Wang J

References (527)

Title : The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs - Zhang_2024_Int.J.Surg__
Author(s) : Zhang Y , Sun Y , Hu X , Yao Y , Wang J
Ref : Int J Surg , : , 2024
Abstract : INTRODUCTION: At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD. METHODS: Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library and Web of Science from inception to May 10, 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0. RESULTS: Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD -1.57; 95% CI -2.64 to -0.51), Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD -0.28; 95% CI -0.41 to -0.15), the Neuropsychiatric Inventory (NPI) (both SMD -1.67; 95% CI -2.88 to -0.47 for 10-tiem total score and SMD -1.83; 95% CI -3.25 to -0.42 for 12-tiem total score), and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI 1.29 to 3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death. CONCLUSIONS: Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.
ESTHER : Zhang_2024_Int.J.Surg__
PubMedSearch : Zhang_2024_Int.J.Surg__
PubMedID: 38573101

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

Title : Two Fluorescent Probes for Recognition of Acetylcholinesterase: Design, Synthesis, and Comparative Evaluation - Lin_2024_Molecules_29_
Author(s) : Lin X , Yi Q , Qing B , Lan W , Jiang F , Lai Z , Huang J , Liu Q , Jiang J , Wang M , Zou L , Huang X , Wang J
Ref : Molecules , 29 : , 2024
Abstract : In this study, two "on-off" probes (BF(2)-cur-Ben and BF(2)-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF(2)-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (K(m) = 16 +/- 1.6 microM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF(2)-cur-Ben forms more hydrogen bonds (seven, while BF(2)-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of K(m) values. These two probes could enable recognition of intracellular AChE and probe BF(2)-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF(2)-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.
ESTHER : Lin_2024_Molecules_29_
PubMedSearch : Lin_2024_Molecules_29_
PubMedID: 38731452

Title : An Esterase-Responsive SLC7A11 shRNA Delivery System Induced Ferroptosis and Suppressed Hepatocellular Carcinoma Progression - Zhang_2024_Pharmaceutics_16_
Author(s) : Zhang H , Wang J , Xiang X , Xie C , Lu X , Guo H , Sun Y , Shi Z , Song H , Qiu N , Xu X
Ref : Pharmaceutics , 16 : , 2024
Abstract : Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G-LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G-LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G-LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment.
ESTHER : Zhang_2024_Pharmaceutics_16_
PubMedSearch : Zhang_2024_Pharmaceutics_16_
PubMedID: 38399303

Title : Genome-wide association studies of egg production traits by whole genome sequencing of Laiwu Black chicken - Lei_2024_Poult.Sci_103_103705
Author(s) : Lei Q , Zhang S , Wang J , Qi C , Liu J , Cao D , Li F , Han H , Liu W , Li D , Tang C , Zhou Y
Ref : Poult Sci , 103 :103705 , 2024
Abstract : Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 x per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.
ESTHER : Lei_2024_Poult.Sci_103_103705
PubMedSearch : Lei_2024_Poult.Sci_103_103705
PubMedID: 38598913

Title : Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING - Fan_2024_Int.Immunopharmacol_131_111904
Author(s) : Fan C , Du J , Yu Z , Wang J , Yao L , Ji Z , He W , Deng Y , Geng D , Wu X , Mao H
Ref : Int Immunopharmacol , 131 :111904 , 2024
Abstract : Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4alpha. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-beta-gal-positive cells and hindered the manifestation of p16INK4alpha and the inflammatory factor IL-1beta in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.
ESTHER : Fan_2024_Int.Immunopharmacol_131_111904
PubMedSearch : Fan_2024_Int.Immunopharmacol_131_111904
PubMedID: 38518595

Title : Multiple strategies to improve extracellular secretion and activity of feruloyl esterase - Zhang_2024_Int.J.Biol.Macromol_269_132082
Author(s) : Zhang S , Wang J , Liu Y , Xu Z
Ref : Int J Biol Macromol , 269 :132082 , 2024
Abstract : Feruloyl esterase has a wide range of applications, but there are still problems with low enzyme yield and activity, and complex purification steps. Our previous research found Lactobacillus amylovorus feruloyl esterase could be secreted extracellular in Escherichia coli. In this study, multiple strategies were implemented to maximize the extracellular production of feruloyl esterase with improved activity in E. coli. Firstly, codon-optimized feruloyl esterase was obtained based on the preference of E. coli, resulting in 41.97 % increase in extracellular secretion. Furthermore, by cascading T7 promoters, replacing the 5' UTR, randomly mutating the N-terminal sequence, and co-expressing secretory cofactors, the extracellular secretion was increased by 36.46 %, 31.25 %, 20.66 % and 25.75 %, respectively. Moreover, the feruloyl esterase were mutated to improve the substrate affinity and activity. The catalytic efficiency of Fae-Q134T and Fae-Q198A increased by 4.62-fold and 5.42-fold. Combining above strategies, extracellular feruloyl esterase activity was increased from 2013.70 U/L to 10,349.04 U/L. These results indicated that the activity and yield of feruloyl esterase secreted by E. coli were significantly increased, which laid a foundation for its industrial application.
ESTHER : Zhang_2024_Int.J.Biol.Macromol_269_132082
PubMedSearch : Zhang_2024_Int.J.Biol.Macromol_269_132082
PubMedID: 38705319
Gene_locus related to this paper: lacam-a0a1c9u7k7

Title : Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects - Lin_2024_Talanta_274_126060
Author(s) : Lin X , Liu M , Yi Q , Zhou Y , Su J , Qing B , Lu Y , Pu C , Lan W , Zou L , Wang J
Ref : Talanta , 274 :126060 , 2024
Abstract : In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF(2)-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF(2)-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF(2)-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF(2)-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.
ESTHER : Lin_2024_Talanta_274_126060
PubMedSearch : Lin_2024_Talanta_274_126060
PubMedID: 38604044

Title : Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats - Yang_2024_BMC.Pharmacol.Toxicol_25_14
Author(s) : Yang Y , Dai C , Chen X , Zhang B , Li X , Yang W , Wang J , Feng J
Ref : BMC Pharmacol Toxicol , 25 :14 , 2024
Abstract : OBJECTIVE: Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. METHODS: Forty male Sprague-Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. RESULTS: TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.001), Cre (z = 3.476; P < 0.001), CysC (z = 4.052; P < 0.001), NGAL (z = 3.661; P < 0.001), and CRP (z = 5.286; P < 0.001) gradually increased after uranium exposure, whereas TAS (z = -3.823; P < 0.001), tissue U (z = -2.736; P = 0.001), Hcy (z = -2.794; P = 0.005), and Lp-PLA2 (z = -4.515; P < 0.001) gradually decreased. The serum U level showed a V-shape change (z = -1.655; P = 0.094). The uranium levels in the kidney tissue and serum were positively correlated with TOS (r = 0.440 and 0.424; P = 0.005 and 0.007) and OSI (r = 0.389 and 0.449; P = 0.013 and 0.004); however, serum U levels were negatively correlated with TAS (r = -0.349; P = 0.027). Partial correlation analysis revealed that NGAL was closely correlated to tissue U (r(partial) = 0.455; P = 0.003), CysC was closely correlated to serum U (r(partial) = 0.501; P = 0.001), and Lp-PLA2 was closely correlated to TOS (r(partial) = 0.391; P = 0.014), TAS (r(partial) = 0.569; P < 0.001), and OSI (r(partial) = -0.494; P = 0.001). Pearson correlation analysis indicated that the Hcy levels were negatively correlated with tissue U (r = -0.344; P = 0.030) and positively correlated with TAS (r = 0.396; P = 0.011). CONCLUSION: The uranium-induced oxidative injury may be mainly reflected in enhanced endothelial inflammation, and the direct chemical toxicity of uranium plays an important role in the process of kidney injury, especially in renal tubular injury. In addition, CysC may be a sensitive marker reflecting the nephrotoxicity of uranium; however, Hcy is not suitable for evaluating short-term endothelial inflammation involving oxidative stress.
ESTHER : Yang_2024_BMC.Pharmacol.Toxicol_25_14
PubMedSearch : Yang_2024_BMC.Pharmacol.Toxicol_25_14
PubMedID: 38308341

Title : Highly Sensitive and Rapid Screening Technique for the Detection of Organophosphate Pesticides and Copper Compounds Using Bifunctional Recombinant TrxA-PvCarE1 - Cao_2024_J.Agric.Food.Chem__
Author(s) : Cao J , Wang M , She Y , Zheng L , Jin F , Shao Y , Wang J , Abd El-Aty AM
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Enabling the detection of organophosphate pesticide (OP) residues through enzyme inhibition-based technology is crucial for ensuring food safety and human health. However, the use of acetylcholinesterase, the primary target enzyme for OPs, isolated from animals in practical production poses challenges in terms of sensitivity and batch stability. To address this issue, we identified a highly sensitive and reproducible biorecognition element, TrxA-PvCarE1, derived from red kidney beans and successfully overexpressed it in Escherichia coli. The resulting recombinant TrxA-PvCarE1 exhibited remarkable sensitivity toward 10 OPs, surpassing that of commercial acetylcholinesterase. Additionally, this approach demonstrated the capability to simultaneously detect copper compounds with high sensitivity, expanding the range of pesticides detectable using the traditional enzyme inhibition method. Spiking recovery tests conducted on cowpea and carrot samples verified the suitability of the TrxA-PvCarE1-based technique for real-life sample analysis. In summary, this study highlights a promising comprehensive candidate for the rapid detection of pesticide residues.
ESTHER : Cao_2024_J.Agric.Food.Chem__
PubMedSearch : Cao_2024_J.Agric.Food.Chem__
PubMedID: 38408326
Gene_locus related to this paper: phavu-PvCarE1

Title : Biotoxicity responses of Zebrafish in environmentally relevant concentration of Di (2-ethylhexyl) phthalate - Li_2024_Environ.Toxicol.Pharmacol__104423
Author(s) : Li X , Hu S , Jiang N , Yao X , Wang C , Wang Q , Yang Z , Wang J
Ref : Environ Toxicol Pharmacol , :104423 , 2024
Abstract : As an emerging environmental contaminant, di (2-ethylhexyl) phthalate (DEHP) is widely present in the aquatic environment, however, the effects and underlying mechanisms of DEHP on the aquatic organisms are poorly understood. This study systematically investigated the ecotoxicity induced by chronic exposure to environmental relevant concentrations of DEHP (0.03mg/L, 0.1mg/L, and 0.3mg/L) on zebrafish brain. Results indicated that DEHP exposure significantly increased the levels of ROS and disturbance of the antioxidant enzymes activities in the brain, which may further enhance lipid peroxidation and DNA damage. Furthermore, acetylcholinesterase activity was first stimulated and inhibited by exposure to DEHP, and the antioxidant and apoptosis related genes were mainly upregulated. Risk assessment indicated that the ecotoxicity of DEHP on the zebrafish showed an "enhancement-reduction" trend as the exposure time was prolonged. Overall, these results provided new insights and useful information to ecological risk assessment and environmental management of DEHP pollution.
ESTHER : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedSearch : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedID: 38521434

Title : Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality - Chen_2024_J.Med.Chem__
Author(s) : Chen Y , Sun J , Tong H , Wang J , Cao R , Xu H , Chen L , Morisseau C , Zhang M , Shi Y , Han C , Zhuang J , Jing Y , Liu Z , Hammock BD , Chen G
Ref : Journal of Medicinal Chemistry , : , 2024
Abstract : Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.
ESTHER : Chen_2024_J.Med.Chem__
PubMedSearch : Chen_2024_J.Med.Chem__
PubMedID: 38236416

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 : Efficient secretion of an enzyme cocktail in Escherichia coli for hemicellulose degradation - Zhang_2024_Int.J.Biol.Macromol__129205
Author(s) : Zhang S , Wang J , Chen Y , Zheng Z , Xu Z
Ref : Int J Biol Macromol , :129205 , 2024
Abstract : The use of host to secrete several hemicellulase is a cost-effective way for hemicellulose degradation. In this study, the xylose utilization gene xylAB of Escherichia coli BL21 was knocked out, and the xylanase (N20Xyl), beta-xylosidase (Xys), and feruloyl esterase (FaeLam) were co-expressed in this strain. By measuring the content of reducing sugars generated by enzymatic hydrolysis of wheat bran in the fermentation supernatant, the order of the three enzymes was screened to obtain the optimal recombinant strain of E. coli BL21/deltaxylAB/pDIII-2. Subsequently, fermentation conditions including culture medium, inducer concentration, induction timing, metal ions, and glycine concentration were optimized. Then, different concentrations of wheat bran and xylan were added to the fermentation medium for degradation. The results showed that the extracellular reducing sugars content reached the highest value of 33.70 +/- 0.46 g/L when 50 g/L xylan was added. Besides, the scavenging rates of hydroxyl radical by the fermentation supernatant was 81.0 +/- 1.41 %, and the total antioxidant capacity reached 2.289 +/- 0.55. Furthermore, it showed the growth promotion effect on different lactic acid bacteria. These results provided a basis for constructing E. coli strain to efficiently degrade hemicellulose, and the strain obtained has great potential application to transform hemicellulose into fermentable carbon source.
ESTHER : Zhang_2024_Int.J.Biol.Macromol__129205
PubMedSearch : Zhang_2024_Int.J.Biol.Macromol__129205
PubMedID: 38185299

Title : Discovery of a novel class of reversible monoacylglycerol lipase inhibitors for potential treatment of depression - Hao_2024_Eur.J.Med.Chem_268_116285
Author(s) : Hao Q , Shi J , Zhang Z , Yang G , Zhi Y , Wang K , Ma D , Fu S , Dong H , Zhi Z , Zhang W , Li T , Wang J
Ref : Eur Journal of Medicinal Chemistry , 268 :116285 , 2024
Abstract : Biological studies on the endocannabinoid system (ECS) have suggested that monoacylglycerol lipase (MAGL), an essential enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), is a novel target for developing antidepressants. A decrease of 2-AG levels in the hippocampus of the brain has been observed in depressive-like models induced by chronic stress. Herein, employing a structure-based approach, we designed and synthesized a new class of (piperazine-1-carbonyl) quinolin-2(1H)-one derivatives as potent, reversible and selective MAGL inhibitors. And detailed structure-activity relationships (SAR) studies were discussed. Compound 27 (IC(50) = 10.3 nM) exhibited high bioavailability (92.7%) and 2-AG elevation effect in vivo. Additionally, compound 27 exerted rapid antidepressant effects caused by chronic restraint stress (CRS) and didn't show signs of addictive properties in the conditioned place preference (CPP) assays. Our study is the first to report that reversible MAGL inhibitors can treat chronic stress-induced depression effectively, which may provide a new potential therapeutic strategy for the discovery of an original class of safe, rapid antidepressant drugs.
ESTHER : Hao_2024_Eur.J.Med.Chem_268_116285
PubMedSearch : Hao_2024_Eur.J.Med.Chem_268_116285
PubMedID: 38428273

Title : Synthesis, biological evaluation and molecular docking of novel nereistoxin derivatives containing phosphonates as insecticidal\/AChE inhibitory agents - Yan_2024_RSC.Adv_14_3996
Author(s) : Yan Q , Lu X , Wang J , Zhang Z , Gao R , Pei C , Wang H
Ref : RSC Adv , 14 :3996 , 2024
Abstract : In continuation of our program aimed at the discovery and development of natural product-based insecticidal agents, a series of novel nereistoxin derivatives containing phosphonate were synthesized and characterized by (31)P, (1)H, (13)C NMR and HRMS. The bioactivities of the derivatives were evaluated for the acetylcholinesterase (AChE) inhibition potency and insecticidal activity. The AChE inhibitory effects of the derivatives were investigated using the in vitro Ellman method. Half of the compounds exhibited excellent inhibition of AChE. All the compounds were assessed for insecticidal activities against Mythimna separate (Walker) and Rhopalosiphum padi in vivo. Some derivatives displayed promising insecticidal activity against Rhopalosiphum padi. Compounds 5b and 6a displayed the highest activity against R. padi, showing LC(50) values of 17.14 and 18.28 microg mL(-1), respectively, close to that of commercial insecticide flunicotamid (LC(50) = 17.13 microg mL(-1)). Compound 9g also showed notable insecticidal activity, with an LC(50) value of 23.98 microg mL(-1). Additionally, the binding modes of the active compounds 5b, 6a and 9g with AChE were analyzed in-depth though molecular docking and the intrinsic reasons for the differences in the strength of the compound's activities were elucidated. In summary, our findings demonstrate the potential of these nereistoxin derivatives as promising candidates for the development of novel pesticides.
ESTHER : Yan_2024_RSC.Adv_14_3996
PubMedSearch : Yan_2024_RSC.Adv_14_3996
PubMedID: 38288150

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 : Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio) - Zhu_2024_Chemosphere__142027
Author(s) : Zhu J , Huang M , Jiang P , Wang J , Zhu R , Liu C
Ref : Chemosphere , :142027 , 2024
Abstract : Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 hours post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.
ESTHER : Zhu_2024_Chemosphere__142027
PubMedSearch : Zhu_2024_Chemosphere__142027
PubMedID: 38621487

Title : Discovery and Mechanistic Understanding of a Lipase from Rhizorhabdus dicambivorans for Efficient Ester Aminolysis in Aromatic Amines - Wang_2024_ChemSusChem__e202301735
Author(s) : Wang J , Huang Z , Xu H , Nian Y , Wu B , He B , Schenk G
Ref : ChemSusChem , :e202301735 , 2024
Abstract : The formation of amide bonds via aminolysis of esters by lipases generates a diverse range of amide frameworks in biosynthetic chemistry. Few lipases have satisfactory activity towards bulky aromatic amines despite numerous attempts to improve the efficiency of this transformation. Here, we report the discovery of a new intracellular lipase (Ndbn) with a broad substrate scope. Ndbn turns over a range of esters and aromatic amines in the presence of water (2%; v/v), producing a high yield of multiple valuable amides. Remarkably, a higher conversion rate was observed for the synthesis of amides from substrates with aromatic amine rather than aliphatic amines. Molecular dynamics (MD) and quantum mechanical/molecular mechanical (QM/MM) studies showcase the mechanism for the preference for aromatic amines, including a more suitable orientation, shorter catalytic distances in the active site pocket and a lower reaction barrier for aromatic than for aliphatic amines. This unique lipase is thus a promising biocatalyst for the efficient synthesis of aromatic amides.
ESTHER : Wang_2024_ChemSusChem__e202301735
PubMedSearch : Wang_2024_ChemSusChem__e202301735
PubMedID: 38183360
Gene_locus related to this paper: 9sphn-a0a2a4g2a9

Title : Progressive expansion of albumin adducts for organophosphorus nerve agent traceability based on single and group adduct collection - Wang_2024_Anal.Bioanal.Chem__
Author(s) : Wang J , Lu X , Gao R , Pei C , Wang H
Ref : Anal Bioanal Chem , : , 2024
Abstract : Protein adducts are important biological targets for traceability of organophosphorus nerve agents (OPNAs). Currently, the recognized biomarkers that can be used in actual samples in the field of chemical forensics only include Y411 in albumin and the active nonapeptide in butyrylcholinesterase (BChE). To explore stable and reliable protein adducts and increase the accuracy of OPNAs traceability further, we gradually expanded OPNAs-albumin adducts based on single and group adduct collection. Several stable peptides were found via LC-MS/MS analysis in human serum albumin (HSA) exposed to OPNAs in a large exposure range. These adducts were present in HSA samples exposed to OPNAs of each concentration, which provided data support for the reliability and stability of using adducts to trace OPNAs. Meanwhile, the formation mechanism of OPNAs-cysteine adduct was clarified via computer simulations. Then, these active sites found and modified peptides were used as raw materials for progressive expansion of albumin adducts. We constructed an OPNAs-HSA adducts group, in which a specific agent is the exposure source, and three or more active peptides constitute data sets for OPNAs traceability. Compared with single or scattered protein adducts, the OPNAs-HSA adduct group improves OPNAs identification by mutual verification using active peptides or by narrowing the identity range of the exposure source. We also determined the minimum detectable concentration of OPNAs for the adduct group. Two or more peptides can be detected when there is an exposure of 50 times the molar excess of OPNAs in relation to HSA. This improved the accuracy of OPNAs exposure and identity confirmation. A collection of OPNAs-albumin adducts was also examined. The collection was established by collecting, classifying, and integrating the existing albumin adducts according to the species to which each albumin belongs, the types of agents, and protease. This method can serve as a reference for discovering new albumin adducts, characteristic phosphonylated peptides, and potential biomarkers. In addition, to avoid a false negative for OPNAs traceability using albumin adducts, we explored OPNAs-cholinesterase adducts because cholinesterase is more reactive with OPNAs than albumin. Seven active peptides in red blood cell acetylcholinesterase (RBC AChE) and serum BChE can assist in OPNAs exposure and identity confirmation.
ESTHER : Wang_2024_Anal.Bioanal.Chem__
PubMedSearch : Wang_2024_Anal.Bioanal.Chem__
PubMedID: 38698257

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

Title : Carboxylesterase 1 family knockout alters drug disposition and lipid metabolism - Gan_2023_Acta.Pharm.Sin.B_13_618
Author(s) : Gan C , Wang J , Martinez-Chavez A , Hillebrand M , de Vries N , Beukers J , Wagenaar E , Wang Y , Lebre MC , Rosing H , Klarenbeek S , Ali RB , Pritchard C , Huijbers I , Beijnen JH , Schinkel AH
Ref : Acta Pharm Sin B , 13 :618 , 2023
Abstract : The mammalian carboxylesterase 1 (Ces1/CES1) family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids. To investigate the pharmacological and physiological roles of Ces1/CES1, we generated Ces1 cluster knockout (Ces1 (-/-) ) mice, and a hepatic human CES1 transgenic model in the Ces1 (-/-) background (TgCES1). Ces1 (-/-) mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues. TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney. Ces1 and hCES1 activity increased irinotecan toxicity, likely by enhancing the formation of pharmacodynamically active SN-38. Ces1 (-/-) mice also showed markedly increased capecitabine plasma exposure, which was moderately decreased in TgCES1 mice. Ces1 (-/-) mice were overweight with increased adipose tissue, white adipose tissue inflammation (in males), a higher lipid load in brown adipose tissue, and impaired blood glucose tolerance (in males). These phenotypes were mostly reversed in TgCES1 mice. TgCES1 mice displayed increased triglyceride secretion from liver to plasma, together with higher triglyceride levels in the male liver. These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification. Ces1 (-/-) and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.
ESTHER : Gan_2023_Acta.Pharm.Sin.B_13_618
PubMedSearch : Gan_2023_Acta.Pharm.Sin.B_13_618
PubMedID: 36873183
Gene_locus related to this paper: mouse-Ces1a , mouse-Ces1b , mouse-Ces1c , mouse-Ces1d , mouse-Ces1e , mouse-Ces1f , mouse-Ces1g , mouse-Ces1h

Title : Role of MRPs transporters in pharmacokinetics and intestinal toxicity of irinotecan - Du_2023_Food.Chem.Toxicol__114171
Author(s) : Du T , Luo T , Wang J , Sun R , Cai H
Ref : Food & Chemical Toxicology , :114171 , 2023
Abstract : To identify additional genetic markers contributing to variability in CPT-11 disposition and toxicity, we assessed impact of the multiple drug-resistant transporters 1, 2, and 3 (MRP1, MRP2, and MRP3) on the intestinal toxicity, pharmacokinetics, tissue distribution and biliary excretion of CPT-11 using a knockout mouse model. Mrp1/3 knockout had minor impact on intestinal toxicity of CPT-11, tissue distribution, biliary excretion, and PK parameter of its active metabolites SN38. Conversely, Mrp2(-/-) mice, with low carboxylesterase activity, displayed insensitivity to CPT-11 toxicity due to reduced intestinal exposure to SN38. In PK studies, Mrp1/2 knockout significantly increased the AUC of CPT-11 compared to their AUC in FVB mice. However, the AUC of SN38 in Mrp2 (-/-) mice was decreased by 3.25-fold. Mrp3 knockout only slightly increased SN38 plasma exposure. Lastly, Mrp2/3 knockout increased biliary excretion amount of CPT-11 by 67.2% and 48.5% compared to wild-type mice, respectively. Consequently, Mrp1/3 deficiency didn't change SN38 tissue distribution. Finally, correlation analysis demonstrated that tissue exposure to SN38 was better correlated with toxicity than plasma AUC of SN38. Mrp1/2/3 deficiency showed a minor impact on PK, biliary excretion, distribution and intestinal exposure of SN38, and as a result, did not affect the intestinal toxicity of CPT-11.
ESTHER : Du_2023_Food.Chem.Toxicol__114171
PubMedSearch : Du_2023_Food.Chem.Toxicol__114171
PubMedID: 37956707

Title : Current advances in the structural biology and molecular engineering of PETase - Liu_2023_Front.Bioeng.Biotechnol_11_1263996
Author(s) : Liu F , Wang T , Yang W , Zhang Y , Gong Y , Fan X , Wang G , Lu Z , Wang J
Ref : Front Bioeng Biotechnol , 11 :1263996 , 2023
Abstract : Poly(ethylene terephthalate) (PET) is a highly useful synthetic polyester plastic that is widely used in daily life. However, the increase in postconsumer PET as plastic waste that is recalcitrant to biodegradation in landfills and the natural environment has raised worldwide concern. Currently, traditional PET recycling processes with thermomechanical or chemical methods also result in the deterioration of the mechanical properties of PET. Therefore, it is urgent to develop more efficient and green strategies to address this problem. Recently, a novel mesophilic PET-degrading enzyme (IsPETase) from Ideonella sakaiensis was found to streamline PET biodegradation at 30 degreesC, albeit with a lower PET-degrading activity than chitinase or chitinase-like PET-degrading enzymes. Consequently, the molecular engineering of more efficient PETases is still required for further industrial applications. This review details current knowledge on IsPETase, MHETase, and IsPETase-like hydrolases, including the structures, ligandprotein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts are highlighted, including metabolic engineering of the cell factories, enzyme immobilization or cell surface display. The information is expected to provide novel insights for the biodegradation of complex polymers.
ESTHER : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedSearch : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedID: 37795175

Title : Enhanced enzyme thermostability of a family I.3 lipase LipSR1 by T118A mutation at the calcium-binding site - Jiang_2023_Biotechnol.Lett__
Author(s) : Jiang S , Zhou Z , Han J , Fan Q , Long Z , Wang J
Ref : Biotechnol Lett , : , 2023
Abstract : OBJECTIVES: The lipase gene lipSR1 isolated from oil-contaminated soil exhibits high hydrolytic activity for short-chain fatty acid substrates. A single calcium ion is required to anchor the lid of LipSR1 in an open conformation by coordination with two aspartate residues and three other residues in the lid. The lid of LipSR1 is anchored by Ca(2+), which is coordinated by side-chain carboxyl oxygens of Asp153 and Asp157, carbonyl oxygens of Thr118 and Ser144, and the side chain of Gln120. RESULTS: D157A, D153R, Q120A, S144A, and T118A mutants were produced by site-directed mutagenesis in this study. Analyses of hydrolytic activity and thermostability showed that the properties of D157A, D153R, Q120A, and S144A were almost lost, suggesting that Asp157, Asp153, Gln120, and Ser144 are important residues for LipSR1. However, the catalytic performance of T118A was clearly maintained. Moreover, the thermostability of mutant T118A was higher than that of wild-type LipSR1. CONCLUSIONS: These results indicated that mutation of threonine at position 118 improved the stability of the enzyme at high temperature.
ESTHER : Jiang_2023_Biotechnol.Lett__
PubMedSearch : Jiang_2023_Biotechnol.Lett__
PubMedID: 37439931
Gene_locus related to this paper: lacac-q5fi30

Title : Design, synthesis, and biological evaluation of novel donepezil-tacrine hybrids as multi-functional agents with low neurotoxicity against Alzheimer's disease - Wang_2023_Bioorg.Chem_143_107010
Author(s) : Wang N , Jia W , Wang J , Yang Z , Liu Y , Huang D , Mei X , Xiong X , Shi J , Tang Y , Chen G , Di D , Hou Y
Ref : Bioorg Chem , 143 :107010 , 2023
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and deficits in cognitive domains. Low choline levels, oxidative stress, and neuroinflammation are the primary mechanisms implicated in AD progression. Simultaneous inhibition of acetylcholinesterase (AChE) and reactive oxygen species (ROS) production by a single molecule may provide a new breath of hope for AD treatment. Here, we describe donepezil-tacrine hybrids as inhibitors of AChE and ROS. Four series of derivatives with a beta-amino alcohol linker were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit AChE and butyrylcholinesterase (BuChE) in vitro, using tacrine (hAChE, IC(50) = 305.78 nM; hBuChE, IC(50) = 56.72 nM) and donepezil (hAChE, IC(50) = 89.32 nM; hBuChE, IC(50) = 9137.16 nM) as positive controls. Compound B19 exhibited an excellent and balanced inhibitory potency against AChE (IC(50) = 30.68 nM) and BuChE (IC(50) = 124.57 nM). The cytotoxicity assays demonstrated that the PC12 cell viability rates of compound B19 (84.37 %) were close to that of tacrine (87.73 %) and donepezil (79.71 %). Potential therapeutic effects in AD were evaluated using the neuroprotective effect of compounds against H(2)O(2)-induced toxicity, and compound B19 (68.77 %) exhibited substantially neuroprotective activity at the concentration of 25 microM, compared with the model group (30.34 %). Furthermore, compound B19 protected PC12 cells from H(2)O(2)-induced apoptosis and ROS production. These properties of compound B19 suggested that it was a multi-functional agent with AChE inhibition, anti-oxidative, anti-inflammatory activities, and low toxicity and that it deserves further investigation as a promising agent for AD treatment.
ESTHER : Wang_2023_Bioorg.Chem_143_107010
PubMedSearch : Wang_2023_Bioorg.Chem_143_107010
PubMedID: 38056387

Title : Introducing Mn into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer for detection of organophosphorus pesticides - Feng_2023_Mikrochim.Acta_190_437
Author(s) : Feng Y , Hu P , Wang M , Sun X , Pan W , Wang J
Ref : Mikrochim Acta , 190 :437 , 2023
Abstract : In order to design and establish a highly efficient and selective nanozyme-based sensing platform for the UV-vis detection of organophosphorus pesticides (OPs), Mn was introduced into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer. The Mn-doped ZIF-8 (Mn-ZIF-8) nanocomposites were synthesized with a very facile one-pot method by heating the mixture of ZnO, 2-methylimidazole (Hmin) and Mn(CH(3)COO)(2).4H(2)O in a solvent-free system at 180 degreesC for 8 h. The Mn-ZIF-8 nanocomposite showed a higher peroxidase activity and an additional thiocholine (TCh)-degradable property compared to the pristine ZIF-8. OPs could inhibit acetylcholinesterase (AChE) to catalyze the hydrolysis of acetylthiocholine (ATCh) to produce TCh, thus blocking the degradation of Mn-ZIF-8 and protecting the catalysis of the oxidation of colorless 3,3',5,5'-tetramethylbenzydine (TMB) to blue oxidized TMB (ox-TMB). Accordingly, a detection method for OPs with high sensitivity and selectivity was designed and established on the basis of the Mn-ZIF-8 nanozyme with a linear range of 0.1-20 nM and a limit of detection (LOD) as low as 54 pM.
ESTHER : Feng_2023_Mikrochim.Acta_190_437
PubMedSearch : Feng_2023_Mikrochim.Acta_190_437
PubMedID: 37843605

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

Title : New Fusarin Derivatives from the Marine Algicolous Fungus Penicillium steckii SCSIO41040 - Song_2023_Mar.Drugs_21_
Author(s) : Song Y , She J , Chen W , Wang J , Tan Y , Pang X , Zhou X , Liu Y
Ref : Mar Drugs , 21 : , 2023
Abstract : Five new fusarin derivatives, steckfusarins A-E (1-5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC(50) value of 74.5 microg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 microM.
ESTHER : Song_2023_Mar.Drugs_21_
PubMedSearch : Song_2023_Mar.Drugs_21_
PubMedID: 37888468

Title : Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities - Gan_2023_Chin.J.Nat.Med_21_154
Author(s) : Gan D , Li C , Shu Y , Wang J , Wang C , Zhu L , Yang Y , Liu J , He B , Cai L , Ding Z
Ref : Chin J Nat Med , 21 :154 , 2023
Abstract : The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C(28)-steroid with an unusual beta- and gamma-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC(50) value of 2.61 +/- 0.05 micromol.L(-1). The beta-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 microg.mL(-1). Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 microg.mL(-1), respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC(50) values of 9.2 +/- 0.03 and 13.3 +/- 0.01 micromol.L(-1), respectively.
ESTHER : Gan_2023_Chin.J.Nat.Med_21_154
PubMedSearch : Gan_2023_Chin.J.Nat.Med_21_154
PubMedID: 36871983

Title : Adipose triglyceride lipase: the first transacylase for FAHFAs - Wang_2023_Life.Metab_2_
Author(s) : Wang J , Liang G , Zhao TJ
Ref : Life Metab , 2 : , 2023
Abstract : In a recent article published in Nature, Patel et al. identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2) as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids (FAHFAs), further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies.
ESTHER : Wang_2023_Life.Metab_2_
PubMedSearch : Wang_2023_Life.Metab_2_
PubMedID: 37168434

Title : Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys - Wang_2023_Mol.Ther.Nucleic.Acids_31_68
Author(s) : Wang J , Zheng W , Zheng S , Yuan Y , Wen W , Cui W , Xue L , Sun X , Shang H , Zhang H , Xiao RP , Gao S , Zhang X
Ref : Mol Ther Nucleic Acids , 31 :68 , 2023
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.
ESTHER : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedSearch : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedID: 36618267

Title : Development of integrated smartphone\/resistive biosensor for on-site rapid environmental monitoring of organophosphate pesticides in food and water - Maanaki_2023_Biosens.Bioelectron.X_15_
Author(s) : Maanaki H , Xu T , Chen G , Du X , Wang J
Ref : Biosensors & Bioelectronics X , 15 : , 2023
Abstract : Organophosphate (OP) pesticides remain a worldwide health concern due to their acute or chronic poisoning and widespread use in agriculture around the world. There is a need for robust and field-deployable tools for onsite detection of OP pesticides in food and water. Herein, we present an integrated smartphone/resistive biosensor for simple, rapid, reagentless, and sensitive monitoring of OP pesticides in food and environmental water. The biosensor leverages the hydrolytic activity of acetylcholinesterase (AChE) to its substrate, acetylcholine (ACh), and unique transport properties of polyaniline nanofibers (PAnNFs) of chitosan/AChE/PAnNF/carbon nanotube (CNT) nanocomposite film on a gold interdigitated electrode. The principle of the sensor relies on OP inhibiting AChE, thus, reducing the rate of ACh hydrolysis and consequently decreasing the rate of protons doping the PAnNFs. Such resulted decrease in conductance of PAnNF can be used to quantify OP pesticides in a sample. A mobile app for the biosensor was developed for analyzing measurement data and displaying and sharing testing results. Under optimal conditions, the biosensor demonstrated a wide linear range (1 ppt-100 ppb) with a low detection limit (0.304 ppt) and high reproducibility (RSD <5%) for Paraoxon-Methyl (PM), a model analyte. Furthermore, the biosensor was successfully applied for analyzing PM spiked food/water samples with an average recovery rate of 98.3% and provided comparable results with liquid chromatography-mass spectrometry. As such, the nanosensing platform provides a promising tool for onsite rapid and sensitive detection of OP pesticides in food and environmental water.
ESTHER : Maanaki_2023_Biosens.Bioelectron.X_15_
PubMedSearch : Maanaki_2023_Biosens.Bioelectron.X_15_
PubMedID: 38124900

Title : Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target - Wang_2023_Science_381_eadd5787
Author(s) : Wang K , Zhang Z , Hang J , Liu J , Guo F , Ding Y , Li M , Nie Q , Lin J , Zhuo Y , Sun L , Luo X , Zhong Q , Ye C , Yun C , Zhang Y , Wang J , Bao R , Pang Y , Wang G , Gonzalez FJ , Lei X , Qiao J , Jiang C
Ref : Science , 381 :eadd5787 , 2023
Abstract : A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.
ESTHER : Wang_2023_Science_381_eadd5787
PubMedSearch : Wang_2023_Science_381_eadd5787
PubMedID: 37535747
Gene_locus related to this paper: bactn-BT4193

Title : Toxic effects of isofenphos-methyl on zebrafish embryonic development - Wu_2023_Ecotoxicol.Environ.Saf_254_114723
Author(s) : Wu Y , Wang J , Xia Y , Tang K , Xu J , Wang A , Hu S , Wen L , Wang B , Yao W
Ref : Ecotoxicology & Environmental Safety , 254 :114723 , 2023
Abstract : Isofenphos-methyl (IFP) is widely used as an organophosphorus for controlling underground insects and nematodes. However, excessive use of IFP may pose potential risks to the environment and humans, but little information is available on its sublethal toxicity to aquatic organisms. To address this knowledge gap, the current study exposed zebrafish embryos to 2, 4, and 8 mg/L IFP within 6-96 h past fertilization (hpf) and measured mortality, hatching, developmental abnormalities, oxidative stress, gene expressions, and locomotor activity. The results showed that IFP exposure reduced the rates of heart and survival rate, hatchability, and body length of embryos and induced uninflated swim bladder and developmental malformations. Reduction in locomotive behavior and inhibition of AChE activity indicated that IFP exposure may induce behavioral defects and neurotoxicity in zebrafish larvae. IFP exposure also led to pericardial edema, longer venous sinus-arterial bulb (SV-BA) distance, and apoptosis of the heart cells. Moreover, IFP exposure increased the accumulation of reactive oxygen species (ROS) and the content of malonaldehyde (MDA), also elevated the levels of antioxidant enzymes of superoxide dismutase (SOD) and catalase (CAT), but decreased glutathione (GSH) levels in zebrafish embryos. The relative expressions of heart development-related genes (nkx2.5, nppa, gata4, and tbx2b), apoptosis-related genes (bcl2, p53, bax, and puma), and swim bladder development-related genes (foxA3, anxa5b, mnx1, and has2) were significantly altered by IFP exposure. Collectively, our results indicated that IFP induced developmental toxicity and neurotoxicity to zebrafish embryos and the mechanisms may be relevant to the activation of oxidative stress and reduction of acetylcholinesterase (AChE) content.
ESTHER : Wu_2023_Ecotoxicol.Environ.Saf_254_114723
PubMedSearch : Wu_2023_Ecotoxicol.Environ.Saf_254_114723
PubMedID: 36871354

Title : Discovery selective acetylcholinesterase inhibitors to control Tetranychus urticae (Acari: Tetranychidae) - Wang_2023_J.Insect.Sci_23_19
Author(s) : Wang J , Cao Y , Lai B , Liu Y , Li C , Bu C
Ref : J Insect Sci , 23 :19 , 2023
Abstract : The two-spotted spider mite, Tetranychus urticae Koch, has a broad host plant range and presents an extreme capacity for developing pesticide resistance, becoming a major economic pest in agriculture. Anticholinesterase insecticides still account for a big part of global insecticide sales. However, there is a growing concern about the serious resistance problems of anticholinesterase insecticides and their nontarget toxicity. In this study, structure-based virtual screening was performed to discover selective AChE inhibitors from the ChemBridge database, and 39 potential species-specific AChE inhibitor were obtained targeting T. urticae AChE, but not human AChE. Among them, compound No. 8 inhibited AChE from T. urticae, but not from human, and had an inhibitory activity comparable to that of eserine. Compound No. 8 had dose-dependent toxicity to T. urticae in glass slide-dipping assay and had significant mite control effects in a pot experiment, but required a high concentration to achieve similar control effects to spirodiclofen. The toxicity evaluation suggested that compound No. 8 had no acute toxicity on pollinator honey bees and natural predator N. californicus and did not affect strawberry growth in our assay. Compound No. 8 is a potential lead compound for developing novel acaricides with reduced nontarget toxicity.
ESTHER : Wang_2023_J.Insect.Sci_23_19
PubMedSearch : Wang_2023_J.Insect.Sci_23_19
PubMedID: 37578847
Gene_locus related to this paper: 9acar-m9t420

Title : Identification, expression profiles and involvement in insecticides tolerance and detoxification of carboxylesterase genes in Bactrocera dorsalis - Li_2023_Pestic.Biochem.Physiol_193_105443
Author(s) : Li Z , Chen M , Bai W , Zhang S , Meng L , Dou W , Wang J , Yuan G
Ref : Pestic Biochem Physiol , 193 :105443 , 2023
Abstract : Carboxylesterases (CarEs) are a multifunctional superfamily of enzymes and play an important role in detoxification of various insecticides in insects. The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive agricultural pests and has developed different degrees of resistance to organophosphates in field. However, the involvement of BdCarEs in tolerance or resistance to other alternative insecticides are still unclear. In the present study, 33 BdCarEs genes were identified based on the genome database of B. dorsalis. Phylogenetic analysis demonstrated that they were classified into nine clades, with abundance of alpha-esterases. Meanwhile, the sequence characterization and the chromosome distribution were also analyzed. The spatiotemporal expression analysis of BdCarEs genes suggested that the diversity of potential function in different physiological processes. With the exception of BdCarE21, all BdCarEs genes responded to at least one insecticide exposure, and BdCarE20 was found to be up-regulated after exposure to all five tested insecticides individually. Eight BdCarEs genes were overexpressed in MR strain when compared to that in SS strain. Subsequently, knockdown the expression of representative BdCarEs genes significantly increased the susceptibility of the oriental fruit fly to corresponding insecticides, which indicated that the tested BdCarEs genes contributed to one or multiple insecticide detoxification. These findings provide valuable insights into the potential role in respond to tolerance or resistance to insecticides with different mode of action, and will facilitate development of efficiency management strategy for B. dorsalis.
ESTHER : Li_2023_Pestic.Biochem.Physiol_193_105443
PubMedSearch : Li_2023_Pestic.Biochem.Physiol_193_105443
PubMedID: 37248012

Title : Molecular insights into the catalytic mechanism of plasticizer degradation by a monoalkyl phthalate hydrolase - Chen_2023_Commun.Chem_6_45
Author(s) : Chen Y , Wang Y , Xu Y , Sun J , Yang L , Feng C , Wang J , Zhou Y , Zhang ZM
Ref : Commun Chem , 6 :45 , 2023
Abstract : Phthalate acid esters (PAEs), a group of xenobiotic compounds used extensively as plasticizers, have attracted increasing concern for adverse effects to human health and the environment. Microbial degradation relying on PAE hydrolases is a promising treatment. However, only a limited number of PAE hydrolases were characterized to date. Here we report the structures of MehpH, a monoalkyl phthalate (MBP) hydrolase that catalyzes the reaction of MBP to phthalic acid and the corresponding alcohol, in apo and ligand-bound form. The structures reveal a positively-charged catalytic center, complementary to the negatively-charged carboxyl group on MBP, and a penetrating tunnel that serves as exit of alcohol. The study provides a first glimpse into the enzyme-substrate binding model for PAE hydrolases, leading strong support to the development of better enzymes in the future.
ESTHER : Chen_2023_Commun.Chem_6_45
PubMedSearch : Chen_2023_Commun.Chem_6_45
PubMedID: 36859434
Gene_locus related to this paper: 9acto-q2mhh5

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 : Strategy of In Situ Electrochemical Regulation for Highly Enhanced Nonenzymatic Sensing of Carbaryl - Lv_2023_Anal.Chem__
Author(s) : Lv Y , Zhang Y , Yang Y , Li J , Wang J , Xiao X , Zhang M
Ref : Analytical Chemistry , : , 2023
Abstract : Specific and sensitive sensing of most pesticide residues relies on enzymes such as acetylcholinesterase and advanced materials, which need to be loaded on the surface of working electrodes, leading to instability, uneven surface, tedious process, and high cost. Meanwhile, employing certain potential or current in electrolyte solution could also modify the surface in situ and overcome these drawbacks. However, this method is only regarded as electrochemical activation widely applied in the pretreatment of electrodes. In this paper, by means of regulating the electrochemical technique and its parameters, we prepared a proper sensing interface and derivatized the carbaryl (a carbamate pesticide) hydrolyzed form (1-naphthol) to enhance sensing by 100 times within several minutes. After regulation I by chronopotentiometry with 0.2 mA for 20 s or chronoamperometry with 2 V for 10 s, abundant oxygen-containing groups form and the ordered carbon structure is destroyed. Sweeping from -0.5 to 0.9 V through cyclic voltammetry for only one segment, following regulation II, the composition of oxygen-containing groups changes and the disordered structure is alleviated. Finally, on the constructed sensing interface, test by regulation III through differential pulse voltammetry from 0.8 to -0.4 V, resulting in derivatization of 1-naphthol during 0.8-0 V, followed by electroreduction of the derivative at around -0.17 V. Compared with the electro-oxidation peak at 0.5 V in previous reports, it is essential to improve specificity, even toward several other carbamate pesticides with similar structures. Hence, the in situ electrochemical regulation strategy has demonstrated great potential for effective sensing of electroactive molecules.
ESTHER : Lv_2023_Anal.Chem__
PubMedSearch : Lv_2023_Anal.Chem__
PubMedID: 36802553

Title : Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease - Tao_2023_Front.Psychiatry_14_1184673
Author(s) : Tao X , Yang C , He J , Liu Q , Wu S , Tang W , Wang J
Ref : Front Psychiatry , 14 :1184673 , 2023
Abstract : BACKGROUND AND PURPOSE: Blood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients. METHODS: This was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (> 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression. RESULTS: (1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p < 0.001) had a weak positively association with HAMD scores, and ChE (r = -0.226, p < 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p < 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p < 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe. CONCLUSION: Hb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD.
ESTHER : Tao_2023_Front.Psychiatry_14_1184673
PubMedSearch : Tao_2023_Front.Psychiatry_14_1184673
PubMedID: 37469359

Title : Curcumin protects against fenvalerate-induced neurotoxicity in zebrafish (Danio rerio) larvae through inhibition of oxidative stress - Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
Author(s) : Zhu J , Huang M , Liu C , Wang J , Zou L , Yang F , Zhu R
Ref : Ecotoxicology & Environmental Safety , 264 :115484 , 2023
Abstract : Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 microg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.
ESTHER : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedSearch : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedID: 37716069

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 : Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease - Yang_2023_Phytomedicine_109_154600
Author(s) : Yang M , Zhang X , Qiao O , Ji H , Zhang Y , Han X , Wang W , Li X , Wang J , Guo L , Huang L , Gao W
Ref : Phytomedicine , 109 :154600 , 2023
Abstract : BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A beta oligomer, inhibit the deposition of A beta, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease.
ESTHER : Yang_2023_Phytomedicine_109_154600
PubMedSearch : Yang_2023_Phytomedicine_109_154600
PubMedID: 36610144

Title : A portable acetylcholinesterase-based electrochemical sensor for field detection of organophosphorus - Wen_2023_RSC.Adv_13_6389
Author(s) : Wen L , Wang J , Liu Z , Tao CA , Rao J , Hang J , Li Y
Ref : RSC Adv , 13 :6389 , 2023
Abstract : A portable acetylcholinesterase (AChE)-based electrochemical sensor based on a screen-printed carbon electrode (SPCE) and a miniature potentiostat was constructed for the rapid field detection of organophosphorus pesticides (OPs). Graphene (GR) and gold nanoparticles (AuNPs) were successively introduced onto SPCE for surface modification. Due to the synergistic effect of the two nanomaterials, the signal of the sensor has a significant enhancement. Take isocarbophos (ICP) as a model for chemical warfare agents (CAWs) and Ops; the SPCE/GR/AuNPs/AChE/Nafion sensor shows a wider linear range (0.1-2000 microg L(-1)), and a lower limit of detection (0.012 microg L(-1)) than SPCE/AChE/Nafion and SPCE/GR/AChE/Nafion sensors. Tests in actual fruit and tap water samples also yielded satisfactory results. Therefore, the proposed method can be used as a simple and cost-effective strategy for construction of portable electrochemical sensors for OP field detection.
ESTHER : Wen_2023_RSC.Adv_13_6389
PubMedSearch : Wen_2023_RSC.Adv_13_6389
PubMedID: 36874943

Title : Genome-wide identification and expression of monoacylglycerol lipase (MAGL) gene family in peanut (Arachis hypogaea L.) and functional analysis of AhMGATs in neutral lipid metabolism - Zhan_2023_Int.J.Biol.Macromol_243_125300
Author(s) : Zhan Y , Wu T , Zhao X , Wang J , Guo S , Chen S , Qu S , Zheng Z
Ref : Int J Biol Macromol , 243 :125300 , 2023
Abstract : Monoacylglycerol lipase (MAGL) involved in regulating plant growth and development and stress responses, hydrolyzes monoacylglycerol (MAG) into free fatty acid and glycerol, which is the last step of triacylglycerol (TAG) breakdown. Here, a genome-wide characterization of MAGL gene family from cultivated peanut (Arachis hypogaea L.) was performed. In total, 24 MAGL genes were identified and unevenly distributed on 14 chromosomes, encoding 229-414 amino acids with molecular weights ranging from 25.91 to 47.01 kDa. Spatiotemporal and stress-induced expression was analyzed by qRT-PCR. Multiple sequence alignment revealed that AhMAGL1a/b and AhMAGL3a/b were the only four bifunctional enzymes with conserved regions of hydrolase and acyltransferase, which could also be named as AhMGATs. GUS histochemical assay showed that AhMAGL1a and -1b were strongly expressed in all tissues of the plants; whereas both AhMAGL3a and -3b were weakly expressed in plants. Subcellular localization analysis indicated that AhMGATs were localized in the endoplasmic reticulum and/or Golgi complex. Seed-specific overexpression of AhMGATs in Arabidopsis decreased the oil content of the seeds and altered the fatty acid compositions, indicating that AhMGATs were involved in TAG breakdown but not TAG biosynthesis in plant seeds. This study lays the foundation for better understanding AhMAGL genes biological function in planta.
ESTHER : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedSearch : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedID: 37315669
Gene_locus related to this paper: arahy-h9lbh7

Title : Do 'Newly Born' orphan proteins resemble 'Never Born' proteins? A study using three deep learning algorithms - Liu_2023_Proteins__
Author(s) : Liu J , Yuan R , Shao W , Wang J , Silman I , Sussman JL
Ref : Proteins , : , 2023
Abstract : "Newly Born" proteins, devoid of detectable homology to any other proteins, known as orphan proteins, occur in a single species or within a taxonomically restricted gene family. They are generated by the expression of novel open reading frames, and appear throughout evolution. We were curious if three recently developed programs for predicting protein structures, namely, AlphaFold2, RoseTTAFold, and ESMFold, might be of value for comparison of such "Newly Born" proteins to random polypeptides with amino acid content similar to that of native proteins, which have been called "Never Born" proteins. The programs were used to compare the structures of two sets of "Never Born" proteins that had been expressed-Group 1, which had been shown experimentally to possess substantial secondary structure, and Group 3, which had been shown to be intrinsically disordered. Overall, although the models generated were scored as being of low quality, they nevertheless revealed some general principles. Specifically, all four members of Group 1 were predicted to be compact by all three algorithms, in agreement with the experimental data, whereas the members of Group 3 were predicted to be very extended, as would be expected for intrinsically disordered proteins, again consistent with the experimental data. These predicted differences were shown to be statistically significant by comparing their accessible surface areas. The three programs were then used to predict the structures of three orphan proteins whose crystal structures had been solved, two of which display novel folds. Surprisingly, only for the protein which did not have a novel fold, and was taxonomically restricted, rather than being a true orphan, did all three algorithms predict very similar, high-quality structures, closely resembling the crystal structure. Finally, they were used to predict the structures of seven orphan proteins with well-identified biological functions, whose 3D structures are not known. Two proteins, which were predicted to be disordered based on their sequences, are predicted by all three structure algorithms to be extended structures. The other five were predicted to be compact structures with only two exceptions in the case of AlphaFold2. All three prediction algorithms make remarkably similar and high-quality predictions for one large protein, HCO_11565, from a nematode. It is conjectured that this is due to many homologs in the taxonomically restricted family of which it is a member, and to the fact that the Dali server revealed several nonrelated proteins with similar folds. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at
ESTHER : Liu_2023_Proteins__
PubMedSearch : Liu_2023_Proteins__
PubMedID: 37092778

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase - Yu_2023_J.Pharm.Anal_13_1024
Author(s) : Yu H , Xu H , Yang X , Zhang Z , Hu J , Lu J , Fu J , Bu M , Zhang H , Zhai Z , Wang J , Jiang J , Wang Y
Ref : J Pharm Anal , 13 :1024 , 2023
Abstract : Specnuezhenide (SNZ) is among the main components of Fructus Ligustri Lucidi, which has anti-inflammation, anti-oxidation, and anti-tumor effect. The low bioavailability makes it difficult to explain the mechanism of pharmacological effect of SNZ. In this study, the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were explored. SNZ can be rapidly metabolized by the gut microbiome, and two intestinal bacterial metabolites of SNZ, salidroside and tyrosol, were discovered. In addition, carboxylesterase may be the main intestinal bacterial enzyme that mediates its metabolism. At the same time, no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate, indicating that the gut microbiota is the main part involved in the metabolism of SNZ. In addition, pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut microbiota. Interestingly, tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ, which indicated that SNZ exhibited potential to inhibit tumor growth, and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor tissues. At the same time, SNZ modulated the structure of gut microbiota and fungal group, which may be the mechanism governing the antitumoral activity of SNZ. Furthermore, SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in vivo. In the future, targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
ESTHER : Yu_2023_J.Pharm.Anal_13_1024
PubMedSearch : Yu_2023_J.Pharm.Anal_13_1024
PubMedID: 37842660

Title : The serum concentration and activity of DPP4 is positively related with the severity of hyperthyroidism in patients with Graves' disease - Chang_2023_Ann.Med_55_2226910
Author(s) : Chang X , Ding X , Wang J , Cai Q , Wang G , Liu J
Ref : Ann Med , 55 :2226910 , 2023
Abstract : OBJECTIVE: Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. METHODS: A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. RESULTS: The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). CONCLUSIONS: The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves' disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves' disease.In patients with Graves 'disease, serum DPP4 activity was positively correlated with TRAb levels.
ESTHER : Chang_2023_Ann.Med_55_2226910
PubMedSearch : Chang_2023_Ann.Med_55_2226910
PubMedID: 37350750

Title : Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study - Zhang_2023_Food.Chem_431_137164
Author(s) : Zhang T , Wang J , Zhao Y , Wang Z , Hu D , Liu Y , Zhang X , Li H , Zhao B , Li B
Ref : Food Chem , 431 :137164 , 2023
Abstract : Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
ESTHER : Zhang_2023_Food.Chem_431_137164
PubMedSearch : Zhang_2023_Food.Chem_431_137164
PubMedID: 37607420

Title : Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect - Gong_2023_Acta.Cir.Bras_38_e385523
Author(s) : Gong Y , Kang P , Wang J , Chen Y , Wei Z
Ref : Acta Cir Bras , 38 :e385523 , 2023
Abstract : PURPOSE: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. METHODS: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. RESULTS: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid beta; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1beta), and tumor necrosis factor-alpha. Sevoflurane significantly reduced the activity of caspase-3. CONCLUSIONS: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.
ESTHER : Gong_2023_Acta.Cir.Bras_38_e385523
PubMedSearch : Gong_2023_Acta.Cir.Bras_38_e385523
PubMedID: 38055394

Title : Genome-wide identification and analysis of the SUPPRESSOR of MAX2 1-LIKE gene family and its interaction with DWARF14 in poplar - Sun_2023_BMC.Plant.Biol_23_105
Author(s) : Sun M , Wang D , Liu C , Liu Y , Niu M , Wang J , Li J
Ref : BMC Plant Biol , 23 :105 , 2023
Abstract : BACKGROUND: Strigolactones (SLs) are important phytohormones that can regulate branch development in plants. Although SUPPRESSOR of MAX2 1-LIKE proteins (SMXLs) play a crucial role in SL signaling transduction, the SMXL gene family has not been well characterized in poplar. RESULTS: In this study, 12 members of the poplar SMXL gene family were identified and phylogenetically classified into four clades. Motif and 3D structural analyses revealed that PtSMXL proteins are structurally very conserved; however, the P-loop NTPase domain at the C-terminal was found to vary substantially among clades. A genomic collinearity analysis indicated that PtSMXL gene family members have expanded during recent genome doubling events in poplar, with all gene pairs subsequently undergoing purifying selection. According to a Cis-element analysis, PtSMXL promoters contain many light-responsive elements. In an expression pattern analysis, all 12 PtSMXL genes displayed tissue-specific expression, especially PtSMXL8a. PtSMXL7b expression was significantly downregulated after axillary bud growth begins. In addition, the expressions of PtSMXL7b and PtSMXL8a were highly induced by 2 microM GR24, a synthetic SL analog, thus suggesting that these genes are involved in SL-regulated axillary bud growth. In a yeast two-hybrid assay, only PtSMXL7b in clade II was able to interact with the SL receptor PtD14a in an SL dependent manner, which indicates that PtSMXL7b may be the functional homolog of D53/SMXL6/7/8 in poplar. Finally, we established its ability to affect axillary bud growth by constructing poplar overexpressing the PtSMXL7b gene. CONCLUSIONS: Our findings may inform future research on the functions of SMXLs in poplar, especially with respect to branch development.
ESTHER : Sun_2023_BMC.Plant.Biol_23_105
PubMedSearch : Sun_2023_BMC.Plant.Biol_23_105
PubMedID: 36814183

Title : Molecular, morphological and behavioral alterations of zebrafish (Danio rerio) embryos\/larvae after clorprenaline hydrochloride exposure - Wang_2023_Food.Chem.Toxicol_176_113776
Author(s) : Wang B , Wang A , Xu C , Tong Z , Wang Y , Zhuo X , Fu L , Yao W , Wang J , Wu Y
Ref : Food & Chemical Toxicology , 176 :113776 , 2023
Abstract : Chlorprenaline hydrochloride (CLOR) is a typical representative of beta-adrenergic agonists that may be used illegally as a livestock feed additive and may have adverse impacts on the environment. In the present study, zebrafish embryos were exposed to CLOR to investigate its developmental toxicity and neurotoxicity. The results demonstrated that CLOR exposure led to adverse effects on developing zebrafish, such as morphological changes, a high heart rate, and increased body length, resulting in developmental toxicity. Moreover, the up-regulation of activities of superoxide dismutase (SOD) and catalase (CAT) and the enhancement of malondialdehyde (MDA) content illustrated that CLOR exposure activated oxidative stress in exposed zebrafish embryos. Meanwhile, CLOR exposure also caused alterations in locomotive behavior in zebrafish embryos, including an increase in acetylcholinesterase (AChE) activity. Quantitative polymerase chain reaction (QPCR) results showed that the transcription of genes related to the central nervous system (CNS) development, namely, mbp, syn2a, alpha1-tubulin, gap43, shha, and elavl3, indicated that CLOR exposure could lead to neurotoxicity in zebrafish embryos. These results showed that CLOR exposure could cause developmental neurotoxicity in the early stages of zebrafish development and that CLOR might induce neurotoxicity by altering the expression of neuro-developmental genes, elevating AChE activity, and activating oxidative stress.
ESTHER : Wang_2023_Food.Chem.Toxicol_176_113776
PubMedSearch : Wang_2023_Food.Chem.Toxicol_176_113776
PubMedID: 37059383

Title : Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C - Kuang_2023_Gen.Physiol.Biophys_42_361
Author(s) : Kuang Y , Wang J , Dong Y , Cheng Y , Li H , Ji Y , Gao H , Cao X
Ref : Gen Physiol Biophys , 42 :361 , 2023
Abstract : Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients were extracted from the Gene Expression Omnibus (GEO) database (GSE130036) and analyzed by weighted gene coexpression network analysis (WGCNA). A total of 31 coexpression modules were identified. The coexpression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packages in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. We further verified the expression of CES1 and CTSC was downregulated in HCM clinical blood and negatively correlated with Maxi LVWT. Finally, we demonstrated that overexpression of CTSC and CES1 could alleviate HCM in an HCM cell model. In summary, the study suggests that CES1 and CTSC negatively regulate the development of HCM and have potential as therapeutic and diagnostic targets for HCM.
ESTHER : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedSearch : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedID: 37449320

Title : Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases - Chen_2023_J.Med.Chem__
Author(s) : Chen Y , Chen L , Xu H , Cao R , Morisseau C , Zhang M , Shi Y , Hammock BD , Wang J , Zhuang J , Liu Z , Chen G
Ref : Journal of Medicinal Chemistry , : , 2023
Abstract : Soluble epoxide hydrolase (sEH) has been identified as an attractive target for anti-inflammatory drug design in recent years. Picomolar level compound G1 against sEH was obtained by introducing the hydrophilic group homopiperazine and hydrophobic fragment propionyl onto the structure of lead compound A. G1 showed good microsomal stability, a moderate plasma protein binding rate, and good oral bioavailability and was well tolerated in rats. G1 has significant analgesic effects on CFA-induced AIA mice, ameliorated the pancreatic injury in acute pancreatitis induced by l-arginine, reversed pancreatic injury, edema, and neutrophil infiltration, and increased the survival time of C57BL/6 mice in a lipopolysaccharide (LPS)-induced sepsis model. Moreover the expression levels of sEH, COX-2, NOS-2, vascular cell adhesion molecule (VCAM), IL-6, MCP-5, and tumor necrosis factor alpha (TNF-alpha) were measured by Western blot or enzyme-linked immunosorbent assay (ELISA), with varying degrees of decrease. These results suggested that G1 is a drug candidate worthy of further evaluation for the treatment of inflammation-induced diseases such as arthritis, acute pancreatitis, and sepsis.
ESTHER : Chen_2023_J.Med.Chem__
PubMedSearch : Chen_2023_J.Med.Chem__
PubMedID: 36689364

Title : Influence of Cry1Ab protein on growth and development of a predatory spider, Pardosa pseudoannulata, from protective perspectives - He_2023_Ecotoxicol.Environ.Saf_269_115799
Author(s) : He Y , Lv B , Chao Y , Tang YE , Wang J , Wang Z , Peng YD
Ref : Ecotoxicology & Environmental Safety , 269 :115799 , 2023
Abstract : The expression of Cry proteins in genetically modified rice varieties safeguards the crop from lepidopteran pests. These proteins have the potential to be transferred through the food chain to arthropods like planthoppers and predatory spiders, triggering defensive responses in these unintended organisms. Hence, we hypothesized that Cry protein might influence the growth and development of spiders by altering protective enzyme activities. The results showed that Cry1Ab protein could accumulate in tissues and subcellular organelles of Pardosa pseudoannulata from Nilaparvata lugens. Cry1Ab protein exposure prolonged the developmental duration in the 5th and 7th instar spiderlings but induced no alterations of other growth indicators, such as body length, median ocular area, and survival rate. In addition, Cry1Ab protein exerted no adverse impacts on several detoxifying enzymes (i.e., superoxide dismutase, catalase, glutathione peroxidase, and acetylcholine esterase) in muscle, midgut, ganglia, and hemolymph at subcellular components (i.e., microsome and cytoplasm). To further explore the effects of Cry1Ab protein on the spiderlings, we performed an integrated transcriptome analysis on spiderlings exposed to Cry1Ab protein. The results showed that Cry1Ab protein might prolong the development duration of P. pseudoannulata via the altered cuticle metabolism (e.g., chitin metabolic process and structural constituent of cuticle). In addition, the gene expression profile associated with detoxifying enzymes and three stress-responsive pathways (JAK/STAT, JNK/SAPK, and Hippo pathways) also displayed no significant alterations under Cry1Ab exposure. Collectively, this integrated analysis generates multidimensional insights to assess the effects of Cry1Ab protein on non-target spiders and demonstrates that Cry1Ab protein exerts no toxicity in P. pseudoannulata.
ESTHER : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedSearch : He_2023_Ecotoxicol.Environ.Saf_269_115799
PubMedID: 38070414

Title : Green biosynthesis of rare DHA-phospholipids by lipase-catalyzed transesterification with edible algal oil in solvent-free system and catalytic mechanism study - Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
Author(s) : Zhang T , Li B , Wang Z , Hu D , Zhang X , Zhao B , Wang J
Ref : Front Bioeng Biotechnol , 11 :1158348 , 2023
Abstract : Docosahexaenoic acid (DHA)-enriched phosphatidylcholine (PC) has received significant scientific attention due to the health benefits in food and pharmaceutical products. In this work, the edible algal oil rich in DHA-triacylglycerol (DHA-TAG) without pretreatment was first used as the DHA donor for the transesterification of phospholipids (PLs) to prepare three kinds of rare PLs, including DHA-PC, DHA-phosphatidylethanolamine (DHA-PE), and DHA-phosphatidylserine (DHA-PS). Here, 153 protein structures of triacylglycerol lipase (EC were virtually screened and evaluated by transesterification. PLA1 was the best candidate due to a higher DHA incorporation. Results showed that the transesterification of PC with DHA-TAG at 45 degreesC and 0.7% water content (without additional water addition) could produce DHA-PC with 39.1% DHA incorporation at 30 min. The different DHA donors, including forms of fatty acid, methyl ester, and triglycerides, were compared. Molecular dynamics (MD) was used to illustrate the catalytic mechanism at the molecular level containing the diffusions of substrates, the structure-activity relationship of PLA1, and the effect of water content.
ESTHER : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedSearch : Zhang_2023_Front.Bioeng.Biotechnol_11_1158348
PubMedID: 37064237

Title : A - 63 Neuropsychiatric and Cognitive Correlates of Pareidolias in Dementia with Lewy Bodies - Smith_2023_Arch.Clin.Neuropsychol__
Author(s) : Smith MP , Wang J , Leverenz JB , Heller NH , Magsaman SH , Bakker A , Zabetian CB , Tsuang DW , Oguh O , Lippa CF , Lopez OL , Berman SB , Irwin DJ , Galasko DR , Litvan I , Fleisher JE , Galvin JE , Bozoki AC , Sabbagh MN , Wint D , Cholerton BA , Pantelyat AY , Kamath V
Ref : Arch Clin Neuropsychol , : , 2023
Abstract : OBJECTIVE: Pareidolias represent visual illusions of meaningful objects in ambiguous stimuli. Prior research has demonstrated phenomenological similarities between pareidolias and visual hallucinations (VH) and the potential clinical utility of pareidolias in discriminating dementia with Lewy bodies (DLB) from Alzheimer's dementia (ad). Though pareidolias have been linked with VH severity in DLB, the relationships between pareidolias and other neuropsychiatric symptoms have not been explored in large DLB samples. METHOD: Individuals meeting 2017 McKeith criteria for probable DLB (n = 114) were enrolled in a multi-site systematic longitudinal study of the US DLB Consortium. Study assessments included an informant-rated psychiatric inventory (NPI), Montreal Cognitive Assessment (MoCA), and Noise Pareidolia Task (NPT). Ninety-five participants completed all clinical assessments. To examine baseline relationships between pareidolias responses (NPT) and the presence of 12 neuropsychiatric symptom dimensions (NPI), we used Poisson regression models with robust standard error estimates adjusted for age, education, disease duration, cognition (MoCA), and cholinesterase inhibitor use. RESULTS: Contrary to expectation, the presence of VH was not associated with pareidolias in DLB (Incidence Rate Ratio = 1.37, p = 0.275). The presence of both delusions (IRR = 2.11, p = 0.01) and depression (IRR = 1.79, p = 0.015) was associated with greater pareidolias. Additionally, overall cognitive dysfunction was associated with pareidolias (IRR = 0.90, p < 0.001). CONCLUSIONS: Our findings indicate that pareidolias are associated with poorer cognition and neuropsychiatric dimensions beyond VH, including depression and delusions. As pareidolias have been put forth as a surrogate marker of VH in DLB, future studies examining pareidolias in conjunction with comprehensive psychiatric/cognitive assessment and neuroimaging will further elucidate the clinical utility of pareidolia testing.
ESTHER : Smith_2023_Arch.Clin.Neuropsychol__
PubMedSearch : Smith_2023_Arch.Clin.Neuropsychol__
PubMedID: 37807184

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 : Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer's disease - Yang_2023_Bioorg.Chem_133_106432
Author(s) : Yang F , Zhao J , Chen G , Han H , Hu S , Wang N , Wang J , Chen Y , Zhou Z , Dai B , Hou Y , Liu Y
Ref : Bioorg Chem , 133 :106432 , 2023
Abstract : Alzheimer's disease (AD) implicates neuronal loss, plaque and neurofibrillary tangle formation, and disturbed neuronal Ca(2+) homeostasis, which leads to severe dementia, memory loss, as well as thinking and behavioral perturbations that could ultimately lead to death. Calcium dysregulation and low acetylcholine levels are two main mechanisms implicated in Alzheimer's disease progression. Simultaneous inhibition of calcium oscillations (store overload-induced Ca(2+) release [SOICR]) and acetylcholinesterase (AChE) by a single molecule may bring a new breath of hope for AD treatment. Here, we described some dantrolene derivatives as dual inhibitors of the ryanodine receptor and AChE. Two series of acylhydrazone/sulfonylhydrazone derivatives with aromaticgroup were designed and synthesized. In this study, the target compounds were evaluated for their ability to inhibit SOICR and AChE in vitro, using dantrolene and donepezil as positive controls. Compound 22a exhibited excellent and balanced inhibitory potency against SOICR (inhibition (%) = 90.1, IC(50) = 0.162 microM) and AChE (inhibition (%) = 93.5, IC(50) = 0.372 microM). Docking simulations showed that several preferred compounds could bind to the active sites of both the proteins, further validating the rationality of the design strategy. Potential therapeutic effects in AD were evaluated using the Barnes maze and Morris water maze tests, which demonstrated that compound 22a significantly improved memory and cognitive behavior in AD model mice. Moreover, it was also found that compound 22a could enhance synaptic strength by measuring hippocampal long-term potentiation (LTP) in brain slices. These results suggested that the introduction of a sulfonyl-hydrazone scaffold and aromatic substitution to dantrolene derivatives provided a useful template for the development of potential chemical entities against AD.
ESTHER : Yang_2023_Bioorg.Chem_133_106432
PubMedSearch : Yang_2023_Bioorg.Chem_133_106432
PubMedID: 36841050

Title : Review of the therapeutic potential of Forsythiae Fructus on the central nervous system: Active ingredients and mechanisms of action - Zhang_2023_J.Ethnopharmacol__117275
Author(s) : Zhang L , Lang F , Feng J , Wang J
Ref : J Ethnopharmacol , :117275 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has gained significant attention in recent years owing to its multi-component, multi-target, and multi-pathway advantages in treating various diseases. Forsythiae Fructus, derived from the dried fruit of Forsythia suspensa (Thunb.) Vahl, is one such traditional Chinese medicine with numerous in vivo and ex vivo therapeutic effects, including anti-inflammatory, antibacterial, and antiviral properties. Forsythiae Fructus contains more than 200 chemical constituents, with forsythiaside, forsythiaside A, forsythiaside B, isoforsythiaside, forsythin, and phillyrin being the most active ingredients. Forsythiae Fructus exerts neuroprotective effects by modulating various pathways, including oxidative stress, anti-inflammation, NF-kappaB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARgamma signaling pathway. AIM OF THE STUDY: This review aims to highlight the potential therapeutic effects of Forsythiae Fructus on the central nervous system and summarize the current knowledge on the active ingredients of Forsythia Fructus and their effects on different pathways involved in neuroprotection. MATERIALS AND METHODS: In this review, we conducted a comprehensive search of databases (PubMed, Google Scholar, Web of Science, China Knowledge Resource Integrated, local dissertations and books) up until June 2023 using key terms such as forsythia suspensa, Forsythiae Fructus, forsythiaside, isoforsythiaside, forsythin, phillyrin, Alzheimer's disease, Parkinson's disease, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, aging, and herpes simplex virus encephalitis. RESULTS: Our findings indicate that Forsythiae Fructus and its active ingredients own therapeutic effects on the central nervous system by modulating various pathways, including oxidative stress, anti-inflammation, NF-kappaB signaling, 2-AG, Nrf2 signaling, acetylcholinesterase, PI3K-Akt signaling, ferroptosis, the gut-brain axis, TLR4 signaling, endoplasmic reticulum stress, PI3K/Akt/mTOR signaling, and PPARgamma signaling pathway. CONCLUSION: Forsythiae Fructus and its active ingredients have demonstrated promising neuroprotective properties. Future in vivo and clinical studies of Forsythiae Fructus and its active ingredients should be conducted to establish precise dosage and standard guidelines for a more effective application in the treatment of neurological disorders.
ESTHER : Zhang_2023_J.Ethnopharmacol__117275
PubMedSearch : Zhang_2023_J.Ethnopharmacol__117275
PubMedID: 37797873

Title : Oligomerization of a plant helper NLR requires cell-surface and intracellular immune receptor activation - Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
Author(s) : Feehan JM , Wang J , Sun X , Choi J , Ahn HK , Ngou BPM , Parker JE , Jones JDG
Ref : Proc Natl Acad Sci U S A , 120 :e2210406120 , 2023
Abstract : Plant disease resistance involves both detection of microbial molecular patterns by cell-surface pattern recognition receptors and detection of pathogen effectors by intracellular NLR immune receptors. NLRs are classified as sensor NLRs, involved in effector detection, or helper NLRs required for sensor NLR signaling. TIR-domain-containing sensor NLRs (TNLs) require helper NLRs NRG1 and ADR1 for resistance, and helper NLR activation of defense requires the lipase-domain proteins EDS1, SAG101, and PAD4. Previously, we found that NRG1 associates with EDS1 and SAG101 in a TNL activation-dependent manner [X. Sun et al., Nat. Commun. 12, 3335 (2021)]. We report here how the helper NLR NRG1 associates with itself and with EDS1 and SAG101 during TNL-initiated immunity. Full immunity requires coactivation and mutual potentiation of cell-surface and intracellular immune receptor-initiated signaling [B. P. M. Ngou, H.-K. Ahn, P. Ding, J. D. G. Jones, Nature 592, 110-115 (2021), M. Yuan et al., Nature 592, 105-109 (2021)]. We find that while activation of TNLs is sufficient to promote NRG1-EDS1-SAG101 interaction, the formation of an oligomeric NRG1-EDS1-SAG101 resistosome requires the additional coactivation of cell-surface receptor-initiated defense. These data suggest that NRG1-EDS1-SAG101 resistosome formation in vivo is part of the mechanism that links intracellular and cell-surface receptor signaling pathways.
ESTHER : Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
PubMedSearch : Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
PubMedID: 36877846

Title : Ecological risk assessment of environmentally relevant concentrations of propofol on zebrafish (Danio rerio) at early life stage: Insight into physiological, biochemical, and molecular aspects - Jiang_2023_Chemosphere__137846
Author(s) : Jiang N , Li X , Wang Q , Baihetiyaer B , Fan X , Li M , Sun H , Yin X , Wang J
Ref : Chemosphere , :137846 , 2023
Abstract : Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L(-1)) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC(50) = 4.260 mg L(-1)), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L(-1) propofol treatment group was activated in response to oxidative damage, while activities of superoxide dismutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L(-1) was significant inhibited compared with the control group (p0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment.
ESTHER : Jiang_2023_Chemosphere__137846
PubMedSearch : Jiang_2023_Chemosphere__137846
PubMedID: 36646180

Title : Effects of Methyl Jasmonate Fumigation on the Growth and Detoxification Ability of Spodoptera litura to Xanthotoxin - Chen_2023_Insects_14_
Author(s) : Chen L , Song J , Wang J , Ye M , Deng Q , Wu X , Ren B
Ref : Insects , 14 : , 2023
Abstract : Methyl jasmonate (MeJA) is a volatile substance derived from jasmonic acid (JA), and it responds to interbiotic and abiotic stresses by participating in interplant communication. Despite its function in interplant communication, the specific role of MeJA in insect defense responses is poorly understood. In this study, we found that carboxylesterase (CarE) activities, glutathione-S-transferase (GSTs) activities, and cytochrome mono-oxygenases (P450s) content increased more after the feeding of diets containing xanthotoxin, while larvae exposed to MeJA fumigation also showed higher enzyme activity in a dose-dependent manner: lower and medium concentrations of MeJA induced higher detoxification enzyme activities than higher concentrations of MeJA. Moreover, MeJA improved the growth of larvae fed on the control diet without toxins and diets with lower concentrations of xanthotoxin (0.05%); however, MeJA could not protect the larvae against higher concentrations of xanthotoxin (0.1%, 0.2%). In summary, we demonstrated that MeJA is effective at inducing S. litura defense response, but the enhanced detoxifying ability could not overcome the strong toxins.
ESTHER : Chen_2023_Insects_14_
PubMedSearch : Chen_2023_Insects_14_
PubMedID: 36835714

Title : Natural deletion of mouse carboxylesterases Ces1c\/d\/e impacts drug metabolism and metabolic syndrome development - Gan_2023_Biomed.Pharmacother_164_114956
Author(s) : Gan C , Wang J , Wang Y , Martinez-Chavez A , Hillebrand M , de Vries N , Beukers J , Lebre MC , Wagenaar E , Rosing H , Klarenbeek S , Bleijerveld OB , Song JY , Altelaar M , Beijnen JH , Schinkel AH
Ref : Biomed Pharmacother , 164 :114956 , 2023
Abstract : Mammalian carboxylesterase 1 enzymes can hydrolyze many xenobiotic chemicals and endogenous lipids. We here identified and characterized a mouse strain (FVB/NKI) in which three of the eight Ces1 genes were spontaneously deleted, removing Ces1c and Ces1e partly, and Ces1d entirely. We studied the impact of this Ces1c/d/e deficiency on drug and lipid metabolism and homeostasis. Ces1c/d/e(-/-) mice showed strongly impaired conversion of the anticancer prodrug irinotecan to its active metabolite SN-38 in plasma, spleen and lung. Plasma hydrolysis of the oral anticancer prodrug capecitabine to 5-DFCR was also profoundly reduced in Ces1c/d/e(-/-) mice. Our findings resolved previously unexplained FVB/NKI pharmacokinetic anomalies. On a medium-fat diet, Ces1c/d/e(-/-) female mice exhibited moderately higher body weight, mild inflammation in gonadal white adipose tissue (gWAT), and increased lipid load in brown adipose tissue (BAT). Ces1c/d/e(-/-) males showed more pronounced inflammation in gWAT and an increased lipid load in BAT. On a 5-week high-fat diet exposure, Ces1c/d/e deficiency predisposed to developing obesity, enlarged and fatty liver, glucose intolerance and insulin resistance, with severe inflammation in gWAT and increased lipid load in BAT. Hepatic proteomics analysis revealed that the acute phase response, involved in the dynamic cycle of immunometabolism, was activated in these Ces1c/d/e(-/-) mice. This may contribute to the obesity-related chronic inflammation and adverse metabolic disease in this strain. While Ces1c/d/e deficiency clearly exacerbated metabolic syndrome development, long-term (18-week) high-fat diet exposure overwhelmed many, albeit not all, observed phenotypic differences.
ESTHER : Gan_2023_Biomed.Pharmacother_164_114956
PubMedSearch : Gan_2023_Biomed.Pharmacother_164_114956
PubMedID: 37267638
Gene_locus related to this paper: human-CES1 , mouse-Ces1c , mouse-Ces1d , mouse-Ces1e

Title : Immobilization of Rhizomucor miehei lipase on magnetic multiwalled carbon nanotubes towards the synthesis of structured lipids rich in sn-2 palmitic acid and sn-1,3 oleic acid (OPO) for infant formula use - Ghide_2022_Food.Chem_390_133171
Author(s) : Ghide MK , Li K , Wang J , Abdulmalek SA , Yan Y
Ref : Food Chem , 390 :133171 , 2022
Abstract : Nowadays, breast milk is considered as the ideal food for infants owing to the most common oleic acid-palmitic acid-oleic acid (OA-PA-OA) fatty acid distribution of the human milk fat (HMF). This study reports the synthesis of 1,3-dioleoyl-2-palmotoylglycerol (OPO)-rich human milk fat substitutes in a two-step enzymatic acidolysis reaction with Rhizomucor miehei lipase (RML) immobilized on magnetic multi-walled carbon nanotubes(mMWCNTs). The immobilized RML (RML-mMWCNTs) showed better thermal and pH stability, convenient recovery and reusability than the free soluble form. Under optimized reaction conditions (1:8 tripalmitin (PPP)/OA, 10%wt. enzyme, 50 degreesC, 5 h), PA content at the sn-2 position and OA incorporation at the sn-1,3 positions reached 93.46% and 59.54%, respectively. Comparison tests have also showed that RML-mMWCNTs has better catalytic activity and reusability than the commercial lipase Lipozyme RM IM. The results suggest that RML-mMWCNTs is a promising biocatalyst for the synthesis of OPO-rich TAGs with potential use in infant formulas.
ESTHER : Ghide_2022_Food.Chem_390_133171
PubMedSearch : Ghide_2022_Food.Chem_390_133171
PubMedID: 35551020

Title : Reduced Fitness and Elevated Oxidative Stress in the Marine Copepod Tigriopus japonicus Exposed to the Toxic Dinoflagellate Karenia mikimotoi - Chen_2022_Antioxidants.(Basel)_11_2299
Author(s) : Chen H , Wang J , Zhuang Y , Yu W , Liu G
Ref : Antioxidants (Basel) , 11 :2299 , 2022
Abstract : Blooms of the toxic dinoflagellate Karenia mikimotoi cause devastation to marine life, including declines of fitness and population recruitment. However, little is known about the effects of them on benthic copepods. Here, we assessed the acute and chronic effects of K. mikimotoi on the marine benthic copepod Tigriopus japonicus. Results showed that adult females maintained high survival (>85%) throughout 14-d incubation, but time-dependent reduction of survival was detected in the highest K. mikimotoi concentration, and nauplii and copepodites were more vulnerable compared to adults. Ingestion of K. mikimotoi depressed the grazing of copepods but significantly induced the generation of reactive oxygen species (ROS), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and acetylcholinesterase. Under sublethal concentrations for two generations, K. mikimotoi reduced the fitness of copepods by prolonging development time and decreasing successful development rate, egg production, and the number of clutches. Our findings suggest that the bloom of K. mikimotoi may threaten copepod population recruitment, and its adverse effects are associated with oxidative stress.
ESTHER : Chen_2022_Antioxidants.(Basel)_11_2299
PubMedSearch : Chen_2022_Antioxidants.(Basel)_11_2299
PubMedID: 36421485

Title : Substrate-free fluorescence ratiometric detection of serum acetylcholinesterase activity with a self-assembled CsPbBr(3) perovskite nanocrystals\/tetraphenylporphyrin tetrasulfonic acid nanocomposite - Wang_2022_Talanta_250_123746
Author(s) : Wang H , Wang J , Li Q , Du J
Ref : Talanta , 250 :123746 , 2022
Abstract : A dual-emission fluorescent nanoprobe was successfully constructed through self-assembling CsPbBr(3) perovskite nanocrystals (CsPbBr(3) PNCs) and tetraphenylporphyrin tetrasulfonic acid (TPPS). Acetylcholinesterase (AChE) is observed to directly quench the green fluorescence of CsPbBr(3) PNCs at 520 nm in the absence of an enzyme substrate, but has no significant influence on the red emission of TPPS at 650 nm. The decreased value of the fluorescence intensities ratio at 520 to 650 nm (deltaF(520)/F(650)) is proportional to the logarithmic value of AChE activity ranging from 0.05 to 1.0 U/L. The limit of detection is as low as 0.0042 U/L. The relative standard deviation is 3.6% in eleven consecutive measurements of 0.2 U/L AChE. The method exhibits a good anti-interference capacity since it does not respond to most concomitant species. Satisfactory results are acquired for the determination of AChE activity in human serum samples.
ESTHER : Wang_2022_Talanta_250_123746
PubMedSearch : Wang_2022_Talanta_250_123746
PubMedID: 35872485

Title : High-Resolution Bioassay Profiling with Complemented Sensitivity and Resolution for Pancreatic Lipase Inhibitor Screening - Jian_2022_Molecules_27_
Author(s) : Jian J , Yuan J , Fan Y , Wang J , Zhang T , Kool J , Jiang Z
Ref : Molecules , 27 : , 2022
Abstract : How to rapidly and accurately screen bioactive components from complex natural products remains a major challenge. In this study, a screening platform for pancreatic lipase (PL) inhibitors was established by combining magnetic beads-based ligand fishing and high-resolution bioassay profiling. This platform was well validated using a mixture of standard compounds, i.e., (-)- epigallocatechin gallate (EGCG), luteolin and schisandrin. The dose-effect relationship of high-resolution bioassay profiling was demonstrated by the standard mixture with different concentrations for each compound. The screening of PL inhibitors from green tea extract at the concentrations of 0.2, 0.5 and 1.0 mg/mL by independent high-resolution bioassay profiling was performed. After sample pre-treatment by ligand fishing, green tea extract at the concentration of 0.2 mg/mL was specifically enriched and simplified, and consequently screened through the high-resolution bioassay profiling. As a result, three PL inhibitors, i.e., EGCG, (-)-Gallocatechin gallate (GCG) and (-)-Epicatechin gallate (ECG), were rapidly identified from the complex matrix. The established platform proved to be capable of enriching affinity binders and eliminating nonbinders in sample pre-treatment by ligand fishing, which overcame the technical challenges of high-resolution bioassay profiling in the aspects of sensitivity and resolution. Meanwhile, the high-resolution bioassay profiling possesses the ability of direct bioactive assessment, parallel structural analysis and identification after separation. The established platform allowed more accurate and rapid screening of PL inhibitors, which greatly facilitated natural product-based drug screening.
ESTHER : Jian_2022_Molecules_27_
PubMedSearch : Jian_2022_Molecules_27_
PubMedID: 36296516

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

Title : Development of indole-2-carbonyl piperazine urea derivatives as selective FAAH inhibitors for efficient treatment of depression and pain - Shang_2022_Bioorg.Chem_128_106031
Author(s) : Shang Y , Wang M , Hao Q , Meng T , Li L , Shi J , Yang G , Zhang Z , Yang K , Wang J
Ref : Bioorg Chem , 128 :106031 , 2022
Abstract : Fatty acid amide hydrolase (FAAH), aserinehydrolase with significant role in thehydrolysis of endocannabinoids, is a promising therapeutic target for peripheral and central nervous system related disorders, including pain, neuroinflammation and depression. Employing a structure-based approach, a novel series of indole-2-carbonyl piperazine urea derivatives were designed and synthesized as FAAH inhibitors for the treatment of pain-depression comorbidity. Among them, compound 4i emerged as the most potent inhibitor (IC(50) = 0.12 microM) with fine selectivity versus CES2, ABHD6, MAGL and the cannabinoid receptor, which also displayed superior metabolic stability in human liver microsome and an adequate pharmacokinetic profile in rodents. Treatment of depressed rats with 4i demonstrated favorable antidepressant-like effects not only by increasing the level of BDNF in the hippocampus but also by restraining the apoptosis of hippocampal neurons. Also, 4i effectively suppressed the LPS-induced neuroinflammation in vitro. Moreover, 4i exhibited potent analgesic activity, which indicated its promising therapeutical application for pain and depression. These meaningful results shed light on FAAH inhibitors as promising pain-depression comorbidity therapeutics.
ESTHER : Shang_2022_Bioorg.Chem_128_106031
PubMedSearch : Shang_2022_Bioorg.Chem_128_106031
PubMedID: 36037600

Title : A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase - Xia_2022_Biosensors.(Basel)_12_
Author(s) : Xia M , Li C , Liu L , He Y , Li Y , Jiang G , Wang J
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.
ESTHER : Xia_2022_Biosensors.(Basel)_12_
PubMedSearch : Xia_2022_Biosensors.(Basel)_12_
PubMedID: 35884287

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

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : Plin5, a New Target in Diabetic Cardiomyopathy - Cui_2022_Oxid.Med.Cell.Longev_2022_2122856
Author(s) : Cui X , Wang J , Zhang Y , Wei J , Wang Y
Ref : Oxid Med Cell Longev , 2022 :2122856 , 2022
Abstract : Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.
ESTHER : Cui_2022_Oxid.Med.Cell.Longev_2022_2122856
PubMedSearch : Cui_2022_Oxid.Med.Cell.Longev_2022_2122856
PubMedID: 35509833

Title : Possible Charged Residue Switch for Acylglycerol Selectivity of Lipase MAS1 - Yang_2022_Appl.Biochem.Biotechnol__
Author(s) : Yang Y , Wang J , Yang B , Lan D , Wang Y
Ref : Appl Biochem Biotechnol , : , 2022
Abstract : The amino acid residues lining the substrate binding pocket play quite an important role during the lipase catalytic process. The conversion of those residues might cause a dramatic change in the lipase properties, such as the substrate selectivity of lipase. In our study, T237 residue sitting on the entrance of the catalytic pocket in lipase MAS1 was important for the catalytic performance. When replacing polar Thr with the positively charged Arg, the synthesis ratio of partial glycerides/triglycerides increases to 6.32 rather than 1.21 of MAS1 wild type (WT), as the substrate ratio of glycerol and fatty acids is 1:3. And the fatty acid preference shifted to long-chain substrates for mutant T237R rather than middle-chain substrates for MAS1 WT. Molecular docking analysis revealed that hydrophobic and side chain properties of Arg might contribute to the change of the MAS1 lipase catalytic performance. This work would pave a way for the accurate rational transformation of the lipases to produce value lipid for industrial application.
ESTHER : Yang_2022_Appl.Biochem.Biotechnol__
PubMedSearch : Yang_2022_Appl.Biochem.Biotechnol__
PubMedID: 35695952
Gene_locus related to this paper: 9actn-h0b8d4

Title : Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies - Sang_2022_Bioorg.Chem_127_106007
Author(s) : Sang Z , Bai P , Ban Y , Wang K , Wu A , Mi J , Hu J , Xu R , Zhu G , Wang J , Zhang J , Wang C , Tan Z , Tang L
Ref : Bioorg Chem , 127 :106007 , 2022
Abstract : Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy. Herein, a series of novel donepezil-chalone-rivastigmine hybrids was rationally designed and synthesized by fusing donepezil, chalone and rivastigmine. The in vitro bioactivity results displayed that compound 10c was a reversible huAChE (IC(50) = 0.87 microM) and huBuChE (IC(50) = 3.3 microM) inhibitor. It also presented significant anti-inflammation effects by suppressing the level of IL-6 and TNF-alpha production, and significantly inhibited self-mediated Abeta(1-42) aggregation (60.6%) and huAChE-mediated induced Abeta(1-40) aggregation (46.2%). In addition, 10c showed significant neuroprotective effect on Abeta(1-42)-induced PC12 cell injury and activated UPS pathway in HT22 cells to degrade tau and amyloid precursor protein (APP). Furthermore, compound 10c presented good stabilty in artificial gastrointestinal fluids and liver microsomes in vitro. The pharmacokinetic study showed that compound 10c was rapidly absorbed in rats and distributed in rat brain after intragastric administration. The PET-CT imaging demonstrated that [(11)C]10c could quickly enter the brain and washed out gradually in vivo. Further, compound 10c at a dose of 5 mg/kg improved scopolamine-induced memory impairment, deserving further investigations.
ESTHER : Sang_2022_Bioorg.Chem_127_106007
PubMedSearch : Sang_2022_Bioorg.Chem_127_106007
PubMedID: 35849893

Title : Design of 2,5-furandicarboxylic based polyesters degraded in different environmental conditions: Comprehensive experimental and theoretical study - Hu_2022_J.Hazard.Mater_425_127752
Author(s) : Hu H , Li J , Luo S , Tian Y , Wang J , Zhao YL , Zhang R , Zhu J
Ref : J Hazard Mater , 425 :127752 , 2022
Abstract : Nowadays, the promotion and application of aliphatic-aromatic copolyesters, such as poly (butylene adipate-co-terephthalate) (PBAT), are growing into a general trend. Although the structures of diacids exerted substantial impacts on degradation behavior, the underlying mechanisms have rarely been studied. In this work, 2,5-Furandicarboxylic acid was combined with succinic acid (PBSF), adipic acid (PBAF) and diglycolic acid (PBDF) to prepare three kinds of copolyesters. They showed unique degradation behaviors in buffer, enzyme environment and artificial seawater. These characteristics are closely related to the structural compositions of diacids. PBAFs displayed impressive biodegradability when catalyzed by Candida antarctica lipase B (CALB), while the more hydrophilic PBDFs exhibited faster hydrolysis in both buffer and artificial seawater. PBSFs, with hydrophobic and short segments, obtained a relatively slower rate of hydrolysis and enzymatic degradation. The reactivity sites and hydrolytic pathway were revealed by the combination of DFT calculation and Fukui function analysis. MD simulations, QM/MM optimizations and theozyme calculations showed that PBAF-CALB was prone to form a pre-reaction state, leading to the reduced energy barrier in the acylation process. This work revealed the effects of different structural features of diacids on polymer degradation and paved a way to design target biodegradable polymers in different degradation conditions.
ESTHER : Hu_2022_J.Hazard.Mater_425_127752
PubMedSearch : Hu_2022_J.Hazard.Mater_425_127752
PubMedID: 34906869
Gene_locus related to this paper: canar-LipB

Title : Engineered small extracellular vesicles as a versatile platform to efficiently load ferulic acid via an esterase-responsive active loading strategy - Man_2022_Front.Bioeng.Biotechnol_10_1043130
Author(s) : Man F , Xing H , Wang H , Wang J , Lu R
Ref : Front Bioeng Biotechnol , 10 :1043130 , 2022
Abstract : As nano-drug carriers, small extracellular vesicles (sEVs) have shown unique advantages, but their drug loading and encapsulation efficiency are far from being satisfied, especially for the loading of hydrophilic small-molecule drugs. Inspired by the strategies of active loading of liposomal nanomedicines, pre-drug design and immobilization enzyme, here we developed a new platform, named "Esterase-responsive Active Loading" (EAL), for the efficient and stable drug encapsulation of sEVs. Widely used ferulic acid ester derivatives were chosen as prodrugs based on the EAL of engineered sEVs to establish a continuous transmembrane ion gradient for achieving efficient loading of active molecule ferulic acid into sEVs. The EAL showed that the drug loading and encapsulation efficiency were around 6-fold and 5-fold higher than passive loading, respectively. Moreover, characterization by nano-flow cytometry and Malvern particle size analyzer showed that differential ultracentrifugation combined with multiple types of membrane filtration methods can achieve large-scale and high-quality production of sEVs. Finally, extracellular and intracellular assessments further confirmed the superior performance of the EAL-prepared sEVs-loaded ferulic acid preparation in terms of slow release and low toxicity. Taken together, these findings will provide an instructive insight into the development of sEV-based delivery systems.
ESTHER : Man_2022_Front.Bioeng.Biotechnol_10_1043130
PubMedSearch : Man_2022_Front.Bioeng.Biotechnol_10_1043130
PubMedID: 36440451

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

Title : Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007 - Zhao_2022_Int.J.Mol.Sci_23_5822
Author(s) : Zhao Z , Chen S , Xu L , Cai J , Wang J , Wang Y
Ref : Int J Mol Sci , 23 :5822 , 2022
Abstract : The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a alpha-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedID: 35628632
Gene_locus related to this paper: 9actn-h0b8d4

Title : Retrospective detection for V-type OPNAs exposure via phosphonylation and disulfide adducts in albumin - Wang_2022_Sci.Rep_12_10979
Author(s) : Wang J , Sun F , Lu X , Gao R , Pei C , Wang H
Ref : Sci Rep , 12 :10979 , 2022
Abstract : Organophosphorus nerve agents (OPNAs) that damage the central nervous system by inhibiting acetylcholinesterase activity, pose severe threats to human health and life security. Reliable biomarkers that quickly and accurately detect OPNAs exposure are urgently needed to help diagnose quickly and treat in time. Albumins that covalently bind to OPNAs could serve as important targets for retrospective verification of OPNAs exposure. The goal of this study is to explore the potential biomarkers in albumins with high reactivity and good stability and expand the group of potential biomarkers in different species for detecting the exposure of V-type OPNAs including O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). Taking human serum albumin (HSA), bovine serum albumin (BSA) and rabbit serum albumin (RSA) as the research objectives, multiple active sites including phosphonylation and disulfide adduct sites were observed in albumins from different species. Numerous phosphonylation sites labeled by all agents in one type of albumin were found. Among the different species, four shared phosphonylation sites with high reactivity include K499, K549, K249, and Y108. In addition, Y108 on ETY*GEMADCCAK, Y287 on Y*ICENQDSISSK, Y377 on TY*ETTLEK and Y164 on YLY*EIAR in HSA were stably phosphonylated by all agents in gradient concentration, making them stable and suitable potential biomarkers for V-type OPNAs exposure. Notably, Y108 on ETY*GEMADCCAK in HSA, on DTY*GDVADCCEK in RSA, and on ETY*GDMADCCEK in BSA were highly reactive to all V-type agents, regardless of species. It was also successfully labeled in HSA exposed to class V agents in gradient concentration. Y108 is expected to be used to screen and identify the exposure of V-type agents in the retrospective research. Disulfide adducts sites, consisted of four sites in HSA and two sites in BSA were also successfully labeled by V-type agents, and characteristic ion fragments from these disulfide adducts were also identified by secondary mass spectrometry. Molecular simulation of the stably modified sites were conducted to discover the promoting factors of covalent adduct formation, which help further clarify formation mechanism of albumin adducts at active sites.
ESTHER : Wang_2022_Sci.Rep_12_10979
PubMedSearch : Wang_2022_Sci.Rep_12_10979
PubMedID: 35768567

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 : Evaluation of the toxicity effects of microplastics and cadmium on earthworms - Liang_2022_Sci.Total.Environ__155747
Author(s) : Liang X , Zhou D , Wang J , Li Y , Liu Y , Ning Y
Ref : Sci Total Environ , :155747 , 2022
Abstract : Microplastics (MPs) and heavy metal pollution have become research hotspots in recent years. This study focused on the comprehensive evaluation of the toxicity effect on Eisenia fetida under combined exposure to MPs and the heavy metal cadmium (Cd). With Cd concentration, MPs concentration and MPs partical size as stress factors, the TOPSIS model was constructed to explore the toxicity levels of the stress factors. A short-term co-exposure test and a long-term co-exposure test were designed by orthogonal combination tests with equivalent toxicity levels. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione peroxidase (GPX), glutathione S transferase (GST), and acetylcholinesterase (AChE) and the contents of protein (TP), glutathione (GSH), and malondialdehyde (MDA) in earthworms were determined. Integrated biological responses version 2 (IBRv2) was used to evaluate the toxicity of MPs and Cd combined exposure on earthworms. The results showed that the toxicity ratio of Cd concentration, MPs concentration and MPs partical size was 46 to 29 to 25. Combined exposure to MPs and Cd enhanced the activities of SOD, POD, CAT, GPX and GST, MDA and GSH contents also increased, while the AChE activities were inhibited. SOD, GPX and GST play important roles in the resistance of earthworms to pollutant stress. During short-term co-exposure, Cd concentration had antagonistic effects with on MPs concentration and MPs partical size, while they showed synergistic effects during long-term co-exposure.
ESTHER : Liang_2022_Sci.Total.Environ__155747
PubMedSearch : Liang_2022_Sci.Total.Environ__155747
PubMedID: 35533859

Title : Probing strigolactone perception mechanisms with rationally designed small-molecule agonists stimulating germination of root parasitic weeds - Wang_2022_Nat.Commun_13_3987
Author(s) : Wang D , Pang Z , Yu H , Thiombiano B , Walmsley A , Yu S , Zhang Y , Wei T , Liang L , Wang J , Wen X , Bouwmeester HJ , Yao R , Xi Z
Ref : Nat Commun , 13 :3987 , 2022
Abstract : The development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10(-8) to 10(-17) M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2'C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds.
ESTHER : Wang_2022_Nat.Commun_13_3987
PubMedSearch : Wang_2022_Nat.Commun_13_3987
PubMedID: 35810153

Title : Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer's Disease - Wang_2022_Molecules_27_
Author(s) : Wang S , Kong X , Chen Z , Wang G , Zhang J , Wang J
Ref : Molecules , 27 : , 2022
Abstract : Alzheimer's disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), beta-secretase, gamma-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD.
ESTHER : Wang_2022_Molecules_27_
PubMedSearch : Wang_2022_Molecules_27_
PubMedID: 35807418

Title : Design, Synthesis and Bioactivity Evaluation of Coumarin-BMT Hybrids as New Acetylcholinesterase Inhibitors - Zeng_2022_Molecules_27_
Author(s) : Zeng F , Lu T , Wang J , Nie X , Xiong W , Yin Z , Peng D
Ref : Molecules , 27 : , 2022
Abstract : Coumarin possesses the aromatic group and showed plentiful activities, such as antioxidant, preventing asthma and antisepsis. In addition, coumarin derivatives usually possess good solubility, low cytotoxicity and excellent cell permeability. In our study, we synthesized the compound bridge methylene tacrine (BMT), which has the classical pharmacophore structure of Tacrine (THA). Based on the principle of active substructure splicing, BMT was used as a lead compound and synthesized coumarin-BMT hybrids by introducing coumarin to BMT. In this work, 21 novel hybrids of BMT and coumarin were synthesized and evaluated for their inhibitory activity on AChE. All obtained compounds present preferable inhibition. Compound 8b was the most active compound, with the value of K(i) as 49.2 nM, which was higher than Galantamine (GAL) and lower than THA. The result of molecular docking showed that the highest binding free energy was -40.43 kcal/mol for compound 8b, which was an identical trend with the calculated K(i).
ESTHER : Zeng_2022_Molecules_27_
PubMedSearch : Zeng_2022_Molecules_27_
PubMedID: 35408542

Title : Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation - Zhang_2022_Int.J.Mol.Sci_23_16182
Author(s) : Zhang H , Wang D , Sun J , Wang Y , Wu S , Wang J
Ref : Int J Mol Sci , 23 :16182 , 2022
Abstract : Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_16182
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_16182
PubMedID: 36555825

Title : Catalytically active inclusion bodies (CatIBs) induced by terminally attached self-assembling coiled-coil domains: To enhance the stability of (R)-hydroxynitrile lyase - Pei_2022_Enzyme.Microb.Technol_153_109915
Author(s) : Pei X , Wang J , Zheng H , Xiao Q , Wang A , Su W
Ref : Enzyme Microb Technol , 153 :109915 , 2022
Abstract : The catalytically-active inclusion bodies (CatIBs) represent a promising strategy for immobilizing enzyme without additional carriers and chemicals, which has aroused great attention in academic and industrial communities. In this work, we discovered two natural parallel right-handed coiled-coil tetramer peptides from PDB database by a structural mining strategy. The two self-assembling peptides, NSPdoT from rotavirus and HVdoT from human Vasodilator-stimulated phosphoprotein, efficiently induced the CatIBs formation of a (R)-Hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) in Escherichia coli cells. This is convenient to simultaneously purify and immobilize the target proteins as biocatalysts. As expected, HVdoT-AtHNL and NSPdoT-AtHNL possessed drastically increased tolerance toward lower pH values, which will be very critical to synthesize cyanohydrins under acidic condition for suppressing the non-enzymatic side reaction. In addition. AtHNL-CatIBs are produced at high yield in host cells as bioactive microparticles, which exhibited high thermal and pH stabilities. Therefore, the CatIBs method represent a promising application for the immobilization of enzymes in the biocatalysis field.
ESTHER : Pei_2022_Enzyme.Microb.Technol_153_109915
PubMedSearch : Pei_2022_Enzyme.Microb.Technol_153_109915
PubMedID: 34670185
Gene_locus related to this paper: arath-HNL

Title : Engineering balanced anions coupling with tailored functional groups of poly(ionic liquid)s immobilized lipase enables effective biodiesel production - Wang_2022_Mol.Catal_531_112673
Author(s) : Wang Q , Guo X , Ge M , Sheng L , Wang J , Yang F , Jia L , Huang A , Guo R
Ref : Molecular Catalysis , 531 :112673 , 2022
Abstract : The catalytic performance of immobilized enzyme is greatly influenced by functional support, which attracts growing interest for designing supports to achieve their promotive catalytic activity. In this work, a series of functional mesoporous poly(ionic liquid)s (PILs) with balanced anions and tailored surface functional organic groups were designed and constructed. Then, Porcine pancreatic lipase (PPL) immobilized mesoporous PILs biocatalysts were synthesized and carefully characterized. Through regulating anions (Br-, SO42-, OH-) along with functional groups (carboxyl, hydroxy, epoxy) of PILs, the sample PIL-COOH-S bearing carboxyl group and bisulfate ion affords improved affinity and open conformation of immobilized PPL, thus contributing to the highest biodiesel yield of 96.6% via esterification of soybean oil within 24 h at 40 degreesC, much outperforming that of bare PPL (66.3%) and commercial Novozym 435 (68.5%). The activity recovery of PPL0.2@PIL-COOH-S reached to 130% and could be reused for 8 cycles in transesterification with a maintained 82% initial activity. Finally, molecular dynamic simulation (molecular docking) was further conducted to identify the origin of PILs functions. Thus, the above devisable PILs provide a green strategy for lipase immobilization and show a synergistic effect to promote biodiesel production with high activity and stability.
ESTHER : Wang_2022_Mol.Catal_531_112673
PubMedSearch : Wang_2022_Mol.Catal_531_112673

Title : Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel - Nan_2022_Curr.Issues.Mol.Biol_44_3779
Author(s) : Nan J , Wang Q , Yan Q , Wang J , Zhang Y , Zhao X
Ref : Curr Issues Mol Biol , 44 :3779 , 2022
Abstract : Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.
ESTHER : Nan_2022_Curr.Issues.Mol.Biol_44_3779
PubMedSearch : Nan_2022_Curr.Issues.Mol.Biol_44_3779
PubMedID: 36005155

Title : Pharmacological treatments for psychotic symptoms in dementia: A systematic review with pairwise and network meta-analysis - Huang_2022_Ageing.Res.Rev_75_101568
Author(s) : Huang YY , Teng T , Shen XN , Chen SD , Wang RZ , Zhang RQ , Dou KX , Zhong XL , Wang J , Chen KL , Zhao QH , Tan L , Dong Q , Zhou XY , Yu JT
Ref : Ageing Res Rev , 75 :101568 , 2022
Abstract : Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted.
ESTHER : Huang_2022_Ageing.Res.Rev_75_101568
PubMedSearch : Huang_2022_Ageing.Res.Rev_75_101568
PubMedID: 35051646

Title : Asperbenzophenone A and Versicolamide C, New Fungal Metabolites from the Soft Coral Derived Aspergillus sp. SCSIO 41036 - Long_2022_Chem.Biodivers__e202100925
Author(s) : Long J , Pang X , Lin X , Liao S , Zhou X , Wang J , Yang B , Liu Y
Ref : Chem Biodivers , :e202100925 , 2022
Abstract : Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10microM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC(50) value of 157.8microM.
ESTHER : Long_2022_Chem.Biodivers__e202100925
PubMedSearch : Long_2022_Chem.Biodivers__e202100925
PubMedID: 35194907

Title : Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus - Sun_2022_Andrology__
Author(s) : Sun T , Xu W , Wang J , Wang T , Wang S , Liu K , Liu J
Ref : Andrology , : , 2022
Abstract : BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved.
ESTHER : Sun_2022_Andrology__
PubMedSearch : Sun_2022_Andrology__
PubMedID: 36113503

Title : Characterization of a new chlorimuron-ethyl-degrading strain Cedecea sp. LAM2020 and biodegradation pathway revealed by multiomics analysis - Ma_2022_J.Hazard.Mater_443_130197
Author(s) : Ma Q , Han X , Song J , Wang J , Li Q , Parales RE , Li L , Ruan Z
Ref : J Hazard Mater , 443 :130197 , 2022
Abstract : The widespread use of the herbicide chlorimuron-methyl is hazard to rotational crops and causes soil degradation problems. Biodegradation is considered a promising way for removing herbicide residues from the environment. Here, a new isolated strain, Cedecea sp. LAM2020, enabled complete degradation of 100 mg/L chlorimuron-methyl within five days. Transcriptome analysis revealed that ABC transporters, atrazine degradation and purine metabolism were enriched in the KEGG pathway. Integrating GO and KEGG classification with related reports, we predict that carboxylesterases are involved in the biodegradation of chlorimuron-methyl by LAM2020. Heterologous expression of the carboxylesterase gene carH showed 26.67% degradation of 50 mg/L chlorimuron-methyl within 6 h. The intracellular potential biological response and extracellular degradation process of chlorimuron-ethyl were analyzed by the nontarget metabolomic and mass spectrometry respectively, and the biodegradation characteristics and complete mineralization pathway was revealed. The cleavage of the sulfonylurea bridge and the ester bond achieved the first step in the degradation of chlorimuron-methyl. Together, these results reveal the presence of acidolysis and enzymatic degradation of chlorimuron-methyl by strain LAM2020. Hydroponic corn experiment showed that the addition of strain LAM2020 alleviated the toxic effects of chlorimuron-ethyl on the plants. Collectively, strain LAM2020 may be a promising microbial agent for plants chlorimuron-ethyl detoxification and soil biofertilizer.
ESTHER : Ma_2022_J.Hazard.Mater_443_130197
PubMedSearch : Ma_2022_J.Hazard.Mater_443_130197
PubMedID: 36272371
Gene_locus related to this paper: 9entr-CarHBioH

Title : Functional enzyme-polymer complexes - Waltmann_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2119509119
Author(s) : Waltmann C , Mills CE , Wang J , Qiao B , Torkelson JM , Tullman-Ercek D , Olvera de la Cruz M
Ref : Proc Natl Acad Sci U S A , 119 :e2119509119 , 2022
Abstract : SignificanceThe use of biological enzyme catalysts could have huge ramifications for chemical industries. However, these enzymes are often inactive in nonbiological conditions, such as high temperatures, present in industrial settings. Here, we show that the enzyme PETase (polyethylene terephthalate [PET]), with potential application in plastic recycling, is stabilized at elevated temperature through complexation with random copolymers. We demonstrate this through simulations and experiments on different types of substrates. Our simulations also provide strategies for designing more enzymatically active complexes by altering polymer composition and enzyme charge distribution.
ESTHER : Waltmann_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2119509119
PubMedSearch : Waltmann_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2119509119
PubMedID: 35312375

Title : Non-classical digestive lipase BmTGL selected by gene amplification reduces the effects of mulberry inhibitor during silkworm domestication - Wen_2022_Int.J.Biol.Macromol__
Author(s) : Wen F , Wang J , Shang D , Yan H , Yuan X , Wang Y , Xia Q , Wang G
Ref : Int J Biol Macromol , : , 2022
Abstract : Efficient utilization of dietary lipids is crucial for Bombyx mori, also known as domesticated silkworms. However, the effects of domestication on the genes encoding lipases remain unknown. In this study, we investigated the expression difference of one triacylglycerol lipase (BmTGL) between B.mori and wild (ancestor) silkworm strains (Bombyx mandarina). An immunofluorescence localization analysis showed that BmTGL was present in all parts of the gut and was released into the intestinal lumen. BmTGL expression was significantly enhanced in different domesticated silkworm strains compared to that in the B. mandarina strains. The genomes of the domesticated silkworm strains harbored 2-to-3-fold higher BmTGL copy numbers than those in the B. mandarina strains and accounted for the enhanced expression of BmTGL in the domesticated silkworm strains. The Ser144Asn substitution in the Ser-Asp-His catalytic triads of BmTGL resulted in relatively lower lipase activity and reduced sensitivity to the lipase inhibitor morachalcone A. Moreover, BmTGL overexpression significantly increased the weights of the B. mori silkworms compared to those of the non-transgenic controls. Thus, the selection of BmTGL by gene amplification may be a trade-off between maintaining high enzymatic activity and reducing the effects of mulberry inhibitors during silkworm domestication.
ESTHER : Wen_2022_Int.J.Biol.Macromol__
PubMedSearch : Wen_2022_Int.J.Biol.Macromol__
PubMedID: 36587639

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 : The binding pocket properties were fundamental to functional diversification of the GDSL-type esterases\/lipases gene family in cotton - Wang_2022_Front.Plant.Sci_13_1099673
Author(s) : Wang J , Zhao H , Qu Y , Yang P , Huang J
Ref : Front Plant Sci , 13 :1099673 , 2022
Abstract : Cotton is one of the most important crops in the world. GDSL-type esterases/lipases (GELPs) are widely present in all kingdoms and play an essential role in regulating plant growth, development, and responses to abiotic and biotic stresses. However, the molecular mechanisms underlying this functional diversity remain unclear. Here, based on the identification of the GELP gene family, we applied genetic evolution and molecular simulation techniques to explore molecular mechanisms in cotton species. A total of 1502 GELP genes were identified in 10 cotton species. Segmental duplication and differences in evolutionary rates are the leading causes of the increase in the number and diversity of GELP genes during evolution for ecological adaptation. Structural analysis revealed that the GELP family has high structural diversity. Moreover, molecular simulation studies have demonstrated significant differences in the properties of the binding pockets among cotton GELPs. In the process of adapting to the environment, GELPs not only have segmental duplication but also have different evolutionary rates, resulting in gene diversity. This diversity leads to significant differences in the 3D structure and binding pocket properties and, finally, to functional diversity. These findings provide a reference for further functional analyses of plant GELPs.
ESTHER : Wang_2022_Front.Plant.Sci_13_1099673
PubMedSearch : Wang_2022_Front.Plant.Sci_13_1099673
PubMedID: 36743561

Title : Point-of-care SARS-CoV-2 sensing using lens-free imaging and a deep learning-assisted quantitative agglutination assay - Potter_2022_Lab.Chip__
Author(s) : Potter CJ , Hu Y , Xiong Z , Wang J , McLeod E
Ref : Lab Chip , : , 2022
Abstract : The persistence of the global COVID-19 pandemic caused by the SARS-CoV-2 virus has continued to emphasize the need for point-of-care (POC) diagnostic tests for viral diagnosis. The most widely used tests, lateral flow assays used in rapid antigen tests, and reverse-transcriptase real-time polymerase chain reaction (RT-PCR), have been instrumental in mitigating the impact of new waves of the pandemic, but fail to provide both sensitive and rapid readout to patients. Here, we present a portable lens-free imaging system coupled with a particle agglutination assay as a novel biosensor for SARS-CoV-2. This sensor images and quantifies individual microbeads undergoing agglutination through a combination of computational imaging and deep learning as a way to detect levels of SARS-CoV-2 in a complex sample. SARS-CoV-2 pseudovirus in solution is incubated with acetyl cholinesterase 2 (ACE2)-functionalized microbeads then loaded into an inexpensive imaging chip. The sample is imaged in a portable in-line lens-free holographic microscope and an image is reconstructed from a pixel superresolved hologram. Images are analyzed by a deep-learning algorithm that distinguishes microbead agglutination from cell debris and viral particle aggregates, and agglutination is quantified based on the network output. We propose an assay procedure using two images which results in the accurate determination of viral concentrations greater than the limit of detection (LOD) of 1.27 x 10(3) copies per mL, with a tested dynamic range of 3 orders of magnitude, without yet reaching the upper limit. This biosensor can be used for fast SARS-CoV-2 diagnosis in low-resource POC settings and has the potential to mitigate the spread of future waves of the pandemic.
ESTHER : Potter_2022_Lab.Chip__
PubMedSearch : Potter_2022_Lab.Chip__
PubMedID: 36047372

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

Title : A new quinolone and acetylcholinesterase inhibitors from a sponge-associated fungus Penicillium sp. SCSIO41033 - Xu_2022_Nat.Prod.Res__1
Author(s) : Xu F , Chen W , Ye Y , Qi X , Zhao K , Long J , Pang X , Liu Y , Wang J
Ref : Nat Prod Res , :1 , 2022
Abstract : The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone (1), three xanthone derivatives (3-5), and four anthraquinones (6-9). Their structures were determined by comprehensive analysis of (1)H and (13)C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5, 8 and 9 exhibited inhibition against AChE with IC(50) values of 45.9, 42.5 and 40.5 microg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors.
ESTHER : Xu_2022_Nat.Prod.Res__1
PubMedSearch : Xu_2022_Nat.Prod.Res__1
PubMedID: 36318871

Title : Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe - Yang_2022_Anal.Chem__
Author(s) : Yang Y , Zhang L , Wang J , Cao Y , Li S , Qin W , Liu Y
Ref : Analytical Chemistry , : , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.
ESTHER : Yang_2022_Anal.Chem__
PubMedSearch : Yang_2022_Anal.Chem__
PubMedID: 36121878

Title : Comparative genomic analysis of carboxylesterase genes in Tenebrio molitor and other four tenebrionids - Yang_2022_Arch.Insect.Biochem.Physiol__e21967
Author(s) : Yang YL , Li X , Wang J , Song QS , Stanley D , Wei SJ , Zhu JY
Ref : Archives of Insect Biochemistry & Physiology , :e21967 , 2022
Abstract : Carboxylesterases (COEs) have various functions in wide taxons of organisms. In insects, COEs are important enzymes involved in the hydrolysis of a variety of ester-containing xenobiotics, neural signal transmission, pheromone degradation, and reproductive development. Understanding the diversity of COEs is basic to illustrate their functions. In this study, we identified 53, 105, 37, and 39 COEs from the genomes of Tenebrio molitor, Asbolus verucosus, Hycleus cichorii, and H. phaleratus in the superfamily of Tenebrionidea, respectively. Phylogenetic analysis showed that 234 COEs from these four species and those reported in Tribolium castaneum (63) could be divided into 12 clades and three major classes. The alpha-esterases significantly expanded in T. molitor, A. verucosus, and T. castaneum compared to dipteran and hymenopteran insects. In T. molitor, most COEs showed tissue and stage-specific but not a sex-biased expression. Our results provide insights into the diversity and evolutionary characteristics of COEs in tenebrionids, and lay a foundation for the functional characterization of COEs in the yellow mealworm.
ESTHER : Yang_2022_Arch.Insect.Biochem.Physiol__e21967
PubMedSearch : Yang_2022_Arch.Insect.Biochem.Physiol__e21967
PubMedID: 36111353

Title : Light-Addressable Paper-Based Photoelectrochemical Analytical Device with Tunable Detection Throughput for On-Site Biosensing - Liu_2022_Anal.Chem_94_583
Author(s) : Liu M , Yang J , Wang J , Liu Z , Hu C
Ref : Analytical Chemistry , 94 :583 , 2022
Abstract : Development of biosensing systems resembling optical 96-well plates using portable single-channel electrochemical analyzers is usually a great challenge. Herein, a light-addressable paper-based photoelectrochemical (PEC) analytical device suitable for on-site high-throughput biosensing is reported. This device consists of a solar cell-type single-channel PEC system with plenty of separated detection zones. Each zone contains a silver nanowires/fullerene-Congo red (AgNWs/C(60)-CR) disc working electrode and a AgNWs ring reference/counter electrode, which can be massively produced by a simple filtration and laser cutting method. Taking advantage of the sensitive photocurrent response of thiocholine (TCl) on AgNWs/C(60)-CR, an acetylcholinesterase (AChE)-based PEC biosensing system with tunable detection throughput for the on-site screening of ultratrace organophosphorus pesticides (OPs) was established.
ESTHER : Liu_2022_Anal.Chem_94_583
PubMedSearch : Liu_2022_Anal.Chem_94_583
PubMedID: 34978797

Title : Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform - Zhao_2022_ACS.Cent.Sci_8_1424
Author(s) : Zhao J , Tang Z , Selvaraju M , Johnson KA , Douglas JT , Gao PF , Petrassi HM , Wang MZ , Wang J
Ref : ACS Cent Sci , 8 :1424 , 2022
Abstract : Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators of signaling pathways by leveraging the power of a clustered regularly interspaced short palindromic repeats (CRISPR) knockout library. This platform links the expression of a suicide gene to the small-molecule-activated signaling pathway to create a selection system. With this system, loss-of-function screening using a CRISPR single-guide (sg) RNA library positively enriches cells in which the target has been knocked out. The identities of the drug targets and other essential genes required for the activity of small molecules of interest are then uncovered by sequencing. We tested this platform on BDW568, a newly discovered type-I interferon signaling activator, and identified stimulator of interferon genes (STING) as its target and carboxylesterase 1 (CES1) to be a key metabolizing enzyme required to activate BDW568 for target engagement. The platform we present here can be a general method applicable for target identification for a wide range of small molecules that activate different signaling pathways.
ESTHER : Zhao_2022_ACS.Cent.Sci_8_1424
PubMedSearch : Zhao_2022_ACS.Cent.Sci_8_1424
PubMedID: 36313155

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

Title : Genome-wide expression analysis of carboxylesterase (CXE) gene family implies GBCXE49 functional responding to alkaline stress in cotton - Rui_2022_BMC.Plant.Biol_22_194
Author(s) : Rui C , Peng F , Fan Y , Zhang Y , Zhang Z , Xu N , Zhang H , Wang J , Li S , Yang T , Malik WA , Lu X , Chen X , Wang D , Chen C , Gao W , Ye W
Ref : BMC Plant Biol , 22 :194 , 2022
Abstract : BACKGROUND: Carboxylesterase (CXE) is a type of hydrolase with alpha/beta sheet hydrolase activity widely found in animals, plants and microorganisms, which plays an important role in plant growth, development and resistance to stress. RESULTS: A total of 72, 74, 39, 38 CXE genes were identified in Gossypium barbadense, Gossypium hirsutum, Gossypium raimondii and Gossypium arboreum, respectively. The gene structure and expression pattern were analyzed. The GBCXE genes were divided into 6 subgroups, and the chromosome distribution of members of the family were mapped. Analysis of promoter cis-acting elements showed that most GBCXE genes contain cis-elements related to plant hormones (GA, IAA) or abiotic stress. These 6 genes we screened out were expressed in the root, stem and leaf tissues. Combined with the heat map, GBCXE49 gene was selected for subcellular locate and confirmed that the protein was expressed in the cytoplasm. CONCLUSIONS: The collinearity analysis of the CXE genes of the four cotton species in this family indicated that tandem replication played an indispensable role in the evolution of the CXE gene family. The expression patterns of GBCXE gene under different stress treatments indicated that GBCXE gene may significantly participate in the response to salt and alkaline stress through different mechanisms. Through the virus-induced gene silencing technology (VIGS), it was speculated that GBCXE49 gene was involved in the response to alkaline stress in G. barbadense.
ESTHER : Rui_2022_BMC.Plant.Biol_22_194
PubMedSearch : Rui_2022_BMC.Plant.Biol_22_194
PubMedID: 35413814

Title : Characterization of the anti-AChE potential and alkaloids in Rhizoma Coptidis from different Coptis species combined with spectrum-effect relationship and molecular docking - Qi_2022_Front.Plant.Sci_13_1020309
Author(s) : Qi L , Zhong F , Liu N , Wang J , Nie K , Tan Y , Ma Y , Xia L
Ref : Front Plant Sci , 13 :1020309 , 2022
Abstract : Coptis species are the main source of Rhizoma Coptidis (RC) drugs, which have always been used to treat Alzheimer's disease in the clinical experience of ancient China. However, many species of this genus have been largely underutilized until now. With this fact, this research has been designed to investigate for the first time the anti-acetylcholinesterase (AChE) property of different extracts for RC drugs from four Coptis species (C. chinensis, C. deltoidea, C. teeta and C. omeiensis) and to quantify the main alkaloids. Petroleum ether, ethyl acetate and n-butanol fractions of RC drugs were sequentially collected using an accelerated solvent extraction technique. Spectrum-effect relationship and molecular docking were applied to analyse the relationships between alkaloids and AChE inhibitory activity. The N-butanol extract was proven to be the main active fraction, and C. teeta may be the best source of RC drugs for Alzheimer's disease treatment, with significantly lower IC 20, IC 50 and IC 80 values for AChE inhibition. The UPLC/QqQ-MS quantitative analysis showed that the accumulations of 10 alkaloids in RC drugs from different sources greatly varied. Three data processing methods (Random forest, Boruta and Pearson correlation) comprehensively analysed the spectrum-effect relationship and revealed that columbamine, berberine and palmatine were the most important AChE inhibitors that could be used as quality markers to select RC drugs for Alzheimer's disease treatment. In addition, the dominant compounds were successfully docked against AChE to verify the binding affinity and interactions with the active site. The present study can contribute to the reasonable development and utilization of RC drugs from different sources, especially to provide certain evidence for their application in the treatment of Alzheimer's disease.
ESTHER : Qi_2022_Front.Plant.Sci_13_1020309
PubMedSearch : Qi_2022_Front.Plant.Sci_13_1020309
PubMedID: 36388527

Title : GR24-mediated enhancement of salt tolerance and roles of H(2)O(2) and Ca(2+) in regulating this enhancement in cucumber - Zhang_2022_J.Plant.Physiol_270_153640
Author(s) : Zhang XH , Ma C , Zhang L , Su M , Wang J , Zheng S , Zhang TG
Ref : J Plant Physiol , 270 :153640 , 2022
Abstract : This study investigated the regulation of the exogenous strigolactone (SL) analog GR24 in enhancing the salt tolerance and the effects of calcium ion (Ca(2+)) and hydrogen peroxide (H(2)O(2)) on GR24's regulation effects in cucumber. The seedlings were sprayed with (1) distilled water (CK), (2) NaCl, (3) GR24, then NaCl, (4) GR24, then H(2)O(2) scavenger, then NaCl, and (5) GR24, then Ca(2+) blocker, then NaCl. The second true leaf was selected for biochemical assays. Under the salt stress, the exogenous GR24 maintained the ion balance, increased the activity of antioxidant enzymes, reduced the membrane lipid peroxidation, and increased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), accompanied by a decrease in relative conductivity, an increase in the proline content, and elevated gene expression levels of antioxidant enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, calcium-dependent protein kinases (CDPKs), salt overly sensitive SOS1, CBL-interacting protein kinase 2 (CIPK2), and calcineurin B-like protein 3 (CBL3). Such protective effects triggered by GR24 were attenuated or almost abolished by ethylene glycol tetraacetic acid (EGTA), lanthanum chloride (LaCl3, Ca(2+) channel blocker), diphenyleneiodonium (DPI, NADPH oxidase inhibitor), and dimethylthiourea (DMTU, hydroxyl radical scavenger). Our data suggest that exogenous GR24 is highly effective in alleviating salt-induced damages via modulating antioxidant capabilities and improving ionic homeostasis and osmotic balance and that H(2)O(2) and Ca(2+) are required for GR24-mediated enhancement of salt tolerance.
ESTHER : Zhang_2022_J.Plant.Physiol_270_153640
PubMedSearch : Zhang_2022_J.Plant.Physiol_270_153640
PubMedID: 35168135

Title : MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR - Wang_2022_Front.Vet.Sci_9_948873
Author(s) : Wang J , Hao Z , Hu L , Qiao L , Luo Y , Hu J , Liu X , Li S , Zhao F , Shen J , Li M , Zhao Z
Ref : Front Vet Sci , 9 :948873 , 2022
Abstract : In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep.
ESTHER : Wang_2022_Front.Vet.Sci_9_948873
PubMedSearch : Wang_2022_Front.Vet.Sci_9_948873
PubMedID: 35990270

Title : Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target - Xu_2022_PLoS.Pathog_18_e1010615
Author(s) : Xu Y , Yang J , Li W , Song S , Shi Y , Wu L , Sun J , Hou M , Wang J , Jia X , Zhang H , Huang M , Lu T , Gan J , Feng Y
Ref : PLoS Pathog , 18 :e1010615 , 2022
Abstract : Tuberculosis (TB) is one of the leading infectious diseases of global concern, and one quarter of the world's population are TB carriers. Biotin metabolism appears to be an attractive anti-TB drug target. However, the first-stage of mycobacterial biotin synthesis is fragmentarily understood. Here we report that three evolutionarily-distinct BioH isoenzymes (BioH1 to BioH3) are programmed in biotin synthesis of Mycobacterium smegmatis. Expression of an individual bioH isoform is sufficient to allow the growth of an Escherichia coli deltabioH mutant on the non-permissive condition lacking biotin. The enzymatic activity in vitro combined with biotin bioassay in vivo reveals that BioH2 and BioH3 are capable of removing methyl moiety from pimeloyl-ACP methyl ester to give pimeloyl-ACP, a cognate precursor for biotin synthesis. In particular, we determine the crystal structure of dimeric BioH3 at 2.27A, featuring a unique lid domain. Apart from its catalytic triad, we also dissect the substrate recognition of BioH3 by pimeloyl-ACP methyl ester. The removal of triple bioH isoforms (deltabioH1/2/3) renders M. smegmatis biotin auxotrophic. Along with the newly-identified Tam/BioC, the discovery of three unusual BioH isoforms defines an atypical 'BioC-BioH(3)' paradigm for the first-stage of mycobacterial biotin synthesis. This study solves a long-standing puzzle in mycobacterial nutritional immunity, providing an alternative anti-TB drug target.
ESTHER : Xu_2022_PLoS.Pathog_18_e1010615
PubMedSearch : Xu_2022_PLoS.Pathog_18_e1010615
PubMedID: 35816546
Gene_locus related to this paper: mycs2-a0r6y0

Title : Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples - Yin_2022_Anal.Chim.Acta_1190_339248
Author(s) : Yin Y , Kong X , Li M , Wang J , Dai X , Zhang Y , Lin W
Ref : Anal Chim Acta , 1190 :339248 , 2022
Abstract : Esterase is a large hydrolysis family, and widely distributed in many kinds of cells. It is responsible for multiple physiological and pathological functions including metabolism, gene expression. While abnormality of esterase is associated with many pathological activities in obesity, Wolman's disease, and cancer. Thereby, it is essential to design an effective tool for esterase in situ detection in biological systems. Herein, a novel fluorescent probe Y-1 for monitoring esterase in living cells was rationally designed. Probe Y-1 was synthesized by the conjugation between an acetylation of 4-hydroxy naphthalimide and benzothiazole group. Benzothiazole moiety is a typical Excited-state intramolecular proton transfer (ESIPT) controller. Acetate group was selected as the responsive site and ESIPT initiator. As the acetate group could block the ESIPT effect, the probe emits no fluorescence under the excitation of 455 nm. When binding with esterase, Y-1 shows distinct fluorescence with the peak at 560 nm with short time when ESIPT is on. Y-1 displays high sensitivity (LOD is 0.216 x 10(-3) U/mL), fast response (within 5 min), high selectivity and photostability towards esterase. Furthermore, the %RSD (relative standard deviation) of within-day and day-to-day precision was no more than 13.0% and the accuracy ranged from -6.5 to -12.3%. Kinetics performance of Y-1 indicates that esterase has high affinity and hydrolysis to Y-1. For biological applications, our probe is a time-dependent visualizing esterase in living HepG2 and CoLo205 cells within 15 min. After the treatment of orlistat (1 and 5 microM) for inhibiting the activity of esterase, the bright fluorescence has also been detected using our probe. Furthermore, it has been successful in monitoring the esterase in zebrafish, the data were consistent with cellular phenomena. Therefore, all these findings indicate that the robust probe Y-1 is a useful qualitative tool for detecting esterase in biological systems.
ESTHER : Yin_2022_Anal.Chim.Acta_1190_339248
PubMedSearch : Yin_2022_Anal.Chim.Acta_1190_339248
PubMedID: 34857133

Title : Effect of propeptide mutations on the directed evolution of Rhizomucor miehei lipase - Wang_2022_Protein.Pept.Lett__
Author(s) : Wang J , Bai R , Wu N , Zhang Y , Hu L
Ref : Protein Pept Lett , : , 2022
Abstract : BACKGROUND: A series of mutants of Rhizomucor miehei lipase (RML) screened through four rounds of directed evolution was studied as the research object. The hydrolysis activity of mutants to triglycerides was determined, and their genes were sequenced. Results showed that mutations in the propeptide can improve the activity of RML during the evolution. Two parts of propeptide (wild-type and mutant) and mature region were connected by molecular simulation technology. METHODS: The spatial structure of the most positive mutants containing the mutations in the propeptide was mainly characterized by the increase in the opening angle of the lid structure in the mature region of RML, the enhancement of the hydrophobicity of the active center, and the triad of the active center shifted outward. RESULTS: The three indexes above explain the mechanism of propeptide mutations on the activity change of the target protein. In addition, statistical analysis of all the mutants screened in directed evolution showed that: (1) most of the mutants with increased activity contained mutations of the propeptide; (2) In the later stage of directed evolution, the number of active mutants decreased gradually, and the mutations of inactivated protein mainly occurred in the mature region; and (3) In the last round of directed evolution, the mutations distributed in the propeptide improved the mutant activity further. The results show the propeptide down the evolutionary pressure of RML and delayed emergence of the evolutionary platform. CONCLUSION: These findings reveal the role of propeptide in the evolution of RML and provide strategies for the molecular transformation of other lipases.
ESTHER : Wang_2022_Protein.Pept.Lett__
PubMedSearch : Wang_2022_Protein.Pept.Lett__
PubMedID: 35289250
Gene_locus related to this paper: rhimi-lipas

Title : Probing the interaction of superparamagnetic iron oxide nanoparticles with lipase and their interacting consequences at the molecular level - Yang_2022_Toxicol.Res.(Camb)_11_654
Author(s) : Yang B , Jia R , Fang M , Wang S , Lv Z , Wang J
Ref : Toxicol Res (Camb) , 11 :654 , 2022
Abstract : BACKGROUND: Although superparamagnetic iron oxide nanoparticles (SPIONs) are used as carriers for candida rugosa lipase (CRL) in biomedical fields, their interactions and the influences on CRL are still unknown. Consequently, SPIONs were synthesized, characterized, and incubated with CRL to explore their molecular interactions and interacting consequences in this study. METHODS: The toxic effects of SPIONs on CRL and their molecular interactions were explored through transmission electron microscope, isothermal titration calorimetry, zeta potential measurements, multi-spectroscopic techniques, and biological enzyme activity tests. RESULTS: Results revealed the adsorption of SPIONs to CRL and the reduction of CRL aggregation. The unfolding and loosening of CRL structure as well as the change of secondary structure with the decrease of alpha-helix were found under SPIONs exposure. Moreover, higher SPIONs concentrations contributed to larger conformational changes and less aggregation of CRL. Meanwhile, it showed that hydrophobic forces were the dominant driving forces in the binding process, with the participation of electrostatic forces. CRL binds to SPIONs with the stoichiometry of 20.7 and the binding constant of 9.9 x 10(6) M(-1). No obvious changes were found in CRL activity due to no interference to Ser-209, Glu-341, and His-449 residues. CONCLUSION: This study examined the biological compatibility of SPIONs at the molecular level and provided important information about the structure and function of CRL upon binding to SPIONs. Our work might contribute to comprehend the molecular toxicity of SPIONs and the risks of engineered nanoparticles to human health.
ESTHER : Yang_2022_Toxicol.Res.(Camb)_11_654
PubMedSearch : Yang_2022_Toxicol.Res.(Camb)_11_654
PubMedID: 36051670

Title : Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA - Liu_2022_Plant.Cell_34_3301
Author(s) : Liu T , Zhang X , Zhang H , Cheng Z , Liu J , Zhou C , Luo S , Luo W , Li S , Xing X , Chang Y , Shi C , Ren Y , Zhu S , Lei C , Guo X , Wang J , Zhao Z , Wang H , Zhai H , Lin Q , Wan J
Ref : Plant Cell , 34 :3301 , 2022
Abstract : Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
ESTHER : Liu_2022_Plant.Cell_34_3301
PubMedSearch : Liu_2022_Plant.Cell_34_3301
PubMedID: 35670739

Title : Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry - Hu_2022_Lab.Med__
Author(s) : Hu C , Zhuang X , Zhang J , Wang T , Du S , Wang J , Peng X , Cao Q , Zhang M , Jiang Y
Ref : Lab Med , : , 2022
Abstract : OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. METHODS: Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. RESULTS: A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. CONCLUSION: The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM.
ESTHER : Hu_2022_Lab.Med__
PubMedSearch : Hu_2022_Lab.Med__
PubMedID: 35075477

Title : The longitudinal triglyceride phenotype in heterozygotes with LPL pathogenic variants - Perera_2022_J.Clin.Lipidol__
Author(s) : Perera SD , Wang J , McIntyre AD , Dron JS , Hegele RA
Ref : J Clin Lipidol , : , 2022
Abstract : BACKGROUND: Biallelic pathogenic variants in lipoprotein lipase (LPL) cause familial chylomicronemia syndrome with severe hypertriglyceridemia (HTG), defined as plasma triglycerides (TG) > 10 mmol/L (> 885 mg/dL). TG levels in individuals with one copy of a pathogenic LPL gene variant is less familiar; some assume that the phenotype is intermediate between homozygotes and controls. OBJECTIVE: We undertook an evaluation of the longitudinal TG phenotype of individuals heterozygous for pathogenic LPL variants. METHODS: Medically stable outpatients were evaluated based on having: (1) a single copy of a rare pathogenic LPL variant; and (2) serial fasting TG measurements obtained over > 1.5 years of follow-up. RESULTS: Fifteen patients with a single pathogenic LPL variant were followed for a mean of 10.3 years (range 1.5 to 30.3 years). TG levels varied widely both within and between patients. One patient had normal TG levels < 2.0 mmol/L (< 175 mg/dL) continuously, while four patients had at least one normal TG level. Most patients fluctuated between mild-to-moderate and severe HTG: five patients had only mild-to-moderate HTG, with TG levels ranging from 2.0 to 9.9 mmol/L (175 to 885 mg/dL), while 6 patients had at least one instance of severe HTG. Of the 203 total TG measurements from these patients, 14.8%, 67.0% and 18.2% were in the normal, mild-to-moderate and severe HTG ranges, respectively. CONCLUSION: The heterozygous LPL deficient phenotype is highly variable both within and between patients. Heterozygosity confers susceptibility to a wide range of TG phenotypes, with severity likely depending on secondary factors.
ESTHER : Perera_2022_J.Clin.Lipidol__
PubMedSearch : Perera_2022_J.Clin.Lipidol__
PubMedID: 36476373

Title : A role of peptidoglycan recognition protein in mediating insecticide detoxification in Glyphodes pyloalis - Jiang_2021_Arch.Insect.Biochem.Physiol__e21842
Author(s) : Jiang DL , Ding JH , Liu ZX , Shao ZM , Liang XH , Wang J , Wu FA , Sheng S
Ref : Archives of Insect Biochemistry & Physiology , :e21842 , 2021
Abstract : Glyphodes pyloalis Walker has become one of the most significant mulberry pests, and it has caused serious economic losses in major mulberry growing regions in China. Peptidoglycan recognition proteins (PGRPs) are responsible for initiating and regulating immune signalling pathways in insects. However, their roles responding to chemical pesticides is still less known. This study aimed to investigate the possible detoxication function of GpPGRP-S2 and GpPGRP-S3 in G. pyloalis in response to chlorfenapyr and phoxim. The chlorfenapyr and phoxim treatment significantly induced the expression level of GpPGRP-S3 at 48 h. In addition, the expression levels of GpPGRP-S2 and GpPGRP-S3 in the chlorfenapyr/phoxim treatment group were significantly higher in midgut than those in the control group at 48 h. The results of the survival experiment showed that silencing either GpPGRP-S2 or GpPGRP-S3 would not influence the survival rate of G. pyloalis which treated with phoxim, however, silencing GpPGRP-S2 or GpPGRP-S3 would cause G. pyloalis to be more easily killed by chlorfenapyr. The expression of carboxylesterase GpCXE1 was significantly induced by chlorfenapyr/phoxim treatment, while it was suppressed once silenced GpPGRP-S2 followed with chlorfenapyr treatment or silenced GpPGRP-S3 followed with phoxim treatment. These results might suggest that under the chlorfenapyr/phoxim treatment condition, the connection between GpPGRPs and detoxification genes in insect was induced to maintain physiological homeostasis; and these results may further enrich the mechanisms of insects challenged by insecticides.
ESTHER : Jiang_2021_Arch.Insect.Biochem.Physiol__e21842
PubMedSearch : Jiang_2021_Arch.Insect.Biochem.Physiol__e21842
PubMedID: 34499777

Title : A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA\/VSD) and tetralogy of Fallot (TOF) - Peng_2021_FEBS.Open.Bio_11_375
Author(s) : Peng J , Wang Q , Meng Z , Wang J , Zhou Y , Zhou S , Song W , Chen S , Chen AF , Sun K
Ref : FEBS Open Bio , 11 :375 , 2021
Abstract : Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N-myc downstream-regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase-9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell-cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF.
ESTHER : Peng_2021_FEBS.Open.Bio_11_375
PubMedSearch : Peng_2021_FEBS.Open.Bio_11_375
PubMedID: 33211401
Gene_locus related to this paper: human-NDRG4

Title : Adsorption mechanism of two pesticides on polyethylene and polypropylene microplastics: DFT calculations and particle size effects - Mo_2021_Environ.Pollut_291_118120
Author(s) : Mo Q , Yang X , Wang J , Xu H , Li W , Fan Q , Gao S , Yang W , Gao C , Liao D , Li Y , Zhang Y
Ref : Environ Pollut , 291 :118120 , 2021
Abstract : Polyethylene (PE) and polypropylene (PP) microplastics (MPs), as carriers, can bind with pesticides, which propose harmful impacts to aqueous ecosystems. Meanwhile, carbofuran and carbendazim (CBD), two widely used carbamate pesticides, are toxic to humans because of the inhibition of acetylcholinesterase activity. The interaction between two MPs and two pesticides could start in farmland and be maintained during transportation to the ocean. Herein, the adsorption behavior and mechanism of carbofuran and carbendazim (CBD) by PE and PP MPs were investigated via characterization and density functional theory (DFT) simulation. The adsorption kinetic and thermodynamic data were best described by pseudo-second-order kinetics and the Freundlich models. The adsorption behaviors of individual carbofuran/CBD on both MPs were very similar. The CBD adsorption rate and capacity of PE and PP MPs were higher than those of carbofuran. This phenomenon explained the lower negative effects of DOM (oxalic acid, glycine (Gly)) on CBD adsorption relative to those of carbofuran. The presence of oxalic acid and Gly decreased the PE adsorption by 20.40-48.02% and the PP adsorption by 19.27-42.11%, respectively. It indicated the significance of DOM in carbofuran cycling. The adsorption capacities were negatively correlated with MPs size, indicating the importance of specific surficial area. Fourier transformation infrared spectroscopy before and after adsorption suggested that the adsorption process did not produce any new covalent bond. Instead, intermolecular van der Waals forces were one of the primary adsorption mechanisms of carbofuran and CBD by MPs, as evidenced by DFT calculations. Based on the zeta potential, the electrostatic interaction explained the higher adsorption CBD by MPs than carbofuran.
ESTHER : Mo_2021_Environ.Pollut_291_118120
PubMedSearch : Mo_2021_Environ.Pollut_291_118120
PubMedID: 34520951

Title : Enhancing the thermostability of a mono- and diacylglycerol lipase from Malassizia globose by stabilizing a flexible loop in the catalytic pocket - Xing_2021_Enzyme.Microb.Technol_149_109849
Author(s) : Xing YN , Tan J , Wang Y , Wang J
Ref : Enzyme Microb Technol , 149 :109849 , 2021
Abstract : A lipase from Malassizia globose, named SMG1, is highly desirable for industrial application due to its substrate specificity towards mono- and diacylglycerol. To improve its thermostability, we constructed a mutant library using an error-prone polymerase chain reaction, which was screened for both initial and residual enzymatic activity. Selected mutants were further studied using purified proteins for their kinetic thermostability at 45 degC, T(50) (the temperature at which the enzyme loses half of its activity), and the optimal reaction temperature. Results showed that the majority of mutations with improved thermostability were on the protein surface. D245N and L270P showed the most significant thermostability enhancement with an approximately 3 degC increase in T(50) compared to wild-type (WT). In addition, combining these two mutations resulted in an increase of T(50) by 5 degreesC. Also, the optimal reaction temperatures of L270P and this double mutant are 10 degC higher than WT. The double mutant showed an approximately 100-fold increase in half-life at 45 degC and higher enzymatic activities at 30 degC and above compared to WT. High-temperature unfolding molecular dynamics simulation suggested that the double mutant stabilized a flexible loop in the catalytic pocket.
ESTHER : Xing_2021_Enzyme.Microb.Technol_149_109849
PubMedSearch : Xing_2021_Enzyme.Microb.Technol_149_109849
PubMedID: 34311886
Gene_locus related to this paper: malgo-a8puy1

Title : Evaluation of Sensitivity to Phoxim and Cypermethrin in an Endoparasitoid, Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae), and Its Parasitization Efficiency Under Insecticide Stress - Sheng_2021_J.Insect.Sci_21_
Author(s) : Sheng S , Wang J , Zhang XR , Liu ZX , Yan MW , Shao Y , Zhou JC , Wu FA
Ref : J Insect Sci , 21 : , 2021
Abstract : Insecticides can have consequences for beneficial arthropods. Insect parasitoids can contact insecticides through direct exposure spray droplets or residues on crop foliage. Here, we focus on better understand the response of Meteorus pulchricornis (Wesmael), a parasitoid wasp of lepidopteran pests, and its detoxification mechanisms on stress caused by phoxim and cypermethrin. Hence, we determined the dose-mortality curves and estimating the sublethal concentrations (LC30 and LC50). Then, we applied the sublethal concentrations against adult parasitoids to assess its survival, parasitism efficacy, and also developmental and morphometric parameters of their offspring. Simultaneously, we check the activities of glutathione S-transferase (GST), acetylcholinesterase (AChE), and peroxidase (POD) after sublethal exposure of both insecticides, which has measured until 48 h after treatment. Overall, phoxim and cypermethrin exhibited acute lethal activity toward the parasitoid with LC50 values 4.608 and 8.570 mg/liter, respectively. Also, we detect that LC30 was able to trigger the enzymatic activity of GST, AChE, and POD, suggesting a potential detoxification mechanism. However, even when subjected to sublethal exposure, our results indicate strong negatives effects, in particular for phoxim, which has affected the parasitism efficacy and also the developmental and morphometric parameters of M. pulchricornis offspring. Therefore, it can be concluded that both phoxim and cypermethrin have negative impacts on M. pulchricornis and we suggest cautioning their use and the need for semifield and field assessments to confirm such an impact.
ESTHER : Sheng_2021_J.Insect.Sci_21_
PubMedSearch : Sheng_2021_J.Insect.Sci_21_
PubMedID: 33580255

Title : Synthesis, biological evaluation and molecular modeling of benzofuran piperidine derivatives as Abeta antiaggregant - Chowdhury_2021_Eur.J.Med.Chem_222_113541
Author(s) : Chowdhury SR , Gu J , Hu Y , Wang J , Lei S , Tavallaie MS , Lam C , Lu D , Jiang F , Fu L
Ref : Eur Journal of Medicinal Chemistry , 222 :113541 , 2021
Abstract : A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Abeta antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Abeta antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Abeta peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC(50) = 61 microM and self induced Abeta (25-35) aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Abeta antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Abeta antiaggregant and good antiacetylholinesterase inhibitor (self induced Abeta (25-35) aggregation 57.71% and hAChE IC(50) = 21 microM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Abeta(25-35) peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Abeta monomer, Abeta fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Abeta antiaggregant, useful candidate for the treatment of AD.
ESTHER : Chowdhury_2021_Eur.J.Med.Chem_222_113541
PubMedSearch : Chowdhury_2021_Eur.J.Med.Chem_222_113541
PubMedID: 34116326

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

Title : Genome-Wide Identification of Tannase Genes and Their Function of Wound Response and Astringent Substances Accumulation in Juglandaceae - Wang_2021_Front.Plant.Sci_12_664470
Author(s) : Wang J , Wang K , Lyu S , Huang J , Huang C , Xing Y , Wang Y , Xu Y , Li P , Hong J , Xi J , Si X , Ye H , Li Y
Ref : Front Plant Sci , 12 :664470 , 2021
Abstract : Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes (TAs) responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that TA genes and neighboring clade genes (TA-like genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of TA genes produced by tandem repeat. TA genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene GGTs and the hydrolase gene TAs was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the CcGGTs' expression was higher than CiGGTs in the initiation of development, but CcTAs continued to be down-regulated while CiTA2a and CiTA2b were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of TAs in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae.
ESTHER : Wang_2021_Front.Plant.Sci_12_664470
PubMedSearch : Wang_2021_Front.Plant.Sci_12_664470
PubMedID: 34079571
Gene_locus related to this paper: camsi-CsTA

Title : Long-Wavelength Ratiometric Fluorescent Probe for the Early Diagnosis of Diabetes - Wang_2021_Anal.Chem_93_11461
Author(s) : Wang J , Zhang L , Qu Y , Yang Y , Cao T , Cao Y , Iqbal A , Qin W , Liu Y
Ref : Analytical Chemistry , 93 :11461 , 2021
Abstract : Diabetes is a metabolic disease caused by high blood sugar. Patients are often suffering from high blood pressure and arteriosclerosis, which may even evolve into liver disease, kidney disease, and other diabetic complications. Dipeptide peptidase IV (DPP-IV) plays an important role in regulating blood sugar levels and is one of the targets for the diagnosis and treatment of diabetes. Here, a long-wavelength ratiometric fluorescent probe DCDHFNH(2)-dpp4 for detecting DPP-IV was designed and synthesized. DCDHFNH(2)-dpp4 was used to detect DPP-IV in healthy, tumor-bearing, and diabetic mice, and only diabetic mice showed strong fluorescence signals. In organ imaging, it is found that DPP-IV is relatively enriched in the liver of diabetic mice. In addition, probe DCDHFNH(2)-dpp4 also exhibited a significant ratiometric fluorescence signal in the serum of diabetic mice. Therefore, the fluorescent probe DCDHFNH(2)-dpp4 has shown outstanding potential in the early diagnosis of diabetes, and DCDHFNH(2)-dpp4 is hopeful to be applied to actual clinical medicine.
ESTHER : Wang_2021_Anal.Chem_93_11461
PubMedSearch : Wang_2021_Anal.Chem_93_11461
PubMedID: 34369744

Title : Inducing new bioactive metabolites production from coculture of Pestalotiopsis sp. and Penicillium bialowiezense - Li_2021_Bioorg.Chem_110_104826
Author(s) : Li F , Yan S , Huang Z , Gao W , Zhang S , Mo S , Lin S , Wang J , Hu Z , Zhang Y
Ref : Bioorg Chem , 110 :104826 , 2021
Abstract : Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The delta(10,11) double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro beta-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant beta-glucuronidase inhibitory potency with IC(50) values of 7.6 and 10.3 microM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC(50) value of 21.3 microM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed.
ESTHER : Li_2021_Bioorg.Chem_110_104826
PubMedSearch : Li_2021_Bioorg.Chem_110_104826
PubMedID: 33780746

Title : Metabolic degradation of lentinan in liver mediated by CYP450 enzymes and epoxide hydrolase - Zheng_2021_Carbohydr.Polym_253_117255
Author(s) : Zheng Z , Zhang Y , Liu Y , Wang J , Cui Z , Pan X , Tang W , Wang K
Ref : Carbohydr Polym , 253 :117255 , 2021
Abstract : Lentinan (LNT), a typical triple helix beta-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other beta-glucans.
ESTHER : Zheng_2021_Carbohydr.Polym_253_117255
PubMedSearch : Zheng_2021_Carbohydr.Polym_253_117255
PubMedID: 33279005

Title : Lipolysis and lipophagy play individual and interactive roles in regulating triacylglycerol and cholesterol homeostasis and mitochondrial form in zebrafish - Han_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1866_158988
Author(s) : Han SL , Qian YC , Limbu SM , Wang J , Chen LQ , Zhang ML , Du ZY
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , 1866 :158988 , 2021
Abstract : Neutral lipases-mediated lipolysis and acid lipases-moderated lipophagy are two main processes for degradation of lipid droplets (LDs). However, the individual and interactive roles of these metabolic pathways are not well known across vertebrates. This study explored the roles of lipolysis and lipophagy from the aspect of neutral and acid lipases in zebrafish. We established zebrafish strains deficient in either adipose triglyceride lipase (atgl(-/-); AKO fish) or lysosomal acid lipase (lal(-/-); LKO fish) respectively, and then inhibited lipolysis in the LKO fish and lipophagy in the AKO fish by feeding diets supplemented with the corresponding inhibitors Atglistatin and 3-Methyladenine, respectively. Both the AKO and LKO fish showed reduced growth, swimming activity, and oxygen consumption. The AKO fish did not show phenotypes in adipose tissue, but mainly accumulated triacylglycerol (TAG) in liver, also, they had large LDs in the hepatocytes, and did not stimulate lipophagy as a compensation response but maintained basal lipophagy. The LKO fish reduced total lipid accumulation in the body but had high cholesterol content in liver; also, they accumulated small LDs in the hepatocytes, and showed increased lipolysis, especially Atgl expression, as a compensatory mechanism. Simultaneous inhibition of lipolysis and lipophagy in zebrafish resulted in severe liver damage, with the potential to trigger mitophagy. Overall, our study illustrates that lipolysis and lipophagy perform individual and interactive roles in maintaining homeostasis of TAG and cholesterol metabolism. Furthermore, the interactive roles of lipolysis and lipophagy may be essential in regulating the functions and form of mitochondria.
ESTHER : Han_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1866_158988
PubMedSearch : Han_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1866_158988
PubMedID: 34111526

Title : Cyclic Peptides from the Soft Coral-Derived Fungus Aspergillus sclerotiorum SCSIO 41031 - Long_2021_Mar.Drugs_19_
Author(s) : Long J , Chen Y , Chen W , Wang J , Zhou X , Yang B , Liu Y
Ref : Mar Drugs , 19 : , 2021
Abstract : Three novel cyclic hexapeptides, sclerotides C-E (1-3), and a new lipodepsipeptide, scopularide I (4), together with a known cyclic hexapeptide sclerotide A (5), were isolated from fermented rice cultures of a soft coral-derived fungus: Aspergillus sclerotiorum SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey's method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (4) exhibited acetylcholinesterase inhibitory activity with an IC(50) value of 15.6 microM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC(50) value of 10.1 microM.
ESTHER : Long_2021_Mar.Drugs_19_
PubMedSearch : Long_2021_Mar.Drugs_19_
PubMedID: 34940700

Title : Molecular response uncovers neurotoxicity of Pardosa pseudoannulata exposed to cadmium pressure - Lv_2021_Environ.Pollut_280_117000
Author(s) : Lv B , Wang J , He Y , Zeng Z , Tang YE , Li N , Chen LJ , Wang Z , Song QS
Ref : Environ Pollut , 280 :117000 , 2021
Abstract : Cadmium (Cd) is a widely distributed heavy metal in south of China. Growing evidence indicates that systemic exposure to Cd, particularly the long-term exposure, may cause neurotoxic effects. Nevertheless, mechanisms underlying Cd neurotoxicity remain not completely understood. In this report, we investigated the neural alterations in the spider Pardosa pseudoannulata (Bosenberg and Strand, 1906) exposed to long-term Cd (LCd) and short-term Cd (SCd) pressure. Cd stress lowered foraging ability and prey consuming time in the spiders. In addition, enzymatic analysis results indicated that Cd exposure reduced the level of acetylcholinesterase at subcellular level. We then identified differentially expressed genes (DEGs) in the Cd exposed spiders using pairwise comparisons and found that a large number of DEGs were related to neurotransmitter receptors and ion transport and binding proteins. Notably, LCd exposure harbored more altered genes in ion transporter activity comparing with SCd exposure. From six K-means clusters, 53 putative transcriptional factors (TFs) belonging to 21 families were characterized, and ZBTB subfamily displayed the most distinctive alterations in the characterized genes, which is assumed to play a key role in the regulation of ion transmembrane process under Cd stress. A protein-to-protein interaction network constructed by the yielded DEGs also showed that ion and receptor binding activities were affected under long-term Cd exposure. Four key modules from the network indicated that Cd may further down-regulate energy metabolism pathway in spiders. Collectively, this comprehensive analysis provides multi-dimensional insights to understand the molecular response of spiders to Cd exposure.
ESTHER : Lv_2021_Environ.Pollut_280_117000
PubMedSearch : Lv_2021_Environ.Pollut_280_117000
PubMedID: 33784568

Title : Sequence and structure-based method to predict diacylglycerol lipases in protein sequence - Ali_2021_Int.J.Biol.Macromol__
Author(s) : Ali S , Liu X , Sen L , Lan D , Wang J , Hassan MI , Wang Y
Ref : Int J Biol Macromol , : , 2021
Abstract : Lipase enzymes play a central role in biotechnology and the food industry. Diacylglyceride lipases (DAG) have received considerable attention due to their physiological significance and potential industrial usage. However, compared to the wide application of triacylglycerol (TAG) lipases, DAG lipases have a limited application due to their low thermostability and specific activity. The molecular basis of substrate specificity of DAG lipases remains elusive, making structure-guided engineering of TAG to DAG lipase difficult. Besides, the number of available DAG lipases is limited compared to TAG lipases. In the current study, we identified structural consensus motifs of DAG lipases that contribute to their DAG specificity on a structural comparison of DAG and TAG lipases. To find potential DAG lipases, sequence motifs and predicted secondary structures were used to screen millions of protein sequences and predict new DAG lipases. In total, 83 new putative DAG lipases were identified. The predicted DAG lipases were validated by expression of randomly chosen putative DAG lipases followed by functional assay for their DAG and TAG specific activity. The reported method is efficient and cost-effective for discovering new DAG lipases used in the food industry after the required characterization to meet potential application needs.
ESTHER : Ali_2021_Int.J.Biol.Macromol__
PubMedSearch : Ali_2021_Int.J.Biol.Macromol__
PubMedID: 33836195

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Fluorescent and colorimetric dual-response sensor based on copper (II)-decorated graphitic carbon nitride nanosheets for detection of toxic organophosphorus - Chen_2021_Food.Chem_345_128560
Author(s) : Chen Y , Zhu Y , Zhao Y , Wang J
Ref : Food Chem , 345 :128560 , 2021
Abstract : An efficient and convenient detection method for organophosphorus pesticide (OP) residues is needed because of their high neurotoxicity and severe threat to food safety. OPs effectively reduce the production of thiocholine in the acetylcholinesterase/acetylthiocholine reaction by inhibiting the activity of acetylcholinesterase. Therefore, we developed a feasible and convenient fluorescent and colorimetric dual-response sensor based on the competitive complexation of Cu(2+) between graphitic carbon nitride nanosheets and thiocholine for the rapid detection of OPs with high sensitivity. Malathion was used as a model OP, and a linear range of 70-800 nM with a detection limit of 6.798 nM for a fluorescent signaling platform and 2.5-25 nM with a detection limit of 1.204 nM for a colorimetric probe were attained. The constructed probe was successfully applied to determine OP in actual samples of cabbages leaves and tap water. The results indicated that the dual-response probe was reliable and sensitive to actual samples.
ESTHER : Chen_2021_Food.Chem_345_128560
PubMedSearch : Chen_2021_Food.Chem_345_128560
PubMedID: 33601648

Title : Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure - Kang_2021_Environ.Sci.Pollut.Res.Int__
Author(s) : Kang L , Chen J , Wang J , Zhao T , Wei Y , Wu Y , Han L , Zheng X , Shen L , Long C , Wei G , Wu S
Ref : Environ Sci Pollut Res Int , : , 2021
Abstract : The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.
ESTHER : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedID: 34595713

Title : Biochemical and Structural Characterization of a Novel Bacterial Tannase From Lachnospiraceae bacterium in Ruminant Gastrointestinal Tract - Guan_2021_Front.Bioeng.Biotechnol_9_806788
Author(s) : Guan L , Wang K , Gao Y , Li J , Yan S , Ji N , Ren C , Wang J , Zhou Y , Li B , Lu S
Ref : Front Bioeng Biotechnol , 9 :806788 , 2021
Abstract : Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds present in hydrolyzable tannins to release gallic acid. Here, a novel tannase from Lachnospiraceae bacterium (TanA(Lb)) was characterized. The recombinant TanA(Lb) exhibited maximal activity at pH 7.0 and 50 degreesC, and it maintained more than 70% relative activity from 30 degreesC to 55 degreesC. The activity of TanA(Lb) was enhanced by Mg(2+) and Ca(2+), and was dramatically reduced by Cu(2+) and Mn(2+). TanA(Lb) is capable of degrading esters of phenolic acids with long-chain alcohols, such as lauryl gallate as well as tannic acid. The Km value and catalytic efficiency (k (cat) /Km) of TanA(Lb) toward five substrates showed that tannic acid (TA) was the favorite substrate. Homology modeling and structural analysis indicated that TanA(Lb) contains an insertion loop (residues 341-450). Based on the moleculer docking and molecular dynamics (MD) simulation, this loop was observed as a flap-like lid to interact with bulk substrates such as tannic acid. TanA(Lb) is a novel bacterial tannase, and the characteristics of this enzyme make it potentially interesting for industrial use.
ESTHER : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedSearch : Guan_2021_Front.Bioeng.Biotechnol_9_806788
PubMedID: 34976993
Gene_locus related to this paper: 9firm-TanALb

Title : Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling - Guo_2021_Nat.Commun_12_2046
Author(s) : Guo L , Iida A , Bhavani GS , Gowrishankar K , Wang Z , Xue JY , Wang J , Miyake N , Matsumoto N , Hasegawa T , Iizuka Y , Matsuda M , Nakashima T , Takechi M , Iseki S , Yambe S , Nishimura G , Koseki H , Shukunami C , Girisha KM , Ikegawa S
Ref : Nat Commun , 12 :2046 , 2021
Abstract : Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53, which encodes a nuclear envelope transmembrane protein. Tmem53(-/-) mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53(-/-) mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation.
ESTHER : Guo_2021_Nat.Commun_12_2046
PubMedSearch : Guo_2021_Nat.Commun_12_2046
PubMedID: 33824347
Gene_locus related to this paper: human-TMEM53

Title : Iridium Single-Atomic Site Catalysts with Superior Oxygen Reduction Reaction Activity for Sensitive Monitoring of Organophosphorus Pesticides - Luo_2021_Anal.Chem__
Author(s) : Luo X , Luo Z , Wei X , Jiao L , Fang Q , Wang H , Wang J , Gu W , Hu L , Zhu C
Ref : Analytical Chemistry , : , 2021
Abstract : Tremendous efforts have been made in developing single-atomic site catalysts (SASCs) for oxygen reduction reaction (ORR), which is regarded as a pivotal cornerstone in electrochemical energy conversion. However, SASCs for ORR have not been explored for electrochemical sensing. Herein, a template-sacrificed strategy is reported for the synthesis of atomically dispersed Ir SASCs, serving as a sensing platform to detect organophosphorus pesticides (OPs) with high sensitivity and selectivity. Owing to abundant Ir single-atom active sites, Ir SASCs show excellent ORR activity and stability in a neutral medium. It is found that the ORR activity of Ir SASCs can be inhibited by thiocholine, which is the hydrolysate of acetylthiocholine. After being integrated with acetylcholinesterase (AChE), the AChE-Ir SASC-based electrochemical sensor is established and shows a superior sensitivity, which shows a wide detection range of 0.5-500 ng mL(-1) with a low detection limit of 0.17 ng mL(-1) for OPs. This work exhibits a broad application prospect of ORR for sensitive detection of biomolecules.
ESTHER : Luo_2021_Anal.Chem__
PubMedSearch : Luo_2021_Anal.Chem__
PubMedID: 34969242

Title : Structural and biochemical mechanisms of NLRP1 inhibition by DPP9 - Huang_2021_Nature__
Author(s) : Huang M , Zhang X , Toh GA , Gong Q , Wang J , Han Z , Wu B , Zhong F , Chai J
Ref : Nature , : , 2021
Abstract : Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)(1-7). In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation(8,9); however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA-CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA-CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome.
ESTHER : Huang_2021_Nature__
PubMedSearch : Huang_2021_Nature__
PubMedID: 33731929
Gene_locus related to this paper: rat-dpp9

Title : Expression of an alkaline feruloyl esterases from thermophilic Chaetomium thermophilum and its boosting effect on delignification of pulp - Hou_2021_Enzyme.Microb.Technol_150_109859
Author(s) : Hou Y , Yang Z , Yin Y , Meng Z , Wang J , Zhao T , Yang Q
Ref : Enzyme Microb Technol , 150 :109859 , 2021
Abstract : Exploration of feruloyl esterase (FAE) with the resistance to heat and alkali conditions in biobleaching process to improve the separation efficiency of lignocellulose is the key to achieving green papermaking. Herein, we expressed FAEB of C. thermophilum and obtained a thermostable alkaline FAE that can effectively promote the removal of lignin from pulp. The faeB gene was successfully obtained through genomic Blast strategy and high-efficiency expressed under the control of strong alcohol oxidase promoter in Pichia pastoris. The recombinant CtFAEB has an optimal temperature of 65 degreesC and pH of 7.0. After treated at 65 degreesC for 1 h, CtFAEB can still retain 63.21 % of its maximum activity, showing a good thermal stability. In addition, the recombinant CtFAEB has broad pH stability and can retain about 56 % of the maximum activity even at pH 11.0. Compared with the effect of mesophilic FAE, pretreatment with thermostable CtFAEB can promote the delignification by laccase and alkaline hydrogen peroxide from the pulp at 70 degreesC and pH 9.0. Alignment of the protein sequences of CtFAEB and mesophilic FAE suggested that the percentage of amino acids that easily form alpha helix in CtFAEB increases, which enhances its structural rigidity and thereby improves its thermal stability and alkali tolerance. Our study provides an effective method to obtain thermostable and alkaline FAEs, which will promote its application in biobleaching and other biorefining industries.
ESTHER : Hou_2021_Enzyme.Microb.Technol_150_109859
PubMedSearch : Hou_2021_Enzyme.Microb.Technol_150_109859
PubMedID: 34489049
Gene_locus related to this paper: neucr-faeb

Title : Role of epoxide hydrolases and cytochrome P450s on metabolism of KZR-616, a first-in-class selective inhibitor of the immunoproteasome - Fang_2021_Drug.Metab.Dispos__
Author(s) : Fang Y , Johnson H , Anderl JL , Muchamuel T , McMinn D , Morisseau C , Hammock BD , Kirk C , Wang J
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and, based on promising therapeutic activity in animal models of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes and a hepatocellular carcinoma cell line revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (CYP) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by co-administration of inhibitors or inducers of CYP and sEH. Significance Statement This work presents a thorough and systematic investigation of metabolism and kinetic of KZR-616 and other peptide epoxyketones in in vitro and cell-based enzymatic systems. Gained information could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. The study also demonstrates a robust source of in vitro metabolism identification that correlated very well with in vivo PK metabolism for peptide epoxyketones.
ESTHER : Fang_2021_Drug.Metab.Dispos__
PubMedSearch : Fang_2021_Drug.Metab.Dispos__
PubMedID: 34234005
Gene_locus related to this paper: human-EPHX1

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

Title : Computational Design and Crystal Structure of a Highly Efficient Benzoylecgonine Hydrolase - Chen_2021_Angew.Chem.Int.Ed.Engl_60_21959
Author(s) : Chen X , Deng X , Zhang Y , Wu Y , Yang K , Li Q , Wang J , Yao W , Tong J , Xie T , Hou S , Yao J
Ref : Angew Chem Int Ed Engl , 60 :21959 , 2021
Abstract : Benzoylecgonine (BZE) is the major toxic metabolite of cocaine, and is responsible for the long-term cocaine-induced toxicity due to its long residence time in humans. BZE is also the main contaminant following cocaine consumption, representing a risk to our environment and non-target organisms. Here, we identified the bacterial cocaine esterase (CocE) as a BZE-metabolizing enzyme (BZEase), which can degrade BZE into biological inactive metabolites (ecgonine and benzoic acid). CocE was redesigned by a reactant-state-based enzyme design theory. An encouraging mutant denoted as BZEase2, presented a >400-fold improved catalytic efficiency against BZE compared with wild-type (WT) CocE. In vivo , a single dose of BZEase2 (1 mg/kg, IV) could eliminate nearly all BZE within only two minutes, suggesting the enzyme have the potential for cocaine overdose treatment and BZE elimination in the environment by accelerating BZE clearance. The crystal structure of a designed BZEase was determined, providing additional insights in support of our simulation results.
ESTHER : Chen_2021_Angew.Chem.Int.Ed.Engl_60_21959
PubMedSearch : Chen_2021_Angew.Chem.Int.Ed.Engl_60_21959
PubMedID: 34351032
Gene_locus related to this paper: rhosm-cocE

Title : Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure - Zhou_2021_J.Hazard.Mater_416_126142
Author(s) : Zhou W , Li X , Wang Y , Wang J , Zhang J , Wei H , Peng C , Wang Z , Li G , Li D
Ref : J Hazard Mater , 416 :126142 , 2021
Abstract : 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.
ESTHER : Zhou_2021_J.Hazard.Mater_416_126142
PubMedSearch : Zhou_2021_J.Hazard.Mater_416_126142
PubMedID: 34492931

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

Title : Directionally Modified Fluorophores for Super-Resolution Imaging of Target Enzymes: A Case Study with Carboxylesterases - Jia_2021_J.Med.Chem__
Author(s) : Jia Y , Wang J , Li P , Ma X , Han K
Ref : Journal of Medicinal Chemistry , : , 2021
Abstract : In the need for improving the labeling quality of super-resolution imaging, multifarious fluorescent labeling strategies have sprang up. Among them, a small molecule inhibitor-probe (SMI-probe) shows its advancement in fine mapping due to its smaller size and its specific binding to a specific site. Herein, we report a novel protocol of mechanism-guided directional modification of fluorophores into fluorescent inhibitors for enzyme targeting, which could half the size of the SMI-probe. To confirm the feasibility of the strategy, carboxylesterase (hCE) inhibitors are designed and developed. Among the constructed molecule candidates, NIC-4 inhibited both isoforms of hCE1 and hCE2, with IC(50) values of 4.56 and 4.11 microM. The CE-targeting specificity of NIC-4 was confirmed by colocalizing with an immunofluorescent probe in fixed-cell confocal imaging. Moreover, NIC-4 was used in live-cell super-resolution microscopy, which indicates dotlike structures instead of the larger staining with the immunofluorescent probe. Moreover, it enables the real-time tracking of dynamic flow of carboxylesterases in live cells.
ESTHER : Jia_2021_J.Med.Chem__
PubMedSearch : Jia_2021_J.Med.Chem__
PubMedID: 34694804

Title : Morphine increases myocardial triacylglycerol through regulating adipose triglyceride lipase S406 phosphorylation - Li_2021_Life.Sci_283_119866
Author(s) : Li L , Wang J , Li D , Zhang H
Ref : Life Sciences , 283 :119866 , 2021
Abstract : AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation.
ESTHER : Li_2021_Life.Sci_283_119866
PubMedSearch : Li_2021_Life.Sci_283_119866
PubMedID: 34352257

Title : The protonation state of Glu202 in acetylcholinesterase - Wang_2021_Proteins__
Author(s) : Wang J , Lai S , Kong Y , Yao W , Chen X , Liu J
Ref : Proteins , : , 2021
Abstract : Acetylcholinesterase (AChE) is the crucial enzyme in the central nervous system. It is the target of various organophosphorus nerve agents and pesticides, and the inhibition of AChE is a therapeutic strategy for the treatment of various neurological-related diseases. The Glu202 is a key residue adjacent to the catalytic His447 and plays important role in catalysis. Although the Glu202 has long been considered as negatively charged in many studies, more and more evidences support a protonated Glu202. However, Glu202 is freely accessible by solvent, and thus it seems more reasonable for Glu202 to majorly take the deprotonated state. In the present work, we carried out a series of molecular dynamics simulations with the Glu202 adopting different protonation states. Our results show that the protonated Glu202 is important in maintaining the key hydrogen bond network that supports the catalytic triad, whereas the deprotonated Glu202 results in the collapse of the key hydrogen bond network which consequently destabilizes the catalytic His447. We also notice that different protonation states of Glu202 merely alters the binding mode of ACh. However, since the catalytic His447 is disrupted if Glu202 is deprotonated, His447 can not facilitate the nucleophilic attack performed by Ser203. Therefore, the catalytic efficiency of ACh hydrolysis should be remarkably decreased if Glu202 is deprotonated. Our findings suggest that, when designing and developing highly active AChE inhibitors or proposing mechanistic hypotheses for AChE-catalyzed reactions, the protonated state of Glu202 should be considered. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Proteins__
PubMedSearch : Wang_2021_Proteins__
PubMedID: 34546589

Title : Structure-Guided Rational Design of a Mono- and Diacylglycerol Lipase from Aspergillus oryzae: A Single Residue Mutant Increases the Hydrolysis Ability - Lan_2021_J.Agric.Food.Chem_69_5344
Author(s) : Lan D , Zhao G , Holzmann N , Yuan S , Wang J , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 69 :5344 , 2021
Abstract : Engineering of enzymes on the basis of protein structures are rational and efficient approaches to acquire biocatalysts of desired performances. In this study, we focused on a special mono- and diacylglycerol lipase (MDGL) isolated from the lipolytic enzyme-enriched fungus Aspergillus oryzae and discovered improved variants based on its crystal structure. We first solved the crystal structure of Aspergillus oryzae lipase (AOL) at 1.7 A resolution. Structure analysis and sequence alignment of AOL and other MDGLs revealed that the residue V269 is of vital importance for catalysis. Replacement of the V269 in AOL with the corresponding residues in other MDGLs has led to noticeable changes in hydrolysis without sacrificing the thermostability and substrate specificity. Among the investigated variants, V269D exhibited about a six-fold higher hydrolysis activity compared to the wild type. Molecular dynamics simulations and protein-ligand interaction frequency analyses revealed that the Asp substitution enhanced the substrate affinity of AOL. Our work sheds light on understanding the catalytic process of AOL and helps tailoring MDGLs with desired catalytic performance to fulfill the demand for biotechnological applications.
ESTHER : Lan_2021_J.Agric.Food.Chem_69_5344
PubMedSearch : Lan_2021_J.Agric.Food.Chem_69_5344
PubMedID: 33929832
Gene_locus related to this paper: aspor-MDLB

Title : Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial - Xiong_2021_Nutrition_86_111155
Author(s) : Xiong K , Wang J , Zhang B , Xu L , Hu Y , Ma A
Ref : Nutrition , 86 :111155 , 2021
Abstract : OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors.
ESTHER : Xiong_2021_Nutrition_86_111155
PubMedSearch : Xiong_2021_Nutrition_86_111155
PubMedID: 33601121

Title : An efficient and robust continuous-flow bioreactor for the enzymatic preparation of phytosterol esters based on hollow lipase microarray - Xu_2021_Food.Chem_372_131256
Author(s) : Xu L , Wang J , Huang F , Zheng M
Ref : Food Chem , 372 :131256 , 2021
Abstract : In this study, a continuous-flow bioreactor packed with well-organized lipase microarrays was developed for the sustainable synthesis of functional lipid-phytosterol esters (PEs). Hollow mesoporous silicon spheres with a suitable pore size were prepared for lipase immobilization, and the hydrophobic modification endowed the lipase with excellent catalytic activity and stability. The results showed that the condensely packed lipase microarrays offered large specific surface areas and guaranteed the thorough interaction between the lipase and substrates in the continuous-flow bioreactor. Meanwhile, the substrate could pass through the reactor at 1 mL/min with a high conversion of 93.6% due to the hollow structure of the packing spheres. Moreover, the reactors were able to produce 1564 g PEs/g catalyst in a continuous 30-day processing period, which set the highest records for PEs synthesis. This sustainable and highly-converting flow system provided a feasible path for scale-up production of PEs in the food processing area.
ESTHER : Xu_2021_Food.Chem_372_131256
PubMedSearch : Xu_2021_Food.Chem_372_131256
PubMedID: 34627092

Title : Accurate prediction of protein structures and interactions using a three-track neural network - Baek_2021_Science_373_871
Author(s) : Baek M , DiMaio F , Anishchenko I , Dauparas J , Ovchinnikov S , Lee GR , Wang J , Cong Q , Kinch LN , Schaeffer RD , Millan C , Park H , Adams C , Glassman CR , DeGiovanni A , Pereira JH , Rodrigues AV , van Dijk AA , Ebrecht AC , Opperman DJ , Sagmeister T , Buhlheller C , Pavkov-Keller T , Rathinaswamy MK , Dalwadi U , Yip CK , Burke JE , Garcia KC , Grishin NV , Adams PD , Read RJ , Baker D
Ref : Science , 373 :871 , 2021
Abstract : DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.
ESTHER : Baek_2021_Science_373_871
PubMedSearch : Baek_2021_Science_373_871
PubMedID: 34282049

Title : An Overview on the Mechanisms and Applications of Enzyme Inhibition-Based Methods for Determination of Organophosphate and Carbamate Pesticides - Cao_2020_J.Agric.Food.Chem_68_7298
Author(s) : Cao J , Wang M , Yu H , She Y , Cao Z , Ye J , Abd El-Aty AM , Hacimuftuoglu A , Wang J , Lao S
Ref : Journal of Agricultural and Food Chemistry , 68 :7298 , 2020
Abstract : Acetylcholinesterase inactivating compounds, such as organophosphate (OP) and carbamate (CM) pesticides, are widely used in agriculture to ensure sustainable production of food and feed. As a consequence of their applications, they would result in neurotoxicity, even death. In this essence, the development of enzyme inhibition methods still shows great significance as rapid detection techniques for on-site large-scale screening of OPs and CMs. Initially, mechanisms and applications of various enzyme-inhibition-based methods and devices, including optical colorimetric assay, fluorometric assays, electrochemical biosensors, rapid test card, and microfluidic device, are highlighted in the present overview. Further, to enhance the enzyme sensitivity for detection; alternative enzyme sources or high yield enrichment methods (such as abzyme, artificial enzyme, and recombinant enzyme), as well as enzyme reactivation and identification, are also addressed in this comprehensive overview.
ESTHER : Cao_2020_J.Agric.Food.Chem_68_7298
PubMedSearch : Cao_2020_J.Agric.Food.Chem_68_7298
PubMedID: 32551623

Title : ABHD5 suppresses cancer cell anabolism through lipolysis-dependent activation of the AMPK\/mTORC1 pathway - Chen_2020_J.Biol.Chem_296_100104
Author(s) : Chen G , Zhou G , Lotvola A , Granneman JG , Wang J
Ref : Journal of Biological Chemistry , 296 :100104 , 2020
Abstract : ABHD5 is an essential coactivator of ATGL, the rate-limiting triglyceride (TG) lipase in many cell types. Importantly, ABHD5 also functions as a tumor suppressor, and ABHD5 mRNA expression levels correlate with patient survival for several cancers. Nevertheless, the mechanisms involved in ABHD5-dependent tumor suppression are not known. We found that overexpression of ABHD5 induces cell-cycle arrest at the G1 phase and causes growth retardation in a panel of prostate cancer cells. Transcriptomic profiling and biochemical analysis revealed that genetic or pharmacological activation of lipolysis by ABHD5 potently inhibits mTORC1 signaling, leading to a significant downregulation of protein synthesis. Mechanistically, we found that ABHD5 elevates intracellular AMP content, which activates AMPK, leading to inhibition of mTORC1. Interestingly, ABHD5-dependent suppression of mTORC1 was abrogated by pharmacological inhibition of DGAT1 or DGAT2, isoenzymes that re-esterify fatty acids in a process that consumes ATP. Collectively, this study maps out a novel molecular pathway crucial for limiting cancer cell proliferation, in which ABHD5-mediated lipolysis creates an energy-consuming futile cycle between TG hydrolysis and resynthesis, leading to inhibition of mTORC1 and cancer cell growth arrest.
ESTHER : Chen_2020_J.Biol.Chem_296_100104
PubMedSearch : Chen_2020_J.Biol.Chem_296_100104
PubMedID: 33219129
Gene_locus related to this paper: human-ABHD5

Title : Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets - Gong_2020_J.Biomed.Nanotechnol_16_827
Author(s) : Gong Y , Lv S , Tian C , Gao Y , Chen B , Wen L , Gao H , Aimaiti W , Ma R , Zhao J , Wang J
Ref : J Biomed Nanotechnol , 16 :827 , 2020
Abstract : Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 mol . L (-1). Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.
ESTHER : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedSearch : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedID: 33187579

Title : Structurally various sorbicillinoids from the deep-sea sediment derived fungus Penicillium sp. SCSIO06871 - Pang_2020_Bioorg.Chem_107_104600
Author(s) : Pang X , Zhou X , Lin X , Yang B , Tian X , Wang J , Xu S , Liu Y
Ref : Bioorg Chem , 107 :104600 , 2020
Abstract : Two new hybrid sorbicillinoids (1 and 5), three new bisorbicillinoids (2-4), and three monomeric sorbicillinoids (6-8), along with eighteen known sorbicillinoids (9-26) were isolated from cultures of the deep-sea sediment derived fungus Penicillium sp. SCSIO06871. Their structures and absolute configurations were elucidated based upon the extensive spectroscopic analysis, X-ray crystallography analysis and the comparison of the experimental and calculated ECD data. Bisorbicillpyrone A (4) is the first example of bisorbicillinoid containing an alpha-pyrone derivative unit. All of the isolated compounds were evaluated for their antibacterial, antifungal and enzyme inhibitory activities against alpha-glycosidase and acetylcholinesterase (AChE) in vitro. Compound 6 displayed more potent inhibitory activity against alpha-glycosidase than acarbose with IC(50) value of 36.0 microM and compounds 4, 12, 18, 22, 23 exhibited moderate inhibitory activity with IC(50) values ranging from 115.8 to 208.5 microM. Compounds 10 and 22 showed weak enzyme inhibitory activities against AChE with 55.1% and 51.1% inhibitions at concentration of 50 microg/mL, respectively. Besides, compounds 11 and 12 exhibited significant antibacterial activities against Staphylococcus aureus with MIC values of 10.0 and 5.0 microg/mL, respectively. The hypothetical biosynthetic pathway of the isolated sorbicillinoids with three different structural types was discussed.
ESTHER : Pang_2020_Bioorg.Chem_107_104600
PubMedSearch : Pang_2020_Bioorg.Chem_107_104600
PubMedID: 33453645

Title : Effect of Massa Medicata Fermentata on the Gut Microbiota of Dyspepsia Mice Based on 16S rRNA Technique - Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528
Author(s) : Zhang X , Zhang H , Huang Q , Sun J , Yao R , Wang J
Ref : Evid Based Complement Alternat Med , 2020 :7643528 , 2020
Abstract : Massa Medicata Fermentata (MMF) is a traditional Chinese medicine (TCM) for treating indigestion and its related disorders. This study analyzes the effect of MMF on intestinal microorganisms in dyspepsia mice based on 16S rRNA technology. We take a dyspepsia model caused by a high-protein, high-calorie, high-fat diet. The 60 specific-pathogen free Kunming (SPF KM) mice were randomly divided into a model group (n=12), an MMF group (LSQ group, n=12), a Jianweixiaoshi group (JWXS group, n=12), a domperidone group (DP group, n=12), and a blank group (n=12). On the seventh day of administration, mice were fasted and deprived of water. After 24 h, take the second feces of stress defecation in mice under strict aseptic conditions and quickly transfer them to a sterile cryotube. This study comprehensively evaluates the alpha-diversity, beta-diversity, flora abundance and composition of each group of mice's intestinal microorganisms, and their correlation with functional dyspepsia based on the 16S rRNA gene sequencing technology. After modeling, some dyspepsia reactions, proximal gastric relaxation reduction, and intestinal microflora changes were noted. Dyspepsia mice showed dyspepsia reactions and proximal gastric relaxation reduction, characterized by a significant decrease of contents of gastrin (P < 0.01) and cholinesterase (P < 0.01). MMF can improve dyspepsia symptoms and promote proximal gastric relaxation. Significant intestinal flora disorders were found in dyspepsia mice, including downregulation of Bacteroidetes, Lactobacillus, and Prevotellaceae and upregulation of Proteobacteria, Verrucomicrobia, Epsilonbacteraeota, Firmicutes, Lachnospiraceae NK4A136 group, and Lachnospiraceae. MMF could alleviate intestinal microflora disturbance, and the regulation effect of MMF on Bacteroidetes, Verrucomicrobia, and Epsilonbacteraeota was more reliable than that of Jianweixiaoshi tables and domperidone. The intestinal microflora may be correlated with the promoted digestion of MMF.
ESTHER : Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528
PubMedSearch : Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528
PubMedID: 33029172

Title : Dipeptidyl Peptidase-4 Is a Target Protein of Epigallocatechin-3-Gallate - Hou_2020_Biomed.Res.Int_2020_5370759
Author(s) : Hou H , Wang Y , Li C , Wang J , Cao Y
Ref : Biomed Res Int , 2020 :5370759 , 2020
Abstract : Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 muM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.
ESTHER : Hou_2020_Biomed.Res.Int_2020_5370759
PubMedSearch : Hou_2020_Biomed.Res.Int_2020_5370759
PubMedID: 32104696

Title : Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007 - Han_2020_Bioorg.Chem_96_103646
Author(s) : Han W , Cai J , Zhong W , Xu G , Wang F , Tian X , Zhou X , Liu Q , Liu Y , Wang J
Ref : Bioorg Chem , 96 :103646 , 2020
Abstract : Three new compounds, including two new 3,4,6-trisubstituted alpha-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), alpha-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 mug/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.
ESTHER : Han_2020_Bioorg.Chem_96_103646
PubMedSearch : Han_2020_Bioorg.Chem_96_103646
PubMedID: 32036160

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 : Protective effect of Soluble Epoxide Hydrolase Inhibition in Retinal Vasculopathy associated with Polycystic Kidney Disease - Lin_2020_Theranostics_10_7857
Author(s) : Lin J , Hu J , Schlotterer A , Wang J , Kolibabka M , Awwad K , Dietrich N , Breitschopf K , Wohlfart P , Kannt A , Lorenz K , Feng Y , Popp R , Hoffmann S , Fleming I , Hammes HP
Ref : Theranostics , 10 :7857 , 2020
Abstract : Rationale: Vasoregression secondary to glial activation develops in various retinal diseases, including retinal degeneration and diabetic retinopathy. Photoreceptor degeneration and subsequent retinal vasoregression, characterized by pericyte loss and acellular capillary formation in the absence diabetes, are also seen in transgenic rats expressing the polycystic kidney disease (PKD) gene. Activated Muller glia contributes to retinal vasodegeneration, at least in part via the expression of the soluble epoxide hydrolase (sEH). Given that an increase in sEH expression triggered vascular destabilization in diabetes, and that vasoregression is similar in diabetic mice and PKD rats, the aim of the present study was to determine whether sEH inhibition could prevent retinal vasoregression in the PKD rat. Methods: One-month old male homozygous transgenic PKD rats were randomly allocated to receive vehicle or a sEH inhibitor (sEH-I; Sar5399, 30 mg/kg) for four weeks. Wild-type Sprague-Dawley (SD) littermates received vehicle as controls. Retinal sEH expression and activity were measured by Western blotting and LC-MS, and vasoregression was quantified in retinal digestion preparations. Microglial activation and immune response cytokines were assessed by immunofluorescence and quantitative PCR, respectively. 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) mediated Notch signaling, microglial activation and migration were assessed in vivo and in vitro. Results: This study demonstrates that sEH expression and activity were increased in PKD retinae, which led to elevated production of 19,20-DHDP and the depression of Notch signaling. The latter changes elicited pericyte loss and the recruitment of CD11b(+)/CD74(+) microglia to the perivascular region. Microglial activation increased the expression of immune-response cytokines, and reduced levels of Notch3 and delta-like ligand 4 (Dll4). Treatment with Sar5399 decreased 19,20-DHDP generation and increased Notch3 expression. Sar5399 also prevented vasoregression by reducing pericyte loss and suppressed microglial activation as well as the expression of immune-response cytokines. Mechanistically, the activation of Notch signaling by Dll4 maintained a quiescent microglial cell phenotype, i.e. reduced both the surface presentation of CD74 and microglial migration. In contrast, in retinal explants, 19,20-DHDP and Notch inhibition both promoted CD74 expression and reversed the Dll4-induced decrease in migration. Conclusions: Our data indicate that 19,20-DHDP-induced alterations in Notch-signaling result in microglia activation and pericyte loss and contribute to retinal vasoregression in polycystic kidney disease. Moreover, sEH inhibition can ameliorate vasoregression through reduced activity of inflammatory microglia. sEH inhibition is thus an attractive new therapeutic approach to prevent retinal vasoregression.
ESTHER : Lin_2020_Theranostics_10_7857
PubMedSearch : Lin_2020_Theranostics_10_7857
PubMedID: 32685025

Title : Design, Synthesis, and Evaluation of a Series of Novel Super Long-Acting DPP-4 Inhibitors for the Treatment of Type 2 Diabetes - Zhang_2020_J.Med.Chem_63_7108
Author(s) : Zhang C , Ye F , Wang J , He P , Lei M , Huang L , Huang A , Tang P , Lin H , Liao Y , Liang Y , Ni J , Yan P
Ref : Journal of Medicinal Chemistry , 63 :7108 , 2020
Abstract : In the present work, a novel series of trifluoromethyl-substituted tetrahydropyran derivatives were rationally designed and synthesized as potent DPP-4 inhibitors with significantly improved duration time of action over current commercially available DPP-4 inhibitors. The incorporation of the trifluoromethyl group on the 6-position of the tetrahydropyran ring of omarigliptin with the configuration of (2R,3S,5R,6S) not only significantly improves the overall pharmacokinetic profiles in mice but also maintains comparable DPP-4 inhibition activities. Further preclinical development of compound 2 exhibited its extraordinary efficacy in vivo and good safety profile. Clinical studies of compound 2 (Haisco HSK7653) are now ongoing in China, which revealed that inhibitor 2 could serve as an efficient candidate with a once-biweekly therapeutic regimen.
ESTHER : Zhang_2020_J.Med.Chem_63_7108
PubMedSearch : Zhang_2020_J.Med.Chem_63_7108
PubMedID: 32452679

Title : Immobilized angiotensin II type I receptor: A powerful method of high throughput screening for antihypertensive compound identification through binding interaction analysis - Liang_2020_J.Chromatogr.A__461003
Author(s) : Liang Q , Fu X , Zhang J , Hao J , Feng G , Wang J , Li Q , Ahmad F , Zhao X
Ref : Journal of Chromatography A , :461003 , 2020
Abstract : The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0mum microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 +/- 0.003, 0.05142 +/- 0.003, 0.07547 +/- 0.004 and 0.01310 +/- 0.005 min(-1) by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12x10(4) and 1.5x10(4)/M) and slower kinetics (kd: 0.6864 +/- 0.03 and 0.3005 +/- 0.01 min(-1)) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds.
ESTHER : Liang_2020_J.Chromatogr.A__461003
PubMedSearch : Liang_2020_J.Chromatogr.A__461003
PubMedID: 32156458

Title : Molecular characterization and functional analysis of a novel candidate of cuticle carboxylesterase in Spodoptera exigua degradating sex pheromones and plant volatile esters - He_2020_Pestic.Biochem.Physiol_163_227
Author(s) : He P , Mang DZ , Wang H , Wang MM , Ma YF , Wang J , Chen GL , Zhang F , He M
Ref : Pestic Biochem Physiol , 163 :227 , 2020
Abstract : Odorant-degrading enzymes (ODEs) are considered to play key roles in odorant inactivation to maintain the odorant receptor sensitivity of insects. Some members of carboxylesterase (CXE) is a major sub-family of ODEs. However, only a few CXEs have been functionally characterized so far. In the present study, we cloned the antennal esterase SexiCXE11 cDNA full-length sequences from the male antennae of a notorious crop pest, Spodoptera exigua, and its encoded 538 amino acids. It was similar to other insect esterases and had the characteristics of a carboxylesterase. We expressed recombinant enzyme in High-Five insect cells and obtained the high level purified recombinant protein by affinity column. Furthermore we test enzyme activity toward its two acetate sex pheromone components (Z9,E12-Tetradecadienyl acetate, Z9E12-14:Ac and Z9-Tetradecenyl acetate, Z9-14:Ac) and other 18 ester plant volatiles. Our results demonstrated that SexiCXE11 degraded acetate sex pheromone components with similar degradation activities (about 15.75% with Z9E12-14:Ac and 19.28% with Z9-14:Ac) and plant volatiles with a relatively high activity such as pentyl acetate and (Z)-3-hexenyl caproate. SexiCXE11 had high hydrolytic activity with these two ester odorants (>50% degradation), which is characterized that although a ubiquitous expression esterase SexiCXE11 may be partly involved with olfaction. This study may facilitate a better understanding of moth ODE differentiation and suggest strategies for the development of new pest behavior inhibitors.
ESTHER : He_2020_Pestic.Biochem.Physiol_163_227
PubMedSearch : He_2020_Pestic.Biochem.Physiol_163_227
PubMedID: 31973861

Title : Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease - Shen_2020_Front.Pharmacol_11_595254
Author(s) : Shen Y , Zhang B , Pang X , Yang R , Chen M , Zhao J , Wang J , Wang Z , Yu Z , Wang Y , Li L , Liu A , Du G
Ref : Front Pharmacol , 11 :595254 , 2020
Abstract : Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.
ESTHER : Shen_2020_Front.Pharmacol_11_595254
PubMedSearch : Shen_2020_Front.Pharmacol_11_595254
PubMedID: 33390981

Title : Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification - Xing_2020_Aquat.Toxicol_231_105736
Author(s) : Xing Q , Liao H , Peng C , Zheng G , Yang Z , Wang J , Lu W , Huang X , Bao Z
Ref : Aquat Toxicol , 231 :105736 , 2020
Abstract : Cholinesterases are key enzymes in central and peripheral cholinergic nerve system functioning on nerve impulse transmission in animals. Though cholinesterases have been identified in most vertebrates, the knowledge about the variable numbers and multiple functions of the genes is still quite meagre in invertebrates, especially in scallops. In this study, the complete cholinesterase (ChE) family members have been systematically characterized in Yesso scallop (Patinopecten yessoensis) via whole-genome scanning through in silico analysis. Ten ChE family members in the genome of Yesso scallop (designated PyChEs) were identified and potentially acted to be the largest number of ChE in the reported species to date. Phylogenetic and protein structural analyses were performed to determine the identities and evolutionary relationships of these genes. The expression profiles of PyChEs were determined in all developmental stages, in healthy adult tissues, and in mantles under low pH stress (pH 6.5 and 7.5). Spatiotemporal expression suggested the ubiquitous functional roles of PyChEs in all stages of development, as well as general and tissue-specific functions in scallop tissues. Regulation expressions revealed diverse up- and down-regulated expression patterns at most time points, suggesting different functional specialization of gene superfamily members in response to ocean acidification (OA). Evidences in gene number, phylogenetic relationships and expression patterns of PyChEs revealed that functional innovations and differentiations after gene duplication may result in altered functional constraints among PyChEs gene clusters. Collectively, our results provide the potential clues that the selection pressures coming from the environment were the potential inducement leading to function allocation of ChE family members in scallop.
ESTHER : Xing_2020_Aquat.Toxicol_231_105736
PubMedSearch : Xing_2020_Aquat.Toxicol_231_105736
PubMedID: 33422860
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210ptr6 , mizye-a0a210ptv1 , mizye-a0a210ptq0 , mizye-P021348901.2

Title : Silencing of soluble epoxide hydrolase 2 gene reduces H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells via activating PI3K\/Akt\/GSK3beta signaling pathway - Li_2020_Cytotech__
Author(s) : Li J , Luo J , Zhang Y , Tang C , Wang J , Chen C
Ref : Cytotechnology , : , 2020
Abstract : Oxidative stress plays a vital role in the occurrence and development of intestinal injury. Soluble epoxide hydrolase 2 gene (EPHX2) is a class of hydrolytic enzymes. We aim to explore the effects and molecular mechanism of siEPHX2 on H2O2-induced oxidative damage in rat intestinal epithelial IEC-6 cells. IEC-6 cells were transfected with EPHX2-siRNA and control si RNA plasmids by lipofectamine 2000 transfection reagent. The transfected samples were treated with H2O2 (50, 100, 200, 300, 400, and 500 micromol/L) for 12, 24, and 48 h, respectively. Cell viability was determined by cell counting kit-8 (CCK-8). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) were assessed by respective detection kits. Mitochondrial membrane potential (MMP), cell apoptosis and reactive oxygen species (ROS) and the levels of factors were determined by flow cytometer, quantitative real-time PCR (qRT-PCR) and western blot assays, respectively. We found that the IC50 of H2O2 was 200 micromol/L at 24 h, and the transfection of siEHPX2 in H2O2-induced IEC-6 cells significantly promoted the cell viability, SOD activity and MMP rate, and reduced the rates of ROS and apoptosis as well as LDH and MDA contents. siEHPX2 up-regulated the B-cell lymphoma-2 (Bcl-2) level and down-regulated the levels of fibroblast-associated (Fas), Fas ligand (Fasl), Bcl-2 associated X protein (Bax), and Caspase-3. Moreover, the phosphorylation levels of phosphoinositide 3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase3beta (GSK3beta) were up-regulated. We proved that siEPHX2 had a protective effect on H2O2-induced oxidative damage in IEC-6 cells through activating PI3K/Akt/GSK3beta signaling pathway.
ESTHER : Li_2020_Cytotech__
PubMedSearch : Li_2020_Cytotech__
PubMedID: 31907700

Title : Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease - Syal_2020_Theranostics_10_6337
Author(s) : Syal C , Kosaraju J , Hamilton L , Aumont A , Chu A , Sarma SN , Thomas J , Seegobin M , Dilworth FJ , He L , Wondisford FE , Zimmermann R , Parent M , Fernandes K , Wang J
Ref : Theranostics , 10 :6337 , 2020
Abstract : Rationale: Monoacylglycerol lipase (Mgll), a hydrolase that breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG) to produce arachidonic acid (ARA), is a potential target for neurodegenerative diseases, such as Alzheimer's disease (AD). Increasing evidence shows that impairment of adult neurogenesis by perturbed lipid metabolism predisposes patients to AD. However, it remains unknown what causes aberrant expression of Mgll in AD and how Mgll-regulated lipid metabolism impacts adult neurogenesis, thus predisposing to AD during aging. Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce beta-amyloid accumulation. Methods: Mgll expression was assessed in both human AD patient post-mortem hippocampal tissues and 3xTg-AD mouse model. In addition, we used both the 3xTg-AD animal model and the CbpS436A genetic knock-in mouse model to identify that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway, involving atypical protein kinase C (aPKC)-stimulated Ser436 phosphorylation of histone acetyltransferase CBP through biochemical methods. Furthermore, we performed in vivo adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway. Finally, we performed in vitro adult neurosphere assays using both animal models to study the role of the aPKC-CBP mediated Mgll repression in determining adult neural stem/progenitor cell (NPC) fate. Results: Here, we demonstrate that aging-dependent induction of Mgll is observed in the 3xTg-AD model and human AD patient post-mortem hippocampal tissues. Importantly, we discover that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway. The accumulation of Mgll in the 3xTg-AD mice reduces the genesis of newborn neurons and perturbs spatial memory. However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD. In addition, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and CbpS436A animal models are responsible for their NPC neuronal differentiation deficits. Conclusion: Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory.
ESTHER : Syal_2020_Theranostics_10_6337
PubMedSearch : Syal_2020_Theranostics_10_6337
PubMedID: 32483456

Title : miR-4454 up-regulated by HPV16 E6\/E7 promotes invasion and migration by targeting ABHD2\/NUDT21 in cervical cancer - Wang_2020_Biosci.Rep_40_
Author(s) : Wang H , Hu H , Luo Z , Liu S , Wu W , Zhu M , Wang J , Liu Y , Lu Z
Ref : Bioscience Reports , 40 : , 2020
Abstract : The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.
ESTHER : Wang_2020_Biosci.Rep_40_
PubMedSearch : Wang_2020_Biosci.Rep_40_
PubMedID: 32816024

Title : Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma - Zhang_2020_Front.Oncol_10_559568
Author(s) : Zhang H , Guo W , Zhang F , Li R , Zhou Y , Shao F , Feng X , Tan F , Wang J , Gao S , Gao Y , He J
Ref : Front Oncol , 10 :559568 , 2020
Abstract : Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in LUAD cells. Moreover, we found that knockdown of MGLL suppresses the expression of matrix metalloproteinase 14 (MMP14) in A549 and H322 cells, and in clinical samples, expression of MMP14 is significantly correlated with MGLL expression. Taken together, our results indicate that MGLL plays an oncogenic role in LUAD progression and metastasis and may serve as a potential biomarker for disease prognosis and as a target for the development of personalized therapies.
ESTHER : Zhang_2020_Front.Oncol_10_559568
PubMedSearch : Zhang_2020_Front.Oncol_10_559568
PubMedID: 33363004

Title : Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities - Zhao_2020_J.Ethnopharmacol__113711
Author(s) : Zhao J , Li K , Wang Y , Li D , Wang Q , Xie S , Wang J , Zuo Z
Ref : J Ethnopharmacol , :113711 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.
ESTHER : Zhao_2020_J.Ethnopharmacol__113711
PubMedSearch : Zhao_2020_J.Ethnopharmacol__113711
PubMedID: 33352242

Title : FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling - Chen_2020_Biol.Open_9_bio048462
Author(s) : Chen Y , Liu P , Shen D , Liu H , Xu L , Wang J , Sun H , Wu H
Ref : Biol Open , 9 : , 2020
Abstract : FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and beta-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling.
ESTHER : Chen_2020_Biol.Open_9_bio048462
PubMedSearch : Chen_2020_Biol.Open_9_bio048462
PubMedID: 31988090
Gene_locus related to this paper: human-f172a

Title : Discovery of Aryl Formyl Piperidine Derivatives as Potent, Reversible, and Selective Monoacylglycerol Lipase Inhibitors - Zhi_2020_J.Med.Chem__
Author(s) : Zhi Z , Zhang W , Yao J , Shang Y , Hao Q , Liu Z , Ren Y , Li J , Zhang G , Wang J
Ref : Journal of Medicinal Chemistry , : , 2020
Abstract : Most of the current MAGL inhibitors function by an irreversible mechanism of action, causing a series of side effects. Herein, starting from irreversible inhibitors, 25 compounds were synthesized and evaluated in vitro for MAGL inhibition, among which, compound 36 showed the most potent inhibitory activity (IC50 = 15 nM).Crucially, docking studies demonstrated that the m-chlorine-substituted aniline fragment occupied a hydrophobic sub-pocket enclosed by side chains of Val191, Tyr194, Val270, and Lys273, which creatively identify a new key anchoring point for the development of new MAGL inhibitors. Furthermore, in vivo evaluation innovatively revealed that this reversible inhibitor 36 significantly displayed the depressive-like behaviors induced by reserpine. To the best of our knowledge, this is the first time that reversible inhibitors of MAGL were developed to support MAGL as a potential therapeutic target for depression.
ESTHER : Zhi_2020_J.Med.Chem__
PubMedSearch : Zhi_2020_J.Med.Chem__
PubMedID: 32429662

Title : MnO(2) switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides - Li_2020_Biosens.Bioelectron_169_112605
Author(s) : Li W , Rong Y , Wang J , Li T , Wang Z
Ref : Biosensors & Bioelectronics , 169 :112605 , 2020
Abstract : Cholinesterases (ChEs) are important indicators of neurological disease, hepatocellular carcinoma, and organophosphate poisoning. In this work, a MnO(2) switch-bridged DNA walker was developed for ultrasensitive sensing of ChEs activity. The fuel strands loaded MnO(2) switch was designed to bridge the hydrolysis activity of ChEs and the running of the DNA walker. Under the action of ChE, the substrate butyrylcholine is first catalytically hydrolyzed to thiocholine, which then mediates MnO(2) nanosheet reduction to Mn(2+), releasing the fuel strands into solution. The fuel strands as substitute targets then trigger the continuous operation of DNA walker with the aid of Mn(2+), generating detectable fluorescence responses. The detection of ChE activity is converted to DNA detection in this method. Benefited from the robust operation and amplification effect of DNA walker, a wide linear range between the BChE activity and fluorescence intensity of nearly six orders of magnitude (1000-0.005 U/mL) and a limit of detection as low as 0.0008 U/mL are achieved. This allows the direct determination of BChE activity in clinical serum samples without any pretreatments. Moreover, the proposed method has remarkable capabilities for inhibitor (organophosphorus pesticide) screening and quantification, and organophosphorus pesticide detection in real samples is also achieved. Therefore, the MnO(2) switch-bridged DNA walker represents a powerful tool for ultrasensitive sensing of ChEs and organophosphorus pesticides, and has great application potential in clinical diagnosis, therapeutics, and drug screening.
ESTHER : Li_2020_Biosens.Bioelectron_169_112605
PubMedSearch : Li_2020_Biosens.Bioelectron_169_112605
PubMedID: 32947079

Title : Evaluation of modes of action of pesticides to Daphnia magna based on QSAR, excess toxicity and critical body residues - Wang_2020_Ecotoxicol.Environ.Saf_203_111046
Author(s) : Wang J , Yang Y , Huang Y , Zhang X , Qin WC , Wen Y , Zhao YH
Ref : Ecotoxicology & Environmental Safety , 203 :111046 , 2020
Abstract : Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna.
ESTHER : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedSearch : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedID: 32888614

Title : Monitoring insecticide resistance and diagnostics of resistance mechanisms in Bemisia tabaci Mediterranean (Q biotype) in China - Wang_2020_Pestic.Biochem.Physiol_163_117
Author(s) : Wang R , Che W , Wang J , Luo C
Ref : Pestic Biochem Physiol , 163 :117 , 2020
Abstract : Bemisia tabaci is one of notorious agricultural insect pests in China, and the strategies of management largely depend on application of insecticides. In order to assess levels of resistance in field populations of B. tabaci to six insecticides including abamectin, cyantraniliprole, pymetrozine, imidacloprid, chlorpyrifos and bifenthrin, we monitored the susceptibility to all tested insecticides in five field populations across China and the results indicated that field populations of B. tabaci have developed various levels of resistance to each chemical agent. Furthermore, para-type voltage gated sodium channel mutations (L925I and T929V) and acetylcholinesterase ace1 mutation (F331W) were confirmed, and expression levels of CYP6CM1, CYP4C64, GSTd7 and ABCG3 were detected for investigating mechanisms of imidacloprid resistance in the five field-collected populations. The results showed that, in all tested populations, frequencies of F331W were 100%, and the frequencies of the L925I and T929V were in the range of 28.5 to 47.0% and 11.0 to 53.5%, respectively. Moreover, CYP6CM1 and CYP4C64 were significantly overexpressed in two tested populations, respectively, and GSTd7 was significantly overexpressed in one population. No overexpression of ABCG3 was observed in all the populations. Above results provided valuable insight into the current status of insecticide resistance and could be contributed to design strategies of management for B. tabaci.
ESTHER : Wang_2020_Pestic.Biochem.Physiol_163_117
PubMedSearch : Wang_2020_Pestic.Biochem.Physiol_163_117
PubMedID: 31973847

Title : Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease - Li_2020_Acta.Pharm.Sin.B_10_646
Author(s) : Li X , Lu J , Xu Y , Wang J , Qiu X , Fan L , Li B , Liu W , Mao F , Zhu J , Shen X , Li J
Ref : Acta Pharm Sin B , 10 :646 , 2020
Abstract : Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (Abeta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD.
ESTHER : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedSearch : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedID: 32322468

Title : Insight into the Functional Diversification of Lipases in the Endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae) by Genome-scale Annotation and Expression Analysis - Wang_2020_Insects_11_
Author(s) : Wang J , Song J , Fang Q , Yao H , Wang F , Song Q , Ye G
Ref : Insects , 11 : , 2020
Abstract : Lipases play essential roles in digestion, transport, and processing of dietary lipids in insects. For parasitoid wasps with a unique life cycle, lipase functions could be multitudinous in particular. Pteromalus puparum is a pupal endoparasitoid of butterflies. The female adult deposits eggs into its host, along with multifunctional venom, and the developing larvae consume host as its main nutrition source. Parasitoid lipases are known to participate in the food digestion process, but the mechanism remains unclear. P. puparum genome and transcriptome data were interrogated. Multiple alignments and phylogenetic trees were constructed. We annotated a total of 64 predicted lipase genes belonging to five lipase families and suggested that eight venom and four salivary lipases could determine host nutrition environment post-parasitization. Many putative venom lipases were found with incomplete catalytic triads, relatively long beta9 loops, and short lids. Data analysis reveals the loss of catalytic activities and weak triacylglycerol (TAG) hydrolytic activities of lipases in venom. Phylogenetic trees indicate various predicted functions of lipases in P. puparum. Our information enriches the database of parasitoid lipases and the knowledge of their functional diversification, providing novel insight into how parasitoid wasps manipulate host lipid storage by using venom lipases.
ESTHER : Wang_2020_Insects_11_
PubMedSearch : Wang_2020_Insects_11_
PubMedID: 32260574

Title : Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis - Tu_2020_Nat.Commun_11_971
Author(s) : Tu L , Su P , Zhang Z , Gao L , Wang J , Hu T , Zhou J , Zhang Y , Zhao Y , Liu Y , Song Y , Tong Y , Lu Y , Yang J , Xu C , Jia M , Peters RJ , Huang L , Gao W
Ref : Nat Commun , 11 :971 , 2020
Abstract : Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
ESTHER : Tu_2020_Nat.Commun_11_971
PubMedSearch : Tu_2020_Nat.Commun_11_971
PubMedID: 32080175
Gene_locus related to this paper: triwf-a0a7j7c8l4

Title : Urethane attenuates early neuropathology of diisopropylfluorophosphate-induced status epilepticus in rats - Rojas_2020_Neurobiol.Dis__104863
Author(s) : Rojas A , Wang J , Glover A , Dingledine R
Ref : Neurobiol Dis , :104863 , 2020
Abstract : Seizures can be evident within minutes of exposure to an organophosphorus (OP) agent and often progress to status epilepticus (SE) resulting in a high mortality if left untreated. Effective medical countermeasures are necessary to sustain patients suffering from OP poisoning and to mitigate the ensuing brain injury. Here, the hypothesis was tested that a single subanesthetic dose of urethane prevents neuropathology measured 24h following diisopropylfluorophosphate (DFP)-induced SE. Adult Sprague-Dawley rats were injected with DFP to induce SE. During SE rats displayed increased neuronal activity in the hippocampus and an upregulation of immediate early genes as well as pro-inflammatory mediators. In additional experiments rats were administered diazepam (10mg/kg, ip) or urethane (0.8g/kg, sc) 1h after DFP-induced SE and compared to rats that experienced uninterrupted SE. Cortical electroencephalography (EEG) and power analysis strengthen the conclusion that urethane effectively terminates SE and prevents the overnight return of seizure activity. Neurodegeneration in limbic brain regions and the seizure-induced upregulation of key inflammatory mediators present 24h after DFP-induced SE were strongly attenuated by administration of urethane. A trivial explanation for these beneficial effects, that urethane simply reactivates acetylcholinesterase, has been ruled out. These findings indicate that, by contrast to rats administered diazepam or rats that experience uninterrupted SE, the early neuropathology after SE is prevented by subanesthetic urethane, which terminates rather than interrupts, SE.
ESTHER : Rojas_2020_Neurobiol.Dis__104863
PubMedSearch : Rojas_2020_Neurobiol.Dis__104863
PubMedID: 32283202

Title : Sequencing of Transcriptome and Small RNA Revealed the Xenobiotic Metabolism-Related Genes and Potential Regulatory miRNA in Asian Tramp Snail - Yang_2020_Front.Genet_11_595166
Author(s) : Yang Q , Yang W , Shang F , Ding B , Niu J , Wang J
Ref : Front Genet , 11 :595166 , 2020
Abstract : The Asian tramp snail, Bradybaena similaris (Ferusssac), is an invasive land snail species and has been a rising agricultural pest in south of China. As a pest, it also plays a role in transmission of Angiostrongylus cantonensis. However, present studies on this species are rare and the molecular information is limited. For this purpose, we sequenced the transcriptome and small RNA of B. similaris collected from citrus orchards. In total, 89,747 unigenes with an N50 size of 1287 bp and an average length of 817 bp were generated from -8.9 Gb transcriptome and 31 Mb clean reads were generated from -36 Mb small RNA library. To demonstrate the usefulness of these two datasets, we analyzed a series of genes associated with xenobiotic metabolism and core RNAi machinery. Analysis of the transcripts resulted in annotation of 126 putative genes encoding cytochrome P450 monooxygenases (CYP, 45), carboxyl/cholinesterases (CCE, 13), glutathione-S-transferases (GST, 24), and ATP-binding cassette transporters (ABC, 44). Analysis of the small RNA detected 42 miRNAs. In addition, four genes involved in small RNA pathways (miRNA, piRNA, and siRNA) were identified, and a total of 430 genes that can be targeted by miRNAs were predicted. Moreover, we found that a few miRNAs could target certain genes involved in xenobiotic metabolism. Therefore, we believe that these two datasets and the characterization of the identified/predicted genes will facilitate the molecular study of this species as well as other land snails with agricultural importance.
ESTHER : Yang_2020_Front.Genet_11_595166
PubMedSearch : Yang_2020_Front.Genet_11_595166
PubMedID: 33519897

Title : Structural optimization of pyrazolo[1,5-a]pyrimidine derivatives as potent and highly selective DPP-4 inhibitors - Shen_2020_Eur.J.Med.Chem_208_112850
Author(s) : Shen J , Deng X , Sun R , Tavallaie MS , Wang J , Cai Q , Lam C , Lei S , Fu L , Jiang F
Ref : Eur Journal of Medicinal Chemistry , 208 :112850 , 2020
Abstract : Our previous discovery of pyrazolo [1,5-a]pyrimidin-7(4H)-one scaffold-based DPP-4 inhibitors yielded two potent compounds b2 (IC(50) = 79 nM) and d1 (IC(50) = 49 nM) but characterized by cytotoxicity. Herein, with scaffold hopping and fragment-based drug design strategies, highly potent and selective pyrazolo [1,5-a]pyrimidine DPP-4 inhibitors were found featured by reduced or diminished cytotoxicity. Specifically, c24 (IC(50) = 2 nM) exhibits a 25 to 40-fold increase of inhibitory activity respect to those of b2 and d1, respectively, 2-fold from Alogliptin (IC(50) = 4 nM), and remarkable selectivity over DPP-8 and DPP-9 (>2000 fold). Further docking studies confirmed that the pyrazolo [1,5-a]pyrimidine core interacts with the S1 pocket whereas its substituted aromatic ring interacts with the sub-S1 pocket. The interactive mode in this case resembles that of Alogliptin and Trelagliptin. Further in vivo IPGTT assays in diabetic mice demonstrated that c24 effectively reduces glucose excursion by 48% at the dose of 10 mg/kg, suggesting that c24 is worthy of further development as a potent anti-diabetes agent.
ESTHER : Shen_2020_Eur.J.Med.Chem_208_112850
PubMedSearch : Shen_2020_Eur.J.Med.Chem_208_112850
PubMedID: 32987315

Title : In Situ Assessment of Donghu Lake China Using Rare Minnow (Gobiocypris rarus) - Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
Author(s) : Xiong X , Qiu N , Su L , Hou M , Xu C , Xiong Y , Dong X , Song Z , Wang J
Ref : Archives of Environmental Contamination & Toxicology , 79 :246 , 2020
Abstract : In this work, rare minnow (Gobiocypris rarus) was applied as a sentinel organism and set in cages at control and test sampling sites in Donghu Lake for 4 weeks in March, June, September, and December 2016 to assess the biological toxicity of in situ water. Sampling for active biomonitoring and physicochemical variables was performed weekly. The control was obtained from the outdoor pool of the Institute of Hydrobiology, China. Superoxide dismutase, lipoperoxidation, metallothioneins, acetylcholinesterase activity, and Vtg mRNA expression were determined as biomarkers during the field exposure period. Survival and growth also were monitored to evaluate the overall physiological condition of the fish. The seasonal changes of organic pollutants and trace metals (As, Hg, Cr, Cu, Zn, Cd, Pb) in surface water were determined. The integrated biomarker response (IBR) index was applied to summarize biomarker responses and correlate stress levels with concentrations of organic pollutants and trace metals in the surface water. Results indicated that complex pollution by persistent organic pollutants and heavy metals was present in Donghu Lake and that the in situ exposed organisms were stressed. Moreover, the complex pollution of Donghu Lake in summer and autumn was more serious than that in spring and winter. Active biomonitoring combined with IBR analysis enabled good discrimination among different exposure seasons. The proposed protocol with caged rare minnow revealed marked biological effects caused by the investigated Lake and a useful approach that can easily be extended to monitor water pollution.
ESTHER : Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
PubMedSearch : Xiong_2020_Arch.Environ.Contam.Toxicol_79_246
PubMedID: 32607658

Title : Cadmium exposure alters expression of protective enzymes and protein processing genes in venom glands of the wolf spider Pardosa pseudoannulata - Lv_2020_Environ.Pollut_268_115847
Author(s) : Lv B , Yang HL , Peng YD , Wang J , Zeng Z , Li N , Tang YE , Wang Z , Song QS
Ref : Environ Pollut , 268 :115847 , 2020
Abstract : Cadmium (Cd) pollution is currently the most serious type of heavy metal pollution throughout the world. Previous studies have shown that Cd elevates the mortality of paddy field spiders, but the lethal mechanism remains to be explored profoundly. In the present study, we measured the activities of protective enzymes (acetylcholinesterase, glutathione peroxidase, phenol oxidase) and a heavy metal chelating protein (metallothionein) in the pond wolf spider Pardosa pseudoannulata after Cd exposure. The results indicated that Cd initially increased the enzyme activities and protein concentration of the spider after 10- and 20-day exposure before inhibiting them at 30-day exposure. Further analysis showed that the enzyme activities in the cephalothorax were inhibited to some extent. Since the cephalothorax region contains important venom glands, we performed transcriptome sequencing (RNA-seq) analysis of the venom glands collected from the spiders after long-term Cd exposure. RNA-seq yielded a total of 2826 differentially expressed genes (DEGs), and most of the DEGs were annotated into the process of protein synthesis, processing and degradation. Furthermore, a mass of genes involved in protein recognition and endoplasmic reticulum (ER) -associated protein degradation were down-regulated. The reduction of protease activities supports the view that protein synthesis and degradation in organelles and cytoplasm were dramatically inhibited. Collectively, our outcomes illustrate that Cd poses adverse effects on the expression of protective enzymes and protein, which potentially down-regulates the immune function in the venom glands of the spiders via the alteration of protein processing and degradation in the ER.
ESTHER : Lv_2020_Environ.Pollut_268_115847
PubMedSearch : Lv_2020_Environ.Pollut_268_115847
PubMedID: 33130443

Title : A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC) - Sun_2020_Molecules_25_
Author(s) : Sun Y , Wang J , Hao K
Ref : Molecules , 25 : , 2020
Abstract : Gemcitabine (dFdC) demonstrates significant effectiveness against solid tumors in vitro and in vivo; however, its clinical application is limited because it tends to easily undergo deamination metabolism. Therefore, we synthesized 4-N-carbobenzoxy-gemcitabine (Cbz-dFdC) as a lead prodrug and conducted a detailed pharmacokinetic, metabolic, and pharmacodynamic evaluation. After intragastric Cbz-dFdC administration, the Cmax of Cbz-dFdC and dFdC was 451.1 +/- 106.7 and 1656.3 +/- 431.5 ng/mL, respectively. The Tmax of Cbz-dFdC and dFdC was 2 and 4 h, respectively. After intragastric administration of Cbz-dFdC, this compound was mainly distributed in the intestine due to low carboxylesterase-1 (CES1) activity. Cbz-dFdC is activated by CES1 in both humans and rats. The enzyme kinetic curves were well fitted by the Michaelis-Menten equation in rats' blood, plasma, and tissue homogenates and S9 of the liver and kidney, as well as human liver S9 and CES1 recombinase. The pharmacodynamic results showed that the Cbz-dFdC have a good antitumor effect in the HepG2 cell and in tumor-bearing mice, respectively. In general, Cbz-dFdC has good pharmaceutical characteristics and is therefore a good candidate for a potential prodrug.
ESTHER : Sun_2020_Molecules_25_
PubMedSearch : Sun_2020_Molecules_25_
PubMedID: 32397338

Title : Identification and Functional Study of Chitin Metabolism and Detoxification-Related Genes in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae) Based on Transcriptome Analysis - Shao_2020_Int.J.Mol.Sci_21_
Author(s) : Shao ZM , Li YJ , Zhang XR , Chu J , Ma JH , Liu ZX , Wang J , Sheng S , Wu FA
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a serious pest in the sericulture industry, which has caused damage and losses in recent years. With the widespread use of insecticides, the insecticide resistance of G. pyloalis has becomes increasingly apparent. In order to find other effective methods to control G. pyloalis, this study performed a transcriptome analysis of the midgut, integument, and whole larvae. Transcriptome data were annotated with KEGG and GO, and they have been shown to be of high quality by RT-qPCR. The different significant categories of differentially expressed genes between the midgut and the integument suggested that the transcriptome data could be used for next analysis. With the exception of Dda9 (GpCDA5), 19 genes were involved in chitin metabolism, most of which had close protein-protein interactions. Among them, the expression levels of 11 genes, including GpCHSA, GpCDA1, GpCDA2, GpCDA4, GPCHT1, GPCHT2a, GPCHT3a, GPCHT7, GpTre1, GpTre2, and GpRtv were higher in the integument than in the midgut, while the expression levels of the last eight genes, including GpCHSB, GpCDA5, GpCHT2b, GpCHT3b, GpCHT-h, GpPAGM, GpNAGK, and GpUAP, were higher in the midgut than in the integument. Moreover, 282 detoxification-related genes were identified and can be divided into 10 categories, including cytochrome P450, glutathione S-transferase, carboxylesterase, nicotinic acetylcholine receptor, aquaporin, chloride channel, methoprene-tolerant, serine protease inhibitor, sodium channel, and calcium channel. In order to further study the function of chitin metabolism-related genes, dsRNA injection knocked down the expression of GpCDA1 and GpCHT3a, resulting in the significant downregulation of its downstream genes. These results provide an overview of chitin metabolism and detoxification of G. pyloalis and lay the foundation for the effective control of this pest in the sericulture industry.
ESTHER : Shao_2020_Int.J.Mol.Sci_21_
PubMedSearch : Shao_2020_Int.J.Mol.Sci_21_
PubMedID: 32164390

Title : An enzyme inhibition-based lab-in-a-syringe device for point-of-need determination of pesticides - Yang_2020_Analyst__
Author(s) : Yang L , Wang J , Qu L , Liu Z , Jiang L
Ref : Analyst , : , 2020
Abstract : An enzyme inhibition-based lab-in-a-syringe (EI-LIS) device was developed by integrating a 1-naphthol-linked bi-enzymatic reaction (sensor core) into the LIS (sensor device) for point-of-need monitoring of pesticide residues. The integration relies on the rational design of two reaction pads. The conjugate pad is a polyester fiber membrane loaded with plant-esterase, an alternative to acetylcholinesterase. Besides pesticide capture, plant-esterase also mediates the hydrolysis of 1-naphthyl acetate, generating 1-naphthol. The detection pad is an agarose gel entrapping oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) from Fe(iii) meso-tetra(N-methyl-4-pyridyl) porphyrin (FeTMPyP4)-catalyzed TMB oxidation. Both pads were embedded into their cartridges and then connected to a syringe. Under syringe pumping, 1-naphthol vertically flowed from the conjugate to the detection cartridge, linking the two pads. If plant-esterase was intact, 1-naphthol would reduce oxTMB, causing a color change of the detection pad from blue to colorless. If the plant-esterase activity was inhibited by pesticides, less 1-naphthol was produced, and the blue color of the detection pad would be partially or wholly retained. The deeper the blue color, the greater the pesticide concentration. This chromogenic pattern is responsible for a highly sensitive readout (detection limits of dichlorvos: 0.1 nM with the naked eye and 0.07 nM with a spectrometer).
ESTHER : Yang_2020_Analyst__
PubMedSearch : Yang_2020_Analyst__
PubMedID: 32319482

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

Title : Silicon-mediated multiple interactions: Simultaneous induction of rice defense and inhibition of larval performance and insecticide tolerance of Chilo suppressalis by sodium silicate - Wang_2020_Ecol.Evol_10_4816
Author(s) : Wang J , Xue R , Ju X , Yan H , Gao Z , Esmail Abdalla Elzaki M , Hu L , Zeng R , Song Y
Ref : Ecol Evol , 10 :4816 , 2020
Abstract : The rice striped stem borer (SSB, Chilo suppressalis) is one of the most destructive pests of rice plants. Si-mediated rice defense against various pests has been widely reported, and sodium silicate (SS) has been used as an effective source of silicon for application to plants. However, there is quite limited information about the direct effects of Si application on herbivorous insects. SSB larval performance and their insecticide tolerance were examined after they had been reared either on rice plants cultivated in nutrient solution containing 0.5 and 2.0 mM SS or on artificial diets with 0.1% and 0.5% SS. SS amendment in either rice culture medium or artificial diets significantly suppressed the enzymatic activities of acetylcholinesterase, glutathione S-transferases, and levels of cytochrome P450 protein in the midgut of C. suppressalis larvae. Larvae fed on diets containing SS showed lower insecticide tolerance. Additionally, RNA-seq analysis showed that SS-mediated larval insecticide tolerance was closely associated with fatty acid biosynthesis and pyruvate metabolism pathways. Our results suggest that Si not only enhances plant resistance against insect herbivore, but also impairs the insect's capacity to detoxify the insecticides. This should be considered as another important aspect in Si-mediated plant-insect interaction and may provide a novel approach of pest management.
ESTHER : Wang_2020_Ecol.Evol_10_4816
PubMedSearch : Wang_2020_Ecol.Evol_10_4816
PubMedID: 32551063

Title : Lipopeptide Epimers and a Phthalide Glycerol Ether with AChE Inhibitory Activities from the Marine-Derived Fungus Cochliobolus Lunatus SCSIO41401 - Dai_2020_Mar.Drugs_18_
Author(s) : Dai Y , Li K , She J , Zeng Y , Wang H , Liao S , Lin X , Yang B , Wang J , Tao H , Dai H , Zhou X , Liu Y
Ref : Mar Drugs , 18 : , 2020
Abstract : A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4-6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo(2) (OAc)(4)-induced ECD methods. The new compounds 1-3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC(50) values of 1.3-2.5 M, and an in silico molecular docking study was also performed.
ESTHER : Dai_2020_Mar.Drugs_18_
PubMedSearch : Dai_2020_Mar.Drugs_18_
PubMedID: 33143384

Title : Self-assembly of lipase hybrid nanoflowers with bifunctional Ca(2+) for improved activity and stability - Zhang_2020_Enzyme.Microb.Technol_132_109408
Author(s) : Zhang Y , Sun W , Elfeky NM , Wang Y , Zhao D , Zhou H , Wang J , Bao Y
Ref : Enzyme Microb Technol , 132 :109408 , 2020
Abstract : Lipase ZC12, a cold-adapted lipase derived from Psychrobacter sp. ZY124, can be effectively activated by Ca(2+). Inspired by this significant property, we developed a novel immobilized lipase ZC12/Ca3(PO4)2 hybrid nanoflowers (LHNs). The LHNs have been characterized as a regular hierarchical flowerlike structure nanoflowers by scanning electron microscopy (SEM). Compared with free lipase ZC12, the LHNs exerted enhanced enzymatic activity of 206% and 2.31-fold in kcat/Km value, especially high specific activity at low temperature. After 7 successive cycles, the LHNs could still maintain its initial activity, demonstrating superior durability than the free lipase ZC12. Meanwhile, its stability basically kept unchanged in a wide range of temperature and pH. Finally, fructose laurate was transformed by the LHNs with 57.39% conversion rate which is twice as much as the free lipase. To sum up, these results validated that LHNs could emerge as an efficient immobilized lipase and possess the promising potential for practical applications.
ESTHER : Zhang_2020_Enzyme.Microb.Technol_132_109408
PubMedSearch : Zhang_2020_Enzyme.Microb.Technol_132_109408
PubMedID: 31731973
Gene_locus related to this paper: 9gamm-a0a1b1ijp3

Title : Experimental determination of the bioluminescence resonance energy transfer (BRET) Frster distances of NanoBRET and red-shifted BRET pairs - Weihs_2020_Anal.Chim.Acta.X_6_100059
Author(s) : Weihs F , Wang J , Pfleger KDG , Dacres H
Ref : Anal Chim Acta X , 6 :100059 , 2020
Abstract : Bioluminescence Resonance Energy Transfer (BRET) is widely applied to study protein-protein interactions, as well as increasingly to monitor both ligand binding and molecular rearrangements. The Forster distance (R(0)) describes the physical distance between the two chromophores at which 50% of the maximal energy transfer occurs and it depends on the choice of RET components. R(0) can be experimentally determined using flexible peptide linkers of known lengths to separate the two chromophores. Knowledge of the R(0) helps to inform on the choice of BRET system. For example, we have previously shown that BRET(2) exhibits the largest R(0) to date for any genetically encoded RET pair, which may be advantageous for investigating large macromolecular complexes if its issues of low and fast-decaying bioluminescence signal can be accommodated. In this study we have determined R(0) for a range of bright and red-shifted BRET pairs, including NanoBRET with tetramethylrhodamine (TMR), non-chloro TOM (NCT), mCherry or Venus as acceptor, and BRET(6), a red-shifted BRET(2)-like system. This study revealed R(0) values of 6.15 nm and 6.94 nm for NanoBRET using TMR or NCT as acceptor ligands, respectively. R(0) was 5.43 nm for NanoLuc-mCherry, 5.59 nm for NanoLuc-Venus and 5.47 nm for BRET(6). This extends the palette of available BRET Forster distances, to give researchers a better-informed choice when considering BRET systems and points towards NanoBRET with NCT as a good alternative to BRET(2) as an analysis tool for large macromolecular complexes.
ESTHER : Weihs_2020_Anal.Chim.Acta.X_6_100059
PubMedSearch : Weihs_2020_Anal.Chim.Acta.X_6_100059
PubMedID: 33392495

Title : Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion - Man_2020_Brain.Res_1736_146782
Author(s) : Man J , Cui K , Fu X , Zhang D , Lu Z , Gao Y , Yu L , Li N , Wang J
Ref : Brain Research , 1736 :146782 , 2020
Abstract : Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis.
ESTHER : Man_2020_Brain.Res_1736_146782
PubMedSearch : Man_2020_Brain.Res_1736_146782
PubMedID: 32184165

Title : Mori Ramulus (Chin.Ph.)-the Dried Twigs of Morus alba L.\/Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract - Yao_2019_Molecules_24_
Author(s) : Yao J , He H , Xue J , Wang J , Jin H , Wu J , Hu J , Wang R , Kuchta K
Ref : Molecules , 24 : , 2019
Abstract : In Traditional Chinese Medicine (TCM), Mori ramulus (Chin.Ph.)-the dried twigs of Morus alba L.-is extensively used as an antirheumatic agent and also finds additional use in asthma therapy. As a pathological high xanthine oxidase (XO, EC activity is strongly correlated to hyperuricemy and gout, standard anti-hyperuremic therapy typically involves XO inhibitors like allopurinol, which often cause adverse effects by inhibiting other enzymes involved in purine metabolism. Mori ramulus may therefore be a promissing source for the development of new antirheumatic therapeutics with less side effects. Coumarins, one of the dominant groups of bioactive constituents of M. alba, have been demonstrated to possess anti-inflammatory, antiplatelet aggregation, antitumor, and acetylcholinesterase (AChE) inhibitory activities. The combination of HPLC (DAD) and Q-TOF technique could give excellent separating and good structural characterization abilities which make it suitable to analyze complex multi-herbal extracts in TCM. The aim of this study was to develop a HPLC (DAD)/ESI-Q-TOF-MS/MS method for the identification and profiling of pharmacologically active coumarin glycosides in Mori ramulus refined extracts for used in TCM. This HPLC (DAD)/ESI-Q-TOF-MS/MS method provided a rapid and accurate method for identification of coumarin glycosides-including new natural products described here for the first time-in the crude extract of M. alba L. In the course of this project, two novel natural products moriramulosid A (umbelliferone-6-beta-d-apiofuranosyl-(1-->6)-beta-d-glucopyranoside) and moriramulosid B (6-[[6-O-(6-deoxy-alpha-l-mannopyranosyl)-beta-d-glucopyranosyl]oxy]-2H-1-benzopy ran-1-one) were newly discovered and the known natural product Scopolin was identified in M. alba L. for the first time.
ESTHER : Yao_2019_Molecules_24_
PubMedSearch : Yao_2019_Molecules_24_
PubMedID: 30754654

Title : High-level expression of Thermomyces dupontii thermo-alkaline lipase in Pichia pastoris under the control of different promoters - Wang_2019_3.Biotech_9_33
Author(s) : Wang J , Zhang T , Li Y , Li L , Wang Y , Yang B
Ref : 3 Biotech , 9 :33 , 2019
Abstract : In this study, 15 methanol-inducible and 9 constitutive promoters were used to drive the expression of Thermomyces dupontii lipase (TDL) in Pichia pastoris. Of the 15 methanol-inducible promoters, formaldehyde dehydrogenase promoter (PFLD1) showed the highest efficiency in driving lipase production, followed by alcohol oxidase 1 (PAOX1) and dihydroxyacetone synthase (PDAS1) promoters. The maximum lipase activity of transformants with PFLD1, PAOX1 and PDAS1 promoters in 5-l bioreactor was 27,076, 24,159 and 22,342 U/ml, respectively. For the nine constitutive promoters, glycosyl phosphatidyl inositol-anchored protein promoter (PGCW14) produced the highest amount of lipases in a medium containing glucose or glycerol as the only carbon source, followed by mitochondrial alcohol dehydrogenase isozyme (P0472) and glyceraldehyde-3-phosphate dehydrogenase (PGAP) promoters. The maximum lipase yields in 5-l bioreactors under the control of PGCW14, P0472 and PGAP promoters were 17,353, 15,046 and 14,276 U/ml, respectively. The result of this study not only identifies a few highly efficient promoters for the heterologous expression of TDL in P. pastoris, but also casts some insight into the optimization of protein production in heterologous systems.
ESTHER : Wang_2019_3.Biotech_9_33
PubMedSearch : Wang_2019_3.Biotech_9_33
PubMedID: 30622871
Gene_locus related to this paper: talth-f6lqk7

Title : HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra\/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents - Alali_2019_Chemistry_25_11892
Author(s) : Alali KT , Liu J , Chen R , Liu Q , Zhang H , Li J , Hou J , Li R , Wang J
Ref : Chemistry , 25 :11892 , 2019
Abstract : Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials.
ESTHER : Alali_2019_Chemistry_25_11892
PubMedSearch : Alali_2019_Chemistry_25_11892
PubMedID: 31309626

Title : Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer's Disease Based on Systems Biology - Guo_2019_Oxid.Med.Cell.Longev_2019_1707218
Author(s) : Guo S , Wang J , Wang Y , Zhang Y , Bi K , Zhang Z , Li Q
Ref : Oxid Med Cell Longev , 2019 :1707218 , 2019
Abstract : Kai-Xin-San (KXS), a classical Chinese traditional prescription, was widely applied in the treatment of Alzheimer's disease (AD), while its functional mechanisms still remain unclear. By using systems biology approaches at animal, cellular, and molecular levels, the improvement of KXS on cognitive impairment was achieved by inhibiting abnormal acetylcholinesterase. The function on the nerve skeleton was performed by regulating the Tau phosphorylation pathway. Its antioxidant, anti-inflammatory, and antiapoptotic effects by modulating the aberrant upregulation of ROS, proinflammatory factors, and apoptosis-related proteins in the brain were studied to reveal the synergistic therapeutic efficacy of KXS. Then, formula dismantling in vitro indicated that ginseng was the principal herb, whereas three other herbs served adjuvant roles to achieve the best effect. After that, the in vivo analysis of components into plasma and brain of AD rats showed that 8 of 23 components in blood and 4 of 10 components in brain were from ginseng, respectively, further verifying the principal status of ginseng and the synergistic effects of the formula. Thus, the anti-AD effects of KXS were achieved by multitargets and multichannels. The systems biology approaches presented here provide a novel way in traditional herbal medicine research.
ESTHER : Guo_2019_Oxid.Med.Cell.Longev_2019_1707218
PubMedSearch : Guo_2019_Oxid.Med.Cell.Longev_2019_1707218
PubMedID: 31976026

Title : Treatment Effects of Jinlingzi Powder and Its Extractive Components on Gastric Ulcer Induced by Acetic Acid in Rats - Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
Author(s) : Zhao X , Li J , Meng Y , Cao M , Wang J
Ref : Evid Based Complement Alternat Med , 2019 :7365841 , 2019
Abstract : Jinlingzi powder comprises Melia toosendan Sieb. et Zucc. and Corydalis yanhusuo (Y.H. Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu and is usually applied in clinic as traditional Chinese medicine for pain. The present study aims to investigate the therapeutic actions of Jinlingzi powder and its extracted components and theirs treatment mechanism on the acetic acid induced-gastric ulcer in rats. The gastric ulcer model was induced by the administration of acetic acid in rats (84 male). Jinlingzi powder water decoction, its polysaccharide, and nonalkaloid and alkaloid components were used to investigate the therapeutic actions on the acetic acid induced-gastric ulcer by measuring the related pharmacy and pharmacodynamic factors, including ulcer index, ulcer area, ulcer healing rate, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), neurotensin (NT), platelet activating factor (PAF), thromboxane B2 (TXB2), and vascular endothelial growth factor (VEGF) in rat serum, acetylcholinesterase (AChE) in brain tissue, prostaglandin E2 (PGE2), and basic fibroblast growth factor (bFGF) in gastric tissue. Among the various groups, Jinlingzi powder and the nonalkaloid components caused significant changes in IL-8, TNF-alpha, NT, PAF TXB2, and VEGF values in the serum. The AChE content in the rats' brain tissue was also reduced after using Jinlingzi powder and the nonalkaloid components. Additionally, Jinlingzi powder and the nonalkaloid components considerably affect the amount of PGE2 and bFGF in a rat's stomach tissue. Therefore, Jinlingzi powder and the nonalkaloid components can effectively inhibit neutral neutrophil activation, prevent capillaries thrombosis, and protect gastric mucosa. Thus, the nonalkaloid components of the Jinlingzi powder play a key role in the treatment of gastric ulcer.
ESTHER : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedSearch : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedID: 30719066

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

Title : Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats - Wang_2019_Front.Pharmacol_10_1003
Author(s) : Wang K , Chen Q , Wu N , Li Y , Zhang R , Wang J , Gong D , Zou X , Liu C , Chen J
Ref : Front Pharmacol , 10 :1003 , 2019
Abstract : Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.
ESTHER : Wang_2019_Front.Pharmacol_10_1003
PubMedSearch : Wang_2019_Front.Pharmacol_10_1003
PubMedID: 31551793

Title : A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition - Rojas_2019_Neurobiol.Dis__104399
Author(s) : Rojas A , Ganesh T , Wang W , Wang J , Dingledine R
Ref : Neurobiol Dis , :104399 , 2019
Abstract : This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.
ESTHER : Rojas_2019_Neurobiol.Dis__104399
PubMedSearch : Rojas_2019_Neurobiol.Dis__104399
PubMedID: 30818067

Title : Rapid colorimetric determination of the pesticides carbofuran and dichlorvos by exploiting their inhibitory effect on the aggregation of peroxidase-mimicking platinum nanoparticles - Cao_2019_Mikrochim.Acta_186_390
Author(s) : Cao J , Wang M , She Y , El-Aty AMA , Hacimuftuoglu A , Wang J , Yan M , Hong S , Lao S , Wang Y
Ref : Mikrochim Acta , 186 :390 , 2019
Abstract : A novel and highly sensitive enzyme inhibition assay was developed for the rapid detection of the organophosphate pesticide dichlorvos and the carbamate pesticide carbofuran. It achieves signal amplification by the secondary catalysis of platinum nanoparticles. Acetylcholinesterase (AChE) is capable of catalyzing the hydrolysis of acetylthiocholine to form thiocholine. Thiocholine causes the aggregation of citrate-capped platinum nanoparticles which then lose their peroxidase-mimicking properties. After addition of pesticides, the activity of AChE is inhibited, less thiocholine is produced, less aggregation occurs, and the peroxidase-mimetic properties are increasingly retained. In the presence of tetramethylbenzidine and H2O2, a deep blue coloration with an absorption maximum at 650 nm will be formed. The assay was applied to the determination of dichlorvos and carbofuran, and detection limits of 2.3 mug.L(-1) and 1.4 mug.L(-1) were obtained, respectively. Recovery experiments with spiked tap water and pears gave satisfactory relative standard deviations. Graphical abstract The blue product formed by platinum nanoparticle-catalyzed oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2 is reduced if acetylthiocholine (ATCh) is hydrolyzed by acetylcholinesterase (AChE) to form thiocholine. However, if AChE is inhibited by pesticides, color formation will recover.
ESTHER : Cao_2019_Mikrochim.Acta_186_390
PubMedSearch : Cao_2019_Mikrochim.Acta_186_390
PubMedID: 31152243

Title : Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure - Wang_2019_Basic.Res.Cardiol_114_41
Author(s) : Wang J , Dai M , Cao Q , Yu Q , Luo Q , Shu L , Zhang Y , Bao M
Ref : Basic Res Cardiol , 114 :41 , 2019
Abstract : Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.
ESTHER : Wang_2019_Basic.Res.Cardiol_114_41
PubMedSearch : Wang_2019_Basic.Res.Cardiol_114_41
PubMedID: 31502080

Title : Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process - Wang_2019_Virol.Sin_34_59
Author(s) : Wang J , Wu F , Liu C , Dai W , Teng Y , Su W , Kong W , Gao F , Cai L , Hou A , Jiang C
Ref : Virol Sin , 34 :59 , 2019
Abstract : Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated. In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.
ESTHER : Wang_2019_Virol.Sin_34_59
PubMedSearch : Wang_2019_Virol.Sin_34_59
PubMedID: 30725320

Title : Apolipoprotein A-I mimetics mitigate intestinal inflammation in COX2-dependent inflammatory bowel disease model - Meriwether_2019_J.Clin.Invest_129_3670
Author(s) : Meriwether D , Sulaiman D , Volpe C , Dorfman A , Grijalva V , Dorreh N , Solorzano-Vargas RS , Wang J , O'Connor E , Papesh J , Larauche M , Trost H , Palgunachari MN , Anantharamaiah GM , Herschman HR , Martin MG , Fogelman AM , Reddy ST
Ref : J Clinical Investigation , 129 :3670 , 2019
Abstract : Cyclooxygenase 2 (Cox2) total knockout and myeloid knockout (MKO) mice develop Crohn's-like intestinal inflammation when fed cholate-containing high fat diet (CCHF). We demonstrated that CCHF impaired intestinal barrier function and increased translocation of endotoxin, initiating TLR/MyD88-dependent inflammation in Cox2 KO but not WT mice. Cox2 MKO increased pro-inflammatory mediators in LPS-activated macrophages, and in the intestinal tissue and plasma upon CCHF challenge. Cox2 MKO also reduced inflammation resolving lipoxin A4 (LXA4) in intestinal tissue, while administration of an LXA4 analog rescued disease in Cox2 MKO mice fed CCHF. The apolipoprotein A-I (APOA1) mimetic 4F mitigated disease in both the Cox2 MKO/CCHF and piroxicam-accelerated Il10-/- models of inflammatory bowel disease (IBD) and reduced elevated levels of pro-inflammatory mediators in tissue and plasma. APOA1 mimetic Tg6F therapy was also effective in reducing intestinal inflammation in the Cox2 MKO/CCHF model. We further demonstrated that APOA1 mimetic peptides: i) inhibited LPS and oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphatidylcholine (oxPAPC) dependent pro-inflammatory responses in human macrophages and intestinal epithelium; and ii) directly cleared pro-inflammatory lipids from mouse intestinal tissue and plasma. Our results support a causal role for pro-inflammatory and inflammation resolving lipids in IBD pathology and a translational potential for APOA1 mimetic peptides for the treatment of IBD.
ESTHER : Meriwether_2019_J.Clin.Invest_129_3670
PubMedSearch : Meriwether_2019_J.Clin.Invest_129_3670
PubMedID: 31184596

Title : Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity - Lin_2019_Int.J.Nanomedicine_14_5817
Author(s) : Lin Y , Wang Y , Lv J , Wang N , Wang J , Li M
Ref : Int J Nanomedicine , 14 :5817 , 2019
Abstract : Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.
ESTHER : Lin_2019_Int.J.Nanomedicine_14_5817
PubMedSearch : Lin_2019_Int.J.Nanomedicine_14_5817
PubMedID: 31440049

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Biodegradation of mycotoxin fumonisin B1 by a novel bacterial consortium SAAS79 - Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
Author(s) : Zhao Z , Zhang Y , Gong A , Liu N , Chen S , Zhao X , Li X , Chen L , Zhou C , Wang J
Ref : Applied Microbiology & Biotechnology , 103 :7129 , 2019
Abstract : Fumonisin B1 (FB1) contamination in cereals and cereal products remains an important aspect of food safety because of its wide distribution and the potential health hazard. However, only a few microorganisms have been reported to effectively degrade FB1. In this present study, a bacterial consortium SAAS79 with highly FB1-degrading activity was isolated from the spent mushroom compost. The combination of antibiotic-driven selection and 16S rDNA sequencing identified the Pseudomonas genus as the key FB1-degrading member. The microbial consortium could degrade more than 90% of 10 microg/mL FB1 after incubation for 24 h at pH of 5-7 and temperature of 28-35 degreesC. The enzymes from the intracellular space were proved to be responsible for FB1 degradation, which eliminated about 90% of 10 microg/mL FB1 in 3 h. Besides, liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) analysis identified two degradation products of FB1, and their toxicity on the monkey kidney cells (MARC-145) was significantly lower (p < 0.05) compared with the parent FB1. Overall, the consortium SAAS79 and its crude enzymes may be a potential choice for the decontamination of FB1 in the feed and food industry. Also, the bacterial consortium provides a new source of genes for the development of enzymatic detoxification agent.
ESTHER : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedSearch : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedID: 31230101

Title : Lycopodium alkaloids from Huperzia serrata - Jiang_2019_Fitoterapia__104277
Author(s) : Jiang F , Qi B , Ding N , Yang H , Jia F , Luo Y , Wang J , Liu X , Wang X , Tu P , Shi S
Ref : Fitoterapia , :104277 , 2019
Abstract : Five new Lycopodium alkaloids, huperzine Y1 (1), huperzine Y2 (2), huperzine Y3 (3), (+)-huperzine Z (4a) and (-)-huperzine Z (4b) as well as ten known alkaloids (5-14) were isolated from Huperzia serrata. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 4a and 4b were a pair of enantiomers successfully separated by chiral HPLC resolution. Compounds 2 and 3 indicated inhibitory activities against acetylcholinesterase with IC50 value of 57.1+/-1.6 and 32.7+/-1.0 muMu, respectively. However, no compound showed inhibitory effect on butyrocholinesterase at the concentration of 100 muMu.
ESTHER : Jiang_2019_Fitoterapia__104277
PubMedSearch : Jiang_2019_Fitoterapia__104277
PubMedID: 31351127

Title : Design, synthesis and biological Evaluation of Dual acetyl cholinesterase and beta-secretase inhibitors in treatment for alzheimer's Disease - Deng_2019_Pak.J.Pharm.Sci_32_2091
Author(s) : Deng Y , Jiang Y , Zhao X , Wang J
Ref : Pak J Pharm Sci , 32 :2091 , 2019
Abstract : With the recent research advances in molecular biology and technology multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)aceta te (1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity.
ESTHER : Deng_2019_Pak.J.Pharm.Sci_32_2091