroclinical characteristics and prognosis of anti-DPPX encephalitis. METHODS: Five patients (all male) with anti-DPPX encephalitis in East China from January 2016 to October 2021 was retrospective analyzed. Electroclinical features and outcomes were reviewed. RESULTS: All five patients were male. The media age at disease onset was 32 years old with a range of 14-56 years. The main symptoms included psychiatric disturbances (2/5), amnesia (4/5), confusion (3/5), and seizures (3/5). Migrating myoclonus were identified in patient 4 with positive DPPX and contactin-associated protein-like 2 antibodies in blood. All of the patients had positive DPPX antibodies in serum. Only one of them had positive antibody in the cerebrospinal fluid. EEG showed diffuse slowing in two patients, but no epileptiform discharges were observed. Eighty percent (4/5) of the patients showed normal brain magnetic resonance imaging. After immunotherapy, improvement of neuropsychiatric symptoms from all of the patients was observed. Over a mean follow-up of 30.8 weeks, all of the patients had marked improvement in the modified Rankin Scale. To date, no tumors were not observed in any patients. CONCLUSIONS: Anti-DPPX encephalitis mainly presents as neuropsychiatric symptoms. Cooperation of DPPX antibodies and CASPR2 antibodies might have contributed to the migration of myoclonus in the patient 4. Prompt immunotherapy often results in improvement.
ESTHER : Miao_2021_Front.Neurol_12_817896
PubMedSearch : Miao_2021_Front.Neurol_12_817896
PubMedID: 35095748
Gene_locus related to this paper: human-DPP6

Title : Protective effects of orally administered shark compound peptides from Chiloscyllium plagiosum against acute inflammation - Wang_2021_J.Food.Biochem__e13618
Author(s) : Wang TX , Shen DY , Wang Q , Xu XH , Wang X , Chen QX , Zhuang JX , Wang YY
Ref : J Food Biochem , :e13618 , 2021
Abstract : The anti-inflammatory effects of shark compound peptides (SCP) from Chiloscyllium plagiosum were investigated. Results showed that SCP enhanced the viability of RAW 264.7 macrophages in vitro in a dose-dependent manner. Orally administered SCP exhibited potent anti-inflammatory activity in lipopolysaccharide (LPS)-challenged mice by suppressing serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), as well as nitric oxide (NO). Moreover, SCP significantly inhibited the inflammatory rise of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatinine (CRE), while blocking the decline of cholinesterase (CHE), with an efficacy close to aspirin. This research showed that orally administered SCP from C. plagiosum notably downregulated uncontrolled inflammatory responses, and conferred substantial protection from endotoxin-induced acute hepatic damage and renal functional impairment. Therefore, oral supplementation of SCP can be used as a preventive approach to reduce the risk of inflammatory-related diseases.
ESTHER : Wang_2021_J.Food.Biochem__e13618
PubMedSearch : Wang_2021_J.Food.Biochem__e13618
PubMedID: 33491226

Title : Identification of a GDSL lipase from Streptomyces bacillaris and its application in the preparation of free astaxanthin - Gao_2021_J.Biotechnol_325_280
Author(s) : Gao K , Wang X , Jiang H , Sun J , Mao X
Ref : J Biotechnol , 325 :280 , 2021
Abstract : Astaxanthin shows multiple biological activities, but it is usually linked to different fatty acids and exists in the form of esters. The complexity of astaxanthin esters limits their application in the preparation of sophisticated drugs. Herein, a novel lipase from Streptomyces bacillaris that could hydrolyze astaxanthin esters, named OUC-Sb-lip12, was expressed in Bacillus subtilis. The active site of OUC-Sb-lip12 is probably composed of a dyad of Ser48 and His254, instead of a typical catalytic triad. The lipase was identified to be a GDSL hydrolase, and it showed highest activity at 45 degreesC and pH 9.0 (glycine-NaOH buffer). OUC-Sb-lip12 showed a good stability at its optimum temperature or a higher temperature, retaining 88.4% and 80.6% of its activity after incubating for 36 h at 45 degreesC and 55 degreesC, respectively. OUC-Sb-lip12 could effectively hydrolyze astaxanthin esters in Haematococcus pluvialis oil, generating free astaxanthin. Under the optimum conditions, 96.29% astaxanthin esters were hydrolyzed in 12 h. In addition, B.subtilis is a GRAS model strain and it could efficiently secrete lipase in 9 h, making the lipase potential for scale production of free astaxanthin, which could be further used in the preparation of specific astaxanthin esters with specific functions.
ESTHER : Gao_2021_J.Biotechnol_325_280
PubMedSearch : Gao_2021_J.Biotechnol_325_280
PubMedID: 33049356

Title : TPPU Pre-Treatment Rescues Dendritic Spine Loss and Alleviates Depressive Behaviours during the Latent Period in the Lithium Chloride-Pilocarpine-Induced Status Epilepticus Rat Model - Peng_2021_Brain.Sci_11_
Author(s) : Peng W , Shen Y , Wang Q , Ding J , Wang X
Ref : Brain Sci , 11 : , 2021
Abstract : Epileptogenesis may be responsible for both of recurrent seizures and comorbid depression in epilepsy. Disease-modifying treatments targeting the latent period before spontaneous recurrent seizures may contribute to the remission of seizures and comorbid depression. We hypothesized that pre-treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase (sEH) inhibitor, which has anti-inflammatory and neuroprotective effects might rescue status epilepticus (SE)-induced dendritic spine loss and alleviate depressive behaviours. Rats were either pre-treated with TPPU (0.1 mg/kg/d) intragastrically or with vehicle (40% polyethylene glycol 400) from 7 days before to 7 days after SE that was induced with lithium chloride and pilocarpine intraperitoneally. Rats in the Control group were given saline instead. The forced swim test (FST) was performed on the 8th day after SE to evaluate the depression-like behaviours in rats. The results showed that seizures severity during SE was significantly decreased, and the immobility time during FST was significantly increased through TPPU pre-treatment. Moreover, pre-treatment with TPPU attenuated inflammations including microglial gliosis and the level of proinflammatory cytokine IL-1beta in the hippocampus; in addition, neuronal and dendritic spine loss in the subfields of hippocampus was selectively rescued, and the expression of NR1 subunit of N-methyl-D-aspartate (NMDA) receptor, ERK1/2, CREB, and their phosphorylated forms involved in the dendritic spine development were all significantly increased. We concluded that pre-treatment with TPPU attenuated seizures severity during SE and depressive behaviours during the period of epileptogenesis probably by rescuing dendritic spine loss in the hippocampus.
ESTHER : Peng_2021_Brain.Sci_11_
PubMedSearch : Peng_2021_Brain.Sci_11_
PubMedID: 34827464

Title : Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model - Xiao_2021_Biomed.Res.Int_2021_5574207
Author(s) : Xiao Y , Wang X , Wang S , Li J , Xu X , Wang M , Li G , Shen W
Ref : Biomed Res Int , 2021 :5574207 , 2021
Abstract : Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-beta production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Abeta (25-35)-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Abeta (25-35)-microinjected rats attenuated hippocampal NF-kappaB activity; inhibited proinflammatory markers, namely, IL-1beta, IL-6, and TNF-alpha; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1beta, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Abeta (25-35)-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Abeta (25-35) through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.
ESTHER : Xiao_2021_Biomed.Res.Int_2021_5574207
PubMedSearch : Xiao_2021_Biomed.Res.Int_2021_5574207
PubMedID: 34350293

Title : Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway - Wu_2021_Clin.Transl.Med_11_e428
Author(s) : Wu D , Gao D , Yu H , Pi G , Xiong R , Lei H , Wang X , Liu E , Ye J , Gao Y , He T , Jiang T , Sun F , Su J , Song G , Peng W , Yang Y , Wang JZ
Ref : Clin Transl Med , 11 :e428 , 2021
Abstract : Tau accumulation and cholinergic impairment are characteristic pathologies in Alzheimer's disease (AD). However, the causal role of tau accumulation in cholinergic lesion is elusive. Here, we observed an aberrant tau accumulation in the medial septum (MS) of 3xTg and 5xFAD mice, especially in their cholinergic neurons. Overexpressing hTau in mouse MS (MS(hTau) ) for 6 months but not 3 months induced spatial memory impairment without changing object recognition and anxiety-like behavior, indicating a specific and time-dependent effect of MS-hTau accumulation on spatial cognitive functions. With increasing hTau accumulation, the MS(hTau) mice showed a time-dependent cholinergic neuron loss with reduced cholinergic projections to the hippocampus. Intraperitoneal administration of donepezil, a cholinesterase inhibitor, for 1 month ameliorated the MS-hTau-induced spatial memory deficits with preservation of MS-hippocampal cholinergic pathway and removal of tau load; and the beneficial effects of donepezil was more prominent at low dose. Proteomics revealed that MS-hTau accumulation deregulated multiple signaling pathways with numerous differentially expressed proteins (DEPs). Among them, the vacuolar protein sorting-associated protein 37D (VP37D), an autophagy-related protein, was significantly reduced in MS(hTau) mice; the reduction of VP37D was restored by donepezil, and the effect was more significant at low dose than high dose. These novel evidences reveal a causal role of tau accumulation in linking MS cholinergic lesion to hippocampus-dependent spatial cognitive damages as seen in the AD patients, and the new tau-removal and autophagy-promoting effects of donepezil may extend its application beyond simple symptom amelioration to potential disease modification.
ESTHER : Wu_2021_Clin.Transl.Med_11_e428
PubMedSearch : Wu_2021_Clin.Transl.Med_11_e428
PubMedID: 34185417

Title : Longitudinal Profile of Laboratory Parameters and Their Application in the Prediction for Fatal Outcome Among Patients Infected With SARS-CoV-2: A Retrospective Cohort Study - Zeng_2021_Clin.Infect.Dis_72_626
Author(s) : Zeng HL , Lu QB , Yang Q , Wang X , Yue DY , Zhang LK , Li H , Liu W , Li HJ
Ref : Clin Infect Dis , 72 :626 , 2021
Abstract : BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.
ESTHER : Zeng_2021_Clin.Infect.Dis_72_626
PubMedSearch : Zeng_2021_Clin.Infect.Dis_72_626
PubMedID: 33048116

Title : Pig Liver Esterases Hydrolyze Endocannabinoids and Promote Inflammatory Response - Zhou_2021_Front.Immunol_12_670427
Author(s) : Zhou Q , Yan B , Sun W , Chen Q , Xiao Q , Xiao Y , Wang X , Shi D
Ref : Front Immunol , 12 :670427 , 2021
Abstract : Endocannabinoids are endogenous ligands of cannabinoid receptors and activation of these receptors has strong physiological and pathological significance. Structurally, endocannabinoids are esters (e.g., 2-arachidonoylglycerol, 2-AG) or amides (e.g., N-arachidonoylethanolamine, AEA). Hydrolysis of these compounds yields arachidonic acid (AA), a major precursor of proinflammatory mediators such as prostaglandin E(2). Carboxylesterases are known to hydrolyze esters and amides with high efficiency. CES1, a human carboxylesterase, has been shown to hydrolyze 2-AG, and shares a high sequence identity with pig carboxylesterases: PLE1 and PLE6 (pig liver esterase). The present study was designed to test the hypothesis that PLE1 and PLE6 hydrolyze endocannabinoids and promote inflammatory response. Consistent with the hypothesis, purified PLE1 and PLE6 efficaciously hydrolyzed 2-AG and AEA. PLE6 was 40-fold and 3-fold as active as PLE1 towards 2-AG and AEA, respectively. In addition, both PLE1 and PLE6 were highly sensitive to bis(4-nitrophenyl) phosphate (BNPP), an aryl phosphodiester known to predominately inhibit carboxylesterases. Based on the study with BNPP, PLEs contributed to the hydrolysis of 2-AG by 53.4 to 88.4% among various organs and cells. Critically, exogenous addition or transfection of PLE6 increased the expression and secretion of proinflammatory cytokines in response to the immunostimulant lipopolysaccharide (LPS). This increase was recapitulated in cocultured alveolar macrophages and PLE6 transfected cells in transwells. Finally, BNPP reduced inflammation trigged by LPS accompanied by reduced formation of AA and proinflammatory mediators. These findings define an innovative connection: PLE-endocannabinoid-inflammation. This mechanistic connection signifies critical roles of carboxylesterases in pathophysiological processes related to the metabolism of endocannabinoids.
ESTHER : Zhou_2021_Front.Immunol_12_670427
PubMedSearch : Zhou_2021_Front.Immunol_12_670427
PubMedID: 34079552
Gene_locus related to this paper: pig-PLE1 , pig-a0a1s6l967

Title : Enantioselective bioaccumulation and detoxification mechanisms of earthworms (Eisenia fetida) exposed to mandipropamid - Fang_2021_Sci.Total.Environ_796_149051
Author(s) : Fang K , Han L , Liu Y , Fang J , Wang X , Liu T
Ref : Sci Total Environ , 796 :149051 , 2021
Abstract : As a novel chiral amide fungicide, the enantioselective behaviors of mandipropamid in the soil environment are unclear. Furthermore, there is a need to understand the stress response mechanisms of soil organisms exposed to mandipropamid isomers. Therefore, the selective bioaccumulation of mandipropamid isomers and detoxification mechanisms of earthworms (Eisenia fetida) were investigated in this study. Our results suggested that the enantioselective bioaccumulation of mandipropamid in earthworms occurred with the preferential enrichment of S-(+)-isomer. The activities of detoxification enzymes, such as cytochrome P450 (CYP450), glutathione-S-transferases (GST), and carboxylesterase (CarE), changed significantly upon exposure to S-(+)- and R-(-)-mandipropamid (particularly for CYP450 and GST). A transcriptome analysis revealed that more differentially expressed genes (DEGs) were observed under S-(+)-isomer exposure (15,798) than those under R-(-)-isomer exposure (12,222), as compared to the control group. These DEGs were mainly enriched in bile secretion and thyroid hormone signaling pathways, which were related to the detoxification process in earthworms. Moreover, the 20 DEGs, which exhibited the most profound changes (such as CYP2 and CYP3A4) in these pathways, were screened, clustered, and observed to be mainly involved in regulating the detoxification function of earthworm cells. These results indicated that detoxification systems played an essential role in the stress response to mandipropamid exposure. Additionally, earthworms were more sensitive to the stress induced by S-(+)-mandipropamid than that induced by R-(-)-mandipropamid. This is the first study to elucidate the mandipropamid detoxification mechanism of earthworms at the enantiomer level, which can be beneficial for remediating chiral pollutants.
ESTHER : Fang_2021_Sci.Total.Environ_796_149051
PubMedSearch : Fang_2021_Sci.Total.Environ_796_149051
PubMedID: 34280637

Title : Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis - Yi_2021_Front.Physiol_12_674023
Author(s) : Yi J , Wang S , Wang Z , Wang X , Li G , Zhang X , Pan Y , Zhao S , Zhang J , Zhou JJ , Wang J , Xi J
Ref : Front Physiol , 12 :674023 , 2021
Abstract : Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.
ESTHER : Yi_2021_Front.Physiol_12_674023
PubMedSearch : Yi_2021_Front.Physiol_12_674023
PubMedID: 34566671

Title : LIPG: an inflammation and cancer modulator - Hong_2021_Cancer.Gene.Ther_28_27
Author(s) : Hong C , Deng R , Wang P , Lu X , Zhao X , Wang X , Cai R , Lin J
Ref : Cancer Gene Therapy , 28 :27 , 2021
Abstract : Endothelial lipase (LIPG/EL) performs fundamental and vital roles in the human body, including cell composition, cytokine expression, and energy provision. Since LIPG predominantly functions as a phospholipase as well as presents low levels of triglyceride lipase activity, it plays an essential role in lipoprotein metabolism, and involves in the metabolic syndromes such as inflammatory response and atherosclerosis. Cytokines significantly affect LIPG expression in endothelial cells in many diseases. Recently, it is suggested that LIPG contributes to cancer initiation and progression, and LIPG attached increasing importance to its potential for future targeted therapy.
ESTHER : Hong_2021_Cancer.Gene.Ther_28_27
PubMedSearch : Hong_2021_Cancer.Gene.Ther_28_27
PubMedID: 32572177
Gene_locus related to this paper: human-LIPG

Title : Structural and biochemical analyses of the tetrameric carboxypeptidase S9Cfn from Fusobacterium nucleatum - Wang_2021_Acta.Crystallogr.D.Struct.Biol_77_1554
Author(s) : Wang X , Cheng MT , Chen ZP , Jiang YL , Ge YS , Xia R , Hou WT
Ref : Acta Crystallographica D Struct Biol , 77 :1554 , 2021
Abstract : As one of the most abundant bacteria in the human oral cavity, Fusobacterium nucleatum is closely involved in various oral diseases and is also a risk factor for other diseases. The peptidases of F. nucleatum can digest exogenous peptides into amino acids to satisfy its nutrient requirements. Here, a putative F. nucleatum peptidase, termed S9Cfn, which belongs to the S9C peptidase family was identified. Enzymatic activity assays combined with mass-spectrometric analysis revealed that S9Cfn is a carboxypeptidase, but not an aminopeptidase as previously annotated. The crystal structure of the S9Cfn tetramer was solved at 2.6A resolution and was found to contain a pair of oligomeric pores in the center. Structural analysis, together with site-directed mutagenesis and enzymatic activity assays, revealed a substrate-entrance tunnel that extends from each oligomeric pore to the catalytic triad, adjacent to which three conserved arginine residues are responsible for substrate binding. Moreover, comparison with other S9 peptidase structures indicated drastic conformational changes of the oligomeric pores during the catalytic cycle. Together, these findings increase the knowledge of this unique type of tetrameric carboxypeptidase and provide insight into the homeostatic control of microbiota in the human oral cavity.
ESTHER : Wang_2021_Acta.Crystallogr.D.Struct.Biol_77_1554
PubMedSearch : Wang_2021_Acta.Crystallogr.D.Struct.Biol_77_1554
PubMedID: 34866611
Gene_locus related to this paper: fusnu-a0a1s1mbe1

Title : Construction and characterization of CRISPR\/Cas9 knockout rat model of carboxylesterase 2a gene - Liu_2021_Mol.Pharmacol__2
Author(s) : Liu J , Shang X , Huang S , Xu Y , Lu J , Zhang Y , Liu Z , Wang X
Ref : Molecular Pharmacology , : , 2021
Abstract : Carboxylesterase 2 (CES2), an important metabolic enzyme, plays a critical role in drug biotransformation and lipid metabolism. Although CES2 is very important, few animal models have been generated to study its properties and functions. Rat Ces2 is similar to human CES2A-CES3A-CES4A gene cluster, with highly similar gene structure, function and substrate. In this report, CRISPR/Cas9 technology was firstly used to knock out rat Ces2a, a main subtype of Ces2 mostly distributed in liver and intestine. This model showed the absence of CES2A protein expression in liver. Further pharmacokinetic studies of diltiazem, a typical substrate of CES2A, confirmed the loss of function of CES2A both in vivo and in vitro. At the same time, the expression of CES2C and CES2J protein in liver decreased significantly. The body and liver weight of Ces2a knockout rats also increased, but the food intake did not change. Moreover, the deficiency of Ces2a led to obesity, insulin resistance and liver fat accumulation, which are consistent with the symptoms of nonalcoholic fatty liver disease (NAFLD). Therefore, this rat model is not only a powerful tool to study drug metabolism mediated by CES2, but also a good disease model to study NAFLD. Significance Statement Human CES2 plays a key role in the first-pass hydrolysis metabolism of most oral prodrugs as well as lipid metabolism. In this study, CRISPR/Cas9 technology was used to knock out Ces2a gene in rats for the first time. This model can be used not only in the study of drug metabolism and pharmacokinetics, but also as a disease model of NAFLD and other metabolic disorder.
ESTHER : Liu_2021_Mol.Pharmacol__2
PubMedSearch : Liu_2021_Mol.Pharmacol__2
PubMedID: 34503976
Gene_locus related to this paper: ratno-LOC246252

Title : Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites - Hu_2021_Sci.Rep_11_21639
Author(s) : Hu Y , Chen R , Gao H , Lin H , Wang J , Wang X , Liu J , Zeng Y
Ref : Sci Rep , 11 :21639 , 2021
Abstract : Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model's outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783-0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784-0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP.
ESTHER : Hu_2021_Sci.Rep_11_21639
PubMedSearch : Hu_2021_Sci.Rep_11_21639
PubMedID: 34737270

Title : Residual behaviors and metabolic pathway of ethylparaben in Drosophila melanogaster - Wang_2021_Ecotoxicol.Environ.Saf_230_113124
Author(s) : Wang Y , Qin M , Wang X , Han J , Chen R , Zhang M , Gu W
Ref : Ecotoxicology & Environmental Safety , 230 :113124 , 2021
Abstract : OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedID: 34968799

Title : Nutritional Status and Body Composition in Wilson Disease: A Cross-Sectional Study From China - Geng_2021_Front.Nutr_8_790520
Author(s) : Geng H , Wang S , Jin Y , Cheng N , Song B , Shu S , Li B , Han Y , Gao L , Ding Z , Xu Y , Wang X , Ma Z , Sun Y
Ref : Front Nutr , 8 :790520 , 2021
Abstract : Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes. Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally. Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P<0.01); while there were no significant differences in muscle and skeletal muscle between these two subtypes. The overall prevalence of abnormal nutritional status in WD patients was 43.41% (56/129). The prevalence of high-nutritional risk and overweight in WD patients was 17.83% (23 of 129) and 25.58% (33 of 129), respectively. Compare with patients with high nutritional risk, macro platelet ratio, alkaline phosphatase, the basal metabolic rate (p < 0.05), creatinine, trunk fat rate (p < 0.01) and appendicular skeletal muscle mass (p < 0.001) were significantly higher in patients without nutritional risk (p < 0.001). Patients with a high nutritional risk tend to have a lower cholinesterase concentration (x (2) = 4.227, p < 0.05). Conclusion: Both patients with H-subtype and N-subtype are prone to have an abnormal nutritional status. Longitudinal studies are required to investigate if nutritional status and body composition could reflect prognosis in WD patients, and which of these body composition indexes contribute to malnutrition and worse prognosis.
ESTHER : Geng_2021_Front.Nutr_8_790520
PubMedSearch : Geng_2021_Front.Nutr_8_790520
PubMedID: 35036410

Title : Detection of organophosphorus pesticides by nanogold\/mercaptomethamidophos multi-residue electrochemical biosensor - Zhao_2021_Food.Chem_354_129511
Author(s) : Zhao G , Zhou B , Wang X , Shen J , Zhao B
Ref : Food Chem , 354 :129511 , 2021
Abstract : Based on the successful synthesis of mercaptomethamidophos as a substrate, a novel nanogold/mercaptomethamidophos multi-residue electrochemical biosensor was designed and fabricated by combining nanoscale effect, strong Au-S bonds as well as interaction between acetylcholinesterase (AChE) and mercaptomethamidophos, which can simultaneously detect 11 kinds of organophosphorus pesticides (OPPs) and total amount of OPPs using indirect competitive method. Electrochemical behavior of the modified electrode was characterized by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The AChE concentration and incubation time were optimized at 37.4 degreesC to achieve the best detection effect. This biosensor exhibits excellent electrochemical properties with a wider linear range of 0.1 ~ 1500 ng.mL(-1), lower detection limit of 0.019 ~ 0.077 ng.mL(-1), better stability and repeatability, which realizes the rapid detection of total amount of OPPs, and can simultaneously detect a large class of OPPs rather than one kind of OPP. Two OPPs (trichlorfon, dichlorvos) were detected in actual samples of apple and cabbage and achieved satisfactory test results.
ESTHER : Zhao_2021_Food.Chem_354_129511
PubMedSearch : Zhao_2021_Food.Chem_354_129511
PubMedID: 33735695

Title : Discovery of a Broad-Spectrum Fluorogenic Agonist for Strigolactone Receptors through a Computational Approach - Wang_2021_J.Agric.Food.Chem__
Author(s) : Wang DW , Yu SY , Pang ZL , Ma DJ , Liang L , Wang X , Wei T , Yang HZ , Ma YQ , Xi Z
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : Strigolactones (SLs) are plant hormones that play various roles in plant physiology, including provoking the germination of parasitic weeds Orobanche and Striga. A family of alpha/beta-hydrolases have been proposed to be the SL receptor proteins. Effective assays for measuring the activity of SL receptors could promote the development of SL-related biology and chemistry. In this study, we developed a new approach called pharmacophore-linked probe virtual screening (PPVS). Its application yielded an effective "off-on" probe named Xilatone Red (XLR). This probe showed a broad spectrum and excellent sensitivity toward SL receptors, including ShD14 (Striga D14), for which the detection limit was determined to be in the micromolar range, outperforming that of the commercial fluorogenic agonist Yoshimulactone Green (YLG). Upon hydrolysis by SL receptors, XLR provided fluorogenic and colorimetric signaling responses. Furthermore, XLR could induce germination of Phelipanche aegyptiaca seeds and prevent Arabidopsis max4-1 branching defects at micromolar concentrations. Our molecular simulations revealed the essential factors in the molecular perception of XLR. We anticipate that this study can prompt the discovery of high-performance SL agonists/antagonists to combat parasitic weeds.
ESTHER : Wang_2021_J.Agric.Food.Chem__
PubMedSearch : Wang_2021_J.Agric.Food.Chem__
PubMedID: 34478295

Title : ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis - Ding_2021_ACS.Chem.Neurosci__
Author(s) : Ding Y , Wang X , Ji J , Zhang X , Chen M , Li S , Zhang Q , Liu P
Ref : ACS Chem Neurosci , : , 2021
Abstract : Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects.
ESTHER : Ding_2021_ACS.Chem.Neurosci__
PubMedSearch : Ding_2021_ACS.Chem.Neurosci__
PubMedID: 33517657

Title : Characterization and functional analysis of two acetylcholinesterase genes in Bradysia odoriphaga Yang et Zhang (Diptera: Sciaridae) - Ding_2021_Pestic.Biochem.Physiol_174_104807
Author(s) : Ding Q , Xu X , Wang X , Ullah F , Gao X , Song D
Ref : Pestic Biochem Physiol , 174 :104807 , 2021
Abstract : Two acetylcholinesterase genes (Boace1 and Boace2) were cloned from Bradysia odoriphaga, a devastating soil pest that mainly damages Chinese chives. The Boace1 encodes BoAChE1 protein consisting of 696 amino acid residues, while Boace2 encodes BoAChE2 containing 638 amino acids. Phylogenetic analysis showed that Boace1 and Boace2 are appeared to be distinct clusters. The gene expression patterns at different development stages and various body parts tissues were examined, and their biological functions were characterized by RNA interference and analog docking prediction. The results showed that both Boace genes were expressed in all developmental stages and examined tissues. The transcript level of Boace2 was significantly higher than Boace1 in all tested samples, and Boace1 was found most abundant in the head while Boace2 was highly expressed in the fat body of B. odoriphaga. The silencing of Boace1 and Boace2 significantly decreased the AChE activity of 36.6% and 14.8% separately, and increased the susceptibility of B. odoriphaga to phoxim, with 60.8% and 44.7% mortality. Besides, overexpression and gene duplication of Boace1 were found in two field resistant populations, and two major mutations, A319S and G400V, were detected in Boace1. Moreover, the docking results revealed that BoAChE1 had a higher affinity towards organophosphorus than BoAChE2. It is concluded that Boace2 is the most abundant ace type in B. odoriphaga, while both Boace play vital roles. Boace1 might play a major neurological function and more likely be the prime target for insecticides, while Boace2 might play some important unidentified roles.
ESTHER : Ding_2021_Pestic.Biochem.Physiol_174_104807
PubMedSearch : Ding_2021_Pestic.Biochem.Physiol_174_104807
PubMedID: 33838708
Gene_locus related to this paper: 9dipt-MT380203 , 9dipt-MT380204

Title : Phenotypic, genotypic and biochemical changes during pyrethroid resistance selection in Anopheles gambiae mosquitoes - Machani_2020_Sci.Rep_10_19063
Author(s) : Machani MG , Ochomo E , Zhong D , Zhou G , Wang X , Githeko AK , Yan G , Afrane YA
Ref : Sci Rep , 10 :19063 , 2020
Abstract : The directional selection for insecticide resistance due to indiscriminate use of insecticides in public health and agricultural system favors an increase in the frequency of insecticide-resistant alleles in the natural populations. Similarly, removal of selection pressure generally leads to decay in resistance. Past investigations on the emergence of insecticide resistance in mosquitoes mostly relied on field survey of resistance in vector populations that typically had a complex history of exposure to various public health and agricultural pest control insecticides in nature, and thus the effect of specific insecticides on rate of resistance emergency or resistance decay rate is not known. This study examined the phenotypic, genotypic, and biochemical changes that had occurred during the process of selection for pyrethroid resistance in Anopheles gambiae, the most important malaria vector in Africa. In parallel, we also examined these changes in resistant populations when there is no selection pressure applied. Through repeated deltamethrin selection in adult mosquitoes from a field population collected in western Kenya for 12 generations, we obtained three independent and highly pyrethroid-resistant An. gambiae populations. Three susceptible populations from the same parental population were generated by removing selection pressure. These two lines of mosquito populations differed significantly in monooxygenase and beta-esterase activities, but not in Vgsc gene mutation frequency, suggesting metabolic detoxification mechanism plays a major role in generating moderate-intensity resistance or high-intensity resistance. Pre-exposure to the synergist piperonyl butoxide restored the susceptibility to insecticide among the highly resistant mosquitoes, confirming the role of monooxygenases in pyrethroid resistance. The rate of resistance decay to become fully susceptible from moderate-intensity resistance took 15 generations, supporting at least 2-years interval is needed when the rotational use of insecticides with different modes of action is considered for resistance management.
ESTHER : Machani_2020_Sci.Rep_10_19063
PubMedSearch : Machani_2020_Sci.Rep_10_19063
PubMedID: 33149227

Title : Neuroprotective effects of the aerial parts of Polygala tenuifolia Willd extract on scopolamine-induced learning and memory impairments in mice - Wang_2020_Biomed.Rep_13_37
Author(s) : Wang X , Zhang D , Song W , Cai CF , Zhou Z , Fu Q , Yan X , Cao Y , Fang M
Ref : Biomed Rep , 13 :37 , 2020
Abstract : Alzheimer's disease is a common neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. Aerial parts of Polygala tenuifolia Willd (APT) is a traditional Chinese medicine used for the treatment of amnesia. The present study aimed to investigate the protective effects of APT on scopolamine-induced learning and memory impairments in mice. Scopolamine-induced mice were used to determine the effects of APT on learning and memory impairment. Mice were orally administered with APT (25, 50 and 100 mg/kg) and piracetam (750 mg/kg) for 14 days, and intraperitoneally injected with scopolamine (2 mg/kg) from days 8 to 14. Morris water maze and step-down tests were performed to evaluate learning and memory. Levels of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), interleukin (IL)-1beta, IL-10 and brain-derived neurotrophic factor (BDNF) in the hippocampus and frontal cortex were measured by ELISA. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were measured via biochemical detection. The results demonstrated that APT ameliorated learning and memory impairment in scopolamine-induced mice. Correspondingly, APT significantly increased ACh and ChAT levels in the hippocampus and prefrontal cortex of scopolamine-induced mice. Additionally, treatment with APT significantly increased BDNF and IL-10 levels, and decreased IL-1beta and AChE levels in the same mice. Furthermore, APT significantly increased SOD activity and GSH content, and decreased MDA levels in brain tissue. These results indicated that APT may ameliorate learning and memory impairment by regulating cholinergic activity, promoting BDNF and inhibiting neuroinflammation and oxidative stress.
ESTHER : Wang_2020_Biomed.Rep_13_37
PubMedSearch : Wang_2020_Biomed.Rep_13_37
PubMedID: 32874571

Title : Antioxidative enzyme activities in the Rhodeinae sinensis Gunther and Macrobrachium nipponense and multi-endpoint assessment under tonalide exposure - Li_2020_Ecotoxicol.Environ.Saf_199_110751
Author(s) : Li W , Wang S , Li J , Wang X , Cui L , Chen J , Liu Z
Ref : Ecotoxicology & Environmental Safety , 199 :110751 , 2020
Abstract : Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 mug/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 mug/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 mug/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 mug/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 mug/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 mug/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 mug/L and 0.000395 mug/L, respectively, which were significantly lower than the PNEC of 2.636 mug/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.
ESTHER : Li_2020_Ecotoxicol.Environ.Saf_199_110751
PubMedSearch : Li_2020_Ecotoxicol.Environ.Saf_199_110751
PubMedID: 32446104

Title : The degraded polysaccharide from Pyropia haitanensis represses amyloid beta peptide-induced neurotoxicity and memory in vivo - Zhang_2020_Int.J.Biol.Macromol_146_725
Author(s) : Zhang Z , Wang X , Pan Y , Wang G , Mao G
Ref : Int J Biol Macromol , 146 :725 , 2020
Abstract : An antioxidant polysaccharide, porphyran, from red algae Pyropia haitanensis, is introduced as a protective agent against neurotoxicity-induced amyloid beta peptide (Abeta) of Alzheimer's disease (AD) mice. Then the activity of acetylcholinesterase (AChE) and choline acetyltransferase (CHAT) in the cortical and hippocampal tissue were examined by colorimetric method. Results showed that porphyran significantly ameliorated the learning and memory impairment induced by Abeta1-40. Biochemical analysis showed that porphyran increased ChAT activity and decreased AChE activity in the cortical and hippocampal tissue. The mechanism may be related with the increase of cerebral acetylcholine content. Porphyran has a potential of developing anti-aging drug.
ESTHER : Zhang_2020_Int.J.Biol.Macromol_146_725
PubMedSearch : Zhang_2020_Int.J.Biol.Macromol_146_725
PubMedID: 31739053

Title : Characterization of an acidic pectin methylesterase from Paenibacillus xylanexedens and its application in fruit processing - Zhong_2020_Protein.Expr.Purif_179_105798
Author(s) : Zhong L , Wang X , Fan L , Ye X , Li Z , Cui Z , Huang Y
Ref : Protein Expr Purif , 179 :105798 , 2020
Abstract : A pectinase-producing bacterial isolate, identified as Paenibacillus xylanexedens SZ 29, was screened by using the soil dilution plate with citrus pectin and congo red. A pectin methylesterase gene (Pxpme) was cloned and expressed in Escherichia coli. The gene coded for a protein with 334 amino acids and a calculated molecular mass of 36.76 kDa. PxPME showed the highest identity of 32.4% with the characterized carbohydrate esterase family 8 pectin methylesterase from Daucus carota. The recombined PxPME showed a specific activity with 39.38 U/mg against citrus pectin with >65% methylesterification. The optimal pH and temperature for PxPME activity were 5.0 and 45 degreeC. Its K(m) and V(max) value were determined to be 1.43 mg/mL and 71.5 mol/mg.min, respectively. Moreover, PxPME could increase the firmness of pineapple cubes by 114% when combined with CaCl(2). The acidic and mesophilic properties make PxPME a potential candidate for application in the fruit processing.
ESTHER : Zhong_2020_Protein.Expr.Purif_179_105798
PubMedSearch : Zhong_2020_Protein.Expr.Purif_179_105798
PubMedID: 33232801

Title : A novel streptonigrin type alkaloid from the Streptomyces flocculus CGMCC 4.1223 mutant stnA\/Q2 - Wang_2020_Nat.Prod.Res__3
Author(s) : Wang X , Xu F , Huang T , Deng Z , Lin S
Ref : Nat Prod Res , :1 , 2020
Abstract : Streptonigrin (STN) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activities. Previously, the biosynthetic gene cluster of STN was identified in Streptomyces flocculus CGMCC 4.1223, revealing an alpha/beta-hydrolase (StnA) and a methyltransferase (StnQ2). In this work, a double mutant delta stnA/Q2 was constructed by genetic manipulation and produced a novel derivative of STN, named as streptonigramide. Structure of streptonigramide was established by spectroscopic analyses. Its biosynthetic pathway has been proposed as well.
ESTHER : Wang_2020_Nat.Prod.Res__3
PubMedSearch : Wang_2020_Nat.Prod.Res__3
PubMedID: 33280413
Gene_locus related to this paper: 9actn-l7pij2

Title : Transcription Factors ZEB1 and CREB Promote the Transcription of Bovine ABHD5 Gene - Wang_2021_DNA.Cell.Biol_40_219
Author(s) : Wang X , Li A , Raza SHA , Liang C , Zhang S , Mei C , Yang W , Zan L
Ref : DNA & Cell Biology , 40 :219 , 2020
Abstract : Alpha/beta hydrolase domain 5 (ABHD5) plays a significant role in intracellular lipid metabolism, which is regulated by a complex network of transcription factors. The transcriptional regulation of the ABHD5 gene in cattle and other livestock, however, has not been previously investigated. Investigations in humans and animal models indicate that the transcription factors zinc finger E-box binding homeobox 1 (ZEB1) and cAMP-response element binding protein (CREB) may play important roles in the transcriptional regulation of ABHD5 in cattle. Our comparison of the sequence similarities in the transcription factor binding sites in Bos taurus, Bos indicus, Bos mutus, and Homo sapiens revealed high homology. Based on the data collected by the Cistrome Data Browser and its visualization window, we found that ZEB1 and CREB have significant ChIP-seq enrichments in the 5'-untranslated region (5' UTR) of the human ABHD5 gene. In bovine adipocytes, we detected ZEB1 and CREB binding sites in the ABHD5 gene. Mutations in the ZEB1 and CREB binding sites significantly reduced the promoter activity (p < 0.05 and p < 0.01, respectively). Moreover, electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP) assays demonstrated the binding of the transcription factors in vivo and in vitro, respectively. And overexpression or silencing the expression of the ZEB1 and CREB, respectively, resulted in significant changes to the ABHD5 promoter activity. Collectively, these results indicate that ZEB1 and CREB are important transcription factors that regulate ABHD5 gene expression in bovine adipocytes. They further our understanding of the transcriptional regulation and biological functions of the bovine ABHD5 gene.
ESTHER : Wang_2021_DNA.Cell.Biol_40_219
PubMedSearch : Wang_2021_DNA.Cell.Biol_40_219
PubMedID: 33332227
Gene_locus related to this paper: bovin-q0vcc8 , human-ABHD5

Title : Enantioselective toxicity and oxidative stress effects of acetochlor on earthworms (Eisenia fetida) by mediating the signaling pathway - Liu_2020_Sci.Total.Environ__142630
Author(s) : Liu Y , Fang K , Zhang X , Liu T , Wang X
Ref : Sci Total Environ , :142630 , 2020
Abstract : Acetochlor (ACT) as a widely used chiral chloroacetamide herbicide is appropriate to evaluate the potential toxicity in soil ecosystems at enantiomeric level. The acute and subchronic toxicities of R-acetochlor (R-ACT) and S-acetochlor (S-ACT) on earthworms (Eisenia fetida) were investigated in the present study. Residual analyses showed that S-ACT degraded faster than R-ACT in artificial soil with half-lives of 16.5 and 21.7 d, respectively. Additionally, significant enantioselective acute toxicity in earthworms from between S-ACT and R-ACT (p < 0.05) was observed, and the acute toxicity of R-ACT were 1.9 and 1.5 times higher than those of S-ACT in the filter paper test and artificial soil test. The hydroxyl radical (OH(-)) content, superoxide dismutase (SOD) and antioxidant enzyme catalase (CAT) activities, and cytochrome P450 content in earthworms significantly increased under the influence of ACT enantiomers; however, the acetylcholinesterase (AchE) activity was significantly inhibited after exposure to the two enantiomers. Moreover, lipid peroxidation and DNA damage were induced by ACT enantiomers. The results of transcriptome sequencing indicated that R-ACT induced a stronger oxidative stress effect than S-ACT in earthworms by mediating signaling pathways, which may be the primary reason for the enantioselective toxicity between S-ACT and R-ACT. Overall, the results demonstrated that R-ACT has a higher risk than S-ACT in the soil environment, which is important for understanding the enantioselective behavior of chloroacetamide pesticides.
ESTHER : Liu_2020_Sci.Total.Environ__142630
PubMedSearch : Liu_2020_Sci.Total.Environ__142630
PubMedID: 33069465

Title : Metal-Organic Frameworks Conjugated Lipase with Enhanced Bio-catalytic Activity and Stability - Zou_2020_Appl.Biochem.Biotechnol__
Author(s) : Zou B , Zhang L , Xia J , Wang P , Yan Y , Wang X , Adesanya IO
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Covalent immobilization of lipase onto a solid carrier is an effective way to enhance stability. Immobilization inhibits the activity of lipase due to decreased flexibility of enzyme structure via the covalent bond. In this study, monomer of the metal-organic frameworks (MOFs) material ZIF-8 (2-methyl imidazole-4-carboxylic acid) was innovatively used as a chemical modifier of Candida nrugosa lipase (CRL). The circular dichroism spectra results show that the CRL molecule was altered by chemical modification and thus its catalytic activity was 1.3 times higher than that of the free CRL. The modified CRL molecule was further immobilized in the "skeleton" of ZIF-8 through the monomer while in situ forming the cell skeleton of the MOFs, which prevent the active center from being destroyed. The results show that conjugation of chemical modification and immobilized enzymes ensure that there was no obvious reduction in the activity of CRL after immobilization and the stability of CRL was improved. Especially, the organic solvent stability of the modified immobilization CRL in isopropanol was significantly improved and retained more than 148% of its activity.
ESTHER : Zou_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Zou_2020_Appl.Biochem.Biotechnol__
PubMedID: 32323142

Title : Efficient biodegradation of highly crystallized polyethylene terephthalate through cell surface display of bacterial PETase - Chen_2020_Sci.Total.Environ_709_136138
Author(s) : Chen Z , Wang Y , Cheng Y , Wang X , Tong S , Yang H , Wang Z
Ref : Sci Total Environ , 709 :136138 , 2020
Abstract : Polyethylene terephthalate (PET) is one of the most widely used plastics in the world. Accumulation of the discarded PET in the environment is creating a global environmental problem. Recently, a bacterial enzyme named PETase was found to have the novel ability to degrade the highly crystallized PET. However, the enzymatic activity of native PETase is still low limiting its possible use in recycling of PET. In this study, we developed a whole-cell biocatalyst by displaying PETase on the surface of yeast (Pichia pastoris) cell to improve its degradation efficiency. Our data shows that PETase could be functionally displayed on the yeast cell with enhanced pH and thermal stability. The turnover rate of the PETase-displaying yeast whole-cell biocatalyst towards highly crystallized PET dramatically increased about 36-fold compared with that of purified PETase. Furthermore, the whole-cell biocatalyst showed stable turnover rate after seven repeated use and under some chemical/solvent conditions, and its ability to degrade different commercial highly crystallized PET bottles. Our results reveal that PETase-displaying whole-cell biocatalyst affords a promising route for efficient biological recycling of PET.
ESTHER : Chen_2020_Sci.Total.Environ_709_136138
PubMedSearch : Chen_2020_Sci.Total.Environ_709_136138
PubMedID: 31887523

Title : Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis - Wang_2020_J.Agric.Food.Chem_68_12358
Author(s) : Wang X , Zhao X , Yang Z , Wang T
Ref : Journal of Agricultural and Food Chemistry , 68 :12358 , 2020
Abstract : Acyl migration occurs in many reactions and is the main obstacle for structured lipid synthesis. In this study, 2-monoacylglycerol (2-MAG) was prepared by enzymatic ethanolysis in three different media to evaluate the effect of environment on product composition. The contents of 2-MAG obtained in ethanol, hexane + ethanol, and t-butanol + ethanol systems were 30.6, 15.7, and 32.4%, respectively, after 3 h reaction. Afterward, the acyl migration kinetics of 2-MAG were studied in solvent and solventless systems without the use of lipase. Results indicate that 2-MAG in the solventless system had the highest acyl migration rate. The isomerization was efficiently prevented by the use of polar solvents, especially t-butanol. The rate constants were shown to be the highest and activation energy values were the lowest in solventless systems. The novel finding in this study was that solvent had inhibitory effect on 2-MAG isomerization, but the nonpolar hexane had the lowest inhibition of acyl migration compared to other solvents.
ESTHER : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedSearch : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedID: 33084305

Title : Synthesis and biological evaluation of 3-arylbenzofuranone derivatives as potential anti-Alzheimer's disease agents - Yang_2020_J.Enzyme.Inhib.Med.Chem_35_805
Author(s) : Yang J , Yun Y , Miao Y , Sun J , Wang X
Ref : J Enzyme Inhib Med Chem , 35 :805 , 2020
Abstract : Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 +/- 0.01 muM) is similar to the positive drug donepezil (0.059 +/- 0.003 muM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease.
ESTHER : Yang_2020_J.Enzyme.Inhib.Med.Chem_35_805
PubMedSearch : Yang_2020_J.Enzyme.Inhib.Med.Chem_35_805
PubMedID: 32183602

Title : Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway - Zhang_2020_Exp.Cell.Res__111856
Author(s) : Zhang Y , Sun L , Sun Y , Chen Y , Wang X , Xu M , Chi P , Xu Z , Lu X
Ref : Experimental Cell Research , :111856 , 2020
Abstract : CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (P<0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment.
ESTHER : Zhang_2020_Exp.Cell.Res__111856
PubMedSearch : Zhang_2020_Exp.Cell.Res__111856
PubMedID: 31981591
Gene_locus related to this paper: human-CES2

Title : Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase - Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
Author(s) : Pu Y , Yang J , Chang L , Qu Y , Wang S , Zhang K , Xiong Z , Zhang J , Tan Y , Wang X , Fujita Y , Ishima T , Wan D , Hwang SH , Hammock BD , Hashimoto K
Ref : Proc Natl Acad Sci U S A , : , 2020
Abstract : Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.
ESTHER : Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
PubMedSearch : Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
PubMedID: 32398374

Title : Widespread Multiple Insecticide Resistance in the Major Dengue Vector Aedes albopictus in Hainan Province, China - Li_2020_Pest.Manag.Sci_77_1945
Author(s) : Li Y , Zhou G , Zhong D , Wang X , Hemming-Schroeder E , David RE , Lee MC , Zhong S , Yi G , Liu Z , Cui G , Yan G
Ref : Pest Manag Sci , 77 :1945 , 2020
Abstract : BACKGROUND: Aedes albopictus is a highly invasive mosquito and has become a potential vector of dengue, chikungunya and Zika viruses. Insecticide-based mosquito interventions are the main tools for vector-borne disease control. However, mosquito resistance to insecticides is a major threat to effective prevention and control. Five Ae. albopictus populations across Hainan Province, China were investigated for susceptibility to multiple insecticides and resistance mechanisms. RESULTS: Larval bioassays indicated that resistance to pyrethroids was common in all larval populations. Adult bioassays revealed all populations were either resistant or highly resistant to at least 4 of the 6 synthetic insecticides (deltamethrin, permethrin, cyfluthrin, propoxur, malathion, and DDT) tested. Pre-exposure of mosquitoes to the synergistic agent piperonyl butoxide (PBO) increased mosquito mortality by 2.4-43.3% in bioassays to DDT, malathion, and permethrin and rendered mosquito sensitive to deltamethrin, cyfluthrin, and propoxur. The frequency of knockdown resistance (kdr) mutations (F1534S and F1534C) ranged from 69.8% to 89.3% and from 38.1% to 87.0% in field resistant and sensitive populations, respectively. F1534S mutation was significantly associated with pyrethroid resistance. No mutation was detected in acetylcholinesterase (ace-1) gene in the two examined populations. CONCLUSION: This study provides evidence of widespread resistance to multiple insecticides in Ae. albopictus in Hainan Province, China. Both kdr mutations and metabolic detoxification were the potential causes of insecticide resistance for Ae. albopictus. Our findings highlight the need for insecticide resistance management and mosquito control measures that do not entirely depend on synthetic insecticides.
ESTHER : Li_2020_Pest.Manag.Sci_77_1945
PubMedSearch : Li_2020_Pest.Manag.Sci_77_1945
PubMedID: 33301644

Title : A novel feruloyl esterase with high rosmarinic acid hydrolysis activity from Bacillus pumilus W3 - Liang_2020_Int.J.Biol.Macromol_161_525
Author(s) : Liang W , Xiong T , Wang X , Deng H , Bai Y , Fan TP , Zheng X , Cai Y
Ref : Int J Biol Macromol , 161 :525 , 2020
Abstract : A novel feruloyl esterase (BpFae12) with rosmarinic acid (RA) hydrolysis activity was isolated from Bacillus pumilus W3 and expressed in Escherichia coli BL21 (DE3). With RA as a substrate, the optimal pH and temperature of BpFae12 were pH 8.0 and 50 degreesC, respectively. The specific enzyme activity was 12.8 U.mg(-1). BpFae12 showed the highest activity and substrate affinity toward RA (V(max) of 13.13 U.mg(-1), K(m) of 0.41 mM). Moreover, it also presented strong hydrolysis performance against chlorogenic acid (190.17 U.mg(-1)). RA was effectively Hydrolyzed into more bioactive caffeic acid and 3,4-dihydroxyphenyllactic acid by BpFae12, which have potential applications in the food industry.
ESTHER : Liang_2020_Int.J.Biol.Macromol_161_525
PubMedSearch : Liang_2020_Int.J.Biol.Macromol_161_525
PubMedID: 32531366
Gene_locus related to this paper: 9baci-BpFae12

Title : Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea - Wang_2020_Environ.Pollut_267_115397
Author(s) : Wang X , Hu M , Gu H , Zhang L , Shang Y , Wang T , Zeng J , Ma L , Huang W , Wang Y
Ref : Environ Pollut , 267 :115397 , 2020
Abstract : In recent years, antibiotics have been widely detected in coastal waters of China, which raising concerns for coastal biodiversity and aquaculture. This study evaluated the effects of short-term exposure of norfloxacin (NOR) on oxidative stress and intestinal health of the large yellow croaker Pseudosciaena crocea. Juvenile fish were exposed to four concentrations of NOR (0.1, 10, 100 and 1000 g/L) for 14 days. The results showed that NOR inhibited growth and threatened the survival of juveniles. According to the changes of intestinal microbiota, we found that NOR led to a significant decrease in intestinal microbiota diversity, with the decreased relative abundance of Proteobacteria, but the increased Tenericutes. From the perspective of microbial function, NOR inhibited metabolism, cellular defence mechanism and information transduction process. In terms of biochemical indicators, NOR caused an increase in malondialdehyde (MDA) level and inhibited superoxide dismutase (SOD) and acetyl cholinesterase (AChE) activities. Catalase (CAT) activity was activated at low concentration but significantly inhibited at high concentration of NOR. Moreover, there was a high correlation between change in biochemical indicators and change in the microbial community. Overall, environmentally relevant concentrations (0.1 g/L) and high concentrations (10, 100 and 1000 g/L) of NOR have negative effects on the defence function and intestinal health of large yellow croaker juveniles.
ESTHER : Wang_2020_Environ.Pollut_267_115397
PubMedSearch : Wang_2020_Environ.Pollut_267_115397
PubMedID: 33254654

Title : Amino acid, fatty acid, and carbohydrate metabolomic profiles with ginsenoside-induced insecticidal efficacy against Ostrinia furnacalis (Guenee) - Liu_2020_J.Ginseng.Res_44_544
Author(s) : Liu S , Wang X , Zhang R , Song M , Zhang N , Li W , Wang Y , Xu Y , Zhang L
Ref : J Ginseng Res , 44 :544 , 2020
Abstract : Background: Previous studies have shown the insecticidal efficacy of ginsenosides. In the present study, we aimed to investigate the metabolic mechanism related to the inhibitory effect of panaxadiol saponins (PDSs) against the Asian corn borer Ostrinia furnacalis (Guenee). Methods: Third instar larvae of O. furnacalis were fed normal diets with different concentrations of PDSs for 4 days. The consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food were recorded. A targeted gas chromatography-mass spectrometry assay was performed to detect the profiles of amino acids, fatty acids, and carbohydrates in larvae of O. furnacalis. In addition, the activity of detoxification-related enzymes was determined. Results and Conclusions: PDSs decreased the consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food in the 3rd instar larvae of O. furnacalis in a dose-dependent manner. PDSs decreased 15 free amino acids, 16 free fatty acids, and 5 carbohydrates and increased the levels of palmitoleic acid, palmitic acid, and 9-octadecenoic acid in the 3rd instar larvae. The activity of detoxification-related enzymes, such as acetylcholinesterase, glutathione S-transferase, cytochrome P450, carboxylesterase, trehalase, acid phosphatase, and alkaline phosphatase, was reduced in a dose-dependent manner in the 3rd instar larvae exposed to PDSs. These data confirmed the inhibitory effect of PDSs against growth, food utilization, and detoxification in the 3rd instar larvae of O. furnacalis and the potential for using PDSs as an efficient tool for insect pest management for O. furnacalis larvae.
ESTHER : Liu_2020_J.Ginseng.Res_44_544
PubMedSearch : Liu_2020_J.Ginseng.Res_44_544
PubMedID: 32617034

Title : Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial - Wang_2020_Curr.Med.Res.Opin_36_1107
Author(s) : Wang W , Yao J , Guo X , Guo Y , Yan C , Liu K , Zhang Y , Wang X , Li H , Wen Z , Li S , Xiao X , Liu W , Li Z , Zhang L , Shao S , Ye S , Qin G , Li Y , Li F , Zhang X , Li X , Peng Y , Deng H , Xu X , Zhou L , Huang Y , Cao M , Xia X , Shi M , Dou J , Yuan J
Ref : Curr Med Res Opin , 36 :1107 , 2020
Abstract : Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
ESTHER : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedSearch : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedID: 32338063

Title : Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein - Liu_2020_Cell.Death.Differ__
Author(s) : Liu R , Wang X , Curtiss C , Sheikh MS , Huang Y
Ref : Cell Death Differ , : , 2020
Abstract : We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. We found that MGL directly interacted with XIAP and enhanced E3-ligase activity and proteasomal degradation of XIAP. MGL overexpression induced cell death that was coupled with caspase activation and reduced XIAP levels. N-terminus of MGL was found to mediate interactions with XIAP and induce cell death. MGL-deficient cells exhibited elevated XIAP levels and exhibited resistance to anticancer drugs. XIAP expression was significantly elevated in tissues of MGL-deficient animals as well as human lung cancers exhibiting reduced MGL expression. Thus, MGL appears to mediate its tumor-suppressive actions by inhibiting XIAP to induce cell death.
ESTHER : Liu_2020_Cell.Death.Differ__
PubMedSearch : Liu_2020_Cell.Death.Differ__
PubMedID: 32376875
Gene_locus related to this paper: human-MGLL

Title : A new fluorescent probe for sensing of biothiols and screening of acetylcholinesterase inhibitors - Wu_2020_Org.Biomol.Chem__
Author(s) : Wu S , Li Y , Deng T , Wang X , Hu S , Peng G , Huang XA , Ling Y , Liu F
Ref : Org Biomol Chem , : , 2020
Abstract : A new N2O-type BODIPY probe (LF-Bop) has been proposed for the selective and sensitive detection of biologically relevant small molecular thiols. This detection is based on the Michael addition reaction between the thiol and nitrostyrene groups in the probe, which decreases the quenching effect from the nitro group, thus resulting in the recovery of the deep-red fluorescence from the BODIPY structure. The results show that LF-Bop is able to detect all tested free thiols through a fluorescence turn-on assay. The lowest limit of detection (LOD) for glutathione was found to be down to nanomolar levels (220 nM). Based on this probe, we have developed a new fluorescence assay for the screening of acetylcholinesterase inhibitors. In total, 11 natural and synthetic alkaloids have been evaluated. Both experimental measurements and theoretical molecular docking results reveal that both natural berberine and its synthetic derivative dihydroberberine are potential inhibitors of acetylcholinesterase.
ESTHER : Wu_2020_Org.Biomol.Chem__
PubMedSearch : Wu_2020_Org.Biomol.Chem__
PubMedID: 32167516

Title : Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats - Sun_2020_J.Int.Med.Res_48_300060520936177
Author(s) : Sun Y , Zhao Z , Li Q , Wang C , Ge X , Wang X , Wang G , Qin Y
Ref : J Internal Medicine Res , 48 :300060520936177 , 2020
Abstract : OBJECTIVES: To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). METHODS: The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. RESULTS: The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. CONCLUSIONS: Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection.
ESTHER : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedSearch : Sun_2020_J.Int.Med.Res_48_300060520936177
PubMedID: 32644834

Title : The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea - Zou_2020_BMC.Complement.Med.Ther_20_236
Author(s) : Zou Y , Hu J , Huang W , Zhu L , Shao M , Dordoe C , Ahn YJ , Wang D , Zhao Y , Xiong Y , Wang X
Ref : BMC Complement Med Ther , 20 :236 , 2020
Abstract : BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human beta-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC(50) from 292.0 to 673.9 microg/mL. Fourteen samples presented potent inhibitory activity against human BACE1 with EC(50) from 236.0 to 881.1 microg/mL. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC(50) from 2.7 to 14.4mG/Ml, 0.9 to 12.7mG/Ml, 5.0 to > 25mG/Ml, 2.7 to 17.7mG/Ml, and 2.4 to 8.7mG/Ml, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.
ESTHER : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedSearch : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedID: 32711521

Title : Susceptibility of fall armyworm, Spodoptera frugiperda (J.E.Smmith), to eight insecticides in China, with special reference to lambda-cyhalothrin - Zhao_2020_Pestic.Biochem.Physiol_168_104623
Author(s) : Zhao YX , Huang JM , Ni H , Guo D , Yang FX , Wang X , Wu SF , Gao CF
Ref : Pestic Biochem Physiol , 168 :104623 , 2020
Abstract : Fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is the main destructive insect pest of grain crops that occurs in all maize growing regions of the Americas. It has rapidly invaded the Southern China since January 2019. However, the current status of insecticide resistance in S. frugiperda has not been reported in China. In this study, we determined the susceptibility of eight populations of FAW to eight insecticides by an artificial diet incorporation method. The results showed that among eight insecticides, emamectin benzoate, spinetoram, chlorantraniliprole, chlorfenapyr, and lufenuron showed higher toxicity to this pest, while lambda-cyhalothrin and azadirachtin exhibited lower toxicity. Susceptibility of S. frugiperda to indoxacarb was significantly different (10.0-fold for LC(50)) across the various geographic populations. To investigate the biochemical mechanism of FAW to lambda-cyhalothrin, we performed the synergism tests and the results showed that piperonyl butoxide (PBO) and triphenyl phosphate (TPP) produced a high synergism of lambda-cyhalothrin effects in the two field populations. Sequencing of the gene encoding the acetylcholinesterase (AChE) gene in the two field populations identified two amino acid mutations, all of which have been shown previously to confer resistance to organophosphates (OPs) in several arthropod species. The results of this study provided valuable information for choosing alternative insecticides and for insecticide resistance management of S. frugiperda.
ESTHER : Zhao_2020_Pestic.Biochem.Physiol_168_104623
PubMedSearch : Zhao_2020_Pestic.Biochem.Physiol_168_104623
PubMedID: 32711763

Title : Thiol inhibition of Hg cold vapor generation in SnCl2\/NaBH4 system: A homogeneous bioassay for H2O2\/glucose and butyrylcholinesterase\/pesticide sensing by atomic spectrometry - Chen_2020_Anal.Chim.Acta_1111_8
Author(s) : Chen P , Zheng C , Chen C , Huang K , Wang X , Hu P , Geng J
Ref : Anal Chim Acta , 1111 :8 , 2020
Abstract : Recently, the use of atomic spectrometry (AS) for biochemical analysis has attracted considerable attention due to its high sensitivity, selectivity and anti-interference ability. In this work, we conducted a detailed study on a phenomenon of thiol inhibition of mercury (Hg(2+)) cold vapor generation (CVG) and found L-cysteine (L-Cys), glutathione (GSH), dithiothreitol, N-Acetyl-L-cysteine, 3-mercaptopropionic acid, beta-mercaptoethanol, and NaI can inhibit the CVG of Hg(2+), while EDTA has no inhibitory effect. Furthermore, changing the content of -SH can effectively adjust the CVG atomic fluorescence spectrometer (CVG-AFS) signal of Hg(2+). As as a consequence, an AS-based homogeneous bioassay was constructed by adjusting the oxidation ratio and production quantity of -SH in the system. The quantitative analysis of the system was demonstrated by using AFS as a representative detector. Hydrogen peroxide (H2O2) and glucose were used as representative analytes for the validation of Hg(2+) atomic fluorescence signal turn-off strategy, and butyrylcholinesterase (BChE) as well as parathion (organophosphorus pesticides, OPs) as utilized as representative targets for the signal turn-on strategy. Under optimal experimental conditions, the homogeneous CVG-AFS sensor can be successfully used to detect 3 muM H2O2, 30 muM glucose, 0.25 U/L BChE, and 0.4 mug/mL parathion. In addition, the detection results of glucose and BChE in human serum samples agreed well with those obtained by using glucometer and kit, showing the promising potential of this method for practical applications. Therefore, this work provides a perspective for the construction of AS-based homogeneous bioassays and shows great potential for the detection of biomarkers.
ESTHER : Chen_2020_Anal.Chim.Acta_1111_8
PubMedSearch : Chen_2020_Anal.Chim.Acta_1111_8
PubMedID: 32312400

Title : Imaging Sarcoplasmic Reticulum Ca(2+) Signaling in Intact Cardiac Myocytes -
Author(s) : Lu F , Zhao Y , Xie W , Guo Q , Wang SQ , Wang X , Cheng H
Ref : Circulation , 142 :1503 , 2020
PubMedID: 33044861

Title : ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis - Liu_2020_Front.Cell.Dev.Biol_8_570
Author(s) : Liu G , Ruan Y , Zhang J , Wang X , Wu W , He P , Wang J , Xiong J , Cheng Y , Liu L , Yang Y , Tian Y , Jian R
Ref : Front Cell Developmental Biology , 8 :570 , 2020
Abstract : Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function.
ESTHER : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedSearch : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedID: 32733886
Gene_locus related to this paper: human-ABHD11

Title : FRACPRED-2D-PRM: A fraction prediction algorithm-assisted two-dimensional liquid chromatography-based parallel reaction monitoring-mass spectrometry approach for measuring low-abundance proteins in human plasma - Shi_2020_Proteomics__e2000175
Author(s) : Shi J , Xiao J , Li J , Wang X , Her L , Sorensen MJ , Zhu HJ
Ref : Proteomics , :e2000175 , 2020
Abstract : Multidimensional fractionation-based enrichment methods improve the sensitivity of proteomic analysis for low-abundance proteins. However, a major limitation of conventional multidimensional proteomics is the extensive labor and instrument time required for analyzing many fractions obtained from the first dimension separation. Here, we present a fraction prediction algorithm-assisted two-dimensional LC-based parallel reaction monitoring-mass spectrometry (FRACPRED-2D-PRM) approach for measuring low-abundance proteins in human plasma. Plasma digests were separated by the first dimension high-pH RP-LC with data-dependent acquisition (DDA). We then used the FRACPRED algorithm to predict the retention time of undetectable target peptides according to those of other abundant plasma peptides during the first dimension separation. Fractions predicted to contain target peptides were analyzed by the second dimension low-pH nano RP-LC PRM. We demonstrated the accuracy and robustness of fraction prediction with the FRACPRED algorithm by measuring two low-abundance proteins, aldolase B and carboxylesterase 1, in human plasma. The FRACPRED-2D-PRM proteomics approach demonstrated markedly improved efficiency and sensitivity over conventional 2D-LC proteomics assays. We expect that this approach will be widely used in the study of low-abundance proteins in plasma and other complex biological samples. This article is protected by copyright. All rights reserved.
ESTHER : Shi_2020_Proteomics__e2000175
PubMedSearch : Shi_2020_Proteomics__e2000175
PubMedID: 33085175

Title : An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment - Wu_2020_Arch.Toxicol_94_3645
Author(s) : Wu Q , Qin Z , Kuca K , You L , Zhao Y , Liu A , Musilek K , Chrienova Z , Nepovimova E , Oleksak P , Wu W , Wang X
Ref : Archives of Toxicology , 94 :3645 , 2020
Abstract : T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms.
ESTHER : Wu_2020_Arch.Toxicol_94_3645
PubMedSearch : Wu_2020_Arch.Toxicol_94_3645
PubMedID: 32910237

Title : Construction and application of a high-content analysis for identifying human carboxylesterase 2 inhibitors in living cell system - Xue_2020_Anal.Bioanal.Chem__
Author(s) : Xue L , Qian X , Jin Q , Zhu Y , Wang X , Wang D , Ge G , Yang L
Ref : Anal Bioanal Chem , : , 2020
Abstract : Human carboxylesterase 2 (hCE2), one of the most principal drug-metabolizing enzymes, catalyzes the hydrolysis of a variety of endogenous esters, anticancer agents, and environmental toxicants. The significant roles of hCE2 in both endobiotic and xenobiotic metabolism sparked great interest in the discovery and development of efficacious and selective inhibitors. However, the safe and effective inhibitors of hCE2 are scarce, due to the lack of efficient screening and evaluation systems for complex biological systems. To offer a solution to this problem, a high-content analysis (HCA)-based cell imaging and multiparametric assay method was constructed for evaluating the inhibitory effect and safety of hCE2 inhibitors in living cell system. In this study, we first established a cell imaging-based method for identifying hCE2 inhibitors at the living cell level with hCE2 fluorescent probe NCEN. Meanwhile, two nuclear probes, Hoechst 33342 and PI, were integrated to evaluate the potential cytotoxicity of compounds simultaneously. Then, the accuracy of the HCA-based method was verified by the LC-FD-based method with a positive inhibitor BNPP, and the results showed that the HCA-based method exhibited excellent precision, robustness, and reliability. Finally, the newly established HCA-based multiparametric assay panel was successfully applied to re-evaluate a series of reported hCE2 inhibitors in living cells. In summary, the HCA-based multiparametric method could serve as an efficient tool for the accuracy measurement inhibitory effect and cytotoxicity of compounds against hCE2 in living cell system. Graphical abstract.
ESTHER : Xue_2020_Anal.Bioanal.Chem__
PubMedSearch : Xue_2020_Anal.Bioanal.Chem__
PubMedID: 32123952

Title : Biodegradation of phthalate esters by Paracoccus kondratievae BJQ0001 isolated from Jiuqu (Baijiu fermentation starter) and identification of the ester bond hydrolysis enzyme - Xu_2020_Environ.Pollut_263_114506
Author(s) : Xu Y , Minhazul K , Wang X , Liu X , Li X , Meng Q , Li H , Zhang C , Sun X , Sun B
Ref : Environ Pollut , 263 :114506 , 2020
Abstract : Phthalate ester (PAE) pollution is an increasing problem globally. Paracoccus kondratievae BJQ0001 was isolated from the fermentation starter of Baijiu and showed an efficient degradation capability toward PAEs. To our poor knowledge, this is the first report of a P. kondratievae strain capable of degrading PAEs. The first complete genome sequence of P. kondratievae was presented without gaps, and composed of two circular chromosomes and one plasmid. The species simultaneously degraded di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP) and di-(2-ethylhexyl) phthalate (DEHP), with DMP and DEP as the preferred substrates. The half-life (t(1/2)) of DMP was only 6.34 h with an initial concentration of 200 mg/L. Combined with gene annotation and metabolic intermediate analysis, a metabolic pathway was proposed for the species. Benzoic acid, the intermediate of anaerobic PAE metabolism, was identified in the aerobic degradation process. Two key enzymes for alkyl ester bond hydrolysis were obtained, and belonged to families IV and VI of hydrolases, respectively. These results will promote the investigation of PAE degradation by P. kondratievae, and provide useful information for improving the quality control of food and environmental PAE treatment.
ESTHER : Xu_2020_Environ.Pollut_263_114506
PubMedSearch : Xu_2020_Environ.Pollut_263_114506
PubMedID: 32268225
Gene_locus related to this paper: 9rhob-a0a5p8jcg2 , 9rhob-a0a5p8jaa4

Title : Discovery and development of a novel short-chain fatty acid ester synthetic biocatalyst under aqueous phase from Monascus purpureus isolated from Baijiu - Xu_2020_Food.Chem_338_128025
Author(s) : Xu Y , Wang X , Liu X , Li X , Zhang C , Li W , Sun X , Wang W , Sun B
Ref : Food Chem , 338 :128025 , 2020
Abstract : Short-chain fatty acid esters are important flavor chemicals in Chinese traditional fermented Baijiu. Monascus purpureus was recognized as an important microorganism contributing to ester synthesis. However, the molecular basis for ester synthesis was still lacking. The present work combined genome sequencing, transcriptome sequencing, gene library construction, and enzyme engineering to discover a novel catalyst from M. purpureus (isolated from Baijiu fermentation starter). Enzyme LIP05, belonging to the alpha/beta hydrolase family, was identified to synthesize short-chain fatty acid esters under aqueous phase. After deleting the lid domain of LIP05, the synthesis of ethyl pentanoate, ethyl hexanoate, ethyl octanoate, or ethyl decanoate was achieved. Ethyl octanoate with the highest conversion ratio of 93.7% was obtained with the assistance of ultrasound. The study reveals the molecular basis for synthesizing short-chain fatty acid esters by M. purpureus and will promote the application of the species or the enzyme in food industry.
ESTHER : Xu_2020_Food.Chem_338_128025
PubMedSearch : Xu_2020_Food.Chem_338_128025
PubMedID: 32927200
Gene_locus related to this paper: monpu-a0a507qkl5

Title : Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences - Zhou_2019_Sci.Rep_9_15564
Author(s) : Zhou Q , Xiao Q , Zhang Y , Wang X , Xiao Y , Shi D
Ref : Sci Rep , 9 :15564 , 2019
Abstract : Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, these enzymes remain to be characterized in farm animals. In this study, we showed that pig liver esterase 1 (PLE1) and pig liver esterase 6 (PLE6) were highly active toward amoxicillin (AMO) and ampicillin (AMP), two major antibiotics that are widely used in food-supplements. Mass-spectrometric analysis established that the hydrolysis occurred at the beta-lactam amide bond and the hydrolysis drastically decreased or completely eliminated the antibacterial activity. Furthermore, hydrolytic activity and proteomic analysis suggested that trace PLEs existed in pig plasma and contributed little to the hydrolysis of AMO and AMP. These results suggested that carboxylesterases-based hydrolysis determines the therapeutic intensity of these and related antibiotics and the magnitude of the determination occurs in a species-dependent manner.
ESTHER : Zhou_2019_Sci.Rep_9_15564
PubMedSearch : Zhou_2019_Sci.Rep_9_15564
PubMedID: 31664043
Gene_locus related to this paper: pig-EST1 , pig-a0a1s6l967

Title : Synthesis and biological evaluation of 4-arylcoumarins as potential anti-Alzheimer's disease agents - Yun_2019_Bioorg.Med.Chem.Lett__126900
Author(s) : Yun Y , Yang J , Miao Y , Wang X , Sun J
Ref : Bioorganic & Medicinal Chemistry Lett , :126900 , 2019
Abstract : Alzheimer's disease (AD) is a progressive neurological degenerative disease that has complex pathogenesis. A variety of studies in humans indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted 4-arylcoumarin derivatives were synthesised, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity, MAO inhibitory activity, and antioxidant activity. Most of the compounds were found to exhibit high inhibitory activity, and individual compounds have extremely excellent activities. Therefore 4-arylcoumarins provides an idea for drugs design for the development of therapeutic or preventive agents for AD.
ESTHER : Yun_2019_Bioorg.Med.Chem.Lett__126900
PubMedSearch : Yun_2019_Bioorg.Med.Chem.Lett__126900
PubMedID: 31882295

Title : CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas - Tao_2019_Mol.Oncol_13_1018
Author(s) : Tao B , Ling Y , Zhang Y , Li S , Zhou P , Wang X , Li B , Jun Z , Zhang W , Xu C , Shi J , Wang L
Ref : Mol Oncol , 13 :1018 , 2019
Abstract : Recent studies have revealed that neurons can promote glioma growth through activity-dependent secretion of neurotrophins, especially neuroligin-3. It has therefore been suggested that blocking neuron-derived neurotrophins may serve as a therapeutic intervention for gliomas. Carbonic anhydrase-related proteins 11 and 10 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 expression of gliomas was associated with short survival in four independent datasets [repository of brain neoplasia data (REMBRANDT), The Cancer Genome Atlas (TCGA) lower grade glioma (LGG), GSE4271, and GSE42669]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. Thus, CA11/CA10 may represent a potential therapeutic target for the treatment of gliomas.
ESTHER : Tao_2019_Mol.Oncol_13_1018
PubMedSearch : Tao_2019_Mol.Oncol_13_1018
PubMedID: 30636076

Title : Purification and biochemical characterization of FrsA protein from Vibrio vulnificus as an esterase - Wang_2019_PLoS.One_14_e0215084
Author(s) : Wang X , Li ZM , Li Q , Shi M , Bao L , Xu D , Li Z
Ref : PLoS ONE , 14 :e0215084 , 2019
Abstract : Fermentation-respiration switch protein (FrsA) was thought to play an important role in controlling the metabolic flux between respiration and fermentation pathways, whereas the biochemical function of FrsA was unclear yet. A gene coding for FrsA protein from Vibrio vulnificus was chemically synthesized. The recombinant VvFrsA was expressed as a soluble protein and purified by Ni-NTA affinity chromatography. The protein had a subunit molecular weight of ca. 45 kDa by SDS-PAGE and preferred short-chain esters when p-nitrophenyl alkanoate esters were used as substrates. Optimum condition for VvFrsA was found to be at pH 9.0 and 50 degrees C. The protein retained high esterase activity at alkaline condition and would denature slowly at over 50 degrees C. With p-nitrophenyl acetate as the substrate, the Km and kcat were determined to be 18.6 mM and 0.67 s-1, respectively, by steady-state kinetic assay. Molecular dynamics simulation and docking model structure revealed that p-nitrophenyl acetate could be the substrate of VvFrsA. In conclusion our results demonstrated that the protein was able to catalyze the hydrolysis of esters, especially p-nitrophenyl acetate, for the first time.
ESTHER : Wang_2019_PLoS.One_14_e0215084
PubMedSearch : Wang_2019_PLoS.One_14_e0215084
PubMedID: 30951551
Gene_locus related to this paper: vibvy-y856

Title : Compartmentalized biosynthesis of mycophenolic acid - Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
Author(s) : Zhang W , Du L , Qu Z , Zhang X , Li F , Li Z , Qi F , Wang X , Jiang Y , Men P , Sun J , Cao S , Geng C , Wan X , Liu C , Li S
Ref : Proc Natl Acad Sci U S A , 116 :13305 , 2019
Abstract : Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.
ESTHER : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedSearch : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedID: 31209052
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica - Qi_2019_J.Nat.Med_73_769
Author(s) : Qi B , Yang W , Ding N , Luo Y , Jia F , Liu X , Wang J , Wang X , Tu P , Shi S
Ref : J Nat Med , 73 :769 , 2019
Abstract : Six new pyrrole 2-carbaldehyde derived alkaloids, dahurines A-F (1-6), along with five known ones (7-11) and butyl 2-pyrrolidone-5-carboxylate (12) were isolated from the roots of Angelica dahurica. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Although compounds 7 and 8 have been chemically synthesized, they were obtained from natural materials for the first time. Compounds 2, 3, 4, 10, and 11 exhibited acetylcholinesterase inhibitory activity with IC50 values in the range of 47.5-52.5 muM. Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica.
ESTHER : Qi_2019_J.Nat.Med_73_769
PubMedSearch : Qi_2019_J.Nat.Med_73_769
PubMedID: 31209724

Title : Insight into the Modification of Phosphatidylcholine with n-3 Polyunsaturated Fatty Acids-Rich Ethyl Esters by Immobilized MAS1 Lipase - Wang_2019_Molecules_24_
Author(s) : Wang X , Qin X , Li X , Zhao Z , Yang B , Wang Y
Ref : Molecules , 24 : , 2019
Abstract : This study reported the modification of phosphatidylcholine (PC) with n-3 polyunsaturated fatty acids (PUFA)-rich ethyl esters (EE) by immobilized MAS1 lipase-catalyzed transesterification in the solvent-free system. Effects of n-3 PUFA-rich EE/PC mass ratio, enzyme loading, reaction temperature, and water dosage on the incorporation of n-3 PUFA into PC were investigated, respectively. The results indicate that the maximum incorporation of n-3 PUFA into PC reached 33.5% (24 h) under the following conditions: n-3 PUFA-rich EE/PC mass ratio of 6:1, enzyme loading of 20%, reaction temperature of 55 degrees C, and water dosage of 1.0%. After 72 h of reaction, the incorporation of n-3 PUFA into PC was 43.55% and the composition of the reaction mixture was analyzed by (31)P nuclear magnetic resonance (NMR). The results show that the reaction product consisted of 32.68% PC, 28.76% 1-diacyl-sn-glycero-3-lysophosphatidylcholine (sn-1 LPC), 4.90% 2-diacyl-sn-glycero-3-lysophosphatidylcholine (sn-2 LPC), and 33.60% sn-glycero-3-phosphatidylcholine (GPC). This study offers insight into the phospholipase activity of immobilized MAS1 lipase and suggests the extended applications of immobilized MAS1 lipase in the modification of phospholipids for industrial purpose.
ESTHER : Wang_2019_Molecules_24_
PubMedSearch : Wang_2019_Molecules_24_
PubMedID: 31569526
Gene_locus related to this paper: 9actn-h0b8d4

Title : Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein - Zhou_2019_Nat.Commun_10_3068
Author(s) : Zhou H , Chen Y , Zhang S , Niu P , Qin K , Jia W , Huang B , Lan J , Zhang L , Tan W , Wang X
Ref : Nat Commun , 10 :3068 , 2019
Abstract : Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.
ESTHER : Zhou_2019_Nat.Commun_10_3068
PubMedSearch : Zhou_2019_Nat.Commun_10_3068
PubMedID: 31296843

Title : Vitisin B as a novel fatty acid synthase inhibitor induces human breast cancer cells apoptosis - Wang_2019_Am.J.Transl.Res_11_5096
Author(s) : Wang X , Jiang B , Lv H , Liang Y , Ma X
Ref : Am J Transl Res , 11 :5096 , 2019
Abstract : Breast cancer is one of the most common cancers and the second leading cause of cancer mortality in women worldwide. Novel therapies and chemo-therapeutic drugs are still in urgent need to be developed for the treatment of breast cancer. One of the most important metabolic hallmarks of breast cancer cells is enhanced lipogenesis. Increasing evidences suggest that fatty acid synthase (FAS) plays an important role in the development of human breast cancer, for the expression of FAS is significantly higher in breast cancer cells than in normal cells. In addition, FAS inhibitors, such as curcumin, ursolic acid, and resveratrol, have shown anti-cancer potential. In the present study, we discovered that vitisin B, a natural stilbene isolated from the seeds of Iris lactea Pall. var. chinensis (Fisch.), was a novel FAS inhibitor. We found that vitisin B could down-regulate FAS expression and inhibit intracellular FAS activity in MDA-MB-231 cells. Also, we reported for the first time that vitisin B exhibited apoptotic effect on human breast cancer cells. Given all of this, we proposed a hypothesis that vitisin B has an application potential in the chemoprevention and treatment of breast cancer.
ESTHER : Wang_2019_Am.J.Transl.Res_11_5096
PubMedSearch : Wang_2019_Am.J.Transl.Res_11_5096
PubMedID: 31497225

Title : Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic - Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
Author(s) : Su X , Guo Y , Deng J , Xu J , Zhou G , Zhou T , Li Y , Zhong D , Kong L , Wang X , Liu M , Wu K , Yan G , Chen XG
Ref : PLoS Negl Trop Dis , 13 :e0007665 , 2019
Abstract : Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.
ESTHER : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedSearch : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedID: 31525199

Title : Molecular characterization of ABHD5 gene promoter in intramuscular preadipocytes of Qinchuan cattle: Roles of Evi1 and C\/EBPalpha - Wang_2019_Gene_690_38
Author(s) : Wang X , Khan R , Raza SHA , Li A , Zhang Y , Liang C , Yang W , Wu S , Zan L
Ref : Gene , 690 :38 , 2019
Abstract : The genetic regulation of lipolytic enzyme is closely related to carcass quality traits through deposition of intramuscular fat (marbling) in beef cattle breeds. The alpha/beta hydrolase domain containing 5 (ABHD5) is an accelerating factor of adipose triglyceride lipase (ATGL), which plays a key role in triglyceride metabolism. In this study, we determined that bovine ABHD5 gene was highly expressed in adult bovine adipose tissue. To elucidate the molecular mechanisms involved in bovine ABHD5 regulation, we cloned and characterized the promoter region of ABHD5. Applying 5'-rapid amplification of cDNA end analysis (RACE), we identified transcriptional start site (TSS) found in the predicted CpG island within promoter region of ABHD5 gene. Using the recombinant dual fluorescent reporter vectors, the fragment of -109/+307 was identified as proximal minimum core promoter region of ABHD5 in bovine intramuscular adipocytes. Site directed mutagenesis and electrophoretic mobility shift assay (EMSA) confirmed the role of two transcription factors, namely Ectopic viral integration site-1 (Evi1) and CCAAT/enhancer binding protein alpha (C/EBPalpha), in the regulation of ABHD5 gene. Taken together these findings we can conclude that ABHD5 gene regulated by Evi1 and C/EBPalpha could be used as potential marker in marker assisted selection for the improvement of Qinchuan cattle breed for carcass quality traits.
ESTHER : Wang_2019_Gene_690_38
PubMedSearch : Wang_2019_Gene_690_38
PubMedID: 30583026
Gene_locus related to this paper: bovin-q0vcc8

Title : Observation of Acetylcholinesterase in Stress-Induced Depression Phenotypes by Two-Photon Fluorescence Imaging in the Mouse Brain - Wang_2019_J.Am.Chem.Soc_141_2061
Author(s) : Wang X , Li P , Ding Q , Wu C , Zhang W , Tang B
Ref : Journal of the American Chemical Society , 141 :2061 , 2019
Abstract : Oxidative stress in depression is a prime cause of neurotransmitter metabolism dysfunction in the brain. Acetylcholinesterase (AChE), a key hydrolase in the cholinergic system, directly determines the degradation of neurotransmitters. However, due to the complexity of the brain and lack of appropriate in situ imaging tools, the mechanism underlying the changes in AChE activity in depression remains unclear. Hence, we generated a two-photon fluorescence probe (MCYN) for real-time visualization of AChE with excellent sensitivity and selectivity. AChE can specifically recognize and cleave the carbamic acid ester bond in MCYN, and MCYN emits bright fluorescence at 560 nm by two-photon excitation at 800 nm. By utilizing MCYN to monitor AChE, we discovered a significant increase in AChE activity in the brains of mice with depression phenotypes. Notably, with the assistance of a two-photon fluorescence imaging probe of the superoxide anion radical (O2(*-)), in vivo visualization for the first time revealed the positive correlation between AChE and O2(*-) levels associated with depressive behaviors. This finding suggests that oxidative stress may induce AChE overactivation, leading to depression-related behaviors. This work provides a new and rewarding perspective to elucidate the role of oxidative stress regulating AChE in the pathology of depression.
ESTHER : Wang_2019_J.Am.Chem.Soc_141_2061
PubMedSearch : Wang_2019_J.Am.Chem.Soc_141_2061
PubMedID: 30638380

Title : Epoxyeicosatrienoic acids alleviate methionine-choline-deficient diet-induced non-alcoholic steatohepatitis in mice - Wang_2019_Scand.J.Immunol__e12791
Author(s) : Wang X , Li L , Wang H , Xiao F , Ning Q
Ref : Scand J Immunol , :e12791 , 2019
Abstract : The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases and have recently been found to have an anti-inflammatory activity. However, the role of EETs in non-alcoholic steatohepatitis has not been fully understood. In this study, we investigated the protective role of EETs in methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice and the potential mechanisms. We used 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea(TPPU), a soluble epoxide hydrolase inhibitor, to increase the endogenous EET level in mice. Upon TPPU treatment, the liver steatosis and inflammatory damage were significantly ameliorated in mice with steatohepatitis, paralleled by the downregulation of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6) as well as chemokines (CXCL1, MCP-1). Compared with untreated NASH mice, mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and inflammation relevant adhesion molecules (ICAM-1, VCAM-1) were downregulated, whereas mRNA level of peroxisome proliferator-activated receptor alpha(PPAR-alpha) was elevated in TPPU-treated mice. In vitro, 11,12-EET treatment remarkably attenuated free fatty acid (FFA)-induced inflammation in HepG2 and THP-1 cells. Further, 11,12-EET inhibited the activation of NF-kappaB signalling pathway in macrophages from mice with steatohepatitis. Collectively, these results suggest that EETs play a protective role and alleviate the MCD diet-induced steatohepatitis in mice mainly by downregulating activation of NF-kappaB pathway in macrophages.
ESTHER : Wang_2019_Scand.J.Immunol__e12791
PubMedSearch : Wang_2019_Scand.J.Immunol__e12791
PubMedID: 31132306

Title : First Genome-wide Association Analysis for Growth Traits in the Largest Coral Reef-Dwelling Bony Fishes, the Giant Grouper (Epinephelus lanceolatus) - Wu_2019_Mar.Biotechnol.(NY)_21_707
Author(s) : Wu L , Yang Y , Li B , Huang W , Wang X , Liu X , Meng Z , Xia J
Ref : Mar Biotechnol (NY) , 21 :707 , 2019
Abstract : The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.
ESTHER : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedSearch : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedID: 31392592

Title : Effects of Lecanicillium lecanii strain JMC-01 on the physiology, biochemistry, and mortality of Bemisia tabaci Q-biotype nymphs - Xie_2019_PeerJ_7_e7690
Author(s) : Xie T , Jiang L , Li J , Hong B , Wang X , Jia Y
Ref : PeerJ , 7 :e7690 , 2019
Abstract : Background: Lecanicillium lecanii is an entomopathogenic fungi, which was isolated from insects suffering from disease. Now, it is an effective bio-control resource that can control agricultural pests such as whitefly and aphids. There are many studies on the control of various agricultural pests by L. lecanii, but no report on its control of Bemisia tabaci biotype-Q exists. In this work, we studied the susceptibility of B. tabaci Q-biotype (from Ningxia, China) to L. lecanii JMC-01 in terms of nymph mortality and the changes in detoxifying protective enzymes activities. Methods: B. tabaci nymphs were exposed to L. lecanii JMC-01 conidia by immersion with the host culture. Mortality was assessed daily for all nymph stages. The detoxifying and protective enzyme activity changes, weight changes, and fat, and water contents of the nymphs were determined spectrophotometrically. Results: All instars of B. tabaci died after being infested with 1 x 10(8) conidia/mL. The 2nd-instar nymphs were the most susceptible, followed by the 3rd-instar nymphs. The corrected cumulative mortality of the 2nd- and 3rd-instar nymphs was 82.22% and 75.55%, respectively. The levels of detoxifying and protective enzymes initially increased and then decreased. The highest activities of carboxylesterase, acetylcholinesterase, peroxidase, and catalase occurred on the 3rd day, reaching 10.5, 0.32, 20, and 6.3 U/mg prot, respectively. These levels were 2.2-, 4.3-, 2.4-, and 1.4-fold the control levels, respectively. The highest activities of glutathione-S transferase and superoxide dismutase on the 2nd day were, respectively, 64 and 43.5 U/mg prot. These levels were, respectively, 2.7 and 1.1-fold that of the control level. The water and fat content in the infected B. tabaci nymphs decreased and differed significantly from the control levels. The weight increased continuously in the first 24 h, decreasing thereafter. At 72 h, the infestation level was about 0.78-fold that of the control level. Conclusions: The studied L. lecanii JMC-01 strain is pathogenic to the B. tabaci Q-biotype. This strain interferes with the normal functioning of detoxifying and protective enzymes, and is also involved in the disruption of normal physiological metabolism in B. tabaci.
ESTHER : Xie_2019_PeerJ_7_e7690
PubMedSearch : Xie_2019_PeerJ_7_e7690
PubMedID: 31576242

Title : Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction - Xu_2019_Lab.Invest_99_1078
Author(s) : Xu H , Chen L , Zhang X , Jiang X , Tian W , Yu W , Wang X , Tian J , Su D
Ref : Lab Invest , 99 :1078 , 2019
Abstract : Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality. However, its mechanism remains poorly understood. We hypothesized that central cholinergic neuronal degeneration facilitates the development of POCD. The impact of anesthesia/surgery (appendectomy) on learning and memory and the levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and choline transporter (CHT) in adult and aged mice were measured. Separate cohorts were analyzed after pretreatment with donepezil, an AChE inhibitor, in aged mice or with murine-p75-saporin (mu-p75-sap), a cholinergic-specific immunotoxin, in adult mice. Morris Water Maze was used to measure the learning and memory changes after anesthesia/surgery. Western blot was used to measure the changes in the protein levels of the biomarkers of the central cholinergic system. We found that anesthesia/surgery-induced memory decline and attenuation of central cholinergic biomarkers (ChAT and VAChT) in aged mice but not in adult mice. Donepezil pretreatment reduced central cholinergic impairment in the aged mice and prevented learning and memory declines after anesthesia/surgery. In contrast, when central cholinergic neurons were pre-injured with mu-p75-sap, cognitive dysfunction developed in the adult mice after anesthesia/surgery. These data suggest that central cholinergic neuronal degeneration facilitates the development of POCD.
ESTHER : Xu_2019_Lab.Invest_99_1078
PubMedSearch : Xu_2019_Lab.Invest_99_1078
PubMedID: 30626892

Title : Label-free absolute protein quantification with data-independent acquisition - He_2019_J.Proteomics_200_51
Author(s) : He B , Shi J , Wang X , Jiang H , Zhu HJ
Ref : J Proteomics , 200 :51 , 2019
Abstract : Despite data-independent acquisition (DIA) has been increasingly used for relative protein quantification, DIA-based label-free absolute quantification method has not been fully established. Here we present a novel DIA method using the TPA algorithm (DIA-TPA) for the absolute quantification of protein expressions in human liver microsomal and S9 samples. To validate this method, both data-dependent acquisition (DDA) and DIA experiments were conducted on 36 individual human liver microsome and S9 samples. The MS2-based DIA-TPA was able to quantify approximately twice as many proteins as the MS1-based DDA-TPA method, whereas protein concentrations determined by the two approaches were comparable. To evaluate the accuracy of the DIA-TPA method, we absolutely quantified carboxylesterase 1 concentrations in human liver S9 fractions using an established SILAC internal standard-based proteomic assay; the SILAC results were consistent with those obtained from DIA-TPA analysis. Finally, we employed a unique algorithm in DIA-TPA to distribute the MS signals from shared peptides to individual proteins or isoforms and successfully applied the method to the absolute quantification of several drug-metabolizing enzymes in human liver microsomes. In sum, the DIA-TPA method not only can absolutely quantify entire proteomes and specific proteins, but also has the capability quantifying proteins with shared peptides. SIGNIFICANCE: Data independent acquisition (DIA) has emerged as a powerful approach for relative protein quantification at the whole proteome level. However, DIA-based label-free absolute protein quantification (APQ) method has not been fully established. In the present study, we present a novel DIA-based label-free APQ approach, named DIA-TPA, with the capability absolutely quantifying proteins with shared peptides. The method was validated by comparing the quantification results of DIA-TPA with that obtained from stable isotope-labeled internal standard-based proteomic assays.
ESTHER : He_2019_J.Proteomics_200_51
PubMedSearch : He_2019_J.Proteomics_200_51
PubMedID: 30880166

Title : A highly sensitive and low-background fluorescence assay for pesticides residues based on hybridization chain reaction amplification assisted by magnetic separation - Yao_2019_Methods.Appl.Fluoresc_7_035006
Author(s) : Yao Y , Liu Y , Zhang H , Wang X
Ref : Methods Appl Fluoresc , 7 :035006 , 2019
Abstract : Due to the concern over food safety, it is important to detect the pesticides residues in agricultural products. Here, a highly sensitive and low background fluorescent strategy for the detection of pesticides residues has been developed. The fluorescence intensity of N-methyl mesoporphyrin IX (NMM) binding G-quadruplex could be turn off because of inhibiting effect of the pesticides on the acetylcholinesterase (AChE) activity. For that, four single-stranded DNAs (named linker, trigger, H1 and H2, respectively) are rational designed and T-Hg-T mismatches duplex DNAs as a recognizer combined with the separation of magnetic beads. The design of hybridization chain reaction (HCR) amplification strategy assisted by magnetic separation has been adopted to improve the detection sensitivity. In the presence of pesticides, the amount of the thiol group generated by hydrolysis reaction of acetylcholine (ACh) is reduced, lead to release of less trigger DNA. Therefor subsequent HCR process is retarded with decreased fluorescence intensity. The reduced fluorescence intensity has a quantitative relationship with the pesticide concentration. The limit of detection of chlorpyrifos was estimated to be 2.0 ng ml(-1). It has been applied to detect the pesticides residues in real samples.
ESTHER : Yao_2019_Methods.Appl.Fluoresc_7_035006
PubMedSearch : Yao_2019_Methods.Appl.Fluoresc_7_035006
PubMedID: 31042679

Title : Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model - Shen_2019_Brain.Behav.Immun_81_535
Author(s) : Shen Y , Peng W , Chen Q , Hammock BD , Liu J , Li D , Yang J , Ding J , Wang X
Ref : Brain Behavior & Immunity , 81 :535 , 2019
Abstract : PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127mg/kg) and pilocarpine (40mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1mg/kg/d) was intragastrically given for 4weeks from the 21st day after SE induction in the SRS+0.1 TPPU group. The SRS+PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element bind