Wang L

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Full name : Wang Li

First name : Li

Mail : State Key Laboratory of Biomembrane and Membrane Biotechnology and the Center for Life Sciences, Institute of Molecular Medicine, Peking University, Beijing 100871

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Country : China

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References (367)

Title : Effect of entomopathogenic fungi on behavior and physiology of Solenopsis invicta (Hymenoptera, Formicidae) - Hassan_2024_J.Econ.Entomol__
Author(s) : Hassan A , Kang L , Zhang K , Wang L , Qin X , Fang G , Lu Y , Huang Q
Ref : J Econ Entomol , : , 2024
Abstract : In an ant colony, a large number of nestmates with a similar gene pool coexist, making them more vulnerable to pathogenic attacks. These pathogens influence the behavior and physiology of the fire ant Solenopsis invicta Buren. Here, we evaluated the impact of entomopathogenic fungi (EPF) Metarhizium anisopliae on the behavior (locomotion and foraging) and physiology (biological molecules, anti-fungal activity, and survival) of S. invicta. Distance traveled and velocity significantly decreased, while turn angle and angular velocity significantly increased in ants exposed to a higher concentration of M. anisopliae compared to ants exposed to control after 36 h, which showed disturbed locomotion. Fungus infection significantly affected the foraging behavior of ants. Fungus-exposed ants spent significantly less time in the food zone (area with food) than in the inner zone (area without food). The activities of 4 enzymes, peroxidase, glutathione-S-transferase, hydrogen peroxide (H2O2), and carboxylesterase were significantly decreased. In contrast, catalase and anti-fungal activities were increased after fungal exposure compared to the control. The activity of acetylcholinesterase, which hydrolyses the important neurotransmitter acetylcholine, also decreased after fungal application compared to the control. Survival of ants was also significantly reduced after fungus infection compared to the control. Our findings help to understand the influence of M. anisopliae on the behavior and physiology of S. invicta, which will help in the management of S. invicta using the EPF M. anisopliae.
ESTHER : Hassan_2024_J.Econ.Entomol__
PubMedSearch : Hassan_2024_J.Econ.Entomol__
PubMedID: 38634604

Title : The acute neurotoxicity of inorganic mercury in Mactra chinensis philippi - Ma_2024_Aquat.Toxicol_270_106896
Author(s) : Ma B , Zhao X , Zhang X , Yang B , Cai Z , Xing Z , Xu M , Mi L , Zhang J , Wang L , Zhao Y , Liu X
Ref : Aquat Toxicol , 270 :106896 , 2024
Abstract : Inorganic mercury (IHg) is hazardous to marine organisms especially resulting in neurotoxicity, bivalves are sensitive to pollutants as "ocean sentinel", but data on the neurotoxicity of IHg in bivalves are sparse. So we chosed M. chinensis philippi with typical neural structures in bivalves to investigate the neurotoxicity of IHg, which could be helpful to understand the specificity of neural regulation and the response characteristics of bivalves. After acute exposed to IHg (HgCl(2)) for 24 h, the metabolites of ganglion tissues in M. chinensis philippi were evaluated using (1)H-nuclear magnetic resonance based metabolomics; Ca(2+), neurotransmitters (nitric oxide, glutamate, acetylcholine) and related enzymes (calcineurin, nitric oxide synthase and acetylcholinesterase) were measured using biochemical detection. Compared to the control group, the levels of the nitric oxide (81.04 +/- 12.84 micromol/g prot) and acetylcholine (30.93 +/- 12.57 microg/mg prot) in M. chinensis philippi of IHg-treated were decreased, while glutamate (2.11 +/- 0.61 mmol/L) increased significantly; the activity of nitric oxide synthase (679.34 +/- 135.33 U/mg prot) was increased, while acetylcholinesterase (1.39 +/- 0.44 U/mg prot) decreased significantly, and the activity of calcineurin (0.52 +/- 0.02 U/mg prot) had a statistically insignificant increasing tendency. The concentration of Ca(2+) (0.92 +/- 0.46 mmol/g prot) in the IHg-treated group was significantly higher than that in the control group. OPLS-DA was performed to reveal the difference in metabolites between the control and IHg-challenged groups, the metabolites of glucose, glutamine, inosine, succinate, glutamate, homarine, and alanine were sensitive to IHg, subsequently metabolic pathways that were affected including glucose metabolism, glutamine metabolism, nucleotide metabolism, Krebs cycle, amino acid metabolism and osmotic regulation. In our study, IHg interfered with metabolites in M. chinensis philippi, thus the corresponding metabolic pathways were changed, which influenced the neurotransmitters subsequently. Furthermore, Ca(2+)overload affected the synthesis or degradation of the neurotransmitters, and then the altered neurotransmitters involved in changes in metabolic pathways again. Overall, we hypothesized that the neurotoxic effects of IHg on bivalve were in close contact with metabolism, neurotransmitters, related enzymes and Ca(2+), which could be effective neurotoxic biomarkers for marine environmental quality assessment, and also provide effective data for the study of the regulatory mechanism of the nervous system in response to IHg in bivalves.
ESTHER : Ma_2024_Aquat.Toxicol_270_106896
PubMedSearch : Ma_2024_Aquat.Toxicol_270_106896
PubMedID: 38490093

Title : Combinatorial preparation and structural characterization of anthocyanins and aglycones from Purple-heart Radish for evaluation of physicochemical stability and pancreatic lipase inhibitory activity - Yuan_2024_Food.Chem_446_138832
Author(s) : Yuan T , Wang L , Chen L , Zhong J , Lin Y , Wang Y , Lin C , Fan H
Ref : Food Chem , 446 :138832 , 2024
Abstract : In this study, an efficient approach to preparation of different anthocyanins from Purple-heart Radish was developed by combining microwave-assisted extraction (MAE), macroporous resin purification (MRP) and ultrasound-assisted acid hydrolysis (UAAH) for evaluation of physicochemical stability and pancreatic lipase (PL) inhibitory activity. By optimization of MAE, MRP and UAAH processes, the anthocyanins reached the yield of 6.081 +/- 0.106 mg/g, the purity of 78.54 +/- 0.62 % (w/w) and the content of 76.29 +/- 1.31 % (w/w), respectively. With high-resolution UHPLC-Q-Orbitrap/MS, 15 anthocyanins were identified as pelargonins with diverse glucosides and confirmed by pelargonidin standard. By glycosylation, pelargonins exhibited higher stability in different pH, temperature, light, metal ions environments than that of pelargonidin. However, PL inhibitory assay, kinetic analysis and molecular docking demonstrated that pelargonidin had higher PL inhibitory activity than pelargonins even though with similar binding sites and a dose-effect relationship. The above results revealed that the effect of glycosylation and deglycosylation on PL inhibitory activity and physicochemical stability.
ESTHER : Yuan_2024_Food.Chem_446_138832
PubMedSearch : Yuan_2024_Food.Chem_446_138832
PubMedID: 38412808

Title : Simultaneous determination of HD56, a novel prodrug, and its active metabolite in cynomolgus monkey plasma using LC-MS\/MS for elucidating its pharmacokinetic profile - Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
Author(s) : Yao S , Zhang W , Xiao J , Zhang Z , Wang L , Ai H , Wu X , Chen A , Zhuang X
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1235 :124045 , 2024
Abstract : An LC-MS/MS method was developed and validated for the simultaneous determination of the carboxylic acid ester precursor HD56 and the active product HD561 in cynomolgus monkey plasma. Then, the pharmacokinetic characteristics of both compounds following single and multiple i.g. administrations in cynomolgus monkeys were elucidated. In the method, chromatographic separation was achieved with a C18 reversed-phase column and the target quantification was carried out by an electrospray ionization (ESI) source coupled with triple quadrupole mess detector in positive ionization mode with multiple reaction monitoring (MRM) approach. Using the quantification method, the in vitro stability of HD56 in plasma and HD56 pharmacokinetic behavior after i.g. administration in cynomolgus monkey were investigated. It was approved that HD56 did convert into HD561 post-administration. The overall systemic exposure of HD561 post-conversion from HD56 accounted for only about 17% of HD56. After repeated administration at the same dose, there was no significant difference in exposure levels of both HD56 and HD561. However, after multiple dosing, the exposure of HD56 tended to decrease while that of HD561 tended to increase, resulting in a 30% in the exposure ratio. Remarkably, with a carboxylesterase (CES) activity profile akin to humans, the observed in vivo pharmacokinetic profile in cynomolgus monkeys holds promise for predicting HD56/HD561 PK profiles in humans.
ESTHER : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedSearch : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedID: 38367406

Title : Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo - Xia_2024_Int.J.Mol.Sci_25_
Author(s) : Xia G , Zhou G , Jiang W , Chu C , Wang L , Moorthy B
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.
ESTHER : Xia_2024_Int.J.Mol.Sci_25_
PubMedSearch : Xia_2024_Int.J.Mol.Sci_25_
PubMedID: 38612589

Title : DPP8\/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathway - Li_2024_Toxicol.Lett__
Author(s) : Li K , Zhang Y , Zhao W , Wang R , Li Y , Wei L , Wang L , Chen X , Chen Z , Liu P , Nie N , Tian X , Fu R
Ref : Toxicol Lett , : , 2024
Abstract : The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9 involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgAN patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-beta1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen , collagen , fibronectin, MMP2, in TGF-beta1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-beta1 via suppressing TGF-beta1/Smad and AKT signaling pathway.
ESTHER : Li_2024_Toxicol.Lett__
PubMedSearch : Li_2024_Toxicol.Lett__
PubMedID: 38458339

Title : Overexpression of an Integument Esterase Gene LbEST-inte4 Infers the Malathion Detoxification in Liposcelis bostrychophila (Psocoptera: Liposcelididae) - Jing_2024_J.Agric.Food.Chem_72_11221
Author(s) : Jing TX , Jiang SD , Tang XP , Guo PY , Wang L , Wang JJ , Wei DD
Ref : Journal of Agricultural and Food Chemistry , 72 :11221 , 2024
Abstract : Liposcelis bostrychophila, commonly known as booklouse, is an important stored-product pest worldwide. Studies have demonstrated that booklices have developed resistance to several insecticides. In this study, an integument esterase gene, LbEST-inte4, with upregulated expression, was characterized in L. bostrychophila. Knockdown of LbEST-inte4 resulted in a substantial increase in the booklice susceptibility to malathion. Overexpression of LbEST-inte4 in Drosophila melanogaster significantly enhanced its malathion tolerance. Molecular modeling and docking analysis suggested potential interactions between LbEST-inte4 and malathion. When overexpressed LbEST-inte4 in Sf9 cells, a notable elevation in esterase activity and malathion tolerance was observed. HPLC analysis indicated that the LbEST-inte4 enzyme could effectively degrade malathion. Taken together, the upregulated LbEST-inte4 appears to contribute to malathion tolerance in L. bostrychophila by facilitating the depletion of malathion. This study elucidates the molecular mechanism underlying malathion detoxification and provides the foundations for the development of effective prevention and control measures against psocids.
ESTHER : Jing_2024_J.Agric.Food.Chem_72_11221
PubMedSearch : Jing_2024_J.Agric.Food.Chem_72_11221
PubMedID: 38703356
Gene_locus related to this paper: lipbo-ESTinte4

Title : Discovery, Structure-Based Modification, In Vitro, In Vivo, and In Silico Exploration of m-Sulfamoyl Benzoamide Derivatives as Selective Butyrylcholinesterase Inhibitors for Treating Alzheimer's Disease - Lu_2024_ACS.Chem.Neurosci__
Author(s) : Lu X , Li Y , Guan Q , Yang H , Liu Y , Du C , Wang L , Wang Q , Pei Y , Wu L , Sun H , Chen Y
Ref : ACS Chem Neurosci , : , 2024
Abstract : For the potential therapy of Alzheimer's disease (AD), butyrylcholinesterase (BChE) has gradually gained worldwide interest in the progression of AD. This study used a pharmacophore-based virtual screening (VS) approach to identify Z32439948 as a new BChE inhibitor. Aiding by molecular docking and molecular dynamics, essential binding information was disclosed. Specifically, a subpocket was found and structure-guided design of a series of novel compounds was conducted. Derivatives were evaluated in vitro for cholinesterase inhibition and physicochemical properties (BBB, log P, and solubility). The investigation involved docking, molecular dynamics, enzyme kinetics, and surface plasmon resonance as well. The study highlighted compounds 27a (hBChE IC(50) = 0.078 +/- 0.03 microM) and (R)-37a (hBChE IC(50) = 0.005 +/- 0.001 microM) as the top-ranked BChE inhibitors. These compounds showed anti-inflammatory activity and no apparent cytotoxicity against the human neuroblastoma (SH-SY5Y) and mouse microglia (BV2) cell lines. The most active compounds exhibited the ability to improve cognition in both scopolamine- and Abeta(1-42) peptide-induced cognitive deficit models. They can be promising lead compounds with potential implications for treating the late stage of AD.
ESTHER : Lu_2024_ACS.Chem.Neurosci__
PubMedSearch : Lu_2024_ACS.Chem.Neurosci__
PubMedID: 38453668

Title : Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for In Vivo Theranostics of Alzheimer's Disease - Wang_2024_J.Med.Chem__
Author(s) : Wang L , Sun T , Zhen T , Li W , Yang H , Wang S , Feng F , Chen Y , Sun H
Ref : Journal of Medicinal Chemistry , : , 2024
Abstract : Butyrylcholinesterase (BChE) is a promising biomarker and effective therapeutic target for Alzheimer's disease (AD). Herein, we designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE inhibitor as the therapeutic unit. DTNP specifically binds BChE with high sensitivity and exhibits strong "turn-on" NIR fluorescence as well as nerve cell protection. In vivo imaging shows DTNP has favorable blood-brain barrier permeability and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the release of ACh, and rescue learning deficits and cognitive impairment. Therefore, DTNP, the first reported and partially validated theranostic probe for the detection of BChE in AD, may provide a foundation and inspiration for imaging and therapy in AD.
ESTHER : Wang_2024_J.Med.Chem__
PubMedSearch : Wang_2024_J.Med.Chem__
PubMedID: 38546542

Title : Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modeling of cetagliptin in patients with type 2 diabetes mellitus - Zhou_2024_Front.Endocrinol.(Lausanne)_15_1359407
Author(s) : Zhou C , Zhou S , Wang J , Xie L , Lv Z , Zhao Y , Wang L , Luo H , Xie D , Shao F
Ref : Front Endocrinol (Lausanne) , 15 :1359407 , 2024
Abstract : AIMS: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients. MATERIALS AND METHODS: 32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix. RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (<=80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC(0-24h) increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-E(max) model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V(2)), and V(2) increased with the increase of TBIL. CONCLUSIONS: Cetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucose-lowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin.
ESTHER : Zhou_2024_Front.Endocrinol.(Lausanne)_15_1359407
PubMedSearch : Zhou_2024_Front.Endocrinol.(Lausanne)_15_1359407
PubMedID: 38529396

Title : Benzofuran Derivatives from Cortex Mori Radicis and Their Cholinesterase-Inhibitory Activity - Cui_2024_Molecules_29_
Author(s) : Cui X , Huang Z , Deng S , Zhang Y , Li G , Wang L , Deng Y , Wu C
Ref : Molecules , 29 : , 2024
Abstract : The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2-5) named albaphenol A-E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7-16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1-16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC(50) 45.5 and 61.0 microM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC(50) 2.5-32.8 microM) than the positive control galantamine (IC(50) 35.3 microM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 microM. The structure-activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor-enzyme complex.
ESTHER : Cui_2024_Molecules_29_
PubMedSearch : Cui_2024_Molecules_29_
PubMedID: 38257228

Title : Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway - Xiang_2024_Neurosci.Lett_830_137769
Author(s) : Xiang X , Xia S , Li S , Zeng Y , Wang L , Zhou Y
Ref : Neuroscience Letters , 830 :137769 , 2024
Abstract : The occurrence and development of Alzheimer's disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.
ESTHER : Xiang_2024_Neurosci.Lett_830_137769
PubMedSearch : Xiang_2024_Neurosci.Lett_830_137769
PubMedID: 38616003

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 : Metal-organic framework-based multienzyme cascade bioreactor for sensitive detection of methyl parathion - Chen_2024_Food.Chem_442_138389
Author(s) : Chen D , Wang L , Wei J , Jiao T , Chen Q , Oyama M , Chen X
Ref : Food Chem , 442 :138389 , 2024
Abstract : In this study, a cascade nanobioreactor was developed for the highly sensitive detection of methyl parathion (MP) in food samples. The simultaneous encapsulation of acetylcholinesterase (AChE) and choline oxidase (CHO) in a zeolitic imidazole ester backbone (ZIF-8) effectively improved the stability and cascade catalytic efficiency of the enzymes. In addition, glutathione-stabilized gold nanoclusters (GSH-AuNCs) were encapsulated in ZIF-8 by ligand self-assembly, conferring excellent fluorescence properties. Acetylcholine (ATCh) is catalyzed by a cascade of AChE/CHO@ZIF-8 as well as Fe(II) to generate hydroxyl radicals (.OH) with strong oxidizing properties. The .OH radicals then oxidize Au(0) in GSH-AuNCs@ZIF-8 to Au(I), resulting in fluorescence quenching. MP, as an inhibitor of AChE, hinders the cascade reaction and thus restores the fluorescence emission, enabling its quantitative detection. The limit of detection of the constructed nanobioreactor for MP was 0.23 microg/L. This MOF-based cascade nanobioreactor has great potential for the detection of trace hazards.
ESTHER : Chen_2024_Food.Chem_442_138389
PubMedSearch : Chen_2024_Food.Chem_442_138389
PubMedID: 38219569

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

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 : Atomistic insight into the binding mode and self-regulation mechanism of IsPETase towards PET substrates with different polymerization degrees - Chen_2023_Phys.Chem.Chem.Phys_25_18332
Author(s) : Chen L , Fan F , Yang M , Wang L , Bai Y , Qiu S , Lyu C , Huang J
Ref : Phys Chem Chem Phys , 25 :18332 , 2023
Abstract : Poly(ethylene terephthalate) (PET) is one of the most widely used synthetic polyesters, however, its extensive use creates a long-term environmental burden. Unlike traditional recycling methods, biodegradation is a sustainable strategy. The emergence of PETase from Ideonella sakaiensis 201-F6 (IsPETase) has brought great potential for the industrialization of degradable PET. In this work, models of enzyme-substrate complexes with different degrees of polymerization were established to study the binding mode using molecular dynamics simulation. We found that the whole binding site can be further subdivided into three parts, including head, middle and tail binding regions. Most importantly, the presence of the middle region formed by both ends of Ser93 and Ser236 provides a potential possibility for the binding of substrates with different chain lengths, and exerts the self-regulation ability of enzymes to accommodate substrates. Meanwhile, the 'pocket bottom' Arg280 in the tail region echoes the 'pocket mouth' Trp185 in the head region, defining the substrate binding region. This work reveals the self-regulation of IsPETase, as well as the key residues for the substrate binding. The solution to these problems enables us to better understand the function of enzymes and design high-performance degradation enzymes, which is of great significance for industrial application research.
ESTHER : Chen_2023_Phys.Chem.Chem.Phys_25_18332
PubMedSearch : Chen_2023_Phys.Chem.Chem.Phys_25_18332
PubMedID: 37401198

Title : Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila - Wang_2023_J.Innate.Immun__
Author(s) : Wang L , Lin J , Yang K , Wang W , Lv Y , Zeng X , Zhao Y , Yu J , Pan L
Ref : J Innate Immun , : , 2023
Abstract : Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.
ESTHER : Wang_2023_J.Innate.Immun__
PubMedSearch : Wang_2023_J.Innate.Immun__
PubMedID: 37742619

Title : A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus - Tse_2023_Sci.Transl.Med_15_eadg5567
Author(s) : Tse LV , Hou YJ , McFadden E , Lee RE , Scobey TD , Leist SR , Martinez DR , Meganck RM , Schafer A , Yount BL , Mascenik T , Powers JM , Randell SH , Zhang Y , Wang L , Mascola J , McLellan JS , Baric RS
Ref : Sci Transl Med , 15 :eadg5567 , 2023
Abstract : The repeated emergence of zoonotic human betacoronaviruses (beta-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)-related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/li/GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/M(pro) protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV-neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo-electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.
ESTHER : Tse_2023_Sci.Transl.Med_15_eadg5567
PubMedSearch : Tse_2023_Sci.Transl.Med_15_eadg5567
PubMedID: 37756379

Title : Alteration of gut microbiota after heat acclimation may reduce organ damage by regulating immune factors during heat stress - Liu_2023_Front.Microbiol_14_1114233
Author(s) : Liu S , Wen D , Feng C , Yu C , Gu Z , Wang L , Zhang Z , Li W , Wu S , Liu Y , Duan C , Zhuang R , Xue L
Ref : Front Microbiol , 14 :1114233 , 2023
Abstract : INTRODUCTION: Heat-related illnesses can lead to morbidity, which are anticipated to increase frequency with predictions of increased global surface temperatures and extreme weather events. Although heat acclimation training (HAT) could prevent heat-related diseases, the mechanisms underlying HAT-promoting beneficial changes in organ function, immunity, and gut microbes remain unclear. METHODS: In the current study, we recruited 32 healthy young soldiers and randomly divided them into 4 teams to conduct HATs for 10 days: the equipment-assisted training team at high temperature (HE); the equipment-assisted training team under normal hot weather (NE); the high-intensity interval training team at high temperature (HIIT), and the control team without training. A standard heat tolerance test (HTT) was conducted before (HTT-1st) and after (HTT-2nd) the training to judge whether the participants met the heat acclimation (HA) criteria. RESULTS: We found that the participants in both HE and NE teams had significantly higher acclimation rates (HA/total population) than whom in the HIIT team. The effects of HAT on the participants of the HE team outperformed that of the NE team. In the HA group, the differences of physiological indicators and plasma organ damage biomarkers (ALT, ALP, creatinine, LDH, alpha-HBDH and cholinesterase) before and after HTT-2nd were significantly reduced to those during HTT-1st, but the differences of immune factors (IL-10, IL-6, CXCL2, CCL4, CCL5, and CCL11) elevated. The composition, metabolism, and pathogenicity of gut microbes changed significantly, with a decreased proportion of potentially pathogenic bacteria (Escherichia-Shigella and Lactococcus) and increased probiotics (Dorea, Blautia, and Lactobacillus) in the HA group. Training for a longer time in a high temperature and humidity showed beneficial effects for intestinal probiotics. CONCLUSION: These findings revealed that pathogenic gut bacteria decrease while probiotics increase following HA, with elevated immune factors and reduced organ damage during heat stress, thereby improving the body's heat adaption.
ESTHER : Liu_2023_Front.Microbiol_14_1114233
PubMedSearch : Liu_2023_Front.Microbiol_14_1114233
PubMedID: 36910226

Title : Platinum nanoflowers stabilized with aloe polysaccharides for detection of organophosphorus pesticides in food - Zhao_2023_Int.J.Biol.Macromol__126552
Author(s) : Zhao H , Li R , Zhang T , Zhou L , Wang L , Han Z , Liu S , Zhang J
Ref : Int J Biol Macromol , :126552 , 2023
Abstract : Organophosphorus pesticides can inhibit the activity of acetylcholinesterase and cause neurological diseases. Therefore, it is crucial to establish an efficient and sensitive platform for organophosphorus pesticide detection. In this work, we extracted aloe polysaccharide (AP) from aloe vera with the number average molecular weight of 29,271 Da and investigated its reducing property. We prepared aloe polysaccharide stabilized platinum nanoflowers (AP-Pt(n) NFs), their particle size ranges were 29.4-67.3 nm. Furthermore, AP-Pt(n) NFs exhibited excellent oxidase-like activity and the catalytic kinetics followed the typical Michaelis-Menten equation. They showed strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of organophosphorus pesticides in food using biocompatible AP-Pt(n) NFs. The detection range was 0.5 microg/L - 140 mg/L, which was wider than many previously reported nanozyme detection systems. This colorimetric biosensor had good selectivity and good promise for bioassay analysis.
ESTHER : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedSearch : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedID: 37660849

Title : Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer's disease - Wang_2023_Neural.Regen.Res_18_226
Author(s) : Wang L , Zhou BQ , Li YH , Jiang QQ , Cong WH , Chen KJ , Wen XM , Wu ZZ
Ref : Neural Regen Res , 18 :226 , 2023
Abstract : Previous studies have shown that berberine has neuroprotective effects against Alzheimer's disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin. Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency. We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer's disease established by injection of amyloid-beta 1-42 into the lateral ventricle. Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus, reduced tau over-phosphorylation in the cerebral cortex, and improved mouse behavior. These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer's disease.
ESTHER : Wang_2023_Neural.Regen.Res_18_226
PubMedSearch : Wang_2023_Neural.Regen.Res_18_226
PubMedID: 35799547

Title : Integration of clinical demographics and routine laboratory analysis parameters for early prediction of gestational diabetes mellitus in the Chinese population - Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
Author(s) : Zhang H , Dai J , Zhang W , Sun X , Sun Y , Wang L , Li H , Zhang J
Ref : Front Endocrinol (Lausanne) , 14 :1216832 , 2023
Abstract : Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy, impairing both maternal and fetal health in short and long term. As early interventions are considered desirable to prevent GDM, this study aims to develop a simple-to-use nomogram based on multiple common risk factors from electronic medical health records (EMHRs). A total of 924 pregnant women whose EMHRs were available at Peking University International Hospital from January 2022 to October 2022 were included. Clinical demographics and routine laboratory analysis parameters at 8-12 weeks of gestation were collected. A novel nomogram was established based on the outcomes of multivariate logistic regression. The nomogram demonstrated powerful discrimination (the area under the receiver operating characteristic curve = 0.7542), acceptable agreement (Hosmer-Lemeshow test, P = 0.3214) and favorable clinical utility. The C-statistics of 10-Fold cross validation, Leave one out cross validation and Bootstrap were 0.7411, 0.7357 and 0.7318, respectively, indicating the stability of the nomogram. A novel nomogram based on easily-accessible parameters was developed to predict GDM in early pregnancy, which may provide a paradigm for repurposing clinical data and benefit the clinical management of GDM. There is a need for prospective multi-center studies to validate the nomogram before employing the nomogram in real-world clinical practice.
ESTHER : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedSearch : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedID: 37900122

Title : Multi- and trans-generational effects of di-n-octyl phthalate on behavior, lifespan and reproduction of Caenorhabditis elegans through neural regulation and lipid metabolism - Zhang_2023_Sci.Total.Environ__165268
Author(s) : Zhang J , Wang L , Liu M , Yu Z
Ref : Sci Total Environ , :165268 , 2023
Abstract : Di-n-octyl phthalate (DOP) is one important phthalate analog whose toxicities need comprehensive investigation to fully demonstrate phthalates health risks. In the present study, apical effects of DOP on behavior, lifespan and reproduction and the underlying mechanisms were explored in Caenorhabditis elegans for four consecutive generations (F1 to F4) and the trans-generational effects were also measured in the great-grand-children (T4 and T4') of F1 and F4. Multi-generational results showed that DOP caused both stimulation and inhibition on head swing, body bending, reverse, Omega steering, pharyngeal pump and satiety quiescence. The stimulation and inhibition altered over concentrations and across generations, and the alteration was the greatest in reverse locomotion which showed both concentration-dependent hormesis and trans-hormesis. DOP stimulated lifespan and inhibited reproduction, showing trade-off relationships. Significant trans-generational residual effects were found in T4 and T4' where the exposure was completed eliminated. Moreover, both similar and different effects were found in comparisons between F1 and F4, between F1 and T4, between F4 and T4' and also between T4 and T4'. Further analysis showed close connections between effects of DOP on neurotransmitters (including dopamine, acetylcholine, gamma-aminobutyric acid and serotonin) and enzymes in lipid metabolism (including lipase, acetyl CoA carboxylase, fatty acid synthetase, carnitine palmitoyl-transferase, glycerol phosphate acyltransferase and acetyl CoA synthetase). Moreover, the close connections were also found between biochemical and apical effects. Notably, the connections were different in multi- and trans-generational effects, which urged further studies to reveal the response strategies underlying the exposure scenarios.
ESTHER : Zhang_2023_Sci.Total.Environ__165268
PubMedSearch : Zhang_2023_Sci.Total.Environ__165268
PubMedID: 37406686

Title : Smartphone-assisted sensor array constructed by copper-based laccase-like nanozymes for specific identification and discrimination of organophosphorus pesticides - Song_2023_Food.Chem_424_136477
Author(s) : Song D , Tian T , Yang X , Wang L , Sun Y , Li Y , Huang H
Ref : Food Chem , 424 :136477 , 2023
Abstract : Accurate pesticide identification is of great importance for regulating food safety. However, the discrimination between organophosphorus pesticides (OPs) and carbamate pesticides (CPs) is still a challenge for existing analytical methods based on cholinesterase inhibition. It mainly because of the similar inhibitory effect of OPs and CPs on cholinesterase. Herein, we found that OPs and CPs differentially affected nanozymes with laccase-like activity, which would be interfered by OPs in different degrees rather than CPs. Thus, we fabricated a nanozyme sensor array and successfully achieved the OPs identification and similar individual discrimination, ignoring the interference from CPs or other potential interferents (antibiotics, ions, other pesticides). On the basis of nanozyme sensor array, a portable method using smartphone was constructed and utilized to determine OPs in fruits and vegetables. This work would contribute to the development of portable sensors and the highly selective identification and discrimination of OPs in complex samples.
ESTHER : Song_2023_Food.Chem_424_136477
PubMedSearch : Song_2023_Food.Chem_424_136477
PubMedID: 37263094

Title : Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients - Liu_2023_Front.Med.(Lausanne)_10_1175089
Author(s) : Liu J , Shao T , Chen H , Ma C , Lu X , Yang X , Song K , Wang L , Lei S , Wang D
Ref : Front Med (Lausanne) , 10 :1175089 , 2023
Abstract : AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.
ESTHER : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedSearch : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedID: 37502364

Title : A chloroplast diacylglycerol lipase modulates glycerolipid pathway balance in Arabidopsis - Yu_2023_Plant.J__
Author(s) : Yu L , Shen W , Fan J , Sah SK , Mavraganis I , Wang L , Gao P , Gao J , Zheng Q , Meesapyodsuk D , Yang H , Li Q , Zou J , Xu C
Ref : Plant J , : , 2023
Abstract : Two parallel pathways compartmentalized in the chloroplast and the endoplasmic reticulum (ER) contribute to thylakoid lipid synthesis in plants, but how these two pathways are coordinated during thylakoid biogenesis and remodeling remain unknown. We report here the molecular characterization of a homologous ADIPOSE TRIGLYCERIDE LIPASE-LIKE gene, previously referred to as ATGLL. The ATGLL gene is ubiquitously expressed throughout development and rapidly upregulated in response to a wide range of environmental cues. We show that ATGLL is a chloroplast non-regioselective lipase with a hydrolytic activity preferentially towards 16:0 of diacylglycerol (DAG). Comprehensive lipid profiling and radiotracer labeling studies revealed negative correlation of ATGLL expression and the relative contribution of the chloroplast lipid pathway to thylakoid lipid biosynthesis. Additionally, we show that genetic manipulation of ATGLL expression resulted in changes in triacylglycerol levels in leaves. We propose that ATGLL, through affecting the level of prokaryotic DAG in the chloroplast, plays important roles in balancing the two glycerolipid pathways and in maintaining lipid homeostasis in plants.
ESTHER : Yu_2023_Plant.J__
PubMedSearch : Yu_2023_Plant.J__
PubMedID: 37006186

Title : Preparation, purification, and biochemical of fat-degrading bacterial enzymes from pig carcass compost and its application - Duan_2023_BMC.Biotechnol_23_48
Author(s) : Duan X , Zhai W , Li X , Wu S , Wang Y , Wang L , Basang W , Zhu Y , Gao Y
Ref : BMC Biotechnol , 23 :48 , 2023
Abstract : BACKGROUND: A lot of kitchen waste oil is produced every day worldwide, leading to serious environmental pollution. As one of the environmental protection methods, microorganisms are widely used treating of various wastes. Lipase, as one of the cleaning agents can effectively degrade kitchen waste oil. The composting process of pig carcasses produces many lipase producing microorganisms, rendering compost products an excellent source for isolating lipase producing microorganisms. To our knowledge, there are no reports isolating of lipase producing strains from the high temperature phase of pig carcass compost. METHODOLOGY: Lipase producing strains were isolated using a triglyceride medium and identified by 16S rRNA gene sequencing. The optimal fermentation conditions for maximum lipase yield were gradually optimized by single-factor tests. The extracellular lipase was purified by ammonium sulfate precipitation and Sephadex G-75 gel isolation chromatography. Amino acid sequence analysis, structure prediction, and molecular docking of the purified protein were performed. The pure lipase's enzymatic properties and application potential were evaluated by characterizing its biochemical properties. RESULTS: In this study, a lipase producing strain of Bacillus sp. ZF2 was isolated from pig carcass compost products, the optimal fermentation conditions of lipase: sucrose 3 g/L, ammonium sulfate 7 g/L, Mn(2+) 1.0 mmol/L, initial pH 6, inoculum 5%, temperature 25 degC, and fermentation time 48 h. After purification, the specific activity of the purified lipase reached 317.59 U/mg, a 9.78-fold improvement. Lipase had the highest similarity to the GH family 46 chitosanase and molecular docking showed that lipase binds to fat via two hydrogen bonds at Gln146 (A) and Glu203 (A). Under different conditions (temperature, metal ions, organic solvents, and surfactants), lipase can maintain enzymatic activity. Under different types of kitchen oils, lipase has low activity only for 'chicken oil', in treating other substrates, the enzyme activity can exceed 50%. CONCLUSIONS: This study reveals the potential of lipase for waste oil removal, and future research will be devoted to the application of lipase.
ESTHER : Duan_2023_BMC.Biotechnol_23_48
PubMedSearch : Duan_2023_BMC.Biotechnol_23_48
PubMedID: 37924095

Title : Rapid detection of carbamate nerve agent analogues using dually functionalized gold nanoclusters - Zhang_2023_Anal.Bioanal.Chem_415_3275
Author(s) : Zhang Q , Lv J , Xia J , Wang L , Qu G , Yang Y , Liu S
Ref : Anal Bioanal Chem , 415 :3275 , 2023
Abstract : Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.
ESTHER : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedSearch : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedID: 37266687

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 : Conjugated linoleic acids inhibit lipid deposition in subcutaneous adipose tissue and alter lipid profiles in serum of pigs - Wang_2023_J.Anim.Sci__
Author(s) : Wang L , Zhang S , Huang Y , Zhou Y , Shan T
Ref : J Anim Sci , : , 2023
Abstract : Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 +/- 10.39 kg) were randomly divided into 2 treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 days. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of lipolytic gene (hormone sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced the content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially cermides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorgammaexpression and further inhibit adipogenic differentiation in adipose tissues of pigs through suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short chain fatty acids (SCFAs) in the gut (P < 0.05) but the abundance of Cers were negatively related to the production and functions of SCFAs (P < 0.05). CLAs altered the lipids distribution in serum and inhibited adipogenic differentiation through suppressing the function of Cers and further decreasing PPARgammaexpression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.
ESTHER : Wang_2023_J.Anim.Sci__
PubMedSearch : Wang_2023_J.Anim.Sci__
PubMedID: 37646838

Title : Enzyme-mediated Ru@UiO-66@MnO(2) NSs\/thiamine-based ratiometric fluorescence sensor for visual detection of organophosphorus pesticide residues - Tong_2023_Food.Chem_429_136945
Author(s) : Tong F , Yang Z , Wang Z , Liu W , Jiang W , Zhu L , Wang L , Zheng M , Hou R , Zhou Y , Liu Y
Ref : Food Chem , 429 :136945 , 2023
Abstract : In view of the potential hazards of organophosphorus pesticides (OPs), this paper constructed a ratiometric fluorescent probe utilizing a functionalized metal-organic framework to detect OPs. Ru(bpy)(3)Cl(2) was encapsulated inside UiO-66 as a reference signal, and MnO(2) nanosheets (MnO(2) NSs) were grown on the surface to obtain Ru@UiO-66@MnO(2) NSs. Acetylcholinesterase catalyzed the decomposition of acetylcholine into reductive thiocholine, which consumed MnO(2) NSs, thus restoring the Ru@UiO-66 fluorescence. Due to the enzymatic inhibition of OPs and the redox reaction between MnO(2) NSs and thiamine, this probe emitted blue fluorescence in the presence of OPs. The probe achieved linear responses to dichlorvos and chlorpyrifos with LODs of 9.99 x 10(-6) microg mL(-1) and 9.99 x 10(-5) microg mL(-1). The probe exhibited a satisfactory recovery rate for OPs in green tea. Furthermore, a hydrogel detection platform was developed by embedding the probe into sodium alginate. Overall, this work provides a visual approach to detect OPs in agricultural products.
ESTHER : Tong_2023_Food.Chem_429_136945
PubMedSearch : Tong_2023_Food.Chem_429_136945
PubMedID: 37487398

Title : Design, Synthesis, and Proof of Concept of Balanced Dual Inhibitors of Butyrylcholinesterase (BChE) and Histone Deacetylase 6 (HDAC6) for the Treatment of Alzheimer's Disease - Wang_2023_ACS.Chem.Neurosci__
Author(s) : Wang L , Sun T , Wang Z , Liu H , Qiu W , Tang X , Guo H , Yang P , Chen Y , Sun H
Ref : ACS Chem Neurosci , : , 2023
Abstract : Concomitant inhibition of butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) is supposed to be effective in the treatment of Alzheimer's disease (AD). Inspired by our previous efforts in designing BChE inhibitors, herein, selective BChE and HDAC6 dual inhibitors were successfully identified through the fusion of the core pharmacophoric moiety of BChE and HDAC6 inhibitors. After the structure-activity relationship (SAR) studies, two compounds (24g and 29a) were confirmed to have superior inhibitory activity against BChE (the IC(50) against hBChE are 4.0 and 1.8 nM, respectively) and HDAC6 (the IC(50) against HDAC6 are 8.9 and 71.0 nM, respectively). These two compounds showed prominently neuroprotective effects in vitro, potent reactive oxygen species (ROS) scavenging effects, and effective metal ion (Fe(2+) and Cu(2+)) chelation. In addition, they exhibited pronounced inhibition of phosphorylated tau and a moderate immunomodulatory effect, with a lack of neurotoxicity at the cellular level. In vivo studies showed that both 24g and 29a ameliorated the cognitive impairment in an Abeta(1-42)-induced mouse model at a low dosage (2.5 mg/kg). Our data demonstrated that BChE/HDAC6 dual inhibitors could establish the basis for a potential new symptomatic and disease-modifying strategy to treat AD.
ESTHER : Wang_2023_ACS.Chem.Neurosci__
PubMedSearch : Wang_2023_ACS.Chem.Neurosci__
PubMedID: 37561893

Title : Biodegradation mechanism of chlorpyrifos by Bacillus sp. H27: Degradation enzymes, products, pathways and whole genome sequencing analysis - Liu_2023_Environ.Res__117315
Author(s) : Liu C , Zhao C , Wang L , Du X , Zhu L , Wang J , Mo Kim Y
Ref : Environ Research , :117315 , 2023
Abstract : Chlorpyrifos (CP) is a pesticide widely used in agricultural production. However, excessive use of CP is risky for human health and the ecological environment. Microbial remediation has become a research hotspot of environmental pollution control. In this study, the effective CP-degrading strain H27 (Bacillus cereus) was screened from farmland soil, and the degradation ratio was more than 80%. Then, the degradation mechanism was discussed in terms of enzymes, pathways, products and genes, and the mechanism was improved in terms of cell motility, secretory transport system and biofilm formation. The key CP-degrading enzymes were mainly intracellular enzymes (IE), and the degradation ratio reached 49.6% within 30 min. The optimal pH for IE was 7.0, and the optimal temperature was 25 degreesC. Using DFT and HPLC-MS analysis, it was found that degradation mainly involved oxidation, hydrolysis and other reactions, and 3 degradation pathways and 14 products were identified, among which TCP (3,5,6-trichloro-2-pyridinol) was the main primary degradation product in addition to small molecules such as CO(2) and H(2)O. Finally, the whole genome of strain H27 was sequenced, and the related degrading genes and enzymes were investigated to improve the metabolic pathways. Strain H27 had perfect genes related to flagellar assembly and chemotaxis and tended to tolerate CP. Moreover, it can secrete esterase, phosphatase and other substances, which can form biofilms and degrade CP in the environment. In addition, CP enters the cell under the action of permeases or transporters, and it is metabolized by IE. The degradation mechanism of CP by strain H27 is speculated in this study, which provided a theoretical basis for enriching CP-degrading bacteria resources, improving degradation metabolic pathways and mechanisms, and applying strain H27 to environmental pollution remediation.
ESTHER : Liu_2023_Environ.Res__117315
PubMedSearch : Liu_2023_Environ.Res__117315
PubMedID: 37805180

Title : A MnO(2) nanosheet-mediated CRISPR\/Cas12a system for the detection of organophosphorus pesticides in environmental water - Yu_2023_Analyst__
Author(s) : Yu HM , Liang GX , Wang HY , Hang XM , Wang HH , Peng JX , Wang L
Ref : Analyst , : , 2023
Abstract : Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO(2) nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO(2) nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO(2) nanosheets to Mn(2+), resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL(-1). In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.
ESTHER : Yu_2023_Analyst__
PubMedSearch : Yu_2023_Analyst__
PubMedID: 38131397

Title : ATG14 plays a critical role in hepatic lipid droplet homeostasis - Huang_2023_Metabolism_148_155693
Author(s) : Huang M , Zhang Y , Park J , Chowdhury K , Xu J , Lu A , Wang L , Zhang W , Ekser B , Yu L , Dong XC
Ref : Metabolism , 148 :155693 , 2023
Abstract : BACKGROUND & AIMS: Autophagy-related 14 (ATG14) is a key regulator of autophagy. ATG14 is also localized to lipid droplet; however, the function of ATG14 on lipid droplet remains unclear. In this study, we aimed to elucidate the role of ATG14 in lipid droplet homeostasis. METHODS: ATG14 loss-of-function and gain-of-function in lipid droplet metabolism were analyzed by fluorescence imaging in ATG14 knockdown or overexpression hepatocytes. Specific domains involved in the ATG14 targeting to lipid droplets were analyzed by deletion or site-specific mutagenesis. ATG14-interacting proteins were analyzed by co-immunoprecipitation. The effect of ATG14 on lipolysis was analyzed in human hepatocytes and mouse livers that were deficient in ATG14, comparative gene identification-58 (CGI-58), or both. RESULTS: Our data show that ATG14 is enriched on lipid droplets in hepatocytes. Mutagenesis analysis reveals that the Barkor/ATG14 autophagosome targeting sequence (BATS) domain of ATG14 is responsible for the ATG14 localization to lipid droplets. Co-immunoprecipitation analysis illustrates that ATG14 interacts with adipose triglyceride lipase (ATGL) and CGI-58. Moreover, ATG14 also enhances the interaction between ATGL and CGI-58. In vitro lipolysis analysis demonstrates that ATG14 deficiency remarkably decreases triglyceride hydrolysis. CONCLUSIONS: Our data suggest that ATG14 can directly enhance lipid droplet breakdown through interactions with ATGL and CGI-58.
ESTHER : Huang_2023_Metabolism_148_155693
PubMedSearch : Huang_2023_Metabolism_148_155693
PubMedID: 37741434
Gene_locus related to this paper: human-ABHD5

Title : Identification of the Flavone-Inducible Counter-Defense Genes and Their cis-Elements in Helicoverpa armigera - Deng_2023_Toxins.(Basel)_15_
Author(s) : Deng Z , Zhang Y , Fang L , Zhang M , Wang L , Ni X , Li X
Ref : Toxins (Basel) , 15 : , 2023
Abstract : Flavone is widely found in plants and plays an important role in plant defense against pests. Many pests, such as Helicoverpa armigera, use flavone as a cue to upregulate counter-defense genes for detoxification of flavone. Yet the spectrum of the flavone-inducible genes and their linked cis-regulatory elements remains unclear. In this study, 48 differentially expressed genes (DEGs) were found by RNA-seq. These DEGs were mainly concentrated in the retinol metabolism and drug metabolism-cytochrome P450 pathways. Further in silico analysis of the promoter regions of 24 upregulated genes predicted two motifs through MEME and five previously characterized cis-elements including CRE, TRE, EcRE, XRE-AhR and ARE. Functional analysis of the two predicted motifs and two different versions of ARE (named ARE1 and ARE2) in the promoter region of the flavone-inducible carboxylesterase gene CCE001j verified that the two motifs and ARE2 are not responsible for flavone induction of H. armigera counter-defense genes, whereas ARE1 is a new xenobiotic response element to flavone (XRE-Fla) and plays a decisive role in flavone induction of CCE001j. This study is of great significance for further understanding the antagonistic interaction between plants and herbivorous insects.
ESTHER : Deng_2023_Toxins.(Basel)_15_
PubMedSearch : Deng_2023_Toxins.(Basel)_15_
PubMedID: 37368666

Title : Rational design of a novel MOF-based ternary nanocomposite for effectively monitoring harmful organophosphates in foods and the environment - Wu_2023_Anal.Methods__
Author(s) : Wu F , Wang B , Guo H , Kang K , Ji X , Wang L , Guo S , Ren J
Ref : Anal Methods , : , 2023
Abstract : Methyl parathion (MP) is a widely used organophosphate insecticide that is extremely toxic due to its ability to irreversibly inhibit acetylcholinesterase in the body and persistently accumulate in the environment. Timely detection of MP can prevent harmful residue exposure to humans. Therefore, the development of fast, efficient electrochemical methods to detect trace MP has been highly beneficial for monitoring harmful residues in foods and environment to ensure food safety and ecological conservation. Herein, a novel hybrid metal-organic framework (MOF) nanocomposite composed of Pt nanoparticles (PtNPs), multi-walled carbon nanotubes (MWCNTs), and UiO-66-NH(2) (PtNPs/UiO-66-NH(2)/MWCNTs) was rationally designed and prepared by a facile two-step strategy for the sensitive determination of MP. The synergistic effects are illustrated in detail using XRD, XPS, FTIR, TEM, and SEM studies as well as electrochemical technologies such as CV, EIS, and DPV. In addition, the performance of the ternary nanocomposite for detecting MP was investigated by comparing it with the binary-component one. The results showed that the PtNPs/UiO-66-NH(2)/MWCNT-based electrochemical sensor exhibited outstanding sensitivity of 21.9 microA microM(-1) cm(-2), satisfactory low detection limit of 0.026 microM and wide linear range of 0.11-227.95 microM for MP analysis. Furthermore, the fabricated sensor delivered distinguished freedom from interferences, outstanding regeneration ability, and adequate recoveries for fresh foods and river water samples. In conclusion, the proposed PtNPs/UiO-66-NH(2)/MWCNT-based sensor provides a potentially useful analytical tool for determining hazardous residues of OPs in foods and the environment.
ESTHER : Wu_2023_Anal.Methods__
PubMedSearch : Wu_2023_Anal.Methods__
PubMedID: 36790872

Title : Kaempferol, a potential neuroprotective agent in neurodegenerative diseases: From chemistry to medicine - Jin_2023_Biomed.Pharmacother_165_115215
Author(s) : Jin S , Zhang L , Wang L
Ref : Biomed Pharmacother , 165 :115215 , 2023
Abstract : Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-beta-rutinoside/6-hydroxykaempferol 3,6-di-O-beta-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Abeta, tau, and alpha-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
ESTHER : Jin_2023_Biomed.Pharmacother_165_115215
PubMedSearch : Jin_2023_Biomed.Pharmacother_165_115215
PubMedID: 37494786

Title : Screening and identification of lipase inhibitors extracted from Dioscorea nipponica Makino by UV-vis and HPLC coupled to UPLC-Q-TOF-MS\/MS - Jin_2023_Int.J.Biol.Macromol__123427
Author(s) : Jin P , Chen L , Zhong J , Yuan T , Gan L , Huang J , Wang L , Fan H , Lin C
Ref : Int J Biol Macromol , :123427 , 2023
Abstract : Dioscoreae nipponica Makino (D. nipponica) as the rhizome of dioscoreaceae rich in steroidal saponins, have been reported to have the hypolipidemic effects etc. However, it is still unclear which exact active components are primary responsible for the beneficial effects. This study was conducted to fish out the lipase inhibitors from D. nipponica, and evaluate the inhibitory activity on porcine pancreatic lipase (PPL) through in vitro kinetic assay using p-nitrophenyl palmitate as substrate. Accordingly, the ethanolic extract was subjected to D101 macroporous resin purification for spectrophotometric screening, high performance liquid chromatography (HPLC) separation and structural characterization by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Through orlistat validation, the PPL inhibitory activity and IC(50) value of the extract were respectively 68.34 +/- 1.47 % and 107.05 microg/mL under the optimized inhibition conditions. From 6 steroidal saponins identified, the inhibitory components named the protodioscin, protogracillin, dioscin and gracillin were fished out by grouping separation and HPLC analysis. Furthermore, dioscin and gracillin with the parent structure of diogenin were confirmed as the major inhibitors by virtue of stability tests based on transformation of protodioscin and protogracillin. Finally, the inhibitory mechanism of the major inhibitors toward PPL was further clarified by kinetic analysis and molecular docking analysis. The proposed method not only revealed the PPL inhibitory components in D. nipponica, but also provided an effective approach to hierarchical screening of PPL inhibitors from natural plants.
ESTHER : Jin_2023_Int.J.Biol.Macromol__123427
PubMedSearch : Jin_2023_Int.J.Biol.Macromol__123427
PubMedID: 36706882

Title : Ultrasensitive Fluorescence Platform Based on AgNPs In Situ-Incorporated Zr-MOFs for the Detection of Organophosphorus Pesticides - Wang_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Wang L , Pan Y , Wang Z , Wang Y , Wei X
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : Organophosphorus pesticides (OPPs) are extensively used in agricultural production, and the contamination caused by their residues has raised significant concerns regarding potential threats to human health. Herein, a novel fluorescence nanoprobe based on an enzyme-mediated silver nanoparticle-modified metal organic framework (AgNPs@PCN-224) was successfully prepared for the rapid detection of OPPs. Initially, AgNPs@PCN-224 were synthesized by reducing silver nitrate (AgNO(3)) using sodium borohydride (NaBH(4)) embedded into luminescent PCN-224. This triggered the inner filter effect, leading to fluorescence quenching. Meanwhile, under the catalysis of acetylcholinesterase (AChE) and choline oxidase (CHO), acetylcholine (ATCh) was decomposed to hydrogen peroxide (H(2)O(2)), which could destroy AgNPs to form Ag(+) released from PCN-224 for fluorescence recovery. Instead, fenitrothion, an OPP, inhibited AChE activity, allowing the quenched fluorescence to be reactivated. Under the current optimum conditions, the fluorescence intensity had a good correlation (Y = -728.5370X + 2178.4248, R(2) = 0.9869) over a dynamic range of fenitrothion concentrations from 0.1 to 500 ng/mL, with an LOD of 0.037 ng/mL. In addition, the anti-interference ability and robustness of the proposed sensor was verified for the monitoring of fenitrothion in tea with recoveries of 87.67-103.72% and the relative standard deviations (RSD) < 5.43%, indicating that the system has excellent prospects for OPP determination in practical applications. Furthermore, this work provides a universal platform for screening other enzyme inhibitors to detect OPPs.
ESTHER : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Wang_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 37676637

Title : Nanoplastics induce neuroexcitatory symptoms in zebrafish (Danio rerio) larvae through a manner contrary to Parkinsonian's way in proteomics - Wang_2023_Sci.Total.Environ__166898
Author(s) : Wang Y , Wang J , Cong J , Zhang H , Gong Z , Sun H , Wang L , Duan Z
Ref : Sci Total Environ , :166898 , 2023
Abstract : Although nanoplastics (NPs) can penetrate the blood-brain barrier and accumulate in the brain, the neurotoxicity of these particles and the mechanisms associated with their unique physio-chemical properties have yet to be sufficiently ascertained. In this study, we assessed the neuroexcitatory symptoms of zebrafish (Danio rerio) larvae treated with polystyrene (PS) NPs based on an examination of locomotory behaviour, dopamine levels, and acetylcholinesterase activity. We found that PS NPs caused oxidative stress and inhibited atoh1a expression in the cerebellum of Tg(atoh1a:dTomato) transgenic zebrafish larvae, thereby indicating damage to the central nervous system. In contrast to the Parkinson's disease (PD) like effects induced by most types of nanoparticles, such as graphene oxide, we established that PS NPs influenced the neuronal proteomic profiles of zebrafish larvae in a manner contrary to the molecular pathways characteristic of PD-like effects, which could be explained by the molecular dynamic simulation. Unlike graphene oxide nanoparticles that promote significant change in the internal structure of neuroproteins, the complex macromolecular polymers of PS NPs promoted the coalescence and increased expression of neuroproteins, thereby plausibly contributing to the neuroexcitatory symptoms observed in treated zebrafish larvae. Consequently, compared with traditional nanoparticles, we believe that the unique physio-chemical properties of NPs could be a potential factor contributing to their toxicity.
ESTHER : Wang_2023_Sci.Total.Environ__166898
PubMedSearch : Wang_2023_Sci.Total.Environ__166898
PubMedID: 37683849

Title : Nanozyme-based dual-signal sensing system for colorimetric and photothermal detection of AChE activity in the blood of liver-injured mice - He_2023_Anal.Bioanal.Chem__
Author(s) : He C , Ke Z , Liu K , Peng J , Yang Q , Wang L , Feng G , Fang J
Ref : Anal Bioanal Chem , : , 2023
Abstract : Acetylcholinesterase (AChE), a crucial enzyme related to liver function, is involved in numerous physiological processes such as neurotransmission and muscular contraction. The currently reported techniques for detecting AChE mainly rely on a single signal output, limiting their high-accuracy quantification. The few reported dual-signal assays are challenging to implement in dual-signal point-of-care testing (POCT) because of the need for large instruments, costly modifications, and trained operators. Herein, we report a colorimetric and photothermal dual-signal POCT sensing platform based on CeO(2)-TMB (3,3',5,5'-tetramethylbenzidine) for the visualization of AChE activity in liver-injured mice. The method compensates for the false positives of a single signal and realizes the rapid, low-cost portable detection of AChE. More importantly, the CeO(2)-TMB sensing platform enables the diagnosis of liver injury and provides an effective tool for studying liver disease in basic medicine and clinical applications. Rapid colorimetric and photothermal biosensor for sensitive detection of acetylcholinesterase (I) and acetylcholinesterase levels in mouse serum (II).
ESTHER : He_2023_Anal.Bioanal.Chem__
PubMedSearch : He_2023_Anal.Bioanal.Chem__
PubMedID: 36995409

Title : Two birds with one stone: An enzyme-regulated ratiometric fluorescent and photothermal dual-mode probe for organophosphorus pesticide detection - Jiang_2023_Biosens.Bioelectron_224_115074
Author(s) : Jiang W , Yang Z , Tong F , Zhang S , Zhu L , Wang L , Huang L , Liu K , Zheng M , Zhou Y , Hou R , Liu Y
Ref : Biosensors & Bioelectronics , 224 :115074 , 2023
Abstract : In this study, based on the oxidase activity and photothermal effect of manganese dioxide nanosheets (MnO(2) NSs), with thiamine (TH) as the fluorescence response signal and tris (2,2'-bipyridyl) ruthenium (II) hexahydrate as the reference signal, an enzyme-regulated ratiometric fluorescence and photothermal dual-mode probe was constructed for the quantitative detection of organophosphorus pesticide (OPs) residues. OPs reduced the production of the reductive product thiocholine by inhibiting the activity of acetylcholinesterase, thereby regulating the residual amount of MnO(2) NSs. With the increase of OPs concentration, the color of the probe solution gradually transitioned from red to blue, and the temperature gradually increased. Using dichlorvos and chlorpyrifos as pesticide models, the developed probes exhibited sensitive responses to OPs in a wide linear range of 0.1-8000sng/mL. The detection limits of dichlorvos and chlorpyrifos in fluorescence mode were 1.13sxs10(-3)sng/mL and 0.86sng/mL, respectively. The corresponding detection limits in photothermal mode were 1.01sng/mL and 1.02sng/mL, respectively. The proposed probe displayed excellent anti-interference and reliability in the analysis of OPs residues in real samples. The dual-mode probe with self-verification function is expected to provide more accurate and robust detection results than the single-mode probe, and has a wider application prospect.
ESTHER : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedSearch : Jiang_2023_Biosens.Bioelectron_224_115074
PubMedID: 36638562

Title : Crystal structure of the GDSL family esterase EstL5 in complex with PMSF reveals a branch channel of the active site pocket - Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
Author(s) : Chen R , Gao X , Nie T , Wu J , Wang L , Osman A , Feng Y , Li X , Zhang Y
Ref : Acta Biochim Biophys Sin (Shanghai) , : , 2023
Abstract : Esterases/lipases from the GDSL family have potential applications in the hydrolysis and synthesis of important esters of pharmaceutical, food, and biotechnical interests. However, the structural and functional understanding of GDSL enzymes is still limited. Here, we report the crystal structure of the GDSL family esterase EstL5 complexed with PMSF at 2.34 A resolution. Intriguingly, the PMSF binding site is not located at the active site pocket but is situated in a surface cavity. At the active site, we note that there is a trapped crystallization solvent 1,6-hexanediol, which mimics the bound ester chain, allowing for further definition of the active site pocket of EstL5. The most striking structural feature of EstL5 is the presence of a unique channel, which extends approximately 18.9 A, with a bottleneck radius of 6.8 A, connecting the active-site pocket and the surface cavity. Replacement of Ser205 with the bulk aromatic residue Trp or Phe could partially block the channel at one end and perturb its access. Reduced enzymatic activity is found in the EstL5 S205W and EstL5 S205F mutants, suggesting the functional relevance of the channel to enzyme catalysis. Our study provides valuable information regarding the properties of the GDSL-family enzymes for designing more efficient and robust biocatalysts.
ESTHER : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedSearch : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedID: 37705347

Title : Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population - Bai_2022_Microbiome_10_147
Author(s) : Bai X , Sun Y , Li Y , Li M , Cao Z , Huang Z , Zhang F , Yan P , Wang L , Luo J , Wu J , Fan D , Chen H , Zhi M , Lan P , Zeng Z , Wu X , Miao Y , Zuo T
Ref : Microbiome , 10 :147 , 2022
Abstract : BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.
ESTHER : Bai_2022_Microbiome_10_147
PubMedSearch : Bai_2022_Microbiome_10_147
PubMedID: 36100953

Title : Fluorescence-activated droplet sorting of PET degrading microorganisms - Qiao_2022_J.Hazard.Mater_424_127417
Author(s) : Qiao Y , Hu R , Chen D , Wang L , Wang Z , Yu H , Fu Y , Li C , Dong Z , Weng YX , Du W
Ref : J Hazard Mater , 424 :127417 , 2022
Abstract : Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology.
ESTHER : Qiao_2022_J.Hazard.Mater_424_127417
PubMedSearch : Qiao_2022_J.Hazard.Mater_424_127417
PubMedID: 34673397

Title : Comprehensive analysis of the carboxylesterase gene reveals that NtCXE22 regulates axillary bud growth through strigolactone metabolism in tobacco - Wang_2022_Front.Plant.Sci_13_1019538
Author(s) : Wang L , Xie X , Xu Y , Li Z , Xu G , Cheng L , Yang J , Li L , Pu W , Cao P
Ref : Front Plant Sci , 13 :1019538 , 2022
Abstract : Carboxylesterases (CXE) are a class of hydrolytic enzymes with alpha/beta-folding domains that play a vital role in plant growth, development, stress response, and activation of herbicide-active substances. In this study, 49 Nicotiana tabacum L. CXE genes (NtCXEs) were identified using a sequence homology search. The basic characteristics, phylogenetic evolution, gene structure, subcellular location, promoter cis-elements, and gene expression patterns of the CXE family were systematically analyzed. RNA-seq data and quantitative real-time PCR showed that the expression level of CXEs was associated with various stressors and hormones; gene expression levels were significantly different among the eight tissues examined and at different developmental periods. As a new class of hormones, strigolactones (SLs) are released from the roots of plants and can control the germination of axillary buds.NtCXE7, NtCXE9, NtCXE22, and NtCXE24 were homologous to Arabidopsis SLs hydrolase AtCXE15, and changes in their expression levels were induced by topping and by GR24 (a synthetic analogue of strigolactone). Further examination revealed that NtCXE22-mutant (ntcxe22) plants generated by CRISPR-Cas9 technology had shorter bud outgrowth with lower SLs content. Validation of NtCXE22 was also performed in NtCCD8-OE plants (with fewer axillary buds) and in ntccd8 mutant plants (with more axillary buds). The results suggest that NtCXE22 may act as an efficient SLs hydrolase and affects axillary bud development, thereby providing a feasible method for manipulating endogenous SLs in crops and ornamental plants.
ESTHER : Wang_2022_Front.Plant.Sci_13_1019538
PubMedSearch : Wang_2022_Front.Plant.Sci_13_1019538
PubMedID: 36600915
Gene_locus related to this paper: tobac-NtCXE49 , tobac-NtCXE48 , tobac-NtCXE46 , tobac-NtCXE44 , tobac-NtCXE41 , tobac-NtCXE40 , tobac-NtCXE39 , tobac-NtCXE38 , tobac-NtCXE36 , tobac-NtCXE34 , tobac-NtCXE33 , tobac-NtCXE28 , tobac-NtCXE27 , tobac-NtCXE26 , tobac-NtCXE25 , tobac-NtCXE24 , tobac-NtCXE23 , tobac-NtCXE21 , tobac-NtCXE19 , tobac-NtCXE18 , tobac-NtCXE17 , tobac-NtCXE15 , tobac-NtCXE14 , tobac-NtCXE13 , tobac-NtCXE12 , tobac-NtCXE11 , tobac-NtCXE10 , tobac-NtCXE8 , tobac-NtCXE7 , tobac-NtCXE6 , tobac-NtCXE5 , tobac-NtCXE4 , tobac-NtCXE3 , tobac-NtCXE2 , tobac-NtCXE1 , tobac-NtCXE30 , tobac-NtCXE32 , tobac-NtCXE22 , tobac-NtCXE29 , tobac-NtCXE35 , tobac-NtCXE45

Title : PFOA exposure causes variations of Acot1 among tissues in rats, and Acot1 in serum can be potentially used as a sensitive marker for health monitoring - Zhou_2022_Toxicol.Res.(Camb)_11_872
Author(s) : Zhou Y , Qiao Y , Zhang X , Ma X , Liu H , Wang L
Ref : Toxicol Res (Camb) , 11 :872 , 2022
Abstract : Perfluorooctanoic acid (PFOA) is a type of 8-carbon perfluoroalkyl substances (PFASs) widely used in industrial and domestic products, which now is a persistent organic pollutant (POP) found in the environment. Its structure is similar to fatty acids, which enables it to induce the expression of ACOT genes. To investigate the expression levels of Acot1 in various tissues and organs after exposure to PFOA for 28 days in rats, and to compare the variations of Acot1 expression in different tissues, we sectioned samples and incubated with Acot1 antibody. The results show that the transcription and protein expression levels of Acot1 in the liver and kidney of rats increased significantly. Meanwhile, the transcription and protein expression of Acot1 gene were also detected in testis, muscle, and adipose. The results of immunohistochemistry were also verified by western blot detection, and we detected the transcription of Acot1 gene in these tissues and found that they all increased in varying degrees. In this study, the expression of Acot1 protein in rat serum was detected for the first time, and the expression of Acot1 in rat serum was found to be significantly increased after PFOA exposure. In addition, the expression level of Acot1 in rat organism was found to be higher than that in the control group after 4 days of depuration for 7 days of acute PFOA exposure, and Acot1 protein expression also showed an increase with increasing exposure time, indicating that Acot1 can be used as a sensitive biomarker for health monitoring of PFOA occupational workers or exposed persons.
ESTHER : Zhou_2022_Toxicol.Res.(Camb)_11_872
PubMedSearch : Zhou_2022_Toxicol.Res.(Camb)_11_872
PubMedID: 36337235

Title : Two Triacylglycerol Lipases Are Negative Regulators of Chilling Stress Tolerance in Arabidopsis - Wang_2022_Int.J.Mol.Sci_23_
Author(s) : Wang L , Qian B , Zhao L , Liang MH , Zhan X , Zhu J
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Cold stress is one of the abiotic stress conditions that severely limit plant growth and development and productivity. Triacylglycerol lipases are important metabolic enzymes for the catabolism of triacylglycerols and, therefore, play important roles in cellular activities including seed germination and early seedling establishment. However, whether they play a role in cold stress responses remains unknown. In this study, we characterized two Arabidopsis triacylglycerol lipases, MPL1 and LIP1 and defined their role in cold stress. The expression of MPL1 and LIP1 is reduced by cold stress, suggesting that they may be negative factors related to cold stress. Indeed, we found that loss-of-function of MPL1 and LIP1 resulted in increased cold tolerance and that the mpl1lip1 double mutant displayed an additive effect on cold tolerance. We performed RNA-seq analysis to reveal the global effect of the mpl1 and lip1 mutations on gene expression under cold stress. The mpl1 mutation had a small effect on gene expression under both under control and cold stress conditions whereas the lip1 mutation caused a much stronger effect on gene expression under control and cold stress conditions. The mpl1lip1 double mutant had a moderate effect on gene expression under control and cold stress conditions. Together, our results indicate that MPL1 and LIP1 triacylglycerol lipases are negative regulators of cold tolerance without any side effects on growth in Arabidopsis and that they might be ideal candidates for breeding cold-tolerant crops through genome editing technology.
ESTHER : Wang_2022_Int.J.Mol.Sci_23_
PubMedSearch : Wang_2022_Int.J.Mol.Sci_23_
PubMedID: 35328798

Title : Isolation and Identification of Efficient Malathion-Degrading Bacteria from Deep-Sea Hydrothermal Sediment - Ma_2022_Microorganisms_10_
Author(s) : Ma L , Dai X , Ai G , Zheng X , Zhang Y , Pan C , Hu M , Jiang C , Wang L , Dong Z
Ref : Microorganisms , 10 : , 2022
Abstract : The genetic and metabolic diversity of deep-sea microorganisms play important roles in phosphorus and sulfur cycles in the ocean, distinguishing them from terrestrial counterparts. Malathion is a representative organophosphorus component in herbicides, pesticides, and insecticides and is analogues of neurotoxic agent. Malathion has been one of the best-selling generic organophosphate insecticides from 1980 to 2012. Most of the sprayed malathion has migrated by surface runoff to ocean sinks, and it is highly toxic to aquatic organisms. Hitherto, there is no report on bacterial cultures capable of degrading malathion isolated from deep-sea sediment. In this study, eight bacterial strains, isolated from sediments from deep-sea hydrothermal regions, were identified as malathion degradators. Two of the tested strains, Pseudidiomarina homiensis strain FG2 and Pseudidiomarina sp. strain CB1, can completely degrade an initial concentration of 500 mg/L malathion within 36 h. Since the two strains have abundant carboxylesterases (CEs) genes, malathion monocarboxylic acid (MMC alpha and MMC beta) and dibasic carboxylic acid were detected as key intermediate metabolites of malathion degradation, and the pathway of malathion degradation between the two strains was identified as a passage from malathion monocarboxylic acid to malathion dicarboxylic acid.
ESTHER : Ma_2022_Microorganisms_10_
PubMedSearch : Ma_2022_Microorganisms_10_
PubMedID: 36144399

Title : Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation - Li_2022_Environ.Sci.Technol__
Author(s) : Li X , Yao Y , Chen H , Zhang Q , Li C , Zhao L , Guo S , Cheng Z , Wang Y , Wang L , Sun H
Ref : Environ Sci Technol , : , 2022
Abstract : The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants.
ESTHER : Li_2022_Environ.Sci.Technol__
PubMedSearch : Li_2022_Environ.Sci.Technol__
PubMedID: 35849551

Title : Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020 - Ma_2022_Front.Public.Health_10_901485
Author(s) : Ma C , Wei D , Liu P , Fan K , Nie L , Song Y , Wang M , Wang L , Xu Q , Wang J , Shi J , Geng J , Zhao M , Jia Z , Huan C , Huo W , Wang C , Mao Z , Huang S , Zeng X
Ref : Front Public Health , 10 :901485 , 2022
Abstract : BACKGROUND: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province. METHODS: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions. RESULTS: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) (P < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all P < 0.05). CONCLUSION: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management.
ESTHER : Ma_2022_Front.Public.Health_10_901485
PubMedSearch : Ma_2022_Front.Public.Health_10_901485
PubMedID: 35757605

Title : The Comparative Analysis of Genomic Diversity and Genes Involved in Carbohydrate Metabolism of Eighty-Eight Bifidobacterium pseudocatenulatum Isolates from Different Niches of China - Lin_2022_Nutrients_14_
Author(s) : Lin G , Liu Q , Wang L , Li H , Zhao J , Zhang H , Wang G , Chen W
Ref : Nutrients , 14 : , 2022
Abstract : Eighty-eight Bifidobacterium pseudocatenulatum strains, which were isolated from human, chicken and cow fecal samples from different niches of China, were compared genomically in this study to evaluate their diversity. It was found that B. pseudocatenulatum displayed a closed pan-genome, including abundant glycoside hydrolase families of the carbohydrate active enzyme (CAZy). A total of 30 kinds of glycoside hydrolases (GHs), 14 kinds of glycosyl transferases (GTs), 13 kinds of carbohydrate-binding modules (CBMs), 6 kinds of carbohydrate-esterases (CEs), and 2 kinds of auxiliary activities (AAs) gene families were identified across the genomes of the 88 B. pseudocatenulatum strains. Specifically, this showed that significant differences were also present in the number of 10 carbohydrate-active enzyme gene families (GT51, GH13_32, GH26, GH42, GH121, GH3, AA3, CBM46, CE2, and CE6) among the strains derived from the hosts of different age groups, particularly between strains from infants and those from other human age groups. Twelve different individuals of B. pseudocatenulatum from four main clusters were selected for further study to reveal the genetic diversity of carbohydrate metabolism-related genes within the same phylogenetics. The animal experiment showed that 3 weeks of oral administration and 1 week after cessation of administration of these strains did not markedly alter the serum routine inflammatory indicators in mice. Furthermore, the administration of these strains did not significantly cause adverse changes in the gut microbiota, as indicated by the alpha- and beta-diversity indexes, relative to the control group (normal diet). Beyond that, FAHBZ9L5 significantly increased the abundance of B. pseudocatenulatum after 3 weeks and significantly increased the abundance of acetic acid and butyric acid in the host's intestinal tract 3 and 4 weeks after the first administration, respectively, compared with the control group. Corresponding to this, comparative genomic analyses of 12 B. pseudocatenulatum suggest that FAHBZ9L5-specific genes were rich in ABC transporters and carbohydrate esterase. Combining the results of comparative genomics analyses and animal experiment, it is suggested that the strains containing certain gene clusters contribute to another competitive growth advantage of B. pseudocatenulatum, which facilitates its intestinal carbohydrate metabolism in a host.
ESTHER : Lin_2022_Nutrients_14_
PubMedSearch : Lin_2022_Nutrients_14_
PubMedID: 35684146

Title : N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer's Disease - Du_2022_J.Med.Chem__
Author(s) : Du C , Wang L , Guan Q , Yang H , Chen T , Liu Y , Li Q , Lyu W , Lu X , Chen Y , Liu H , Feng F , Liu W , Liu Z , Li W , Sun H
Ref : Journal of Medicinal Chemistry , : , 2022
Abstract : Herein, we report a series of selective sub-nanomolar inhibitors against butyrylcholinesterase (BChE). These compounds, bearing a novel N-benzyl benzamide scaffold, inhibited BChE with IC(50) from picomolar to nanomolar. The inhibitory activity was confirmed by the surface plasmon resonance assay, showing a sub-nanomolar K(D) value, which revealed that the compounds exert the inhibitory effect through directly binding to BChE. Several compounds showed neuroprotective effects verified by the oxidative damage model. Furthermore, the safety of S11-1014 and S11-1033 was demonstrated by the in vivo acute toxicity test. In the behavior study, 0.5 mg/kg S11-1014 or S11-1033 exhibited a marked therapeutic effect, which was almost equal to the treatment with 1 mg/kg rivastigmine, against the cognitive impairment induced by Abeta(1-42). The pharmacokinetics studies characterized the metabolic stability of S11-1014. Thus, N-benzyl benzamide inhibitors are promising compounds with drug-like properties for improving cognitive dysfunction, providing a potential strategy for the treatment of Alzheimer's disease.
ESTHER : Du_2022_J.Med.Chem__
PubMedSearch : Du_2022_J.Med.Chem__
PubMedID: 35969197

Title : Carthamus tinctorius L.: A natural neuroprotective source for anti-Alzheimer's disease drugs - Liang_2022_J.Ethnopharmacol__115656
Author(s) : Liang Y , Wang L
Ref : J Ethnopharmacol , :115656 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multicausal neurodegenerative disease clinically characterized by generalized dementia. The pathogenic process of AD not only is progressive and complex but also involves multiple factors and mechanisms, including beta-amyloid (Abeta) aggregation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. As the first-line treatment for AD, cholinesterase inhibitors can, to a certain extent, relieve AD symptoms and delay AD progression. Nonetheless, the current treatment strategies for AD are far from meeting clinical expectations, and more options for AD treatment should be applied in clinical practice. AIM OF THE REVIEW: The aim of this review was to investigate published reports of C. tinctorius L. and its active constituents in AD treatment through a literature review. MATERIALS AND METHODS: Information was retrieved from scientific databases including Web of Science, ScienceDirect, Scopus, Google Scholar, Chemical Abstracts Services and books, PubMed, dissertations and technical reports. Keywords used for the search engines were "Honghua" or "Carthamus tinctorius L." or "safflower" in conjunction with "(native weeds OR alien invasive)"AND "Chinese herbal medicine". RESULTS: A total of 47 literatures about C. tinctorius L. and its active constituents in AD treatment through signaling pathways, immune cells, and disease-related mediators and systematically elucidates potential mechanisms from the point of anti-Abeta aggregation, suppressing tau protein hyperphosphorylation, increasing cholinergic neurotransmitters levels, inhibiting oxidative stress, anti-neuroinflammation, ameliorating synaptic plasticity, and anti-apoptosis. CONCLUSIONS: Chinese herbal medicine (CHM) is a treasure endowed by nature to mankind. Emerging studies have confirmed that CHM and its active constituents play a positive role in AD treatment. Carthamus tinctorius L., the most commonly used CHM, can be used with medicine and food, with the effect of activating blood circulation and eliminating blood stasis. In the paper, we have concluded that the existing therapeutic mechanisms of C. tinctorius L. and summarized the potential mechanisms of C. tinctorius L. and its active constituents in AD treatment through a literature review.
ESTHER : Liang_2022_J.Ethnopharmacol__115656
PubMedSearch : Liang_2022_J.Ethnopharmacol__115656
PubMedID: 36041691

Title : Biosensor Based on Covalent Organic Framework Immobilized Acetylcholinesterase for Ratiometric Detection of Carbaryl - Luo_2022_Biosensors.(Basel)_12_
Author(s) : Luo Y , Wu N , Wang L , Song Y , Du Y , Ma G
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : A ratiometric electrochemical biosensor based on a covalent organic framework (COF(Thi-TFPB)) loaded with acetylcholinesterase (AChE) was developed. First, an electroactive COF(Thi-TFPB) with a two-dimensional sheet structure, positive charge and a pair of inert redox peaks was synthesized via a dehydration condensation reaction between positively charged thionine (Thi) and 1,3,5-triformylphenylbenzene (TFPB). The immobilization of AChE on the positively charged electrode surface was beneficial for maintaining its bioactivity and achieving the best catalytic effect; therefore, the positively charged COF(Thi-TFPB) was an appropriate support material for AChE. Furthermore, the COF(Thi-TFPB) provided a stable internal reference signal for the constructed AChE inhibition-based electrochemical biosensor to eliminate various effects which were unrelated to the detection of carbaryl. The sensor had a linear range of 2.2-60 microM with a detection limit of 0.22 microM, and exhibited satisfactory reproducibility, stability and anti-interference ability for the detection of carbaryl. This work offers a possibility for the application of COF-based materials in the detection of low-level pesticide residues.
ESTHER : Luo_2022_Biosensors.(Basel)_12_
PubMedSearch : Luo_2022_Biosensors.(Basel)_12_
PubMedID: 36005021

Title : Anti-human Glioma Cancer Potentials of Neobavaisoflavone as Natural Antioxidant Compound and Its Inhibition Profiles for Acetylcholinesterase and Butyrylcholinesterase Enzymes with Molecular Modeling and Spin Density Distributions Studies - Chen_2022_J.Oleo.Sci_71_277
Author(s) : Chen M , Zhao H , Cheng Y , Wang L , Alotaibi SH , Zhang Y
Ref : J Oleo Sci , 71 :277 , 2022
Abstract : In this study, the carcinogenic potential of Neobavaisoflavone as a natural antioxidant compound and the inhibitory profiles of acetylcholinesterase and butyrylcholinesterase were investigated by molecular modeling and spin density distribution studies. To evaluate the antioxidant properties of neobavaisoflavone, DPPH test was performed in the presence of butyl hydroxytoluene as a control. Neobavaisoflavone cell viability was low compared to normal human glioma cancer cell lines, namely LN-229, U-87 and A-172 cell lines, without any effect of cytotoxicity on normal cell line. Neobavaisoflavone inhibited half of DPPH at 125 microg/mL. The best effects of Neobavaisoflavone antihypertensive glioma against the above cell lines were in the LN-229 cell line. In addition, the significant anti-cancer potential of human glioma Neobavaisoflavone against the popular human glioma cancer cell lines is related in this study. IC(50) values were calculated by Neobavaisoflavone diagrams, 63.87 nM for AChE and 112.98 nM for BuChE, % Activity- [Inhibitor]. According to the above results, Neobavaisoflavone can be used to treat a variety of human glioma cancers in humans. In addition, molecular modeling calculations were performed to compare the biochemical activities of the Neobavaisoflavone molecule with enzymes. After molecular insertion calculations, ADME/T analysis was performed to investigate the properties of the neobavaisoflavone molecule, which will be used as a drug in the future. Then, different parameters for the antioxidant activity of the neobavaisoflavone molecule were calculated.
ESTHER : Chen_2022_J.Oleo.Sci_71_277
PubMedSearch : Chen_2022_J.Oleo.Sci_71_277
PubMedID: 35110469

Title : Knockdown of DPP4 promotes the proliferation and the activation of the CREB\/aromatase pathway in ovarian granulosa cells - Lin_2022_Mol.Med.Rep_25_
Author(s) : Lin L , Wang L
Ref : Mol Med Rep , 25 : , 2022
Abstract : Dipeptidyl peptidase 4 (DPP4) has been revealed to be upregulated in women suffering from polycystic ovary syndrome (PCOS), which is a common reproductive disorder. The present study was designed to investigate the effects of inhibition of DPP4 expression on the proliferation of ovarian granulosa cells as well as on the activation of the cAMP response elementbinding protein (CREB)/aromatase pathway. The expression levels of DPP4 in rat serum samples with or without PCOS and ovarian granulosa cells (KGN cells) were detected using reverse transcriptionquantitative PCR (RTqPCR) and western blot analyses. Cell viability and cell cycle progression were detected using the Cell Counting Kit8 assay and flow cytometric analysis, respectively. The 5ethynyl2'deoxyuridine assay was employed to detect the proliferation of glycolaldehydebovine serum albumin (GOABSA)treated KGN cells. In addition, RTqPCR and western blot analyses were applied to detect the expression levels of CREB, specific cell cycleassociated proteins and cytochrome P450 (CYP) 19A1 and CYP11A1 enzymes in KGN cells. The expression levels of DPP4 were upregulated in rats with PCOS. Inhibition of DPP4 expression promoted the proliferation and cell cycle arrest of KGN cells. It was also revealed that the expression levels of cell cycleassociated proteins were upregulated in DPP4silenced KGN cells. In addition, their proliferation was decreased following treatment with GOABSA, while the addition of sitagliptin partially reversed these effects. Additionally, sitagliptin reversed the inhibitory effects caused by GOABSA treatment on the cell cycle progression and on the activation of the CREB/aromatase pathway in KGN cells, as determined by the increased expression levels of the cell cycleassociated proteins as well as those of the CREB protein and the CYP19A1 and CYP11A1 enzymes. In conclusion, inhibition of DPP4 expression promoted the proliferation of KGN cells and the activation of the CREB/aromatase pathway.
ESTHER : Lin_2022_Mol.Med.Rep_25_
PubMedSearch : Lin_2022_Mol.Med.Rep_25_
PubMedID: 35014677

Title : Directional-path modification strategy enhances PET hydrolase catalysis of plastic degradation - Chen_2022_J.Hazard.Mater_433_128816
Author(s) : Chen XQ , Guo ZY , Wang L , Yan ZF , Jin CX , Huang QS , Kong DM , Rao DM , Wu J
Ref : J Hazard Mater , 433 :128816 , 2022
Abstract : Poly (ethylene terephthalate) (PET) is a widely used type of general plastic that produces a significant amount of waste due to its non-degradable properties. We propose a novel directional-path modification (DPM) strategy, involving positive charge amino acid introduction and binding groove remodeling, and apply it to Thermobifida fusca cutinase to enhance PET degradation. The highest value of PET degradation (90%) was achieved in variant 4Mz (H184S/Q92G/F209I/I213K), exhibiting values almost 30-fold that of the wild-type. We employed molecular docking, molecular dynamics simulations, and QM/MM MD for the degradation process of PET, accompanied by acylation and deacylation. We found that the distance of nucleophilic attack was reduced from about 4.6 A in the wild type to 3.8 A in 4Mz, and the free energy barrier of 4Mz dropped from 14.3 kcal/mol to 7.1 kcal/mol at the acylation which was the rate-limiting step. Subsequently, the high efficiency and universality of the DPM strategy were successfully demonstrated in LCC, Est119, and BhrPETase enhancing the degradation activity of PET. Finally, the highest degradation rate of the pretreated commercial plastic bottles had reached to 73%. The present study provides insight into the molecular binding mechanism of PET into the PET hydrolases structure and proposes a novel DPM strategy that will be useful for the engineering of more efficient enzymes for PET degradation.
ESTHER : Chen_2022_J.Hazard.Mater_433_128816
PubMedSearch : Chen_2022_J.Hazard.Mater_433_128816
PubMedID: 35390614
Gene_locus related to this paper: thefu-q6a0i3

Title : Protective effect of Juglanin against doxorubicin-induced cognitive impairment in rats: Effect on oxidative, inflammatory and apoptotic machineries - Wei_2022_Metab.Brain.Dis__
Author(s) : Wei T , Wang L , Tang J , Ashaolu TJ , Olatunji OJ
Ref : Metabolic Brain Disease , : , 2022
Abstract : Doxorubicin (DOX) is an effective anticancer drug, however, side effects such as cognitive impairment and cardiotoxicity have limited its clinical use. Juglanin (JUG) is a flavonoid with excellent antioxidant, anti-inflammatory, neuroprotective and anticancer properties. This study investigated the protective effects of JUG against DOX-induced cognitive decline, oxidative stress and inflammatory response in rats. The rats were orally administrated with JUG or JUG in combination with DOX. After treatment, the animals were subjected to series of behavioral test including Morris water maze, Y-maze and forced swimming tests. After the study, the rats were sacrificed and the level of acetylcholinesterase (AchE), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), caspase 3 and Nuclear factor kappa B (NF-B) were assayed in the brain. Histopathological analysis was also performed on the brain of the rats. JUG significantly protected against DOX-induced cognitive impairment and depressive behaviors. In addition, JUG attenuated altered brain histopathological architecture, reduced oxido-inflammatory responses, acetylcholinesterase and caspase 3 activity in the brain of the treated rats. Collectively, the results suggested that JUG offered neuroprotection against DOX induced Chemobrain via ameliorating oxidative stress and inflammation.
ESTHER : Wei_2022_Metab.Brain.Dis__
PubMedSearch : Wei_2022_Metab.Brain.Dis__
PubMedID: 35138546

Title : Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection - Pang_2022_Cell.Rep_39_110698
Author(s) : Pang Y , Cheng Z , Zhang S , Li S , Li X , Zhang X , Feng Y , Cui H , Chen Z , Liu L , Li Q , Huang J , Zhang M , Zhu S , Wang L , Feng L
Ref : Cell Rep , 39 :110698 , 2022
Abstract : Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection.
ESTHER : Pang_2022_Cell.Rep_39_110698
PubMedSearch : Pang_2022_Cell.Rep_39_110698
PubMedID: 35443182

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : Lipase-Catalyzed Phospha-Michael Addition Reactions under Mild Conditions - Xu_2022_Molecules_27_7798
Author(s) : Xu Y , Li F , Ma J , Li J , Xie H , Wang C , Chen P , Wang L
Ref : Molecules , 27 :7798 , 2022
Abstract : Organophosphorus compounds are the core structure of many active natural products. The synthesis of these compounds is generally achieved by metal catalysis requiring specifically functionalized substrates or harsh conditions. Herein, we disclose the phospha-Michael addition reaction of biphenyphosphine oxide with various substituted beta-nitrostyrenes or benzylidene malononitriles. This biocatalytic strategy provides a direct route for the synthesis of C-P bonds with good functional group compatibility and simple and practical operation. Under the optimal conditions (styrene (0.5 mmol), biphenyphosphine oxide (0.5 mmol), Novozym 435 (300 U), and EtOH (1 mL)), lipase leads to the formation of organophosphorus compounds in yields up to 94% at room temperature. Furthermore, we confirm the role of the catalytic triad of lipase in this phospha-Michael addition reaction. This new biocatalytic system will have broad applications in organic synthesis.
ESTHER : Xu_2022_Molecules_27_7798
PubMedSearch : Xu_2022_Molecules_27_7798
PubMedID: 36431898

Title : A novel monoacylglycerol lipase-targeted (18)F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network - Cheng_2022_Acta.Pharmacol.Sin__
Author(s) : Cheng R , Fujinaga M , Yang J , Rong J , Haider A , Ogasawara D , Van RS , Shao T , Chen Z , Zhang X , Calderon Leon ER , Zhang Y , Mori W , Kumata K , Yamasaki T , Xie L , Sun S , Wang L , Ran C , Shao Y , Cravatt B , Josephson L , Zhang MR , Liang SH
Ref : Acta Pharmacol Sin , : , 2022
Abstract : Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [(18)F]FEPAD. Pharmacokinetics and binding studies on [(18)F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [(18)F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies.
ESTHER : Cheng_2022_Acta.Pharmacol.Sin__
PubMedSearch : Cheng_2022_Acta.Pharmacol.Sin__
PubMedID: 35513432
Gene_locus related to this paper: human-MGLL

Title : Analysis of the performance of the efficient di-(2-ethylhexyl) phthalate-degrading bacterium Rhodococcus pyridinovorans DNHP-S2 and associated catabolic pathways - Wang_2022_Chemosphere_306_135610
Author(s) : Wang L , Gan D , Gong L , Zhang Y , Wang J , Guan R , Zeng L , Qu J , Dong M
Ref : Chemosphere , 306 :135610 , 2022
Abstract : The widespread use of plastic has led to the global occurrence of phthalate esters (PAEs) pollution. PAEs can be effectively removed from polluted environments by microbe-mediated degradation. Di-(2-ethylhexyl) phthalate (DEHP) has the highest residual concentration in agricultural soil-contaminated areas compared to other PAEs in most of China. The Rhodococcus pyridinovorans DNHP-S2 microbial isolate identified was found to efficiently degrade DEHP. Within a 72 h period, the bacteria were able to degrade 52.47% and 99.75% of 500 mg L(-1) DEHP at 10 degreesC and 35 degreesC, respectively. Dimethyl phthalate (DMP) was first identified as an intermediate metabolite of DEHP, which is different from the previously reported DEHP catabolic pathway. Genomic sequencing of DNHP-S2 identified benzoate 1,2-dioxygenase and catechol 2,3/1,2-dioxygenase as potential mediators of DEHP degradation, consistent with the existence of two downstream metabolic pathways governing DEHP degradation. Three targets DEHP metabolism-related enzymes were found to be DEHP-inducible at the mRNA level, and DNHP-S2 was able to mediate the complete degradation of DEHP at lower temperatures, as confirmed via RT-qPCR. DNHP-S2 was also found to readily break down other PAEs including DMP, di-n-butyl phthalate (DBP), di-n-octyl phthalate (DnOP), and n-butyl benzyl phthalate (BBP). Together, these results thus highlight DNHP-S2 as a bacterial strain with great promise as a tool for the remediation of PAE pollution. In addition to providing new germplasm and genetic resources for use in the context of PAE degradation, these results also offer new insight into the potential mechanisms whereby PAEs undergo catabolic degradation, making them well-suited for use in PAE-contaminated environments.
ESTHER : Wang_2022_Chemosphere_306_135610
PubMedSearch : Wang_2022_Chemosphere_306_135610
PubMedID: 35810862

Title : Similarities and differences among the responses to three chlorinated organophosphate esters in earthworm: Evidences from biomarkers, transcriptomics and metabolomics - Gao_2022_Sci.Total.Environ_815_152853
Author(s) : Gao Y , Wang L , Zhang X , Shi C , Ma L , Wang G
Ref : Sci Total Environ , 815 :152853 , 2022
Abstract : The wide use of chlorinated organophosphate esters (Cl-OPEs) as additive flame retardants has aroused concern about their potential risks on ecosystem and human health. However, knowledge about the toxicity of Cl-OPEs on soil organisms remains limited. In this study, earthworms, Eisenia fetida, were exposed to three representative Cl-OPEs, i.e., tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in artificial soil. Using a combination of biochemical indicators (biomarkers), transcriptomics, and metabolomics, we compared the Cl-OPE-induced toxicity to E. fetida and provide new insight into the related molecular mechanism. All three Cl-OPEs elicited immune defense by the earthworms, as evidenced by increased acid phosphatase and alkaline phosphatase activities, and the genes involved in immune-related pathways (e.g., lysosomal and interleukin-17 signaling pathways). Furthermore, no effects on acetylcholinesterase activity were observed among the three Cl-OPEs. However, the TCPP and TDCPP treatments significantly decreased the neurotransmitter serotonin, suggesting the potential neurotoxicity of Cl-OPEs. Although TCEP affected the genes involved in carbohydrate and amino acid metabolism, the changes in the corresponding metabolites were not statistically significant. In contrast, exposure to TCPP and TDCPP induced oxidative stress, and affected xenobiotic metabolism and energy metabolism, leading to the decreased body weight in E. fetida. Based on these toxic effects, TCPP and TDCPP were more severely toxic than TCEP, despite their structural similarity. Given that the use of TCEP has been tightly regulated, our results suggest the potentially toxic effects of TCPP and TDCPP should not be ignored in future risk assessments of flame retardants.
ESTHER : Gao_2022_Sci.Total.Environ_815_152853
PubMedSearch : Gao_2022_Sci.Total.Environ_815_152853
PubMedID: 34998776

Title : First Report of Mutations Associated With Pyrethroid (L1014F) and Organophosphate (G119S) Resistance in Belgian Culex (Diptera: Culicidae) Mosquitoes - Wang_2022_J.Med.Entomol__
Author(s) : Wang L , Soto A , Remue L , Rosales Rosas AL , De Coninck L , Verwimp S , Bouckaert J , Vanwinkel M , Matthijnssens J , Delang L
Ref : Journal of Medical Entomology , : , 2022
Abstract : The emergence of West Nile virus and Usutu virus in Europe poses a significant risk to public health. In the absence of efficient antiviral therapy or vaccine candidates, the only strategy to control these arboviruses is to target the Culex (Diptera: Culicidae) mosquito vector. However, the selection pressure caused by exposure to insecticides for vector control or agricultural pest control can lead to insecticide resistance, thereby reducing the efficacy of insecticide-based vector control interventions. In Culex mosquitoes, two of the most common amino acid substitutions associated with insecticide resistance are the kdr L1014F in voltage gated sodium channels and G119S in acetylcholinesterase. In this study, Culex pipiens biotype pipiens, Culex torrentium, and Culex modestus were sampled from 2019 to 2021 in three distinct environmental habitats (urban, peri-urban, and agricultural) in and around the city of Leuven, Belgium. Individual mosquitoes were screened for two mutations resulting in L1014F and G119S amino acid substitutions. Both mutations were observed in Cx. pipiens and Cx. modestus but not in Cx. torrentium mosquitoes across the four collection sites. Furthermore, multi-resistance or cross-resistance in Cx. pipiens could be a threat in these areas, as both mutations were observed at low frequencies. These results provide the first report of kdr L1014F and ace-1 G119S resistance mutations in Cx. pipiens and Cx. modestus mosquitoes from Belgium, highlighting the importance of mosquito surveillance to design effective arbovirus outbreak control strategies.
ESTHER : Wang_2022_J.Med.Entomol__
PubMedSearch : Wang_2022_J.Med.Entomol__
PubMedID: 36130161

Title : A Novel Paper-Based Electrochemical Biosensor Based on N,O-Rich Covalent Organic Frameworks for Carbaryl Detection - Xiao_2022_Biosensors.(Basel)_12_
Author(s) : Xiao Y , Wu N , Wang L , Chen L
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : A new N,O-rich covalent organic framework (COF(DHNDA-BTH)) was synthesized by an amine-aldehyde condensation reaction between 2,6-dialdehyde-1,5-dihydroxynaphthalene (DHNDA) and 1,3,5-phenyltriformylhydrazine (BTH) for carbaryl detection. The free NH, OH, and C=O groups of COF(DHNDA-BTH) not only covalently couples with acetylcholinesterase (AChE) into the pores of COF(DHNDA-BTH), but also greatly improves the catalytic activity of AChE in the constrained environment of COF(DHNDA-BTH)'s pore. Under the catalysis of AChE, the acetylthiocholine (ATCl) was decomposed into positively charged thiocholine (TCl), which was captured on the COF(DHNDA-BTH) modified electrode. The positive charges of TCl can attract anionic probe [Fe(CN)(6)](3-/4-) on the COF(DHNDA-BTH)-modified electrode to show a good oxidation peak at 0.25 V (versus a saturated calomel electrode). The carbaryl detection can inhibit the activity of AChE, resulting in the decrease in the oxidation peak. Therefore, a turn-off electrochemical carbaryl biosensor based on a flexible carbon paper electrode loaded with COF(DHNDA-BTH) and AChE was constructed using the oxidation peak of an anionic probe [Fe(CN)(6)](3-/4-) as the detection signal. The detection limit was 0.16 microM (S/N = 3), and the linear range was 0.48~35.0 microM. The sensor has good selectivity, repeatability, and stability, and has a good application prospect in pesticide detection.
ESTHER : Xiao_2022_Biosensors.(Basel)_12_
PubMedSearch : Xiao_2022_Biosensors.(Basel)_12_
PubMedID: 36291036

Title : A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin - Lu_2022_Br.J.Clin.Pharmacol_88_2946
Author(s) : Lu J , Wang L , Zhou S , Zhou C , Xie L , Chen J , Tang D , Tian X , Xie D , Ding J , Wang T , Yu Q , Shao F
Ref : British Journal of Clinical Pharmacology , 88 :2946 , 2022
Abstract : AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin. METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200mg cetagliptin. Positive control (sitagliptin 100mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study. RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses <=50mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (<=80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29ng/mL) was lower than that of sitagliptin (7.03ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses <=100mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied. CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin.
ESTHER : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedSearch : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedID: 34965609

Title : Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism - Wang_2022_Mol.Psychiatry__
Author(s) : Wang L , Mirabella VR , Dai R , Su X , Xu R , Jadali A , Bernabucci M , Singh I , Chen Y , Tian J , Jiang P , Kwan KY , Pak C , Liu C , Comoletti D , Hart RP , Chen C , Sudhof TC , Pang ZP
Ref : Mol Psychiatry , : , 2022
Abstract : Mutations in many synaptic genes are associated with autism spectrum disorders (ASD), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C mutation on human neurons has not been investigated. Here, we generated human knockin neurons with the NLGN3 R451C and NLGN3 null mutations. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses; meanwhile NLGN3 knockout neurons showed reduction in excitatory synaptic strengths. Moreover, overexpression of NLGN3 R451C recapitulated the synaptic enhancement in human neurons. Notably, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons corresponding to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASD.
ESTHER : Wang_2022_Mol.Psychiatry__
PubMedSearch : Wang_2022_Mol.Psychiatry__
PubMedID: 36280753

Title : Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder - Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
Author(s) : Huang S , Huang Y , Lin W , Wang L , Yang Y , Li P , Xiao L , Chen Y , Chu Q , Yuan X
Ref : Oxid Med Cell Longev , 2022 :2586305 , 2022
Abstract : Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and gamma-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.
ESTHER : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedSearch : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedID: 35620578

Title : Butenolide derivatives from Aspergillus terreus selectively inhibit butyrylcholinesterase - Cui_2022_Front.Chem_10_1063284
Author(s) : Cui X , Deng S , Li G , Zhang Y , Wang L , Wu C , Deng Y
Ref : Front Chem , 10 :1063284 , 2022
Abstract : Two undescribed butenolide derivatives, asperteretal J (1) and K (2), together with 13 known ones (3-15) were isolated from an endophytic fungus Aspergillus terreus SGP-1, the fermentation product of which exhibited selective inhibitory activity toward butyrylcholinesterase. The structures of the new compounds were elucidated based on HRMS and NMR data, and the absolute configurations were determined by specific optical rotation comparison. All compounds were evaluated for cholinesterase inhibitory effects with galantamine as a positive control. Compounds 4-8 selectively inhibited butyrylcholinesterase with IC(50) values of 18.4-45.8smicroM in a competitive manner, with Ki values of 12.3-38.2smicroM. The structure-activity relationship was discussed. Molecular docking and dynamic simulation of the inhibitor-enzyme complex were performed to better understand the interactions.
ESTHER : Cui_2022_Front.Chem_10_1063284
PubMedSearch : Cui_2022_Front.Chem_10_1063284
PubMedID: 36618870

Title : Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity - Cao_2022_Toxicol.Lett_361_1
Author(s) : Cao C , Wang L , Zhang J , Liu Z , Li M , Xie S , Chen G , Xu X
Ref : Toxicol Lett , 361 :1 , 2022
Abstract : The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)- 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity.
ESTHER : Cao_2022_Toxicol.Lett_361_1
PubMedSearch : Cao_2022_Toxicol.Lett_361_1
PubMedID: 35331841

Title : Distinct AMPK-Mediated FAS\/HSL Pathway Is Implicated in the Alleviating Effect of Nuciferine on Obesity and Hepatic Steatosis in HFD-Fed Mice - Xu_2022_Nutrients_14_
Author(s) : Xu H , Lyu X , Guo X , Yang H , Duan L , Zhu H , Pan H , Gong F , Wang L
Ref : Nutrients , 14 : , 2022
Abstract : Nuciferine (Nuci), the main aporphine alkaloid component in lotus leaf, was reported to reduce lipid accumulation in vitro. Herein we investigated whether Nuci prevents obesity in high fat diet (HFD)-fed mice and the underlying mechanism in liver/HepG2 hepatocytes and epididymal white adipose tissue (eWAT) /adipocytes. Male C57BL/6J mice were fed with HFD supplemented with Nuci (0.10%) for 12 weeks. We found that Nuci significantly reduced body weight and fat mass, improved glycolipid profiles, and enhanced energy expenditure in HFD-fed mice. Nuci also ameliorated hepatic steatosis and decreased the size of adipocytes. Furthermore, Nuci remarkably promoted the phosphorylation of AMPK, suppressed lipogenesis (SREBP1, FAS, ACC), promoted lipolysis (HSL, ATGL), and increased the expressions of adipokines (FGF21, ZAG) in liver and eWAT. Besides, fatty acid oxidation in liver and thermogenesis in eWAT were also activated by Nuci. Similar results were further observed at cellular level, and these beneficial effects of Nuci in cells were abolished by an effective AMPK inhibitor compound C. In conclusion, Nuci supplementation prevented HFD-induced obesity, attenuated hepatic steatosis, and reduced lipid accumulation in liver/hepatocytes and eWAT/adipocytes through regulating AMPK-mediated FAS/HSL pathway. Our findings provide novel insight into the clinical application of Nuci in treating obesity and related complications.
ESTHER : Xu_2022_Nutrients_14_
PubMedSearch : Xu_2022_Nutrients_14_
PubMedID: 35565866

Title : Preparation, characterization and bioactivities of selenized polysaccharides from Lonicera caerulea L. fruits - Shao_2022_Int.J.Biol.Macromol__
Author(s) : Shao C , Zhong J , Liu J , Yang Y , Li M , YangYu , Xu Y , Wang L
Ref : Int J Biol Macromol , : , 2022
Abstract : Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO(3)-Na(2)SeO(3) method, where the selenium (Se) contents were 228 +/-24 and 353 +/- 36 microg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 10(4), 5.6 10(4), and 5.1 10(4) kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE.
ESTHER : Shao_2022_Int.J.Biol.Macromol__
PubMedSearch : Shao_2022_Int.J.Biol.Macromol__
PubMedID: 36403769

Title : Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma - Chen_2022_Mol.Metab__101600
Author(s) : Chen X , Liu Q , Chen Y , Wang L , Yang R , Zhang W , Pan X , Zhang S , Chen C , Wu T , Xia J , Cheng B , Ren X
Ref : Mol Metab , :101600 , 2022
Abstract : OBJECTIVE: Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear. METHODS: The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC. RESULTS: CES2 was downregulated in OSCC patients, especially those with recurrence or metastasis. CES2(high) OSCC patients showed better overall survival than CES2(low) OSCC patients. Restoring CES2 expression reduced OSCC cell viability and suppressed their migration and invasion in vitro, and it inhibited OSCC tumor growth in vivo. CES2 reprogrammed lipid metabolism in OSCC cells by hydrolyzing neutral lipid diacylglycerols (DGs) to release free fatty acids and reduce the membrane structure lipid phospholipids (PLs) synthesis. Free FAs were converted to acyl-carnitines (CARs) and transferred to mitochondria for oxidation, which induced reactive oxygen species (ROS) accumulation, mitochondrial damage, and apoptosis activation. Furthermore, the reduction in signaling lipids, e.g., DGs, PLs and substrates, suppressed PI3K/AKT/MYC signaling pathways. Restoring MYC rescued the diminished cell viability, suppressed migratory and invasive abilities, damaged mitochondria and reduced apoptosis rate induced by CES2. CONCLUSIONS: We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC.
ESTHER : Chen_2022_Mol.Metab__101600
PubMedSearch : Chen_2022_Mol.Metab__101600
PubMedID: 36113774

Title : An in vitro nerve agent brain poisoning transwell model for convenient and accurate antidote evaluation - Huang_2022_Toxicol.In.Vitro__105541
Author(s) : Huang L , Li Y , Zhang Z , Huang J , Xing H , Wang L , Sui X , Luo Y , Wang Y , Yang J
Ref : Toxicol In Vitro , :105541 , 2022
Abstract : Nerve agent (NA) can inhibit acetylcholinesterase (AChE) causing seriously injury at extremely low doses. However, the cruel reality is that the lack of effective cerebral antidotes for treatment of NA poisoning. There is an urgent requirement for the large-scale evaluation and screening of antidotes. An effective NA antidote should include two characteristics: a) to permeate the blood-brain barrier (BBB); 2) to reactivate the inhibited AChE in brain. Existing methods for evaluating reactivators in vitro can only examine the reactivation effect, while the current Transwell model can only evaluate the drug penetration performance for crossing the barrier. In this work, brain microvascular endothelial cells (RBMECs) were inoculated to establish a Transwell model. AChE, NAs and antidotes of reactivators were added into the different chambers to simulate central poisoning and peripheral drug administration. This method can evaluate the reactivation ability and brain penetration ability of compounds at same time, which is a rapidly and accurately way for drug preliminary screening. In addition to small-molecule drugs, a liposomal nanoantidote loaded with the reactivator Asoxime chloride (HI-6)was prepared. This nanoantidote show high reactivation rate against the NA (sarin), evaluated by both this modified model in vitro and animal test, gaining the consistence results.
ESTHER : Huang_2022_Toxicol.In.Vitro__105541
PubMedSearch : Huang_2022_Toxicol.In.Vitro__105541
PubMedID: 36572320

Title : Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) - Zhang_2022_Pest.Manag.Sci__
Author(s) : Zhang L , Wang L , Chen J , Zhang J , He Y , Lu Y , Cai J , Chen X , Wen X , Xu Z , Wang C
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2022_Pest.Manag.Sci__
PubMedSearch : Zhang_2022_Pest.Manag.Sci__
PubMedID: 35192738

Title : Lipase-catalyzed hydrazine insertion for the synthesis of N'-alkyl benzohydrazides - Yu_2022_Biotechnol.Appl.Biochem__
Author(s) : Yu Y , Li F , Li J , Zheng X , Tian H , Mahmut Z , Du Y , Dai Y , Wang L
Ref : Biotechnol Appl Biochem , : , 2022
Abstract : N'-alkyl benzohydrazides are classic organic compounds that have been widely utilized in organic chemistry. In this study, an efficient method was developed for the synthesis of N'-alkyl benzohydrazides by hydrazine insertion catalyzed by lipase. Under the optimal conditions (Morita-Baylis-Hillman ketone [1 mmol], phenylhydrazine [1.3 mmol], N,N-dimethylformamide [2 mL], lipase [20 mg], room temperature, 12 h), satisfactory yields (71%-97%) and substrate tolerance were obtained when porcine pancreatic lipase was used as biocatalyst. These findings imply the great potential for the lipase-catalyzed synthesis of N'-alkyl benzohydrazides and extend the utilization of lipase in organic chemistry. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2022_Biotechnol.Appl.Biochem__
PubMedSearch : Yu_2022_Biotechnol.Appl.Biochem__
PubMedID: 35285069

Title : Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study - Yamasaki_2021_Theranostics_11_9492
Author(s) : Yamasaki T , Hatori A , Zhang Y , Mori W , Kurihara Y , Ogawa M , Wakizaka H , Rong J , Wang L , Liang S , Zhang MR
Ref : Theranostics , 11 :9492 , 2021
Abstract : Hypoxia caused by ischemia induces acidosis and neuroexcitotoxicity, resulting in neuronal death in the central nervous system (CNS). Monoacylglycerol lipase (MAGL) is a modulator of 2-arachidonoylglycerol (2-AG), which is involved in retrograde inhibition of glutamate release in the endocannabinoid system. In the present study, we used positron emission tomography (PET) to monitor MAGL-positive neurons and neuroinflammation in the brains of ischemic rats. Additionally, we performed PET imaging to evaluate the neuroprotective effects of an MAGL inhibitor in an ischemic injury model. Methods: Ischemic-injury rat models were induced by intraluminal right middle cerebral artery occlusion (MCAO). PET studies of the brains of the ischemic rats were performed at several experimental time points (pre-occlusion, days 2, 4, and 7 after the MCAO surgery) using [(11)C]SAR127303 for MAGL and [(18)F]FEBMP for 18 kDa translocator protein (TSPO, a hall-mark of neuroinflammation). Medication using minocycline (a well-known neuroprotective agent) or KML29 (a potent MAGL inhibitor) was given immediately after the MCAO surgery and then daily over the subsequent three days. Results: PET imaging of the ischemic rats using [(11)C]SAR127303 showed an acute decline of radioactive accumulation in the ipsilateral side at two days after MCAO surgery (ratio of the area under the curve between the ipsilateral and contralateral sides: 0.49 +/- 0.04 in the cortex and 0.73 +/- 0.02 in the striatum). PET imaging with [(18)F]FEBMP, however, showed a moderate increase in accumulation of radioactivity in the ipsilateral hemisphere on day 2 (1.36 +/- 0.11), and further increases on day 4 (1.72 +/- 0.15) and day 7 (1.99 +/- 0.06). Treatment with minocycline or KML29 eased the decline in radioactive accumulation of [(11)C]SAR127303 for MAGL (minocycline-treated group: 0.82 +/- 0.06 in the cortex and 0.81 +/- 0.05 in the striatum; KML29-treated group: 0.72 +/- 0.07 in the cortex and 0.88 +/- 0.04 in the striatum) and increased uptake of [(18)F]FEBMP for TSPO (minocycline-treated group: 1.52 +/- 0.21 in the cortex and 1.56 +/- 0.11 in the striatum; KML29-treated group: 1.63 +/- 0.09 in the cortex and 1.50 +/- 0.17 in the striatum). In MCAO rats, minocycline treatment showed a neuroprotective effect in the sensorimotor cortex suffering from severe hypoxic injury, whereas KML29 treatment saved neurons in the striatum, including bundles of myelinated axons. Conclusions: PET imaging allowed visualization of the different neuroprotective effects of minocycline and KML29, and indicated that combination pharmacotherapy using these drugs may be an effective therapy in acute ischemia.
ESTHER : Yamasaki_2021_Theranostics_11_9492
PubMedSearch : Yamasaki_2021_Theranostics_11_9492
PubMedID: 34646382

Title : Host-pathogen interaction between Asian citrus psyllid and entomopathogenic fungus (Cordyceps fumosorosea) is regulated by modulations in gene expression, enzymatic activity and HLB-bacterial population of the host - Qasim_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109112
Author(s) : Qasim M , Xiao H , He K , Omar MAA , Hussain D , Noman A , Rizwan M , Khan KA , Al-Zoubi OM , Alharbi SA , Wang L , Li F
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109112 , 2021
Abstract : The host-pathogen interaction has been explored by several investigations, but the impact of fungal pathogens against insect resistance is still ambiguous. Therefore, we assessed the enzymatic activity and defense-related gene expression of Asian citrus psyllid (ACP) nymphal and adult populations on Huanglongbing-diseased citrus plants under the attack of Cordyceps fumosorosea. Overall, five enzymes viz. superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione S-transferase (GST), carboxylesterase (CarE), and four genes, namely SOD, 16S, CYP4C68, CYP4BD1, were selected for respective observations from ACP populations. Enzymatic activity of four enzymes (SOD, POD, GST, CarE) was significantly decreased after 5-days post-treatment (dpt) and 3-dpt fungal exposure in fungal treated ACP adult and nymphal populations, respectively, whereas the activity of CAT was boosted substantially post-treatment time schedule. Besides, we recorded drastic fluctuations in the expression of CYP4 genes among fungal treated ACP populations. After 24 hours post-treatment (hpt), expression of both CYP4 genes was boosted in fungal treated populations than controlled populations (adult and nymph). After 3-dpt, however, the expression of CYP4 genes was declined in the given populations. Likewise, fungal attack deteriorated the resistance of adult and nymphal of ACP population, as SOD expression was down-regulated in fungal-treated adult and nymphs after 5-dpt and 3-dpt exposure, respectively. Moreover, bacterial expression via the 16S gene was significantly increased in fungal-treated adult and nymphal ACP populations with increasing post-treatment time. Overall, our data illustrate that the fungal application disrupted the insect defense system. The expression of these genes and enzymes suppress the immune function of adult and nymphal ACP populations. As it is reported first time that the applications of C. fumosorosea against ACP reduce insect resistance by interfering with the CYP4 and SOD system. Therefore, we propose new strategies to discover the role of certain toxic compounds from fungus, which can reduce insect resistance, focusing on resistance-related genes and enzymes.
ESTHER : Qasim_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109112
PubMedSearch : Qasim_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109112
PubMedID: 34153507

Title : Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells - Zhang_2021_Pharmacol.Res_169_105630
Author(s) : Zhang Y , Li K , Li Y , Zhao W , Wang L , Chen Z , Ma X , Yao T , Wang J , Dong W , Li X , Tian X , Fu R
Ref : Pharmacol Res , 169 :105630 , 2021
Abstract : BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-beta1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-beta1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF.
ESTHER : Zhang_2021_Pharmacol.Res_169_105630
PubMedSearch : Zhang_2021_Pharmacol.Res_169_105630
PubMedID: 33932609
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays - Song_2021_Food.Funct_12_162
Author(s) : Song YQ , Guan XQ , Weng ZM , Liu JL , Chen J , Wang L , Cui LT , Fang SQ , Hou J , Ge GB
Ref : Food Funct , 12 :162 , 2021
Abstract : Human carboxylesterase 2 (hCES2A) is a key target to ameliorate the intestinal toxicity triggered by irinotecan that causes severe diarrhea in 50%-80% of patients receiving this anticancer agent. Herbal medicines are frequently used for the prevention and treatment of the intestinal toxicity of irinotecan, but it is very hard to find strong hCES2A inhibitors from herbal medicines in an efficient way. Herein, an integrated strategy via combination of chemical profiling, docking-based virtual screening and fluorescence-based high-throughput inhibitor screening assays was utilized. Following the screening of a total of 73 herbal products, licorice (the dried root of Glycyrrhiza species) was found with the most potent hCES2A inhibition activity. Further investigation revealed that the chalcones and several flavonols in licorice displayed strong hCES2A inhibition activities, while isoliquiritigenin, echinatin, naringenin, gancaonin I and glycycoumarin exhibited moderate inhibition of hCES2A. Inhibition kinetic analysis demonstrated that licochalcone A, licochalcone C, licochalcone D and isolicoflavonol potently inhibited hCES2A-mediated fluorescein diacetate hydrolysis in a reversible and mixed inhibition manner, with K(i) values less than 1.0 microM. Further investigations demonstrated that licochalcone C, the most potent hCES2A inhibitor identified from licorice, dose-dependently inhibited intracellular hCES2A in living HepG2 cells. In summary, this study proposed an integrated strategy to find hCES2A inhibitors from herbal medicines, and our findings suggested that the chalcones and isolicoflavonol in licorice were the key ingredients responsible for hCES2A inhibition, which would be very helpful to develop new herbal remedies or drugs for ameliorating hCES2A-associated drug toxicity.
ESTHER : Song_2021_Food.Funct_12_162
PubMedSearch : Song_2021_Food.Funct_12_162
PubMedID: 33291124

Title : Ciclesonide activates glucocorticoid signaling in neonatal rat lung but does not trigger adverse effects in the cortex and cerebellum - Jaumotte_2021_Neurobiol.Dis__105422
Author(s) : Jaumotte JD , Franks AL , Bargerstock EM , Kisanga EP , Menden HL , Ghersi A , Omar M , Wang L , Rudine A , Short KL , Silswal N , Cole TJ , Sampath V , Monaghan-Nichols AP , DeFranco DB
Ref : Neurobiol Dis , :105422 , 2021
Abstract : Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections.
ESTHER : Jaumotte_2021_Neurobiol.Dis__105422
PubMedSearch : Jaumotte_2021_Neurobiol.Dis__105422
PubMedID: 34126164

Title : Preparation and properties of a dual-function cellulose nanofiber-based bionic biosensor for detecting silver ions and acetylcholinesterase - Wang_2021_J.Hazard.Mater_403_123921
Author(s) : Wang L , Guo W , Zhu H , He H , Wang S
Ref : J Hazard Mater , 403 :123921 , 2021
Abstract : A dual-function cellulose nanofiber (CNF)-based bionic biosensor with good biocompatibility was developed for detecting Ag(+) and acetylcholinesterase (AChE) by grafting deoxyribonucleic acid (DNA) onto CNF. The Ag(+) ions captured by the biosensor acted as recognition sites for the detection of AChE. The CNF-based bionic biosensor (CNF-DNA) could detect Ag(+) concentrations as low as 10(-6) nM in the presence of interference metal ions (Hg(2+), Ba(2+), Cd(2+), Mg(2+), Mn(2+), Pb(2+), and Zn(2+)). DNA-template silver nanoclusters (DNA-AgNCs) were formed on the surface of CNF-DNA during the detection of Ag(+) (CNF-DNA-AgNCs). This new strategy yielded CNF-DNA-AgNCs through the adsorption of Ag(+) ions onto the cytosine base of the single-stranded DNA in CNF-DNA without the use of any additional reducer. Meanwhile, the CNF-DNA-AgNCs exhibited excellent sensitivity and selectivity for trace levels (0.053 mU/mL) of AChE in the presence of interference reagents. The novel strategy proposed in this paper may establish a foundation for further research on DNA-template AgNCs for developing biosensors and biomarkers for in vivo and in vitro detection.
ESTHER : Wang_2021_J.Hazard.Mater_403_123921
PubMedSearch : Wang_2021_J.Hazard.Mater_403_123921
PubMedID: 33264972

Title : Synergistic biodegradation of poly(ethylene terephthalate) using Microbacterium oleivorans and Thermobifida fusca cutinase - Yan_2021_Appl.Microbiol.Biotechnol__
Author(s) : Yan ZF , Wang L , Xia W , Liu ZZ , Gu LT , Wu J
Ref : Applied Microbiology & Biotechnology , : , 2021
Abstract : Poly(ethylene terephthalate) (PET) is a major source of plastic pollution. Biodegradation technologies are of paramount interest in reducing or recycling PET waste. In particular, a synergistic microbe-enzyme treatment may prove to be a promising approach. In this study, a synergistic system composed of Microbacterium oleivorans JWG-G2 and Thermobifida fusca cutinase (referred to as TfC) was employed to degrade bis(hydroxyethyl) terephthalate (BHET) oligomers and a high crystalline PET film. A novel degradation product that was obtained by M. oleivorans JWG-G2 treatment alone was identified as ethylene glycol terephthalate (EGT). With the addition of TfC as a second biocatalyst, the highest synergy degrees for BHET oligomers and PET film degradation were 2.79 and 2.26, respectively. The largest amounts of terephthalic acid (TPA) and mono(2-hydroxyethyl) terephthalate (MHET) (47 nM and 330 nM, respectively) were detected after combined treatment of PET film with M. oleivorans JWG-G2 at 5 x 10(3) microL/cm(2) and TfC at 120 microg/cm(2), and the degree of PET film surface destruction was more significant than those produced by each treatment alone. The presence of extracellular PET hydrolases in M. oleivorans JWG-G2, including three carboxylesterases, an esterase and a lipase, was predicted by whole genome sequencing analysis, and a predicted PET degradation pathway was proposed for the synergistic microbe-enzyme treatment. The results indicated that synergistic microbe-enzyme treatment may serve as a potentially promising tool for the future development of effective PET degradation. KEY POINTS: An ecofriendly synergistic microbe-enzyme PET degradation system operating at room temperature was first introduced for degrading PET. A novel product (EGT) was first identified during PET degradation. Potential PET hydrolases in M. oleivorans JWG-G2 were predicted by whole genome sequencing analysis.
ESTHER : Yan_2021_Appl.Microbiol.Biotechnol__
PubMedSearch : Yan_2021_Appl.Microbiol.Biotechnol__
PubMedID: 34037842

Title : Rational Design for Broadened Substrate Specificity and Enhanced Activity of a Novel Acetyl Xylan Esterase from Bacteroides thetaiotaomicron - Wang_2021_J.Agric.Food.Chem_69_6665
Author(s) : Wang L , Han X , Wang Y , Wei X , Liu S , Shao S , Yang S , Sun L , Xin F
Ref : Journal of Agricultural and Food Chemistry , 69 :6665 , 2021
Abstract : Gut bacteria-derived enzymes play important roles in the metabolism of dietary fiber through enabling the hydrolysis of polysaccharides. In this study, we identified and characterized a 29 kDa novel acetyl xylan esterase, BTAxe1, from Bacteroides thetaiotaomicron VPI5482. Then, we solved the structure of BTAxe1 and performed the rational design. Mutants N65S and N65A increased the activities toward short-chain (pNPA, pNPB) to near four-fold, and gained the activities toward longer-chain substrate (pNPO). Molecular docking analysis showed that the mutant N65S had a larger substrate binding pocket than the wild type. Hydrolysis studies using natural substrates showed that either N65S or N65A showed higher activity of that of wild-type, yielding 131.31 and 136.09 mM of acetic acid from xylan. This is the first study on the rational design of gut bacteria-derived Axes with broadened substrate specificity and enhanced activity, which can be referenced by other acetyl esterases or gut-derived enzymes.
ESTHER : Wang_2021_J.Agric.Food.Chem_69_6665
PubMedSearch : Wang_2021_J.Agric.Food.Chem_69_6665
PubMedID: 34074097
Gene_locus related to this paper: bacth-BT1008

Title : Identification and characterization of a novel carboxylesterase EstQ7 from a soil metagenomic library - Yan_2021_Arch.Microbiol__
Author(s) : Yan Z , Ding L , Zou D , Wang L , Tan Y , Guo S , Zhang Y , Xin Z
Ref : Arch Microbiol , : , 2021
Abstract : A novel lipolytic gene, estq7, was identified from a fosmid metagenomic library. The recombinant enzyme EstQ7 consists of 370 amino acids with an anticipated molecular mass of 42 kDa. Multiple sequence alignments showed that EstQ7 contained a pentapeptide motif GHSMG, and a putative catalytic triad Ser174-Asp306-His344. Interestingly, EstQ7 was found to have very little similarity to the characterized lipolytic enzymes. Phylogenetic analysis revealed that EstQ7 may be a member of a novel family of lipolytic enzymes. Biochemical characterization of the recombinant enzyme revealed that it constitutes a slightly alkalophilic, moderate thermophilic and highly active carboxylesterase against short-chain fatty acid esters with optimum temperature 50 degC and pH 8.2. The Km and kcat values toward p-nitrophenyl acetate were determined to be 0.17 mM and 1910s(-1), respectively. Moreover, EstQ7 was demonstrated to have acyltransferase activity by GC-MS analysis. Structural modeling of the three-dimensional structure of this new enzyme showed that it exhibits a typical alpha/beta hydrolase fold, and the catalytic triad residues are spatially close. Molecular docking revealed the interactions between the enzyme and the ligand. The high levels of lipolytic activity of EstQ7, combined with its moderate thermophilic property and acyltransferase activity, render this novel enzyme a promising candidate biocatalyst for food, pharmaceutical and biotechnological applications.
ESTHER : Yan_2021_Arch.Microbiol__
PubMedSearch : Yan_2021_Arch.Microbiol__
PubMedID: 34057548
Gene_locus related to this paper: 9bact-MW804671

Title : Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development - Hou_2021_J.Med.Chem_64_123
Author(s) : Hou L , Rong J , Haider A , Ogasawara D , Varlow C , Schafroth MA , Mu L , Gan J , Xu H , Fowler CJ , Zhang MR , Vasdev N , Ametamey S , Cravatt BF , Wang L , Liang SH
Ref : Journal of Medicinal Chemistry , 64 :123 , 2021
Abstract : The endocannabinoid system (ECS) is involved in a wide range of biological functions and comprises cannabinoid receptors and enzymes responsible for endocannabinoid synthesis and degradation. Over the past 2 decades, significant advances toward developing drugs and positron emission tomography (PET) tracers targeting different components of the ECS have been made. Herein, we summarized the recent development of PET tracers for imaging cannabinoid receptors 1 (CB1R) and 2 (CB2R) as well as the key enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), particularly focusing on PET neuroimaging applications. State-of-the-art PET tracers for the ECS will be reviewed including their chemical design, pharmacological properties, radiolabeling, as well as preclinical and human PET imaging. In addition, this review addresses the current challenges for ECS PET biomarker development and highlights the important role of PET ligands to study disease pathophysiology as well as to facilitate drug discovery.
ESTHER : Hou_2021_J.Med.Chem_64_123
PubMedSearch : Hou_2021_J.Med.Chem_64_123
PubMedID: 33379862

Title : The alpha-Helical Cap Domain of a Novel Esterase from Gut Alistipes shahii Shaping the Substrate-Binding Pocket - Wei_2021_J.Agric.Food.Chem__
Author(s) : Wei X , Wang YL , Wen BT , Liu SJ , Wang L , Sun L , Gu TY , Li Z , Bao Y , Fan SL , Zhou H , Wang F , Xin F
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : The human gut microbiota regulates nutritional metabolism, especially by encoding specific ferulic acid esterases (FAEs) to release functional ferulic acid (FA) from dietary fiber. In our previous study, we observed seven upregulated FAE genes during in vitro fecal slurry fermentation using wheat bran. Here, a 29 kDa FAE (AsFAE) from Alistipes shahii of Bacteroides was characterized and identified as the type-A FAE. The X-ray structure of AsFAE has been determined, revealing a unique alpha-helical domain comprising five alpha-helices, which was first characterized in FAEs from the gut microbiota. Further molecular docking analysis and biochemical studies revealed that Tyr100, Thr122, Tyr219, and Ile220 are essential for substrate binding and catalytic efficiency. Additionally, Glu129 and Lys130 in the cap domain shaped the substrate-binding pocket and affected the substrate preference. This is the first report on A. shahii FAE, providing a theoretical basis for the dietary metabolism in the human gut.
ESTHER : Wei_2021_J.Agric.Food.Chem__
PubMedSearch : Wei_2021_J.Agric.Food.Chem__
PubMedID: 33979121
Gene_locus related to this paper: 9bact-d4inh0

Title : Novel Reversible-Binding PET Ligands for Imaging Monoacylglycerol Lipase Based on the Piperazinyl Azetidine Scaffold - Rong_2021_J.Med.Chem__
Author(s) : Rong J , Mori W , Xia X , Schafroth MA , Zhao C , Van RS , Yamasaki T , Chen J , Xiao Z , Haider A , Ogasawara D , Hiraishi A , Shao T , Zhang Y , Chen Z , Pang F , Hu K , Xie L , Fujinaga M , Kumata K , Gou Y , Fang Y , Gu S , Wei H , Bao L , Xu H , Collier TL , Shao Y , Carson RE , Cravatt BF , Wang L , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , : , 2021
Abstract : Monoacylglycerol lipase (MAGL) is a 33 kDa serine protease primarily responsible for hydrolyzing 2-arachidonoylglycerol into the proinflammatory eicosanoid precursor arachidonic acid in the central nervous system. Inhibition of MAGL constitutes an attractive therapeutic concept for treating psychiatric disorders and neurodegenerative diseases. Herein, we present the design and synthesis of multiple reversible MAGL inhibitor candidates based on a piperazinyl azetidine scaffold. Compounds 10 and 15 were identified as the best-performing reversible MAGL inhibitors by pharmacological evaluations, thus channeling their radiolabeling with fluorine-18 in high radiochemical yields and favorable molar activity. Furthermore, evaluation of [(18)F]10 and [(18)F]15 ([(18)F]MAGL-2102) by autoradiography and positron emission tomography (PET) imaging in rodents and nonhuman primates demonstrated favorable brain uptakes, heterogeneous radioactivity distribution, good specific binding, and adequate brain kinetics, and [(18)F]15 demonstrated a better performance. In conclusion, [(18)F]15 was found to be a suitable PET radioligand for the visualization of MAGL, harboring potential for the successful translation into humans.
ESTHER : Rong_2021_J.Med.Chem__
PubMedSearch : Rong_2021_J.Med.Chem__
PubMedID: 34569803
Gene_locus related to this paper: human-MGLL

Title : Ensemble machine learning to evaluate the in vivo acute oral toxicity and in vitro human acetylcholinesterase inhibitory activity of organophosphates - Wang_2021_Arch.Toxicol__
Author(s) : Wang L , Ding J , Shi P , Fu L , Pan L , Tian J , Cao D , Jiang H , Ding X
Ref : Archives of Toxicology , : , 2021
Abstract : Organophosphates (OPs) are hazardous chemicals widely used in industry and agriculture. Distribution of their residues in nature causes serious risks to humans, animals, and plants. To reduce hazards from OPs, quantitative structure-activity relationship (QSAR) models for predicting their acute oral toxicity in rats and mice and inhibition constants concerning human acetylcholinesterase were developed according to the bioactivity data of 456 unique OPs. Based on robust, two-dimensional molecular descriptors and quantum chemical descriptors, which accurately reflect OP electronic structures and reactivities, the influences of eight machine-learning algorithms on the prediction performance of the QSAR models were explored, and consensus QSAR models were constructed. Several strict model validation indices and the results of applicability domain evaluations show that the established consensus QSAR models exhibit good robustness, practical prediction abilities, and wide application scopes. Poor correlation was observed between acute oral toxicity at the mammalian level and the inhibition constants at the molecular level, indicating that the acute toxicity of OPs cannot be evaluated only by the experimental data of enzyme inhibitory activity, their toxicokinetic characteristics must also be considered. The constructed QSAR models described herein provide rapid, theoretical assessment of the bioactivity of unstudied or unknown OPs, as well as guidance for making decisions regarding their regulation.
ESTHER : Wang_2021_Arch.Toxicol__
PubMedSearch : Wang_2021_Arch.Toxicol__
PubMedID: 33934188

Title : CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum - Freed_2021_Am.J.Med.Genet.A_185_827
Author(s) : Freed AS , Schwarz AC , Brei BK , Clowes Candadai SV , Thies J , Mah JK , Chabra S , Wang L , Innes AM , Bennett JT
Ref : American Journal of Medicine Genet A , 185 :827 , 2021
Abstract : CHRNB1 encodes the beta subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2weeks of life. Furthermore, we note that CHRNB1 variants may be under-recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing.
ESTHER : Freed_2021_Am.J.Med.Genet.A_185_827
PubMedSearch : Freed_2021_Am.J.Med.Genet.A_185_827
PubMedID: 33296147

Title : Supplemental Choline Modulates Growth Performance and Gut Inflammation by Altering the Gut Microbiota and Lipid Metabolism in Weaned Piglets - Qiu_2021_J.Nutr_151_20
Author(s) : Qiu Y , Liu S , Hou L , Li K , Wang L , Gao K , Yang X , Jiang Z
Ref : J Nutr , 151 :20 , 2021
Abstract : BACKGROUND: Whether dietary choline and bile acids affect lipid use via gut microbiota is unclear. OBJECTIVES: This study aimed to investigate the effect of choline and bile acids on growth performance, lipid use, intestinal immunology, gut microbiota, and bacterial metabolites in weaned piglets. METHODS: A total of 128 weaned piglets [Duroc x (Landrace x Yorkshire), 21-d-old, 8.21 +/- 0.20 kg body weight (BW)] were randomly allocated to 4 treatments (8 replicate pens per treatment, each pen containing 2 males and 2 females; n = 32 per treatment) for 28 d. Piglets were fed a control diet (CON) or the CON diet supplemented with 597 mg choline/kg (C), 500 mg bile acids/kg (BA) or both (C + BA) in a 2 x 2 factorial design. Growth performance, intestinal function, gut microbiota, and metabolites were determined. RESULTS: Compared with diets without choline, choline supplementation increased BW gain (6.13%), average daily gain (9.45%), gain per feed (8.18%), jejunal lipase activity (60.2%), and duodenal IL10 gene expression (51%), and decreased the mRNA abundance of duodenal TNFA (TNFalpha) (40.7%) and jejunal toll-like receptor 4 (32.9%) (P < 0.05); additionally, choline increased colonic butyrate (29.1%) and the abundance of Lactobacillus (42.3%), while decreasing the bile acid profile (55.8% to 57.6%) and the abundance of Parabacteroides (75.8%), Bacteroides (80.7%), and unidentified-Ruminococcaceae (32.5%) (P >= 0.05). Compared with diets without BA, BA supplementation decreased the mRNA abundance of colonic TNFA (37.4%), NF-kappaB p65 (42.4%), and myeloid differentiation factor 88 (42.5%) (P >= 0.01); BA also increased colonic butyrate (20.9%) and the abundance of Lactobacillus (39.7%) and Faecalibacterium (71.6%) and decreased that of Parabacteroides (67.7%) (P < 0.05). CONCLUSIONS: Choline supplementation improved growth performance and prevented gut inflammation in weaned piglets by altering gut microbiota and lipid metabolism. BA supplementation suppressed intestinal inflammation with no effect on growth performance, which was associated with changed gut microbiota and metabolites.
ESTHER : Qiu_2021_J.Nutr_151_20
PubMedSearch : Qiu_2021_J.Nutr_151_20
PubMedID: 33245135

Title : First-in-Human, Single-Ascending Dose and Food Effect Studies to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Cetagliptin, a Dipeptidyl Peptidase-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus - Wang_2021_Clin.Drug.Investig_41_999
Author(s) : Wang L , Lu J , Zhou S , Zhao Y , Xie L , Zhou C , Chen J , Ding S , Xie D , Ding J , Yu Q , Shen H , Hao G , Shao F
Ref : Clin Drug Investig , 41 :999 , 2021
Abstract : BACKGROUND AND OBJECTIVES: Cetagliptin is a highly selective dipeptidyl peptidase-4 inhibitor under development to treat type 2 diabetes mellitus. This first-in-human study was conducted to characterise the pharmacokinetics, pharmacodynamics and tolerability of single-ascending oral doses of cetagliptin in healthy subjects. In addition, the effect of food on pharmacokinetics was evaluated. METHODS: Study 1 enrolled 66 healthy subjects in a double-blind, randomised, placebo-controlled, single-dose escalation study; sitagliptin was employed as a positive open-label control. Forty-four subjects were assigned to seven cohorts (cetagliptin 12.5, 25, 50, 100, 200, 300 or 400 mg); 12 subjects were assigned to the placebo group. The remaining ten subjects received sitagliptin 100 mg as the positive control. Blood, urine and faeces were collected for the pharmacokinetic analysis and determination of plasma dipeptidyl peptidase-4 inhibition, active glucagon-like peptide-1, glucose and insulin levels. In Study 2, 14 healthy subjects were assigned to a randomised, open-label, two-period crossover study, and received a single oral dose of cetagliptin 100 mg in the fasted state or after a high-fat meal, with a 14-day washout period between treatments. Blood samples were collected to evaluate the effects of food on the pharmacokinetics of cetagliptin. RESULTS: Following administration of a single oral dose, cetagliptin was rapidly absorbed, presenting a median time to maximum concentration of 1.0-3.25 h. The terminal half-life ranged between 25.8 and 41.3 h, which was considerably longer than that of sitagliptin. The area under the plasma concentration-time curve was approximately dose proportional between 25 mg and 400 mg, and the increase in maximum concentration was greater than dose proportional. The unchanged drug was mainly excreted in the urine (27.2-46.2% of dose) and minimally via the faeces (1.4% of dose). Dipeptidyl peptidase-4 inhibition, an increase in active glucagon-like peptide-1 and a slight decrease in blood glucose were observed, whereas insulin was not significantly altered when compared with placebo. The weighted average dipeptidyl peptidase-4 inhibition by cetagliptin 100 mg was higher than that mediated by sitagliptin 100 mg. Cetagliptin was well tolerated up to a single oral dose of 400 mg. No food effects were noted. CONCLUSIONS: Cetagliptin inhibited plasma dipeptidyl peptidase-4 activity, increased levels of active glucagon-like peptide-1 and was well tolerated at single doses up to 400 mg, eliciting no dose-limiting toxicity in healthy volunteers. Food did not affect the pharmacokinetics of cetagliptin. CLINICAL TRIAL REGISTRATION: The studies were registered at http://www.chinadrugtrials.org.cn (Nos. CTR20180167 and CTR20181331).
ESTHER : Wang_2021_Clin.Drug.Investig_41_999
PubMedSearch : Wang_2021_Clin.Drug.Investig_41_999
PubMedID: 34655432

Title : Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder - Zou_2021_Open.Biol_11_200306
Author(s) : Zou M , Liu Y , Xie S , Wang L , Li D , Li L , Wang F , Zhang Y , Xia W , Sun C , Wu L
Ref : Open Biol , 11 :200306 , 2021
Abstract : Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg(-1), which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.
ESTHER : Zou_2021_Open.Biol_11_200306
PubMedSearch : Zou_2021_Open.Biol_11_200306
PubMedID: 33529552

Title : Lysosome Function and Dysfunction in Hereditary Spastic Paraplegias - Edmison_2021_Brain.Sci_11_
Author(s) : Edmison D , Wang L , Gowrishankar S
Ref : Brain Sci , 11 : , 2021
Abstract : Hereditary Spastic Paraplegias (HSPs) are a genetically diverse group of inherited neurological diseases with over 80 associated gene loci. Over the last decade, research into mechanisms underlying HSPs has led to an emerging interest in lysosome dysfunction. In this review, we highlight the different classes of HSPs that have been linked to lysosome defects: (1) a subset of complex HSPs where mutations in lysosomal genes are causally linked to the diseases, (2) other complex HSPs where mutation in genes encoding membrane trafficking adaptors lead to lysosomal defects, and (3) a subset of HSPs where mutations affect genes encoding proteins whose function is primarily linked to a different cellular component or organelle such as microtubule severing and Endoplasmic Reticulum-shaping, while also altering to lysosomes. Interestingly, aberrant axonal lysosomes, associated with the latter two subsets of HSPs, are a key feature observed in other neurodegenerative diseases such as Alzheimer's disease. We discuss how altered lysosome function and trafficking may be a critical contributor to HSP pathology and highlight the need for examining these features in the cortico-spinal motor neurons of HSP mutant models.
ESTHER : Edmison_2021_Brain.Sci_11_
PubMedSearch : Edmison_2021_Brain.Sci_11_
PubMedID: 33498913

Title : Molecular Detection of Insecticide Resistance Mutations in Anopheles gambiae from Sierra Leone Using Multiplex SNaPshot and Sequencing - Yin_2021_Front.Cell.Infect.Microbiol_11_666469
Author(s) : Yin J , Yamba F , Zheng C , Zhou S , Smith SJ , Wang L , Li H , Xia Z , Xiao N
Ref : Front Cell Infect Microbiol , 11 :666469 , 2021
Abstract : Vector control interventions including long-lasting insecticidal nets and indoor residual spraying are important for malaria control and elimination. And effectiveness of these interventions depends entirely on the high level of susceptibility of malaria vectors to insecticides. However, the insecticide resistance in majority of mosquito vector species across African countries is a serious threat to the success of vector control efforts with the extensive use of insecticides, while no data on insecticide resistance was reported from Sierra Leone in the past decade. In the present study, the polymerase chain reaction was applied for the identification of species of 757 dry adult female Anopheles gambiae mosquitoes reared from larvae collected from four districts in Sierra Leone during May and June 2018. And the mutations of kdr, rdl, ace-1 genes in An. gambiae were detected using SNaPshot and sequencing. As a result, one sample from Western Area Rural district belonged to Anopheles melas, and 748 An. gambiae were identified. Furthermore, the rdl mutations, kdr west mutations and ace-1 mutation were found. The overall frequency was 35.7%, 0.3%, 97.6% and 4.5% in A296G rdl, A296S rdl, kdrW and ace-1, respectively. The frequencies of A296G rdl mutation (P < 0.001), kdrW mutation (P = 0.001) and ace-1 mutation (P < 0.001) were unevenly distributed in four districts, respectively, while no statistical significance was found in A296S rdl mutation (P = 0.868). In addition, multiple resistance patterns were also found. In conclusion, multiple mutations involved in insecticide resistance in An. gambiae populations in Sierra Leone were detected in the kdrW, A296G rdl and ace-1 alleles in the present study. It is necessary to monitor vector susceptibility levels to insecticides used in this country, and update the insecticide resistance monitoring and management strategy.
ESTHER : Yin_2021_Front.Cell.Infect.Microbiol_11_666469
PubMedSearch : Yin_2021_Front.Cell.Infect.Microbiol_11_666469
PubMedID: 34490134

Title : Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis - Wang_2021_Front.Immunol_12_753247
Author(s) : Wang S , Yang H , Guo R , Wang L , Zhang Y , Lv J , Zhao X , Zhang J , Fang H , Zhang Q , Yang J , Cui X , Gao P , Chang T , Gao F
Ref : Front Immunol , 12 :753247 , 2021
Abstract : This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.
ESTHER : Wang_2021_Front.Immunol_12_753247
PubMedSearch : Wang_2021_Front.Immunol_12_753247
PubMedID: 34956185

Title : The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence - Zhang_2021_Front.Pharmacol_12_731453
Author(s) : Zhang T , Tong X , Zhang S , Wang D , Wang L , Wang Q , Fan H
Ref : Front Pharmacol , 12 :731453 , 2021
Abstract : CD26/Dipeptidyl peptidase 4 (DPP4) is a type II transmembrane glycoprotein that is widely expressed in various organs and cells. It can also exist in body fluids in a soluble form. DPP4 participates in various physiological and pathological processes by regulating energy metabolism, inflammation, and immune function. DPP4 inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus. More evidence has shown the role of DPP4 in the pathogenesis of lung diseases, since it is highly expressed in the lung parenchyma and the surface of the epithelium, vascular endothelium, and fibroblasts of human bronchi. It is a potential biomarker and therapeutic target for various lung diseases. During the coronavirus disease-19 (COVID-19) global pandemic, DPP4 was found to be an important marker that may play a significant role in disease progression. Some clinical trials on DPP4 inhibitors in COVID-19 are ongoing. DPP4 also affects other infectious respiratory diseases such as Middle East respiratory syndrome and non-infectious lung diseases such as pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and asthma. This review aims to summarize the roles of DPP4 and its inhibitors in infectious lung diseases and non-infectious diseases to provide new insights for clinical physicians.
ESTHER : Zhang_2021_Front.Pharmacol_12_731453
PubMedSearch : Zhang_2021_Front.Pharmacol_12_731453
PubMedID: 34955820

Title : Data for the lipase catalyzed synthesis of cyano-containing multi-substituted indoles - Li_2021_Data.Brief_36_107045
Author(s) : Li F , Xu Y , Wang C , Zhao R , Wang L
Ref : Data Brief , 36 :107045 , 2021
Abstract : The data presented here are related to the research paper entitled "Efficient Synthesis of Cyano-containing Multi-substituted Indoles Catalyzed by Lipase" [1]. In this data article, the lipase catalyzed synthetic procedures for the preparation of multi-substituted indoles and their derivatives were described. In total, 11 compounds were obtained and the optimum pH, reaction time and substrate ratio were screened through this study.
ESTHER : Li_2021_Data.Brief_36_107045
PubMedSearch : Li_2021_Data.Brief_36_107045
PubMedID: 33997196

Title : An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility - Wang_2021_Genome.Med_13_83
Author(s) : Wang L , Balmat TJ , Antonia AL , Constantine FJ , Henao R , Burke TW , Ingham A , McClain MT , Tsalik EL , Ko ER , Ginsburg GS , DeLong MR , Shen X , Woods CW , Hauser ER , Ko DC
Ref : Genome Med , 13 :83 , 2021
Abstract : BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. RESULTS: Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity. CONCLUSIONS: Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .
ESTHER : Wang_2021_Genome.Med_13_83
PubMedSearch : Wang_2021_Genome.Med_13_83
PubMedID: 34001247

Title : Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1 - Zhou_2021_Clin.Transl.Med_11_e449
Author(s) : Zhou L , Zhang C , Yang X , Liu L , Hu J , Hou Y , Tao H , Sugimura H , Chen Z , Wang L , Chen K
Ref : Clin Transl Med , 11 :e449 , 2021
Abstract : BACKGROUND: Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration-resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. METHODS: We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. RESULTS: We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta-analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1-knockout (Ces(-/-) ) mice verified the important role of endogenous Ces1 in PCa. CONCLUSIONS: Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa.
ESTHER : Zhou_2021_Clin.Transl.Med_11_e449
PubMedSearch : Zhou_2021_Clin.Transl.Med_11_e449
PubMedID: 34185414
Gene_locus related to this paper: human-CES1

Title : Secoyanhusamine A, an Oxidatively Ring-Opened Isoquinoline Inner Salt From Corydalis yanhusuo - Wang_2021_Front.Chem_9_831173
Author(s) : Wang L , Xia H , Wu Y , Wang Y , Lin P , Lin S
Ref : Front Chem , 9 :831173 , 2021
Abstract : Secoyanhusamine A (1), a rare rearranged seco-isoquinoline alkaloid derived from ring oxidative cleavage, was isolated from an aqueous extract of Corydalis yanhusuo tubers, together with its biosynthetic precursor dehydrocorybulbine (2). Secoyanhusamine A (1) was the first example of a highly oxidized isoquinoline inner salt resulting in a 5-(2-azanylethyl)-2-carboxylate-4-oxo-4H-pyran ring system. The biosynthetic pathway of 1 was also postulated. Secoyanhusamine A (1) exhibited potent inhibition against acetylcholinesterase (AChE) with an IC(50) value of 0.81 +/- 0.13 microM. Molecular simulation docking demonstrated that 1 created a strong interaction with the Asp-74 residue of AChE via attractive charge of the quaternary nitrogen.
ESTHER : Wang_2021_Front.Chem_9_831173
PubMedSearch : Wang_2021_Front.Chem_9_831173
PubMedID: 35178381

Title : Identification and Antioxidant Abilities of Enzymatic-Transesterification (-)-Epigallocatechin-3-O-gallate Stearyl Derivatives in Non-Aqueous Systems - Jiang_2021_Antioxidants.(Basel)_10_
Author(s) : Jiang C , Wang L , Huang X , Zhu S , Ma C , Wang H
Ref : Antioxidants (Basel) , 10 : , 2021
Abstract : Vinyl stearate was added to enzymatic transesterification of (-)-Epigallocatechin-3-O-gallate (EGCG) to enhance its lipophilicity and antioxidant ability in a non-aqueous system. The lipase DF "Amano" 15 was used as the catalyst. The optimal reaction conditions were: acetonitrile as the solvent, the molar ratio of vinyl stearate: EGCG as 3:1, an enzyme amount of 4.0% (ratio of substrate mass), and a reaction temperature and time of 50 degreesC and 96 h, respectively, achieving 65.2% EGCG conversion. HPLC-MS and NMR were used to determine the structure of EGCG stearyl derivative (3'',5''-2-O-stearyl-EGCG). The lipophilicity of EGCG stearyl derivatives (3.49 +/- 0.34) was higher (5.06 times) than that of the parent EGCG (0.69 +/- 0.08). Furthermore, EGCG stearyl derivatives had excellent lipid oxidation compared with BHT, BHA, and parent EGCG. The POVs of soybean oil with EGCG stearyl derivatives (18.17 +/- 0.92 mEq/kg) were significantly reduced (by 62.5%) at 21 d compared with those of EGCG (48.50 +/- 1.23 mEq/kg). These results indicate that EGCG derivatives have broad antioxidant application prospects in lipophilic environments/high-fat food.
ESTHER : Jiang_2021_Antioxidants.(Basel)_10_
PubMedSearch : Jiang_2021_Antioxidants.(Basel)_10_
PubMedID: 34439530

Title : Two new organic acids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities - Liu_2021_Nat.Prod.Res__1
Author(s) : Liu P , Wang L , Li H , Tan L , Ying X , Ju B
Ref : Nat Prod Res , :1 , 2021
Abstract : Two new organic acids, identified as (7E,9E,12E)-pentadecyl-7,9,12-trienoic acid, named Oleraceacid A (1), and 6,7-dihydroxy-4-(4-hydroxy-3,5-dimethoxyphenyl)-2-naphthoic acid, named Oleraceacid B (2), were isolated from Portulaca oleracea L.. The structures were verified by spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1 D and 2 D NMR. Both Oleraceacid A (1) and Oleraceacid B (2) at 20 microM inhibited the inflammatory factor, IL-1beta in the RAW 264.7 cells induced by LPS, moreover, Oleraceacid A (1) can inhibit cholinesterase activity.
ESTHER : Liu_2021_Nat.Prod.Res__1
PubMedSearch : Liu_2021_Nat.Prod.Res__1
PubMedID: 34749551

Title : A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase - Gao_2021_Nat.Microbiol__
Author(s) : Gao H , Bai L , Jiang Y , Huang W , Wang L , Li S , Zhu G , Wang D , Huang Z , Li X , Cao J , Jiang L , Jacobs-Lorena M , Zhan S , Wang S
Ref : Nat Microbiol , : , 2021
Abstract : The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.
ESTHER : Gao_2021_Nat.Microbiol__
PubMedSearch : Gao_2021_Nat.Microbiol__
PubMedID: 33958765

Title : Structural characterization and antioxidant property of enzymatic-transesterification derivatives of (-)-epigallocatechin-3-O-gallate and vinyl laurate - Jiang_2021_J.Food.Sci__
Author(s) : Jiang C , Wang L , Huang X , Zhu S , Ma C , Wang H
Ref : J Food Sci , : , 2021
Abstract : (-)-Epigallocatechin-3-O-gallate(EGCG) was enzymatically modified to enhance the lipophilicity and the antioxidant property. The determination of optimal reaction conditions are as follows: Lipase DF "Amano" 15 and acetone were used as catalyst and solvent, respectively. Equal molar of EGCG and vinyl laurate (1:1); lipase addition of 6.0% (w/w of total substrates); reaction temperature of 50 degreesC and reaction time of 96 h, which obtained the conversion rate of EGCG at 80.1%. The structure of EGCG lauroyl derivatives were 5''-O-lauroyl-EGCG, 3'',5''-2-O-lauroyl-EGCG, and 5',3'',5''-3-O-lauroyl-EGCG, identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR). Compared with the logP of precursor EGCG (0.69 +/- 0.03), the logP of EGCG lauroyl derivatives was 1.37 +/- 0.19, 2.27 +/- 0.33, and 3.28 +/- 0.37, increasing by 0.98, 2.28, and 3.75 times, respectively (p < 0.05), suggesting the grafted fatty acid chains make EGCG derivatives more lipophilic, and the lipid solubility gradually increased as the number of substituents increased. Furthermore, EGCG lauroyl derivatives had excellent lipid oxidation than that of EGCG. The POVs (peroxide values) of soybean oil with mono-, di-, tri-lauroyl EGCG were significantly reduced by 42%, 47%, and 57% than that of EGCG at 21 days, respectively, indicating the antioxidative inhibition of these derivatives decreased with the increase in substituents. This indicates that these derivatives have broad prospects of the antioxidant application while improving their solubility properties in lipophilic environments/high-fat food. Practical Application: The lipophilic esterification reaction of EGCG catalyzed by new catalytic lipase DF "Amano" 15 was carried out in a non-aqueous solvent.Various reaction factors on a higher conversion rate of EGCG lauroyl derivatives were evaluated. The lipophilicity and antioxidant properties of EGCG lauroyl derivatives were much excellent than that of parent EGCG.
ESTHER : Jiang_2021_J.Food.Sci__
PubMedSearch : Jiang_2021_J.Food.Sci__
PubMedID: 34553787

Title : DECR1 directly activates HSL to promote lipolysis in cervical cancer cells - Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
Author(s) : Zhou H , Zhang J , Yan Z , Qu M , Zhang G , Han J , Wang F , Sun K , Wang L , Yang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159090 , 2021
Abstract : Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth.
ESTHER : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedSearch : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedID: 34896618

Title : A novel biosensor based on multienzyme microcapsules constructed from covalent-organic framework - Liang_2021_Biosens.Bioelectron_193_113553
Author(s) : Liang H , Wang L , Yang Y , Song Y
Ref : Biosensors & Bioelectronics , 193 :113553 , 2021
Abstract : Electrochemical biosensors based on enzymes modified electrode are attracting special attention due to their broad applications. However, the immobilization of enzymes on electrode is always an important challenge because it's not conducive to conformational expansion of enzymes and affects the bioactivity of enzymes accordingly. Although the imobilization of enzymes in micropores of crystalline covalent-organic framework (COF) and metal-organic framework (MOF) to construct electrochemical biosensors based on pore embedding can achive good reuslts, their micropores can still not guarantee that the enzyme's conformation is well extended. Herein, a multienzyme microcapsules (enzymes@COF) containing glucose oxidase, horseradish peroxidase and acetylcholinesterase with a 600 nm-sized cavity and a shell of COF was used to construct electrochemical biosensors. The 600 nm-sized cavity ensures free conformation expansion of encapsulated enzymes and the shell of COF with good chemical stablity protects encapsulated enzymes against external harsh environments. And the specific catalytic substrates of the enzymes can infiltrated into the microcapsule through the pores of COF shell. So, the biosensor based on enzymes@COF microcapsules demonstrated preeminent performances as compared with those of enzymes assembled on electrode. The detection limits were 0.85 microM, 2.81 nM, 3.0x10(-13) g/L, and the detection range were 2.83 microM-8.0 mM, 9.53 nM-7.0 microM, 10(-12) g/L-10(-8) g/L for glucose, H2O2 and malathion detection. This work shows that it is feasible to fabricate electrochemical sensors using enzymes@COF microcapsules.
ESTHER : Liang_2021_Biosens.Bioelectron_193_113553
PubMedSearch : Liang_2021_Biosens.Bioelectron_193_113553
PubMedID: 34385018

Title : In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease - Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
Author(s) : Song X , Wang T , Guo L , Jin Y , Wang J , Yin G , Jiang K , Wang L , Huang H , Zeng L
Ref : Evid Based Complement Alternat Med , 2020 :2804849 , 2020
Abstract : Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.
ESTHER : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedSearch : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedID: 32148536

Title : [Predictive value of early detection of hs-cTnI and sST2 for secondary cardiac damage in severe acute organophosphorus pesticide poisoning] - Liu_2020_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_38_241
Author(s) : Liu XT , Wang L , Chen J , Qi HN , Ma GY
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 38 :241 , 2020
Abstract : Objective: To investigate the value of high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity 2 (sST2) in predicting cardiac complications of severe acute organophosphorus pesticide poisoning (SAOPP) . Methods: All 274 SAOPP patients from September 2014 to February 2019 were selected. According to the results of hs-cTnI detection, the patients were divided into non-elevated troponin group (78 cases) and troponin elevation group (196 cases) at 1 hour after admission. 3 days after admission, there were 109 cases of complication and 165 cases of non-complication according to the presence or absence of cardiac complications. The changes of hs-cTnI, sST2, N-terminal B-type brain natriuretic peptide (NT proBNP) , acute physiology and chronic health (APACHE-) , cholinesterase activity, left ventricular ejection fraction (LVEF) , short axis shortening rate (FS) were observed and analyzed. The predictive value of hs-cTnI and sST2 were evaluated by receiver operating characteristic curve (ROC) analysis. Results: The sST2 level in patients with troponin elevation group was significantly higher than that in non-elevated troponin group (P<0.05) . Compared with the non-complication and non-elevated troponin group, the patients with non-complication and troponin elevation group had elevated hs-cTnI, sST2 and decreased cholinesterase (P<0.05) . Compared with other groups, the hs-cTnI, sST2, NT-proBNP, and APACHE- scores in the complication and troponin elevation group were significantly increased, and cholinesterase was significantly reduced (P<0.05) . In the non-complication group, LVEF and FS were in the normal range, and there was no significant difference between the groups (P>0.05) . Compared with other groups, the LVEF and FS of patients with elevated troponin in the complications group were significantly decreased (P<0.05) . Correlation analysis showed that hs-cTnI and sST2 were positively correlated in patients with SAOPP complications (r=0.725, P<0.01) . hs-cTnI, sST2 and APACHE- scores were positively correlated in the complications group (r=0.846, 0.885, P<0.01) . ROC results showed that the areas under the curve for predicting SAOPP secondary heart damage of hs-cTnI (1 hour after admission) and sST2 (3 days after admission) were 0.945 and 0.833, respectively. Conclusion: hs-cTnI and sST2 may have important clinical value in the early diagnosis and prognosis evaluation of patients with SAOPP secondary cardiac damage.
ESTHER : Liu_2020_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_38_241
PubMedSearch : Liu_2020_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_38_241
PubMedID: 32447883

Title : Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study - Li_2020_Aging.Clin.Exp.Res__
Author(s) : Li M , Chen Y , Zhang Y , Liu X , Xie T , Yin J , Wang L , Gang S , Chen J , Liu L , Yang F , Geng T
Ref : Aging Clin Exp Res , : , 2020
Abstract : BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (>/= 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged >/= 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged >/= 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS.
ESTHER : Li_2020_Aging.Clin.Exp.Res__
PubMedSearch : Li_2020_Aging.Clin.Exp.Res__
PubMedID: 32067216

Title : Pentacyclic triterpenoid acids in Styrax as potent and highly specific inhibitors against human carboxylesterase 1A - Wang_2020_Food.Funct_11_8680
Author(s) : Wang L , Guan XQ , He RJ , Qin WW , Xiong Y , Zhang F , Song YQ , Huo PC , Song PF , Tang H , Ge GB
Ref : Food Funct , 11 :8680 , 2020
Abstract : Human carboxylesterase 1A1 (hCES1A) is a promising target for the treatment of hyperlipidemia and obesity-associated metabolic diseases. To date, the highly specific and efficacious hCES1A inhibitors are rarely reported. This study aims to find potent and highly specific hCES1A inhibitors from herbs, and to investigate their inhibitory mechanisms. Following large-scale screening of herbal products, Styrax was found to have the most potent hCES1A inhibition activity. After that, a practical bioactivity-guided fractionation coupling with a chemical profiling strategy was used to identify the fractions from Styrax with strong hCES1A inhibition activity and the major constituents in these bioactive fractions were characterized by LC-TOF-MS/MS. The results demonstrated that seven pentacyclic triterpenoid acids (PTAs) in two bioactive fractions from Styrax potently inhibit hCES1A, with IC50 values ranging from 41 nM to 478 nM. Among all the identified PTAs, epibetulinic acid showed the most potent inhibition activity and excellent specificity towards hCES1A. Both inhibition kinetic analyses and in silico analysis suggested that epibetulinic acid potently inhibited hCES1A in a mixed inhibition manner. Collectively, our findings demonstrate that some PTAs in Styrax are potent and highly specific inhibitors of hCES1A and these constituents can be used as promising lead compounds for the development of more efficacious hCES1A inhibitors.
ESTHER : Wang_2020_Food.Funct_11_8680
PubMedSearch : Wang_2020_Food.Funct_11_8680
PubMedID: 32940318

Title : Detoxification enzymes associated with butene-fipronil resistance in Epacromius coerulipes - Jin_2020_Pest.Manag.Sci_76_227
Author(s) : Jin Y , Gao Y , Zhang H , Wang L , Yang K , Dong H
Ref : Pest Manag Sci , 76 :227 , 2020
Abstract : BACKGROUND: Epacromius coerulipes is a widely distributed locust pest species. Chemical control is the main method used to kill locusts; however, this can result in the selection of locusts with resistance to chemical pesticides. Therefore, the study of resistance is of great significance for the sustainable management of locusts. RESULTS: In this study, to investigate the relationship between detoxification enzymes and butene-fipronil resistance in E. coerulipes, resistant strains of the locust were compared with sensitive strains. The synergism of synergistic agents was significantly enhanced, and the activities of multifunctional oxidase, carboxylesterase, and glutathione sulfur transferase were significantly increased. Transcriptome sequencing revealed 226 detoxification enzyme genes and 23 upregulated genes. Neighbor-joining was used to construct a phylogenetic tree of related gene families, which included 59 P450 genes, 52 carboxylesterases (CarE) genes, and 25 glutathione S-transferase (GST) genes. Reverse transcription polymerase chain reaction (RT-PCR) analysis results of overexpressed genes in the resistant population combined with a phylogenetic tree showed that four P450 genes belonged to the CYP6, CYP4, CYP18 and CYP302 families, two CarE genes belonged to Clade A families, and one GST gene belonged to the Sigma family. These family members were annotated as detoxification enzyme genes of metabolic insecticide in the transcriptome databases. CONCLUSIONS: This study showed that P450, CarE and GST together resulted in moderate resistance to butene-fipronil in locusts. The analysis revealed several overexpressed detoxification enzyme genes that will be the focus of future studies on the mechanism of resistance to butene-fipronil. (c) 2019 Society of Chemical Industry.
ESTHER : Jin_2020_Pest.Manag.Sci_76_227
PubMedSearch : Jin_2020_Pest.Manag.Sci_76_227
PubMedID: 31150148

Title : Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression - Liang_2020_J.Exp.Clin.Cancer.Res_39_176
Author(s) : Liang M , Chen X , Wang L , Qin L , Wang H , Sun Z , Zhao W , Geng B
Ref : J Exp Clin Cancer Research , 39 :176 , 2020
Abstract : BACKGROUND: Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. METHODS: Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. RESULTS: We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1beta. CONCLUSIONS: Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1beta secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.
ESTHER : Liang_2020_J.Exp.Clin.Cancer.Res_39_176
PubMedSearch : Liang_2020_J.Exp.Clin.Cancer.Res_39_176
PubMedID: 32867817
Gene_locus related to this paper: human-ABHD5

Title : Efficient synthesis of cyano-containing multi-substituted indoles catalyzed by lipase - Li_2020_Bioorg.Chem_107_104583
Author(s) : Li F , Xu Y , Wang C , Zhao R , Wang L
Ref : Bioorg Chem , 107 :104583 , 2020
Abstract : BACKGROUND: Indoles are important bioactive compounds that have been extensively studied in organic chemistry. In this work, a green and efficient process for the synthesis of Indoles from 1,3-diketones with fumaronitrile was developed. RESULTS: Under optimal conditions (1,3-diketones (0.5 mmol), fumaronitrile (1 mmol), water (2 ml), lipase (15 mg), 30 degreesC, 24 h), high yields and satisfactory regioselectivity of cyano-containing multi-substituted indoles could be obtained when CRL (C. rugosa lipase) was used as the catalyst. CONCLUSION: This enzymatic method demonstrates the great potential for the synthesis of indoles and extends the application of enzyme in organic synthesis.
ESTHER : Li_2020_Bioorg.Chem_107_104583
PubMedSearch : Li_2020_Bioorg.Chem_107_104583
PubMedID: 33421956

Title : A Dual-Protein Cascade Reaction for the Regioselective Synthesis of Quinoxalines - Li_2020_Org.Lett__
Author(s) : Li F , Tang X , Xu Y , Wang C , Wang Z , Li Z , Wang L
Ref : Org Lett , : , 2020
Abstract : In this work, an efficient dual-protein (lipase and hemoglobin) system was successfully constructed for the regioselective synthesis of quinoxalines in water. A set of quinoxalines were obtained in high yields under optimal reaction conditions. This dual-protein method exhibited a regioselectivity higher than those of previously reported methods. This study not only provides a green and mild strategy for the synthesis of quinoxalines but also expands the application of lipase and hemoglobin in organic synthesis.
ESTHER : Li_2020_Org.Lett__
PubMedSearch : Li_2020_Org.Lett__
PubMedID: 32337998

Title : Mechanisms of Increased Indoxacarb Toxicity in Methoxyfenozide-Resistant Cotton Bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) - Wang_2020_Toxics_8_
Author(s) : Wang Q , Rui C , Wang L , Li F , Nahiyoon SA , Yuan H , Cui L
Ref : Toxics , 8 : , 2020
Abstract : Indoxacarb is an important insecticide for the selective control of Helicoverpa armigera. It can be bioactivated to the more effective N-decarbomethoxylated indoxacarb (DCJW) by esterases in pests. It was observed that both field and laboratory selected populations of H. armigera showed negative cross-resistance between indoxacarb and methoxyfenozide. The Handan population exhibited moderate resistance to indoxacarb, but was susceptible to methoxyfenozide; the Baoding and Yishui populations exhibited moderate resistance to methoxyfenozide, but they were susceptible to indoxacarb. Moreover, the toxicity of indoxacarb was enhanced 1.83-fold in the laboratory methoxyfenozide-resistant H. armigera, and susceptibility to methoxyfenozide was increased 2.81-fold in the laboratory indoxacarb-resistant H. armigera. In vivo, DCJW concentrations in the susceptible and methoxyfenozide-selected (laboratory methoxyfenozide-resistant) populations were 4.59- and 4.31-fold greater than in the indoxacarb-resistant Handan population 1 h after dosing. After 2 h, the highest concentrations of DCJW and indoxacarb appeared in the methoxyfenozide-selected population. Meanwhile, increased carboxyl esterase (CarE) and decreased glutathione S-transferase (GST) activities were observed in the methoxyfenozide-selected population. However, the indoxacarb-selected (laboratory indoxacarb-resistant) and Handan populations showed a higher disappearance of indoxacarb and DCJW, and the activity of cytochrome P450 mono-oxygenase in these populations were significantly increased. This study showed that the improved toxicity of indoxacarb, as observed in the methoxyfenozide-selected H. armigera, was correlated with increased CarE activity, decreased GST activity, and the in vivo accumulation of indoxacarb and DCJW. The significantly increased cytochrome P450 activity and higher disappearance of indoxacarb and DCJW in indoxacarb-resistant H. armigera resulted in the decreased toxicity of indoxacarb.
ESTHER : Wang_2020_Toxics_8_
PubMedSearch : Wang_2020_Toxics_8_
PubMedID: 32957560

Title : Small molecule therapeutics for tauopathy in Alzheimer's disease: Walking on the path of most resistance - Wang_2020_Eur.J.Med.Chem__112915
Author(s) : Wang L , Bharti , Kumar R , Pavlov PF , Winblad B
Ref : Eur Journal of Medicinal Chemistry , :112915 , 2020
Abstract : Alzheimer's disease (AD) is the most common form of dementia characterized by presence of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of tau protein. Currently there are close to 50 million people living with dementia and this figure is expected to increase to 75 million by 2030 putting a huge burden on the economy due to the health care cost. Considering the effects on quality of life of patients and the increasing burden on the economy, there is an enormous need of new disease modifying therapies to tackle this disease. The current therapies are dominated by only symptomatic treatments including cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers but no disease modifying treatments exist so far. After several failed attempts to develop drugs against amyloidopathy, tau targeting approaches have been in the main focus of drug development against AD. After an overview of the tauopathy in AD, this review summarizes recent findings on the development of small molecules as therapeutics targeting tau modification, aggregation, and degradation, and tau-oriented multi-target directed ligands. Overall, this work aims to provide a comprehensive and critical overview of small molecules which are being explored as a lead candidate for discovering drugs against tauopathy in AD.
ESTHER : Wang_2020_Eur.J.Med.Chem__112915
PubMedSearch : Wang_2020_Eur.J.Med.Chem__112915
PubMedID: 33139110

Title : An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility - Wang_2020_Medrxiv__
Author(s) : Wang L , Balmat TJ , Antonia AL , Constantine FJ , Henao R , Burke TW , Ingham A , McClain MT , Tsalik EL , Ko ER , Ginsburg GS , DeLong MR , Shen X , Woods CW , Hauser ER , Ko DC
Ref : Medrxiv , : , 2020
Abstract : While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb); http://cpag.oit.duke.edu ) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs with severe COVID-19 demonstrated colocalization of the GWAS signal of the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN), pointing to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity. Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches.
ESTHER : Wang_2020_Medrxiv__
PubMedSearch : Wang_2020_Medrxiv__
PubMedID: 33398303

Title : Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1 - Yu_2020_Ecotoxicol.Environ.Saf_194_110378
Author(s) : Yu H , Wang L , Lin Y , Liu W , Tuyiringire D , Jiao Y , Zhang L , Meng Q , Zhang Y
Ref : Ecotoxicology & Environmental Safety , 194 :110378 , 2020
Abstract : The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics.
ESTHER : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedSearch : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedID: 32146194

Title : Lycosquarrines A-R, Lycopodium Alkaloids from Phlegmariurus squarrosus - Zhu_2020_J.Nat.Prod_83_2831
Author(s) : Zhu X , Xia D , Zhou Z , Xie S , Shi Z , Chen G , Wang L , Pan K
Ref : Journal of Natural Products , 83 :2831 , 2020
Abstract : Eighteen new Lycopodium alkaloids, lycosquarrines A-R (1-18), and eight known alkaloids were isolated from the aerial parts of Phlegmariurus squarrosus. Compounds 1-5 and 19, identified from natural sources for the first time, are uncommon lycopodine-type alkaloids with beta-oriented H-4. Pentacyclic 4 and 5 represent the first examples of 5,12- and 5,11-epoxy Lycopodium alkaloids, respectively, and an epoxide-opening cyclization reaction is suggested to be a key step in their biosynthesis. Compound 18 possesses the same carbon skeleton as carinatine A (22), which was previously reported as a unique Lycopodium alkaloid with a 5/6/6/6 ring system. X-ray crystallographic data analysis was used to determine the absolute configuration of 18, leading to the establishment of the absolute configuration of 22 by comparison of the ECD spectra. An anti-acetylcholinesterase activity assay showed that 11 and 20 exhibited inhibitory activities with IC(50) values of 4.2 and 2.1 microM, respectively.
ESTHER : Zhu_2020_J.Nat.Prod_83_2831
PubMedSearch : Zhu_2020_J.Nat.Prod_83_2831
PubMedID: 32941036

Title : Karrikin Signaling Acts Parallel to and Additively with Strigolactone Signaling to Regulate Rice Mesocotyl Elongation in Darkness - Zheng_2020_Plant.Cell_32_2780
Author(s) : Zheng J , Hong K , Zeng L , Wang L , Kang S , Qu M , Dai J , Zou L , Zhu L , Tang Z , Meng X , Wang B , Hu J , Zeng D , Zhao Y , Cui P , Wang Q , Qian Q , Wang Y , Li J , Xiong G
Ref : Plant Cell , 32 :2780 , 2020
Abstract : Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCF(D3) ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3 OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR24(5DS) and GR24 (ent-5DS) specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark.
ESTHER : Zheng_2020_Plant.Cell_32_2780
PubMedSearch : Zheng_2020_Plant.Cell_32_2780
PubMedID: 32665307

Title : Effects of nucleo(s)tide analogs therapy on chronic hepatitis B as evaluated by hepatosplenic radionuclide angiography - Wang_2020_Nucl.Med.Commun__
Author(s) : Wang L , Wu Z , Wang A , Jin X , Qiu Y
Ref : Nucl Med Commun , : , 2020
Abstract : OBJECTIVES: Hepatosplenic radionuclide angiography is a relatively noninvasive method for evaluating hepatic portal perfusion. We used hepatosplenic radionuclide angiography to assess the effects of nucleo(s)tide analogs therapy on patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent hepatosplenic radionuclide angiography from January 2012 to May 2017 at the First Affiliated Hospital, College of Medicine, Zhejiang University. The correlations between the results of routine laboratory tests and hepatic perfusion index (HPI) were evaluated. The Wilcoxon signed-rank test and one-way ANOVA of repeated measures were used to compare the HPIs of patients who received nucleo(s)tide analogs therapy. RESULTS: There is a positive correlation between HPI and cholinesterase and serum albumin (ALB) and a negative correlation between HPI and aspartate aminotransferase-to-platelet ratio index and bilirubin (TBiL). An improvement in HPI was observed in patients with an initial HPI <61% after nucleo(s)tide analogs therapy. CONCLUSIONS: Hepatosplenic radionuclide angiography can reflect the functional reserve of the liver and monitor liver fibrosis indirectly. It can also comprehensively assess the effects of antiviral therapy on patients with CHB, and antiviral therapy is critical for the treatment of hepatitis.
ESTHER : Wang_2020_Nucl.Med.Commun__
PubMedSearch : Wang_2020_Nucl.Med.Commun__
PubMedID: 31939901

Title : Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line - Sun_2020_Proteomics.Clin.Appl_14_e1900080
Author(s) : Sun R , Dong C , Li R , Chu H , Liu J , Hao D , Zhang L , Zhao B , Wang L , Zhang Y
Ref : Proteomics Clin Appl , 14 :e1900080 , 2020
Abstract : PURPOSE: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with HCC. EXPERIMENTAL DESIGN: In this study, proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent are performed. Then the expression level and function of differentially expressed plasma membrane proteins are verified. RESULTS: In total, 25 plasma membrane proteins are shown differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 are upregulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 is closely related to the chemoresistance of Bel/5Fu to 5-Fu. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with HCC.
ESTHER : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedSearch : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedID: 32067389
Gene_locus related to this paper: human-EPHX1

Title : Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation - Huang_2020_Int.J.Biol.Macromol_164_1927
Author(s) : Huang X , Zhu J , Wang L , Jing H , Ma C , Kou X , Wang H
Ref : Int J Biol Macromol , 164 :1927 , 2020
Abstract : This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC(50) value of 3.60 +/- 0.19 microM) was superior to those of three polymethoxylated flavones (PMFs), indicating it may be related to the methoxy groups at the 3'-position in its molecular structure. Inhibition kinetic analyses demonstrated that the inhibition types of the 4 PMFs were consistent with the mixed inhibition model, which agreed well with the results from the ultraviolet-visible (UV-Vis) spectroscopy, Circular dichroism (CD), fluorescence spectroscopy, molecular docking, and MD simulation that PMFs could bind to the PPL catalytic site and non-catalytic site, affecting the normal spatial conformation of PPL and weakening its ability to decompose the substrate. All these findings suggest that PMFs are a kind of natural lipase inhibitors, and NBT has the potential as a lipase inhibition precursor because of its unique flavone skeleton structure.
ESTHER : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedSearch : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedID: 32795575

Title : An enhanced staining method K-B-2R staining for three-dimensional nerve reconstruction - Luo_2019_BMC.Neurosci_20_32
Author(s) : Luo P , Dong J , Qi J , Zhang Y , Liu X , Zhong Y , Xian CJ , Wang L
Ref : BMC Neurosci , 20 :32 , 2019
Abstract : BACKGROUND: Three-dimensional (3D) reconstruction of human peripheral nerves, as a useful tool to understand the nerve internal information and functional basis, has become an important area of research in the peripheral nerve field. METHODS: In this study, we proposed a two-dimensional (2D) Karnovsky-Roots toluidine blue ponceau 2R (K-B-2R) staining method based upon conventional Karnovsky-Roots staining. It significantly improved the ability to display nerve fascicles, motor and sensory nerve fiber textures. In this method, Karnovsky-Roots staining was carried out, followed by toluidine blue counterstain and ponceau 2R counterstain. RESULTS: Comparisons were conducted between the three methods in staining of median nerve sections, which showed similar distribution characters in acetylcholinesterase-positive sites. The additional counterstaining did not change the basis of Karnovsky-Roots staining. However, the resulting images from this new method significantly facilitated the subsequent 3D nerve reconstruction and 3D printing. CONCLUSIONS: These results show that the new staining method significantly enhanced the display qualities of nerve fascicle edges and fiber textures of motor and sensory nerves and facilitated 3D nerve reconstruction.
ESTHER : Luo_2019_BMC.Neurosci_20_32
PubMedSearch : Luo_2019_BMC.Neurosci_20_32
PubMedID: 31286881

Title : Pharmacokinetics, excretion and metabolites analysis of DL0410, a dualacting cholinesterase inhibitor and histamine3 receptor antagonist - Pang_2019_Mol.Med.Rep_20_1103
Author(s) : Pang X , Zhao Y , Song J , Kang , Wu S , Wang L , Liu A , Du G
Ref : Mol Med Rep , 20 :1103 , 2019
Abstract : DL0410, a dualaction cholinesterase inhibitor and histamine3 receptor antagonist with a novel structural scaffold, may be a potential candidate for the treatment of Alzheimer's disease (AD). To the best of the authors' knowledge, this is the first study to demonstrate a reliable method for the measurement of DL0410 in rat plasma, brain, bile, urine and feces samples, and identification of its primary metabolites. The pharmacokinetic properties of DL0410 were analyzed by liquid chromatographymass spectrometry at oral doses of 25, 50 and 100 mg/kg and intravenous dose of 5 mg/kg. The investigation of the excretion and metabolism of DL0410 was determined following liquidliquid extraction for biliary, urinary and fecal samples. Finally, the cytochrome (CY)P450 isoforms involved in the production of DL0410 metabolites with recombinant human cytochrome P450 enzymes were characterized. The results suggested that DL0410 was not well absorbed; however, was distributed to the entorhinal cortex and hippocampus of the brain. A total of two common metabolites of the reduction of DL0140 in the bile, urine and feces were identified and CYP2D6 was involved in this reaction. The pharmacokinetic results of DL0410 provided information for the illustration of its pharmacodynamic properties, mechanism of action and promoted its continued evaluation as a therapeutic agent for AD treatment.
ESTHER : Pang_2019_Mol.Med.Rep_20_1103
PubMedSearch : Pang_2019_Mol.Med.Rep_20_1103
PubMedID: 31173186

Title : Pediatric reference intervals of liver and renal function tests from birth to adolescence in Chinese children as performed on the Olympus AU5400 - Liu_2019_Clin.Chim.Acta_490_142
Author(s) : Liu J , Dai Y , Lee Y , Yuan E , Wang Q , Wang L , Su Y
Ref : Clinica Chimica Acta , 490 :142 , 2019
Abstract : BACKGROUND: The growth and development of children and adolescents influence values of liver and renal function tests. The purpose of this study was to determine age- and gender-specific reference intervals for liver and renal function tests in apparently healthy Chinese children and adolescents. METHODS: A total of 63,086 apparently healthy children and adolescents (0-15 y) were chosen as reference individuals in this study. The 15 biochemical analytes relating to liver and renal function were measured using an Olympus AU5400 analyzer. Reference intervals were partitioned according to age and/or gender subgroups using the Harris and Boyd's method and established using non-parametric methods. RESULTS: Our results showed that all analytes except for cholinesterase (ChE) and alpha1-microglobulin (alpha1-MG) required partitioning by age. Gender partitions were also required for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), creatinine (Cre), and uric acid (UA). Age- and gender-appropriate reference intervals for liver and renal function tests were established for apparently healthy Chinese children and adolescents. CONCLUSIONS: When establishing pediatric reference intervals, partitioning by age and/or gender is essential. Those reference intervals can be adopted in other clinical laboratories after appropriate validation.
ESTHER : Liu_2019_Clin.Chim.Acta_490_142
PubMedSearch : Liu_2019_Clin.Chim.Acta_490_142
PubMedID: 30611730

Title : Linarin improves the dyskinesia recovery in Alzheimer's disease zebrafish by inhibiting the acetylcholinesterase activity - Pan_2019_Life.Sci_222_112
Author(s) : Pan H , Zhang J , Wang Y , Cui K , Cao Y , Wang L , Wu Y
Ref : Life Sciences , 222 :112 , 2019
Abstract : BACKGROUND: Due to complex pathogenesis of Alzheimer's disease (AD), currently there is no effective disease-modifying treatment. Acetylcholinesterase (AChE) has introduced itself as an important target for AD therapy. Linarin as the representative active ingredient of flavonoid glycoside in Flos chrysanthemi indici has been found to have anti-acetylcholinesterase effect. AIMS: The present study intended to explore the potential effect of linarin for treatment of AD. MAIN METHODS: In this study, molecular docking simulation was used to evaluate whether linarin could dock with AChE and decipher the mechanism of linarin as an AChE inhibitor. After molecular docking simulation, AlCl3-induced Alzheimer's disease zebrafish model was established. Effects of linarin on treating AD zebrafish dyskinesia and AChE inhibition were compared with donepezil (DPZ) which was used as a positive control drug. KEY FINDINGS: Molecular docking simulation showed that linarin plays a critical role in AChE inhibition by binding AChE active sites. The experiments illustrated that the dyskinesia recovery rate of AD zebrafish could be significantly improved by linarin. The dyskinesia recovery and AChE inhibition rate were 88.0% and 74.5% respectively, while those of DPZ were 79.3% and 43.6%. SIGNIFICANCE: These findings provide evidences for supporting linarin to be developed into an AD drug by inhibiting the activity of AChE.
ESTHER : Pan_2019_Life.Sci_222_112
PubMedSearch : Pan_2019_Life.Sci_222_112
PubMedID: 30802512

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 : Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment - Zhou_2019_J.Proteome.Res_18_1542
Author(s) : Zhou X , Xiao W , Su Z , Cheng J , Zheng C , Zhang Z , Wang Y , Wang L , Xu B , Li S , Yang X , Pui Man Hoi M
Ref : J Proteome Res , 18 :1542 , 2019
Abstract : Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3xTg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3xTg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Abeta1-40 and Abeta1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3xTg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target.
ESTHER : Zhou_2019_J.Proteome.Res_18_1542
PubMedSearch : Zhou_2019_J.Proteome.Res_18_1542
PubMedID: 30484658

Title : ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield - Ou_2019_Nat.Commun_10_1078
Author(s) : Ou J , Peng Y , Yang W , Zhang Y , Hao J , Li F , Chen Y , Zhao Y , Xie X , Wu S , Zha L , Luo X , Xie G , Wang L , Sun W , Zhou Q , Li J , Liang H
Ref : Nat Commun , 10 :1078 , 2019
Abstract : The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.
ESTHER : Ou_2019_Nat.Commun_10_1078
PubMedSearch : Ou_2019_Nat.Commun_10_1078
PubMedID: 30842415
Gene_locus related to this paper: human-ABHD5

Title : Sevoflurane-induced inflammation development: involvement of cholinergic anti-inflammatory pathway - Yin_2019_Behav.Pharmacol_30_730
Author(s) : Yin J , Zhao X , Wang L , Xie X , Geng H , Zhan X , Teng J
Ref : Behav Pharmacol , 30 :730 , 2019
Abstract : Chronic inflammation plays an important role in the mechanisms underpinning the development of anesthesia-induced cognitive dysfunction. However, less is known about how anesthesia causes inflammation. One possibility is that the inflammation is related to alteration of the activity of the alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway. This study analyzed the effect of sevoflurane administration on the cognitive function by using a novel object recognition test and Y-maze test, and on acetylcholinesterase activity and expression in hippocampal tissue by using an acetylcholinesterase assay kit and quantitative real-time PCR. This study also evaluated the effect of alpha 7 nicotinic acetylcholine receptor agonist PNU-282987 and antagonist methyllycaconitine on cognitive function and the level of hippocampal tumor necrosis factor-alpha in aged rats exposed to sevoflurane anesthesia. We found that 3% sevoflurane significantly impaired cognitive function and increased acetylcholinesterase activity by upregulating its expression in hippocampal tissue. Sevoflurane-induced impairment of cognitive function was significantly rescued by PNU-282987 but aggravated by methyllycaconitine. In addition to impairment of cognitive function, sevoflurane also significantly increased tumor necrosis factor-alpha level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-alpha level in rats was antagonized by PNU-282987 but amplified by methyllycaconitine. In conclusion, our data show that the development of inflammation in sevoflurane-induced cognitive decline is associated with the downregulation of alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway in aged rats.
ESTHER : Yin_2019_Behav.Pharmacol_30_730
PubMedSearch : Yin_2019_Behav.Pharmacol_30_730
PubMedID: 31625977

Title : Structural and functional analyses of the lipase CinB from Enterobacter asburiae - Shang_2019_Biochem.Biophys.Res.Commun_519_274
Author(s) : Shang F , Lan J , Liu W , Chen Y , Wang L , Zhao J , Chen J , Gao P , Ha NC , Quan C , Nam KH , Xu Y
Ref : Biochemical & Biophysical Research Communications , 519 :274 , 2019
Abstract : Lipases are widely present in various plants, animals and microorganisms, constituting a large category of enzymes. They have the ability to catalyze the cleavage of ester bonds. The lipase CinB from Enterobacter asburiae (E. asburiae) is an acetyl esterase. The primary amino acid sequence suggests that the EaCinB protein belongs to the alpha/beta-hydrolase (ABH) superfamily of the esterase/lipase superfamily. However, its molecular functions have not yet been determined. Here, we report the crystal structure of E. asburiae CinB at a 1.45A resolution. EaCinB contains a signal peptide, cap domain and catalytic domain. The active site of EaCinB contains the catalytic triad (Ser180-His307-Asp277) on the catalytic domain. The oxyanion hole is composed of Gly106 and Gly107 within the conserved sequence motif HGGG (amino acid residues 106-109). The substrate is accessible between the alpha1 and alpha2 helices or the alpha1 helix and catalytic domain. Narrow substrate pockets are formed by the alpha2 helix of the cap domain. Site-directed mutagenesis showed that EaCinB-W208H exhibits a higher catalytic ability than EaCinB-WT by approximately nine times. Our results provide insight into the molecular function of EaCinB.
ESTHER : Shang_2019_Biochem.Biophys.Res.Commun_519_274
PubMedSearch : Shang_2019_Biochem.Biophys.Res.Commun_519_274
PubMedID: 31493870
Gene_locus related to this paper: entas-cinB

Title : Biochemical characterization of a novel lipase from Malbranchea cinnamomea suitable for production of lipolyzed milkfat flavor and biodegradation of phthalate esters - Duan_2019_Food.Chem_297_124925
Author(s) : Duan X , Xiang M , Wang L , Yan Q , Yang S , Jiang Z
Ref : Food Chem , 297 :124925 , 2019
Abstract : A novel lipase gene (McLipB) was cloned from a thermophilic fungus Malbranchea cinnamomea and expressed in Pichia pastoris. The deduced amino acid sequence of the lipase (McLipB) shared the highest identity of 46% with the Candida rugosa lipase LIP4. The extracellular lipase activity of 4304 U/mL with protein concentration of 7.7 mg/mL was achieved in a 5-L fermentor. The optimal pH and temperature of McLipB were 7.5 and 40 degreesC, respectively. The lipase showed high specificity towards triglycerides with short and medium chain fatty acids, and had non-position specificity. McLipB hydrolyzed butter to produce mainly butyric acid, hexanoic acid and a small amount of octanoic acid and decanoic acid. Furthermore, it degraded more than 90% dipropyl phthalate, dibutyl phthalate and dihexyl phthalate to their corresponding monoalkyl phthalates. The properties of McLipB indicate that it has great application potential for production of lipolyzed milkfat flavor and biodegradation of phthalate esters.
ESTHER : Duan_2019_Food.Chem_297_124925
PubMedSearch : Duan_2019_Food.Chem_297_124925
PubMedID: 31253266
Gene_locus related to this paper: malci-McLipB

Title : Hydroxy-alpha-sanshool isolated from Zanthoxylum bungeanum attenuates learning and memory impairments in scopolamine-treated mice - Zhang_2019_Food.Funct_10_7315
Author(s) : Zhang M , Xie M , Wei D , Wang L , Hu M , Zhang Q , He Z , Peng W , Wu C
Ref : Food Funct , 10 :7315 , 2019
Abstract : Learning and memory impairments are common symptoms of dementia in neurodegenerative disorders. Occasionally, we found that Zanthoxylum bungeanum pericarps (ZBP) significantly activated the spontaneous activity of the hippocampus (HIPP) and paraHIPP (P < 0.001, uncorrected), implying the potential ability of ZBP to improve cognitive impairments. Thus, this study aimed to investigate the improving effect of hydroxy-alpha-sanshool (HAS), a characteristic ingredient of ZBP, against scopolamine (1 mg kg(-1), i.p.)-induced learning and memory deficits. HAS (5 mg kg(-1), p.o.) markedly reversed scopolamine-induced cognitive impairments, as indicated by its performance in the passive avoidance test and Morris water maze test (P < 0.01). Furthermore, HAS (2.5 and 5.0 mg kg(-1), p.o.) also dose-dependently prevented changes in hippocampal neuronal morphology and apoptosis, inhibited acetylcholinesterase (AChE) activity, increased the acetylcholine (ACh) content, and increased the protein and mRNA expression of brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding (p-CREB) compared with those in the model group (P < 0.05 & P < 0.01). These findings demonstrated that HAS attenuated scopolamine-induced cognitive impairments mainly by enhancing the activity of the cholinergic system and increasing the CREB/BDNF signalling pathway.
ESTHER : Zhang_2019_Food.Funct_10_7315
PubMedSearch : Zhang_2019_Food.Funct_10_7315
PubMedID: 31637395

Title : Design, Synthesis, and Evaluation of (18)F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes - Chen_2019_J.Med.Chem_62_8866
Author(s) : Chen Z , Mori W , Fu H , Schafroth MA , Hatori A , Shao T , Zhang G , Van RS , Zhang Y , Hu K , Fujinaga M , Wang L , Belov V , Ogasawara D , Giffenig P , Deng X , Rong J , Yu Q , Zhang X , Papisov MI , Shao Y , Collier TL , Ma JA , Cravatt BF , Josephson L , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 62 :8866 , 2019
Abstract : Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for (18)F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel (18)F-labeled MAGL PET probes.
ESTHER : Chen_2019_J.Med.Chem_62_8866
PubMedSearch : Chen_2019_J.Med.Chem_62_8866
PubMedID: 31518130

Title : Structural insight into the carboxylesterase BioH from Klebsiella pneumoniae - Wang_2019_Biochem.Biophys.Res.Commun_520_538
Author(s) : Wang L , Chen Y , Shang F , Liu W , Lan J , Gao P , Ha NC , Nam KH , Dong Y , Quan C , Xu Y
Ref : Biochemical & Biophysical Research Communications , 520 :538 , 2019
Abstract : The BioH carboxylesterase which is a typical alpha/beta-hydrolase enzyme involved in biotin synthetic pathway in most bacteria. BioH acts as a gatekeeper and blocks the further elongation of its substrate. In the pathogen Klebsiella pneumoniae, BioH plays a critical role in the biosynthesis of biotin. To better understand the molecular function of BioH, we determined the crystal structure of BioH from K. pneumoniae at 2.26A resolution using X-ray crystallography. The structure of KpBioH consists of an alpha-beta-alpha sandwich domain and a cap domain. B-factor analysis revealed that the alpha-beta-alpha sandwich domain is a rigid structure, while the loops in the cap domain shows the structural flexibility. The active site of KpBioH contains the catalytic triad (Ser82-Asp207-His235) on the interface of the alpha-beta-alpha sandwich domain, which is surrounded by the cap domain. Size exclusion chromatography shows that KpBioH prefers the monomeric state in solution, whereas two-fold symmetric dimeric formation of KpBioH was observed in the asymmetric unit, the conserved Cys31-based disulfide bonds can maintain the irreversible dimeric formation of KpBioH. Our study provides important structural insight for understanding the molecular mechanisms of KpBioH and its homologous proteins.
ESTHER : Wang_2019_Biochem.Biophys.Res.Commun_520_538
PubMedSearch : Wang_2019_Biochem.Biophys.Res.Commun_520_538
PubMedID: 31615653
Gene_locus related to this paper: klep3-bioh

Title : Transcript-Level Analysis of Detoxification Gene Mutation-Mediated Chlorpyrifos Resistance in Laodelphax striatellus (Hemiptera: Delphacidae) - Zhang_2019_J.Econ.Entomol_112_1285
Author(s) : Zhang Y , Ma X , Han Y , Wang L , Liu Z , Guo H , Fang J
Ref : J Econ Entomol , 112 :1285 , 2019
Abstract : Enhanced detoxification and target mutations that weaken insecticide binding ability are major mechanisms of insecticide resistance. Among these, over-expression or site mutations of carboxylesterase (CarE), cytochrome P450s (CYP450), and glutathione-S-transferase (GST) were the main form responsible for insecticide detoxification; however, transcript-level analysis of the relationship of detoxification gene mutations with chlorpyrifos (an organophosphorus insecticide) resistance is scarce thus far. In this study, multiple sites exhibiting polymorphisms within three detoxification genes were firstly examined via sequencing among different chlorpyrifos-resistant and susceptible individuals of Laodelphax striatellus. For example, the mutation frequencies of A374V in LsCarE16 were 83, 33, and 3%, S277A in LsCarE24 were 88, 28, and 3%, E36K in LsCYP426A1 were 100, 65, and 0% for chlorpyrifos-resistant, resistant decay, and susceptible individuals, respectively. Analysis also found expression levels of GSTd1, GSTt1, GSTs2, CYP4DE1U1, and CYP425B1 are coordinated with chlorpyrifos resistance levels; moreover, we found the deficiencies of 43S and 44A as well as two point mutations of E60D and Q61H at N-terminal region of the OP potential target acetylcholinesterase (AChE) in high resistant but not in low-chlorpyrifos resistant individuals. The results above all demonstrated the dynamic evolutionary process of insecticide resistance and revealed some resistance factors that only played roles at certain resistance level; high insecticide resistance in this example is the result of synergistic impact from multiple resistance factors.
ESTHER : Zhang_2019_J.Econ.Entomol_112_1285
PubMedSearch : Zhang_2019_J.Econ.Entomol_112_1285
PubMedID: 30615131

Title : Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a Tail Switching Strategy on a Piperazinyl Azetidine Skeleton - Chen_2019_J.Med.Chem_62_3336
Author(s) : Chen Z , Mori W , Deng X , Cheng R , Ogasawara D , Zhang G , Schafroth MA , Dahl K , Fu H , Hatori A , Shao T , Zhang Y , Yamasaki T , Zhang X , Rong J , Yu Q , Hu K , Fujinaga M , Xie L , Kumata K , Gou Y , Chen J , Gu S , Bao L , Wang L , Collier TL , Vasdev N , Shao Y , Ma JA , Cravatt BF , Fowler C , Josephson L , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 62 :3336 , 2019
Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with (11)C or (18)F. [(11)C]8 ([(11)C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [(11)C]17 ([(11)C]PAD) and [(18)F]37 ([(18)F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms.
ESTHER : Chen_2019_J.Med.Chem_62_3336
PubMedSearch : Chen_2019_J.Med.Chem_62_3336
PubMedID: 30829483
Gene_locus related to this paper: human-MGLL

Title : Interspecies variation of clopidogrel hydrolysis in liver microsomes from various manmmals - Wang_2019_Chem.Biol.Interact__108871
Author(s) : Wang YQ , Shang XF , Wang L , Zhang P , Zou LW , Song YQ , Hao DC , Fang SQ , Ge GB , Tang H
Ref : Chemico-Biological Interactions , :108871 , 2019
Abstract : Clopidogrel, a clinically used antiplatelet agent, can be readily hydrolyzed by human carboxylesterase 1A (CES1A) to release an inactive metabolite clopidogrel carboxylic acid (CCA). In this study, clopidogrel was used as a tool substrate to investigate the interspecies variation of clopidogrel hydrolysis in hepatic microsomes from various mammals including human and six laboratory animals (such as mouse, rat, rabbit, beagle dog, minipig and cynomolgus monkey). The results demonstrated that clopidogrel could be hydrolyzed into CCA by all tested hepatic microsomes from human or other mammals, but the hydrolytic rates greatly varied among species. Inhibition assays demonstrated that BNPP (an inactivator of mammalian CES) strongly inactivated clopidogrel hydrolytic activity in all tested hepatic microsomes, suggested that mammalian CES were major contributor(s) responsible for clopidogrel hydrolysis in hepatic preparations from all above-mentioned species. By contrast, the response of a reversible inhibitor of human CES1A on clopidogrel hydrolysis in these liver preparations varied significantly among different species. Moreover, the enzymatic kinetics and the apparent kinetic parameters of clopidogrel hydrolysis in hepatic microsomes from various animal species were evaluated and compared to each other. These findings provide crucial information for deeply understanding the differences in catalytic behaviors of mammalian CES, which will be very helpful for choosing suitable laboratory animal(s) for whole tests of CES1A substrate-drugs.
ESTHER : Wang_2019_Chem.Biol.Interact__108871
PubMedSearch : Wang_2019_Chem.Biol.Interact__108871
PubMedID: 31669218

Title : Mutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated Neutralization - Kleine-Weber_2019_J.Virol_93_
Author(s) : Kleine-Weber H , Elzayat MT , Wang L , Graham BS , Muller MA , Drosten C , Pohlmann S , Hoffmann M
Ref : J Virol , 93 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) poses a threat to public health. The virus is endemic in the Middle East but can be transmitted to other countries by travel activity. The introduction of MERS-CoV into the Republic of Korea by an infected traveler resulted in a hospital outbreak of MERS that entailed 186 cases and 38 deaths. The MERS-CoV spike (S) protein binds to the cellular protein DPP4 via its receptor binding domain (RBD) and mediates viral entry into target cells. During the MERS outbreak in Korea, emergence and spread of viral variants that harbored mutations in the RBD, D510G and I529T, was observed. Counterintuitively, these mutations were found to reduce DPP4 binding and viral entry into target cells. In this study, we investigated whether they also exerted proviral effects. We confirm that changes D510G and I529T reduce S protein binding to DPP4 but show that this reduction only translates into diminished viral entry when expression of DPP4 on target cells is low. Neither mutation modulated S protein binding to sialic acids, S protein activation by host cell proteases, or inhibition of S protein-driven entry by interferon-induced transmembrane proteins. In contrast, changes D510G and I529T increased resistance of S protein-driven entry to neutralization by monoclonal antibodies and sera from MERS patients. These findings indicate that MERS-CoV variants with reduced neutralization sensitivity were transmitted during the Korean outbreak and that the responsible mutations were compatible with robust infection of cells expressing high levels of DPP4.IMPORTANCE MERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted proviral effects. We demonstrate that these mutations reduce sensitivity to antibody-mediated neutralization and are compatible with robust infection of target cells expressing large amounts of the viral receptor DPP4.
ESTHER : Kleine-Weber_2019_J.Virol_93_
PubMedSearch : Kleine-Weber_2019_J.Virol_93_
PubMedID: 30404801

Title : Insecticide Resistance Status and Mechanisms of Anopheles sinensis (Diptera: Culicidae) in Wenzhou, an Important Coastal Port City in China - Chen_2019_J.Med.Entomol_56_803
Author(s) : Chen S , Qin Q , Zhong D , Fang X , He H , Wang L , Dong L , Lin H , Zhang M , Cui L , Yan G
Ref : Journal of Medical Entomology , 56 :803 , 2019
Abstract : Although scaled-up interventions and effective control efforts have drastically reduced malaria morbidity and mortality, malaria remains a serious threat to public health worldwide. Anopheles sinensis Wiedemann 1828 is a historically important vector of Plasmodium vivax (Haemosporida: Plasmodiidae) malaria in China. Insecticide resistance has become a major obstacle to vector-borne disease control. However, little is known about the insecticide resistance of An. sinensis in Wenzhou, an important coastal port city in Zhejiang province, China. The aim of this study was to examine insecticide resistance and mechanisms in An. sinensis field mosquito populations. Evidence of multiple insecticide resistance was found in An. sinensis adult female populations. Medium to high frequencies of target site kdr together with fixed ace-1 mutations was detected in both the Ruian and Yongjia populations. Both populations showed an association between kdr L1014 mutation and resistance phenotype when tested against deltamethrin and DDT. Significantly different metabolic enzyme activities were found between the susceptible laboratory strain and field-collected mosquitoes from both Ruian and Yongjia. Both field collected An. sinensis populations exhibited significantly higher P450 enzyme activity compared with the laboratory strain, while the field-collected resistant mosquitoes exhibited various GST and COE enzyme activities. These results indicate multiple resistance mechanisms in An. sinensis field populations. Effective implementation of insecticide resistance management strategies is urgently needed. The data collected in this study will be valuable for modeling insecticide resistance spread and vector-control interventions.
ESTHER : Chen_2019_J.Med.Entomol_56_803
PubMedSearch : Chen_2019_J.Med.Entomol_56_803
PubMedID: 30715428

Title : Hybrids of oxoisoaporphine-tetrahydroisoquinoline: novel multi-target inhibitors of inflammation and amyloid-beta aggregation in Alzheimer's disease - Chen_2019_Mol.Divers_23_709
Author(s) : Chen Y , Su C , Wang L , Qin J , Wei S , Tang H
Ref : Mol Divers , 23 :709 , 2019
Abstract : A series of 8- and 11-substituted hybrids of oxoisoaporphine-tetrahydroisoquinoline have been designed and synthesized. The new derivatives strongly suppressed NO and iNOS production and modulated the production of cytokines by decreasing TNF-alpha and IL-1beta formation in lipopolysaccharide-activated BV-2 microglia and RAW 264.7 macrophages. Meanwhile, incubation of these derivatives with SH-SY5Y cells that were transfected with human APP containing the Swedish mutations significantly decreased the secretion of Abeta42. Moreover, these hybrids could strongly inhibit the activity of acetylcholinesterase and butyrylcholinesterase. Further investigations in vivo indicated that the 8-substituted hybrid 3b significantly delayed paralysis caused by Abeta1-42 toxicity in GMC101. In sum, these new hybrids could target multiple pathogenetic factors in Alzheimer's disease and merit further investigation.
ESTHER : Chen_2019_Mol.Divers_23_709
PubMedSearch : Chen_2019_Mol.Divers_23_709
PubMedID: 30603938

Title : Cell-Membrane-Cloaked Oil Nanosponges Enable Dual-Modal Detoxification - Chen_2019_ACS.Nano_13_7209
Author(s) : Chen Y , Zhang Y , Zhuang J , Lee JH , Wang L , Fang RH , Gao W , Zhang L
Ref : ACS Nano , 13 :7209 , 2019
Abstract : The lack of pharmaceutical antidotes for deadly toxicants has motivated tremendous research interests in seeking synthetic nanoscavengers to absorb and neutralize harmful biological or chemical agents. Herein, we report a cell-membrane-cloaked oil nanosponge formulation capable of dual-modal detoxification. The biomimetic oil nanosponge consists of an olive oil nanodroplet wrapped by a red blood cell membrane. In such a construct, the oil core can nonspecifically soak up toxicants through physical partition and the cell membrane shell can specifically absorb and neutralize toxicants through biological binding. The dual-modal detoxification capability of the oil nanosponges was validated using three distinct organophosphates (OPs), including paraoxon, diisopropyl fluorophosphate, and dichlorvos. By inhibiting acetylcholinesterase, OPs cause the accumulation of acetylcholine, which leads to neuromuscular disorders and even death. In mouse models of OP poisoning, the oil nanosponges reduced clinical signs of OP intoxication, lowered OP concentration in tissues, and greatly enhanced mouse survival in both the therapeutic regimen and the prophylactic regimen. Overall, oil nanosponges combine the merits of both cell membrane and oil nanodroplets for safe and effective detoxification, which also serve as a prototype of multimodal detoxification platforms.
ESTHER : Chen_2019_ACS.Nano_13_7209
PubMedSearch : Chen_2019_ACS.Nano_13_7209
PubMedID: 31117372

Title : Two new species of marine flatworm from southern China facilitate determination of the phylogenetic position of the genus Nerpa Marcus, 1948 and the histochemical structure of the nervous system in the genus Paucumara Sluys, 1989 (Platyhelminthes, Tricladida, Maricola) - Chen_2019_Zootaxa_4568_zootaxa 4568 1 9
Author(s) : Chen JJ , Li WX , Sluys R , Wu MQ , Wang L , Li SF , Wang AT
Ref : Zootaxa , 4568 :zootaxa 4568 1 9 , 2019
Abstract : Two new species of flatworm, collected from a beach at eastern Shenzhen, China, were studied through an integrative approach by combining morphological, histological, histochemical (acetylcholinesterase, AChE), and molecular (18S r- DNA) data. These species belong to two genera of marine triclads, previously unrecorded from China, viz. Nerpa Marcus, 1948 and Paucumara Sluys, 1989. Nerpa fistulata Wang Chen, sp. nov. is characterized by: transparent body; principally pentamerous intestine with three distinct commissures; two very large, prepharyngeal testis follicles; a semi-circular lens in each eye cup; a penis papilla provided with a chitinized, pointed stylet; lateral bursae communicating with the oviduct and opening ventrally to the exterior via a duct. Phylogenetically N. fistulata groups with one member of the family Bdellouridae. This new, Chinese species of Nerpa introduces a major geographic disjunction, as the type species N. evelinae was described from the bay of Santos, Brazil, so that the genus is now known from both Atlantic as well as Pacific coasts. The species Paucumara falcata Wang Li, sp. nov. is characterized by: three distinct pale yellow transverse pigmentation bands on its dorsal side, between which some snowflake-like specks are randomly distributed, and a brown transverse band anteriorly to the eyes; 8-11 testicular follicles on either side of the body, the follicles extending from immediately behind the ovaries to half-way along the pharyngeal pocket; a musculo-parenchymatic organ with a sclerotic, curved tip projecting from the anterior wall of the male atrium, ventrally to the root of the penis papilla. Phylogenetically P. falcata groups with its congener P. trigonocephala, with the genus Paucumara forming the sister taxon of the genus Ectoplana. Comparison of the nerve structure of P. falcata, as revealed by AChE histochemistry, with that of eight other species of triclad suggested that the nervous system of marine planarians is simpler than that of species of freshwater planarians, but revealed also that the nerve structure is rather variable among species. The copulatory position exhibited by two partners in Paucumara falcata is remarkable in that they intertwine, with their heads pointing downwards and the tails pointing upwards, the entire process lasting about 10 min. Such a copulatory position has never before been reported for triclad flatworms.
ESTHER : Chen_2019_Zootaxa_4568_zootaxa 4568 1 9
PubMedSearch : Chen_2019_Zootaxa_4568_zootaxa 4568 1 9
PubMedID: 31715876

Title : Proteomic and metabolomic responses in hepatopancreas of whiteleg shrimp Litopenaeus vannamei infected by microsporidian Enterocytozoon hepatopenaei - Ning_2019_Fish.Shellfish.Immunol_87_534
Author(s) : Ning M , Wei P , Shen H , Wan X , Jin M , Li X , Shi H , Qiao Y , Jiang G , Gu W , Wang W , Wang L , Meng Q
Ref : Fish Shellfish Immunol , 87 :534 , 2019
Abstract : Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. HPM is not normally associated with shrimp mortality, but is associated with significant growth retardation. In this study, the responses induced by EHP were investigated in hepatopancreas of shrimp Litopenaeus vannamei using proteomics and metabolomics. Among differential proteins identified, several (e.g., peritrophin-44-like protein, alpha2 macroglobulin isoform 2, prophenoloxidase-activating enzymes, ferritin, Rab11A and cathepsin C) were related to pathogen infection and host immunity. Other proteomic biomarkers (i.e., farnesoic acid o-methyltransferase, juvenile hormone esterase-like carboxylesterase 1 and ecdysteroid-regulated protein) resulted in a growth hormone disorder that prevented the shrimp from molting. Both proteomic KEGG pathway (e.g., "Glycolysis/gluconeogenesis" and "Glyoxylate and dicarboxylate metabolism") and metabolomic KEGG pathway (e.g., "Galactose metabolism" and "Biosynthesis of unsaturated fatty acids") data indicated that energy metabolism pathway was down-regulated in the hepatopancreas when infected by EHP. More importantly, the changes of hormone regulation and energy metabolism could provide much-needed insight into the underlying mechanisms of stunted growth in shrimp after EHP infection. Altogether, this study demonstrated that proteomics and metabolomics could provide an insightful view into the effects of microsporidial infection in the shrimp L. vannamei.
ESTHER : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedSearch : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedID: 30721776

Title : Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD - Wang_2019_Cell.Rep_28_3395
Author(s) : Wang N , Rosen O , Wang L , Turner HL , Stevens LJ , Corbett KS , Bowman CA , Pallesen J , Shi W , Zhang Y , Leung K , Kirchdoerfer RN , Becker MM , Denison MR , Chappell JD , Ward AB , Graham BS , McLellan JS
Ref : Cell Rep , 28 :3395 , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.
ESTHER : Wang_2019_Cell.Rep_28_3395
PubMedSearch : Wang_2019_Cell.Rep_28_3395
PubMedID: 31553909

Title : Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells - Tang_2018_Gene_667_95
Author(s) : Tang L , Wang G , Jiang L , Chen P , Wang W , Chen J , Wang L
Ref : Gene , 667 :95 , 2018
Abstract : OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. MATERIALS AND METHODS: 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. RESULTS: sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. CONCLUSION: Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study.
ESTHER : Tang_2018_Gene_667_95
PubMedSearch : Tang_2018_Gene_667_95
PubMedID: 29665449
Gene_locus related to this paper: human-EPHX2

Title : The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas - Liu_2018_Front.Immunol_9_284
Author(s) : Liu Z , Wang L , Lv Z , Zhou Z , Wang W , Li M , Yi Q , Qiu L , Song L
Ref : Front Immunol , 9 :284 , 2018
Abstract : It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a "nervous-hemocyte"-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system. After hemocytes were exposed to lipopolysaccharide (LPS) stimulation, acetylcholine (ACh), and norepinephrine (NE) in the cell supernatants, both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05) comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase and dopamine beta-hydroxylase in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase and monoamine oxidase, two enzymes essential in the metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF) genes, the activities of superoxide dismutase, catalase and lysosome, and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that oyster hemocyte could de novo synthesize and release cholinergic and adrenergic neurotransmitters, and the hemocyte-derived ACh/NE could then execute a negative regulation on hemocyte phagocytosis and synthesis of immune effectors with similar autocrine/paracrine signaling pathway identified in vertebrate macrophages. Findings in the present study demonstrated that the immune and neuroendocrine system evolved from a common origin and enriched our knowledge on the evolution of NEI system.
ESTHER : Liu_2018_Front.Immunol_9_284
PubMedSearch : Liu_2018_Front.Immunol_9_284
PubMedID: 29535711

Title : Hierarchical nanocomposites with an N-doped carbon shell and bimetal core: Novel enzyme nanocarriers for electrochemical pesticide detection - Ma_2018_Biosens.Bioelectron_121_166
Author(s) : Ma L , Zhou L , He Y , Wang L , Huang Z , Jiang Y , Gao J
Ref : Biosensors & Bioelectronics , 121 :166 , 2018
Abstract : Core-shell structured nanocomposites (named PtPd@NCS) with N-doped carbon shell and bimetal core (Pt and Pd) were fabricated through a facile strategy for the first time. The PtPd@NCS nanocomposites were obtained through reduction of K2PtCl4, H2PtCl6 and Na2PdCl4 species, self-polymerization of dopamine (DA) and co-assembly of Pluronic F127 using a one-pot approach. DA serves as a reductant, as well as a carbon and nitrogen source. The core-shell structure of the PtPd@NCS nanocomposites was characterized and the result indicated that Pt-Pd nanoparticle core with a diameter of approximately 15nm was encased in the N-doped carbon shells with a thickness of approximately 35nm. The PtPd@NCS nanocomposites were used as an electrode material to prepare acetylcholinesterase (AChE) biosensors for detecting organophosphate pesticides. The obtained AChE biosensor exhibited a linear range of 1x10(-14) to 1x10(-10) M and 1x10(-9) to 1x10(-5) M within the detection limit of 7.9x10(-15) M for malathion, 1x10(-13) to 1x10(-6) within the detection limit of 7.1x10(-14) M for chlopyrifos, and 1x10(-14) to 1x10(-11) M and 1x10(-10) to 1x10(-5) M within the detection limit of 8.6x10(-15) M for parathion methyl. The proposed biosensor also exhibited high selectivity, reproducibility and stability. The AChE biosensor was also applied in real samples for detecting organophosphate pesticides and exhibited acceptable recovery. This work demonstrated that the PtPd@NCS had great potential in constructing biosensors to detect organophosphate pesticides and other analytes.
ESTHER : Ma_2018_Biosens.Bioelectron_121_166
PubMedSearch : Ma_2018_Biosens.Bioelectron_121_166
PubMedID: 30218924

Title : Preparation of Margarine Stock Rich in Naturally Bioactive Components by Enzymatic Interesterification - Yu_2018_J.Oleo.Sci_67_29
Author(s) : Yu D , Qi X , Jiang Y , Zou D , Wang L , Jiang L , Qin L
Ref : J Oleo Sci , 67 :29 , 2018
Abstract : Fully hydrogenated expanded press soybean oil (FHEPSO) rich in naturally bioactive components was prepared using Palladium on Carbon (Pd/C) catalyst. Interesterified fat was prepared from binary blends of FHEPSO and cold press corn oil (CPCO) with FHEPSO/CPCO mass ratios of 50:50, 40:60 and 30:70. Lipozyme RM IM (6 wt% of total substrate) was used in a supercritical CO(2) system to catalyze the transesterification. The fatty acid compositions had no significant changes in the fats before and after interesterification, and trans-fatty acid (TFA) was not detected. The fatty acid compositions within triacylglycerol (TAG) were rearranged, and the amounts of trisaturated and triunsaturated TAG decreased, whereas that of mixed TAG increased as a result of interesterification. The enzymatic interesterified fats (EIEF) had a lower solid fat content (SFC), broader melting and plasticity ranges compared to the noninteresterified blend (NIB). According to X-ray diffraction (XRD), the predominant crystal form had changed from beta to beta'. EIEF contained 0.33-0.51 g/100 g phospholipids, 88.6-105.6 mg/100 g total tocopherols, and 916-1053 mg/100 g total phytosterols, which could confer health benefits. The results indicated that EIEF may have a potential use in trans-free margarine stock preparation.
ESTHER : Yu_2018_J.Oleo.Sci_67_29
PubMedSearch : Yu_2018_J.Oleo.Sci_67_29
PubMedID: 29238024

Title : Synthesis and bioactivity of novel C2-glycosyl oxadiazole derivatives as acetylcholinesterase inhibitors - Wang_2018_Heterocycl.Commun_24_333
Author(s) : Wang L , Wu YR , Ren ST , Yin L , Liu XJ , Cheng FC , Liu WW , Shi DH , Cao ZL , Sun HM
Ref : Heterocycl Commun , 24 :333 , 2018
Abstract : A series of glycosyl-substituted 1,3,4-oxadiazoles were synthesized by cyclization of glycosyl-acylthiosemicarbazides via a base-catalyzed reaction. The starting glycosyl-acylthiosemicarbazide derivatives were obtained by the reaction of glycosyl isothiocyanate with various hydrazides. The acetylcholinesterase (AChE) inhibitory activities of the products were tested by Ellman's method. The most active compounds were subsequently evaluated for the 50% inhibitory concentration (IC50) values. N-(1,-3,4,6-tetra-O-benzyl-2-deoxy-beta-D-glucopyranosyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole-2-amine (6i) possesses the best AChE -inhibition activity with an IC50 of 1.61 +/- 0.34 microm.
ESTHER : Wang_2018_Heterocycl.Commun_24_333
PubMedSearch : Wang_2018_Heterocycl.Commun_24_333
PubMedID:

Title : IL-6 release of Rv0183 antigen-stimulated whole blood is a potential biomarker for active tuberculosis patients - Liu_2018_J.Infect_76_376
Author(s) : Liu Y , Li X , Liu W , Zhong Z , Wang L , Ge S , Zhang J , Xia N
Ref : J Infect , 76 :376 , 2018
Abstract : OBJECTIVE: New tests for diagnosing active tuberculosis (aTB) are urgently needed, and TB antigen-specific cell-mediated immunity can be expected to develop new testing methods of aTB. MATERIALS AND METHODS: Rv0183 protein, the only monoglyceride lipase identified in mycobacteria, was used to stimulate freshly heparin-treated whole blood. The Rv0183-specific cytokines/chemokines response associated with aTB was screened firstly with 4 aTB patients and 4 LTBIs, and further evaluated in 192 suspected aTB patients and 372 healthy individuals. RESULTS: Out of 71 cytokines/chemokines, the response of IL-6 against Rv0183 protein was found to be associated with aTB. The Rv0183-specific IL-6 response was significantly higher in aTB patients (n = 128) than in those with non-TB lung disease (n = 64) and in healthy individuals (n = 327) (p < 0.0001), and not affected by latent TB infection. In IGRA+ suspected active TB patients, the sensitivity, specificity, PPV and NPV of IL-6 response (with cutoff of 235.2 pg/ml) were 85.7%, 100%, 100% and 51.5% for diagnosing aTB, respectively. While in IGRA- ones, they were 87.5%, 80.5%, 60.9% and 95.0% with 174.2 pg/ml IL-6 response as cutoff, respectively. CONCLUSIONS: These results clearly show that the Rv0183 antigen-specific IL-6 response has the potential to be used as an immune-diagnosis test for active TB in clinical practice.
ESTHER : Liu_2018_J.Infect_76_376
PubMedSearch : Liu_2018_J.Infect_76_376
PubMedID: 29174965
Gene_locus related to this paper: myctu-rv0183

Title : Karrikin-KAI2 signalling provides Arabidopsis seeds with tolerance to abiotic stress and inhibits germination under conditions unfavourable to seedling establishment - Wang_2018_New.Phytol_219_605
Author(s) : Wang L , Waters MT , Smith SM
Ref : New Phytol , 219 :605 , 2018
Abstract : The control of seed germination in response to environmental conditions is important for plant success. We investigated the role of the karrikin receptor KARRIKIN INSENSITIVE2 (KAI2) in the response of Arabidopsis seeds to osmotic stress, salinity and high temperature. Germination of the kai2 mutant was examined in response to NaCl, mannitol and elevated temperature. The effect of karrikin on germination of wild-type seeds, hypocotyl elongation and the expression of karrikin-responsive genes was also examined in response to such stresses. The kai2 seeds germinated less readily than wild-type seeds and germination was more sensitive to inhibition by abiotic stress. Karrikin-induced KAI2 signalling stimulated germination of wild-type seeds under favourable conditions, but, surprisingly, inhibited germination in the presence of osmolytes or at elevated temperature. By contrast, GA stimulated germination of wild-type seeds and mutants under all conditions. Karrikin induced expression of DLK2 and KUF1 genes and inhibited hypocotyl elongation independently of osmotic stress. Under mild osmotic stress, karrikin enhanced expression of DREB2A, WRKY33 and ERF5 genes, but not ABA signalling genes. Thus, the karrikin-KAI2 signalling system can protect against abiotic stress, first by providing stress tolerance, and second by inhibiting germination under conditions unfavourable to seedling establishment.
ESTHER : Wang_2018_New.Phytol_219_605
PubMedSearch : Wang_2018_New.Phytol_219_605
PubMedID: 29726620

Title : Characterization of two novel thermostable esterases from Thermoanaerobacterium thermosaccharolyticum - Li_2018_Protein.Expr.Purif_152_64
Author(s) : Li W , Shi H , Ding H , Wang L , Zhang Y , Li X , Wang F
Ref : Protein Expr Purif , 152 :64 , 2018
Abstract : This paper first describes characterization of two thermostable esterases (ThLip1 and ThLip2) from the thermophilic bacterium Thermoanaerobacterium thermosaccharolyticum DSM 571. The recombinant esterase ThLip1 was active at 80 degrees C, pH 6.5 and maintained approx. 85% of original activity after 2h incubation at 75 degrees C. Kinetic parameters, Km, Vmax and kcat/Km for 4-Nitrophenyl caprylate (pNPC) were 3.52+/-0.47mM, 191.18+/-1.82mumolmin(-1) mg(-1) and 20.80+/-0.07mM(-1)s(-1), respectively. The purified recombinant esterase ThLip2 was optimally active at pH 6.5 and 75 degrees C and it was stable against a pH range of 6.0-8.0 possessing 2h half-life at 80 degrees C. Kinetic experiments at 75 degrees C with pNPC as a substrate gave a Km of 3.37mM, Vmax of 578.14mumolmin(-1) mg(-1)and kcat of 231.2 s(-1). The hydrolysis of linalyl acetate were carried out using ThLip1 and ThLip2 as catalyst, affording linalool yields over 140mg/l in 10h.
ESTHER : Li_2018_Protein.Expr.Purif_152_64
PubMedSearch : Li_2018_Protein.Expr.Purif_152_64
PubMedID: 29684442

Title : Protein Crystallography and Site-Direct Mutagenesis Analysis of the Poly(ethylene terephthalate) Hydrolase PETase from Ideonella sakaiensis - Liu_2018_Chembiochem_19_1471
Author(s) : Liu B , He L , Wang L , Li T , Li C , Liu H , Luo Y , Bao R
Ref : Chembiochem , 19 :1471 , 2018
Abstract : Unlike traditional recycling strategies, biodegradation is a sustainable solution for disposing of poly(ethylene terephthalate) (PET) waste. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET and is, thus, a prominent candidate for PET degradation. On the basis of biochemical analysis, we propose that a wide substrate-binding pocket is critical for its excellent ability to hydrolyze crystallized PET. Structure-guided site-directed mutagenesis revealed an improvement in PETase catalytic efficiency, providing valuable insight into how the molecular engineering of PETase can optimize its application in biocatalysis.
ESTHER : Liu_2018_Chembiochem_19_1471
PubMedSearch : Liu_2018_Chembiochem_19_1471
PubMedID: 29603535
Gene_locus related to this paper: idesa-peth

Title : In Vitro and in Vivo Evaluation of (11)C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies - Cheng_2018_J.Med.Chem_61_2278
Author(s) : Cheng R , Mori W , Ma L , Alhouayek M , Hatori A , Zhang Y , Ogasawara D , Yuan G , Chen Z , Zhang X , Shi H , Yamasaki T , Xie L , Kumata K , Fujinaga M , Nagai Y , Minamimoto T , Svensson M , Wang L , Du Y , Ondrechen MJ , Vasdev N , Cravatt BF , Fowler C , Zhang MR , Liang SH
Ref : Journal of Medicinal Chemistry , 61 :2278 , 2018
Abstract : Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including (11)C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [(11)C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.
ESTHER : Cheng_2018_J.Med.Chem_61_2278
PubMedSearch : Cheng_2018_J.Med.Chem_61_2278
PubMedID: 29481079

Title : Characterization, in vitro binding properties, and inhibitory activity on pancreatic lipase of beta-glucans from different Qingke (Tibetan hulless barley) cultivars - Guo_2018_Int.J.Biol.Macromol_120_2517
Author(s) : Guo H , Lin S , Lu M , Gong JDB , Wang L , Zhang Q , Lin DR , Qin W , Wu DT
Ref : Int J Biol Macromol , 120 :2517 , 2018
Abstract : In order to explore Qingke beta-glucans as functional food ingredients for prevention of obesity, the physicochemical structures, in vitro binding properties, and inhibitory activities on pancreatic lipase of beta-glucans from three different Qingke cultivars, including Ganyucang (black), Dingqing (blue), and Zangqing 320 (white), were investigated and compared. Results showed that molecular weights, particle sizes, and intrinsic viscosities of beta-glucans from colored (black and blue) Qingke cultivars were much higher than those of white Qingke beta-glucans, respectively. In addition, the constituent monosaccharides of beta-glucans from colored Qingke cultivars were determined as arabinose, xylose, glucose, and galactose, and glucose was the dominant monosaccharide. Furthermore, colored Qingke beta-glucans exerted strong fat binding, cholesterol binding, and bile-acid binding capacities, as well as inhibitory activities on pancreatic lipase, which were much higher than those of white Qingke beta-glucans. Indeed, the fat binding, cholesterol binding, and bile-acid binding capacities, as well as the inhibitory activities on pancreatic lipase of Qingke beta-glucans were positively associated with their molecular weights and intrinsic viscosities. Results are beneficial for better understanding of the structure-function relationship of Qingke beta-glucans, and beta-glucans from colored Qingke cultivars (Ganyucang and Dingqing) could be further explored as functional food ingredients for prevention of obesity.
ESTHER : Guo_2018_Int.J.Biol.Macromol_120_2517
PubMedSearch : Guo_2018_Int.J.Biol.Macromol_120_2517
PubMedID: 30195000

Title : Rice DWARF14 acts as an unconventional hormone receptor for strigolactone - Yao_2018_J.Exp.Bot_69_2355
Author(s) : Yao R , Wang L , Li Y , Chen L , Li S , Du X , Wang B , Yan J , Li J , Xie D
Ref : J Exp Bot , 69 :2355 , 2018
Abstract : Strigolactones (SLs) act as an important class of phytohormones to regulate plant shoot branching, and also serve as rhizosphere signals to mediate interactions of host plants with soil microbes and parasitic weeds. SL receptors in dicots, such as DWARF14 in Arabidopsis (AtD14), RMS3 in pea, and ShHTL7 in Striga, serve as unconventional receptors that hydrolyze SLs into a D-ring-derived intermediate CLIM and irreversibly bind CLIM to trigger SL signal transduction. Here, we show that D14 from the monocot rice can complement Arabidopsis d14 mutant and interact with the SL signaling components in Arabidopsis. Our results further reveal that rice D14, similar to SL receptors in dicots, also serves as an unconventional hormone receptor that generates and irreversibly binds the active form of SLs. These findings uncover the conserved functions of D14 proteins in monocots and dicots.
ESTHER : Yao_2018_J.Exp.Bot_69_2355
PubMedSearch : Yao_2018_J.Exp.Bot_69_2355
PubMedID: 29365172

Title : Bushen recipe and its disassembled prescriptions inhibit inflammation of liver injury associated with Concanavalin A through Tolllike receptor 3\/9 signaling pathway - Nie_2018_Mol.Med.Rep_18_1682
Author(s) : Nie H , Mei Z , Wang R , Zhao B , Gao Y , Chen J , Wang L
Ref : Mol Med Rep , 18 :1682 , 2018
Abstract : The aim of the present study was to explore the effect of Bushen recipe and its disassembled prescriptions on liver injury and chronic hepatitis B. Liver injury was induced in normal and hepatitis B virus (HBV)transgenic mice through injection of Concanavalin A, followed by treatment with Bushen recipe and its disassembled prescriptions including the Bushenyang, the Bushenyin and the QingHua groups as well as the GanYanLing group (positive control). Subsequently, their liver function indexes were investigated by a microplate method and liver sections were blindly evaluated using an optical microscope by a pathologist. Subsequently, the activation state of Tolllike receptor (TLR)3/9 signaling pathway in liver tissues was analyzed by western blotting. Additionally, the inflammatory factors produced following liver injury in peripheral blood were detected via ELISA. Following intervention with the Bushen recipe and its disassembled prescriptions, the liver function indexe alanine aminotransferase had declined, whereas cholinesterase increased. The pathological alterations of liver tissue in HBV transgenic mice were reversed by Bushen recipe and its disassembled prescriptions. In addition, the TLR3/9 signaling pathway in liver tissues of HBV transgenic mice was inhibited and inflammatory factors such as interleukin (IL)6, IL1, tumor necrosis factoralpha and interferongamma were reduced significantly. In conclusion, the present study demonstrated that Bushen recipe and its disassembled prescriptions repaired liver injury induced by Concanavalin A through inhibition of TLR3/9 signaling pathway.
ESTHER : Nie_2018_Mol.Med.Rep_18_1682
PubMedSearch : Nie_2018_Mol.Med.Rep_18_1682
PubMedID: 29845244

Title : High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer - Luo_2018_Cancer.Biomark_21_461
Author(s) : Luo X , Hou N , Chen X , Xu Z , Xu J , Wang L , Yang S , Liu S , Xu L , Chen Y , Xiong L , Wang J , Fan W
Ref : Cancer Biomark , 21 :461 , 2018
Abstract : BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis.
ESTHER : Luo_2018_Cancer.Biomark_21_461
PubMedSearch : Luo_2018_Cancer.Biomark_21_461
PubMedID: 29171988

Title : Dioxin induces expression of hsa-miR-146b-5p in human neuroblastoma cells - Xu_2018_J.Environ.Sci.(China)_63_260
Author(s) : Xu T , Xie HQ , Li Y , Xia Y , Sha R , Wang L , Chen Y , Xu L , Zhao B
Ref : J Environ Sci (China) , 63 :260 , 2018
Abstract : Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3'-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.
ESTHER : Xu_2018_J.Environ.Sci.(China)_63_260
PubMedSearch : Xu_2018_J.Environ.Sci.(China)_63_260
PubMedID: 29406108

Title : Assessment of novel azaanthraquinone derivatives as potent multi-target inhibitors of inflammation and amyloid-beta aggregation in Alzheimer's disease - Wang_2018_Bioorg.Chem_83_477
Author(s) : Wang J , Li W , Qin J , Wang L , Wei S , Tang H
Ref : Bioorg Chem , 83 :477 , 2018
Abstract : A series of 6-substituted azaanthraquinone derivatives have been designed, synthesized, and their anti-inflammatory activities, antiaggregation effects on beta-amyloid proteins, anticholinesterase and neuroprotective activity were tested. The new derivatives strongly suppressed NO and iNOS production and modulate the production of cytokines by decreasing TNF-a, IL-1beta and IL-6 formation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Meanwhile, the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human b-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Abeta42 secretion levels. Moreover, the derivatives exhibited moderate inhibitory potency toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Further investigations indicated that compound 7b could attenuate H2O2-induced neurotoxicity toward SH-SY5Y neuroblastoma cells and half of the synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Taken together, azaanthraquinone derivatives targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD.
ESTHER : Wang_2018_Bioorg.Chem_83_477
PubMedSearch : Wang_2018_Bioorg.Chem_83_477
PubMedID: 30448726

Title : Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration - Kukreja_2018_J.Neurosci_38_6045
Author(s) : Kukreja L , Shahidehpour R , Kim G , Keegan J , Sadleir KR , Russell T , Csernansky J , Mesulam M , Vassar RJ , Wang L , Dong H , Geula C
Ref : Journal of Neuroscience , 38 :6045 , 2018
Abstract : Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) using tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43, which is placed downstream of the tetracycline response element. The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in postweaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3, and loss of neurons. The atrophy associated with tTA expression was rescuable by the tetracycline analog, doxycycline, in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration, and behavioral deficits in FTLD.SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing genes. Here, we report on a mouse model that overexpresses human TDP-43 using tTA and attempt to recapitulate features of TDP-43 pathology present in human FTLD. The tTA expression system is problematic, resulting in dramatic degeneration of the hippocampus. Thus, our study adds a note of caution for the use of the tTA system. However, because FTLD is primarily characterized by cortical degeneration and our mouse model shows significant atrophy in most cortical areas due to human TDP-43 overexpression, our animal model remains useful for providing critical insight on this human disease.
ESTHER : Kukreja_2018_J.Neurosci_38_6045
PubMedSearch : Kukreja_2018_J.Neurosci_38_6045
PubMedID: 29807909

Title : Repellent action and contact toxicity mechanisms of the essential oil extracted from Chinese chive against Plutella xylostella larvae - Gao_2018_Arch.Insect.Biochem.Physiol__e21509
Author(s) : Gao Q , Song L , Sun J , Cao HQ , Wang L , Lin H , Tang F
Ref : Archives of Insect Biochemistry & Physiology , :e21509 , 2018
Abstract : Botanical pesticides play increasingly important roles in the control of agricultural pests. In this study, the insecticidal effects, specifically the repellent action and contact toxicity, of the essential oil extracted from Chinese chive (EOC) against Plutella xylostella larvae were confirmed. The mechanisms of repellent's action were studied using electroantennograms (EAGs), and the effects on glutathione S-transferase (GST), carboxylesterase (CarE), and acetyl cholinesterase were investigated after EOC treatments. The EOC affected the EAG results and inhibited the activities of GST and CarE in treated P. xylostella larvae, which could explain its insecticidal effects. And, four pyrazines showed greater repellent activities than that of the EOC, which was confirmed as the main active compounds of EOC.
ESTHER : Gao_2018_Arch.Insect.Biochem.Physiol__e21509
PubMedSearch : Gao_2018_Arch.Insect.Biochem.Physiol__e21509
PubMedID: 30390324

Title : Online screening of acetylcholinesterase inhibitors in natural products using monolith-based immobilized capillary enzyme reactors combined with liquid chromatography-mass spectrometry - Wang_2018_J.Chromatogr.A_1563_135
Author(s) : Wang L , Zhao Y , Zhang Y , Zhang T , Kool J , Somsen GW , Wang Q , Jiang Z
Ref : Journal of Chromatography A , 1563 :135 , 2018
Abstract : In order to develop a direct and reliable method for discovering lead compounds from traditional Chinese medicines (TCMs), a comparative online ligand fishing platform was developed using immobilized capillary enzyme reactors (ICERs) in combination with liquid chromatography-mass spectrometry (LC-MS). Methacrylate-based monolithic capillaries (400mum I.D.x10cm) containing epoxy reactive groups were used as support to immobilize the target enzyme acetylcholinesterase (AChE). The activity and kinetic parameters of the AChE-ICER were investigated using micro-LC-UV. Subsequently, ligand fishing and identification from mixtures was carried out using the complete AChE-ICER-LC-MS platform. For efficient distinction of true actives from false positives, highly automated comparative analyses were run alternatingly using AChE-ICERs and negative control-ICERs, both online installed in the system. After washing unbound compounds to the waste, bound ligands were eluted from the AChE-ICER to a trapping loop using a denaturing solution. The trapped ligands were further separated and identified using LC-MS. Non-specific binding to the monolith support or non-functional sites of the immobilized enzyme was investigated by exposing analytes to the negative control-ICER. The specificity of the proposed approach was verified by analyzing a known AChE inhibitor in the presence of an inactive compound. The platform was applied to screen for AChE inhibitors in extracts of Corydalis yanhusuo. Eight compounds (columbamine, jatrorrhizine, coptisine, palmatine, berberine, dehydrocorydaline, tetrahydropalmatine and corydaline) with AChE binding affinity were detected and identified, and their AChE inhibitory activities were further verified by an in vitro enzymatic inhibition assay. Experimental results show that the proposed comparative online ligand fishing platform is suitable for rapid screening and mass-selective detection of AChE inhibitors in complex mixtures.
ESTHER : Wang_2018_J.Chromatogr.A_1563_135
PubMedSearch : Wang_2018_J.Chromatogr.A_1563_135
PubMedID: 29866504

Title : Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease - Hu_2018_Alzheimers.Dement.(N.Y)_4_542
Author(s) : Hu Z , Wang L , Ma S , Kirisci L , Feng Z , Xue Y , Klunk WE , Kamboh MI , Sweet RA , Becker J , Lv Q , Lopez OL , Xie XQ
Ref : Alzheimers Dement (N Y) , 4 :542 , 2018
Abstract : Introduction: We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping. Methods: We compared the effect of aHTN drugs on Mini-Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects. Results: The combination of diuretics, calcium channel blockers, and renin-angiotensin-aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (Deltabeta = +1.46, P < .0001). aHTN medications slow down cognitive decline in ChEI users (Deltabeta = +0.56, P = .006), but not in non-ChEI users (Deltabeta = -0.31, P = .53). Discussion: aHTN and ChEI drugs showed synergistic effects. A combination of diuretics, renin-angiotensin-aldosterone system blockers, and calcium channel blockers had the slowest cognitive decline. The chemogenomics systems pharmacology-identified molecular targets provide system pharmacology interpretation of the synergism of the drugs in clinics. The results suggest that improving vascular health is essential for AD treatment and provide a novel direction for AD drug development.
ESTHER : Hu_2018_Alzheimers.Dement.(N.Y)_4_542
PubMedSearch : Hu_2018_Alzheimers.Dement.(N.Y)_4_542
PubMedID: 30386819

Title : First demonstration of in vivo mapping for regional brain monoacylglycerol lipase using PET with [(11)C]SAR127303 - Yamasaki_2018_Neuroimage_176_313
Author(s) : Yamasaki T , Mori W , Zhang Y , Hatori A , Fujinaga M , Wakizaka H , Kurihara Y , Wang L , Nengaki N , Ohya T , Liang SH , Zhang MR
Ref : Neuroimage , 176 :313 , 2018
Abstract : Monoacylglycerol lipase (MAGL) is a main regulator of the endocannabinoid system within the central nervous system (CNS). Recently, [(11)C]SAR127303 was developed as a promising radioligand for MAGL imaging. In this study, we aimed to quantify regional MAGL concentrations in the rat brain using positron emission tomography (PET) with [(11)C]SAR127303. An irreversible two-tissue compartment model (2-TCMi, k4=0) analysis was conducted to estimate quantitative parameters (k3, Ki(2-TCMi), and lambdak3). These parameters were successfully obtained with high identifiability (<10 %COV) for the following regions ranked in order from highest to lowest: cingulate cortex>striatum>hippocampus>thalamus>cerebellum>hypothalamus approximately pons. In vitro autoradiographs using [(11)C]SAR127303 showed a heterogeneous distribution of radioactivity, as seen in the PET images. The Ki(2-TCMi) and lambdak3 values correlated relatively highly with in vitro binding (r>0.4, P<0.005). The Ki(2-TCMi) values showed high correlation and low underestimation (<10%) compared with the slope of a Patlak plot analysis with linear regression (Ki(Patlak)). In conclusion, we successfully estimated regional net uptake value of [(11)C]SAR127303 reflecting MAGL concentrations in rat brain regions for the first time.
ESTHER : Yamasaki_2018_Neuroimage_176_313
PubMedSearch : Yamasaki_2018_Neuroimage_176_313
PubMedID: 29738910

Title : Association between FASN gene polymorphisms ultrasound carcass traits and intramuscular fat in Qinchuan cattle - Raza_2018_Gene_645_55
Author(s) : Raza SHA , Gui L , Khan R , Schreurs NM , Xiaoyu W , Wu S , Mei C , Wang L , Ma X , Wei D , Guo H , Zhang S , Wang X , Kaleri HA , Zan L
Ref : Gene , 645 :55 , 2018
Abstract : Fatty acid synthase (FASN) is an enzyme involved with fat deposition and fatty acid composition in cattle. This study was conducted to detect single nucleotide polymorphisms (SNPs) of the FASN gene and explore their relationships with ultrasound carcass traits in order to assess the potential use of the FASN gene for the breeding selection of Qinchuan cattle for desirable carcass traits. The frequencies of SNP g.12740C>T, g.13192T>C and g.13232C>T were identified in 525 individual Qinchuan cattle which were also assessed for backfat depth, eye muscle area and intramuscular fat by ultrasound. According to the PIC values, g.13192T>C possessed an intermediate polymorphism (0.25T, g.12740C>T possessed low polymorphism (PIC<0.25). Chi-square tests showed that g.13192T>C were in Hardy-Weinberg disequilibrium (c2C was associated with a greater eye muscle area and the TT genotype at g.13232C>T was associated with greater intramuscular fat. When these genotypes were combined there was no difference in eye muscle area and intramuscular fat between the diplotypes. The H2H2 diplotype was associated with carcass traits that are likely to provide economic advantage in Qinchuan cattle. Variations in the FASN genes and their corresponding genotypes may be considered as molecular markers for economic traits in cattle breeding.
ESTHER : Raza_2018_Gene_645_55
PubMedSearch : Raza_2018_Gene_645_55
PubMedID: 29273553
Gene_locus related to this paper: bovin-fas

Title : Effects of P-Glycoprotein on the Transport of DL0410, a Potential Multifunctional Anti-Alzheimer Agent - Pang_2017_Molecules_22_2
Author(s) : Pang X , Wang L , Kang , Zhao Y , Wu S , Liu AL , Du GH
Ref : Molecules , 22 : , 2017
Abstract : In our study, we attempted to investigate the influences of P-glycoprotein (P-gp) on DL0410, a novel synthetic molecule for Alzheimer's disease (AD) treatment, for intestinal absorption and blood-brain barrier permeability in vitro and related binding mechanisms in silico. Caco-2, MDCK, and MDCK-MDR1 cells were utilized for transport studies, and homology modelling of human P-gp was built for further docking study to uncover the binding mode of DL0410. The results showed that the apparent permeability (Papp) value of DL0410 was approximately 1 x 10(-6) cm/s, indicating the low permeability of DL0410. With the presence of verapamil, the directional transport of DL0410 disappeared in Caco-2 and MDCK-MDR1 cells, suggesting that DL0410 should be a substrate of P-gp, which was also confirmed by P-gp ATPase assay. In addition, DL0410 could competitively inhibit the transport of Rho123, a P-gp known substrate. According to molecular docking, we also found that DL0410 could bind to the drug binding pocket (DBP), but not the nucleotide binding domain (NBD). In conclusion, DL0410 was a substrate as well as a competitive inhibitor of P-gp, and P-gp had a remarkable impact on the intestine and brain permeability of DL0410, which is of significance for drug research and development.
ESTHER : Pang_2017_Molecules_22_2
PubMedSearch : Pang_2017_Molecules_22_2
PubMedID: 28757552

Title : Design, Synthesis, and Biological Evaluation of a New Series of Biphenyl\/Bibenzyl Derivatives Functioning as Dual Inhibitors of Acetylcholinesterase and Butyrylcholinesterase - Wang_2017_Molecules_22_
Author(s) : Wang DM , Feng B , Fu H , Liu AL , Wang L , Du GH , Wu S
Ref : Molecules , 22 : , 2017
Abstract : Alzheimer's disease (AD), the most common form of dementia in adults, is a progressive neurodegenerative disorder of the brain characterized by loss of memory and steady deterioration of cognition. Here, a series of symmetrical molecules containing biphenyl/bibenzyl scaffolds (12-36) were designed, synthesized, and evaluated for their ability to inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A biological evaluation showed that most of these biphenyl derivatives were potent AChE and BuChE inhibitors. Among them, compound 15 displayed the greatest ability to inhibit BuChE (IC50 = 0.74 microM) and was also a good AChE inhibitor (IC50 = 1.18 microM). Compound 19 was not only a potent AChE inhibitor (IC50 = 0.096 microM), but also a mild BuChE inhibitor (IC50 =1.25 microM). Overall, these results suggested that compound 19 may be a promising agent in the treatment of AD.
ESTHER : Wang_2017_Molecules_22_
PubMedSearch : Wang_2017_Molecules_22_
PubMedID: 28117700

Title : ANNALS EXPRESS: Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China - Dai_2017_Ann.Clin.Biochem__4563217738801
Author(s) : Dai Y , Liu J , Yuan E , Lee Y , Wang Q , Jia L , Wang L , Su Y
Ref : Annals of Clinical Biochemistry , :4563217738801 , 2017
Abstract : AIMS: Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish essential to establish reference intervals for a range of analytes during pregnancy.
METHODS: The cross-sectional study was performed in 13656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analyzed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method.
RESULTS: Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid, and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, beta2-microglobulin, and cystatin-C fell significantly during the first trimestersand then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established.
CONCLUSIONS: The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.
ESTHER : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedSearch : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedID: 29153025

Title : Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy - Hu_2017_Nature_552_248
Author(s) : Hu J , Dziumbla S , Lin J , Bibli SI , Zukunft S , de Mos J , Awwad K , Fromel T , Jungmann A , Devraj K , Cheng Z , Wang L , Fauser S , Eberhart CG , Sodhi A , Hammock BD , Liebner S , Muller OJ , Glaubitz C , Hammes HP , Popp R , Fleming I
Ref : Nature , 552 :248 , 2017
Abstract : Diabetic retinopathy is an important cause of blindness in adults, and is characterized by progressive loss of vascular cells and slow dissolution of inter-vascular junctions, which result in vascular leakage and retinal oedema. Later stages of the disease are characterized by inflammatory cell infiltration, tissue destruction and neovascularization. Here we identify soluble epoxide hydrolase (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid, derived from docosahexaenoic acid. The expression of sEH and the accumulation of 19,20-dihydroxydocosapentaenoic acid were increased in diabetic mouse retinas and in the retinas and vitreous humour of patients with diabetes. Mechanistically, the diol targeted the cell membrane to alter the localization of cholesterol-binding proteins, and prevented the association of presenilin 1 with N-cadherin and VE-cadherin, thereby compromising pericyte-endothelial cell interactions and inter-endothelial cell junctions. Treating diabetic mice with a specific sEH inhibitor prevented the pericyte loss and vascular permeability that are characteristic of non-proliferative diabetic retinopathy. Conversely, overexpression of sEH in the retinal Muller glial cells of non-diabetic mice resulted in similar vessel abnormalities to those seen in diabetic mice with retinopathy. Thus, increased expression of sEH is a key determinant in the pathogenesis of diabetic retinopathy, and inhibition of sEH can prevent progression of the disease.
ESTHER : Hu_2017_Nature_552_248
PubMedSearch : Hu_2017_Nature_552_248
PubMedID: 29211719

Title : O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3 - Wu_2017_J.Biol.Chem_292_10014
Author(s) : Wu D , Zhao L , Feng Z , Yu C , Ding J , Wang L , Wang F , Liu D , Zhu H , Xing F , Conaway JW , Conaway RC , Cai Y , Jin J
Ref : Journal of Biological Chemistry , 292 :10014 , 2017
Abstract : The human males absent on the first (MOF)-containing histone acetyltransferase nonspecific lethal (NSL) complex comprises nine subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase, isoform 1 (OGT1). However, whether the O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remain unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3. Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8. Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex. Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3. In addition, wheat germ agglutinin affinity purification verified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O-GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3. This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1(C964A), that lacks O-GlcNAc transferase activity. Furthermore, stabilization of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4 Lys-5, Lys-8, and Lys-16 in cells. These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3.
ESTHER : Wu_2017_J.Biol.Chem_292_10014
PubMedSearch : Wu_2017_J.Biol.Chem_292_10014
PubMedID: 28450392
Gene_locus related to this paper: human-KANSL3

Title : Simultaneous detection of dual biomarkers from humans exposed to organophosphorus pesticides by combination of immunochromatographic test strip and ellman assay - Yang_2017_Biosens.Bioelectron_104_39
Author(s) : Yang M , Zhao Y , Wang L , Paulsen M , Simpson CD , Liu F , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 104 :39 , 2017
Abstract : A novel sandwich immunoassay based immunochromatographic test strip (ICTS) has been developed for simultaneously measuring both butyrylcholinesterase (BChE) activity and the total amount of BChE (including inhibited and active enzyme) from 70 muLpost-exposure human plasma sample. The principle of this method is based on the BChE monoclonal antibody (MAb) capable of acting as both capture antibody and detection antibody. The BChE MAb which was immobilized on the test line was able to recognize both organophosphorus BChE adducts (OP-BChE) and BChE and provided equal binding affinity, permitting detection of the total enzyme amount in post-exposure human plasma samples. The formed immunocomplexes on the test line can further be excised from the test-strip for subsequent off-line measurement of BChE activity using the Ellman assay. Therefore, dual biomarkers of BChE activity and phosphorylation (OP-BChE) will be obtained simultaneously. The whole sandwich-immunoassay was performed on one ICTS, greatly reducing analytical time. The ICTS sensor showed excellent linear responses for assaying total amount of BChE and active BChE ranging from 0.22 to 3.58nM and 0.22-7.17nM, respectively. Both the signal detection limits are 0.10nM. We validated the practical application of the proposed method to measure 124 human plasma samples from orchard workers and cotton farmers with long-term exposure to organophosphorus pesticides (OPs). The results were in highly agreement with LC/MS/MS which verified our method is extremely accurate. Combining the portability and rapidity of test strip and the compatibility of BChE MAb as both capture antibody and detection antibody, the developed method provides a baseline-free, low-cost and rapid tool for in-field monitoring of OP exposures.
ESTHER : Yang_2017_Biosens.Bioelectron_104_39
PubMedSearch : Yang_2017_Biosens.Bioelectron_104_39
PubMedID: 29306031

Title : The sea cucumber genome provides insights into morphological evolution and visceral regeneration - Zhang_2017_PLoS.Biol_15_e2003790
Author(s) : Zhang X , Sun L , Yuan J , Sun Y , Gao Y , Zhang L , Li S , Dai H , Hamel JF , Liu C , Yu Y , Liu S , Lin W , Guo K , Jin S , Xu P , Storey KB , Huan P , Zhang T , Zhou Y , Zhang J , Lin C , Li X , Xing L , Huo D , Sun M , Wang L , Mercier A , Li F , Yang H , Xiang J
Ref : PLoS Biol , 15 :e2003790 , 2017
Abstract : Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.
ESTHER : Zhang_2017_PLoS.Biol_15_e2003790
PubMedSearch : Zhang_2017_PLoS.Biol_15_e2003790
PubMedID: 29023486
Gene_locus related to this paper: stija-a0a2g8k9s2 , stija-a0a2g8ka54 , stija-a0a2g8jd52 , stija-a0a2g8l0w8

Title : Hepatotoxicity induced by radix Sophorae tonkinensis in mice and increased serum cholinesterase as a potential supplemental biomarker for liver injury - Wang_2017_Exp.Toxicol.Pathol_69_193
Author(s) : Wang L , Lu J , Sun W , Gu Y , Zhang C , Jin R , Li L , Zhang Z , Tian X
Ref : Exp Toxicol Pathol , 69 :193 , 2017
Abstract : Radix Sophorae tonkinensis (S. tonkinensis) is used in Chinese folk medicine to treat sore throats, viral hepatitis, and jaundice. However, little is known about the hepatotoxicity induced by it. This study is to investigate hepatotoxicity induced by radix S. tonkinensis and a potential supplemental biomarker for liver injury through acute toxicity, accumulative toxicity, tolerance test, and sub-chronic toxicity. The contents of cytisine (CYT), matrine (MT), and oxymatrine (OMT) in radix S. tonkinensis extracts were determined simultaneously by the method we developed. In the acute toxicity study, mice were scheduled for single oral gavage at doses of 0, 2.4, 3.2, 4.2, 5.6, 7.5g/kg of radix S. tonkinensis extracts respectively. Another three groups of mice received radix S. tonkinensis extracts orally in single doses of 0, 4.3, 5.6g/kg, while the two groups of the hepatic injury model were induced by intraperitoneal injection with 0.1% and 0.2% carbon tetrachloride (CCl4). Mortality rate, analysis of serum biochemistry, and histopathological examination were used to assess the acute toxicity. In the accumulative toxicity study, mice were treated radix S. tonkinensis extracts orally by the method of dose escalation for 20days respectively. Accumulative toxicity was assessed by mortality rate. In the tolerance test, half of the mice of test group in the accumulative toxicity were administered the dose of 4.3g/kg radix S. tonkinensis extracts, and the rest of the mice in the test group were assigned to receive the dose of 5.6g/kg radix S. tonkinensis extracts. In the sub-chronic toxicity study, mice were treated with daily doses of 0, 0.25, 1.0, 2.5g/kg radix S. tonkinensis extracts for 90days. Assessments of body weights, serum biochemical analysis, and histopathological examination were performed. An enzyme-inhibition assay for butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) of CYT, MT, and OMT was also carried out. The contents of CYT, MT, and OMT in radix S. tonkinensis extracts were 5.63mg/g, 27.63mg/g, and 16.20mg/g respectively. In the acute toxicity study, LD50 of radix S. tonkinensis extracts was 4.3g/kg. No mice were found dead in the accumulative toxicity study. In the acute toxicity and tolerance test, increased ALT, AST, and CHE levels were observed in a dose-response manner, while the severity of histological changes in liver was shown in a dose-dependent mode. In the sub-chronic toxicity, though there was a decline trend of ALT and AST levels found in 0.25g/kg, 1.0g/kg, and 2.5g/kg radix S. tonkinensis extracts as compared to control, which might be related to weight loss, the severity of histopathological changes in the liver and the increased serum CHE level was shown in a dose-response manner. MT, OMT, and CYT showed inhibitory effects on BuChE and AChE in the enzyme-inhibition assay. The results of this study indicate that radix S. tonkinensis should have hepatotoxicity, and increased serum CHE is a potential supplemental biomarker for liver injury.
ESTHER : Wang_2017_Exp.Toxicol.Pathol_69_193
PubMedSearch : Wang_2017_Exp.Toxicol.Pathol_69_193
PubMedID: 28126209

Title : Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease - Li_2017_J.Alzheimers.Dis_56_1403
Author(s) : Li L , Xu S , Liu L , Feng R , Gong Y , Zhao X , Li J , Cai J , Feng N , Wang L , Wang X , Peng Y
Ref : J Alzheimers Dis , 56 :1403 , 2017
Abstract : The dyshomeostasis of transition metal ions, accumulation of amyloid-beta (Abeta) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Abeta species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Abeta aggregation in vitro and showed disassembly of Abeta aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Abeta25-35 were studied in rats. Compared to sham group, Abeta25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-alpha and IL-1beta). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Abeta25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-alpha and IL-1beta release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1beta production, but failed to block astrocyte activation and TNF-alpha production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD.
ESTHER : Li_2017_J.Alzheimers.Dis_56_1403
PubMedSearch : Li_2017_J.Alzheimers.Dis_56_1403
PubMedID: 28157092

Title : DWARF14, A Receptor Covalently Linked with the Active Form of Strigolactones, Undergoes Strigolactone-Dependent Degradation in Rice - Hu_2017_Front.Plant.Sci_8_1935
Author(s) : Hu Q , He Y , Wang L , Liu S , Meng X , Liu G , Jing Y , Chen M , Song X , Jiang L , Yu H , Wang B , Li J
Ref : Front Plant Sci , 8 :1935 , 2017
Abstract : Strigolactones (SLs) are the latest confirmed phytohormones that regulate shoot branching by inhibiting bud outgrowth in higher plants. Perception of SLs depends on a novel mechanism employing an enzyme-receptor DWARF14 (D14) that hydrolyzes SLs and becomes covalently modified. This stimulates the interaction between D14 and D3, leading to the ubiquitination and degradation of the transcriptional repressor protein D53. However, the regulation of SL perception in rice remains elusive. In this study, we provide evidences that D14 is ubiquitinated after SL treatment and degraded through the 26S proteasome system. The Lys280 site of the D14 amino acid sequence was important for SL-induced D14 degradation, but did not change the subcellular localization of D14 nor disturbed the interaction between D14 and D3, nor D53 degradation. Biochemical and genetic analysis indicated that the key amino acids in the catalytic center of D14 were essential for D14 degradation. We further showed that D14 degradation is dependent on D3 and is tightly correlated with protein levels of D53. These findings revealed that D14 degradation takes place following D53 degradation and functions as an important feedback regulation mechanism of SL perception in rice.
ESTHER : Hu_2017_Front.Plant.Sci_8_1935
PubMedSearch : Hu_2017_Front.Plant.Sci_8_1935
PubMedID: 29170677

Title : Aii810, a Novel Cold-Adapted N-Acylhomoserine Lactonase Discovered in a Metagenome, Can Strongly Attenuate Pseudomonas aeruginosa Virulence Factors and Biofilm Formation - Fan_2017_Front.Microbiol_8_1950
Author(s) : Fan X , Liang M , Wang L , Chen R , Li H , Liu X
Ref : Front Microbiol , 8 :1950 , 2017
Abstract : The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti-infection therapeutic strategy that does not rely on antibiotics. Here, a novel gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao-tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the highest activity at 20 degrees C, and it maintained 76.5% of activity at 0 degrees C and more than 50% activity at 0-40 degrees C. The optimal pH was 8.0. It was stable in both neutral and slightly alkaline conditions and at temperatures below 40 degrees C. The enzyme hydrolyzed several rho-nitrophenyl esters, but its best substrate was rho-nitrophenyl acetate. Its kcat and Km values were 347.7 S(-1) and 205.1 muM, respectively. It efficiently degraded N-butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, exceeding hydrolysis rates of 72.3 and 100%, respectively. Moreover, Aii810 strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase reported, which makes it an attractive enzyme for use as a therapeutic agent against P. aeruginosa infection.
ESTHER : Fan_2017_Front.Microbiol_8_1950
PubMedSearch : Fan_2017_Front.Microbiol_8_1950
PubMedID: 29067011
Gene_locus related to this paper: 9bact-Aii810

Title : The Synergistic Effect of Microwave Radiation and Hypergravity on Rats and the Intervention Effect of Rana Sylvatica Le Conte Oil - Sun_2017_Dose.Response_15_1559325817711511
Author(s) : Sun W , Yang Y , Yu H , Wang L , Pan S
Ref : Dose Response , 15 :1559325817711511 , 2017
Abstract : AIM: The phenomena of hypergravity and microwave radiation are widespread, which cause more and more concern for the hazards to human health. The aim of this study was to investigate the synergistic effect of microwave radiation and hypergravity on rats and observe the protective effect of Rana sylvatica Le conte oil.
METHODS: Rats were exposed to microwave radiation and hypergravity, and the rat weight, the climbing pole height, serum enzyme activities, blood urea nitrogen concentration, and total antioxidant capacity were detected.
RESULTS: The climbing pole height, the activities of choline acetyl transferase and cholinesterase, and the total antioxidant capacity decreased, whereas the activities of alanine aminotransferase, aspartate aminotransferase, areatine kinase, isocitric dehydrogenase, hydroxybutyrate dehydrogenase, and the blood urea nitrogen concentration increased in the hypergravity irradiation group as compared with the others. CONCLUSION: These results imply that the motion and nervous system of rats might be affected critically by the synergistic effect of microwave radiation and hypergravity, and it causes damage to most rat organs, such as the bone, skeletal muscle, liver, heart, and kidney, and the antioxidant effect is also damaged, while the injury resulted from it could be protected by Rana sylvatica Le conte oil.
ESTHER : Sun_2017_Dose.Response_15_1559325817711511
PubMedSearch : Sun_2017_Dose.Response_15_1559325817711511
PubMedID: 28717348

Title : Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells - Pan_2017_Sci.Rep_7_44440
Author(s) : Pan H , Zhang X , Jiang H , Jiang X , Wang L , Qi Q , Bi Y , Wang J , Shi Q , Li R
Ref : Sci Rep , 7 :44440 , 2017
Abstract : The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3(+/-) germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse.
ESTHER : Pan_2017_Sci.Rep_7_44440
PubMedSearch : Pan_2017_Sci.Rep_7_44440
PubMedID: 28290521

Title : Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer's Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches - Pang_2017_Molecules_22_
Author(s) : Pang X , Fu H , Yang S , Wang L , Liu AL , Wu S , Du GH
Ref : Molecules , 22 : , 2017
Abstract : DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer's disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR) models were performed. The R(2) of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future.
ESTHER : Pang_2017_Molecules_22_
PubMedSearch : Pang_2017_Molecules_22_
PubMedID: 28933746

Title : Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors - Wang_2017_Bioorg.Med.Chem_25_360
Author(s) : Wang L , Wang Y , Tian Y , Shang J , Sun X , Chen H , Wang H , Tan W
Ref : Bioorganic & Medicinal Chemistry , 25 :360 , 2017
Abstract : A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer's disease (AD) treatment.
ESTHER : Wang_2017_Bioorg.Med.Chem_25_360
PubMedSearch : Wang_2017_Bioorg.Med.Chem_25_360
PubMedID: 27856236

Title : The cholinergic immune regulation mediated by a novel muscarinic acetylcholine receptor through TNF pathway in oyster Crassostrea gigas - Liu_2016_Dev.Comp.Immunol_65_139
Author(s) : Liu Z , Zhou Z , Wang L , Dong W , Qiu L , Song L
Ref : Dev Comp Immunol , 65 :139 , 2016
Abstract : Muscarinic receptors, which selectively take muscarine as their ligand, are critical for the immunological and physiological processes in animals. In the present study, the open region frame (ORF) of a homologue of muscarinic acetylcholine (ACh) receptor (mAChR) was amplified from oyster Crassostrea gigas (named as CgmAChR-1), whose full length was 1983 bp and the protein it encoded contained 660 amino acids with a seven transmembrane region. Phylogeny analysis suggested that CgmAChR-1 shared homology with M5 muscarinic receptor found in invertebrates including Habropoda laboriosa, Acromyrmex echinatior and Echinococcus granulosus. After cell transfection of CgmAChR-1 into HEK293T cells and ACh incubation, the level of intracellular Ca(2+) and cAMP increased significantly (p < 0.05). Such trend could be reverted with the addition of M3 and M5 muscarinic receptor antagonists DAMP and DAR. The CgmAChR-1 transcripts were ubiquitously detectable in seven different tissues with the maximal expression level in adductor muscle. When the oysters received LPS stimulation, CgmAChR-1 mRNA expression in haemocyte was increased to the highest level (6.05-fold, p < 0.05) at 24 h, while blocking CgmAChR-1 using receptor antagonists before LPS stimulation promoted the expression of oyster TNF, resulting in the increase of haemocyte apoptosis index. These results suggested that CgmAChR-1 was the key molecule in cholinergic neuroendocrine-immune system contributing to the regulation of TNF expression and apoptosis process.
ESTHER : Liu_2016_Dev.Comp.Immunol_65_139
PubMedSearch : Liu_2016_Dev.Comp.Immunol_65_139
PubMedID: 27394930

Title : New perspectives for multi-level regulations of neuronal acetylcholinesterase by dioxins - Xie_2016_Chem.Biol.Interact_259_286
Author(s) : Xie HQ , Xu T , Chen Y , Li Y , Xia Y , Xu SL , Wang L , Tsim KWK , Zhao B
Ref : Chemico-Biological Interactions , 259 :286 , 2016
Abstract : Acetylcholinesterase (AChE; EC 3.1.1.7) is a vital functional enzyme in cholinergic neurotransmission which can rapidly hydrolyze the neurotransmitter, acetylcholine, in the central and peripheral nervous systems. Emerging evidence showed that in addition to classical environmental AChE inhibitors, such as organophosphate and carbamate pesticides, dioxins are a new type of xenobiotic causing impairment of AChE. Dioxin can transcriptionally or post-transcriptionally suppress AChE expression in human neuroblastoma cells or mouse immune cells via the aryl hydrocarbon receptor (AhR) pathway, respectively. Dioxins affect gene expression through multiple mechanisms, such as cross-talk with other signaling cascades and epigenetic modulations. Therefore, in this review, by summarizing the known mechanisms of AChE regulation and dioxin-induced gene alterations, additional potential signaling cascades and epigenetic mechanisms are proposed for dioxin-induced changes in neuronal AChE. Mitogen activated protein (MAP) kinase, 3'-5'-cyclic adenosine monophosphate (cAMP) and calcium-related pathways, as well as potential epigenetic mechanisms, such as DNA methylation, and post-transcriptional regulation via microRNAs, including hsa-miR-132, hsa-miR-212 and hsa-miR-25-3p are discussed in here. These proposed mechanisms may be invaluable not only to promote comprehensive understanding of the action mechanisms for dioxin, but to illustrate the molecular basis of dioxin-induced health impacts.
ESTHER : Xie_2016_Chem.Biol.Interact_259_286
PubMedSearch : Xie_2016_Chem.Biol.Interact_259_286
PubMedID: 27374124

Title : Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation - Wu_2016_Eur.J.Med.Chem_121_864
Author(s) : Wu MY , Esteban G , Brogi S , Shionoya M , Wang L , Campiani G , Unzeta M , Inokuchi T , Butini S , Marco-Contelles J
Ref : Eur Journal of Medicinal Chemistry , 121 :864 , 2016
Abstract : Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a new series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f exhibited moderate antioxidant properties as found by in vitro assessment. This compound represents a novel donepezil-hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD.
ESTHER : Wu_2016_Eur.J.Med.Chem_121_864
PubMedSearch : Wu_2016_Eur.J.Med.Chem_121_864
PubMedID: 26471320

Title : Adhesions of extracellular surface-layer associated proteins in Lactobacillus M5-L and Q8-L - Zhang_2016_J.Dairy.Sci_99_1011
Author(s) : Zhang Y , Xiang X , Lu Q , Zhang L , Ma F , Wang L
Ref : J Dairy Sci , 99 :1011 , 2016
Abstract : Surface-layer associated proteins (SLAP) that envelop Lactobacillus paracasei ssp. paracasei M5-L and Lactobacillus casei Q8-L cell surfaces are involved in the adherence of these strain to the human intestinal cell line HT-29. To further elucidate some of the properties of these proteins, we assessed the yields and expressions of SLAP under different incubation conditions. An efficient and selective extraction of SLAP was obtained when cells of Lactobacillus were treated with 5 M LiCl at 37 degrees C in aerobic conditions. The SLAP of Lactobacillus M5-L and Q8-L in cell extracts were visualized by SDS-PAGE and identified by Western blotting with sulfo-N-hydroxysuccinimide-biotin-labeled HT-29 cells as adhesion proteins. Atomic force microscopy contact imaging revealed that Lactobacillus strains M5-L and Q8-L normally display a smooth, homogeneous surface, whereas the surfaces of M5-L and Q8-L treated with 5 M LiCl were rough and more heterogeneous. Analysis of adhesion forces revealed that the initial adhesion forces of 1.41 and 1.28 nN obtained for normal Lactobacillus M5-L and Q8-L strains, respectively, decreased to 0.70 and 0.48 nN, respectively, following 5 M LiCl treatment. Finally, the dominant 45-kDa protein bands of Lactobacillus Q8-L and Lactobacillus M5-L were identified as elongation factor Tu and surface antigen, respectively, by liquid chromatography-tandem mass spectrometry.
ESTHER : Zhang_2016_J.Dairy.Sci_99_1011
PubMedSearch : Zhang_2016_J.Dairy.Sci_99_1011
PubMedID: 26709174
Gene_locus related to this paper: lacpl-LP.0796

Title : Multitarget-directed oxoisoaporphine derivatives: Anti-acetylcholinesterase, anti-beta-amyloid aggregation and enhanced autophagy activity against Alzheimer's disease - Wei_2016_Bioorg.Med.Chem_24_6031
Author(s) : Wei S , Chen W , Qin J , Huangli Y , Wang L , Shen Y , Tang H
Ref : Bioorganic & Medicinal Chemistry , 24 :6031 , 2016
Abstract : A series of 8- and 11-substituted oxoisoaporphine derivatives have been designed, synthesized, and tested for their ability to inhibit cholinesterase (ChE) in vitro and in vivo, and self-induced beta-amyloid (Abeta) aggregation. Their autophagy activity and blood-brain barrier (BBB) permeability were also assessed. The new derivatives exhibited high AChE inhibitory activity in vivo and in intro. Over half the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Abeta aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Abeta secretion levels. Moreover, one-third of the synthetic compounds were predicted to be able to cross the BBB to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Compounds 5b and 6b were chosen for assessing their autophagy activity. The fluorescence intensity of the BC12921 was decreased significantly after treatment with compounds. The result encourages us to study such compounds thoroughly and systematically.
ESTHER : Wei_2016_Bioorg.Med.Chem_24_6031
PubMedSearch : Wei_2016_Bioorg.Med.Chem_24_6031
PubMedID: 27720328

Title : Draft Genome Sequence of Aspergillus niger Strain An76 - Gong_2016_Genome.Announc_4_e01700
Author(s) : Gong W , Cheng Z , Zhang H , Liu L , Gao P , Wang L
Ref : Genome Announc , 4 : , 2016
Abstract : The filamentous fungus Aspergillus niger has become one of the most important fungi in industrial biotechnology, and it can efficiently secrete both polysaccharide-degrading enzymes and organic acids. We report here the 6,074,961,332-bp draft sequence of A. niger strain An76, and the findings provide important information related to its lignocellulose-degrading ability.
ESTHER : Gong_2016_Genome.Announc_4_e01700
PubMedSearch : Gong_2016_Genome.Announc_4_e01700
PubMedID: 26893421
Gene_locus related to this paper: aspna-g3y5a6 , aspna-g3xpw9 , aspkw-g7xq95 , aspng-a0a100iew6 , asptc-a0a1l9nby7 , aspng-a0a100i8t9

Title : Effects of Light Intensity and Color on the Biomass, Extracellular Red Pigment, and Citrinin Production of Monascus ruber - Wang_2016_J.Agric.Food.Chem_64_9506
Author(s) : Wang L , Dai Y , Chen W , Shao Y , Chen F
Ref : Journal of Agricultural and Food Chemistry , 64 :9506 , 2016
Abstract : Light is a crucial environmental signal for fungi. In this work, the effects of different light intensities and colors on biomass, Monascus pigments (MPs) and citrinin production of Monascus ruber M7 were investigated. We have demonstrated that low intensity of blue light (500 lx) decreased Monascus biomass, increased MPs accumulation via upregulation of MpigA, MpigB, and MpigJ genes expression, but had no significant influence on citrinin production. High intensity of blue light (1500 lx) decreased citrinin accumulation but had no significant influence on biomass and MPs production after 14 days cultivation. Low intensity of green light (500 lx) stimulated citrinin production via upregulation of pksCT, mrl1, mrl2, and ctnA genes expression. One putative red light photoreceptor and two putative green light photoreceptors were identified in M. ruber M7. These observations will not only guide the practical production of Monascus but also contribute to our understanding light effects on Monascus.
ESTHER : Wang_2016_J.Agric.Food.Chem_64_9506
PubMedSearch : Wang_2016_J.Agric.Food.Chem_64_9506
PubMedID: 27998068
Gene_locus related to this paper: monpu-cita

Title : Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression - Gong_2016_Oncotarget_7_68688
Author(s) : Gong Y , Wang L , Chippada-Venkata U , Dai X , Oh WK , Zhu J
Ref : Oncotarget , 7 :68688 , 2016
Abstract : To understand the heterogeneity of prostate cancer (PCa) and identify novel underlying drivers, we constructed integrative molecular Bayesian networks (IMBNs) for PCa by integrating gene expression and copy number alteration data from published datasets. After demonstrating such IMBNs with superior network accuracy, we identified multiple sub-networks within IMBNs related to biochemical recurrence (BCR) of PCa and inferred the corresponding key drivers. The key drivers regulated a set of common effectors including genes preferentially expressed in neuronal cells. NLGN4Y-a protein involved in synaptic adhesion in neurons-was ranked as the top gene closely linked to key drivers of myogenesis subnetworks. Lower expression of NLGN4Y was associated with higher grade PCa and an increased risk of BCR. We show that restoration of the protein expression of NLGN4Y in PC-3 cells leads to decreased cell proliferation, migration and inflammatory cytokine expression. Our results suggest that NLGN4Y is an important negative regulator in prostate cancer progression. More importantly, it highlights the value of IMBNs in generating biologically and clinically relevant hypotheses about prostate cancer that can be validated by independent studies.
ESTHER : Gong_2016_Oncotarget_7_68688
PubMedSearch : Gong_2016_Oncotarget_7_68688
PubMedID: 27626693
Gene_locus related to this paper: human-NLGN4Y

Title : Olfactory Transcriptional Analysis of Salmon Exposed to Mixtures of Chlorpyrifos and Malathion Reveal Novel Molecular Pathways of Neurobehavioral Injury - Wang_2016_Toxicol.Sci_149_145
Author(s) : Wang L , Espinoza HM , MacDonald JW , Bammler TK , Williams CR , Yeh A , Louie KW , Marcinek DJ , Gallagher EP
Ref : Toxicol Sci , 149 :145 , 2016
Abstract : Pacific salmon exposed to sublethal concentrations of organophosphate pesticides (OP) have impaired olfactory function that can lead to loss of behaviors that are essential for survival. These exposures often involve mixtures and can occur at levels below those which inhibit acetylcholinesterase (AChE). In this study, juvenile Coho salmon were exposed for 24 h to either 0.1, 0.5, or 2.5 ppb chlorpyrifos (CPF), 2, 10, or 50 ppb malathion (MAL), or binary mixtures of 0.1 CPF:2 ppb MAL, 0.5 CPF:10 ppb MAL, or 2.5 CPF:10 ppb MAL to mimic single and binary environmental exposures. Microarray analysis of olfactory rosettes from pesticide-exposed salmon revealed differentially expressed genes involved in nervous system function and signaling, aryl hydrocarbon receptor signaling, xenobiotic metabolism, and mitochondrial dysfunction. Coho exposed to OP mixtures exhibited a more pronounced loss in detection of a predatory olfactory cue relative to those exposed to single compounds, whereas respirometry experiments demonstrated that exposure to OPs, individually and in mixtures, reduced maximum respiratory capacity of olfactory rosette mitochondria. The observed molecular, biochemical, and behavioral effects occurred largely in the absence of effects on brain AChE. In summary, our results provide new insights associated with the sublethal neurotoxic effects of OP mixtures relevant to environmental exposures involving molecular and cellular pathways of injury to the salmon olfactory system that underlie neurobehavioral injury.
ESTHER : Wang_2016_Toxicol.Sci_149_145
PubMedSearch : Wang_2016_Toxicol.Sci_149_145
PubMedID: 26494550

Title : ABHD5 interacts with BECN1 to regulate autophagy and tumorigenesis of colon cancer independent of PNPLA2 - Peng_2016_Autophagy_12_2167
Author(s) : Peng Y , Miao H , Wu S , Yang W , Zhang Y , Xie G , Xie X , Li J , Shi C , Ye L , Sun W , Wang L , Liang H , Ou J
Ref : Autophagy , 12 :2167 , 2016
Abstract : Autophagy critically contributes to metabolic reprogramming and chromosomal stability. It has been reported that monoallelic loss of the essential autophagy gene BECN1 (encoding BECN1/Beclin 1) promotes cancer development and progression. However, the mechanism by which BECN1 is inactivated in malignancy remains largely elusive. We have previously reported a tumor suppressor role of ABHD5 (abhydrolase domain containing 5), a co-activator of PNPLA2 (patatin like phospholipase domain containing 2) in colorectal carcinoma (CRC). Here we report a noncanonical role of ABHD5 in regulating autophagy and CRC tumorigenesis. ABHD5 directly competes with CASP3 for binding to the cleavage sites of BECN1, and consequently prevents BECN1 from being cleaved by CASP3. ABHD5 deficiency provides CASP3 an advantage to cleave and inactivate BECN1, thus impairing BECN1-induced autophagic flux and augmenting genomic instability, which subsequently promotes tumorigenesis. Notably, clinical data also confirm that ABHD5 proficiency is significantly correlated with the expression levels of BECN1, LC3-II and CASP3 in human CRC tissues. Our findings suggest that ABHD5 possesses a PNPLA2-independent function in regulating autophagy and tumorigenesis, further establishing the tumor suppressor role of ABHD5, and offering an opportunity to develop new approaches aimed at preventing CRC carcinogenesis.
ESTHER : Peng_2016_Autophagy_12_2167
PubMedSearch : Peng_2016_Autophagy_12_2167
PubMedID: 27559856
Gene_locus related to this paper: human-ABHD5

Title : DWARF14 is a non-canonical hormone receptor for strigolactone - Yao_2016_Nature_536_469
Author(s) : Yao R , Ming Z , Yan L , Li S , Wang F , Ma S , Yu C , Yang M , Chen L , Li Y , Yan C , Miao D , Sun Z , Yan J , Sun Y , Wang L , Chu J , Fan S , He W , Deng H , Nan F , Li J , Rao Z , Lou Z , Xie D
Ref : Nature , 536 :469 , 2016
Abstract : Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
ESTHER : Yao_2016_Nature_536_469
PubMedSearch : Yao_2016_Nature_536_469
PubMedID: 27479325
Gene_locus related to this paper: arath-AtD14

Title : Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora - Zhang_2016_Sci.Rep_6_23122
Author(s) : Zhang L , Zhou Z , Guo Q , Fokkens L , Miskei M , Pocsi I , Zhang W , Chen M , Wang L , Sun Y , Donzelli BG , Gibson DM , Nelson DR , Luo JG , Rep M , Liu H , Yang S , Wang J , Krasnoff SB , Xu Y , Molnar I , Lin M
Ref : Sci Rep , 6 :23122 , 2016
Abstract : Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle.
ESTHER : Zhang_2016_Sci.Rep_6_23122
PubMedSearch : Zhang_2016_Sci.Rep_6_23122
PubMedID: 26975455
Gene_locus related to this paper: 9hypo-a0a151ga75 , 9hypo-a0a151gbh5 , 9hypo-a0a151gd50 , 9hypo-a0a151ggb9 , 9hypo-a0a151gjd5 , 9hypo-a0a151gtv2 , 9hypo-a0a151gxh2 , 9hypo-a0a151gaw8 , 9hypo-a0a151gia2

Title : [Role of acetylcholine in gelsenicine-induced death in mice] - Lai_2016_Sheng.Li.Xue.Bao_68_249
Author(s) : Lai ZY , Wang HB , Lv RL , Tan QC , Deng ZQ , Wang Y , Sun XX , Wu JB , Zhu LY , Wang L , Chen LX , Ye WC , Wang LW
Ref : Sheng Li Xue Bao , 68 :249 , 2016
Abstract : The aim of this study was to investigate the relationship between the acetylcholine concentration in the blood and gelsenicine-induced death in mice. Kunming mice were given intraperitoneal injections of normal saline, gelsenicine or different doses of acetylcholine chloride. Atropine was given to the mice which received gelsenicine or medium dose acetylcholine chloride injection. The blood was sampled immediately when the mice died or survived for 20 min after injection. The acetylcholine concentration and acetylcholinesterase activity in the blood were measured by the testing kits, and the mortality was calculated and analyzed. The results showed that half lethal dose of gelsenicine (0.15 mg/kg) reduced the acetylcholinesterase activity and increased the blood acetylcholine concentration. The blood acetylcholine concentration of the dead mice in the gelsenicine group was increased to 43.0 mug/mL (from 31.1 mug/mL in the control), which was lower than that (53.9 mug/mL) of the dead mice in the medium dose acetylcholine chloride group, but almost equal to that (42.7 mug/mL) of the survival mice in the medium dose acetylcholine chloride group. Atropine could successfully rescue the mice from acetylcholine poisoning, but its efficiency of rescuing the mice from gelsenicine intoxication was weak. These results suggest that gelsenicine can inhibit acetylcholinesterase activity and increase blood acetylcholine concentration, but the accumulation of acetylcholine may not be the only or main cause of the death induced by gelsenicine in mice.
ESTHER : Lai_2016_Sheng.Li.Xue.Bao_68_249
PubMedSearch : Lai_2016_Sheng.Li.Xue.Bao_68_249
PubMedID: 27350197

Title : Expression and characterization of a lipase-related protein in the malpighian tubules of the Chinese oak silkworm, Antheraea pernyi - Wang_2016_Bull.Entomol.Res_106_615
Author(s) : Wang L , Li J , Zhao X , Qian C , Wei G , Zhu B , Liu C
Ref : Bull Entomol Res , 106 :615 , 2016
Abstract : Lipases are ubiquitous enzymes in nature, which play a crucial role in fat metabolism by catalyzing the hydrolysis of triacylglycerol to free fatty acids and glycerol. However, reports concerning insect lipase are rare. In this study, we studied the expression and activity of a lipase-related protein from Antheraea pernyi (ApLRP). Recombinant ApLRP was expressed in Escherichia coli cells and used to raise rabbit anti-ApLRP polyclonal antibodies. ApLRP mRNA and protein expression were abundant in the midgut and malpighian tubules, respectively. After challenge with four different microorganisms (E. coli, Beauveria bassiana, Micrococcus luteus and nuclear polyhedrosis virus), the expression levels of ApLRP mRNA in midgut were inducted significantly compared with the control. The different pathogens induced different ApLRP gene expression patterns. The optimum temperature and pH for the enzyme's activity were 35 degrees C and 7.0, respectively. ApLRP activity was stimulated in the presence of Mg2+, Na+, Ca2+ and b-mercaptoethanol; while Zn2+, Cu2+ and Fe3+ inhibited its activity. Detergents such as SDS, glycerol and Tween-20 increased the lipase activity by 20-30%. Our results indicated that ApLRP might play an important role in the innate immunity of insects.
ESTHER : Wang_2016_Bull.Entomol.Res_106_615
PubMedSearch : Wang_2016_Bull.Entomol.Res_106_615
PubMedID: 27297450
Gene_locus related to this paper: antpe-a0a191xqw7

Title : Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system - Wang_2016_Neuropharmacol_111_323
Author(s) : Wang L , Almeida LE , Nettleton M , Khaibullina A , Albani S , Kamimura S , Nouraie M , Quezado ZM
Ref : Neuropharmacology , 111 :323 , 2016
Abstract : Caretakers and clinicians alike have long recognized that individuals with autism spectrum disorder (ASD) can have altered sensory processing, which can contribute to its core symptoms. However, the pathobiology of sensory alterations in ASD is poorly understood. Here we examined nocifensive behavior in ASD mouse models, the BTBR T+Itpr3tf/J (BTBR) and the fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also examined the effects of nicotine on nocifensive behavior given that nicotine, a nicotinic cholinergic receptor (nAChR) agonist that has antinociceptive effects, was shown to improve social deficits and decrease repetitive behaviors in BTBR mice. Compared to respective controls, both BTBR and Fmr1-KO had hyporesponsiveness to noxious thermal stimuli and electrical stimulation of C-sensory fibers, normal responsiveness to electrical stimulation of Abeta- and Adelta-fiber, and hyperresponsiveness to visceral pain after acetic acid intraperitoneal injection. In BTBR, nicotine at lower doses increased, whereas at higher doses, it decreased hotplate latency compared to vehicle. In a significantly different effect pattern, in control mice, nicotine had antinociceptive effects to noxious heat only at the high dose. Interestingly, these nocifensive behavior alterations and differential responses to nicotine antinociceptive effects in BTBR mice were associated with significant downregulation of alpha3, alpha4, alpha5, alpha7, beta2, beta3, and beta4 nAChR subunits in several cerebral regions both, during embryonic development and adulthood. Taken together, these findings further implicate nAChRs in behaviors alterations in the BTBR model and lend support to the hypothesis that nAChRs may be a target for treatment of behavior deficits and sensory dysfunction in ASD.
ESTHER : Wang_2016_Neuropharmacol_111_323
PubMedSearch : Wang_2016_Neuropharmacol_111_323
PubMedID: 27638450

Title : DL0410, a novel dual cholinesterase inhibitor, protects mouse brains against Abeta-induced neuronal damage via the Akt\/JNK signaling pathway - Zhou_2016_Acta.Pharmacol.Sin_37_1401
Author(s) : Zhou D , Zhou W , Song JK , Feng ZY , Yang RY , Wu S , Wang L , Liu AL , Du GH
Ref : Acta Pharmacol Sin , 37 :1401 , 2016
Abstract : AIM: 1,1'-([1,1'-Biphenyl]-4,4'-diyl)bis(3-(piperidin-1-yl)propan-1-one)dihydrochlorid e (DL0410) is a novel synthetic dual acetylcholinesterase (AChE)/butyrocholinesterase (BuChE) inhibitor, which has shown a potential therapeutic effect on Alzheimer's disease (AD). In this study we examined whether DL0410 produced neuroprotective effects in an AD cellular model and an Abeta1-42-induced amnesia mouse model.
METHODS: The in vitro inhibitory activities against AChE and BuChE were estimated using Ellman's assay. Copper-induced toxicity in APPsw-SY5Y cells was used as AD cellular model, the cell viability was assessed using MTS assay, and cell apoptosis was evaluated based on mitochondrial membrane potential detection. Abeta1-42-induced amnesia mouse model was made in male mice by injecting aggregated Abeta1-42 (2 mug in 2 muL 0.1% DMSO) into the right cerebral ventricle. Before and after Abeta1-42 injection, the mice were orally administered DL0410 (1, 3, 9 mg.kg-1.d-1) or rivastigmine (2 mg.kg-1.d-1) for 3 and 11 d, respectively. Memory impairments were examined using Morris water maze (MWM) test and passive avoidance test. The expression levels of APP, CREB, BDNF, JNK and Akt in the mouse brains were measured with either immunohistochemistry or Western blotting.
RESULTS: DL0410 exhibited in vitro inhibitory abilities against AChE and BuChE with IC50 values of 0.286+/-0.004 and 3.962+/-0.099 mumol/L, respectively, which were comparable to those of donepezil and rivastigmine. In APPsw-SY5Y cells, pretreatment with DL0410 (1, 3, and 10 mumol/L) decreased the phosphorylation of JNK and increased the phosphorylation of Akt, markedly decreased copper-stimulated Abeta1-42 production, reversed the loss of mitochondrial membrane potential, and dose-dependently increased the cell viability. In Abeta1-42-treated mice, DL0410 administration significantly ameliorated learning and memory deficits in MWM test and passive avoidance test. Furthermore, DL0410 administration markedly decreased Abeta1-40/42 deposits in mouse cerebral cortices, and significantly up-regulated neurotrophic CREB/BDNF. Meanwhile, Akt/JNK signaling pathway may play a key role in the neuroprotective effect of DL0410. CONCLUSION: DL0410 ameliorates cognitive deficit and exerts neuronal protection in AD models, implicating this compound as a candidate drug for the prevention and therapy of AD.
ESTHER : Zhou_2016_Acta.Pharmacol.Sin_37_1401
PubMedSearch : Zhou_2016_Acta.Pharmacol.Sin_37_1401
PubMedID: 27498773

Title : Complete Genome Sequence of Elizabethkingia meningoseptica, Isolated from a T-Cell Non-Hodgkin's Lymphoma Patient - Sun_2015_Genome.Announc_3_e00673
Author(s) : Sun G , Wang L , Bao C , Li T , Ma L , Chen L
Ref : Genome Announc , 3 : , 2015
Abstract : An Elizabethkingia meningoseptica infection was detected at the end stage of a patient with T-cell non-Hodgkin's lymphoma. The complete genome of this isolated strain, FMS-007, was generated in one contig with a total size of 3,938,967 bp. A preliminary screening indicated that the genome contains drug resistance genes to aminoglycosides and beta-lactams. A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (CRISPR/Cas) system with 16 direct repeats and 15 spacers was identified.
ESTHER : Sun_2015_Genome.Announc_3_e00673
PubMedSearch : Sun_2015_Genome.Announc_3_e00673
PubMedID: 26112786
Gene_locus related to this paper: elimr-a0a0a2h0j3

Title : Strigolactone Signaling in Arabidopsis Regulates Shoot Development by Targeting D53-Like SMXL Repressor Proteins for Ubiquitination and Degradation - Wang_2015_Plant.Cell_27_3128
Author(s) : Wang L , Wang B , Jiang L , Liu X , Li X , Lu Z , Meng X , Wang Y , Smith SM , Li J
Ref : Plant Cell , 27 :3128 , 2015
Abstract : Strigolactones (SLs) are carotenoid-derived phytohormones that control many aspects of plant development, including shoot branching, leaf shape, stem secondary thickening, and lateral root growth. In rice (Oryza sativa), SL signaling requires the degradation of DWARF53 (D53), mediated by a complex including D14 and D3, but in Arabidopsis thaliana, the components and mechanism of SL signaling involving the D3 ortholog MORE AXILLARY GROWTH2 (MAX2) are unknown. Here, we show that SL-dependent regulation of shoot branching in Arabidopsis requires three D53-like proteins, SUPPRESSOR OF MORE AXILLARY GROWTH2-LIKE6 (SMXL6), SMXL7, and SMXL8. The smxl6 smxl7 smxl8 triple mutant suppresses the highly branched phenotypes of max2 and the SL-deficient mutant max3. Overexpression of a mutant form of SMXL6 that is resistant to SL-induced ubiquitination and degradation enhances shoot branching. Exogenous application of the SL analog rac-GR24 causes ubiquitination and degradation of SMXL6, 7, and 8; this requires D14 and MAX2. D53-like SMXLs form complexes with MAX2 and TOPLESS-RELATED PROTEIN2 (TPR2) and interact with D14 in a GR24-responsive manner. Furthermore, D53-like SMXLs exhibit TPR2-dependent transcriptional repression activity and repress the expression of BRANCHED1. Our findings reveal that in Arabidopsis, D53-like SMXLs act with TPR2 to repress transcription and so allow lateral bud outgrowth but that SL-induced degradation of D53-like proteins activates transcription to inhibit outgrowth.
ESTHER : Wang_2015_Plant.Cell_27_3128
PubMedSearch : Wang_2015_Plant.Cell_27_3128
PubMedID: 26546446

Title : Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population - Zhang_2015_PLoS.One_10_e0144719
Author(s) : Zhang Z , Yu H , Jiang S , Liao J , Lu T , Wang L , Zhang D , Yue W
Ref : PLoS ONE , 10 :e0144719 , 2015
Abstract : Multiple risk variants of schizophrenia have been identified by Genome-wide association studies (GWAS). As a complement for GWAS, previous pathway-based analysis has indicated that cell adhesion molecules (CAMs) pathway might be involved in the pathogenesis of schizophrenia. However, less replication studies have been reported. Our objective was to investigate the association between CAMs pathway and schizophrenia in the Chinese Han population. We first performed a pathway analysis utilizing our previous GWAS data. The CAMs pathway (hsa04514) was significantly associated with schizophrenia using hybrid gene set-based test (P = 1.03x10-10) and hypergeometric test (P = 5.04x10-6). Moreover, 12 genes (HLA-A, HLA-C, HLA-DOB, HLA-DPB1, HLA-DQA2, HLA-DRB1, MPZ, CD276, NLGN1, NRCAM, CLDN1 and ICAM3) were modestly significantly associated with schizophrenia (P<0.01). Then, we selected one promising gene neuroligin 1 (NLGN1) to further investigate the association between eight significant SNPs and schizophrenia in an independent sample (1814 schizophrenia cases and 1487 healthy controls). Our study showed that seven SNPs of NLGN1 and two haplotype blocks were significantly associated with schizophrenia. This association was confirmed by the results of combined analysis. Among them, SNP rs9835385 had the most significant association with schizophrenia (P = 2.83x10-7). Furthermore, in silico analysis we demonstrated that NLGN1 is preferentially expressed in human brain and SNP rs1488547 was related to the expression level. We validated the association of CAMs pathway with schizophrenia in pathway-level and identified one susceptibility gene NLGN1. Further investigation of the roles of CAMs pathway in the pathogenesis of schizophrenia is warranted.
ESTHER : Zhang_2015_PLoS.One_10_e0144719
PubMedSearch : Zhang_2015_PLoS.One_10_e0144719
PubMedID: 26674772

Title : Draft Genome Sequence of Norvancomycin-Producing Strain Amycolatopsis orientalis CPCC200066 - Lei_2015_Genome.Announc_3_
Author(s) : Lei X , Yuan F , Shi Y , Li X , Wang L , Hong B
Ref : Genome Announc , 3 : , 2015
Abstract : Amycolatopsis orientalis CPCC200066 is an actinomycete that can produce the glycopeptide antibiotic norvancomycin, which has significant inhibitory activity against Gram-positive cocci and bacilli. Here, we report the draft genome sequence of A. orientalis CPCC200066 and identified the genes involved in norvancomycin biosynthesis.
ESTHER : Lei_2015_Genome.Announc_3_
PubMedSearch : Lei_2015_Genome.Announc_3_
PubMedID: 25977416
Gene_locus related to this paper: amyor-a0a193bq04 , amyor-a0a193bty5 , amyor-a0a193bvz8 , amyor-a0a193byg1 , amyor-a0a193by54 , amyor-a0a193c2b2 , amyor-a0a193bzy5 , amyor-a0a193cbs3

Title : Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease - Zhou_2015_J.Mol.Model_21_277
Author(s) : Zhou A , Hu J , Wang L , Zhong G , Pan J , Wu Z ,