Chen J

References (292)

Title : Microarray and Functional Pathway Analyses Revealed Significantly Elevated Gene Expressions Associated with Metabolic Resistance to Oxamyl (Vydate) in Lygus lineolaris - Zhu_2024_Toxics_12_
Author(s) : Zhu YC , Du Y , Liu X , Portilla M , Chen J , Wang Y
Ref : Toxics , 12 : , 2024
Abstract : The tarnished plant bug (TPB, Lygus lineolaris) remains a major pest for a variety of crops. Frequent sprays on row crops, especially cotton, prompted resistance development in field populations. To maintain chemical control as an effective tool against the pest, knowledge of global gene regulations is desirable for better understanding and managing the resistance. Novel microarray expressions of 6688 genes showed 685 significantly upregulated and 1382 significantly downregulated genes in oxamyl-selected TPBs (Vyd1515FF[R]) from a cotton field. Among the 685 upregulated genes (participated in 470 pathways), 176 genes code 30 different enzymes, and 7 of the 30 participate in 24 metabolic pathways. Six important detoxification pathways were controlled by 20 genes, coding 11 esterases, two P450s, two oxidases, and three pathway-associated enzymes (synthases, reductase, and dehydrogenase). Functional analyses showed substantially enhanced biological processes and molecular functions, with hydrolase activity as the most upregulated molecular function (controlled by 166 genes). Eleven esterases belong to the acting on ester bond subclass of the 166 hydrolases. Surprisingly, only one GST showed significant upregulation, but it was not involved in any detoxification pathway. Therefore, this research reports a set of 20 genes coding 6 enzyme classes to detoxify a carbamate insecticide oxamyl in Vyd1515FF. Together with three previous reports, we have obtained the best knowledge of resistance mechanisms to all four conventional insecticide classes in the economically important crop pest. This valuable finding will greatly facilitate the development of molecular tools to monitor and manage the resistance and to minimize risk to environment.
ESTHER : Zhu_2024_Toxics_12_
PubMedSearch : Zhu_2024_Toxics_12_
PubMedID: 38535921

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

Title : Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung carcinogenesis - Wang_2024_Environ.Int_185_108494
Author(s) : Wang PS , Liu Z , Sweef O , Xie J , Chen J , Zhu H , Zeidler-Erdely PC , Yang C , Wang Z
Ref : Environ Int , 185 :108494 , 2024
Abstract : Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating beta-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis.
ESTHER : Wang_2024_Environ.Int_185_108494
PubMedSearch : Wang_2024_Environ.Int_185_108494
PubMedID: 38364571

Title : Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response - Gao_2024_Adv.Mater__e2312153
Author(s) : Gao G , Jiang YW , Chen J , Xu X , Sun X , Xu H , Liang G , Liu X , Zhan W , Wang M , Xu Y , Zheng J , Wang G
Ref : Adv Mater , :e2312153 , 2024
Abstract : The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate anti-tumor immunity, herein we rationally design a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic ciprofloxacin derivative (Cip-OH) and chemotherapeutic drug camptothecin (CPT) are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment. This article is protected by copyright. All rights reserved.
ESTHER : Gao_2024_Adv.Mater__e2312153
PubMedSearch : Gao_2024_Adv.Mater__e2312153
PubMedID: 38444205

Title : Clinical Features of Non-Hodgkin Lymphoma-Associated Hemophagocytic Syndrome: a Retrospective Study - Wu_2024_Clin.Lab_70_
Author(s) : Wu C , Liu H , Chen J
Ref : Clin Lab , 70 : , 2024
Abstract : BACKGROUND: This study aims to improve the understanding of lymphoma-associated hemophagocytic syndrome, and find effective methods to identify and manage this fatal disease. METHODS: Patients diagnosed with non-Hodgkin lymphoma-associated hemophagocytic syndrome from January 2008 to December 2022 in our center were included. Univariate and multivariate analyses were also conducted using the Cox proportional hazards model. RESULTS: Among 26 patients, 22 patients were diagnosed with T/NK cell lymphoma, while 4 patients were diagnosed with diffuse large B cell lymphoma. A total of 16 patients died with a median follow-up of 71 (26, 236) days. Compared with B cell lymphoma-associated hemophagocytic syndrome patients, T/NK cell lymphoma patients are younger, have lower platelet count, fibrinogen concentration, and serum albumin, have higher blood beta2-mi-croglobulin levels and ferritin, are more likely to be infected with Epstein-Barr virus, are more inclined have a simultaneously occurrence of lymphoma and hemophagocytic syndrome. In multivariate analysis, fibrinogen, albumin, cholinesterase, uric acid, triglyceride, and ferritin are significantly associated with overall mortality. CONCLUSIONS: LAHS is a rare disease with poor prognosis. Early anti-inflammatory treatment combined with anti-lymphoma therapy can improve the overall survival time of patients. Prospective multi-center studies with larger sample sizes and longer follow-up periods are needed to further investigate optimal treatment and prognosis.
ESTHER : Wu_2024_Clin.Lab_70_
PubMedSearch : Wu_2024_Clin.Lab_70_
PubMedID: 38623661

Title : Computational Design of Phosphotriesterase Improves V-Agent Degradation Efficiency - Kronenberg_2024_ChemistryOpen__e202300263
Author(s) : Kronenberg J , Chu S , Olsen A , Britton D , Halvorsen L , Guo S , Lakshmi A , Chen J , Kulapurathazhe MJ , Baker CA , Wadsworth BC , Van Acker CJ , Lehman JG, 3rd , Otto TC , Renfrew PD , Bonneau R , Montclare JK
Ref : ChemistryOpen , :e202300263 , 2024
Abstract : Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target. Here we describe a library of computationally designed variants of phosphotriesterase (PTE), an enzyme that is known to break down OPs. The mutations G208D, F104A, K77A, A80V, H254G, and I274N broadly improve catalytic efficiency of VX and VR hydrolysis without impacting the structure of the enzyme. The mutation I106A improves catalysis of VR and L271E abolishes activity, likely due to disruptions of PTE's structure. This study elucidates the importance of these residues and contributes to the design of enzymatic OP scavengers with improved efficiency.
ESTHER : Kronenberg_2024_ChemistryOpen__e202300263
PubMedSearch : Kronenberg_2024_ChemistryOpen__e202300263
PubMedID: 38426687

Title : A Novel Bacillus Velezensis for Efficient Degradation of Zearalenone - Li_2024_Foods_13_
Author(s) : Li Y , Chen S , Yu Z , Yao J , Jia Y , Liao C , Chen J , Wei Y , Guo R , He L , Ding K
Ref : Foods , 13 : , 2024
Abstract : Zearalenone (ZEN) is considered one of the most serious mycotoxins contaminating grains and their by-products, causing significant economic losses in the feed and food industries. Biodegradation pathways are currently considered the most efficient solution to remove ZEN contamination from foods. However, low degradation rates and vulnerability to environmental impacts limit the application of biodegradation pathways. Therefore, the main research objective of this article was to screen strains that can efficiently degrade ZEN and survive under harsh conditions. This study successfully isolated a new strain L9 which can efficiently degrade ZEN from 108 food ingredients. The results of sequence alignment showed that L9 is Bacillus velezensis. Meanwhile, we found that the L9 degradation rate reached 91.14% at 24 h and confirmed that the primary degradation mechanism of this strain is biodegradation. The strain exhibits resistance to high temperature, acid, and 0.3% bile salts. The results of whole-genome sequencing analysis showed that, it is possible that the strain encodes the key enzyme, such as chitinase, carboxylesterases, and lactone hydrolase, that work together to degrade ZEN. In addition, 227 unique genes in this strain are primarily involved in its replication, recombination, repair, and protective mechanisms. In summary, we successfully excavated a ZEN-degrading, genetically distinct strain of Bacillus velezensis that provides a solid foundation for the detoxification of feed and food contamination in the natural environment.
ESTHER : Li_2024_Foods_13_
PubMedSearch : Li_2024_Foods_13_
PubMedID: 38397507

Title : Effects of monitoring exercise rehabilitation with target intensity on the patient with twice PCI: A case report - Liu_2023_Medicine.(Baltimore)_102_e33583
Author(s) : Liu X , Chen Y , Chen J , Li A , Zhong M , Zhou W , Tang L
Ref : Medicine (Baltimore) , 102 :e33583 , 2023
Abstract : RATIONALE: As the core of cardiac rehabilitation (CR), early exercise rehabilitation is beneficial for patients with coronary heart disease (CHD), and center-based CR with target intensity is superior to home-based CR. However, there was no research to observe the effects of exercise rehabilitation on cardiopulmonary exercise capacity, oxygen uptake efficiency slope, endothelial function evaluated as flow-mediated vasodilation (FMD), and blood plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) in CHD patients undergone percutaneous coronary intervention (PCI) for 3 months. PATIENT CONCERNS: A 57-year-old woman had been identified with triple vessel disease and undergone twice PCI for complete revascularization, however, there was no improvement in Lp-PLA2, FMD, and related indicators of cardiopulmonary exercise testing. DIAGNOSIS: Coronary angiography showed an 85% stenosis in the middle left anterior descending artery, an 85% stenosis in the proximity of a thick first-diagonal branch, a long 75 to 85% stenosis in the middle left circumflex artery, and a 90 to 95% stenosis in the proximal. The case was diagnosed as CHD. INTERVENTIONS: The patient obtained optimal medical therapy comprising therapeutic lifestyle changes, and began monitoring exercise rehabilitation with target intensity 3 months after the second PCI in the CR center. OUTCOMES: There were changes in cardiopulmonary exercise capacity, oxygen uptake efficiency slope, FMD, and Lp-PLA2 in the patient with 3 apparent stenotic coronary arteries who was done PCI twice, without or with postoperative exercise rehabilitation, respectively. LESSONS: We proved that monitoring exercise rehabilitation training with target intensity could improve the prognosis of chronic coronary syndrome patients, and it was never too late to do regular exercise rehabilitation.
ESTHER : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedSearch : Liu_2023_Medicine.(Baltimore)_102_e33583
PubMedID: 37083775

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : Ent-Pimaranes isolated from Flickingeria fimbriata and their acetylcholinesterase inhibitory activities - Zhang_2023_Fitoterapia__105687
Author(s) : Zhang X , Zheng R , Hu S , Cao W , Tan J , Yang W , Chen J
Ref : Fitoterapia , :105687 , 2023
Abstract : Two new and six known ent-pimaranes were isolated from Flickingeria fimbriata. One of them possesses a rare carbon skeleton. It is the first time such a compound with this specific carbon skeleton has been isolated from a natural source. The structure and absolute configuration were determined by NMR, MS, and X-ray diffraction analysis. The biosynthetic pathway of the rare skeleton was proposed and suggested a new pathway for these nor-ent-pimarane analogues. All isolated compounds were screened for inhibitory activity against acetylcholinesterase (AChE). The compound 4 exhibits potent inhibitory effect on AChE with the 50% inhibitory concentration (IC(50)) being 5.8 microM, which is close to that of the positive control (Huperzine A). This is the first report about inhibitory activity on AChE of ent-pimaranes.
ESTHER : Zhang_2023_Fitoterapia__105687
PubMedSearch : Zhang_2023_Fitoterapia__105687
PubMedID: 37769998

Title : Acetylcholinesterase Inhibition in Rats and Humans Following Acute Fenitrothion Exposure Predicted by Physiologically Based Kinetic Modeling-Facilitated Quantitative In Vitro to In Vivo Extrapolation - Chen_2023_Environ.Sci.Technol__
Author(s) : Chen J , Zhao S , Wesseling S , Kramer NI , Rietjens I , Bouwmeester H
Ref : Environ Sci Technol , : , 2023
Abstract : Worldwide use of organophosphate pesticides as agricultural chemicals aims to maintain a stable food supply, while their toxicity remains a major public health concern. A common mechanism of acute neurotoxicity following organophosphate pesticide exposure is the inhibition of acetylcholinesterase (AChE). To support Next Generation Risk Assessment for public health upon acute neurotoxicity induced by organophosphate pesticides, physiologically based kinetic (PBK) modeling-facilitated quantitative in vitro to in vivo extrapolation (QIVIVE) approach was employed in this study, with fenitrothion (FNT) as an exemplary organophosphate pesticide. Rat and human PBK models were parametrized with data derived from in silico predictions and in vitro incubations. Then, PBK model-based QIVIVE was performed to convert species-specific concentration-dependent AChE inhibition obtained from in vitro blood assays to corresponding in vivo dose-response curves, from which points of departure (PODs) were derived. The obtained values for rats and humans were comparable with reported no-observed-adverse-effect levels (NOAELs). Humans were found to be more susceptible than rats toward erythrocyte AChE inhibition induced by acute FNT exposure due to interspecies differences in toxicokinetics and toxicodynamics. The described approach adequately predicts toxicokinetics and acute toxicity of FNT, providing a proof-of-principle for applying this approach in a 3R-based chemical risk assessment paradigm.
ESTHER : Chen_2023_Environ.Sci.Technol__
PubMedSearch : Chen_2023_Environ.Sci.Technol__
PubMedID: 38008925

Title : Screening of Tyrosinase, Xanthine Oxidase, and alpha-Glucosidase Inhibitors from Polygoni Cuspidati Rhizoma et Radix by Ultrafiltration and HPLC Analysis - Chen_2023_Molecules_28_
Author(s) : Chen J , Huang Q , He Z , Tan G , Zou Y , Xie J , Qian Z
Ref : Molecules , 28 : , 2023
Abstract : Polygoni Cuspidati Rhizoma et Radix (PCR), the rhizome and root of Polygonum cuspidatum Sieb. et Zucc., has been used as an herbal medicine for a long time. In this study, the ultrafiltration combined with high performance liquid chromatography (UF-HPLC) method was developed to screen tyrosinase (TYR), alpha-glucosidase (alpha-GLU), and xanthine oxidase (XOD) inhibitors from PCR. Firstly, the inhibitory activity of 50% methanol PCR extract on TYR, alpha-GLU, XOD, and acetylcholinesterase (ACHE) was tested. The extract showed a good inhibition on the enzymes, except for ACHE. Therefore, UF-HPLC experiments were carried out to screen TYR, alpha-GLU, and XOD inhibitors from PCR extract. Seven potential bioactive components were discovered, including methylgallate (1), 1,6-di-O-galloyl-D-glucose (2), polydatin-4'-O-D-glucoside (3), resveratrol-4'-O-D-glucoside (4), polydatin (5), malonyl glucoside resveratrol (6), and resveratrol-5-O-D-glucoside (7). Most of them were found as enzyme inhibitors from PCR for the first time, except polydatin (5), which had been reported as an alpha-GLUI in PCR in the literature. Finally, molecular docking analysis was applied to validate the interactions of these seven potential active components with the enzymes. Compounds 1-7 were proven as TYR inhibitors, compounds 2, 4-7 were identified as XOD inhibitors, and compounds 4-6 were confirmed as alpha-GLU inhibitors. In short, the current study provides a good reference for the screening of enzyme inhibitors through UF-HPLC, and provides scientific data for future studies of PCR.
ESTHER : Chen_2023_Molecules_28_
PubMedSearch : Chen_2023_Molecules_28_
PubMedID: 37241909

Title : Developmental Neurotoxicity of Difenoconazole in Zebrafish Embryos - Yang_2023_Toxics_11_353
Author(s) : Yang Q , Deng P , Xing D , Liu H , Shi F , Hu L , Zou X , Nie H , Zuo J , Zhuang Z , Pan M , Chen J , Li G
Ref : Toxics , 11 :353 , 2023
Abstract :
ESTHER : Yang_2023_Toxics_11_353
PubMedSearch : Yang_2023_Toxics_11_353
PubMedID: 37112580

Title : The primary neurotoxic factor, Lansamide I, from Clausena lansium fruits and metabolic dysfunction invoked - Chen_2023_Food.Chem.Toxicol_181_114087
Author(s) : Chen J , Zhang X , Zhang Y , Zhang H , Zhang Q
Ref : Food & Chemical Toxicology , 181 :114087 , 2023
Abstract : Wampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 +/- 0.16 mg/kg of dried seed and 0.08 +/- 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo, with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful molecules in wampee, which could inform the rational usage of wampee resources.
ESTHER : Chen_2023_Food.Chem.Toxicol_181_114087
PubMedSearch : Chen_2023_Food.Chem.Toxicol_181_114087
PubMedID: 37804914

Title : Aptamer recognition-promoted hybridization chain reaction for amplified label-free and enzyme-free fluorescence analysis of pesticide - Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
Author(s) : Chen J , Yang C , Nie H , Li H
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 293 :122451 , 2023
Abstract : Development of high-performance fluorescence sensors for pesticide is highly urgent but remains a grand challenge. It is due to that most of known fluorescence sensors detect pesticides based on enzyme-inhibited strategy, which requires high-price cholinesterase, suffers from serious interference of reductive materials, and can't difference pesticides with each other; the known aptamer-based fluorescence ones entail tool enzymes or nanomaterials to transducer/amplify the signal and demand signalers to be tagged in nucleic acid, which are expensive and intricate. Herein, we develop a novel aptamer-based fluorescence system for label-free, enzyme-free and highly sensitive detection of pesticide (profenofos) based on target-initiated hybridization chain reaction (HCR)-assisted signal amplification and specific intercalation of N-methylmesoporphyrin IX (NMM) in G-quadruplex DNA. Hairpin probe ON1 recognizes profenofos to generate profenofos@ON1 complex, which switches the HCR to yield multiple G-quadruplex DNA, consequently making large numbers of NMM be locked. In comparison with profenofos absence, a sharply improved fluorescence signal was recorded and it was dependent on profenofos dose. Hence, label-free, enzyme-free and highly sensitive detection of profenofos is achieved with limit of detection of 0.085 nM, which compared favorably with or superior to those of known fluorescence methods. Furthermore, the present method was applied to determine the profenofos residue in rice with agreeable result, and will provide more valuable information for guaranteeing the pesticide-related food safety.
ESTHER : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
PubMedSearch : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
PubMedID: 36801730

Title : Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis - Wei_2023_CNS.Neurosci.Ther__
Author(s) : Wei N , Liu H , Ye W , Xu S , Lu C , Dai A , Hou T , Zeng X , Wu J , Chen J
Ref : CNS Neurosci Ther , : , 2023
Abstract : BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Abeta), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.
ESTHER : Wei_2023_CNS.Neurosci.Ther__
PubMedSearch : Wei_2023_CNS.Neurosci.Ther__
PubMedID: 37088953

Title : Green-emitting carbon dots as a turn on fluorescence bio-probe for highly sensitive and selective detection of lipase in human serum - Al-Mashriqi_2023_Anal.Bioanal.Chem__
Author(s) : Al-Mashriqi HS , Sanga P , Chen J , Li X , Xiao J , Li Y , Qiu H
Ref : Anal Bioanal Chem , : , 2023
Abstract : Enzyme activity assays play a crucial role in numerous fields, including biotechnology, the food industry, and clinical diagnostics. Lipases are particularly important enzymes due to their widespread use in lipid metabolism and esterification reactions. Here, we present a pioneering method for the sensitive and selective determination of lipase activity using green carbon dots (G-CDs) for first time. G-CDs are a fascinating class of carbon nanomaterials with unique optical properties and biocompatibility, making them ideal candidates for enzyme activity assays. This approach eliminates the need for traditional fluorophores or chromogenic substrates, reducing costs, fast response time (1 min), and environmental impact with a quantum yield (QY) of 7.42%. As designed, the G-CDs fluorescent probe turn-on demonstrated a reliable linear detection range from 0 to 9 mg/mL under ideal conditions, with detection limit of 0.01 mg/mL and limit of quantification (LOQ) of 0.045 mg/mL, respectively. Furthermore, the G-CDs system was thoroughly evaluated in human serum samples, showing recoveries ranging from 100.0 to 105.0%. These findings highlight the promising applicability of the G-CDs probe for lipase detection, yielding highly favorable results.
ESTHER : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedSearch : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedID: 38082135

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

Title : Degradation of poly(butylene adipate-co-terephthalate) films by Thermobifida fusca FXJ-1 isolated from compost - Jia_2023_J.Hazard.Mater_441_129958
Author(s) : Jia X , Zhao K , Zhao J , Lin C , Zhang H , Chen L , Chen J , Fang Y
Ref : J Hazard Mater , 441 :129958 , 2023
Abstract : In recent years, Poly(butylene adipate-co-terephthalate) (PBAT) films were wildly used due to its biodegradable properties. However, there are few reports of strains that can high efficiently degrade PBAT. Thermobifida fusca FXJ-1, a thermophilic actinomycete, was screened and identified from compost. FXJ-1 can efficiently degrade PBAT at 55C in MSM medium. The degradation rates of the pure PBAT film (PF), PBAT film used for mulching on agricultural fields (PAF), and PBAT-PLA-ST film (PPSF) were 82.871.01%, 87.832.00% and 52.530.54%, respectively, after nine days of incubation in MSM medium. Cracking areas were monitored uniformly distributed on the surfaces of three kinds of PBAT-based films after treatment with FXJ-1 using scanning electron microscopy. The LC-MS results showed that PBAT might be degraded into adipic acid, terephthalic acid, butylene adipate, butylene terephthalate and butylene adipate-co-terephthalate, and these products are involved in the cleavage of ester bonds. We also found that amylase produced by FXJ-1 played an important role in the degradation of PPSF. FXJ-1 also showed an efficient PBAT-based films degradation ability in simulating compost environment, which implied its potential application in PBAT and starch-based film degradation by industrial composting.
ESTHER : Jia_2023_J.Hazard.Mater_441_129958
PubMedSearch : Jia_2023_J.Hazard.Mater_441_129958
PubMedID: 36122523

Title : Reusable carboxylesterase immobilized in ZIF for efficient degradation of chlorpyrifos in enviromental water - Wang_2023_Pestic.Biochem.Physiol_194_105519
Author(s) : Wang B , Chen J , Wu S , Fang J , Li Q , Wang G
Ref : Pestic Biochem Physiol , 194 :105519 , 2023
Abstract : The past few decades have witnessed biodegradation of pesticides as a significant method in remediation of the environment for its specificity, efficiency and biocompatibility. However, the tolerability and recyclability of the enzymes in pesticide degradation and the development of enzymes that biodegrad pesticides are still urgent problems to be solved so far. Herein, a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC was immobilized by biomineralization using zeolitic imidazolate framework (ZIF), one of the metal-organic frameworks (MOFs) with highly diverse structure and porosity. Compared with free enzyme, EstC@ZIF with a cruciate flower-like morphology presented scarcely variation in catalytic efficiency and generally improved the tolerance to organic solvents or detergents. Furthermore, there was scarcely decrease in the catalytic efficiency of EstC@ZIF and it also showed good reusability with about 50% residual activity after 12 continuous uses. Notably, EstC@ZIF could be used in actual water environment with an excellent value of degradation rate of 90.27% in 120 min, and the degradation efficiency remained about 50% after 9 repetitions. The present strategy of immobilizing carboxylesterase to treat pesticide-contaminated water broadens the method of immobilized enzymes on MOFs, and envisions its recyclable applicability in globe environmental remediation.
ESTHER : Wang_2023_Pestic.Biochem.Physiol_194_105519
PubMedSearch : Wang_2023_Pestic.Biochem.Physiol_194_105519
PubMedID: 37532333
Gene_locus related to this paper: strco-estli

Title : Label free impedance based acetylcholinesterase enzymatic biosensors for the detection of acetylcholine - Chen_2023_Biosens.Bioelectron_235_115340
Author(s) : Chen J , Lin KC , Prasad S , Schmidtke DW
Ref : Biosensors & Bioelectronics , 235 :115340 , 2023
Abstract : Realtime monitoring of neurotransmitters is of great interest for understanding their fundamental role in a wide range of biological processes in the central and peripheral nervous system, as well as their role, in several degenerative brain diseases. The measurement of acetylcholine in the brain is particularly challenging due to the complex environment of the brain and the low concentration and short lifetime of acetylcholine. In this paper, we demonstrated a novel, label-free biosensor for the detection of Ach using a single enzyme, acetylcholinesterase (ACHE), and electrochemical impedance spectroscopy (EIS). Acetylcholinesterase was covalently immobilized onto the surface of gold microelectrodes through an amine-reactive crosslinker dithiobis(succinimidyl propionate) (DSP). Passivation of the gold electrode with SuperBlock eliminated or reduced any non-specific response to other major interfering neurotransmitter molecules such as dopamine (DA), norepinephrine (NE) and epinephrine (EH). The sensors were able to detect acetylcholine over a wide concentration range (5.5-550 microM) in sample volumes as small as 300 microL by applying a 10 mV AC voltage at a frequency of 500 Hz. The sensors showed a linear relationship between Ach concentration and deltaZmod(R2 = 0.99) in PBS. The sensor responded to acetylcholine not only when evaluated in a simple buffer (PBS buffer) but in several more complex environments such as rat brain slurry and rat whole blood. The sensor remained responsive to acetylcholine after being implanted ex vivo in rat brain tissue. These results bode well for the future application of these novel sensors for real time in vivo monitoring of acetylcholine.
ESTHER : Chen_2023_Biosens.Bioelectron_235_115340
PubMedSearch : Chen_2023_Biosens.Bioelectron_235_115340
PubMedID: 37216844

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : CES1-Triggered Liver-Specific Cargo Release of CRISPR\/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration - Zhao_2023_Adv.Sci.(Weinh)__e2300502
Author(s) : Zhao Y , Li Y , Wang F , Gan X , Zheng T , Chen M , Wei L , Chen J , Yu C
Ref : Adv Sci (Weinh) , :e2300502 , 2023
Abstract : The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA). The copolymer can self-assemble with Cas9-mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG-b-P(Met/n-PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low-density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed-point release, which expand the application of CRISPR delivery systems.
ESTHER : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedSearch : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedID: 37083231

Title : Triacylglycerol lipase, OsSG34, plays an important role in grain shape and appearance quality in rice - Jin_2023_Plant.J__
Author(s) : Jin X , Chen J , Khan A , Chen Z , Gao R , Lu Y , Zheng X
Ref : Plant J , : , 2023
Abstract : Optimal grain-appearance quality is largely determined by grain size. To date, dozens of grain size-related genes have been identified. However, the regulatory mechanism of slender grain formation is not fully clear. We identified the OsSG34 gene by map-based cloning. A 9-bp deletion on 5'-untranslated region of OsSG34, which resulted in the expression difference between the wild-type and sg34 mutant, led to the slender grains and good transparency in sg34 mutant. OsSG34 as an alpha/beta fold triacylglycerol lipase affected the triglyceride content directly, and the components of cell wall indirectly, especially the lignin between the inner and outer lemmas in rice grains, which could affect the change in grain size by altering cell proliferation and expansion, while the change in starch content and starch granule arrangement in endosperm could affect the grain-appearance quality. Moreover, the OsERF71 was identified to directly bind to cis-element on the mutant site, thereby regulating the OsSG34 expression. Knockout of three OsSG34 homologous genes resulted in slender grains as well. The study demonstrated OsSG34, involved in lipid metabolism, affected grain size and quality. Our findings suggest that the OsSG34 gene could be used in rice breeding for high yield and good grain-appearance quality via marker-assisted selection and gene-editing approaches.
ESTHER : Jin_2023_Plant.J__
PubMedSearch : Jin_2023_Plant.J__
PubMedID: 37938788
Gene_locus related to this paper: orysa-Q8H025 , orysa-Q8H024 , orysa-Q8RUY8 , orysa-Q7XI46 , orysa-q75lp9

Title : Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants - Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
Author(s) : Ye Z , Bonam SR , McKay LGA , Plante JA , Walker J , Zhao Y , Huang C , Chen J , Xu C , Li Y , Liu L , Harmon J , Gao S , Song D , Zhang Z , Plante KS , Griffiths A , Hu H , Xu Q
Ref : Proc Natl Acad Sci U S A , 120 :e2311752120 , 2023
Abstract : The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4(+) and CD8(+) T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3beta (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs.
ESTHER : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedSearch : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedID: 38134199

Title : Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers - Li_2023_Clinics.(Sao.Paulo)_78_100208
Author(s) : Li J , Wen Z , Lou Y , Chen J , Gao L , Li X , Wang F
Ref : Clinics (Sao Paulo) , 78 :100208 , 2023
Abstract : OBJECTIVE: Oral ulcers are a lesion in the oral mucosa that impacts chewing or drinking. Epoxyeicosatrienoic Acids (EETs) have enhanced angiogenic, regenerative, anti-inflammatory, and analgesic effects. The present study aims to evaluate the effects of 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea (TPPU), a soluble epoxide hydrolase inhibitor for increasing EETs level, on the healing of oral ulcers. METHODS: The chemically-induced oral ulcers were established in Sprague Dawley rats. The ulcer area was treated with TPPU to evaluate the healing time and pain threshold of ulcers. The expression of angiogenesis and cell proliferation-related protein in the ulcer area was detected using immunohistochemical staining. The effects of TPPU on migration and angiogenesis capability were measured with scratch assay and tube formation. RESULTS: Compared with the control group, TPPU promoted wound healing of oral ulcers with a shorter healing time, and raised pain thresholds. Immunohistochemical staining showed that TPPU increased the expression of angiogenesis and cell proliferation-related protein with reduced inflammatory cell infiltration in the ulcer area. TPPU enhanced cell migration and tube-forming potential in vitro. CONCLUSIONS: The present results support the potential of TPPU with multiple biological effects for the treatment of oral ulcers by targeting soluble epoxide hydrolase.
ESTHER : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedSearch : Li_2023_Clinics.(Sao.Paulo)_78_100208
PubMedID: 37148830

Title : beta-cyclocitral, a novel AChE inhibitor, contributes to the defense of Microcystis aeruginosa against Daphnia grazing - Chen_2023_J.Hazard.Mater_465_133248
Author(s) : Chen W , Dou J , Xu X , Ma X , Chen J , Liu X
Ref : J Hazard Mater , 465 :133248 , 2023
Abstract : beta-cyclocitral is one of the major compounds in cyanobacterial volatile organic compound (VOCs) and can poison other aquatic organisms. To investigate the effect of beta-cyclocitral on cyanobacterial-grazer interactions, Daphnia sinensis was fed Microcystis aeruginosa and exposed to beta-cyclocitral. Our present study demonstrated that M. aeruginosa could significantly inhibit D. sinensis grazing. And the grazing inhibition by Microcystis aeruginosa results from the suppression of feeding rate, heart rate, thoracic limb activity and swimming speed of D. sinensis. In addition, M. aeruginosa could also induce intestinal peristalsis and emptying in D. sinensis. Interestingly, our present study found that the exposure to beta-cyclocitral could mimic a range of phenotypes induced by M. aeruginosa in D. sinensis. These results suggested that M. aeruginosa could release beta-cyclocitral to inhibit Daphnia grazing. To further examine the toxic mechanism of beta-cyclocitral in Daphnia, several in vivo and in vitro experiments displayed that beta-cyclocitral was a novel inhibitor of acetylcholinesterase (AChE). It could induce the accumulation of acetylcholine (ACh) by inhibiting AchE activity in D. sinensis. High level of endogenous Ach could inhibit feeding rate and induce intestinal peristalsis and emptying in D. sinensis.
ESTHER : Chen_2023_J.Hazard.Mater_465_133248
PubMedSearch : Chen_2023_J.Hazard.Mater_465_133248
PubMedID: 38147752
Gene_locus related to this paper: dapul-ACHE1

Title : A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network - Zhang_2023_Adv.Sci.(Weinh)__e2301004
Author(s) : Zhang Z , Liu Z , Wu P , Guo X , Luo X , Yang Y , Chen J , Tian Y
Ref : Adv Sci (Weinh) , :e2301004 , 2023
Abstract : A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.
ESTHER : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedSearch : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedID: 37635166

Title : Mechanistic Basis for Enhanced Strigolactone Sensitivity in KAI2 Triple Mutant - Sobecks_2023_bioRxiv__
Author(s) : Sobecks BL , Chen J , Shukla D
Ref : Biorxiv , : , 2023
Abstract : Striga hermonthica is a parasitic weed that destroys billions of dollars' worth of staple crops every year. Its rapid proliferation stems from an enhanced ability to metabolize strigolactones (SLs), plant hormones that direct root branching and shoot growth. Striga ' s SL receptor, Sh HTL7, bears more similarity to the staple crop karrikin receptor KAI2 than to SL receptor D14, though KAI2 variants in plants like Arabidopsis thaliana show minimal SL sensitivity. Recently, studies have indicated that a small number of point mutations to HTL7 residues can confer SL sensitivity to At KAI2. Here, we analyze both wild-type At KAI2 and SL-sensitive mutant Var64 through all-atom, long-timescale molecular dynamics simulations to determine the effects of these mutations on receptor function at a molecular level. We demonstrate that the mutations stabilize SL binding by about 2 kcal/mol. They also result in a doubling of the average pocket volume, and eliminate the dependence of binding on certain pocket conformational arrangements. While the probability of certain non-binding SL-receptor interactions increases in the mutant compared with the wild-type, the rate of binding also increases by a factor of ten. All these changes account for the increased SL sensitivity in mutant KAI2, and suggest mechanisms for increasing functionality of host crop SL receptors.
ESTHER : Sobecks_2023_bioRxiv__
PubMedSearch : Sobecks_2023_bioRxiv__
PubMedID: 36712135

Title : Assessment of the therapeutic potential of probiotics against carbon quantum dots-induced neurotoxicity in common carp (Cyprinus carpio) - Cao_2023_Aquat.Toxicol_258_106508
Author(s) : Cao X , Yuan R , Sun D , Ji X , Wei Y , Li L , Guo S , Li B , Chen J
Ref : Aquat Toxicol , 258 :106508 , 2023
Abstract : Carbon quantum dots (CQDs) have received increasing attention in recent years for their potential toxicity. However, little is known about their neurobehavioral toxicity. This study aimed to investigate the potential mechanisms by which probiotics reduce CQDs neurotoxicity from a brain-gut axis perspective by exposing carp to CQDs and/or probiotics for five weeks. The results showed that CQDs accumulation in the brain reduces the expression of blood-brain-barrier (BBB) related genes in carp, leading to brain damage. In addition, CQDs impaired motor behavior and inhibited acetylcholinesterase activity. These abnormalities were alleviated by probiotic supplementation. Microbiomic analysis showed that probiotics improved the imbalance of intestinal flora caused by CQDs and increased the abundance of Firmicutes. Serum metabolomic analysis showed that probiotic supplementation restored the abnormal metabolic levels associated with neurological, inflammatory, and apoptotic cell death caused by CQDs. Overall, probiotic supplementation improved the CQDs-induced changes in brain damage, gut microbiology, and systemic metabolism. These results suggests that CQDs may cause neurotoxicity via the brain-gut microbial axis.
ESTHER : Cao_2023_Aquat.Toxicol_258_106508
PubMedSearch : Cao_2023_Aquat.Toxicol_258_106508
PubMedID: 37001197

Title : Integrated transcriptomic and biochemical characterization of the mechanisms governing stress responses in soil-dwelling invertebrate (Folsomia candida) upon exposure to dibutyl phthalate - Zheng_2023_J.Hazard.Mater_462_132644
Author(s) : Zheng Y , Liu C , Chen J , Tang J , Luo J , Zou D , Tang Z , He J , Bai J
Ref : J Hazard Mater , 462 :132644 , 2023
Abstract : Dibutyl phthalate (DBP) is one of the most commonly utilized plasticizers and a frequently detected phthalic acid ester (PAE) compound in soil samples. However, the toxicological effects of DBP on soil-dwelling organisms remain poorly understood. This study employed a multi-biomarker approach to investigate the impact of DBP exposure on Folsomia candida's survival, reproduction, enzyme activity levels, and transcriptional profiles. Analyses of antioxidant biomarkers, including catalase (CAT) and glutathione S-transferase (GST), as well as detoxifying enzymes such as acetylcholinesterase (AChE), Cytochrome P450 (CYP450), and lipid peroxidation (LPO), revealed significant increases in CAT activity, GST levels, and CYP450 expression following treatment with various doses of DBP for 2, 4, 7, or 14 days. Additionally, LPO induction was observed along with significant AChE inhibition. In total, 3175 differentially expressed genes (DEGs) were identified following DBP treatment that were enriched in six Gene Ontology (GO) terms and 144 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including 85 upregulated and 59 downregulated primarily associated with lipid metabolism, signal transduction, DNA repair, and cell growth and death. Overall these results provide foundational insights for further research into the molecular mechanisms underlying responses of soil invertebrates to DBP exposure.
ESTHER : Zheng_2023_J.Hazard.Mater_462_132644
PubMedSearch : Zheng_2023_J.Hazard.Mater_462_132644
PubMedID: 37820532

Title : Exploration of DPP-IV Inhibitory Peptide Design Rules Assisted by the Deep Learning Pipeline That Identifies the Restriction Enzyme Cutting Site - Guan_2023_ACS.Omega_8_39662
Author(s) : Guan C , Luo J , Li S , Tan ZL , Wang Y , Chen H , Yamamoto N , Zhang C , Lu Y , Chen J , Xing XH
Ref : ACS Omega , 8 :39662 , 2023
Abstract : The mining of antidiabetic dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (DPP-IV-IPs) is currently a costly and laborious process. Due to the absence of rational peptide design rules, it relies on cumbersome screening of unknown enzyme hydrolysates. Here, we present an enhanced deep learning model called bidirectional encoder representation (BERT)-DPPIV, specifically designed to classify DPP-IV-IPs and explore their design rules to discover potent candidates. The end-to-end model utilizes a fine-tuned BERT architecture to extract structural/functional information from input peptides and accurately identify DPP-IV-Ips from input peptides. Experimental results in the benchmark data set showed BERT-DPPIV yielded state-of-the-art accuracy and MCC of 0.894 and 0.790, surpassing the 0.797 and 0.594 obtained by the sequence-feature model. Furthermore, we leveraged the attention mechanism to uncover that our model could recognize the restriction enzyme cutting site and specific residues that contribute to the inhibition of DPP-IV. Moreover, guided by BERT-DPPIV, proposed design rules for DPP-IV inhibitory tripeptides and pentapeptides were validated, and they can be used to screen potent DPP-IV-IPs.
ESTHER : Guan_2023_ACS.Omega_8_39662
PubMedSearch : Guan_2023_ACS.Omega_8_39662
PubMedID: 37901493

Title : siRNA Silencing of FpVtg Induces Ovarian Cell Apoptosis in Redtail Prawn, Fenneropenaeus penicillatus - Tan_2023_Mar.Biotechnol.(NY)__
Author(s) : Tan K , Dong Y , Lim LS , Waiho K , Chen J , Xu P , Kwan KY
Ref : Mar Biotechnol (NY) , : , 2023
Abstract : Inadequate gonadal maturation and poor spawning performance increasingly threaten the sustainability of shrimp aquaculture. Unraveling the mechanisms regulating ovarian development and maturation hence is critical to address industry challenges. Vitellogenin (Vtg), a precursor of yolk protein found in the hepatopancreas and ovary of shrimp, plays a key role in facilitating shrimp's oocyte maturation and embryonic development after oviposition. This study found that FpVtg was specifically expressed in F. penicillatus hepatopancreas and ovary. FpVtg was localized predominantly in the oocyte cytoplasm and distributed uniformly in the hepatopancreas tissue. Silencing FpVtg led to apoptosis in both hepatopancreas and ovary tissues. Furthermore, FpVtg depletion upregulated the expression of ovarian peritrophin 1, ovarian peritrophin 2, serine proteinase inhibitor 6, and juvenile hormone esterase-like carboxylesterase 1, while downregulated that of vitellogenin, delta-9 desaturase, and insulin-like receptor. KEGG pathway analysis implicated such as PI3K-AKT signaling, RNA transport, ECM-receptor interaction, hippo signaling, oocyte meiosis, and apoptosis were enriched and involved in ovarian development. These findings have provided insights into the FpVtg's reproductive role and the associated regulatory genes and pathways in F. penicillatus. This knowledge can contribute to establishing strategies to improve the breeding and aquaculture production of F. penicillatus by elucidating its vitellogenesis regulation in redtail prawn and other penaeid species. Further characterization of the implicated pathways and genes will clarify the intricacies underlying ovarian maturation.
ESTHER : Tan_2023_Mar.Biotechnol.(NY)__
PubMedSearch : Tan_2023_Mar.Biotechnol.(NY)__
PubMedID: 38010485

Title : Effects of walnut seed coat polyphenols on walnut protein hydrolysates: Structural alterations, hydrolysis efficiency, and acetylcholinesterase inhibitory capacity - Su_2023_Food.Chem_437_137905
Author(s) : Su G , Chen J , Huang L , Zhao M , Huang Q , Zhang J , Zeng X , Zhang Y , Deng L , Zhao T
Ref : Food Chem , 437 :137905 , 2023
Abstract : The walnut meal is rich in nutrients such as protein from the kernel and polyphenolic compounds from the seed coat. However, the influences of seed coat polyphenols on walnut protein (WP) hydrolysis remained unclear. In this study, our findings indicated that polyphenols induced alterations in the secondary structure and amino acid composition of WP. These changes resulted in both a hindrance of hydrolysis and an enhancement of acetylcholinesterase (AChE) inhibition. Furthermore, four peptides of 119 identified peptides (LR, SF, FQ, and FR) were synthesized based on higher predicted bioactivity and Vinascores in silico. Among them, FQ showed interaction with amino acid residues in AChE through the formation of four Pi-Pi stacking bonds and two hydrogen bonds, resulting in the highest AChE inhibitory capacity. The combination index showed that chlorogenic acid derived from the seed coat and FQ at the molar ratio of 1:4 exhibited synergistic effects of AChE inhibition.
ESTHER : Su_2023_Food.Chem_437_137905
PubMedSearch : Su_2023_Food.Chem_437_137905
PubMedID: 37922803

Title : Inhibition mechanisms of four ellagitannins from terminalia chebula fruits on acetylcholinesterase by inhibition kinetics, spectroscopy and molecular docking analyses - Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
Author(s) : Li YJ , Liang CC , Jin L , Chen J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 302 :123115 , 2023
Abstract : Acetylcholinesterase (AChE) is an important therapeutic target for the treatment of Alzheimer's disease (AD), and the development of natural AChE inhibitors as candidates has played a significant role in drug discovery. In this study, the inhibition mechanisms of four ellagitannins, punicalagin, chebulinic acid, geraniin and corilagin, from Terminalia chebula fruits on AChE were investigated systematically by a combination of inhibition kinetics, multi-spectroscopic methods and molecular docking. The kinetic results showed that punicalagin, chebulinic acid and geraniin exhibited strong reversible inhibitory effects on AChE in an uncompetitive manner with the IC(50) values of 0.43, 0.50, and 0.51 mM, respectively, while corilagin inhibited AChE activity in a mixed type with the IC(50) value of 0.72 mM. The results of fluorescence and UV-vis spectra and fluorescence resonance energy transfer (FRET) revealed that four ellagitannins could significantly quenched the intrinsic fluorescence of AChE though a static quenching along with non-radiative energy transfer. Thermodynamic analyses showed that values of deltaG, deltaH and deltaS were negative, indicating that all binding processes were spontaneous, and the hydrogen bonding and Van der Waals forces might make a great contribution to the formation of inhibitor-AChE complexes. The synchronous fluorescence, three-dimensional (3D) fluorescence, UV-vis, and FT-IR spectra studies suggested that four ellagitannins could lead to alterations in the micro-environment and secondary structure of AChE, and thus the conformational change of AChE. Moreover, molecular docking demonstrated that four ellagitannins could interacted with main amino acid residues of AChE with affinity energies ranging from -9.9 to -8.7 kJ/mol, and further confirmed the above experimental results. This study provided valuable findings for the potential application of four ellagitannins as promising candidates in the exploration of natural AChE inhibitors for the treatment of AD.
ESTHER : Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
PubMedSearch : Li_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_302_123115
PubMedID: 37453379

Title : Soluble DPP4 can act as a diagnostic biomarker in Hashimoto's thyroiditis with thyroid papillary carcinoma - Zhang_2023_J.Cancer.Res.Ther_19_1048
Author(s) : Zhang Y , Zhang Q , Zheng Y , Chen J , Liu N , Liu K , Song W
Ref : J Cancer Research Ther , 19 :1048 , 2023
Abstract : BACKGROUND: Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. MATERIALS AND METHODS: Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. RESULTS: Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. CONCLUSIONS: The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC.
ESTHER : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedSearch : Zhang_2023_J.Cancer.Res.Ther_19_1048
PubMedID: 37675735

Title : Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition - Cao_2023_Virol.J_20_77
Author(s) : Cao X , Jiang W , Shi L , Wang Y , Chen J , Huang W , Zhang S
Ref : Virol J , 20 :77 , 2023
Abstract : BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 +/- 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 +/- 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.
ESTHER : Cao_2023_Virol.J_20_77
PubMedSearch : Cao_2023_Virol.J_20_77
PubMedID: 37095526

Title : Lysosomal phospholipase A2 contributes to the biosynthesis of the atypical late endosome lipid bis(monoacylglycero)phosphate - Chen_2023_Commun.Biol_6_210
Author(s) : Chen J , Cazenave-Gassiot A , Xu Y , Piroli P , Hwang R, Jr. , DeFreitas L , Chan RB , Di Paolo G , Nandakumar R , Wenk MR , Marquer C
Ref : Commun Biol , 6 :210 , 2023
Abstract : The late endosome/lysosome (LE/Lys) lipid bis(monoacylglycero)phosphate (BMP) plays major roles in cargo sorting and degradation, regulation of cholesterol and intercellular communication and has been linked to viral infection and neurodegeneration. Although BMP was initially described over fifty years ago, the enzymes regulating its synthesis remain unknown. The first step in the BMP biosynthetic pathway is the conversion of phosphatidylglycerol (PG) into lysophosphatidylglycerol (LPG) by a phospholipase A2 (PLA2) enzyme. Here we report that this enzyme is lysosomal PLA2 (LPLA2). We show that LPLA2 is sufficient to convert PG into LPG in vitro. We show that modulating LPLA2 levels regulates BMP levels in HeLa cells, and affects downstream pathways such as LE/Lys morphology and cholesterol levels. Finally, we show that in a model of Niemann-Pick disease type C, overexpressing LPLA2 alleviates the LE/Lys cholesterol accumulation phenotype. Altogether, we shed new light on BMP biosynthesis and contribute tools to regulate BMP-dependent pathways.
ESTHER : Chen_2023_Commun.Biol_6_210
PubMedSearch : Chen_2023_Commun.Biol_6_210
PubMedID: 36823305
Gene_locus related to this paper: human-PLA2G15

Title : Overexpression and truncation of a novel cold-adapted lipase with improved enzymatic characteristics - Zhang_2023_Protein.Expr.Purif__106376
Author(s) : Zhang Y , Gao Y , Chen J , Yu F , Bao Y
Ref : Protein Expr Purif , :106376 , 2023
Abstract : The novel cold-adapted lipase (Lip ZC12) derived from Psychrobacter sp. ZY124 exhibited higher catalytic activity at 20-40 degreesC, the whole gene was then sequenced, analyzed, and overexpressed. However, its intrinsic structural characteristics lead to a decreased affinity toward the substrate, thus limiting the improvement of catalytic efficiency. Modeling the homologous structure and simulating the binding process of Lip ZC12 with the substrate. It was found that truncated lid (lip-deltalid) could not only increase the k(cat), but also significantly enhance the substrate affinity, the substrate affinity and catalytic efficiency of Lip ZC12 modified by lid truncation were significantly improved. The results revealed that the k(cat)/K(m) value of lip-deltalid was 1.6 times higher than that of free lipase. This improved catalytic performance of cold-adapted lipase, and these findings laid an important foundation for further application.
ESTHER : Zhang_2023_Protein.Expr.Purif__106376
PubMedSearch : Zhang_2023_Protein.Expr.Purif__106376
PubMedID: 37839629
Gene_locus related to this paper: 9gamm-a0a1b1ijp3

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : Effect of Histidine Covalent Modification on Strigolactone Receptor Activation and Selectivity - Chen_2023_Biophys.J__
Author(s) : Chen J , Shukla D
Ref : Biophysical Journal , : , 2023
Abstract : The parasitic weed Striga has led to billions of dollars' worth of agricultural productivity loss worldwide. Striga detects host plants using compounds of the strigolactone class of phytohormones. Early steps in the strigolactone signaling pathway involve substrate binding and hydrolysis followed by a conformational change to an "active" or "closed" state, after which it associates with a MAX2-family downstream signaling partner. The structures of the inactive and active states of strigolactone receptors are known through X-ray crystallography, and the transition pathway of from the inactive to active state in apo receptors has previously been characterized using molecular dynamics simulations. However, it also has been suggested that a covalent butenolide modification of the receptor on the catalytic histidine through substrate hydrolysis promotes formation of the active state. Using molecular dynamics simulations, we show that the presence of the covalent butenolide enhances activation in both AtD14, a receptor found in Arabidopsis, and ShHTL7, a receptor found in Striga, but the enhancement is -50 times greater in ShHTL7. We also show that several conserved interactions with the covalent butenolide modification promote transition to the active state in both AtD14 (non-parasite) and ShHTL7 (parasite). Finally, we demonstrate that the enhanced activation of ShHTL7 likely results from disruption of ShHTL7-specific histidine interactions that inhibited activation in the apo case. These results provide a possible explanation for difference in strigolactone sensitivity seen between different strigolactone-sensitive proteins and can be used to aid the design of selective modulators to control Striga parasites.
ESTHER : Chen_2023_Biophys.J__
PubMedSearch : Chen_2023_Biophys.J__
PubMedID: 36798027

Title : Activation Mechanism of Strigolactone Receptors and Its Impact on Ligand Selectivity between Host and Parasitic Plants - Chen_2022_J.Chem.Inf.Model__
Author(s) : Chen J , Nelson DC , Shukla D
Ref : J Chem Inf Model , : , 2022
Abstract : Parasitic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate hydrolysis followed by a conformational change of the receptor to a "closed" or "active" state that associates with a signaling partner, MAX2/D3. Crystal structures of active and inactive AtD14 receptors have helped elucidate the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of AtD14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to associate with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga, ShHTL7, and AtD14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both AtD14 and ShHTL7 could adopt an active conformation in the absence of ligand. However, ShHTL7 exhibits a higher population in the inactive apo state as compared to the AtD14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and interactions with the catalytic histidine that prevent full binding pocket closure in ShHTL7. These results indicate that ligand hydrolysis would enhance the active state population by destabilizing the inactive state in ShHTL7 as compared to AtD14. We also show that the mechanism of activation is more concerted in AtD14 than in ShHTL7 and that the main barrier to activation in ShHTL7 is closing of the binding pocket.
ESTHER : Chen_2022_J.Chem.Inf.Model__
PubMedSearch : Chen_2022_J.Chem.Inf.Model__
PubMedID: 35192364

Title : Characterization of a Novel Esterase Est33 From an Antarctic Bacterium: A Representative of a New Esterase Family - Liu_2022_Front.Microbiol_13_855658
Author(s) : Liu X , Zhou M , Sun R , Xing S , Wu T , He H , Chen J , Bielicki JK
Ref : Front Microbiol , 13 :855658 , 2022
Abstract : Studies of microorganisms from extreme environments can sometimes reveal novel proteins with unique properties. Here, we identified a novel esterase gene (Est33) from an Antarctic bacterium. The protein was expressed and purified for biochemical characterizations. Site-mutation variants including S94A, D205A, and H233A were constructed to explore the structure-function relationship of the catalytic triad of Est33, and we found mutating Ser(94), Asp(205), and His(233) residues lead to a complete loss of enzyme activity. In addition, the catalytic Ser(94) located in a conserved pentapeptide motif GVSWG. Phylogenetic analysis showed that Est33 and its closely related homologs belonged to an independent group apart from other known family members, indicating that Est33 represented a new family of esterase. The Est33 enzyme was found to be a cold-active esterase retaining 25%-100% activity from 10 degreesC to 30 degreesC and to have optimal catalytic activity toward p-nitrophenol acetate (30 degreesC and pH7.5). The serine modifying reagent phenylmethylsulfonyl fluoride inhibited the activity of Est33 by 77.34%, while thiol reagents such as dithiol threitol (DTT) activated the enzyme by 3-fold. Metal chelating reagents EDTA had no effects, indicating that Est33 is not a metalloenzyme. Collectively, these results indicate that Est33 constitutes the first member of a novel esterase family XXI that has been identified.
ESTHER : Liu_2022_Front.Microbiol_13_855658
PubMedSearch : Liu_2022_Front.Microbiol_13_855658
PubMedID: 35655995
Gene_locus related to this paper: psesp-Est33

Title : Bisphenol AF induces multiple behavioral and biochemical changes in zebrafish (Danio rerio) at different life stages - Rao_2022_Aquat.Toxicol_253_106345
Author(s) : Rao C , Cao X , Li L , Zhou J , Sun D , Li B , Guo S , Yuan R , Cui H , Chen J
Ref : Aquat Toxicol , 253 :106345 , 2022
Abstract : As common environmental endocrine-disrupting chemicals (EDCs), bisphenol AF (BPAF) raises potential concerns for aquatic organisms due to its widespread presence and continued release in the aquatic environment. This research aimed to use zebrafish embryos and adult fish to explore the effects of environmentally relevant concentrations (5 g/L), 50 g/L and 500 g/L of BPAF on zebrafish embryonic development, behavioral alterations, and the potential mechanisms driving these effects. The results showed that 500 g/L of BPAF severely affected the growth and development of embryos. In behavioral experiments, all concentrations of BPAF significantly inhibited the locomotor activity of larvae, 50 and 500 g/L BPAF significantly altered the anxiety-like and aggressive behavior of adult zebrafish. Furthermore, environmentally relevant concentrations and higher concentrations of BPAF induced varying degrees of oxidative stress in both embryonic and adult fish. The most significant histopathological changes and decreased acetylcholinesterase (AChE) activity were observed in the brain at 50 and 500 g/L of BPAF. We hypothesized that oxidative stress is an important cause of behavioral disturbances in larvae and adult fish. To our best knowledge, the present experiment is a pioneer in studying the effects of BPAF on a variety of complex behaviors (swimming performance, anxiety-like, social behavior, aggression) in zebrafish, which emphasizes the potential health risk of higher concentrations of BPAF in terms of induced neurotoxicity.
ESTHER : Rao_2022_Aquat.Toxicol_253_106345
PubMedSearch : Rao_2022_Aquat.Toxicol_253_106345
PubMedID: 36351319

Title : SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice - Xiang_2022_Cell.Death.Dis_13_638
Author(s) : Xiang L , Wu Q , Sun H , Miao X , Lv Z , Liu H , Chen L , Gu Y , Chen J , Zhou S , Jiang H , Du S , Zhou Y , Dong H , Fan Y , Miao S , Lu Q , Chang L , Wang H , Lu Y , Xu X , Wang W , Huang Z
Ref : Cell Death Dis , 13 :638 , 2022
Abstract : Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD.
ESTHER : Xiang_2022_Cell.Death.Dis_13_638
PubMedSearch : Xiang_2022_Cell.Death.Dis_13_638
PubMedID: 35869039

Title : The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos - Yu_2022_Chemosphere_307_135751
Author(s) : Yu H , Zhang J , Chen Y , Chen J , Qiu Y , Zhao Y , Li H , Xia S , Chen S , Zhu J
Ref : Chemosphere , 307 :135751 , 2022
Abstract : Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.
ESTHER : Yu_2022_Chemosphere_307_135751
PubMedSearch : Yu_2022_Chemosphere_307_135751
PubMedID: 35863420

Title : Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease - Wu_2022_Bioorg.Chem_122_105760
Author(s) : Wu D , Chen J , Luo K , Li H , Liu T , Li L , Dai Z , Li Y , Zhao Y , Fu X
Ref : Bioorg Chem , 122 :105760 , 2022
Abstract : In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD.
ESTHER : Wu_2022_Bioorg.Chem_122_105760
PubMedSearch : Wu_2022_Bioorg.Chem_122_105760
PubMedID: 35349945

Title : Gelsemine relieves the neuropathic pain by down-regulating DPP4 level in rats - Yang_2022_Neurosci.Lett_792_136961
Author(s) : Yang L , Zhou G , Chen J , Zhang S
Ref : Neuroscience Letters , 792 :136961 , 2022
Abstract : BACKGROUND: Based on the previous findings on the relieving role of gelsemine in neuropathic pain, this research aims to further investigate the relevant regulatory mechanism. METHODS: Targets of gelsemine were predicted using SwissTargetPrediction. The peripheral neuropathic pain rat model was established by ligating spinal nerves, and then gelsemine (10 g for one day) or dipeptidyl peptidase 4 (DPP4) oligonucleotides (5 g/day, for 7 days) was injected into intrathecal bolus of rats. The mechanical threshold (0, 1, 2, 4 h after the last injection) was examined to evaluate the mechanical allodynia of rats. After the mechanical threshold measurement, the rats were anesthetized with isoflurane and then sacrificed by cervical dislocation. IBA1- and DPP4-positive cells in the spinal dorsal horn of rats were determined using immunohistochemistry and immunofluorescence assays. The expressions of DPP4, IL-1 and TNF-alpha in the spinal dorsal horn of rats were measured by Western blot and quantitative real-time PCR. RESULTS: DPP4 was one of the targets of gelsemine. Gelsemine could elevate the down-regulated mechanical threshold, and lessen the up-regulated IBA1- and DPP4-positive cells and expressions of DPP4, IL-1 and TNF-alpha in the spinal dorsal horn of rats with neuropathic pain. DPP4 overexpression reversed the role of gelsemine in neuropathic pain. CONCLUSION: Gelsemine relieves neuropathic pain by down-regulating DPP4 level in rats, providing a novel drug candidate and biomarker for neuropathic pain treatment.
ESTHER : Yang_2022_Neurosci.Lett_792_136961
PubMedSearch : Yang_2022_Neurosci.Lett_792_136961
PubMedID: 36370955

Title : Glutathione-modified graphene quantum dots as fluorescent probes for detecting organophosphorus pesticide residues in Radix Angelica Sinensis - Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
Author(s) : Mu XQ , Wang D , Meng LY , Wang YQ , Chen J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 286 :122021 , 2022
Abstract : A novel fluorescent sensor was developed in this study based on glutathione-functionalized graphene quantum dots (GQDs@GSH) to detect organophosphorus pesticide residues in Radix Angelica Sinensis. GQDs@GSH was synthesized by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.9% and its structure was characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. GQDs@GSH exhibited excellent fluorescence property showing strong blue fluorescence under UV irradiation. The fluorescence of GQDs@GSH could be quenched by Fe(3+) by electron transfer and the quenched fluorescence could be recovered due to the strong chelating and reducing ability of phytic acid (PA). Under the catalyzation of acetylcholinesterase (AChE) and choline oxidase (ChOx), acetylcholine (ACh) could be decomposed to H(2)O(2), which could further oxidize Fe(2+) to Fe(3+) thus quenching the fluorescence of GQDs@GSH once again. Coumaphos, a kind of organophosphorus pesticide, could inhibit AChE activity, thus making the quenched fluorescence turn on again. Several parameters influencing the fluorescence response such as Fe(3+), PA, ACh and coumaphos concentration, pH value and reaction time were optimized. Based on such a fluorescence "off-on-off-on" ngkmechanism, GQDs@GSH was successfully applied to the detection of coumaphos in Radix Angelica Sinensis. A good linear relationship between the fluorescence intensity and coumaphos concentration was obtained in the range of 0.1-10.0 micromol.L(-1). By a standard addition method, the recoveries were measured to be 101.44-117.90% with RSDs lower than 1.98%. The biosensor system is simple, sensitive and accurate. It has a good application prospect in the detection of organophosphorus pesticide residues in traditional Chinese medicine and agricultural products, and also expanded the application scope for glutathione as a highly selective biological molecule.
ESTHER : Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
PubMedSearch : Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
PubMedID: 36283209

Title : Screening of acetylcholinesterase inhibitory and antioxidant active compounds from Terminalia chebula fruits by spectrum-effect relationship and liquid chromatography-mass spectrometry analysis -
Author(s) : Zhao HH , Li YJ , Guo ZH , Chen J
Ref : J Sep Sci , : , 2022
PubMedID: 35819997

Title : A novel approach for on-site screening of organophosphorus nerve agents based on DTNB modified AgNPs using surface-enhanced Raman spectrometry - Wu_2022_Anal.Methods__
Author(s) : Wu J , Zhu Y , Liu Y , Chen J , Guo L , Xie J
Ref : Anal Methods , : , 2022
Abstract : Organophosphorus nerve agents (OPNAs), such as Sarin (GB), Tabun (GA), Soman (GD) and VX, would cause tremendous harm in military and terrorist attacks, and thus the development of simple methods for the rapid and efficient detection of these hazardous substances is of great necessity. Herein, we present a novel approach for the facile, rapid and sensitive detection of real OPNAs. The detection substrate is fabricated using functionalized silver nanoparticles (AgNPs) immobilized with acetylcholinesterase (AChE) and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In the absence of OPs, AChE catalyzes the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which continues to interact quickly with DTNB to produce a very sensitive Raman probing molecule, TNB. The inhibition of the activity of AChE by OPs could induce an obvious decrease of characteristic Raman peaks of 5-thio-2-nitrobenzoic acid (TNB) at 1335 cm(-1). The introduction of DTNB as an enzyme activity indicator significantly improves the detection sensitivity with distinct characteristic Raman peaks. The LOD of GD, which is one of the most easily aged OPNAs, could reach 0.1 nM due to its strongest inhibition of AChE. Moreover, various OPNAs exhibit different SERS intensities due to their different inhibition capacities of AChE. Hence, the new strategy has great potential in public security early warning and environmental analysis.
ESTHER : Wu_2022_Anal.Methods__
PubMedSearch : Wu_2022_Anal.Methods__
PubMedID: 36285727

Title : Ternary heterostructures of 1D\/2D\/2D CuCo(2)S(4)\/CuS\/Ti(3)C(2) MXene: Boosted amperometric sensing for chlorpyrifos - Mi_2022_J.Hazard.Mater_438_129419
Author(s) : Mi Y , Zhao Y , Chen J , Li X , Yang Y , Gao F
Ref : J Hazard Mater , 438 :129419 , 2022
Abstract : Multicomponent heterogeneous Ti(3)C(2) transition metal carbide (MXene)-based materials are receiving extensive research attention due to their interesting synergistic interactions and catalytic properties. However, the morphology-controllable synthesis of heterostructures as structural stabilizers for Ti(3)C(2) MXene remains a challenge owing the complicated synthesis procedure. In this work, a kind of ternary heterogeneous nanomaterials CuCo(2)S(4)/CuS/Ti(3)C(2) MXene with a nanorod/nanoplate/nanosheet hybrid architecture is constructed through a one-step low-temperature solvothermal method. The well-designed ternary one-dimensional (1D)/two-dimensional (2D)/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterials exhibit synergistic improvements in substrate-catalyzed reactions for electrochemical acetylcholinesterase (AChE) biosensor. The Michaelis-Menten constant for the Nafion/AChE/CuCo(2)S(4)/CuS/Ti(3)C(2) MXene/GCE biosensor is 228 microM, which is smaller than ones reported in previous literatures, indicating a higher affinity of the fabricated enzyme biosensor to acetylthiocholine chloride. The biosensor exhibits a well linear relationship with chlorpyrifos concentration ranging from 2.852 x 10(-12) M to 2.852 x 10(-6) M. The multicomponent 1D/2D/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterial may shine a light in more electrochemical applications.
ESTHER : Mi_2022_J.Hazard.Mater_438_129419
PubMedSearch : Mi_2022_J.Hazard.Mater_438_129419
PubMedID: 35780734

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

Title : Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor - Zhang_2022_PLoS.One_17_e0266608
Author(s) : Zhang C , Li W , Li X , Wan D , Mack S , Zhang J , Wagner K , Wang C , Tan B , Chen J , Wu CW , Tsuji K , Takeuchi M , Chen Z , Hammock BD , Pinkerton KE , Yang J
Ref : PLoS ONE , 17 :e0266608 , 2022
Abstract : Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.
ESTHER : Zhang_2022_PLoS.One_17_e0266608
PubMedSearch : Zhang_2022_PLoS.One_17_e0266608
PubMedID: 35443010

Title : Graphitic-phase C(3)N(4) nanosheets combined with MnO(2) nanosheets for sensitive fluorescence quenching detection of organophosphorus pesticides - Liu_2022_J.Environ.Sci.Health.B__1
Author(s) : Liu B , Chen J , Peng Y , Xiao W , Peng Z , Qiu P
Ref : J Environ Sci Health B , :1 , 2022
Abstract : In this study, we have developed a sensitive approach to measure organophosphorus pesticides (OPs) using graphitic-phase C(3)N(4) nanosheets (g-C(3)N(4)) combined with a nanomaterial-based quencher, MnO(2) nanosheets (MnO(2) NS). Since MnO(2) NS can quench the fluorescence of g-C(3)N(4) via the inner-filter effect (IFE), enzymatic hydrolysate (thiocholine, TCh) can efficiently trigger the decomposition of MnO(2) nanosheets in the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCh), resulting in the fluorescence recovery of g-C(3)N(4). OPs, as inhibitors to AChE activity, can prevent the generation of TCh and decomposition of MnO(2) nanosheets while exhibiting fluorescence quenching. Therefore, the AChE-ATCh-MnO(2)-g-C(3)N(4) system can be utilized to quantitatively detect OPs based on g-C(3)N(4) fluorescence. Under optimal conditions, the linear ranges for the determination of parathion-methyl (PM) and 2,2-dichlorovinyl dimethyl phosphate (DDVP) were found to be 0.1-2.1 ng/mL and 0.5-16 ng/mL, respectively, with limits of detection of 0.069 ng/mL and 0.20 ng/mL, respectively. The advantages of this assay are user-friendliness, ease of use, and cost effectiveness compared to other more sophisticated analytical instruments.
ESTHER : Liu_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Liu_2022_J.Environ.Sci.Health.B__1
PubMedID: 35414329

Title : Dual Role of Strigolactone Receptor Signaling Partner in Inhibiting Substrate Hydrolysis - Sobecks_2022_J.Phys.Chem.B_126_2188
Author(s) : Sobecks BL , Chen J , Shukla D
Ref : J Phys Chem B , 126 :2188 , 2022
Abstract : Plant branch and root growth relies on metabolism of the strigolactone (SL) hormone. The interaction between the SL molecule, Oryza sativa DWARF14 (D14) SL receptor, and D3 F-box protein has been shown to play a critical role in SL perception. Previously, it was believed that D3 only interacts with the closed form of D14 to induce downstream signaling, but recent experiments indicate that D3, as well as its C-terminal helix (CTH), can interact with the open form as well to inhibit strigolactone signaling. Two hypotheses for the CTH induced inhibition are that either the CTH affects the conformational ensemble of D14 by stabilizing catalytically inactive states or the CTH interacts with SLs in a way that prevents them from entering the binding pocket. In this study, we have performed molecular dynamics (MD) simulations to assess the validity of these hypotheses. We used an apo system with only D14 and the CTH to test the active site conformational stability and a holo system with D14, the CTH, and an SL molecule to test the interaction between the SL and CTH. Our simulations show that the CTH affects both active site conformation and the ability of SLs to move into the binding pocket. In the apo system, the CTH allosterically stabilized catalytic residues into their inactive conformation. In the holo system, significant interactions between SLs and the CTH hindered the ability of SLs to enter the D14 binding pocket. These two mechanisms account for the observed decrease in SL binding to D14 and subsequent ligand hydrolysis in the presence of the CTH.
ESTHER : Sobecks_2022_J.Phys.Chem.B_126_2188
PubMedSearch : Sobecks_2022_J.Phys.Chem.B_126_2188
PubMedID: 35275626

Title : [(18)F]MAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models - Shao_2022_Acta.Pharm.Sin.B_12_308
Author(s) : Shao T , Chen Z , Rong J , Belov V , Chen J , Jeyarajan A , Deng X , Fu H , Yu Q , Rwema SH , Lin W , Papisov M , Josephson L , Chung RT , Liang SH
Ref : Acta Pharm Sin B , 12 :308 , 2022
Abstract : Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an (18)F-labeled MAGL inhibitor ([(18)F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [(18)F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl(4)) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [(18)F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [(18)F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [(18)F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [(18)F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.
ESTHER : Shao_2022_Acta.Pharm.Sin.B_12_308
PubMedSearch : Shao_2022_Acta.Pharm.Sin.B_12_308
PubMedID: 35127387

Title : Improved liver lipid catabolism and utilization in growth hormone transgenic common carp (Cyprinus carpio L.) through enhanced lipolytic and fatty acid beta-oxidation pathways - Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
Author(s) : Wu Y , Li R , Wu X , Guo W , Li Y , Song Y , Tao B , Chen J , Han D , Xie S , Wang Y , Zhu Z , Hu W
Ref : Front Endocrinol (Lausanne) , 13 :982488 , 2022
Abstract : Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid beta-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 +/- 0.32 g) and WT (initial weight 3.30 +/- 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 +/- 0.33 g) and WT (initial weight 3.27 +/- 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid beta-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.
ESTHER : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedSearch : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedID: 36171901

Title : Acetylcholinesterase Activity Monitoring and Natural Anti-neurological Disease Drug Screening via Rational Design of Deep Eutectic Solvents and CeO(2)-Co(OH)(2) Nanosheets - Liu_2022_Anal.Chem_94_5970
Author(s) : Liu Y , Wei X , Chen J , Yu YL , Wang JH , Qiu H
Ref : Analytical Chemistry , 94 :5970 , 2022
Abstract : The activity monitoring of acetylcholinesterase (AChE) and the screening of its inhibitors are critical for the diagnosis and therapy of neurological diseases. Herein, CeO(2)-Co(OH)(2) nanosheets were synthesized for the first time in a newly designed deep eutectic solvent (DES) composed of l-proline and Ce(NO(3))(3).6H(2)O, and a colorimetric assay was developed for quantitative detection of AChE and anti-neurological disease drug screening. Impressively, CeO(2)-Co(OH)(2) composites prepared in DESs have more prominent oxidase-like activity than Co(OH)(2), CeO(2), and CeO(2)-Co(OH)(2) produced in aqueous solution. The mechanism study shows that the oxygen vacancies of CeO(2)-Co(OH)(2) play a vital role in oxidase-like catalysis. Based on their excellent oxidase-like activity, the CeO(2)-Co(OH)(2) nanosheets have been successfully applied for highly sensitive and selective detection of AChE with a linear range of 0.2-20 mU/mL. This strategy can also be used for inhibitor screening. The sensor displays an excellent linear response in the range of 0.001-2 microg/mL toward an irreversible inhibitor (paraoxon-ethyl). Moreover, five alkaloids, namely, berberine hydrochloride, caffeine, camptothecin, matrine, and evodiamine, were screened by using neostigmine bromide as a control; berberine hydrochloride exhibited a good inhibitory effect on AChE with an IC(50) of 0.94 microM, while the other four had no obvious inhibitory effect. The mechanism of the different effects of alkaloids on inhibiting acetylcholinesterase activity was explored via molecular docking and kinetic simulation.
ESTHER : Liu_2022_Anal.Chem_94_5970
PubMedSearch : Liu_2022_Anal.Chem_94_5970
PubMedID: 35385268

Title : Toxic effects of glyphosate on the intestine, liver, brain of carp and on epithelioma papulosum cyprinid cells: Evidence from in vivo and in vitro research - Cao_2022_Chemosphere__134691
Author(s) : Cao X , Rao C , Cui H , Sun D , Li L , Guo S , Zhou J , Yuan R , Yang S , Chen J
Ref : Chemosphere , :134691 , 2022
Abstract : Glyphosate (GLY) is the most widely used organophosphorus herbicide in agriculture. The present study aimed to analyze the comprehensive toxicological effects of GLY on juvenile common carp and an epithelioma papulosum cyprinid (EPC) cell line. In the in vivo experiments, exposure to GLY (5 and 15 mg/L) for 30 days induced liver inflammation and oxidative damage in common carp and changed the physical barrier of the intestine. Histopathological analysis of the intestine, liver, brain, and changes in oxidative stress biomarkers provided evidence of damage and immune system responses to GLY. Moreover, an inhibitory effect of 15 mg/L GLY on acetylcholinesterase (AChE) activity was found in the brain, which may be an important reason for the significant decrease in both swimming distance and average acceleration of common carp. Cell experiments showed that 0.65 and 3.25 mg/L GLY inhibited the viability of EPCs. Furthermore, oxidative DNA damage, mitochondrial dysfunction, and reactive oxygen species (ROS) production were observed in EPC cells following GLY exposure. Taken together, this study not only highlights the negative effects of GLY on common carp but also enriches the knowledge of the cytotoxicity mechanism to further clarify the comprehensive toxicity of GLY in common carp.
ESTHER : Cao_2022_Chemosphere__134691
PubMedSearch : Cao_2022_Chemosphere__134691
PubMedID: 35489457

Title : Knockdown of hepatocyte Perilipin-3 mitigates hepatic steatosis and steatohepatitis caused by hepatocyte CGI-58 deletion in mice - Bao_2022_J.Mol.Cell.Biol__
Author(s) : Bao X , Ma X , Huang R , Chen J , Xin H , Zhou M , Li L , Tong S , Zhang Q , Shui G , Deng F , Yu L , Li MD , Zhang Z
Ref : J Molecular & Cellular Biology , : , 2022
Abstract : Comparative gene identification-58 (CGI-58), also known as alpha/beta hydrolase domain containing 5 (ABHD5), is the co-activator of adipose triglyceride lipase that hydrolyzes triglycerides stored in the cytosolic lipid droplets. Mutations in CGI-58 gene cause Chanarin-Dorfman syndrome (CDS), an autosomal recessive neutral lipid storage disease with ichthyosis. The liver pathology of CDS manifests as steatosis and steatohepatitis, which currently has no effective treatments. Perilipin-3 (Plin3) is a member of the Perilipin-ADRP-TIP47 (PAT) protein family that is essential for lipid droplet biogenesis. The objective of this study was to test a hypothesis that deletion of a major lipid droplet protein alleviates fatty liver pathogenesis caused by CGI-58 deficiency in hepatocytes. Adult CGI-58-floxed mice were injected with adeno-associated vectors simultaneously expressing the Cre recombinase and microRNA against Plin3 under the control of a hepatocyte-specific promoter, followed by high-fat diet (HFD) feeding for 6 weeks. Liver and blood samples were then collected from these animals for histological and biochemical analysis. Plin3 knockdown in hepatocytes prevented steatosis, steatohepatitis, and necroptosis caused by hepatocyte CGI-58 deficiency. Our work is the first to show that inhibiting Plin3 in hepatocytes is sufficient to mitigate hepatocyte CGI-58 deficiency-induced hepatic steatosis and steatohepatitis in mice.
ESTHER : Bao_2022_J.Mol.Cell.Biol__
PubMedSearch : Bao_2022_J.Mol.Cell.Biol__
PubMedID: 36107452

Title : Effects of Lipase and Xylanase Pretreatment on the Structure and Pulping Properties of Wheat Straw - Jia_2022_Polymers.(Basel)_14_
Author(s) : Jia Q , Chen J , Yang G , Liu K , Wang Y , Zhang K
Ref : Polymers (Basel) , 14 : , 2022
Abstract : Based on the reduction of environmental pollution, a biological enzyme assisted alkali-oxygen pulping method was explored to improve the delignification efficiency and fiber accessibility of wheat straw and improve the properties of wheat straw pulp. In this paper, lipase and xylanase were used to pretreat wheat straw and the effects of different enzyme types and enzyme dosage on the microstructure and pulp properties of wheat straw were investigated and experimented. The results showed that the lipase can remove fat and wax on the surface of wheat straw, while xylanase degraded the hemicellulose components, such as xylan, of wheat straw fiber, destroyed the structure of the lignin-carbohydrate complex, increasing lignin removal as a result and enhancing the impregnating, diffusion and penetration of alkali. Compared with wheat straw without enzyme pretreatment, the skeleton of wheat straw pretreated by enzyme became looser, the internal cavity appeared and the wall cavity became thin and transparent. The fines decreased obviously and the length of fibers increased. After combined pretreatment with lipase (15 U.g(-1)) and xylanase (15 U.g(-1)), the pulping performance of wheat straw was improved and the tensile index (97.37 N.m.g(-1)), brightness (40.9% ISO) and yield (58.10%) of the pulp increased by 12.9%, 19.9% and 9.9%, respectively. It can be seen that enzyme pretreatment is a green and effective approach to improving the alkali-oxygen pulping performance of wheat straw.
ESTHER : Jia_2022_Polymers.(Basel)_14_
PubMedSearch : Jia_2022_Polymers.(Basel)_14_
PubMedID: 36501524

Title : Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination - Wang_2022_Curr.Drug.Metab__
Author(s) : Wang D , Zhao T , Zhao S , Chen J , Dou T , Ge G , Wang C , Sun H , Liu K , Meng Q , Wu J
Ref : Curr Drug Metab , : , 2022
Abstract : BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2.
ESTHER : Wang_2022_Curr.Drug.Metab__
PubMedSearch : Wang_2022_Curr.Drug.Metab__
PubMedID: 35114918

Title : Lipase induced highly hydrophobic nanofibrillated cellulose film for strain sensor application - Wang_2022_Carbohydr.Polym_284_119193
Author(s) : Wang Y , Wang Q , Liu S , Ji X , Yang G , Chen J
Ref : Carbohydr Polym , 284 :119193 , 2022
Abstract : An environmental-friendly lipase induced highly hydrophobic NFC film was fabricated through lipase induced dimethyl adipate (DA) esterification followed by silver nanowires (AgNWs) coating for strain sensor application. Due to the lipase activation, the substitution degree (DS(NMR)) of 0.18 was achieved, which was three times higher than that of the control sample (without lipase treatment of NFC-DA). As a result, the water contact angle (WCA) of lipase induced adipated-NFC film was reached to 105 +/- 3 degrees from 50 +/- 2.3 degrees of NFC-DA. In addition, the cellulose structure and performance were well maintained after lipase induced esterification, confirmed by AFM, SEM, TG/DTG, and XRD analysis. After AgNWs coating and annealing, the hydrophobic NFC film-based strain sensor exhibited excellent sensitivity towards human motion, such as finger/wrist movement in real-time, even under wet conditions. Overall, a highly hydrophobic NFC film-based strain sensor was fabricated, which has promising application in wearable devices for human motion monitoring.
ESTHER : Wang_2022_Carbohydr.Polym_284_119193
PubMedSearch : Wang_2022_Carbohydr.Polym_284_119193
PubMedID: 35287910

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

Title : FAM135B sustains the reservoir of Tip60-ATM assembly to promote DNA damage response - Zhang_2022_Clin.Transl.Med_12_e945
Author(s) : Zhang K , Wu Q , Liu W , Wang Y , Zhao L , Chen J , Liu H , Liu S , Li J , Zhang W , Zhan Q
Ref : Clin Transl Med , 12 :e945 , 2022
Abstract : BACKGROUND: Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat-interactive protein 60-kDa/ataxia-telangiectasia-mutated (TIP60/ATM) axis-mediated DNA damage response (DDR) is vital for maintaining genomic integrity. METHODS: Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co-immunoprecipitation, proximity ligation assay and GST pull-down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. RESULTS: We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of gammaH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non-homologous end-joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre-existing TIP60-ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre-assembled TIP60-ATM complex participates in DDR. CONCLUSIONS: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60-ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment.
ESTHER : Zhang_2022_Clin.Transl.Med_12_e945
PubMedSearch : Zhang_2022_Clin.Transl.Med_12_e945
PubMedID: 35979619
Gene_locus related to this paper: human-FAM135B

Title : Insights into the microbial degradation and catalytic mechanisms of chlorpyrifos - Huang_2021_Environ.Res_194_110660
Author(s) : Huang Y , Zhang W , Pang S , Chen J , Bhatt P , Mishra S , Chen S
Ref : Environ Research , 194 :110660 , 2021
Abstract : Chlorpyrifos is extensively used worldwide as an insecticide to control various insect pests. Long-term and irregular applications of chlorpyrifos have resulted in large-scale soil, groundwater, sediment, and air pollution. Numerous studies have shown that chlorpyrifos and its major intermediate metabolite 3,5,6-trichloropyridinol (TCP) accumulate in non-target organisms through biomagnification and have a strong toxic effect on non-target organisms, including human beings. Bioremediation based on microbial metabolism is considered an eco-friendly and efficient strategy to remove chlorpyrifos residues. To date, a variety of bacterial and fungal species have been isolated and characterized for the biodegradation of chlorpyrifos and TCP. The metabolites and degradation pathways of chlorpyrifos have been investigated. In addition, the chlorpyrifos-degrading enzymes and functional genes in microbes have been reported. Hydrolases can catalyze the first step in ester-bond hydrolysis, and this initial regulatory metabolic reaction plays a key role in the degradation of chlorpyrifos. Previous studies have shown that the active site of hydrolase contains serine residues, which can initiate a catalytic reaction by nucleophilic attack on the P-atom of chlorpyrifos. However, few reviews have focused on the microbial degradation and catalytic mechanisms of chlorpyrifos. Therefore, this review discusses the deep understanding of chlorpyrifos degradation mechanisms with microbial strains, metabolic pathways, catalytic mechanisms, and their genetic basis in bioremediation.
ESTHER : Huang_2021_Environ.Res_194_110660
PubMedSearch : Huang_2021_Environ.Res_194_110660
PubMedID: 33387540

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

Title : Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study - Mu_2021_Neurol.Res.Int_2021_6009342
Author(s) : Mu L , Chen J , Li J , Sobotka S , Nyirenda T
Ref : Neurol Res Int , 2021 :6009342 , 2021
Abstract : BACKGROUND: Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause "foot drop," a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). METHODS: As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. RESULTS: The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. CONCLUSION: NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.
ESTHER : Mu_2021_Neurol.Res.Int_2021_6009342
PubMedSearch : Mu_2021_Neurol.Res.Int_2021_6009342
PubMedID: 34925918

Title : The Role of Clt1-Regulated Xylan Metabolism in Melanin and Toxin Formation for the Pathogenicity of Curvularia lunata in Maize - Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
Author(s) : Gao J , Chen J
Ref : Mol Plant Microbe Interact , :MPMI08200235R , 2021
Abstract : We previously reported that the BTB (brica-brac, tramtrack, and broad) domain-containing protein Clt1 regulates melanin and toxin synthesis, conidiation, and pathogenicity in Curvularia lunata, but the interacting proteins and regulative mechanism of Clt1 are unclear. In this research, we identified two proteins, which respectively correspond to xylanase (Clxyn24) and acetyl xylan esterase (Claxe43) from C. lunata, that were regulated by Clt1. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation assays were conducted to verify the interaction of Clt1 with full-length Clxyn24 and Claxe43. Furthermore, the Y2H assay revealed that Clt1 physically interacted with Clxyn24 and Claxe43 through its BTB domain to degrade xylan, which was used as a carbon source for C. lunata growth. The utilization of xylan provides acetyl-CoA for the synthesis of melanin and toxin as well as energy and other intermediate metabolites for conidiation. Furthermore, transcriptome analysis revealed that PKS18 and its 13 flanking genes found clustered in a region spanning 57.89 kb on scaffold 9 of the C. lunata CX-3 genome were down-regulated in toxin production-deficient mutant T806, and this cluster is possibly responsible for toxin biosynthesis of C. lunata. [Formula: see text] Copyright 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
ESTHER : Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
PubMedSearch : Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
PubMedID: 33417477

Title : A methyl esterase 1 (PvMES1) promotes the salicylic acid pathway and enhances Fusarium wilt resistance in common beans - Xue_2021_Theor.Appl.Genet__
Author(s) : Xue R , Feng M , Chen J , Ge W , Blair MW
Ref : Theor Appl Genet , : , 2021
Abstract : Methyl esterase (MES), PvMES1, contributes to the defense response toward Fusarium wilt in common beans by regulating the salicylic acid (SA) mediated signaling pathway from phenylpropanoid synthesis and sugar metabolism as well as others. Common bean (Phaseolus vulgaris L.) is an important food legume. Fusarium wilt caused by Fusarium oxysporum f. sp. phaseoli is one of the most serious soil-borne diseases of common bean found throughout the world and affects the yield and quality of the crop. Few sources of Fusarium wilt resistance exist in legumes and most are of quantitative inheritance. In this study, we have identified a methyl esterase (MES), PvMES1, that contributes to plant defense response by regulating the salicylic acid (SA) mediated signaling pathway in response to Fusarium wilt in common beans. The result showed the role of PvMES1 in regulating SA levels in common bean and thus the SA signaling pathway and defense response mechanism in the plant. Overexpression of the PvMES1 gene enhanced Fusarium wilt resistance; while silencing of the gene caused susceptibility to the diseases. RNA-seq analysis with these transiently modified plants showed that genes related to SA level changes included the following gene ontologies: (a) phenylpropanoid synthesis; (b) sugar metabolism; and (c) interaction between host and pathogen as well as others. These key signal elements activated the defense response pathway in common bean to Fusarium wilt. Collectively, our findings indicate that PvMES1 plays a pivotal role in regulating SA biosynthesis and signaling, and increasing Fusarium wilt resistance in common bean, thus providing novel insight into the practical applications of both SA and MES genes and pathways they contribute to for developing elite crop varieties with enhanced broad-spectrum resistance to this critical disease.
ESTHER : Xue_2021_Theor.Appl.Genet__
PubMedSearch : Xue_2021_Theor.Appl.Genet__
PubMedID: 34128089
Gene_locus related to this paper: phavu-v7cf29

Title : Long-term exposure to polyethylene microplastics and glyphosate interferes with the behavior, intestinal microbial homeostasis, and metabolites of the common carp (Cyprinus carpio L.) - Chen_2021_Sci.Total.Environ__152681
Author(s) : Chen J , Rao C , Yuan R , Sun D , Guo S , Li L , Yang S , Qian D , Lu R , Cao X
Ref : Sci Total Environ , :152681 , 2021
Abstract : Polyethylene microplastics (PE-MPs) and glyphosate (GLY) occur widely and have toxic characteristics, resulting in increased research interest. In this study, common carp were used to assess the individual and combined toxicity of PE-MPs (0, 1.5, or 4.5 mg/L) and GLY (0, 5, or 15 mg/L) on the brain-gut axis. After 60 days of exposure, the developmental toxicity, blood-brain barrier (BBB), locomotor behavior, intestinal barrier (physical barrier, chemical barrier, microbial barrier), and intestinal content metabolism of common carp were evaluated. Results showed that 15 mg/L of GLY exposure significantly reduced the mRNA expression of tight-junction genes (occludin, claudin-2, and ZO-1) in the brain, and acetylcholinesterase (AChE) activity was clearly inhibited by high concentrations of GLY. However, different concentrations of PE-MPs had no significant effect on the activity of AChE. Furthermore, the free-swimming behavior of common carp was distinctly inhibited by treatment with a combination of 15 mg/L GLY and 4.5 mg/L PE-MPs. Histological studies indicated that PE-MPs alone and in combination with GLY could disrupt the physical and chemical intestinal barriers of common carp. Additionally, the abundance and diversity of gut microbiota in common carp were significantly changed when exposed to a combination of PE-MPs and GLY. Metabolomics further revealed that PE-MPs combined with GLY triggered metabolic changes and that differential metabolites were related to amino acid and lipid metabolism. These findings illustrate that exposure to PE-MPs or GLY alone is toxic to fish and results in physiological changes to the brain-gut axis. This work offers a robust analysis to understand the mechanisms underlying GLY and MP-induced aquatic toxicity.
ESTHER : Chen_2021_Sci.Total.Environ__152681
PubMedSearch : Chen_2021_Sci.Total.Environ__152681
PubMedID: 34973326

Title : Synergistic enhancement of the emergency treatment effect of organophosphate poisoning by a supramolecular strategy - Chen_2021_Chem.Sci_12_5202
Author(s) : Chen J , Zhang Y , Chai Y , Meng Z , Chen L , Quan D , Wang Y , Meng Q , Li C
Ref : Chem Sci , 12 :5202 , 2021
Abstract : Poisoning by organophosphorus agents (OPs) is a serious public health issue across the world. These compounds irreversibly inhibit acetylcholinesterase (AChE), resulting in the accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. A supramolecular detoxification system (SDS) has been designed with a view to deliver pyridine-2-aldoxime methochloride (PAM) with a synergistic inhibition effect on the ACh-induced hyperstimulation through host-guest encapsulation. NMR and fluorescence titration served to confirm the complexation between carboxylatopillar[6]arene (CP6A) and PAM as well as ACh with robust affinities. Patch-clamp studies proved that CP6A could exert an inhibition effect on the ACh-induced hyperstimulation of ACh receptors. Support for the feasibility of this strategy came from fluorescence imaging results. In vivo studies revealed that complexation by CP6A serves to increase the AChE reactivation efficiency of PAM. The formation of the PAM/CP6A complex contributed to enhance in a statistically significant way the ability of PAM not only to relieve symptoms of seizures but also to improve the survival ratio in paraoxon-poisoned model rats. These favorable findings are attributed to synergistic effects that PAM reactivates AChE to hydrolyze ACh and excess ACh is encapsulated in the cavity of CP6A to relieve cholinergic crisis symptoms.
ESTHER : Chen_2021_Chem.Sci_12_5202
PubMedSearch : Chen_2021_Chem.Sci_12_5202
PubMedID: 34163757

Title : Trelagliptin ameliorates IL-1beta-impaired chondrocyte function via the AMPK\/SOX-9 pathway - Liu_2021_Mol.Immunol_140_70
Author(s) : Liu J , Zuo Q , Li Z , Chen J , Liu F
Ref : Mol Immunol , 140 :70 , 2021
Abstract : Chondrocyte dysregulation plays a critical role in the development of osteoarthritis (OA). The pro-inflammatory cytokine interleukin-1beta (IL-1beta) activates chondrocytes and degrades the structural extracellular matrix (ECM). These events are the important mechanism of OA. Trelagliptin, a selective inhibitor of dipeptidyl Peptidase 4 (DPP-4) used for the treatment of type 2 diabetes mellitus (T2DM), has displayed a wide range of anti-inflammatory capacities. The effects of Trelagliptin in OA and chondrocytes have not been tested before. Here, we show that Trelagliptin mitigates IL-1beta-induced production of inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in human chondrocytes. Trelagliptin ameliorates IL-1beta-induced oxidative stress by reducing the generation of reactive oxygen species (ROS). Particularly, the presence of Trelagliptin prevents IL-1beta-induced reduction of Acan genes and the protein Aggrecan. Moreover, we show that Trelagliptin restores IL-1beta-induced reduction of SOX-9 and that the knockdown of SOX-9 abolishes the protective effects of Trelagliptin. Mechanistically, we demonstrate that AMPK is required for the amelioration of Trelagliptin on SOX-9- reduction by IL-1beta. Collectively, our study demonstrates that the DPP-4 inhibitor Trelagliptin has a protective effect on chondrocyte function. Trelagliptin may have the potential role to antagonize chondrocyte-derived inflammation in OA.
ESTHER : Liu_2021_Mol.Immunol_140_70
PubMedSearch : Liu_2021_Mol.Immunol_140_70
PubMedID: 34666245

Title : High-efficiency degradation of phthalic acid esters (PAEs) by Pseudarthrobacter defluvii E5: Performance, degradative pathway, and key genes - Chen_2021_Sci.Total.Environ_794_148719
Author(s) : Chen F , Chen Y , Chen C , Feng L , Dong Y , Chen J , Lan J , Hou H
Ref : Sci Total Environ , 794 :148719 , 2021
Abstract : Phthalic acid esters (PAEs) are a class of biologically accumulated carcinogenic and teratogenic toxic chemicals that exist widely in the environment. This study, Pseudarthrobacter defluvii E5 was isolated from agricultural soils and showed efficient PAEs-degradation and -mineralization abilities for five PAEs, and encouraging PAEs tolerance and bioavailable range for dibutyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) (0.25-1200 mg/L). The complete catalytic system in E5 genome enables PAEs to be degraded into monoester, phthalate (PA) and Protocatechuic acid (PCA), which eventually enter the tricarboxylic acid cycle (TCA cycle). The preferred PAEs-metabolic pathway in soil by E5 is the metabolism induced by enzymes encoded by pehA, mehpH, pht Operon and pca Operon. For the first time, two para-homologous pht gene clusters were found to coexist on the plasmid and contribute to PAEs degradation. Further study showed that P. defluvii E5 has a broad application prospect in microplastics-contaminated environments.
ESTHER : Chen_2021_Sci.Total.Environ_794_148719
PubMedSearch : Chen_2021_Sci.Total.Environ_794_148719
PubMedID: 34214821

Title : Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice - Yang_2021_Int.J.Mol.Sci_22_
Author(s) : Yang Y , Xu X , Wu H , Yang J , Chen J , Morisseau C , Hammock BD , Bettaieb A , Zhao L
Ref : Int J Mol Sci , 22 : , 2021
Abstract : 17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1alpha expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFkappaB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.
ESTHER : Yang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Yang_2021_Int.J.Mol.Sci_22_
PubMedID: 34361032

Title : Nitrogen-Doped Graphdiyne as a Robust Electrochemical Biosensing Platform for Ultrasensitive Detection of Environmental Pollutants - Niu_2021_Anal.Chem__
Author(s) : Niu K , Gao J , Wu L , Lu X , Chen J
Ref : Analytical Chemistry , : , 2021
Abstract : Owing to its unique chemical structure, natural pores, high structure defects, good surface hydrophilicity and biocompatibility, and favorable electrical conductivity, nitrogen-doped graphdiyne (NGDY) has been attracting attention in the application of electrochemical sensing. Taking advantage of these fascinating electrochemical properties, for the first time, two types of electrochemical enzymatic biosensors were fabricated for the respective detection of organophosphorus pesticides (OPs) and phenols based on the immobilization of acetylcholinesterase or tyrosinase with NGDY. Results revealed that the sensitivities of the NGDY-based enzymatic biosensors were almost twice higher than that of the matching biosensor in the absence of NGDY, proving that NGDY plays a vital role in immobilizing the enzymes and improving the performance of the fabricated biosensors. The effects of nitrogen doping on improving the biosensing performance were studied in depth. Graphitic N atoms can enhance the electrical conductivity, while imine N and pyridinic N can help to adsorb and accumulate the substance molecules to the electrode surface, all of which contribute to the significantly improved performance. Furthermore, these two types of biosensors also demonstrated excellent reproducibility, high stability, and good recovery rate in real environmental samples, which showed a valuable way for the rapid detection of OPs and phenols in the environment. With these excellent performances, it is strongly anticipated that NGDY has tremendous potential to be applied to many other biomedical and environmental fields.
ESTHER : Niu_2021_Anal.Chem__
PubMedSearch : Niu_2021_Anal.Chem__
PubMedID: 34110153

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

Title : Characterization of a carboxylesterase with hyper-thermostability and alkali-stability from Streptomyces lividans TK24 - Chang_2021_Extremophiles__
Author(s) : Chang X , Wu S , Chen J , Xiong S , Wang P , Shi X , Wang A , Wang B
Ref : Extremophiles , : , 2021
Abstract : A gene (estA', 804 bp) from Streptomyces lividans TK24 was artificially synthesized and successfully overexpressed as a 6His-tagged fusion protein in Escherichia coli. It encoded a carboxylesterase (EstA) that composed of 267 amino acids with a predicted molecular weight of 28.56 kDa. Multiple sequence alignment indicated that EstA has typical characteristics of esterases, including a catalytic triad (Ser93-Asp194-His224) and a conserved pentapeptide motif (Gly91-Leu92-Ser93-Met94-Gly95). Simultaneously, phylogenetic analysis indicated that EstA belongs to family VI. Biochemical characterization displayed its optimum enzyme activity was at 55 and pH 8.5. Additionally, EstA exhibited higher activity towards short carbon substrates and showed the outstanding catalytic efficiency for pNPA2 with k(cat)/K(m) of 2296.14 +/- 10.35 s(-1) mM(-1). Notably, EstA has hyper-thermostability and good alkali stability. The activity of EstA did not change obviously when incubated at 50 and 100 for 337 and 1 h, independently. Besides, by incubating at 100 for 6 h, EstA remained about half of its initial activity. Moreover, EstA showed stability at pH ranging from 8.0 to 11.0, and about 90% residual enzyme activity was reserved by being treated at pH 8.0 or 9.0 for 80 h, especially. Such multiple features prepare EstA for a potential candidate in the field of biological catalysis of some industrial applications under harsh conditions.
ESTHER : Chang_2021_Extremophiles__
PubMedSearch : Chang_2021_Extremophiles__
PubMedID: 33515353
Gene_locus related to this paper: strco-SCO2123

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

Title : Screening and identification of acetylcholinesterase inhibitors from Terminalia chebula fruits by immobilized enzyme on cellulose filter paper coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and molecular docking - Li_2021_J.Chromatogr.A_1663_462784
Author(s) : Li YJ , He FQ , Zhao HH , Li Y , Chen J
Ref : Journal of Chromatography A , 1663 :462784 , 2021
Abstract : With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-beta-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC(50) values of 0.43 +/- 0.03, 0.46 +/- 0.02, 0.50 +/- 0.03 and 0.51 +/- 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs.
ESTHER : Li_2021_J.Chromatogr.A_1663_462784
PubMedSearch : Li_2021_J.Chromatogr.A_1663_462784
PubMedID: 34974370

Title : Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 - Zhao_2021_Curr.Drug.Metab__
Author(s) : Zhao T , Wang D , Shan Z , Chen J , Dou T , Ge G , Wang C , Meng Q , Sun H , Liu K , Wu J
Ref : Curr Drug Metab , : , 2021
Abstract : BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
ESTHER : Zhao_2021_Curr.Drug.Metab__
PubMedSearch : Zhao_2021_Curr.Drug.Metab__
PubMedID: 33568030

Title : Reproductive stimulation and energy allocation variation of BDE-47 and its derivatives on Daphnia magna - Liu_2021_Chemosphere_288_132492
Author(s) : Liu Y , Chen M , Ma Y , Guo R , Yan Z , Chen J
Ref : Chemosphere , 288 :132492 , 2021
Abstract : As endocrine disrupting chemical, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is widely distributed in water environment with a high detection rate. 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE-47) are two main derivatives of BDE-47. To explore the aquatic risk of BDE-47 and its derivatives, the effects of them and their ternary mixture on the reproduction, growth, energy allocation, and neurological and antioxidant responses of Daphnia magna were monitoring during different exposure periods, i.e., daphnids exposed to compounds for 21 days or pre-exposed to compounds for 14 days and then recovered 7 days in clean water. In general, in 21-day test, reproductive parameters of exposed daphnids were significantly stimulated, and the growth and enzymatic activities of super oxidase dimutase (SOD), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) were significantly depressed by the single- or mixture compounds. In (14 + 7)-day test, the levels of body length, number of living offspring per female and the enzyme activities recovered to some degree. However, after 7 days of recovery in pollution free medium, the reproductive parameters and enzymatic activities of D. magna were unable to restore control values. These results showed that D. magna has a tendency that the energy allocated to reproduction was greater than that to grow after exposure. The energy distribution of D. magna occurred autonomously after being exposed, which can make it better adapt to environmental changes. Moreover, based on the behavioral and enzymology indicators of D. magna, the spider chart's application in the characteristic analysis of function indicators of D. magna implied that SOD, GPx and AChE could become sensitive biomarkers for different exposure periods. Those findings enable us to better understand BDE-47 and metabolites, and are conducive to better take measures to solve the pressure it brings.
ESTHER : Liu_2021_Chemosphere_288_132492
PubMedSearch : Liu_2021_Chemosphere_288_132492
PubMedID: 34626654

Title : Aggregation-induced emission luminogen@manganese dioxide core-shell nanomaterial-based paper analytical device for equipment-free and visual detection of organophosphorus pesticide - Chen_2021_J.Hazard.Mater_413_125306
Author(s) : Chen J , Chen X , Wang P , Liu S , Chi Z
Ref : J Hazard Mater , 413 :125306 , 2021
Abstract : Organophosphorus pesticide (OP) residues have gathered considerable attention because of their significant threat to society development and healthy life. Developing a sensitive and practical OPs sensor is highly urgent, whereas remains a huge challenge. To this end, we fabricated a high-performance fluorescence paper analytical device (PAD) for apparatus-free and visual sensing of OPs based on aggregation-induced emission (AIE) luminogen's bright emission in aggregated state, unique response of MnO(2) to thiol compounds, and difference of MnO(2) and Mn(2+) in quenching fluorescence. AIE nanoparticles PTDNPs-0.10 and MnO(2) respectively acted as core and shell to prepare PTDNPs@MnO(2), which possessed high stability and were dripped on cellulose paper's surface to fabricate AIE-PAD. The sensing mechanism is that OPs-treated acetylcholinesterase (AChE) prevents the formation of thiocholine, thereby minimizing the reduction of MnO(2) into Mn(2+) and changing the output signal. As a result, equipment-free and visual sensing of OPs was acquired with limit of detection of 1.60 ng/mL. This work justifies the feasibility of applying core-shell material to develop high-performance sensor and substituting complex/expensive solution-phase sensor with PAD, providing a new avenue to bring OPs analysis out of the lab and into the world.
ESTHER : Chen_2021_J.Hazard.Mater_413_125306
PubMedSearch : Chen_2021_J.Hazard.Mater_413_125306
PubMedID: 33588332

Title : Development of a highly-specific (18)F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping - Chen_2021_Acta.Pharm.Sin.B_11_1686
Author(s) : Chen Z , Mori W , Rong J , Schafroth MA , Shao T , Van RS , Ogasawara D , Yamasaki T , Hiraishi A , Hatori A , Chen J , Zhang Y , Hu K , Fujinaga M , Sun J , Yu Q , Collier TL , Shao Y , Cravatt BF , Josephson L , Zhang MR , Liang SH
Ref : Acta Pharm Sin B , 11 :1686 , 2021
Abstract : As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile S(N)Ar reaction to form 2-[(18)F]fluoropyridine scaffold. Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [(18)F]14 (also named as [(18)F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent (18)F-labeled MAGL PET tracers.
ESTHER : Chen_2021_Acta.Pharm.Sin.B_11_1686
PubMedSearch : Chen_2021_Acta.Pharm.Sin.B_11_1686
PubMedID: 34221877
Gene_locus related to this paper: human-MGLL

Title : The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure - Wang_2021_Ecotoxicol.Environ.Saf_228_112959
Author(s) : Wang S , Zhao Q , Li G , Wang M , Liu H , Yu X , Chen J , Li P , Dong L , Zhou G , Cui Y , Liu L , Wang A
Ref : Ecotoxicology & Environmental Safety , 228 :112959 , 2021
Abstract : Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_228_112959
PubMedID: 34808511

Title : Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression - He_2021_Cell.Death.Dis_12_992
Author(s) : He W , Huang J , Liu Y , Xie C , Zhang K , Zhu X , Chen J , Huang H
Ref : Cell Death Dis , 12 :992 , 2021
Abstract : Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
ESTHER : He_2021_Cell.Death.Dis_12_992
PubMedSearch : He_2021_Cell.Death.Dis_12_992
PubMedID: 34689162

Title : Identification and Biochemical Characterization of a Novel Hormone-Sensitive Lipase Family Esterase Est19 from the Antarctic Bacterium Pseudomonas sp. E2-15 - Liu_2021_Biomolecules_11_1552
Author(s) : Liu X , Zhou M , Xing S , Wu T , He H , Bielicki JK , Chen J
Ref : Biomolecules , 11 :1552 , 2021
Abstract : Esterases represent an important class of enzymes with a wide variety of industrial applications. A novel hormone-sensitive lipase (HSL) family esterase, Est19, from the Antarctic bacterium Pseudomonas sp. E2-15 is identified, cloned, and expressed. The enzyme possesses a GESAG motif containing an active serine (S) located within a highly conserved catalytic triad of Ser155, Asp253, and His282 residues. The catalytic efficiency (kcat/Km) of Est19 for the pNPC6 substrate is 148.68 s-1 mM-1 at 40 C. Replacing Glu154 juxtaposed to the critical catalytic serine with Asp (E154->D substitution) reduced the -activity and catalytic efficiency of the enzyme two-fold, with little change in the substrate affinity. The wild-type enzyme retained near complete activity over a temperature range of 10-60 C, while ~50% of its activity was retained at 0 C. A phylogenetic analysis suggested that Est19 and its homologs may represent a new subfamily of HSL. The thermal stability and stereo-specificity suggest that the Est19 esterase may be useful for cold and chiral catalyses.
ESTHER : Liu_2021_Biomolecules_11_1552
PubMedSearch : Liu_2021_Biomolecules_11_1552
PubMedID: 34827549
Gene_locus related to this paper: psesp-MT761613

Title : A GRN Autocrine-Dependent FAM135B\/AKT\/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression - Dong_2021_Cancer.Res_81_910
Author(s) : Dong D , Zhang W , Xiao W , Wu Q , Cao Y , Gao X , Huang L , Wang Y , Chen J , Wang W , Zhan Q
Ref : Cancer Research , 81 :910 , 2021
Abstract : Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B (FAM135B) was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo, likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. Patients with ESCC with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for patients with ESCC. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. In addition, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for patients with ESCC. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC. SIGNIFICANCE: These findings investigate the mechanisms of FAM135B in promoting ESCC progression and suggest new potential prognostic biomarkers and therapeutic targets in patients with ESCC.
ESTHER : Dong_2021_Cancer.Res_81_910
PubMedSearch : Dong_2021_Cancer.Res_81_910
PubMedID: 33323378
Gene_locus related to this paper: human-FAM135B

Title : Novel amide derivatives containing an imidazo[1,2-a]pyridine moiety: Design, synthesis as potential nematicidal and antibacterial agents - Wei_2021_Pestic.Biochem.Physiol_175_104857
Author(s) : Wei C , Huang J , Luo Y , Wang S , Wu S , Xing Z , Chen J
Ref : Pestic Biochem Physiol , 175 :104857 , 2021
Abstract : To discover new nematicides, a series of novel amide derivatives containing an imidazo[1,2-a]pyridine moeity were designed and synthesized. Among the title compounds, compounds 3 and 27 exhibited good nematicidal activities against Aphelenchoides besseyi (rice white-tip nematode), with LC(50) values against of 27.3 and 35.9 mg/L, respectively, which were superior to that of fosthiazate (45.4 mg/L). Meanwhile, the LC(50) value of compound 27 against Caenorhabditis elegans was 5.7 mg/L, which was superior to that of fosthiazate (77.2 mg/L). Compound 27 not only binds well to acetylcholinesterase (AChE) of nematodes, but also has a good inhibitory activity against AChE. Thus, AChE may be a potential target of compound 27 against nematodes. Unexpectedly, compound 28 exhibited excellent antibacterial activities with EC(50) values of 1.2 and 3.1 mg/L against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, which were superior to those of bismerthiazol (68.6 and 77.1 mg/L) and thiodiazole copper (80.8 and 96.6 mg/L). The curative and protective activities of compound 28 against bacterial leaf blight were 37.0% and 36.8% at 50 mg/L, respectively, which were higher than those of thiodiazole copper (16.1% and 15.5%). In addition, compound 28 may inhibit the growth of Xoo by affecting the production of cell membranes and extracellular polysaccharides. Amide derivatives containing an imidazo[1,2-a]pyridine moeity can be used as good lead-structures to discover new nematicidal and antibacterial agents in the future.
ESTHER : Wei_2021_Pestic.Biochem.Physiol_175_104857
PubMedSearch : Wei_2021_Pestic.Biochem.Physiol_175_104857
PubMedID: 33993975

Title : PubChem in 2021: new data content and improved web interfaces - Kim_2021_Nucleic.Acids.Res_49_D1388
Author(s) : Kim S , Chen J , Cheng T , Gindulyte A , He J , He S , Li Q , Shoemaker BA , Thiessen PA , Yu B , Zaslavsky L , Zhang J , Bolton EE
Ref : Nucleic Acids Research , 49 :D1388 , 2021
Abstract : PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
ESTHER : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedSearch : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedID: 33151290

Title : Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK\/HO-1 pathway - Wu_2020_Biochem.Biophys.Res.Commun__
Author(s) : Wu J , Zhao Y , Fan Z , Chen Q , Chen J , Sun Y , Jiang X , Xiao Q
Ref : Biochemical & Biophysical Research Communications , : , 2020
Abstract : Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation.
ESTHER : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedSearch : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedID: 32001002

Title : Re-pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population - Chan_2020_Australas.J.Dermatol_61_e417
Author(s) : Chan LKM , Braidy N , Ng W , Xu YH , Chen J , McDonald R , Chan DKY
Ref : Australas J Dermatol , 61 :e417 , 2020
Abstract : Eighty consecutive Chinese patients diagnosed with Alzheimer disease were assessed for darkening of grey hair. Of the 62 eligible patients (mean age = 79.3 +/- 7.9 years; male: female = 1:1.48), 24/62 (38.7%, 95%CI: 26.6 - 51.9) reported hair darkening after prolonged usage of cholinesterase inhibitor for at least 6 months. Of the 24 patients with hair darkening, 17 (70.9%) experienced hair darkening in the occipital region, 3 (12.5%) in the parietal region, 2 (8.3%) patients in the frontal region and 2 (8.3%) patients experienced hair darkening in multiple regions. Analysis of melanin concentration showed no significant difference between darkened hair of patients after prolonged drug use and the dark hair of controls (P = 0.381).
ESTHER : Chan_2020_Australas.J.Dermatol_61_e417
PubMedSearch : Chan_2020_Australas.J.Dermatol_61_e417
PubMedID: 32597493

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

Title : Screening acetylcholinesterase inhibitors from traditional Chinese medicines by paper-immobilized enzyme combined with capillary electrophoresis analysis - Zhao_2020_J.Pharm.Biomed.Anal_190_113547
Author(s) : Zhao HH , Liu YQ , Chen J
Ref : J Pharm Biomed Anal , 190 :113547 , 2020
Abstract : Discovering acetylcholinesterase (AChE) inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease. In this work, a simple strategy was developed for screening AChE inhibitors from traditional Chinese medicines (TCMs) by capillary electrophoresis (CE) analysis combined with enzymatic assay, in which immobilized AChE was employed. For AChE immobilization, cellulose filter paper (CFP) was used as the carrier material and physically coated with chitosan owing to moderate viscosity of chitosan to be introduced into amino groups, and then AChE was covalently bonded to the amino-functionalized CFP through a Schiff base reaction using glutaraldehyde (GA) as a cross-linking agent. The CFP-immobilized AChE exhibited enhanced endurance to pH and temperature, improved storage stability, excellent repeatability and reusability. More remarkably, CFP-immobilized AChE can be instantly separated from enzyme reaction mixture thus greatly simplifying the operational process. For immobilized AChE, the Michaelis-Menten constant, inhibition constant and IC(50) were determined using huperzine A as a model inhibitor. Finally, CFP-immobilized AChE was applied to inhibitor screening from 17 TCMs, among which Chebulae Fructus (ripe fruits of Terminalia chebula) exhibited the strongest inhibitory effect on AChE. The positive results indicated that such a screening strategy may open up a new avenue to discover active components from TCMs.
ESTHER : Zhao_2020_J.Pharm.Biomed.Anal_190_113547
PubMedSearch : Zhao_2020_J.Pharm.Biomed.Anal_190_113547
PubMedID: 32866747

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

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

Title : Positive correlation between human exposure to organophosphate esters and gastrointestinal cancer in patients from Wuhan, China - Li_2020_Ecotoxicol.Environ.Saf_196_110548
Author(s) : Li Y , Fu Y , Hu K , Zhang Y , Chen J , Zhang S , Zhang B , Liu Y
Ref : Ecotoxicology & Environmental Safety , 196 :110548 , 2020
Abstract : As kinds of endocrine disruptors, organophosphate esters (OPEs) pollution in the environment had received increasing attention recently. Food and water intake were two important exposure pathways for OPEs. However, the studies about the potential association between OPEs and gastrointestinal cancer were limited. This study investigated the possible association between OPEs and gastrointestinal cancer. All cancer patients were diagnosed with gastrointestinal cancer from a Grade 3 A hospital in Wuhan, China, while the control group was non-cancer healthy persons. The results showed that 6 OPEs were found in the control samples, while 8 in the samples from patients with gastrointestinal cancer. The detection frequencies of OPEs in gastrointestinal cancer patients were significantly higher than those in the control group (p < 0.05 or p < 0.01), except for triethyl phosphate (TEP) and tris (methylphenyl) phosphate (TMPP) in the gastric cancer group. The concentrations of OPEs in the control group were significantly lower than those in the gastric cancer group and colorectal cancer group (p < 0.01). In the control group and gastrointestinal cancer group, TEP was the dominant pollutant. Correlation analysis found that concentrations of TEP, tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), TMPP, tris(2-ethylhexyl) phosphate (TEHP), and 2-ethylhexyl diphenyl phosphate (EHDPP) were associated with gastric cancer (p < 0.01), and concentrations of TEP, TCIPP, TPHP, TMPP and TEHP were associated with colorectal cancer (p < 0.01). A cluster analysis divided the 34 patients with gastric cancer and 40 patients with colorectal cancer in four groups. The results showed that the elderly male patients with gastric cancer were more sensitive to the exposure of EHDPP, while the TEP exposure was more sensitive to the relatively young gastrointestinal cancer patients. These findings indicated that OPEs might play a role in developing gastrointestinal cancer.
ESTHER : Li_2020_Ecotoxicol.Environ.Saf_196_110548
PubMedSearch : Li_2020_Ecotoxicol.Environ.Saf_196_110548
PubMedID: 32278140

Title : Genome-Wide Identification, Evolution, and Expression of GDSL-Type Esterase\/Lipase Gene Family in Soybean - Su_2020_Front.Plant.Sci_11_726
Author(s) : Su HG , Zhang XH , Wang TT , Wei WL , Wang YX , Chen J , Zhou YB , Chen M , Ma YZ , Xu ZS , Min DH
Ref : Front Plant Sci , 11 :726 , 2020
Abstract : GDSL-type esterase/lipase proteins (GELPs) belong to the SGNH hydrolase superfamily and contain a conserved GDSL motif at their N-terminus. GELPs are widely distributed in nature, from microbes to plants, and play crucial roles in growth and development, stress responses and pathogen defense. However, the identification and functional analysis of GELP genes are hardly explored in soybean. This study describes the identification of 194 GELP genes in the soybean genome and their phylogenetic classification into 11 subfamilies (A-K). GmGELP genes are disproportionally distributed on 20 soybean chromosomes. Large-scale WGD/segmental duplication events contribute greatly to the expansion of the soybean GDSL gene family. The Ka/Ks ratios of more than 70% of duplicated gene pairs ranged from 0.1-0.3, indicating that most GmGELP genes were under purifying selection pressure. Gene structure analysis indicate that more than 74% of GmGELP genes are interrupted by 4 introns and composed of 5 exons in their coding regions, and closer homologous genes in the phylogenetic tree often have similar exon-intron organization. Further statistics revealed that approximately 56% of subfamily K members contain more than 4 introns, and about 28% of subfamily I members consist of less than 4 introns. For this reason, the two subfamilies were used to simulate intron gain and loss events, respectively. Furthermore, a new model of intron position distribution was established in current study to explore whether the evolution of multi-gene families resulted from the diversity of gene structure. Finally, RNA-seq data were used to investigate the expression profiles of GmGELP gene under different tissues and multiple abiotic stress treatments. Subsequently, 7 stress-responsive GmGELP genes were selected to verify their expression levels by RT-qPCR, the results were consistent with RNA-seq data. Among 7 GmGELP genes, GmGELP28 was selected for further study owing to clear responses to drought, salt and ABA treatments. Transgenic Arabidopsis thaliana and soybean plants showed drought and salt tolerant phenotype. Overexpression of GmGELP28 resulted in the changes of several physiological indicators, which allowed plants to adapt adverse conditions. In all, GmGELP28 is a potential candidate gene for improving the salinity and drought tolerance of soybean.
ESTHER : Su_2020_Front.Plant.Sci_11_726
PubMedSearch : Su_2020_Front.Plant.Sci_11_726
PubMedID: 32670311

Title : Soluble epoxide hydrolase inhibitors improve angiogenic function of endothelial progenitor cells via ERK\/p38-mediated miR-126 upregulation in myocardial infarction mice after exercise - Gui_2020_Exp.Cell.Res__112360
Author(s) : Gui Y , Chen J , Hu J , Liao C , Ouyang M , Deng L , Yang J , Xu D
Ref : Experimental Cell Research , :112360 , 2020
Abstract : It is well established that exercise could protect against myocardial infarction (MI). Previously, we found that epoxyeicosatrienoic acids (EETs) could be induced by exercise and has been found to protect against MI via promoting angiogenic function of endothelial progenitor cells (EPCs). However, the underling mechanism of EETs in promoting EPC functions is unclear. C57BL/6 mice were fed with a novel soluble epoxide hydrolase inhibitor (sEHi), TPPU, to increase EET levels, for 1 week before undergoing MI surgery. Mice were then subjected to exercise training for 4 weeks. Bone marrow-derived EPCs were isolated and cultured in vitro. Exercise upregulated miR-126 expression but downregulated the protein levels of its target gene, Spred1, in EPCs from MI mice. TPPU further enhanced the effects of exercise on EPCs. Spred1 overexpression abolished the protective effects of TPPU on EPC functions. Downregulation of miR-126 by antagomiR-126 impaired the inhibitor effects of TPPU on Spred1 mRNA and protein expression. Additionally, TPPU upregulated miR-126 is partially mediated through ERK/p38 MAPK pathway. This study showed that sEHi promoted miR-126 expression, which might be related to the beneficial effect of sEHi on EPC functions in MI mice under exercise conditions, by increasing ERK and p38 MAPK phosphorylation and inhibiting Spred1.
ESTHER : Gui_2020_Exp.Cell.Res__112360
PubMedSearch : Gui_2020_Exp.Cell.Res__112360
PubMedID: 33188851

Title : Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry - Wan_2020_J.Virol_94_
Author(s) : Wan Y , Shang J , Sun S , Tai W , Chen J , Geng Q , He L , Chen Y , Wu J , Shi Z , Zhou Y , Du L , Li F
Ref : J Virol , 94 : , 2020
Abstract : Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.
ESTHER : Wan_2020_J.Virol_94_
PubMedSearch : Wan_2020_J.Virol_94_
PubMedID: 31826992

Title : Biodegradation mechanism of polycaprolactone by a novel esterase MGS0156: a QM\/MM approach - Feng_2020_Environ.Sci.Process.Impacts_22_2332
Author(s) : Feng S , Yue Y , Chen J , Zhou J , Li Y , Zhang Q
Ref : Environ Sci Process Impacts , 22 :2332 , 2020
Abstract : Nowadays micro-plastic pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastic waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics such as polycaprolactone, polylactide, etc. Here a combined molecular dynamics, molecular mechanics Poisson-Boltzmann surface area, and quantum mechanics/molecular mechanism method was used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from a monomer to tetramer), we found that longer oligomers have relatively stronger binding energy. The degradation process involves two concerted elementary steps: triad-assisted nucleophilic attack and C-O bond cleavage. C-O bond cleavage is the rate determining step with an average barrier of 15.7 kcal mol-1, which is consistent with the experimentally determined kcat (1101 s-1, corresponds to 13.3 kcal mol-1). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as potential mutation targets for designing more efficient MGS0156 mutants.
ESTHER : Feng_2020_Environ.Sci.Process.Impacts_22_2332
PubMedSearch : Feng_2020_Environ.Sci.Process.Impacts_22_2332
PubMedID: 33146659
Gene_locus related to this paper: 9zzzz-A0A0G3FEJ8

Title : Characterization of a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC: A representative of the new esterase family XIX - Wang_2020_Pestic.Biochem.Physiol_170_104704
Author(s) : Wang B , Wu S , Chang X , Chen J , Ma J , Wang P , Zhu G
Ref : Pestic Biochem Physiol , 170 :104704 , 2020
Abstract : Carboxylesterases have widely been used in a series of industrial applications, especially, the detoxification of pesticide residues. In the present study, EstC, a novel carboxylesterase from Streptomyces lividans TK24, was successfully heterogeneously expressed, purified and characterized. Phylogenetic analysis showed that EstC can be assigned as the first member of a novel family XIX. Multiple sequence alignment indicated that EstC has highly conserved structural features, including a catalytic triad formed by Ser155, Asp248 and His278, as well as a canonical Gly-His-Ser-Ala-Gly pentapeptide. Biochemical characterization indicated that EstC exhibited maximal activity at pH 9.0 (Tris-HCl buffer) and 55 degC. It also showed higher activity towards short-chain substrates, with the highest activity for p-nitrophenyl acetate (pNPA2) (K(m) = 0.31 +/- 0.02 mM, k(cat)/K(m) = 1923.35 +/- 9.62 s(-1) mM(-1)) compared to other pNP esters used in this experiment. Notably, EstC showed hyper-thermostability and good alkali stability. The activity of EstC had no significant changes when it was incubated under 55 degC for 100 h and reached half-life after incubation at 100 degC for 8 h. Beyond that, EstC also showed stability at pH ranging from 6.0 to 11.0 and about 90% residual activity still reserved after treatment at pH 8.0 or 9.0 for 26 h, especially. Furthermore, EstC had outstanding potential for bioremediation of chlorpyrifos-contaminated environment. The recombinant enzyme (0.5 U mL(-1)) could hydrolyze 79.89% chlorpyrifos (5 mg L(-1)) at 37 degC within 80 min. These properties will make EstC have a potential application value in various industrial productions and detoxification of chlorpyrifos residues.
ESTHER : Wang_2020_Pestic.Biochem.Physiol_170_104704
PubMedSearch : Wang_2020_Pestic.Biochem.Physiol_170_104704
PubMedID: 32980065
Gene_locus related to this paper: strco-estli

Title : Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM\/MM study - Zhou_2020_Sci.Total.Environ_709_135897
Author(s) : Zhou J , Zhu L , Chen J , Wang W , Zhang R , Li Y , Zhang Q
Ref : Sci Total Environ , 709 :135897 , 2020
Abstract : The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals.
ESTHER : Zhou_2020_Sci.Total.Environ_709_135897
PubMedSearch : Zhou_2020_Sci.Total.Environ_709_135897
PubMedID: 31887512
Gene_locus related to this paper: 9euro-a0a0d2ilk1

Title : Insecticidal and Enzyme Inhibitory Activities of Isothiocyanates against Red Imported Fire Ants, Solenopsis invicta - Du_2020_Biomolecules_10_
Author(s) : Du Y , Grodowitz MJ , Chen J
Ref : Biomolecules , 10 : , 2020
Abstract : Contact and fumigation toxicity of four isothiocyanates (ITCs), including allyl isothiocyanate (AITC), 3-butenyl isothiocyanate (3BITC), 3-(methylthio) propyl isothiocyanate (3MPITC) and 2-phenylethyl isothiocyanate (2PEITC), were evaluated against the red imported fire ant worker, Solenopsis invicta Buren. 2PEITC and 3MPITC exhibited strong contact toxicity. The median lethal dose (LD50)value of AITC, 2PEITC and 3MPITC were 7.99, 2.36 and 2.09 microg/ant respectively. In addition, AITC and 3MPITC also showed strong fumigation toxicity but not 2PEITC. The median lethal concentration (LC50) values of AITC and 3MPITC were 32.49 and 57.6 microg/L, respectively. In contrast, 3BITC did not exhibit any contact and fumigation toxicity even at 100 mug/muL. Esterase (EST), glutathione S-transferase (GST) and acetylcholinesterase (AChE)-inhibiting activities were assessed for three ITCs in S. invicta workers. All three ITCs inhibited both EST and GST activities but not AChE. The in vitro half maximal inhibitory concentration (IC50)values of AITC, 2PEITC and 3MPITC for GST were 3.32, 0.61 and 0.66 microg/microL, respectively. These results suggested that naturally occurring ITCs might be potentially useful for developing fire ants control products.
ESTHER : Du_2020_Biomolecules_10_
PubMedSearch : Du_2020_Biomolecules_10_
PubMedID: 32380698

Title : Reduced insecticide sensitivity of the wheat aphid Sitobion miscanthi after infection by the secondary bacterial symbiont Hamiltonella defensa - Li_2020_Pest.Manag.Sci_77_1936
Author(s) : Li Q , Sun J , Qin Y , Fan J , Zhang Y , Tan X , Hou M , Chen J
Ref : Pest Manag Sci , 77 :1936 , 2020
Abstract : BACKGROUND: Bacterial symbionts in insects, especially aphids, have a major influence on host adaptation. The authors previously showed that infection with the secondary symbiont Hamiltonella defensa increases the fitness of the wheat aphid Sitobion miscanthi, yielding increases in fitness parameters such as adult weight and offspring number. However, whether H. defensa affects the sensitivity of host aphids to insecticides remains unknown. RESULTS: We tested the effects of H. defensa on host aphid susceptibility to the insecticides chlorpyrifos methyl, imidacloprid, cyantraniliprole and acetamiprid. Our results showed that compared with Hamiltonella-free aphid clones, Hamiltonella-infected aphid clones exhibited lower sensitivity to most of the tested insecticides at low concentrations. Quantitative PCR showed that the density of H. defensa in the infected clones was slightly decreased at 24 h but then sharply increased until the late stage after treatment with the different insecticides. H. defensa in the host aphids was detected by fluorescence in situ hybridization and was localized to the aphid hindgut. The levels of the detoxification enzymes acetylcholinesterase (AChE), glutathione transferase (GST) and carboxylesterase (CarE) were significantly higher in the Hamiltonella-infected clones than in the Hamiltonella-free clones. CONCLUSIONS: The findings indicated that infection with H. defensa reduced aphid sensitivity to the investigated insecticides at low concentrations, potentially by increasing detoxification enzyme activity in the host. Therefore, symbiont-mediated insecticide resistance should be taken into account when performing resistance-monitoring studies. Studies of symbiont-mediated insecticide resistance may enhance our understanding of the emergence of insecticide resistance in agricultural systems. This article is protected by copyright. All rights reserved.
ESTHER : Li_2020_Pest.Manag.Sci_77_1936
PubMedSearch : Li_2020_Pest.Manag.Sci_77_1936
PubMedID: 33300163

Title : Aberrant mPFC GABAergic Synaptic Transmission and Fear Behavior in Neuroligin-2 R215H Knock-in Mice - Chen_2020_Brain.Res__146671
Author(s) : Chen J , Dong B , Feng X , Jiang D , Chen G , Long C , Yang L
Ref : Brain Research , :146671 , 2020
Abstract : Aberrant medial prefrontal cortex (mPFC) activity is associated with neuropsychiatric disorders such as schizophrenia, but the precise role of mPFC GABAergic neurotransmission in the pathogenesis of schizophrenia remains not well understood. Neuroligin-2 (Nlgn 2) is a postsynaptic cell-adhesion protein playing an important role in inhibitory synapse formation and function. Mutations of Nlgn 2 have been reported to be associated with schizophrenia. Using a Nlgn 2 Arg(215)-->His(215) mutation knock-in (NL2 R215H KI) mouse model of schizophrenia, we show here that inhibitory synaptic transmission, such as miniature and evoked inhibitory postsynaptic currents (mIPSCs, eIPSCs), is significantly reduced in the mPFC of NL2 R215H KI mice. The levels of inhibition-related proteins, including parvalbumin (PV), the gamma2 subunit of the GABAA receptor, and a vesicular GABA transporter vGAT, are also reduced significantly in NL2 R215H KI mPFC. The reduction of GABAergic inhibition disrupts the excitation/inhibition (E/I) ratio in mPFC, and results in the subsequent abnormal gamma oscillation in the mPFC of R215H KI mice. Behavioral evaluation suggests that GABAergic deficits contribute, at least in part, to alterations in fear response, which requires balanced E/I ratio of mPFC neurons. These results suggest a pivotal role of Nlgn 2 in maintaining E/I balance in the mPFC and in the maintenance of normal behaviors governed by the mPFC.
ESTHER : Chen_2020_Brain.Res__146671
PubMedSearch : Chen_2020_Brain.Res__146671
PubMedID: 31953212

Title : Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice - Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
Author(s) : Wu R , Zhong S , Ni M , Zhu X , Chen Y , Chen X , Zhang L , Chen J
Ref : Evid Based Complement Alternat Med , 2020 :8617143 , 2020
Abstract : BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products.
ESTHER : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedSearch : Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143
PubMedID: 33014116

Title : Instrument-free and visual detection of organophosphorus pesticide using a smartphone by coupling aggregation-induced emission nanoparticle and two-dimension MnO(2) nanoflake - Chen_2020_Biosens.Bioelectron_170_112668
Author(s) : Chen J , Chen X , Zhao J , Liu S , Chi Z
Ref : Biosensors & Bioelectronics , 170 :112668 , 2020
Abstract : Given the importance of food safety, it is highly desirable to develop a convenient, low-cost, and practical sensor for organophosphorus pesticides (OPs) detection. Here, a fluorescent paper analytical device (FPAD) based on aggregation-induced emission (AIE) nanoparticles (PTDNPs-0.10) and two-dimension MnO(2) nanoflakes (2D-MnNFs) was developed for instrument-free and naked-eye analysis of OPs. PTDNP-MnNFs composites were obtained through 2D-MnNFs and PTDNPs-0.10 by electrostatic interaction and the fluorescence emission of PTDNPs-0.10 was quenched through fluorescence resonance energy transfer (FRET). When acetylcholinesterase (AChE) was present, acetylthiocholine (ATCh) was catalytically hydrolyzed into thiocholine, which reduced MnO(2) of PTDNP-MnNFs into Mn(2+), subsequently blocking the FRET and enhancing the fluorescence. Upon the addition of OP, AChE activity was depressed and thus the FRET between 2D-MnNFs and PTDNPs-0.10 was not affected, resulting in a slight change in fluorescence. On the basis of the variation in fluorescence intensity, highly sensitive detection of OP was readily achieved with a detection limit of 0.027 ng/mL; on the basis of the variation in brightness of FPAD, instrument-free and visual detection of OP was realized using a smartphone with a detection limit of 0.73 ng/mL. The application of FPAD has significantly simplified the detection procedure and decreased the test cost, supplying a new approach for on-site detection of OPs.
ESTHER : Chen_2020_Biosens.Bioelectron_170_112668
PubMedSearch : Chen_2020_Biosens.Bioelectron_170_112668
PubMedID: 33032200

Title : Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis - Shang_2019_Cancer.Res_79_5513
Author(s) : Shang S , Ji X , Zhang L , Chen J , Li C , Shi R , Xiang W , Kang X , Zhang D , Yang F , Dai R , Chen P , Chen S , Chen Y , Li Y , Miao H
Ref : Cancer Research , 79 :5513 , 2019
Abstract : Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg.
ESTHER : Shang_2019_Cancer.Res_79_5513
PubMedSearch : Shang_2019_Cancer.Res_79_5513
PubMedID: 31439546
Gene_locus related to this paper: human-ABHD5

Title : Synergistic effect of acetyl xylan esterase from Talaromyces leycettanus JCM12802 and xylanase from Neocallimastix patriciarum achieved by introducing carbohydrate-binding module-1 - Zhang_2019_AMB.Express_9_13
Author(s) : Zhang Y , Yang H , Yu X , Kong H , Chen J , Luo H , Bai Y , Yao B
Ref : AMB Express , 9 :13 , 2019
Abstract : Wheat bran is an effective raw material for preparation xylooligosaccharides; however, current research mainly focuses on alkali extraction and enzymatic hydrolysis methods. Since ester bonds are destroyed during the alkali extraction process, xylanase and arabinofuranosidase are mainly used to hydrolyze xylooligosaccharides. However, alkali extraction costs are very high, and the method also causes pollution. Therefore, this study focuses on elucidating a method to efficiently and directly degrade destarched wheat bran. First, an acidic acetyl xylan esterase (AXE) containing a carbohydrate-binding module-1 (CBM1) domain was cloned from Talaromyces leycettanus JCM12802 and successfully expressed in Pichia pastoris. Characterization showed that the full-length acetyl xylan esterase AXE + CBM1 was similar toe uncovered AXE with an optimum temperature and pH of 55 degrees C and 6.5, respectively. Testing the acetyl xylan esterase and xylanase derived from Neocallimastix patriciarum in a starch-free wheat bran cooperative experiment revealed that AXE + CBM1 and AXE produced 29% and 16% reducing sugars respectively, compared to when only NPXYN11 was used. In addition, introduced the CBM1 domain into NPXYN11, and the results indicated that the CBM1 domain showed little effect on NPXYN11 properties. Finally, the systematically synergistic effects between acetyl xylan esterase and xylanase with/without the CBM1 domain demonstrated that the combined ratio of AXE + CBM1 coming in first and NPXYN11 + CBM1 s increased reducing sugars by almost 35% with AXE and NPXYN11. Furthermore, each component's proportion remained the same with respect to xylooligosaccharides, with the largest proportion (86%) containing of 49% xylobiose and 37% xylotriose.
ESTHER : Zhang_2019_AMB.Express_9_13
PubMedSearch : Zhang_2019_AMB.Express_9_13
PubMedID: 30694400
Gene_locus related to this paper: 9euro-a0a411dz87

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

Title : 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 : Nox4 and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells - Liu_2019_Vascul.Pharmacol_120_106544
Author(s) : Liu X , Qin Z , Liu C , Song M , Luo X , Zhao H , Qian D , Chen J , Huang L
Ref : Vascul Pharmacol , 120 :106544 , 2019
Abstract : BACKGROUND: Hyperhomocysteinemia leads to a vascular smooth muscle cell (VSMC) inflammatory response. Meanwhile, Nox4 dependent reactive oxygen species (ROS) signaling and soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids (EETs) are both involved in vascular inflammation. Herein, we hypothesized that Nox4 and soluble epoxide hydrolase cross regulated during homocysteine-induced VSMC inflammation. METHODS AND RESULTS: In cultured VSMCs, the expression of the inflammatory factors VCAM1 and ICAM1 was measured by real-time PCR and Western blotting, while supernatant MCP1 was measured by ELISA. Upon VSMC stimulation with 50 muMu homocysteine, we observed the VCAM1 and ICAM1 mRNA levels were increased by 1.15 and 1.0 folds, respectively. The MCP1 levels in the supernatant of cultured VSMCs treated with 100 muMu increased to 1.76 folds. As expected, homocysteine induced Nox4 expression and Nox4-dependent ROS generation. The sEH expression was also upregulated in the presence of homocysteine in a dose-dependent manner. Furthermore, we knocked down Nox4 with siRNA. Knockdown of Nox4 decreased ROS generation and homocysteine-induced sEH expression. Overexpression of Nox4 with an adenovirus stimulated sEH expression. Similarly, knockdown or chemical inhibition of sEH blunted the upregulation of Nox4 by homocysteine. In vivo, in homocysteine-fed mice, concomitant upregulation of Nox4 and sEH was associated with increased VCAM1 and ICAM1 expression in the aortic wall. CONCLUSIONS: The inflammatory response induced by homocysteine in VSMCs was accompanied by Nox4 and sEH upregulation. Nox4 and soluble epoxide hydrolase synergistically contribute to homocysteine-induced inflammation.
ESTHER : Liu_2019_Vascul.Pharmacol_120_106544
PubMedSearch : Liu_2019_Vascul.Pharmacol_120_106544
PubMedID: 30610956

Title : Different durations of cognitive stimulation therapy for Alzheimer's disease: a systematic review and meta-analysis - Chen_2019_Clin.Interv.Aging_14_1243
Author(s) : Chen J , Duan Y , Li H , Lu L , Liu J , Tang C
Ref : Clin Interv Aging , 14 :1243 , 2019
Abstract : Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of cognitive stimulation therapy (CST) of different durations for Alzheimer's disease (AD). Methods: A comprehensive search was carried out in three databases. The primary outcome was Mini-Mental State Examination (MMSE) score. We conducted a meta-analysis with Review Manager, version 5.3 and assessed the methodological quality of the included studies using the Cochrane Collaboration Recommendations assessment tool. Results: Treatment effects from the meta-analysis showed that CST plus acetylcholinesterase inhibitors (ChEIs) was better than the control assessed by MMSE. In addition, the meta-analysis indicated that long-term CST was better than short-term or maintenance CST. Conclusion: Our study confirmed that the combination of CST and drug treatment for AD is effective in AD, regardless of whether short-term CST, maintenance CST, or long-term CST is used. The long-term CST appears to be more effective.
ESTHER : Chen_2019_Clin.Interv.Aging_14_1243
PubMedSearch : Chen_2019_Clin.Interv.Aging_14_1243
PubMedID: 31371930

Title : Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin - Fu_2019_Toxicology_430_152346
Author(s) : Fu F , Chen J , Zhao P , Lu X , Gao R , Chen D , Liu H , Wang H , Pei C
Ref : Toxicology , 430 :152346 , 2019
Abstract : V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and 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). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans.
ESTHER : Fu_2019_Toxicology_430_152346
PubMedSearch : Fu_2019_Toxicology_430_152346
PubMedID: 31857189

Title : Discovery of a highly specific and efficacious inhibitor of human carboxylesterase 2 by large-scale screening - Song_2019_Int.J.Biol.Macromol_137_261
Author(s) : Song YQ , Guan XQ , Weng ZM , Wang YQ , Chen J , Jin Q , Fang SQ , Fan B , Cao YF , Hou J , Ge GB
Ref : Int J Biol Macromol , 137 :261 , 2019
Abstract : Human carboxylesterase 2 (CES2A), one of the most abundant hydrolases distributed in human small intestine and colon, play key roles in the hydrolysis of a wide range of prodrugs and other esters. Recent studies have demonstrated that CES2A inhibitors may ameliorate irinotecan-induced severe diarrhea, but the specific and efficacious inhibitors targeting intracellular CES2A are rarely reported. Herein, a large-scale screening campaign was conducted for discovery of potent and specific CES2A inhibitor(s). Following screening of more than one hundred of natural products, glabridin (a bioactive compound of Glycyrrhiza glabra L.) was found displaying potent inhibition on CES2A and high specificity over CES1A (>500-fold) and other serine hydrolases. Further investigation showed that glabridin was cell permeable and low cytotoxic, as well as capable of inhibiting intracellular CES2A in living cells, with the IC50 value of 0.52muM. Molecular dynamics simulations showed that glabridin formed strong and stable interactions with both the catalytic cavity and Z site of CES2A via hydrophobic interactions. In summary, glabridin was a potent and specific inhibitor targeting intracellular CES2A, which could be used as an ideal lead compound to develop more efficacious CES2A inhibitors for modulating the pharmacokinetic behaviors of CES2A-substrate drugs and alleviating irinotecan-induced diarrhea.
ESTHER : Song_2019_Int.J.Biol.Macromol_137_261
PubMedSearch : Song_2019_Int.J.Biol.Macromol_137_261
PubMedID: 31260759

Title : Ester-Producing Mechanism of Ethanol O-acyltransferase EHT1 Gene in Pichia pastoris from Shanxi Aged Vinegar - Chen_2019_Biomed.Res.Int_2019_4862647
Author(s) : Chen J , Nan R , Wang R , Zhang L , Shi J
Ref : Biomed Res Int , 2019 :4862647 , 2019
Abstract : The ethanol O-acyltransferase EHT1 is an important element of key signaling pathways and is widely expressed in yeast strains. In this study, we investigated the expression of EHT1 in the overexpression lines or knockout system of Pichia pastoris using qRT-PCR and western blotting. The amount of total protein was determined using the Bradford method; the esterase activity was determined using p-nitrophenyl acetate as a substrate, and the production of volatile fatty acids in wild-type, knockout, and over-expression systems was detected using SPME GC-MS. The esterase activity of EHT1-knockout P. pastoris was significantly lower than that in wild type (P<0.01), and the activities of esterase in three EHT1-overexpressing strains-OE-1, OE-2, and OE-3-were significantly higher than those in wild type (P<0.01). In the EHT1-knockout strain products, the contents of nine volatile fatty acids were significantly lower than those in wild type (P<0.01), and the relative percentages of three fatty acids, methyl nonanoate, methyl decanoate, and ethyl caprate, were significantly lower than those in the other six species in the wild-type and knockout groups (P<0.05). The nine volatile fatty acids in the fermentation products of the overexpressed EHT1 gene were significantly higher than those in the wild-type group (P<0.01). The relative percentages of the three fatty acid esters, methyl nonanoate, methyl caprate, and ethyl caprate, were significantly higher than those in the other six species (P<0.05). EHT1 plays an important regulatory role in esterase activity and the production of medium-chain volatile fatty acids.
ESTHER : Chen_2019_Biomed.Res.Int_2019_4862647
PubMedSearch : Chen_2019_Biomed.Res.Int_2019_4862647
PubMedID: 30719444
Gene_locus related to this paper: kompc-f2qms6

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

Title : Food up-take and reproduction performance of Daphnia magna under the exposure of Bisphenols - Liu_2018_Ecotoxicol.Environ.Saf_170_47
Author(s) : Liu Y , Yan Z , Zhang L , Deng Z , Yuan J , Zhang S , Chen J , Guo R
Ref : Ecotoxicology & Environmental Safety , 170 :47 , 2018
Abstract : Because the application of Bisphenol A (BPA) was restricted, many substitutes, such as Bisphenol F (BPF) and Bisphenol S (BPS), were developed as BPA substitutes. Therefore, environmental impacts of BPA and its substitutes on aquatic organisms should be concerned, especially their combined toxicity. In this study, the impacts of BPA, BPF, BPS and their mixture on the feeding behavior, reproduction and physiological function of daphnids were synthetically evaluated, involving the duration and mode of exposure. In short-term exposure tests, feeding rates of D. magna decreased after exposure to BPA, BPF, BPS and their mixture, while the inhibition reversed into stimulation in the recovery period. It may benefit from overcompensation of D. magna. In long-term exposure tests, the inhibition effect on the reproduction and growth of the exposed D. magna was difficult to recover, and only some experimental groups have a certain recovery. In conclusion, environmental risk of BPA, BPF, BPS and their mixture on the behavior of D. magna increased with prolonged exposure time. Moreover, relative activities of trypsin, amylase (AMS), acetylcholinesterase (AChE), carbonic anhydrase (CA), glutathione peroxidase (GPx) and super oxidase dimutase (SOD) of the exposed daphnids decreased in most treatment groups, indicating the disorder of digestive, nervous and antioxidative system of D. magna. Interestingly, inhibition of enzymes activities decreased with the increase of the exposure time, which implied the tolerance may be occurred.
ESTHER : Liu_2018_Ecotoxicol.Environ.Saf_170_47
PubMedSearch : Liu_2018_Ecotoxicol.Environ.Saf_170_47
PubMedID: 30522006

Title : Deciphering the Role of Lipid Droplets in Cardiovascular Disease: A Report From the 2017 National Heart, Lung, and Blood Institute Workshop - Goldberg_2018_Circulation_138_305
Author(s) : Goldberg IJ , Reue K , Abumrad NA , Bickel PE , Cohen S , Fisher EA , Galis ZS , Granneman JG , Lewandowski ED , Murphy R , Olive M , Schaffer JE , Schwartz-Longacre L , Shulman GI , Walther TC , Chen J
Ref : Circulation , 138 :305 , 2018
Abstract : Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver. The National Heart, Lung, and Blood Institute convened a working group to discuss how LDs affect cardiovascular diseases. The goal of the working group was to examine the current state of knowledge on the cell biology of LDs, including current methods to study them in cells and organs and reflect on how LDs influence the development and progression of cardiovascular diseases. This review summarizes the working group discussion and recommendations on research areas ripe for future investigation that will likely improve our understanding of atherosclerosis and heart function.
ESTHER : Goldberg_2018_Circulation_138_305
PubMedSearch : Goldberg_2018_Circulation_138_305
PubMedID: 30012703

Title : Metabolic engineering of Escherichia coli for the synthesis of polyhydroxyalkanoates using acetate as a main carbon source - Chen_2018_Microb.Cell.Fact_17_102
Author(s) : Chen J , Li W , Zhang ZZ , Tan TW , Li ZJ
Ref : Microb Cell Fact , 17 :102 , 2018
Abstract : BACKGROUND: High production cost of bioplastics polyhydroxyalkanoates (PHA) is a major obstacle to replace traditional petro-based plastics. To address the challenges, strategies towards upstream metabolic engineering and downstream fermentation optimizations have been continuously pursued. Given that the feedstocks especially carbon sources account up to a large portion of the production cost, it is of great importance to explore low cost substrates to manufacture PHA economically. RESULTS: Escherichia coli was metabolically engineered to synthesize poly-3-hydroxybutyrate (P3HB), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) using acetate as a main carbon source. Overexpression of phosphotransacetylase/acetate kinase pathway was shown to be an effective strategy for improving acetate assimilation and biopolymer production. The recombinant strain overexpressing phosphotransacetylase/acetate kinase and P3HB synthesis operon produced 1.27 g/L P3HB when grown on minimal medium supplemented with 10 g/L yeast extract and 5 g/L acetate in shake flask cultures. Further introduction succinate semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, and CoA transferase lead to the accumulation of P3HB4HB, reaching a titer of 1.71 g/L with a 4-hydroxybutyrate monomer content of 5.79 mol%. When 1 g/L of alpha-ketoglutarate or citrate was added to the medium, P3HB4HB titer increased to 1.99 and 2.15 g/L, respectively. To achieve PHBV synthesis, acetate and propionate were simultaneously supplied and propionyl-CoA transferase was overexpressed to provide 3-hydroxyvalerate precursor. The resulting strain produced 0.33 g/L PHBV with a 3-hydroxyvalerate monomer content of 6.58 mol%. Further overexpression of propionate permease improved PHBV titer and 3-hydroxyvalerate monomer content to 1.09 g/L and 10.37 mol%, respectively. CONCLUSIONS: The application of acetate as carbon source for microbial fermentation could reduce the consumption of food and agro-based renewable bioresources for biorefineries. Our proposed metabolic engineering strategies illustrate the feasibility for producing polyhydroxyalkanoates using acetate as a main carbon source. Overall, as an abundant and renewable resource, acetate would be developed into a cost-effective feedstock to achieve low cost production of chemicals, materials, and biofuels.
ESTHER : Chen_2018_Microb.Cell.Fact_17_102
PubMedSearch : Chen_2018_Microb.Cell.Fact_17_102
PubMedID: 29970091

Title : Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos - Guo_2018_Environ.Pollut_241_1018
Author(s) : Guo X , Zhang S , Lu S , Zheng B , Xie P , Chen J , Li G , Liu C , Wu Q , Cheng H , Sang N
Ref : Environ Pollut , 241 :1018 , 2018
Abstract : Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6mg/L PFDoA for 120h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system.
ESTHER : Guo_2018_Environ.Pollut_241_1018
PubMedSearch : Guo_2018_Environ.Pollut_241_1018
PubMedID: 30029309

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

Title : Nevadensin is a naturally occurring selective inhibitor of human carboxylesterase 1 - Wang_2018_Int.J.Biol.Macromol_120_1944
Author(s) : Wang YQ , Weng ZM , Dou TY , Hou J , Wang DD , Ding LL , Zou LW , Yu Y , Chen J , Tang H , Ge GB
Ref : Int J Biol Macromol , 120 :1944 , 2018
Abstract : Human carboxylesterase 1 (hCE1) is a key enzyme responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters, but the highly selective inhibitors against hCE1 are rarely reported. This study aimed to assess the inhibitory effects of natural flavonoids against hCE1 and to find potential specific hCE1 inhibitors. To this end, fifty-eight natural flavonoids were collected and their inhibitory effects against both hCE1 and hCE2 were assayed. Among all tested compounds, nevadensin, an abundant natural constitute from Lysionotus pauciflorus Maxim., displayed the best combination of inhibition potency and selectivity towards hCE1. The inhibition mechanism of nevadensin on hCE1 was further investigated using two site-specific hCE1 substrates including D-luciferin methyl ester (DME) and 2(2benzoyloxy3methoxyphenyl)benzothiazole (BMBT). Furthermore, docking simulations demonstrated that the binding area of nevadensin on hCE1 was highly overlapped with that of DME but was far away from that of BMBT, which was highly consistent with the inhibition modes of nevadensin. These findings found a natural occurring specific inhibitor of hCE1, which could be served as a lead compound for the development of novel hCE1 inhibitor with improved properties, and also hold great promise for investigating hCE1-ligand interactions.
ESTHER : Wang_2018_Int.J.Biol.Macromol_120_1944
PubMedSearch : Wang_2018_Int.J.Biol.Macromol_120_1944
PubMedID: 30268757

Title : Studies on the lipid-regulating mechanism of alisol-based compounds on lipoprotein lipase - Xu_2018_Bioorg.Chem_80_347
Author(s) : Xu F , Lu C , Wu Q , Gu W , Chen J , Fang F , Zhao B , Du W , You M
Ref : Bioorg Chem , 80 :347 , 2018
Abstract : Studies on the lipid-regulating effects of alisol compounds are reported that include alisol B, alisol A 24-acetate (24A), alisol A and an alisol B - 24A - alisol A mixture (content ratio=1:1:1). The effects on the activity of lipoprotein lipase (LPL), a key lipid-modulating enzyme, were studied to investigate the molecular mechanism of lipid-regulating activity of alisols. The effects of alisols on regulating blood lipids and the activities of LPL were determined using a reagent kit method. The structure of LPL was obtained by homology modeling and the interactive mechanism of alisol monomers and the mixture with LPL was investigated by molecular simulation. The alisol monomer and mixture were shown to regulate blood lipids, suggesting that alisols may decrease the level of triglyceride (TG) by improving the activity of LPL. The order of intensity was: mixture>alisol A>alisol B>24A, indicating that alisols of alismatis rhizoma feature a synergistic effect on LPL. The N- and C-terminus of LPL both represented the catalytic active domains of this lipid-regulating effect. Cys306, Gln129 and Ser166 were the key amino acid residues resulting in the lipid-regulating effect of the alisol monomer while Ser166 and Arg18 were found to be responsible for the lipid-regulating effect of the mixture. The C-terminus of LPL was indirectly involved in the enzymatic process. A folded side chain of alisols or the parent ring was found to bind somewhat weaker to LPL than an open side chain or parent ring. The hydroxyl groups on the C14-, C22-, C28-, C30- and C31-terminus in the side chain, the ring ether structure in C23-position, and the acetyl group in C29-position represented the key sites for the lipid-regulating action of alisols. Meanwhile, the C30-site hydroxyl group played an important role in the synergistic effect of the alisol mixture.
ESTHER : Xu_2018_Bioorg.Chem_80_347
PubMedSearch : Xu_2018_Bioorg.Chem_80_347
PubMedID: 29986183

Title : Soluble epoxide hydrolase inhibitors, t-AUCB, downregulated miR-133 in a mouse model of myocardial infarction - Gui_2018_Lipids.Health.Dis_17_129
Author(s) : Gui Y , Li D , Chen J , Wang Y , Hu J , Liao C , Deng L , Xiang Q , Yang T , Du X , Zhang S , Xu D
Ref : Lipids Health Dis , 17 :129 , 2018
Abstract : BACKGROUND: It has been demonstrated that soluble epoxide hydrolase inhibitors (sEHIs) are protective against ischemia-induced lethal arrhythmias, but the mechanisms involved are unknown. Previously, we showed that sEHIs might reduce the incidence of ischemic arrhythmias by suppressing microRNA-1 (miR-1) in the myocardium. As miR-1 and miR-133 have the same proarrhythmic effects in the heart, we assumed that the beneficial effects of sEHIs might also relate to the regulation of miR-133. METHODS: A mouse model of myocardial infarction (MI) was established by ligating the coronary artery. The sEHI t-AUCB (trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) was administered daily for 7 days before MI. Myocardial infarct size and cardiac function was assessed at 24 h post-MI. The miRNA expression profiles of sham and MI mice treated with or without t-AUCB were determined by microarray and verified by real-time PCR. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. The mRNA levels of miR-133, its target genes (KCNQ1 [potassium voltage-gated channel subfamily Q member 1] and KCNH2 [potassium voltage-gated channel subfamily H member 2]), and serum response factor (SRF) were measured by real-time PCR; KCNQ1, KCNH2, and SRF protein levels were assessed by western blotting. RESULTS: We demonstrated that the treatment with sEHIs could reduce infarct size, improve cardia function, and prevent the development of cardiac arrhythmias in MI mice. The expression levels of 14 miRNAs differed between the sham and MI groups. t-AUCB treatment altered the expression of eight miRNAs: two were upregulated and six were downregulated. Of these, the muscle-specific miR-133 was downregulated in the ischemic myocardium. In line with this, up-regulation of miR-133 and down-regulation of KCNQ1 and KCNH2 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-133 overexpression inhibited expression of the target mRNA, whereas t-AUCB reversed the effects. Furthermore, SRF might participate in the negative regulation of miR-133 by t-AUCB. CONCLUSIONS: In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.
ESTHER : Gui_2018_Lipids.Health.Dis_17_129
PubMedSearch : Gui_2018_Lipids.Health.Dis_17_129
PubMedID: 29843720

Title : Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis - Duan_2018_BMC.Geriatr_18_175
Author(s) : Duan Y , Lu L , Chen J , Wu C , Liang J , Zheng Y , Wu J , Rong P , Tang C
Ref : BMC Geriatr , 18 :175 , 2018
Abstract : BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice.
ESTHER : Duan_2018_BMC.Geriatr_18_175
PubMedSearch : Duan_2018_BMC.Geriatr_18_175
PubMedID: 30086714

Title : Pezizomycetes genomes reveal the molecular basis of ectomycorrhizal truffle lifestyle - Murat_2018_Nat.Ecol.Evol_2_1956
Author(s) : Murat C , Payen T , Noel B , Kuo A , Morin E , Chen J , Kohler A , Krizsan K , Balestrini R , Da Silva C , Montanini B , Hainaut M , Levati E , Barry KW , Belfiori B , Cichocki N , Clum A , Dockter RB , Fauchery L , Guy J , Iotti M , Le Tacon F , Lindquist EA , Lipzen A , Malagnac F , Mello A , Molinier V , Miyauchi S , Poulain J , Riccioni C , Rubini A , Sitrit Y , Splivallo R , Traeger S , Wang M , Zifcakova L , Wipf D , Zambonelli A , Paolocci F , Nowrousian M , Ottonello S , Baldrian P , Spatafora JW , Henrissat B , Nagy LG , Aury JM , Wincker P , Grigoriev IV , Bonfante P , Martin FM
Ref : Nat Ecol Evol , 2 :1956 , 2018
Abstract : Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Perigord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries.
ESTHER : Murat_2018_Nat.Ecol.Evol_2_1956
PubMedSearch : Murat_2018_Nat.Ecol.Evol_2_1956
PubMedID: 30420746
Gene_locus related to this paper: 9pezi-a0a3n4l4q5 , 9pezi-a0a3n4lpg7

Title : Correlation between antibiotic-induced feeding depression and body size reduction in zooplankton (rotifer, Brachionus calyciflorus): Neural response and digestive enzyme inhibition - Yan_2018_Chemosphere_218_376
Author(s) : Yan Z , Yang Q , Wang X , Torres OL , Tang S , Zhang S , Guo R , Chen J
Ref : Chemosphere , 218 :376 , 2018
Abstract : The study analyzed the correlation between the antibiotic-induced feeding depression and body size reduction in rotifer, Brachionus calyciflorus, involving exposure, post-exposure and re-exposure periods. The filtration and ingestion rates of the rotifers were inhibited in these three exposure periods at any given concentration of the antibiotic sulfamethazine (SMZ). As food for rotifer, the cell size of the green algae was unchanged, which indicated that it could not drive feeding depression. Secondly, several corresponding physiological responses were considered. Reactive oxygen species (ROS) levels increased in the post-exposure and the re-exposure; acetylcholinesterase (AChE) activity was significantly decreased in the exposure and the re-exposure, whereas it was induced in the post-exposure. The activities of amylase and lipase were always inhibited in these three exposure periods. Additionally, significant decreases in lorica length, width and biovolume of rotifers occurred after the feeding depression. Statistical analysis indicated a positive correlation between the activity of the digestive enzyme and the body size. Our results demonstrated that SMZ could influence the neurotransmission, inhibit the activity of the digestive enzyme, and finally result in body size reduction. These results provided an integrated perspective on assessing the toxicity effects of antibiotic in non-lethal dosage on the feeding behavior of non-target aquatic organisms.
ESTHER : Yan_2018_Chemosphere_218_376
PubMedSearch : Yan_2018_Chemosphere_218_376
PubMedID: 30476769

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

Title : Glioblastoma recurrence correlates with NLGN3 levels - Liu_2018_Cancer.Med_7_2848
Author(s) : Liu R , Qin XP , Zhuang Y , Zhang Y , Liao HB , Tang JC , Pan MX , Zeng FF , Lei Y , Lei RX , Wang S , Liu AC , Chen J , Zhang ZF , Zhao D , Wu SL , Liu RZ , Wang ZF , Wan Q
Ref : Cancer Med , 7 :2848 , 2018
Abstract : Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum.
ESTHER : Liu_2018_Cancer.Med_7_2848
PubMedSearch : Liu_2018_Cancer.Med_7_2848
PubMedID: 29777576

Title : Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane - Wang_2018_Phys.Chem.Chem.Phys_20_20540
Author(s) : Wang J , Tang X , Li Y , Zhang R , Zhu L , Chen J , Sun Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , 20 :20540 , 2018
Abstract : The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts.
ESTHER : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedSearch : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedID: 30051124

Title : Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease - Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
Author(s) : Chen Y , Zhu J , Mo J , Yang H , Jiang X , Lin H , Gu K , Pei Y , Wu L , Tan R , Hou J , Chen J , Lv Y , Bian Y , Sun H
Ref : J Enzyme Inhib Med Chem , 33 :290 , 2018
Abstract : Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid beta-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50 = 10.2 +/- 1.2, 16.5 +/- 1.7, and 15.3 +/- 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.
ESTHER : Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
PubMedSearch : Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
PubMedID: 29278947

Title : Clinical diagnostic significance of prealbumin, cholinesterase and retinol binding protein in liver cirrhosis combined with encephalopathy - Tan_2018_Br.J.Biomed.Sci__1
Author(s) : Tan L , Meng Y , Zeng T , Wang Q , Long T , Wu S , Guan X , Fu H , Zheng W , Tian Y , Chen J , Yu J , Wu Y , Li H , Cao L
Ref : Br J Biomed Sci , :1 , 2018
Abstract : OBJECTIVE: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy. METHODS: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy. RESULTS: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01). CONCLUSIONS: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy.
ESTHER : Tan_2018_Br.J.Biomed.Sci__1
PubMedSearch : Tan_2018_Br.J.Biomed.Sci__1
PubMedID: 30392460

Title : Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes - Sun_2018_Nat.Genet_50_1289
Author(s) : Sun S , Zhou Y , Chen J , Shi J , Zhao H , Song W , Zhang M , Cui Y , Dong X , Liu H , Ma X , Jiao Y , Wang B , Wei X , Stein JC , Glaubitz JC , Lu F , Yu G , Liang C , Fengler K , Li B , Rafalski A , Schnable PS , Ware DH , Buckler ES , Lai J
Ref : Nat Genet , 50 :1289 , 2018
Abstract : Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.
ESTHER : Sun_2018_Nat.Genet_50_1289
PubMedSearch : Sun_2018_Nat.Genet_50_1289
PubMedID: 30061735
Gene_locus related to this paper: maize-a0a1d6kqc9 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a3l6d913

Title : Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester - Hui_2018_Drug.Deliv.Transl.Res_8_787
Author(s) : Hui A , Yin H , Zhang Z , Zhou A , Chen J , Yang L , Wu Z , Zhang W
Ref : Drug Deliv Transl Res , 8 :787 , 2018
Abstract : Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.
ESTHER : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedSearch : Hui_2018_Drug.Deliv.Transl.Res_8_787
PubMedID: 29524164

Title : Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery - Chen_2017_Molecules_22_E1598
Author(s) : Chen J , Chen Y , Cheng Y , Gao Y
Ref : Molecules , 22 : , 2017
Abstract : Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy.
ESTHER : Chen_2017_Molecules_22_E1598
PubMedSearch : Chen_2017_Molecules_22_E1598
PubMedID: 28946644

Title : [MEGDEL syndrome with an SERAC1 mutation: a case report] -
Author(s) : Chen J , Peng J , Yin F
Ref : Zhonghua Er Ke Za Zhi , 55 :394 , 2017
PubMedID: 28482397
Gene_locus related to this paper: human-SERAC1

Title : Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice - Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
Author(s) : Li N , Liu C , Jing S , Wang M , Wang H , Sun J , Wang C , Chen J , Li H
Ref : Evid Based Complement Alternat Med , 2017 :8632016 , 2017
Abstract : Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement.
ESTHER : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedSearch : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedID: 28814961

Title : Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis - Whitson_2017_Invest.Ophthalmol.Vis.Sci_58_2666
Author(s) : Whitson JA , Zhang X , Medvedovic M , Chen J , Wei Z , Monnier VM , Fan X
Ref : Invest Ophthalmol Vis Sci , 58 :2666 , 2017
Abstract : Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes. Results: RNA-Seq results were in excellent agreement with qPCR (correlation coefficients 0.87-0.94 and P < 5E-6 for a subset of 36 mRNAs). Of 24,415 transcripts mapped to the mouse genome, 441 genes showed significantly modulated expression. Pathway analysis indicated major changes in epithelial-mesenchymal transition (EMT) signaling, visual cycle, small molecule biochemistry, and lipid metabolism. GSH-deficient lenses showed upregulation of detoxification genes, including Aldh1a1, Aldh3a1 (aldehyde dehydrogenases), Mt1, Mt2 (metallothioneins), Ces1g (carboxylesterase), and Slc14a1 (urea transporter UT-B). Genes in canonical EMT pathways, including Wnt10a, showed upregulation in lens epithelia samples. Severely GSH-deficient lens epithelia showed downregulation of vision-related genes (including crystallins). The BSO-treated LEGSKO lens epithelia transcriptome has significant correlation (r = 0.63, P < 0.005) to that of lens epithelia undergoing EMT. Protein expression data correlated with transcriptomic data and confirmed EMT signaling activation. Conclusions: These results show that GSH-deficiency in the lens leads to expression of detoxifying genes and activation of EMT signaling, in addition to changes in transport systems and lipid homeostasis. These data provide insight into the adaptation and consequences of GSH-deficiency in the lens and suggest that GSH plays an important role in lenticular EMT pathology.
ESTHER : Whitson_2017_Invest.Ophthalmol.Vis.Sci_58_2666
PubMedSearch : Whitson_2017_Invest.Ophthalmol.Vis.Sci_58_2666
PubMedID: 28525556

Title : Selective Inhibitors of Human Liver Carboxylesterase Based on a beta-Lapachone Scaffold: Novel Reagents for Reaction Profiling - Hatfield_2017_J.Med.Chem_60_1568
Author(s) : Hatfield MJ , Chen J , Fratt EM , Chi L , Bollinger JC , Binder RJ , Bowling J , Hyatt JL , Scarborough J , Jeffries C , Potter PM
Ref : Journal of Medicinal Chemistry , 60 :1568 , 2017
Abstract : Carboxylesterases (CEs) are ubiquitous enzymes that are responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition of CEs significantly modulates the efficacy of such agents. We report here that beta-lapachone is a potent, reversible CE inhibitor with Ki values in the nanomolar range. A series of amino and phenoxy analogues have been synthesized, and although the former are very poor inhibitors, the latter compounds are highly effective in modulating CE activity. Our data demonstrate that tautomerism of the amino derivatives to the imino forms likely accounts for their loss in biological activity. A series of N-methylated amino derivatives, which are unable to undergo such tautomerism, were equal in potency to the phenoxy analogues and demonstrated selectivity for the liver enzyme hCE1. These specific inhibitors, which are active in cell culture models, will be exceptionally useful reagents for reaction profiling of esterified drugs in complex biological samples.
ESTHER : Hatfield_2017_J.Med.Chem_60_1568
PubMedSearch : Hatfield_2017_J.Med.Chem_60_1568
PubMedID: 28112927

Title : Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai Sea, China - Wang_2017_Sci.Total.Environ_607-608_103
Author(s) : Wang Y , Wu X , Zhang Q , Hou M , Zhao H , Xie Q , Du J , Chen J
Ref : Sci Total Environ , 607-608 :103 , 2017
Abstract : Concentrations and vertical distributions of organophosphate esters (OPEs) were investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of China. The total concentrations of OPEs in the sediment core (CA) collected near the Yellow River Estuary were in the range of 11.8-102ng/g, while the total concentrations in the sediment core (CB) near a mariculture area were 6.65-41.5ng/g. Significantly high concentrations of OPEs were found in the sediments near the Yellow River Estuary than those in the mariculture area. Vertical distributions in the sediment cores demonstrated a recent increase of OPE emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP and TCPP were the dominant congeners in the sediment cores, while the profiles of TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA core may be remarkably influenced by the discharge of Yellow River, whereas OPEs in the CB core may originate from the transport through seawater. The remarkable increase of OPE flame retardants in the surface sediments raises the concern about their emissions and risks to the environment and indicates the need for further monitoring.
ESTHER : Wang_2017_Sci.Total.Environ_607-608_103
PubMedSearch : Wang_2017_Sci.Total.Environ_607-608_103
PubMedID: 28688252

Title : Evaluation and application of constitutive promoters for cutinase production by Saccharomyces cerevisiae - Zhang_2017_J.Microbiol_55_538
Author(s) : Zhang J , Cai Y , Du G , Chen J , Wang M , Kang Z
Ref : J Microbiol , 55 :538 , 2017
Abstract : Cutinase as a promising biocatalyst has been intensively studied and applied in processes targeted for industrial scale. In this work, the cutinase gene tfu from Thermobifida fusca was artificially synthesized according to codon usage bias of Saccharomyces cerevisiae and investigated in Saccharomyces cerevisiae. Using the alpha-factor signal peptide, the T. fusca cutinase was successfully overexpressed and secreted with the GAL1 expression system. To increase the cutinase level and overcome some of the drawbacks of induction, four different strong promoters (ADH1, HXT1, TEF1, and TDH3) were comparatively evaluated for cutinase production. By comparison, promoter TEF1 exhibited an outstanding property and significantly increased the expression level. By fed-batch fermentation with a constant feeding approach, the activity of cutinase was increased to 29.7 U/ml. The result will contribute to apply constitutive promoter TEF1 as a tool for targeted cutinase production in S. cerevisiae cell factory.
ESTHER : Zhang_2017_J.Microbiol_55_538
PubMedSearch : Zhang_2017_J.Microbiol_55_538
PubMedID: 28664516

Title : Single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 on the feeding activity of Daphnia magna: From behavior assessment to neurotoxicity - Liu_2017_Chemosphere_195_542
Author(s) : Liu Y , Guo R , Tang S , Zhu F , Zhang S , Yan Z , Chen J
Ref : Chemosphere , 195 :542 , 2017
Abstract : Although 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47), 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE-47) clearly disrupt the endocrine system, current knowledge of their single and/or mixture toxicities on other behaviors of aquatic organisms remains limited. In the present study, Daphnia magna was used to investigate the single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 as measured by inhibition of feeding during exposure and post-exposure periods. Additionally, the biochemical performance, i.e., the activities of super oxidase dismutase (SOD), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) of the test organism was studied to investigate the potential mechanisms of the toxicity of the target compounds. The three target compounds produced an obvious depressive effect on feeding behavior during the exposure period, and the effect increased with increasing concentrations. D. magna was most sensitive to 6-OH-BDE-47. The toxicity of the ternary mixture showed an obvious concentration-dependent effect, whereas the binary mixture toxicity showed the characteristics of hormesis. During the post-exposure period, overcompensation occurred, indicating a short-term effect of the target compounds on D. magna. Additionally, significant changes occurred in neurological responses, indicating that these compounds might have neurobehavioral toxicity in D. magna. The decrease in oxidative stress enzymes (SOD and GPx) indicated that the antioxidant response of D. magna was destroyed.
ESTHER : Liu_2017_Chemosphere_195_542
PubMedSearch : Liu_2017_Chemosphere_195_542
PubMedID: 29277034

Title : The impact assessment of anticancer drug imatinib on the feeding behavior of rotifers with an integrated perspective: Exposure, post-exposure and re-exposure - Yan_2017_Chemosphere_185_423
Author(s) : Yan Z , Yan K , He X , Liu Y , Zhang J , Lopez Torres O , Guo R , Chen J
Ref : Chemosphere , 185 :423 , 2017
Abstract : The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib. Although the filtration and ingestion rate of the rotifers recovered to a certain extent after the exposure, the significant feeding inhibition still persisted even if the exposure was ended. In the re-exposure period, the feeding behavior was less depressed than those of the exposure period, which implied that rotifers might develop a tolerance to the same toxics. The activities of acetylcholine esterase (AchE) and the levels of reactive oxygen species (ROS) in rotifers were also detected. Imatinib inhibited the activities of AchE in the exposure and re-exposure while ROS levels increased significantly in the re-exposure period. Our present study provided an integrated assessment the potential environmental risks of imatinib at a new perspective.
ESTHER : Yan_2017_Chemosphere_185_423
PubMedSearch : Yan_2017_Chemosphere_185_423
PubMedID: 28710991

Title : Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease - Chen_2017_Eur.J.Med.Chem_125_784
Author(s) : Chen Z , Digiacomo M , Tu Y , Gu Q , Wang S , Yang X , Chu J , Chen Q , Han Y , Chen J , Nesi G , Sestito S , Macchia M , Rapposelli S , Pi R
Ref : Eur Journal of Medicinal Chemistry , 125 :784 , 2017
Abstract : A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD.
ESTHER : Chen_2017_Eur.J.Med.Chem_125_784
PubMedSearch : Chen_2017_Eur.J.Med.Chem_125_784
PubMedID: 27736684

Title : Discovery of a Selective Covalent Inhibitor of Lysophospholipase-like 1 (LYPLAL1) as a Tool to Evaluate the Role of this Serine Hydrolase in Metabolism - Ahn_2016_ACS.Chem.Biol_11_2529
Author(s) : Ahn K , Boehm M , Brown MF , Calloway J , Che Y , Chen J , Fennell KF , Geoghegan KF , Gilbert AM , Gutierrez JA , Kalgutkar AS , Lanba A , Limberakis C , Magee TV , O'Doherty I , Oliver R , Pabst B , Pandit J , Parris K , Pfefferkorn JA , Rolph TP , Patel R , Schuff B , Shanmugasundaram V , Starr JT , Varghese AH , Vera NB , Vernochet C , Yan J
Ref : ACS Chemical Biology , 11 :2529 , 2016
Abstract : Lysophospholipase-like 1 (LYPLAL1) is an uncharacterized metabolic serine hydrolase. Human genome-wide association studies link variants of the gene encoding this enzyme to fat distribution, waist-to-hip ratio, and nonalcoholic fatty liver disease. We describe the discovery of potent and selective covalent small-molecule inhibitors of LYPLAL1 and their use to investigate its role in hepatic metabolism. In hepatocytes, selective inhibition of LYPLAL1 increased glucose production supporting the inference that LYPLAL1 is a significant actor in hepatic metabolism. The results provide an example of how a selective chemical tool can contribute to evaluating a hypothetical target for therapeutic intervention, even in the absence of complete biochemical characterization.
ESTHER : Ahn_2016_ACS.Chem.Biol_11_2529
PubMedSearch : Ahn_2016_ACS.Chem.Biol_11_2529
PubMedID: 27391855
Gene_locus related to this paper: human-LYPLAL1

Title : NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9 - Chang_2016_Pathol.Oncol.Res_22_789
Author(s) : Chang X , Xu X , Xue X , Ma J , Li Z , Deng P , Chen J , Zhang S , Zhi Y , Dai D
Ref : Pathol Oncol Res , 22 :789 , 2016
Abstract : The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p < 0.01), invasion depth (p < 0.05), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), whereas MMP-9 was positive correlated with the degree of tumor cell differentiation (p < 0.01), lymph node metastasis (p < 0.05) and TNM stage (p < 0.05), but not correlated with invasion depth (p>0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9.
ESTHER : Chang_2016_Pathol.Oncol.Res_22_789
PubMedSearch : Chang_2016_Pathol.Oncol.Res_22_789
PubMedID: 27154576

Title : alpha\/beta-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors - Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
Author(s) : Wei M , Zhang J , Jia M , Yang C , Pan Y , Li S , Luo Y , Zheng J , Ji J , Chen J , Hu X , Xiong J , Shi Y , Zhang C
Ref : Proc Natl Acad Sci U S A , 113 :E2695 , 2016
Abstract : In the brain, AMPA-type glutamate receptors are major postsynaptic receptors at excitatory synapses that mediate fast neurotransmission and synaptic plasticity. alpha/beta-Hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor macromolecular complexes, but its physiological significance in the function of AMPA receptors (AMPARs) has remained unclear. The present study shows that overexpression of ABHD6 in neurons drastically reduced excitatory neurotransmission mediated by AMPA but not by NMDA receptors at excitatory synapses. Inactivation of ABHD6 expression in neurons by either CRISPR/Cas9 or shRNA knockdown methods significantly increased excitatory neurotransmission at excitatory synapses. Interestingly, overexpression of ABHD6 reduced glutamate-induced currents and the surface expression of GluA1 in HEK293T cells expressing GluA1 and stargazin, suggesting a direct functional interaction between these two proteins. The C-terminal tail of GluA1 was required for the binding between of ABHD6 and GluA1. Mutagenesis analysis revealed a GFCLIPQ sequence in the GluA1 C terminus that was essential for the inhibitory effect of ABHD6. The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6.
ESTHER : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedSearch : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedID: 27114538
Gene_locus related to this paper: human-ABHD6

Title : A liquid chromatography tandem mass spectrometric method on in vitro nerve agents poisoning characterization and reactivator efficacy evaluation by determination of specific peptide adducts in acetylcholinesterase - Yan_2016_J.Chromatogr.A_1450_86
Author(s) : Yan L , Chen J , Xu B , Guo L , Xie Y , Tang J , Xie J
Ref : Journal of Chromatography A , 1450 :86 , 2016
Abstract : The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified. A key termination procedure is focused to make the reaction system "frozen" and precisely "capture" the poisoning, aging and spontaneous reactivation status of AChE, and the abundance of such specific peptides can thus be simultaneously measured. In our established method, as low as 0.72% and 0.84% inhibition level of AChE induced by 0.5nM sarin and VX can be detected from the measurement of peptide adducts, which benefits a confirmation of NAs exposure, especially at extremely low levels. Comparing with conventional colorimetric Ellman assays, our method provides not only enzyme activity and inhibition rate, but also the precise poisoning status of NAs exposed AChE. Based on the full information provided by this method, the efficacy of reactivators, such as HI-6, obidoxime and pralidoxime, in the typical treatment of NAs poisoned AChE in in vitro was further evaluated. Our results showed that this method is a promising tool for the characterization of NAs poisoning and the evaluation of reactivator efficacy.
ESTHER : Yan_2016_J.Chromatogr.A_1450_86
PubMedSearch : Yan_2016_J.Chromatogr.A_1450_86
PubMedID: 27179675

Title : Antifungal Indole Alkaloids from Winchia calophylla - Yang_2016_Planta.Med_82_712
Author(s) : Yang ML , Chen J , Sun M , Zhang DB , Gao K
Ref : Planta Med , 82 :712 , 2016
Abstract : Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 microM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 microM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 microM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 microM, respectively.
ESTHER : Yang_2016_Planta.Med_82_712
PubMedSearch : Yang_2016_Planta.Med_82_712
PubMedID: 27002397

Title : Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats - Liu_2016_Metab.Brain.Dis_31_417
Author(s) : Liu X , Mo Y , Gong J , Li Z , Peng H , Chen J , Wang Q , Ke Z , Xie J
Ref : Metabolic Brain Disease , 31 :417 , 2016
Abstract : Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1beta and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-alpha, IL-1beta and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects.
ESTHER : Liu_2016_Metab.Brain.Dis_31_417
PubMedSearch : Liu_2016_Metab.Brain.Dis_31_417
PubMedID: 26686502

Title : Multi-biomarker responses as indication of contaminant effects in Gambusia affinis from impacted rivers by municipal effluents - Huang_2016_Sci.Total.Environ_563-564_273
Author(s) : Huang GY , Liu YS , Liang YQ , Shi WJ , Hu LX , Tian F , Chen J , Ying GG
Ref : Sci Total Environ , 563-564 :273 , 2016
Abstract : This study investigated toxic effects in mosquitofish from two urban rivers of South China impacted by municipal effluents by using multiple biomarkers including fish morphology, biochemical indicators and transcriptional responses, and explored potential cause-effect relationship with a list of chemicals (metals, polycyclic aromatic hydrocarbons (PAHs) and pesticides). The results showed significant alterations in metallothionein (MT) protein and mRNA expression in mosquitofish collected from the two rivers and a strong association between MT protein and mRNA expression levels and heavy metals in the river water. Both ethoxyresorufin-O-deethylase (EROD) activity and cytochromes P450 1A (CYP1A) mRNA expression were significantly enhanced in mosquitofish at most sampling sites. There existed a strong correlation between EROD activity and CYP1A mRNA expression levels, but no clear correlations between these responses and PAHs in the river water possibly because of the presence of many other agonists of the aryl hydrocarbon receptor in the two rivers. Significant acetylcholinesterase (AChE) inhibition was observed in mosquitofish brain samples. The pesticides in the two rivers showed an influence on the AChE activity, which was also found to be significantly negatively correlated to fipronil concentrations. Moreover, the result also indicates that metals and pesticides present in the two rivers might cause the observed estrogenic and androgenic effects in mosquitofish. The findings from this study clearly showed morphological, biochemical and transcriptional responses in mosquitofish due to chemical contamination of the two urban rivers. This multi-biomarker approach using mosquitofish can be applied to evaluate contamination of riverine environments.
ESTHER : Huang_2016_Sci.Total.Environ_563-564_273
PubMedSearch : Huang_2016_Sci.Total.Environ_563-564_273
PubMedID: 27135591

Title : Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation - Kodani_2016_Toxicol.Lett_262_92
Author(s) : Kodani SD , Overby HB , Morisseau C , Chen J , Zhao L , Hammock BD
Ref : Toxicol Lett , 262 :92 , 2016
Abstract : Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids.
ESTHER : Kodani_2016_Toxicol.Lett_262_92
PubMedSearch : Kodani_2016_Toxicol.Lett_262_92
PubMedID: 27659731

Title : Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure - Piermartiri_2015_Neuromolecular.Med_17_251
Author(s) : Piermartiri TC , Pan H , Chen J , McDonough J , Grunberg N , Apland JP , Marini AM
Ref : Neuromolecular Med , 17 :251 , 2015
Abstract : Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naive animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism.
ESTHER : Piermartiri_2015_Neuromolecular.Med_17_251
PubMedSearch : Piermartiri_2015_Neuromolecular.Med_17_251
PubMedID: 25920465

Title : Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population - Cai_2015_BMC.Cardiovasc.Disord_15_14
Author(s) : Cai A , Li G , Chen J , Li X , Li L , Zhou Y
Ref : BMC Cardiovasc Disord , 15 :14 , 2015
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD).
METHODS: Totally 781 participants were enrolled and performed coronary angiography (CAG) to figure out the number of coronary artery stenosis. According to clinical presentation, electrocardiography, cardiac biomarker, and CAG result, participants were divided into control (excluded CAD), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) groups. Baseline characteristics were recorded. Statistical analyses were performed to evaluate the relationship between Lp-PLA2 level and CAD severity.
RESULTS: Plasma levels of Lp-PLA2 in control, SA, UA and AMI groups were 7.38(3.33-9.26) mug/L, 5.94(2.89-8.55) mug/L, 8.56(5.34-11.95) mug/L and 8.68(5.56-13.27) mug/L respectively (P < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apoprotein A (apoA) and statins, Lp-PLA2 level was still independently associated with CAD severity, with odd ratio (OR) of 1.055 (AMI group versus control group, 95% confidence interval (CI) 1.021-1.090, P < 0.05). Additionally, the relationship between Lp-PLA2 level and the number of stenosis coronary artery was also assessed. Lp-PLA2 levels in control, single-vessel, and multiple-vessels stenosis groups were 7.38(3.33-9.26) mug/L, 7.80 (4.05-10.76) mug/L and 8.29(5.18-11.76) mug/L respectively (P for trend < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, LDL-C and HDL-C, apoA and statins, Lp-PLA2 level remained independently associated with the number of coronary artery stenosis, with OR of 1.053 (multiple-vessels stenosis group versus control group, 95% CI 1.025-1.069, P < 0.05). CONCLUSION: Increased Lp-PLA2 level is independently associated with CAD severity, and Lp-PLA2 level may be used to discriminate those who are at increased risk of cardiovascular events.
ESTHER : Cai_2015_BMC.Cardiovasc.Disord_15_14
PubMedSearch : Cai_2015_BMC.Cardiovasc.Disord_15_14
PubMedID: 25879827

Title : Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits - Xu_2015_Gene_557_146
Author(s) : Xu H , Tao X , Wei Y , Chen J , Xing S , Cen W , Wen A , Zhu L , Tang G , Li M , Jiang A , Jiang Y , Li X
Ref : Gene , 557 :146 , 2015
Abstract : Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits.
ESTHER : Xu_2015_Gene_557_146
PubMedSearch : Xu_2015_Gene_557_146
PubMedID: 25498336

Title : Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure - Pan_2015_Neurotoxicol_51_38
Author(s) : Pan H , Piermartiri TC , Chen J , McDonough J , Oppel C , Driwech W , Winter K , McFarland E , Black K , Figueiredo T , Grunberg N , Marini AM
Ref : Neurotoxicology , 51 :38 , 2015
Abstract : Exposure to nerve agents results in severe seizures or status epilepticus caused by the inhibition of acetylcholinesterase, a critical enzyme that breaks down acetylcholine to terminate neurotransmission. Prolonged seizures cause brain damage and can lead to long-term consequences. Current countermeasures are only modestly effective against the brain damage supporting interest in the evaluation of new and efficacious therapies. The nutraceutical alpha-linolenic acid (LIN) is an essential omega-3 polyunsaturated fatty acid that has a wide safety margin. Previous work showed that a single intravenous injection of alpha-linolenic acid (500nmol/kg) administered before or after soman significantly protected against soman-induced brain damage when analyzed 24h after exposure. Here, we show that administration of three intravenous injections of alpha-linolenic acid over a 7 day period after soman significantly improved motor performance on the rotarod, enhanced memory retention, exerted an anti-depressant-like activity and increased animal survival. This dosing schedule significantly reduced soman-induced neuronal degeneration in four major vulnerable brain regions up to 21 days. Taken together, alpha-linolenic acid reduces the profound behavioral deficits induced by soman possibly by decreasing neuronal cell death, and increases animal survival.
ESTHER : Pan_2015_Neurotoxicol_51_38
PubMedSearch : Pan_2015_Neurotoxicol_51_38
PubMedID: 26386148

Title : Novibacillus thermophilus gen. nov., sp. nov., a Gram-staining-negative and moderately thermophilic member of the family Thermoactinomycetaceae - Yang_2015_Int.J.Syst.Evol.Microbiol_65_2591
Author(s) : Yang G , Chen J , Zhou S
Ref : Int J Syst Evol Microbiol , 65 :2591 , 2015
Abstract : Two Gram-staining-negative, facultatively anaerobic bacterial strains, SG-1T and SG-2, were isolated from a saline soil sample and a compost sample, respectively. The cells were non-motile rods that occurred singly or in chains, and endospores were not observed under tested growth conditions. Optimum growth occurred at 50 degreesC, pH 7.5-8.0 and with 5-7% (w/v) NaCl. The DNA G+C content was 49.5-50.5mol%. The strains contained MK-7 as the predominant menaquinone and iso-C15 : 0 and anteiso-C15 : 0 as the major fatty acids. The polar lipids consisted mainly of diphosphatidylglycerol and phosphatidylglycerol. The cell-wall peptidoglycan type was A1gamma (meso-DAP direct). Phylogenetic analyses revealed that the new isolates belonged to the family Thermoactinomycetaceae, exhibiting low 16S rRNA gene sequence similarity (90.8-91.3%) to the nearest type strain, Mechercharimyces asporophorigenens YM11-542T, and formed a well-supported lineage that was clearly distinguished from all currently described genera in this family. Based on our polyphasic taxonomic characterization, we propose that strains SG-1T and SG-2 represent a novel genus and species within the family Thermoactinomycetaceae, for which we propose the name Novibacillus thermophilus gen. nov., sp. nov. The type strain of Novibacillus thermophilus is SG-1T ( = KCTC 33118T = CGMCC 1.12771T).
ESTHER : Yang_2015_Int.J.Syst.Evol.Microbiol_65_2591
PubMedSearch : Yang_2015_Int.J.Syst.Evol.Microbiol_65_2591
PubMedID: 25951858
Gene_locus related to this paper: 9bacl-a0a1u9k3n4 , 9bacl-a0a1u9ka40

Title : Complete Genome Sequence of Rhodococcus sp. B7740, a Carotenoid-Producing Bacterium Isolated from the Arctic Sea - Zhang_2015_Genome.Announc_3_e00333
Author(s) : Zhang D , Li L , Zhu S , Zhang N , Yang J , Ma X , Chen J
Ref : Genome Announc , 3 : , 2015
Abstract : Rhodococcus sp. B7740 was isolated from Arctic seawater and selected for its capacity to synthesize carotenoids. Here, we report the complete genome sequence of Rhodococcus sp. B7740 to provide the genetic basis for a better understanding of its carotenoid-accumulating capabilities, and we describe the major features of the genome.
ESTHER : Zhang_2015_Genome.Announc_3_e00333
PubMedSearch : Zhang_2015_Genome.Announc_3_e00333
PubMedID: 25931596
Gene_locus related to this paper: 9noca-a0a0d5a5c6 , 9noca-a0a0d5abf5 , 9noca-a0a0d5ae28 , 9noca-a0a0d5ahw4

Title : (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-beta aggregation with high antioxidant potency for Alzheimer's therapy - Cheng_2015_Bioorg.Med.Chem_23_3110
Author(s) : Cheng S , Zheng W , Gong P , Zhou Q , Xie Q , Yu L , Zhang P , Chen L , Li J , Chen J , Chen H
Ref : Bioorganic & Medicinal Chemistry , 23 :3110 , 2015
Abstract : The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-beta (Abeta) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Abeta self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD.
ESTHER : Cheng_2015_Bioorg.Med.Chem_23_3110
PubMedSearch : Cheng_2015_Bioorg.Med.Chem_23_3110
PubMedID: 26025073

Title : A general method to improve fluorophores for live-cell and single-molecule microscopy - Grimm_2015_Nat.Methods_12_244
Author(s) : Grimm JB , English BP , Chen J , Slaughter JP , Zhang Z , Revyakin A , Patel R , Macklin JJ , Normanno D , Singer RH , Lionnet T , Lavis LD
Ref : Nat Methods , 12 :244 , 2015
Abstract : Specific labeling of biomolecules with bright fluorophores is the keystone of fluorescence microscopy. Genetically encoded self-labeling tag proteins can be coupled to synthetic dyes inside living cells, resulting in brighter reporters than fluorescent proteins. Intracellular labeling using these techniques requires cell-permeable fluorescent ligands, however, limiting utility to a small number of classic fluorophores. Here we describe a simple structural modification that improves the brightness and photostability of dyes while preserving spectral properties and cell permeability. Inspired by molecular modeling, we replaced the N,N-dimethylamino substituents in tetramethylrhodamine with four-membered azetidine rings. This addition of two carbon atoms doubles the quantum efficiency and improves the photon yield of the dye in applications ranging from in vitro single-molecule measurements to super-resolution imaging. The novel substitution is generalizable, yielding a palette of chemical dyes with improved quantum efficiencies that spans the UV and visible range.
ESTHER : Grimm_2015_Nat.Methods_12_244
PubMedSearch : Grimm_2015_Nat.Methods_12_244
PubMedID: 25599551

Title : In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-\/-) mice - Chen_2015_Physiol.Rep_3_
Author(s) : Chen J , Kaiyala KJ , Lam J , Agrawal N , Nguyen L , Ogimoto K , Spencer D , Morton GJ , Schwartz MW , Dichek HL
Ref : Physiol Rep , 3 : , 2015
Abstract : The lean body weight phenotype of hepatic lipase (HL)-deficient mice (hl(-/-)) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl(-/-)) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) in which the catalytic Serine 145 was mutated to Alanine. As expected, HL activity in postheparin plasma was restored to physiologic levels only in hHL-transgenic mice (hl(-/-)hHL). During high-fat diet feeding, hHL-transgenic mice exhibited increased body weight gain and body adiposity relative to hl(-/-)ciHL mice. A similar, albeit less robust effect was observed in female hHL-transgenic relative to hl(-/-)ciHL mice. To delineate the basis for this effect, we determined cumulative food intake and measured energy expenditure using calorimetry. Interestingly, in both genders, food intake was 5-10% higher in hl(-/-)hHL mice relative to hl(-/-)ciHL controls. Similarly, energy expenditure was ~10% lower in HL-transgenic mice after adjusting for differences in total body weight. Our results demonstrate that (1) the catalytic function of HL is required to rescue the lean body weight phenotype of hl(-/-) mice; (2) this effect involves complementary changes in both sides of the energy balance equation; and (3) the bridging function alone is insufficient to rescue the lean phenotype of hl(-/-)ciHL mice.
ESTHER : Chen_2015_Physiol.Rep_3_
PubMedSearch : Chen_2015_Physiol.Rep_3_
PubMedID: 25862097
Gene_locus related to this paper: mouse-1hlip

Title : Inhibition of monoacylglycerol lipase reduces nicotine withdrawal - Muldoon_2015_Br.J.Pharmacol_172_869
Author(s) : Muldoon PP , Chen J , Harenza JL , Abdullah RA , Sim-Selley LJ , Cravatt BF , Miles MF , Chen X , Lichtman AH , Damaj MI
Ref : British Journal of Pharmacology , 172 :869 , 2015
Abstract : BACKGROUND AND PURPOSE: Abrupt discontinuation of nicotine, the main psychoactive component in tobacco, induces a withdrawal syndrome in nicotine-dependent animals, consisting of somatic and affective signs, avoidance of which contributes to drug maintenance. While blockade of fatty acid amide hydrolase, the primary catabolic enzyme of the endocannabinoid arachidonoylethanolamine (anandamide), exacerbates withdrawal responses in nicotine-dependent mice, the role of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of a second endocannabinoid 2-arachidonylglycerol (2-AG), in nicotine withdrawal remains unexplored. EXPERIMENTAL APPROACH: To evaluate the role of MAGL enzyme inhibition in nicotine withdrawal, we initially performed a genetic correlation approach using the BXD recombinant inbred mouse panel. We then assessed nicotine withdrawal intensity in the mouse after treatment with the selective MAGL inhibitor, JZL184, and after genetic deletion of the enzyme. Lastly, we assessed the association between genotypes and smoking withdrawal phenotypes in two human data sets. KEY
RESULTS: BXD mice displayed significant positive correlations between basal MAGL mRNA expression and nicotine withdrawal responses, consistent with the idea that increased 2-AG brain levels may attenuate withdrawal responses. Strikingly, the MAGL inhibitor, JZL184, dose-dependently reduced somatic and aversive withdrawal signs, which was blocked by rimonabant, indicating a CB1 receptor-dependent mechanism. MAGL-knockout mice also showed attenuated nicotine withdrawal. Lastly, genetic analyses in humans revealed associations of the MAGL gene with smoking withdrawal in humans. CONCLUSIONS AND IMPLICATIONS: Overall, our findings suggest that MAGL inhibition maybe a promising target for treatment of nicotine dependence.
ESTHER : Muldoon_2015_Br.J.Pharmacol_172_869
PubMedSearch : Muldoon_2015_Br.J.Pharmacol_172_869
PubMedID: 25258021
Gene_locus related to this paper: human-MGLL

Title : The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin - Lin_2015_Mil.Med.Res_2_13
Author(s) : Lin NN , Chen J , Xu B , Wei X , Guo L , Xie JW
Ref : Mil Med Res , 2 :13 , 2015
Abstract : BACKGROUND: T-2 toxin poses a great threat to human health because it has the highest toxicity of the currently known trichothecene mycotoxins. To understand the in vivo toxicity and transformation mechanism of T-2 toxin, we investigated the role of one kind of principal phase I drug-metabolizing enzymes (cytochrome P450 [CYP450] enzymes) on the metabolism of T-2 toxin, which are crucial to the metabolism of endogenous substances and xenobiotics. We also investigated carboxylesterase, which also plays an important role in the metabolism of toxic substances.
METHODS: A chemical inhibition method and a recombinant method were employed to investigate the metabolism of the T-2 toxin by the CYP450 enzymes, and a chemical inhibition method was used to study carboxylesterase metabolism. Samples incubated with human liver microsomes were analyzed by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC- QqQ MS) after a simple pretreatment.
RESULTS: In the presence of a carboxylesterase inhibitor, only 20 % T-2 toxin was metabolized. When CYP enzyme inhibitors and a carboxylesterase inhibitor were both present, only 3 % of the T-2 toxin was metabolized. The contributions of the CYP450 enzyme family to T-2 toxin metabolism followed the descending order CYP3A4, CYP2E1, CYP1A2, CYP2B6 or CYP2D6 or CYP2C19. CONCLUSION: Carboxylesterase and CYP450 enzymes are of great importance in T-2 toxin metabolism, in which carboxylesterase is predominant and CYP450 has a subordinate role. CYP3A4 is the principal member of the CYP450 enzyme family responsible for T-2 toxin metabolism. The primary metabolite produced by carboxylesterase is HT-2, and the main metabolite produced by CYP 3A4 is 3'-OH T-2. The different metabolites show different toxicities. Our results will provide useful data concerning the toxic mechanism, the safety evaluation, and the health risk assessment of T-2 toxin.
ESTHER : Lin_2015_Mil.Med.Res_2_13
PubMedSearch : Lin_2015_Mil.Med.Res_2_13
PubMedID: 26140218

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : A simple electrochemical biosensor based on AuNPs\/MPS\/Au electrode sensing layer for monitoring carbamate pesticides in real samples - Song_2015_J.Hazard.Mater_304_103
Author(s) : Song Y , Chen J , Sun M , Gong C , Shen Y , Wang L
Ref : J Hazard Mater , 304 :103 , 2015
Abstract : A simple electrochemical biosensor for quantitative determination of carbamate pesticide was developed based on a sensing interface of citrate-capped gold nanoparticles (AuNPs)/(3-mercaptopropyl)-trimethoxysilane (MPS)/gold electrode (Au). The biosensor was fabricated by firstly assembling three-dimensional (3D) MPS networks on Au electrode and subsequently assembling citrate-capped AuNPs on 3D MPS network via AuS bond. The interface of AuNPs/MPS/Au was negatively charged originating from the citrate coated on AuNPs that would repulse the negatively charged ferricyanide ([Fe(CN)6]3-/4-) to produce a negative response. In the presence of acetylcholinesterase (AChE) and acetylthiocholine (ATCl), the AChE catalyzes the hydrolysis of ATCl into positively charged thiocholine which would replace the citrate on AuNPs through the strong AuS bond and convert the negative charged surface to be positively charged. The resulted positively charged AuNPs/MPS/Au then attracted the [Fe(CN)6]3-/4- to produce a positive response. Based on the inhibition of carbamate pesticides on the activity of AChE, the pesticide could be quantitatively determined at a very low potential. The linear range was from 0.003 to 2.00muM. The sensing platform was also proved to be suitable for carbamate pesticides detection in practical sample.
ESTHER : Song_2015_J.Hazard.Mater_304_103
PubMedSearch : Song_2015_J.Hazard.Mater_304_103
PubMedID: 26547618

Title : Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence - Hancock_2015_Transl.Psychiatry_5_e651
Author(s) : Hancock DB , Reginsson GW , Gaddis NC , Chen X , Saccone NL , Lutz SM , Qaiser B , Sherva R , Steinberg S , Zink F , Stacey SN , Glasheen C , Chen J , Gu F , Frederiksen BN , Loukola A , Gudbjartsson DF , Bruske I , Landi MT , Bickeboller H , Madden P , Farrer L , Kaprio J , Kranzler HR , Gelernter J , Baker TB , Kraft P , Amos CI , Caporaso NE , Hokanson JE , Bierut LJ , Thorgeirsson TE , Johnson EO , Stefansson K
Ref : Transl Psychiatry , 5 :e651 , 2015
Abstract : We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 x 10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 x 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences.
ESTHER : Hancock_2015_Transl.Psychiatry_5_e651
PubMedSearch : Hancock_2015_Transl.Psychiatry_5_e651
PubMedID: 26440539

Title : Identification of effective combinatorial markers for quality standardization of herbal medicines - Shi_2014_J.Chromatogr.A_1345_78
Author(s) : Shi ZQ , Song DF , Li RQ , Yang H , Qi LW , Xin GZ , Wang DQ , Song HP , Chen J , Hao H , Li P
Ref : Journal of Chromatography A , 1345 :78 , 2014
Abstract : Quality standardization of herbal medicines (HMs) is an important task with great challenges. Selection of abundant compounds as markers is currently a major approach for the quality control of HMs; however, such marker compounds are irrelevant to the bioactivities in many cases. Taking Lycoridis Radiatae Bulbus (LRB) as an example, we proposed a universal strategy to identify the effective combinatorial markers (ECMs) that are representative of the bioactivities of HMs, and took them as chemical markers for quality standardization. Fingerprinting and quantification were employed to find out the common components in various batches of medicines. The contribution of each common compound to the overall bioactivity was determined through fingerprint-bioactivity modeling, which based on the absolute quantification of each compound and the acetylcholinesterase (AChE) inhibitory activity of LRB. Two most effective compounds, ungerimine and galanthamine, were therefore proposed as ECMs. Interestingly, these two compounds could synergistically inhibit AChE. This approach demonstrated its strong advantage of the bioactivity relevant quality assessment when compared with conventional methods. And the success of applying this ECMs-based method to the quality assessment of unknown LRB samples proved that our approach was reliable and reproducible. In conclusion, this approach is not only useful for the bioactivity relevant quality control of HMs but also helpful for the discovery of ECMs as new drug candidates.
ESTHER : Shi_2014_J.Chromatogr.A_1345_78
PubMedSearch : Shi_2014_J.Chromatogr.A_1345_78
PubMedID: 24794938

Title : Lipase immobilized catalytically active membrane for synthesis of lauryl stearate in a pervaporation membrane reactor - Zhang_2014_Bioresour.Technol_172C_16
Author(s) : Zhang W , Qing W , Ren Z , Li W , Chen J
Ref : Bioresour Technol , 172C :16 , 2014
Abstract : A composite catalytically active membrane immobilized with Candida rugosa lipase has been prepared by immersion phase inversion technique for enzymatic synthesis of lauryl stearate in a pervaporation membrane reactor. SEM images showed that a "sandwich-like" membrane structure with a porous lipase-PVA catalytic layer uniformly coated on a polyvinyl alcohol (PVA)/polyethersulfone (PES) bilayer was obtained. Optimum conditions for lipase immobilization in the catalytic layer were determined. The membrane was proved to exhibit superior thermal stability, pH stability and reusability than free lipase under similar conditions. In the case of pervaporation coupled synthesis of lauryl stearate, benefited from in-situ water removal by the membrane, a conversion enhancement of approximately 40% was achieved in comparison to the equilibrium conversion obtained in batch reactors. In addition to conversion enhancement, it was also found that excess water removal by the catalytically active membrane appears to improve activity of the lipase immobilized.
ESTHER : Zhang_2014_Bioresour.Technol_172C_16
PubMedSearch : Zhang_2014_Bioresour.Technol_172C_16
PubMedID: 25218626

Title : Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization - Lin_2014_Anal.Bioanal.Chem_406_5213
Author(s) : Lin Y , Chen J , Yan L , Guo L , Wu B , Li C , Feng J , Liu Q , Xie J
Ref : Anal Bioanal Chem , 406 :5213 , 2014
Abstract : A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.
ESTHER : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedSearch : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedID: 24633564

Title : Structural insights into enzymatic degradation of oxidized polyvinyl alcohol - Yang_2014_Chembiochem_15_1882
Author(s) : Yang Y , Ko TP , Liu L , Li J , Huang CH , Chan HC , Ren F , Jia D , Wang AH , Guo RT , Chen J , Du G
Ref : Chembiochem , 15 :1882 , 2014
Abstract : The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel alpha/beta-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like beta-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of beta-diketone, although it has a catalytic triad similar to that of most alpha/beta-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving beta-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications.
ESTHER : Yang_2014_Chembiochem_15_1882
PubMedSearch : Yang_2014_Chembiochem_15_1882
PubMedID: 25044912
Gene_locus related to this paper: psesp-OPH , sphs1-OPH

Title : [Cloning of feruloyl esterase gene from Aspergillus niger h408 and high-efficient expression in Pichia pastoris] - Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
Author(s) : Zhou Y , Liu X , Chen J , Hu H , Hou Y
Ref : Wei Sheng Wu Xue Bao , 54 :876 , 2014
Abstract : OBJECTIVE: To achieve the high-efficiency expression of feruloyl estrase gene (AnfaeA) from Aspergillus niger h408 in Pichia pastoris and characterize the recombinant feruloyl esterase (FAE).
METHODS: Using gene splicing by overlap extension (SOE), we cloned AnfaeA gene from A. niger h408 and subcloned into T vector for sequencing analysis. The expression vector pPIC9K-Anfae was constructed by the ligation of the Anfae A gene into the shuttle vector pPIC9K. The plasmid pPIC9K-Anfae was linearized and then electrotransformed into P. pastoris GS115. The recombinant strain with high level of FAE activity was obtained through plate screening. Effects of pH and temperature on recombinant FAE were determined by ultraviolet (UV) methods.
RESULTS: We have successfully cloned and high-efficiently expressed the AnfaeA gene (GenBank: KF911349) from A. niger h408 in P. pastoris GS115. The sequencing result showed that the length of Anfae A was 783bp. The gene contained an Open Reading Frame encoding 260 amino acids and was similar to feruloyl esterase A from A. niger by homology analysis. The deduced amino acids contained a typical active lid and catalytic triad of lipase. The SDS-PAGE result indicated that molecular weight of the recombinant FAE was about 30 kDa and the activity of the recombinant enzyme was 24.72 U/mL. The specific activity of the recombinant FAE was 40.84 U/mg. Compared with A. niger h408, the recombinant enzyme activity increased about to 1100 times. The optimal temperature and pH for recombinant FAE was 50 degrees C and 5.0, respectively. Recombinant FAE showed nearly 80% of its maximal activity at 60 degrees C and was active in the pH range 4.0-9.0.
CONCLUSIONS: The high-efficient expression of AnfaeA gene in P. pastoris provided a prerequisite for achieving industrial application in feed and paper-making industry. In addition, the results established the experimental basis for further improvement of recombinant feruloyl esterase by directed evolution.
ESTHER : Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
PubMedSearch : Zhou_2014_Wei.Sheng.Wu.Xue.Bao_54_876
PubMedID: 25345018

Title : Roles of tryptophan residue and disulfide bond in the variable lid region of oxidized polyvinyl alcohol hydrolase - Yang_2014_Biochem.Biophys.Res.Commun_452_509
Author(s) : Yang Y , Ko TP , Liu L , Li J , Huang CH , Chen J , Guo RT , Du G
Ref : Biochemical & Biophysical Research Communications , 452 :509 , 2014
Abstract : Oxidized polyvinyl alcohol hydrolase (OPH) catalyzes the cleavage of C-C bond in beta-diketone. It belongs to the alpha/beta-hydrolase family and contains a unique lid region that covers the active site. The lid is the most variable region when pOPH from Pseudomonas sp. VM15C and sOPH from Sphingopyxis sp. 113P3 are compared. The wild-type enzymes and the pOPH mutants W255A, W255Y and W255F were analyzed for lipase activity by using p-nitrophenyl (pNP) esters as the substrates. The wild-type enzymes showed increased Km and decreased kcat/Km with the acyl chain length, and the mutants showed reduced kcat/Km for pNP acetate, indicating the importance of Trp255 in sequestering the active site from solvent. The significantly lower activity for pNP butyrate can be a result of product inhibition, as suggested by the complex crystal structures, in which butyric acid, DMSO or PEG occupied the same substrate-binding cleft. The mutant activity was retained with pNP caprylate and pNP laurate as the substrates, reflecting the amphipathic nature of the cleft. Moreover, the disulfide bond formation of Cys257/267 is important for the activity of pOPH, but it is not essential for sOPH, which has a shorter lid structure.
ESTHER : Yang_2014_Biochem.Biophys.Res.Commun_452_509
PubMedSearch : Yang_2014_Biochem.Biophys.Res.Commun_452_509
PubMedID: 25173935
Gene_locus related to this paper: sphs1-OPH

Title : Association between copy number variation losses and alcohol dependence across African American and European American ethnic groups - Ulloa_2014_Alcohol.Clin.Exp.Res_38_1266
Author(s) : Ulloa AE , Chen J , Vergara VM , Calhoun V , Liu J
Ref : Alcohol Clin Exp Res , 38 :1266 , 2014
Abstract : BACKGROUND: Copy number variations (CNVs) are structural genetic mutations consisting of segmental gains or losses in DNA sequence. Although CNVs contribute substantially to genomic variation, few genetic and imaging studies report association of CNVs with alcohol dependence (AD). Our purpose is to find evidence of this association across ethnic populations and genders. This work is the first AD-CNV study across ethnic groups and the first to include the African American (AA) population.
METHODS: This study considers 2 CNV data sets, one for discovery (2,345 samples) and the other for validation (239 samples), both including subjects with AD and healthy controls of European and African ancestry. Our analysis assesses the association between AD and CNV losses across ethnic groups and gender by examining the effect of overall losses across the whole genome, collective losses within individual cytogenetic bands, and specific losses in CNV regions.
RESULTS: Results from the discovery data set showed an association between CNV losses within 16q12.2 and AD diagnosis (p = 4.53 x 10(-3) ). An overlapping CNV region from the validation data set exhibited the same direction of effect with respect to AD (p = 0.051). This CNV region affects the genes CES1p1 and CES1, which are members of the carboxylesterase (CES) family. The enzyme encoded by CES1 is a major liver enzyme that typically catalyzes the decomposition of ester into alcohol and carboxylic acid and is involved in drug or xenobiotics, fatty acid, and cholesterol metabolisms. In addition, the most significantly associated CNV region was located at 9p21.2 (p = 1.9 x 10(-3) ) in our discovery data set. Although not observed in the validation data set, probably due to small sample size, this result might hold potential connection to AD given its connection with neuronal death. In contrast, we did not find any association between AD and the overall total losses or the collective losses within individual cytogenetic bands.
CONCLUSIONS: Overall, our study provides evidence that the specific CNVs at 16q12.2 contribute to the development of alcoholism in AA and European American populations.
ESTHER : Ulloa_2014_Alcohol.Clin.Exp.Res_38_1266
PubMedSearch : Ulloa_2014_Alcohol.Clin.Exp.Res_38_1266
PubMedID: 24512105

Title : High-resolution melting analysis reveals genetic polymorphisms in MicroRNAs confer hepatocellular carcinoma risk in Chinese patients - Qi_2014_BMC.Cancer_14_643
Author(s) : Qi JH , Wang J , Chen J , Shen F , Huang JT , Sen S , Zhou X , Liu SM
Ref : BMC Cancer , 14 :643 , 2014
Abstract : BACKGROUND: Although several single-nucleotide polymorphisms in microRNA (miRNA) genes have been associated with primary hepatocellular carcinoma, published findings regarding this relationship are inconsistent and inconclusive.
METHODS: The high-resolution melting (HRM) analysis was used to determine whether the occurrence of the SNPs of miR-146a C > G (rs2910164), miR-196a2 C > T (rs11614913), miR-301b A > G (rs384262), and miR-499 C > T (rs3746444) differs in frequency-matched 314 HCC patients and 407 controls by age and sex.
RESULTS: The groups' genotype distributions of miR-196a2 C > T and miR-499 C > T differed significantly (P < 0.01), both of them increased the risk of HCC in different dominant genetic models (P < 0.01); compared with individuals carrying one or neither of the unfavorable genotypes, individuals carrying both unfavorable genotypes (CT + CC) had a 3.11-fold higher HCC risk (95 % confidence interval (CI), 1.89-5.09; P = 7.18 x 10-6). Moreover, the allele frequency of miR-499 C > T was significantly different between the two groups, and the HCC risk of carriers of the C allele was higher than that of carriers of the T allele (odds ratio, 1.53; 95 % CI, 1.15-2.03; P = 0.003). Further, we found that the activated partial thromboplastin time (APTT) in HCC patients with miR-196a2 CC genotype was longer than patients with TT genotypes (P < 0.05), and HCC patients with miR-499 C allele had higher serum levels of direct bilirubin, globulin, gamma-glutamyltranspeptidase, alkaline phosphatase, and lower serum cholinesterase (P < 0.05).
CONCLUSIONS: Our findings suggest that the SNPs in miR-196a2 C > T and miR-499 C > T confer HCC risk and that affect the clinical laboratory characteristics of HCC patients.
ESTHER : Qi_2014_BMC.Cancer_14_643
PubMedSearch : Qi_2014_BMC.Cancer_14_643
PubMedID: 25176041

Title : Biochemical characterization and high-level production of oxidized polyvinyl alcohol hydrolase from Sphingopyxis sp. 113P3 expressed in methylotrophic Pichia pastoris - Yang_2014_Bioprocess.Biosyst.Eng_37_777
Author(s) : Yang Y , Liu L , Li J , Du G , Chen J
Ref : Bioprocess Biosyst Eng , 37 :777 , 2014
Abstract : The Sphingopyxis sp. 113P3 gene oph, encoding oxidized polyvinyl alcohol hydrolase (OPH), was optimized with the preferred codons of Pichia pastoris and ligated into the pPIC9K vector behind the alpha-factor signal sequence. The vector was then transfected into P. pastoris GS115 and genomic integration was confirmed. Large-scale production of recombinant protein was performed by induction with 14.4 g/L methanol at 22 degrees C in a 3-L bioreactor. The maximal OPH activity obtained was 68.4 U/mL, which is the highest activity reported. The optimal pH and temperature of recombinant OPH were 8.0 and 45 degrees C, respectively. OPH activity was stable over a pH range of 5.0-8.5, and at a maximal temperature of 45 degrees C. The K cat /K m of recombinant OPH was 598 mM(-1) s(-1), which was 4.27-fold higher than that of recombinant OPH derived from Escherichia coli. The improved catalytic efficiency of OPH expressed in recombinant P. pastoris makes it favorable for industrial applications.
ESTHER : Yang_2014_Bioprocess.Biosyst.Eng_37_777
PubMedSearch : Yang_2014_Bioprocess.Biosyst.Eng_37_777
PubMedID: 24068496

Title : (-)-phenserine attenuates soman-induced neuropathology - Chen_2014_PLoS.One_9_e99818
Author(s) : Chen J , Pan H , Chen C , Wu W , Iskandar K , He J , Piermartiri T , Jacobowitz DM , Yu QS , McDonough JH , Greig NH , Marini AM
Ref : PLoS ONE , 9 :e99818 , 2014
Abstract : Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy.
ESTHER : Chen_2014_PLoS.One_9_e99818
PubMedSearch : Chen_2014_PLoS.One_9_e99818
PubMedID: 24955574

Title : Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes - You_2014_Nat.Commun_5_5594
Author(s) : You X , Bian C , Zan Q , Xu X , Liu X , Chen J , Wang J , Qiu Y , Li W , Zhang X , Sun Y , Chen S , Hong W , Li Y , Cheng S , Fan G , Shi C , Liang J , Tom Tang Y , Yang C , Ruan Z , Bai J , Peng C , Mu Q , Lu J , Fan M , Yang S , Huang Z , Jiang X , Fang X , Zhang G , Zhang Y , Polgar G , Yu H , Li J , Liu Z , Ravi V , Coon SL , Yang H , Venkatesh B , Shi Q
Ref : Nat Commun , 5 :5594 , 2014
Abstract : Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates.
ESTHER : You_2014_Nat.Commun_5_5594
PubMedSearch : You_2014_Nat.Commun_5_5594
PubMedID: 25463417
Gene_locus related to this paper: 9gobi-a0a3b4bh68 , 9gobi-a0a3b4bmj6 , 9gobi-a0a3b4alj9 , 9gobi-a0a3b4biy6 , 9gobi-a0a3b4ah01 , 9gobi-a0a3b3z8m7 , 9gobi-a0a3b4aaj5 , 9gobi-a0a3b4b6y7

Title : Synaptic proteins and receptors defects in autism spectrum disorders - Chen_2014_Front.Cell.Neurosci_8_276
Author(s) : Chen J , Yu S , Fu Y , Li X
Ref : Front Cell Neurosci , 8 :276 , 2014
Abstract : Recent studies have found that hundreds of genetic variants, including common and rare variants, rare and de novo mutations, and common polymorphisms contribute to the occurrence of autism spectrum disorders (ASDs). The mutations in a number of genes such as neurexin, neuroligin, postsynaptic density protein 95, SH3, and multiple ankyrin repeat domains 3 (SHANK3), synapsin, gephyrin, cadherin, and protocadherin, thousand-and-one-amino acid 2 kinase, and contactin, have been shown to play important roles in the development and function of synapses. In addition, synaptic receptors, such as gamma-aminobutyric acid receptors and glutamate receptors, have also been associated with ASDs. This review will primarily focus on the defects of synaptic proteins and receptors associated with ASDs and their roles in the pathogenesis of ASDs via synaptic pathways.
ESTHER : Chen_2014_Front.Cell.Neurosci_8_276
PubMedSearch : Chen_2014_Front.Cell.Neurosci_8_276
PubMedID: 25309321

Title : NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells - Chang_2014_Mol.Biol.Rep_41_6215
Author(s) : Chang X , Xu X , Ma J , Xue X , Li Z , Deng P , Zhang S , Zhi Y , Chen J , Dai D
Ref : Mol Biol Rep , 41 :6215 , 2014
Abstract : N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.
ESTHER : Chang_2014_Mol.Biol.Rep_41_6215
PubMedSearch : Chang_2014_Mol.Biol.Rep_41_6215
PubMedID: 24985974

Title : The Extract of Ziziphus jujuba Fruit (Jujube) Induces Expression of Erythropoietin Via Hypoxia-Inducible Factor-1alpha in Cultured Hep3B Cells - Chen_2014_Planta.Med_80_1622
Author(s) : Chen J , Lam CT , Kong AY , Zhang WL , Zhan JY , Bi CWC , Chan GK , Lam KY , Yao P , Dong TTX , Tsim KWK
Ref : Planta Med , 80 :1622 , 2014
Abstract : The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement or herbal medicine worldwide. To study the beneficial role of jujube in enhancing hematopoietic function, we investigated its roles on the expression of erythropoietin in cultured Hep3B human hepatocellular carcinoma cells. Application of chemically standardized jujube water extract stimulated erythropoietin expression in a dose-dependent manner, with the highest response by ~ 100 % of increase. A plasmid containing hypoxia response element, a critical regulator for erythropoietin transcription, was transfected into Hep3B cells. Application of jujube water extract onto the transfected cells induced the transcriptional activity of the hypoxia response element. To account for its transcriptional activation, the expression of hypoxia-inducible factor-1alpha was increased after treatment with jujube water extract: the increase was in both mRNA and protein levels. These results confirmed the hematopoietic function of jujube in the regulation of erythropoietin expression in liver cells.
ESTHER : Chen_2014_Planta.Med_80_1622
PubMedSearch : Chen_2014_Planta.Med_80_1622
PubMedID: 25184890

Title : Whole-Genome Sequence of Streptococcus suis Serotype 4 Reference Strain 6407 - Wang_2014_Genome.Announc_2_e00770
Author(s) : Wang K , Chen J , Yao H , Lu C
Ref : Genome Announc , 2 : , 2014
Abstract : We report here the second complete genome sequence of Streptococcus suis serotype 4 (strain 6407). The genome is 2,292,360 bp in length, covering 2,239 coding sequences, 58 tRNAs, and 4 rRNA loci.
ESTHER : Wang_2014_Genome.Announc_2_e00770
PubMedSearch : Wang_2014_Genome.Announc_2_e00770
PubMedID: 25125641
Gene_locus related to this paper: strsu-b9wvz1

Title : Draft Genome Sequence of Xylella fastidiosa Pear Leaf Scorch Strain in Taiwan - Su_2014_Genome.Announc_2_e00166
Author(s) : Su CC , Deng WL , Jan FJ , Chang CJ , Huang H , Chen J
Ref : Genome Announc , 2 : , 2014
Abstract : The draft genome sequence of Xylella fastidiosa pear leaf scorch strain PLS229, isolated from the pear cultivar Hengshan (Pyrus pyrifolia) in Taiwan, is reported here. The bacterium has a genome size of 2,733,013 bp, with a G+C content of 53.1%. The PLS229 genome was annotated and has 3,259 open reading frames and 50 RNA genes.
ESTHER : Su_2014_Genome.Announc_2_e00166
PubMedSearch : Su_2014_Genome.Announc_2_e00166
PubMedID: 24652975
Gene_locus related to this paper: xylfs-z9jn15 , 9gamm-z9jk30 , 9gamm-z9jmt7

Title : Cutinase: Characteristics, preparation, and application - Chen_2013_Biotechnol.Adv_31_1754
Author(s) : Chen S , Su L , Chen J , Wu J
Ref : Biotechnol Adv , 31 :1754 , 2013
Abstract : Cutinases (E.C. 3.1.1.74) belong to the alpha/beta-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes.
ESTHER : Chen_2013_Biotechnol.Adv_31_1754
PubMedSearch : Chen_2013_Biotechnol.Adv_31_1754
PubMedID: 24055682

Title : Whole-Genome Sequencing of Lactobacillus shenzhenensis Strain LY-73T - Lin_2013_Genome.Announc_1_e00972
Author(s) : Lin Z , Liu Z , Yang R , Zou Y , Wan D , Chen J , Guo M , Zhao J , Fang C , Liu F
Ref : Genome Announc , 1 : , 2013
Abstract : Lactobacillus shenzhenensis strain LY-73(T) is a novel species which was first isolated from fermented goods. Here, we report the draft genome sequence of Lactobacillus shenzhenensis LY-73(T).
ESTHER : Lin_2013_Genome.Announc_1_e00972
PubMedSearch : Lin_2013_Genome.Announc_1_e00972
PubMedID: 24265500
Gene_locus related to this paper: 9laco-u4tvs6 , 9laco-u4ti93

Title : Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids - Sun_2013_Bioorg.Med.Chem_21_7406
Author(s) : Sun Y , Chen J , Chen X , Huang L , Li X
Ref : Bioorganic & Medicinal Chemistry , 21 :7406 , 2013
Abstract : A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9nM and 0.401muM, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD).
ESTHER : Sun_2013_Bioorg.Med.Chem_21_7406
PubMedSearch : Sun_2013_Bioorg.Med.Chem_21_7406
PubMedID: 24128814

Title : Draft Genome Sequence of Xylella fastidiosa subsp. multiplex Strain Griffin-1 from Quercus rubra in Georgia - Chen_2013_Genome.Announc_1_e00756
Author(s) : Chen J , Huang H , Chang CJ , Stenger DC
Ref : Genome Announc , 1 :e00756 , 2013
Abstract : The draft genome sequence of Xylella fastidiosa subsp. multiplex strain Griffin-1, isolated from a red oak tree (Quercus rubra) in Georgia, is reported here. The bacterium has a genome size of 2,387,314 bp, with a G+C content of 51.7%. The Griffin-1 strain genome contains 2,903 predicted open reading frames and 50 RNA genes.
ESTHER : Chen_2013_Genome.Announc_1_e00756
PubMedSearch : Chen_2013_Genome.Announc_1_e00756
PubMedID: 24115539
Gene_locus related to this paper: xylfa-pip

Title : Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens - Chang_2013_Cell.Biochem.Biophys_66_93
Author(s) : Chang X , Zhang S , Ma J , Li Z , Zhi Y , Chen J , Lu Y , Dai D
Ref : Cell Biochem Biophys , 66 :93 , 2013
Abstract : NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.
ESTHER : Chang_2013_Cell.Biochem.Biophys_66_93
PubMedSearch : Chang_2013_Cell.Biochem.Biophys_66_93
PubMedID: 23099645

Title : Extracellular location of Thermobifida fusca cutinase expressed in Escherichia coli BL21(DE3) without mediation of a signal peptide - Su_2013_Appl.Environ.Microbiol_79_4192
Author(s) : Su L , Woodard RW , Chen J , Wu J
Ref : Applied Environmental Microbiology , 79 :4192 , 2013
Abstract : Cutinase is a multifunctional esterase with potential industrial applications. In the present study, a truncated version of the extracellular Thermobifida fusca cutinase without a signal peptide (referred to as cutinase(NS)) was heterologously expressed in Escherichia coli BL21(DE3). The results showed that the majority of the cutinase activity was located in the culture medium. In a 3-liter fermentor, the cutinase activity in the culture medium reached 1,063.5 U/ml (2,380.8 mg/liter), and the productivity was 40.9 U/ml/h. Biochemical characterization of the purified cutinase(NS) showed that it has enzymatic properties similar to those of the wild-type enzyme. In addition, E. coli cells producing inactive cutinase(NS)S130A were constructed, and it was found that the majority of the inactive enzyme was located in the cytoplasm. Furthermore, T. fusca cutinase was confirmed to have hydrolytic activity toward phospholipids, an important component of the cell membrane. Compared to the cells expressing the inactive cutinase(NS)S130A, the cells expressing cutinase(NS) showed increased membrane permeability and irregular morphology. Based on these results, a hypothesis of "cell leakage induced by the limited phospholipid hydrolysis of cutinase(NS)" was proposed to explain the underlying mechanism for the extracellular release of cutinase(NS).
ESTHER : Su_2013_Appl.Environ.Microbiol_79_4192
PubMedSearch : Su_2013_Appl.Environ.Microbiol_79_4192
PubMedID: 23603671

Title : Distinct loci in the CHRNA5\/CHRNA3\/CHRNB4 gene cluster are associated with onset of regular smoking - Stephens_2013_Genet.Epidemiol_37_846
Author(s) : Stephens SH , Hartz SM , Hoft NR , Saccone NL , Corley RC , Hewitt JK , Hopfer CJ , Breslau N , Coon H , Chen X , Ducci F , Dueker N , Franceschini N , Frank J , Han Y , Hansel NN , Jiang C , Korhonen T , Lind PA , Liu J , Lyytikainen LP , Michel M , Shaffer JR , Short SE , Sun J , Teumer A , Thompson JR , Vogelzangs N , Vink JM , Wenzlaff A , Wheeler W , Yang BZ , Aggen SH , Balmforth AJ , Baumeister SE , Beaty TH , Benjamin DJ , Bergen AW , Broms U , Cesarini D , Chatterjee N , Chen J , Cheng YC , Cichon S , Couper D , Cucca F , Dick D , Foroud T , Furberg H , Giegling I , Gillespie NA , Gu F , Hall AS , Hallfors J , Han S , Hartmann AM , Heikkila K , Hickie IB , Hottenga JJ , Jousilahti P , Kaakinen M , Kahonen M , Koellinger PD , Kittner S , Konte B , Landi MT , Laatikainen T , Leppert M , Levy SM , Mathias RA , McNeil DW , Medland SE , Montgomery GW , Murray T , Nauck M , North KE , Pare PD , Pergadia M , Ruczinski I , Salomaa V , Viikari J , Willemsen G , Barnes KC , Boerwinkle E , Boomsma DI , Caporaso N , Edenberg HJ , Francks C , Gelernter J , Grabe HJ , Hops H , Jarvelin MR , Johannesson M , Kendler KS , Lehtimaki T , Magnusson PK , Marazita ML , Marchini J , Mitchell BD , Nothen MM , Penninx BW , Raitakari O , Rietschel M , Rujescu D , Samani NJ , Schwartz AG , Shete S , Spitz M , Swan GE , Volzke H , Veijola J , Wei Q , Amos C , Cannon DS , Grucza R , Hatsukami D , Heath A , Johnson EO , Kaprio J , Madden P , Martin NG , Stevens VL , Weiss RB , Kraft P , Bierut LJ , Ehringer MA
Ref : Genet Epidemiol , 37 :846 , 2013
Abstract : Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.
ESTHER : Stephens_2013_Genet.Epidemiol_37_846
PubMedSearch : Stephens_2013_Genet.Epidemiol_37_846
PubMedID: 24186853

Title : The genome of the hydatid tapeworm Echinococcus granulosus - Zheng_2013_Nat.Genet_45_1168
Author(s) : Zheng H , Zhang W , Zhang L , Zhang Z , Li J , Lu G , Zhu Y , Wang Y , Huang Y , Liu J , Kang H , Chen J , Wang L , Chen A , Yu S , Gao Z , Jin L , Gu W , Wang Z , Zhao L , Shi B , Wen H , Lin R , Jones MK , Brejova B , Vinar T , Zhao G , McManus DP , Chen Z , Zhou Y , Wang S
Ref : Nat Genet , 45 :1168 , 2013
Abstract : Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
ESTHER : Zheng_2013_Nat.Genet_45_1168
PubMedSearch : Zheng_2013_Nat.Genet_45_1168
PubMedID: 24013640
Gene_locus related to this paper: echgr-k4epc5 , echmu-u6hbw4 , echgr-w6ugl0 , echgr-w6u7y4 , echgr-w6vaq5 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , echgr-a0a068wl60

Title : In situ formation of metal coordination polymer: a strategy for fluorescence turn-on assay of acetylcholinesterase activity and inhibitor screening - Liao_2013_Anal.Chem_85_2667
Author(s) : Liao D , Chen J , Zhou H , Wang Y , Li Y , Yu C
Ref : Analytical Chemistry , 85 :2667 , 2013
Abstract : A novel method for the sensing of acetylcholinesterase (AChE) activity and inhibitor screening based on the formation of metal coordination polymer has been developed. Acetylthiocholine (ATCh) was selected as the substrate. In the presence of AChE, ATCh was hydrolyzed to thiocholine and acetate. Thiocholine interacted with Ag(I) to form a metal coordination polymer. A positively charged perylene probe (probe 1) was employed. The fluorescence of probe 1 was very efficiently quenched by a polyanion [PVS, poly(vinyl sulfonate)]. In the presence of acetylcholinesterase, the positively charged metal coordination polymer newly formed in situ would interact with PVS, probe 1 monomer molecules were released, and a turn on fluorescence signal was detected. The assay is highly sensitive, a limit of detection of 0.04 mU/mL AChE was obtained. The assay is also highly selective, a number of potential interference proteins (enzymes) were tested, and none of them show noticeable interference. Sensing of AChE inhibitor was also demonstrated. Our assay is fairly simple and inexpensive. We envision that it could be used for the sensitive detection of other hydrolytic enzyme activities with properly selected substrates and for the screening of potential inhibitor drugs.
ESTHER : Liao_2013_Anal.Chem_85_2667
PubMedSearch : Liao_2013_Anal.Chem_85_2667
PubMedID: 23379662

Title : A novel strategy for enhancing extracellular secretion of recombinant proteins in Escherichia coli - Su_2013_Appl.Microbiol.Biotechnol_97_6705
Author(s) : Su L , Xu C , Woodard RW , Chen J , Wu J
Ref : Applied Microbiology & Biotechnology , 97 :6705 , 2013
Abstract : Secretion of cytoplasmic expressed proteins into culture medium has significant commercial advantages in large-scale production of proteins. Our previous study demonstrated that the membrane permeability of Escherichia coli could be significantly improved when Thermobifida fusca cutinase, without a signal peptide, was expressed in cytoplasm. This study investigated the extracellular production of other recombinant proteins, including both secretory and cytosolic proteins, with co-expression of cutinase. When the secretory enzymes, xylanase and alpha-amylase, were co-expressed with cutinase, the culture period was shortened by half, and the productivity was 7.9 and 2.0-fold to that of their individual control without co-expression, respectively. When the normally cytosolic proteins, xylose isomerase and trehalose synthase, were co-expressed with cutinase, more than half of the target proteins were "secreted" into the culture medium. Moreover, by using beta-galactosidase to detect membrane leakage, the improved secretion of the above model proteins was confirmed not to be due to cell lysis. The study provides a novel strategy for enhancing extracellular secretion of recombinant proteins in E. coli.
ESTHER : Su_2013_Appl.Microbiol.Biotechnol_97_6705
PubMedSearch : Su_2013_Appl.Microbiol.Biotechnol_97_6705
PubMedID: 23722267

Title : Enhanced activity toward PET by site-directed mutagenesis of Thermobifida fusca cutinase-CBM fusion protein - Zhang_2013_Carbohydr.Polym_97_124
Author(s) : Zhang Y , Wang L , Chen J , Wu J
Ref : Carbohydr Polym , 97 :124 , 2013
Abstract : In the present study, cutinase-CBMCenA fusion protein was genetically modified in the carbohydrate-binding module (CBM) binding sites, by site-directed mutagenesis, to enhance its activity toward polyethylene terephthalate (PET) fiber. The effects of tryptophan at particular positions of CBMCenA on the binding and hydrolysis of polyester substrate were investigated by replacing each of Trp14, Trp50 and Trp68 with leucine or tyrosine, respectively. All the mutants were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that the mutants displayed similar thermostability and pH stabilities in response to the native enzyme. Furthermore, W68L and W68Y, among all the mutants, exhibited significant improvement in binding and catalytic efficiency (1.4-1.5 fold) toward PET fiber when compared to that of the native enzyme. The enhanced binding and hydrolytic activity might be a result of creating new hydrogen bond or hydrophobic interaction between the enzyme and PET fiber.
ESTHER : Zhang_2013_Carbohydr.Polym_97_124
PubMedSearch : Zhang_2013_Carbohydr.Polym_97_124
PubMedID: 23769527

Title : Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration - Liu_2013_Biomaterials_34_3870
Author(s) : Liu Z , Jiang M , Kang T , Miao D , Gu G , Song Q , Yao L , Hu Q , Tu Y , Pang Z , Chen H , Jiang X , Gao X , Chen J
Ref : Biomaterials , 34 :3870 , 2013
Abstract : Development of effective non-invasive drug delivery systems is of great importance to the treatment of Alzheimer's diseases and has made great progress in recent years. In this work, lactoferrin (Lf), a natural iron binding protein, whose receptor is highly expressed in both respiratory epithelial cells and neurons is here utilized to facilitate the nose-to-brain drug delivery of neuroprotection peptides. The Lf-conjugated PEG-PCL nanoparticle (Lf-NP) was constructed via a maleimide-thiol reaction with the Lf conjugation confirmed by CBQCA Protein Quantitation and XPS analysis. Other important parameters such as particle size distribution, zeta potential and in vitro release of fluorescent probes were also characterized. Compared with unmodified nanoparticles (NP), Lf-NP exhibited a significantly enhanced cellular accumulation in 16HBE14o-cells through both caveolae-/clathrin-mediated endocytosis and direct translocation. Following intranasal administration, Lf-NP facilitated the brain distribution of the coumarin-6 incorporated with the AUC0-8h in rat cerebrum (with hippocampus removed), cerebellum, olfactory tract, olfactory bulb and hippocampus 1.36, 1.53, 1.70, 1.57 and 1.23 times higher than that of coumarin-6 carried by NP, respectively. Using a neuroprotective peptide - NAPVSIPQ (NAP) as the model drug, the neuroprotective and memory improvement effect of Lf-NP was observed even at lower dose than that of NP in a Morris water maze experiment, which was also confirmed by the evaluation of acetylcholinesterase, choline acetyltransferase activity and neuronal degeneration in the mice hippocampus. In conclusion, Lf-NP may serve as a promising nose-to-brain drug delivery carrier especially for peptides and proteins.
ESTHER : Liu_2013_Biomaterials_34_3870
PubMedSearch : Liu_2013_Biomaterials_34_3870
PubMedID: 23453061

Title : Poster: In vitro exposure to nicotine modulate the function of presynaptic NMDA receptors present on dopaminergic terminals in rat Nucleus Accumbens -
Author(s) : Marchi M , Salamone A , Zappettini S , Grilli M , Olivero G , Chen J , Cunha R , Pittaluga A
Ref : Biochemical Pharmacology , 86 :1228 , 2013
PubMedID:

Title : Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans - Zhang_2013_Genome.Announc_1_E00213
Author(s) : Zhang J , Cao G , Xu X , Jin H , Zhang Q , Chen J , Yang X , Pan H , Zhang X , Allard M , Brown E , Meng J
Ref : Genome Announc , 1 :E00213 , 2013
Abstract : Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China.
ESTHER : Zhang_2013_Genome.Announc_1_E00213
PubMedSearch : Zhang_2013_Genome.Announc_1_E00213
PubMedID: 23661485
Gene_locus related to this paper: salty-STY1441

Title : Complete Genome Sequence of Glaciecola psychrophila Strain 170T - Yin_2013_Genome.Announc_1_e00199
Author(s) : Yin J , Chen J , Liu G , Yu Y , Song L , Wang X , Qu X
Ref : Genome Announc , 1 : , 2013
Abstract : Here, we report the complete genome sequence of Glaciecola psychrophila strain 170(T), a novel species of the genus Glaciecola, isolated from sea ice at high-latitude Arctic locations. The genome consists of a single chromosome (5,413,691 bp) and 5,363 genes. The genomics information will facilitate the study of the physiology, cold adaptation, and evolution of this genus.
ESTHER : Yin_2013_Genome.Announc_1_e00199
PubMedSearch : Yin_2013_Genome.Announc_1_e00199
PubMedID: 23640379
Gene_locus related to this paper: 9alte-k7ach6 , 9alte-k7ahj1 , 9alte-k7ava9 , 9alte-k6ynu0 , 9alte-k6z391 , 9alte-k7a5n7 , 9alte-k7a8i8

Title : In vivo readout of CFTR function: ratiometric measurement of CFTR-dependent secretion by individual, identifiable human sweat glands - Wine_2013_PLoS.One_8_e77114
Author(s) : Wine JJ , Char JE , Chen J , Cho HJ , Dunn C , Frisbee E , Joo NS , Milla C , Modlin SE , Park IH , Thomas EA , Tran KV , Verma R , Wolfe MH
Ref : PLoS ONE , 8 :e77114 , 2013
Abstract : To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a beta-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.
ESTHER : Wine_2013_PLoS.One_8_e77114
PubMedSearch : Wine_2013_PLoS.One_8_e77114
PubMedID: 24204751

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Association of lipoprotein lipase polymorphism rs2197089 with serum lipid concentrations and LPL gene expression - Mo_2013_J.Hum.Genet_58_160
Author(s) : Mo X , Liu X , Wang L , Lu X , Chen S , Li H , Huang J , Chen J , Cao J , Li J , Tang Y , Gu D
Ref : J Hum Genet , 58 :160 , 2013
Abstract : Many single-nucleotide polymorphisms (SNPs) have been reported to be associated with lipid concentrations in recent genome-wide association studies. The aim of this study was to validate the associations of rs2197089 in the lipoprotein lipase (LPL) gene with serum lipid concentrations and gene expression levels in the Chinese Han population and examine the potential interactions. A total of 9339 participants were recruited and genotyped for rs2197089. Gene expression levels of LPL in blood cells of 309 participants were evaluated by real-time PCR. We observed significant associations between rs2197089 and decreased triglycerides (TG) (P=0.0006), but not high-density lipoprotein cholesterol (HDL-C) concentration (P=0.0881). However, weak evidence of interaction between cigarette smoking and rs2197089 was detected (P=0.0362). In smokers, significant association between rs2197089 and increased HDL-C concentration was found (P=0.0068). Participants with the minor allele A had higher expression levels of LPL (P=0.0243). The results of our study indicated that rs2197089 was significantly associated with TG but it was associated with HDL-C only in smokers. This SNP seemed to have influence on the expression level of LPL.
ESTHER : Mo_2013_J.Hum.Genet_58_160
PubMedSearch : Mo_2013_J.Hum.Genet_58_160
PubMedID: 23344322

Title : Free energy landscape for the binding process of Huperzine A to acetylcholinesterase - Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
Author(s) : Bai F , Xu Y , Chen J , Liu Q , Gu J , Wang X , Ma J , Li H , Onuchic JN , Jiang H
Ref : Proc Natl Acad Sci U S A , 110 :4273 , 2013
Abstract : Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, k(off) and activation free energy of dissociation (DeltaG(off) not equal). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzheimer's disease drug (-)-Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/mol. The method also provides atomic resolution information for the (-)-Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect this methodology to be widely applicable to drug discovery and development.
ESTHER : Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
PubMedSearch : Bai_2013_Proc.Natl.Acad.Sci.U.S.A_110_4273
PubMedID: 23440190

Title : D14-SCFD3-dependent degradation of D53 regulates strigolactone signalling - Zhou_2013_Nature_504_406
Author(s) : Zhou F , Lin Q , Zhu L , Ren Y , Zhou K , Shabek N , Wu F , Mao H , Dong W , Gan L , Ma W , Gao H , Chen J , Yang C , Wang D , Tan J , Zhang X , Guo X , Wang J , Jiang L , Liu X , Chen W , Chu J , Yan C , Ueno K , Ito S , Asami T , Cheng Z , Lei C , Zhai H , Wu C , Wang H , Zheng N , Wan J
Ref : Nature , 504 :406 , 2013
Abstract : Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.
ESTHER : Zhou_2013_Nature_504_406
PubMedSearch : Zhou_2013_Nature_504_406
PubMedID: 24336215

Title : A randomized, 4-week double-blind placebo control study on the efficacy of donepezil augmentation of lithium for treatment of acute mania - Chen_2013_Neuropsychiatr.Dis.Treat_9_839
Author(s) : Chen J , Lu Z , Zhang M , Zhang J , Ni X , Jiang X , Xu H , Heeramun-Aubeeluck A , Hu Q , Jin H , Davis JM
Ref : Neuropsychiatr Dis Treat , 9 :839 , 2013
Abstract : INTRODUCTION: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period, would benefit patients with acute mania.
METHODS: We conducted a 4-week double-blind, placebo-controlled trial of donepezil as an adjunctive treatment to lithium in patients with acute mania. Eligible subjects were randomly assigned to receive donepezil or placebo in addition to lithium. Donepezil was started at 5 mg/day, and increased to 10 mg/day in the first week. Patients were rated with the Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS) at baseline, day 1, week 1, week 2, and week 4.
RESULTS: Out of the 30 patients who were enrolled, 15 were on donepezil and 15 were on placebo. All patients completed the 4-week trial. On the first day, there was a difference of 1.97 units on the psychomotor symptoms scale of the YMRS in the donepezil group as compared to the placebo group (t = 2.39, P = 0.02). There was a difference of 0.57 units (t = 2.09, P = 0.04) in the speech item and a difference of 0.29 units in the sexual interest item (t = 2.11, P = 0.04) in the donepezil group as compared to the placebo group. The total YMRS difference on the first day approached the conventional significance level (1.97 units, t = 1.84, P = 0.07). Over the course of 4 weeks, we failed to find that donepezil produced any significant difference in the YMRS (6.71 units difference, t = -1.44, P = 0.16) or the BPRS scale (1.29 units difference, t = -0.33, P = 0.75) as compared to placebo. Ten subjects (66.67%) in both groups met the criteria for clinical response (Fisher's exact P = 1.00). Five subjects (33.33%) in the donepezil group met the criteria for clinical remission while nine subjects (60.00%) in the placebo group met the remission criteria (Fisher's exact P = 0.27). CONCLUSION: Use of the oral anticholinergic donepezil had some benefit in the augmentation of lithium treatment on the first day, but did not provide any significant benefits in the long-term.
ESTHER : Chen_2013_Neuropsychiatr.Dis.Treat_9_839
PubMedSearch : Chen_2013_Neuropsychiatr.Dis.Treat_9_839
PubMedID: 23807849

Title : Novel tacrine-ebselen hybrids with improved cholinesterase inhibitory, hydrogen peroxide and peroxynitrite scavenging activity - Mao_2013_Bioorg.Med.Chem.Lett_23_6737
Author(s) : Mao F , Chen J , Zhou Q , Luo Z , Huang L , Li X
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :6737 , 2013
Abstract : A series of tacrine-ebselen hybrids were synthesised and evaluated as possible multifunctional anti-Alzheimer's disease (AD) agents. Compound 6i, which is tacrine linked with 5,6-dimethoxybenzo[d][1,2]selenazol-3(2H)-one by a six-carbon spacer, was the most potent acetylcholinesterase (AChE) and butylcholinesterase (BCHE) inhibitor, with IC50 values of 2.55 and 2.80nM, respectively. Furthermore, this compound demonstrated similar hydrogen peroxide and peroxynitrite scavenging activity as ebselen by horseradish peroxidase assay and peroxynitrite scavenging activity assay, indicating that this hybrid is a good multifunctional drug candidate for the treatment of AD.
ESTHER : Mao_2013_Bioorg.Med.Chem.Lett_23_6737
PubMedSearch : Mao_2013_Bioorg.Med.Chem.Lett_23_6737
PubMedID: 24220172

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J ,