Zhu Y

References (123)

Title : AChE activity self-breathing control mechanisms regulated by H(2)S(n) and GSH: Persulfidation and glutathionylation on sulfhydryl after disulfide bonds cleavage - Zhu_2024_Int.J.Biol.Macromol_259_129117
Author(s) : Zhu Y , Hu Z , Liu Y , Yan T , Liu L , Wang Y , Bai B
Ref : Int J Biol Macromol , 259 :129117 , 2024
Abstract : Hydrogen sulfide (H(2)S), or dihydrogen sulfane (H(2)S(n)), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H(2)S. However, little is known about the mechanisms by which H(2)S(n) and GSH affect the disulfide bonds. In this study, we provide direct evidences that H(2)S(n) and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first CS bond is broken, then the SS bond is broken to release H(2)S. H(2)S(n) and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H(2)S(n) and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H(2)S(n) and GSH. These theoretical findings shed light on the biological functions of H(2)S(n) and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.
ESTHER : Zhu_2024_Int.J.Biol.Macromol_259_129117
PubMedSearch : Zhu_2024_Int.J.Biol.Macromol_259_129117
PubMedID: 38211930

Title : Discovery of Enzyme Inhibitors from Mangrove Sediment Derived Fungus Trichoderma harzianum SCSIO 41051 - Huang_2024_Chem.Biodivers__e202400070
Author(s) : Huang L , Chen C , Cai J , Chen Y , Zhu Y , Yang B , Zhou X , Liu Y , Tao H
Ref : Chem Biodivers , :e202400070 , 2024
Abstract : One new fatty acid derivative, (2E,4E)-6,7-dihydroxy-2-methylocta-2,4-dienoic acid (1), and 16 known compounds (2-17) were isolated from the mangrove sediment derived fungus Trichoderma harzianum SCSIO 41051. Their structures were established by spectroscopic methods, computational ECD, and Mo2(OAc)4-induced ECD experiment. All the compounds were evaluated for their acetylcholinesterase (AChE) and pancreatic lipase (PL) inhibition. Compounds 9 and 14 exhibited moderate AChE inhibitory activities with IC50 values of 2.49 and 2.92 microM, respectively, which compounds 8 and 9 displayed moderate inhibition on PL with IC50 value of 2.30 and 2.34 microM, respectively.
ESTHER : Huang_2024_Chem.Biodivers__e202400070
PubMedSearch : Huang_2024_Chem.Biodivers__e202400070
PubMedID: 38356321

Title : Biochemical and molecular characterization of neonicotinoids resistance in the tarnished plant bug, Lygus lineolaris - Du_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109765
Author(s) : Du Y , Scheibener S , Zhu Y , Portilla M , Reddy GVP
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109765 , 2023
Abstract : In the southern United States, neonicotinoids are commonly applied as foliar insecticides to control sucking insect pests, such as the tarnished plant bug (TPB, Lygus lineolaris). In this study, spraying bioassays were conducted to determine the toxicity of five neonicotinoids and sulfoxaflor to susceptible and late fall field-collected TPB adults from Mississippi Delta region. Compared to a susceptible population, the field-collected TPBs exhibited the highest resistance to imidacloprid (up to 19.5-fold), a moderate resistance to acetamiprid (9.43-fold), clothianidin (13.68-fold), thiamethoxam (7.88-fold) and the least resistance to thiacloprid (4.61-fold) and sulfoxaflor (1.82-fold), respectively. A synergist study demonstrated that piperonyl butoxide (PBO) significantly increased the toxicity of imidacloprid and thiamethoxam by 22.2- and 15.3-fold, respectively, while triphenyl phosphate (TPP) and diethyl maleate (DEM) only showed 2-3-fold synergism to both neonicotinoids. In the field-collected TPBs, activities of the three detoxification enzymes esterase, glutathione S-transferase (GST) and CYP450 monooxygenase (P450) were significantly increased by 3.43-, 1.48- and 2.7-fold, respectively, when compared to the susceptible population. Additionally, after 48 h exposure to imidacloprid or thiamethoxam, resistant TPB adults exhibited elevated esterase activities, decreased GST activities, and no significant changes in P450 activities. Further examinations revealed that the expression of certain esterase and P450 detoxification genes were significantly elevated in resistant TPBs. Overall, these results suggest that elevated esterase and P450s expression and enzyme activity are key mechanisms for metabolic resistance in TPBs to neonicotinoids. Our findings also provide valuable information for selection and adoption of neonicotinoid insecticides for resistance management of TPBs and minimizing toxic risk to foraging bees.
ESTHER : Du_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109765
PubMedSearch : Du_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109765
PubMedID: 37844747

Title : Resistance risk assessment of six pyrethroids and acephate toward the resistant adult tarnished plant bug, Lygus lineolaris - Du_2023_Insect.Sci__
Author(s) : Du Y , Scheibener S , Zhu Y , Portilla M , Zhang M
Ref : Insect Sci , : , 2023
Abstract : Due to rapidly developed resistance, pest management relies less on pyrethroids to control economically damaging infestations of the tarnished plant bug (TPB), Lygus lineolaris (Palisot de Beauvois) in cotton fields of Mississippi. Yet, pyrethroid resistance remains prevalent in TPB populations. This study assessed the resistance levels in adult TPB to six common pyrethroids and acephate. Resistant TBPs were collected from wild host plants in late October after harvest in the Mississippi Delta region of the United States. Based on LC(50) values, the field-resistant TPBs displayed higher resistance to permethrin, esfenvalerate, and bifenthrin (approximately 30 fold) and moderate resistance to lambda-cyhalothrin, beta-cyfluthrin, -cypermethrin, and acephate (approximately 15 fold). Further investigations showed that the inhibitors of three detoxification enzyme, triphenyl phosphate (TPP), diethyl maleate (DEM), and piperonyl butoxide (PBO) had synergistic effects on permethrin, lambda-cyhalothrin, and bifenthrin in resistant TPBs. Furthermore, elevated esterase, GST, and P450 activities were significantly expressed in field-resistant TPBs. Additionally, GST and esterase were reduced after 48 h exposure to certain pyrethroids at LC(50) dose. The synergistic and biochemical assays consistently indicated that P450 and esterase were involved in pyrethroid detoxification in TPBs. This study provides valuable information for the continued use of pyrethroids and acephate in controlling TPBs in cotton fields in the Mississippi Delta region of the United States.
ESTHER : Du_2023_Insect.Sci__
PubMedSearch : Du_2023_Insect.Sci__
PubMedID: 37850504

Title : Computational design of highly efficient thermostable MHET hydrolases and dual enzyme system for PET recycling - Zhang_2023_Commun.Biol_6_1135
Author(s) : Zhang J , Wang H , Luo Z , Yang Z , Zhang Z , Wang P , Li M , Zhang Y , Feng Y , Lu D , Zhu Y
Ref : Commun Biol , 6 :1135 , 2023
Abstract : Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 degreesC) to that of the PET hydrolase FAST-PETase (67.80 degreesC) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.
ESTHER : Zhang_2023_Commun.Biol_6_1135
PubMedSearch : Zhang_2023_Commun.Biol_6_1135
PubMedID: 37945666
Gene_locus related to this paper: geost-est30

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

Title : Recent advances in the biodegradation of polyethylene terephthalate with cutinase-like enzymes - Sui_2023_Front.Microbiol_14_1265139
Author(s) : Sui B , Wang T , Fang J , Hou Z , Shu T , Lu Z , Liu F , Zhu Y
Ref : Front Microbiol , 14 :1265139 , 2023
Abstract : Polyethylene terephthalate (PET) is a synthetic polymer in the polyester family. It is widely found in objects used daily, including packaging materials (such as bottles and containers), textiles (such as fibers), and even in the automotive and electronics industries. PET is known for its excellent mechanical properties, chemical resistance, and transparency. However, these features (e.g., high hydrophobicity and high molecular weight) also make PET highly resistant to degradation by wild-type microorganisms or physicochemical methods in nature, contributing to the accumulation of plastic waste in the environment. Therefore, accelerated PET recycling is becoming increasingly urgent to address the global environmental problem caused by plastic wastes and prevent plastic pollution. In addition to traditional physical cycling (e.g., pyrolysis, gasification) and chemical cycling (e.g., chemical depolymerization), biodegradation can be used, which involves breaking down organic materials into simpler compounds by microorganisms or PET-degrading enzymes. Lipases and cutinases are the two classes of enzymes that have been studied extensively for this purpose. Biodegradation of PET is an attractive approach for managing PET waste, as it can help reduce environmental pollution and promote a circular economy. During the past few years, great advances have been accomplished in PET biodegradation. In this review, current knowledge on cutinase-like PET hydrolases (such as TfCut2, Cut190, HiC, and LCC) was described in detail, including the structures, ligand-protein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts were highlighted, such as improving the PET hydrolytic activity by constructing fusion proteins. The review is expected to provide novel insights for the biodegradation of complex polymers.
ESTHER : Sui_2023_Front.Microbiol_14_1265139
PubMedSearch : Sui_2023_Front.Microbiol_14_1265139
PubMedID: 37849919

Title : Mechanism of active acetylcholinesterase inhibition by organic sulfanes in garlic: Non-covalent binding and covalent modifications - Zhu_2023_Int.J.Biol.Macromol__124972
Author(s) : Zhu Y , Shi D , Chen A , Wang Y , Liu L , Bai B
Ref : Int J Biol Macromol , :124972 , 2023
Abstract : Numerous secondary metabolites in medicinal food homology plants such as Allium inhibit the activity of acetylcholinesterase (AChE), but the current understanding of the inhibition mechanism is limited. In this study, we employed ultrafiltration, spectroscopic, molecular docking, and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS/MS) techniques to investigate the inhibition mechanism of AChE by garlic organic sulfanes, including diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). The results of UV-spectrophotometry and ultrafiltration experiments showed the inhibition of AChE activity by DAS and DADS was reversible (competitive inhibition), but inhibition by DATS was irreversible. Molecular fluorescence and molecular docking indicated DAS and DADS changed the positions of key amino acids inside the catalytic cavity through hydrophobic interactions with AChE. By using MALDI-TOF-MS/MS, we found DATS irreversibly inhibited AChE activity by opening disulfide-bond switching of disulfide bond 1 (Cys-69 and Cys-96) and disulfide bond 2 (Cys-257 and Cys-272) in AChE, as well as by covalently modifying Cys-272 in disulfide bond 2 to generate AChE-SSA derivatives (strengthened switch). This study provides a basis for further exploration of natural AChE inhibitors using organic active substances in garlic and presents a hypothesis of U-shaped spring force arm effect based on the disulfide bond-switching reaction of DATS that can be used to evaluate the stability of disulfide bonds in proteins.
ESTHER : Zhu_2023_Int.J.Biol.Macromol__124972
PubMedSearch : Zhu_2023_Int.J.Biol.Macromol__124972
PubMedID: 37285891

Title : Chromium exposure altered metabolome and microbiome-associated with neurotoxicity in zebrafish - Yan_2023_J.Appl.Toxicol__
Author(s) : Yan T , Xu Y , Zhu Y , Jiang P , Zhang Z , Li L , Wu Q
Ref : J Appl Toxicol , : , 2023
Abstract : In recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1mg/L Cr (III) and 1mg/L Cr (VI) for seven days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr- exposed groups, as compared to that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification.
ESTHER : Yan_2023_J.Appl.Toxicol__
PubMedSearch : Yan_2023_J.Appl.Toxicol__
PubMedID: 36727205

Title : Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction: Evidence from Metabolomics - Peng_2023_Phenomics_3_34
Author(s) : Peng L , Song Z , Zhao C , Abuduwufuer K , Wang Y , Wen Z , Ni L , Li C , Yu Y , Zhu Y , Jiang H , Shen J , Jiang X , Chen C , Zhang X , Wang DW
Ref : Phenomics , 3 :34 , 2023
Abstract : Epoxyeicosatrienoic acids (EETs) have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Heart failure with preserved ejection fraction (HFpEF) has shown an increased prevalence and worse prognosis over the decades. However, the role of sEH activity in HFpEF remains unclear. We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016. Eight types of sEH-related eicosanoids were measured according to target metabolomics, and their correlation with clinical endpoints was also analyzed. The primary endpoint was cardiac mortality, and the secondary endpoint was a composite of cardiac events, including heart failure (HF) readmission, cardiogenic hospitalization, and all-cause mortality. Furthermore, the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro. Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls. More importantly, sEH activity was positively correlated with cardiac mortality in patients with HFpEF, especially in older patients with arrhythmia. A consistent result was obtained in the multiple adjusted models. Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model. This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function. Clinical trial identifier: NCT03461107 (https://clinicaltrials.gov). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-022-00069-8.
ESTHER : Peng_2023_Phenomics_3_34
PubMedSearch : Peng_2023_Phenomics_3_34
PubMedID: 36939801

Title : Oxymatrine-mediated prevention of amyloid beta-peptide-induced apoptosis on Alzheimer's model PC12 cells: in vitro cell culture studies and in vivo cognitive assessment in rats - Zhu_2023_Inflammopharmacology__
Author(s) : Zhu Y , Wang Z , Gao C , Zhang L , Sui R
Ref : Inflammopharmacology , : , 2023
Abstract : Alzheimer's disease (AD) is a major neurological disease affecting elderly individuals worldwide. Existing drugs only reduce the symptoms of the disease without addressing the underlying causes. Commonly, Abeta25-35 peptide aggregation is the main reason for AD development. Recently, the discovery of multiple protein-targeting molecules has provided a new strategy for treating AD. This study demonstrates the neuroprotective potential of oxymatrine against multiple mechanisms, such as acetylcholinesterase, mitochondrial damage, and beta-amyloid-induced cell toxicity. The in vitro cell culture studies showed that oxymatrine possesses significant potential to inhibit acetylcholine esterase and promotes antioxidant, antiapoptotic effects while preventing Abeta25-35 peptide aggregation in PC12 cells. Furthermore, oxymatrine protects PC12 cells against Abeta25-35-induced cytotoxicity and down-regulates the reactive oxygen species generation. The in vivo acute toxicological studies confirm the safety of oxymatrine without causing organ damage or death in animals. Overall, this study provided evidence that oxymatrine is an efficient neuroprotective agent, with a potential to be a multifunctional drug for Alzheimer's disease treatment. These findings present a reliable and synergistic approach for treating AD.
ESTHER : Zhu_2023_Inflammopharmacology__
PubMedSearch : Zhu_2023_Inflammopharmacology__
PubMedID: 37515653

Title : Application of Marine Natural Products against Alzheimer's Disease: Past, Present and Future - Hu_2023_Mar.Drugs_21_
Author(s) : Hu D , Jin Y , Hou X , Zhu Y , Chen D , Tai J , Chen Q , Shi C , Ye J , Wu M , Zhang H , Lu Y
Ref : Mar Drugs , 21 : , 2023
Abstract : Alzheimer's disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer's disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD.
ESTHER : Hu_2023_Mar.Drugs_21_
PubMedSearch : Hu_2023_Mar.Drugs_21_
PubMedID: 36662216

Title : Eucommia ulmoides Olive Male Flower Extracts Ameliorate Alzheimer's Disease-Like Pathology in Zebrafish via Regulating Autophagy, Acetylcholinesterase, and the Dopamine Transporter - Sun_2022_Front.Mol.Neurosci_15_901953
Author(s) : Sun C , Zhang S , Ba S , Dang J , Ren Q , Zhu Y , Liu K , Jin M
Ref : Front Mol Neurosci , 15 :901953 , 2022
Abstract : Alzheimer's disease (AD) is the most prevalent neural disorder. However, the therapeutic agents for AD are limited. Eucommia ulmoides Olive (EUO) is widely used as a traditional Chinese herb to treat various neurodegenerative disorders. Therefore, we investigated whether the extracts of EUO male flower (EUMF) have therapeutic effects against AD. We focused on the flavonoids of EUMF and identified the composition using a targeted HPLC-MS analysis. As a result, 125 flavonoids and flavanols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins were identified. Then, the anti-AD effects of the EUMF were tested by using zebrafish AD model. The behavioral changes were detected by automated video-tracking system. Abeta deposition was assayed by thioflavin S staining. Ache activity and cell apoptosis in zebrafish were tested by, Acetylcholine Assay Kit and TUNEL assay, respectively. The results showed that EUMF significantly rescued the dyskinesia of zebrafish and inhibited Abeta deposition, Ache activity, and occurrence of cell apoptosis in the head of zebrafish induced by AlCl(3). We also investigated the mechanism underlying anti-AD effects of EUMF by RT-qPCR and found that EUMF ameliorated AD-like symptoms possibly through inhibiting excessive autophagy and the abnormal expressions of ache and slc6a3 genes. In summary, our findings suggested EUMF can be a therapeutic candidate for AD treatment.
ESTHER : Sun_2022_Front.Mol.Neurosci_15_901953
PubMedSearch : Sun_2022_Front.Mol.Neurosci_15_901953
PubMedID: 35754707

Title : Flavin-enabled reductive and oxidative epoxide ring opening reactions - De_Nat.Commun_13_4896
Author(s) : De BC , Zhang W , Yang C , Mandi A , Huang C , Zhang L , Liu W , Ruszczycky MW , Zhu Y , Ma M , Bashiri G , Kurtan T , Liu Hw , Zhang C
Ref : Nat Commun , 13 :4896 , 2022
Abstract : Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis.
ESTHER : De_Nat.Commun_13_4896
PubMedSearch : De_Nat.Commun_13_4896
PubMedID: 35986005

Title : Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice - Huang_2022_Nutrients_14_
Author(s) : Huang X , Zhuo Y , Jiang D , Zhu Y , Fang Z , Che L , Lin Y , Xu S , Hua L , Zou Y , Huang C , Li L , Wu D , Feng B
Ref : Nutrients , 14 : , 2022
Abstract : A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.
ESTHER : Huang_2022_Nutrients_14_
PubMedSearch : Huang_2022_Nutrients_14_
PubMedID: 36235710

Title : The Acaricidal Potential of a New Agent GC16 for Tetranychus pueraricola (Acari: Tetranychidae) Based on Developmental Performance and Physiological Enzyme Activity - He_2022_J.Econ.Entomol__
Author(s) : He Y , Du G , Xie S , Long X , He X , Zhu Y , Chen B
Ref : J Econ Entomol , : , 2022
Abstract : The spider mite, Tetranychus pueraricola (Ehara & Gotoh; Acari: Tetranychidae), is a serious pest in agriculture and horticulture. Application of chemical pesticides is the main mode of this pest control. Due to pesticide residues and resistance-induced resurgence of pests, there is a need to discover alternatives for spider mite management. GC16 comprises a mixture of calcium chloride (CaCl2, 45%) and lecithin (55%), which was recently found to have acaricidal properties. We evaluated the sublethal effects of GC16 on T. pueraricola using life table and enzyme [catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), carboxylesterase (CarE), glutathione S-transferases (GST), and Ca2+-ATPase (Ca2+-ATP)] activity assays. The results showed that fecundity of T. pueraricola increased at LC30 but decreased at LC50 of GC16. The intrinsic rate of increase (r) of T. pueraricola decreased under the LC30 and LC50 of GC16. GC16 concentration and exposure time significantly influenced the activities of CAT, POD, CarE, GST, and Ca2+-ATP in adult mites. Twelve hours later after the treatment, GST and Ca2+-ATP activities were significantly inhibited by LC30 but enhanced by LC50. Moreover, the demographic parameter r and enzyme activities were negatively correlated. In sum, sublethal amounts of GC16 had an adverse effect on mites, and there was a trade-off between developmental performance and physiological enzyme activity of mites under GC16 stress, and GC16 showed an acaricidal potential for T. pueraricola. This work provides guidance for the application of GC16 to control T. pueraricola.
ESTHER : He_2022_J.Econ.Entomol__
PubMedSearch : He_2022_J.Econ.Entomol__
PubMedID: 35512629

Title : Phenylbutyrate modulates polyamine acetylase and ameliorates Snyder-Robinson syndrome in a Drosophila model and patient cells - Tao_2022_JCI.Insight_7_
Author(s) : Tao X , Zhu Y , Diaz-Perez Z , Yu SH , Foley JR , Stewart TM , Casero RA, Jr. , Steet R , Zhai RG
Ref : JCI Insight , 7 : , 2022
Abstract : Polyamine dysregulation plays key roles in a broad range of human diseases from cancer to neurodegeneration. Snyder-Robinson syndrome (SRS) is the first known genetic disorder of the polyamine pathway, caused by X-linked recessive loss-of-function mutations in spermine synthase. In the Drosophila SRS model, altered spermidine/spermine balance has been associated with increased generation of ROS and aldehydes, consistent with elevated spermidine catabolism. These toxic byproducts cause mitochondrial and lysosomal dysfunction, which are also observed in cells from SRS patients. No efficient therapy is available. We explored the biochemical mechanism and discovered acetyl-CoA reduction and altered protein acetylation as potentially novel pathomechanisms of SRS. We repurposed the FDA-approved drug phenylbutyrate (PBA) to treat SRS using an in vivo Drosophila model and patient fibroblast cell models. PBA treatment significantly restored the function of mitochondria and autolysosomes and extended life span in vivo in the Drosophila SRS model. Treating fibroblasts of patients with SRS with PBA ameliorated autolysosome dysfunction. We further explored the mechanism of drug action and found that PBA downregulates the first and rate-limiting spermidine catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1), reduces the production of toxic metabolites, and inhibits the reduction of the substrate acetyl-CoA. Taken together, we revealed PBA as a potential modulator of SAT1 and acetyl-CoA levels and propose PBA as a therapy for SRS and potentially other polyamine dysregulation-related diseases.
ESTHER : Tao_2022_JCI.Insight_7_
PubMedSearch : Tao_2022_JCI.Insight_7_
PubMedID: 35801587

Title : Threaded 3D microfluidic paper analytical device-based ratiometric fluorescent sensor for background-free and visual detection of organophosphorus pesticides - Tong_2022_Biosens.Bioelectron_222_114981
Author(s) : Tong X , Cai G , Xie L , Wang T , Zhu Y , Peng Y , Tong C , Shi S , Guo Y
Ref : Biosensors & Bioelectronics , 222 :114981 , 2022
Abstract : With the increasing concerns of food safety and environmental protection, it is desirable to develop reliable, effective, and portable sensors for detection of organophosphorus pesticides (OPs). Here, a cascade reaction system integrated with threaded 3D microfluidic paper analytical device (3D microPAD) was firstly developed for background-free and visual detection of OPs in agricultural samples. Butyrylcholinesterase (BChE) hydrolyzed acetylcholine into thiocholine (TCh), which reduced MnO(2) nanosheets into Mn(2+). With addition of OPs, BChE activity was irreversibly inhibited, and the generation of TCh and the reduction of MnO(2) nanosheets were prevented. Then the remaining MnO(2) nanosheets oxidized o-phenylenediamine into 2,3-diaminophenazine with yellow-emission fluorescence, which quenched the fluorescence intensity of red-emission carbon dots (RCDs) via inner-filter effect. Based on above mechanism, a ratiometric fluorescent system was established for OPs detection. Threaded 3D microPAD consisted of 4 layers, which allowed to load and/or add reagents to trigger the cascade reaction system for OPs detection. The fluorescent images presented distinguishable color variations from red to yellow with dichlorvos concentrations ranging from 2.5 to 120 microgsL(-1), and the limit of detection was 1.0 microgsL(-1). In the practical samples testing, threaded 3D microPAD can eliminate background influence on fluorescent signal for OPs detection. Threaded 3D microPAD integrated with ratiometric sensing platform has merits of accuracy response, facile operation, and background-free detection, which supplies a new alternative approach for on-site pesticide detection.
ESTHER : Tong_2022_Biosens.Bioelectron_222_114981
PubMedSearch : Tong_2022_Biosens.Bioelectron_222_114981
PubMedID: 36473422

Title : Biochemical characterization of a novel feruloyl esterase from Burkholderia pyrrocinia B1213 and its application for hydrolyzing wheat bran - Fu_2022_3.Biotech_12_24
Author(s) : Fu Z , Zhu Y , Teng C , Fan G , Li X
Ref : 3 Biotech , 12 :24 , 2022
Abstract : In this study, a novel feruloyl esterase (BpFae) from Burkholderia pyrrocinia B1213 was purified, biochemically characterized, and applied in releasing ferulic acid from wheat bran. The molecular mass of BpFae was approximately 60 kDa by SDS-PAGE, and the enzyme was a homomultimer in solution. BpFae displayed maximum activity at pH 4.5-5.0 and was stable at pH 3.0-7.0. The optimal temperature for BpFae was 50 degreesC. BpFae activity was not affected by most metal ions tested and was significantly increased by Tween-20 and Triton-100. Purified BpFae exhibited a preference for methyl ferulate (41.78 U mg(-1)) over methyl p-coumarate (38.51 U mg(-1)) and methyl caffeate (35.36 U mg(-1)) and had the lowest activity on methyl sinapate (1.79 U mg(-1)). Under the optimum conditions, the K (m) and V (max) for methyl ferulate were 0.53 mM and 86.74 U mg(-1), respectively. Residues Ser209, His492, and Glu245 in the catalytic pocket of BpFae could form hydrogen bonds with the substrate and were crucial for catalytic activity and substrate specificity. When G11 xylanase XynA and BpFae were used separately for hydrolyzing de-starched wheat bran (DSWB), the ferulic acid released was undetectable and 1.78%, respectively, whereas it was increased to 59.26% using the mixture of the two enzymes. Thus, BpFae is considered an attractive candidate for the production of ferulic acid from agricultural by-products. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03066-2.
ESTHER : Fu_2022_3.Biotech_12_24
PubMedSearch : Fu_2022_3.Biotech_12_24
PubMedID: 35036272
Gene_locus related to this paper: 9burk-BpFae

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 : Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes - Yu_2022_PLoS.Pathog_18_e1010552
Author(s) : Yu X , Tong L , Zhang L , Yang Y , Xiao X , Zhu Y , Wang P , Cheng G
Ref : PLoS Pathog , 18 :e1010552 , 2022
Abstract : Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.
ESTHER : Yu_2022_PLoS.Pathog_18_e1010552
PubMedSearch : Yu_2022_PLoS.Pathog_18_e1010552
PubMedID: 35679229

Title : Alzheimer's disease medication use and adherence patterns by race and ethnicity - Olchanski_2022_Alzheimers.Dement__
Author(s) : Olchanski N , Daly AT , Zhu Y , Breslau R , Cohen JT , Neumann PJ , Faul JD , Fillit HM , Freund KM , Lin PJ
Ref : Alzheimers Dement , : , 2022
Abstract : BACKGROUND: We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD). METHODS: We examined cholinesterase inhibitors and memantine initiation, non-adherence, and discontinuation by race and ethnicity, using data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. RESULTS: Among newly diagnosed ADRD patients (n = 1299), 26% filled an ADRD prescription >=90 days and 36% >=365 days after diagnosis. Among individuals initiating ADRD-targeted treatment (n = 1343), 44% were non-adherent and 24% discontinued the medication during the year after treatment initiation. Non-Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 [95% confidence interval: 1.07-2.09]). DISCUSSION: Initiation of ADRD-targeted medications did not vary by ethnoracial group, but non-Hispanic Blacks had lower adherence than Whites. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. HIGHLIGHTS: Initiation of anti-dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish. Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.
ESTHER : Olchanski_2022_Alzheimers.Dement__
PubMedSearch : Olchanski_2022_Alzheimers.Dement__
PubMedID: 35939325

Title : Dual-Modal Nanoscavenger for Detoxification of Organophosphorus Compounds - Zou_2022_ACS.Appl.Mater.Interfaces__
Author(s) : Zou S , Wang B , Wang Q , Liu G , Song J , Zhang F , Li J , Wang F , He Q , Zhu Y , Zhang L
Ref : ACS Appl Mater Interfaces , : , 2022
Abstract : Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.
ESTHER : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zou_2022_ACS.Appl.Mater.Interfaces__
PubMedID: 36089739

Title : Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative - Liu_2022_Molecules_27_9062
Author(s) : Liu W , Zhao D , He Z , Hu Y , Zhu Y , Zhang L , Jin L , Guan L , Wang S
Ref : Molecules , 27 :9062 , 2022
Abstract : Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.
ESTHER : Liu_2022_Molecules_27_9062
PubMedSearch : Liu_2022_Molecules_27_9062
PubMedID: 36558194

Title : 3D origami paper-based ratiometric fluorescent microfluidic device for visual point-of-care detection of alkaline phosphatase and butyrylcholinesterase - Zhu_2021_Biosens.Bioelectron_196_113691
Author(s) : Zhu Y , Tong X , Wei Q , Cai G , Cao Y , Tong C , Shi S , Wang F
Ref : Biosensors & Bioelectronics , 196 :113691 , 2021
Abstract : On-site multiplex enzyme detection is crucial for diagnosis, therapeutics and prognostic. To date, it is still a daunting challenge to develop portable, low-cost, and efficient multi-enzyme detection methods. Herein, a novel sample-in-result-out platform integrating ratiometric fluorescent assays with 3D origami microfluidic paper-based device (microPAD) was developed for simultaneous visual point-of-care testing (POCT) of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Cascade catalytic reaction with the same two fluorescent signal indicators was rationally designed to ratiometric fluorescent detection of ALP and BChE: substrate of ALP (pyrophosphate) and product of BChE (thiocholine) can strongly complex with Cu(2+), Cu(2+) oxidizes o-phenylenediamine to fluorescent 2,3-diaminophenazine (oxOPD) (emission, 565 nm), oxOPD quenches the fluorescence of carbon dots (CDs, emission at 445 nm) via inner filter effect, thus oxOPD/CDs values are relevant to ALP and BChE activities. Then 3D origami microPAD composing of four layers and two parallel channels was fabricated and simply prepared by one-step plotting with black oil-based marker and specific metal molds. After simple folding and unfolding neighboring layers to sequentially initiate reactions of pre-loaded reagents, fluorescent images on the detection zone can be captured by smartphone and analyzed by red-green-blue software for quantitative analysis. Under optimal conditions, the proposed platform was successfully performed to detect ALP and BChE with activity difference at 3 orders of magnitude in human serum samples without any pretreatment procedures. Excellent selectivity, good precision, favorable linear range, and high accuracy were exhibited. Importantly, the platform opens a promising horizon for high-throughput POCT of multiplex biomarkers.
ESTHER : Zhu_2021_Biosens.Bioelectron_196_113691
PubMedSearch : Zhu_2021_Biosens.Bioelectron_196_113691
PubMedID: 34637993

Title : Preliminary study of the consciousness-promotion mechanism of electroacupuncture in comatose patients with diffuse axonal injuries - Dai_2021_J.Neurosurg.Sci__
Author(s) : Dai W , Guo X , Cai W , Zheng Y , Chen Y , Zhu Y , Tian X
Ref : Journal of Neurosurgery Sci , : , 2021
Abstract : BACKGROUND: Diffuse axonal injury (DAI) accounts for 30-40% of total neurotrauma,majority among them manifest with consciousness disturbance.At present, the understanding of the treatment of coma and awakening in patients with DAIs is still limited.This study is characterized by the use of electroacupuncture along with conventional Western medicine to promote consciousness more effectively in comatose patients with DAIs, shorten their time spent in a coma, and gain time for more favorable treatments during follow-up rehabilitation in order to improve the cure rate, reduce the morbidity rate, and achieve better therapeutic effects. METHODS: In this randomized controlled study, 145 comatose patients with DAIs (type III) were divided into the treatment group (n = 71) and control group (n = 74). The patients in the control group were treated with conventional Western medicine, while those in the treatment group were treated with both electroacupuncture and conventional treatment. The Glasgow Coma Scale (GCS) scores and consciousness-promotion rates of both groups were observed before treatment as well as 10, 20, and 30 days after treatment. Meanwhile, serum acetylcholinesterase E (AchE) concentrations in both groups were measured with ELISA, while AchE activity was determined with the rate method. Correlations between GCS score, AchE concentration, and AchE activity in the treatment group were analyzed by using the stepwise multiple regression method. RESULTS: The GCS scores in the treatment group showed significant increases after the first, second, and third courses of treatment when compared to the pre-treatment scores (P <0.05). After 1 course of treatment, the GCS scores in the control group were not statistically significantly different compared to the pre-treatment scores(P >0.05), whereas after 2 and 3 courses of treatment, the differences were of greater statistical significance (P <0.05). Statistically significant differences between the 2 groups were found in GCS scores in the same course of treatment (P <0.05). The consciousness-promotion rates between the 2 groups after the same treatment course were statistically significantly different (P <0.05). Both the standardized regression coefficients and partial correlation coefficients showed that AchE concentration had a certain influence on GCS score (|Beta| = 0.3601; r Y2.1 = 0.726). CONCLUSIONS: Conventional Western medicine combined with electroacupuncture treatment may promote the consciousness of patients with DAIs and shorten the amount of time they spend comatose. Furthermore, the neurotransmitter AchE may play a role in the pathophysiological mechanism of consciousness promotion.
ESTHER : Dai_2021_J.Neurosurg.Sci__
PubMedSearch : Dai_2021_J.Neurosurg.Sci__
PubMedID: 33709661

Title : A Novel Microbial Zearalenone Transformation through Phosphorylation - Zhu_2021_Toxins.(Basel)_13_
Author(s) : Zhu Y , Drouin P , Lepp D , Li XZ , Zhu H , Castex M , Zhou T
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Zearalenone (ZEA) is a mycotoxin widely occurring in many agricultural commodities. In this study, a purified bacterial isolate, Bacillus sp. S62-W, obtained from one of 104 corn silage samples from various silos located in the United States, exhibited activity to transform the mycotoxin ZEA. A novel microbial transformation product, ZEA-14-phosphate, was detected, purified, and identified by HPLC, LC-MS, and NMR analyses. The isolate has been identified as belonging to the genus Bacillus according to phylogenetic analysis of the 16S rRNA gene and whole genome alignments. The isolate showed high efficacy in transforming ZEA to ZEA-14-phosphate (100% transformation within 24 h) and possessed advantages of acid tolerance (work at pH = 4.0), working under a broad range of temperatures (22-42 degreesC), and a capability of transforming ZEA at high concentrations (up to 200 microg/mL). In addition, 23 Bacillus strains of various species were tested for their ZEA phosphorylation activity. Thirteen of the Bacillus strains showed phosphorylation functionality at an efficacy of between 20.3% and 99.4% after 24 h incubation, suggesting the metabolism pathway is widely conserved in Bacillus spp. This study established a new transformation system for potential application of controlling ZEA although the metabolism and toxicity of ZEA-14-phosphate requires further investigation.
ESTHER : Zhu_2021_Toxins.(Basel)_13_
PubMedSearch : Zhu_2021_Toxins.(Basel)_13_
PubMedID: 33919181

Title : Progesterone activates the cyclic AMP-protein kinase A signalling pathway by upregulating ABHD2 in fertile men - Jiang_2021_J.Int.Med.Res_49_300060521999527
Author(s) : Jiang F , Zhu Y , Chen Y , Tang X , Liu L , Chen G , Liu Y , Sun X
Ref : J Internal Medicine Res , 49 :300060521999527 , 2021
Abstract : OBJECTIVE: This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via alpha/beta hydrolase domain-containing protein 2 (ABHD2). METHODS: Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in ABHD2 were detected by quantitative PCR, western blot, and gene sequencing. The expression of ABHD2 in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively. RESULTS: Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively. CONCLUSION: Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility.
ESTHER : Jiang_2021_J.Int.Med.Res_49_300060521999527
PubMedSearch : Jiang_2021_J.Int.Med.Res_49_300060521999527
PubMedID: 33752482
Gene_locus related to this paper: human-ABHD2

Title : The Role of N-myc Downstream-Regulated Gene Family in Glioma Based on Bioinformatics Analysis - Tang_2021_DNA.Cell.Biol_40_949
Author(s) : Tang T , Wang H , Han Y , Huang H , Niu W , Fei M , Zhu Y
Ref : DNA & Cell Biology , 40 :949 , 2021
Abstract : Glioma is the most common type of primary tumor in the central nervous system, and the molecular mechanisms remain elusive. N-myc downstream-regulated gene (NDRG) family is reported to take part in the pathogenesis of various diseases, including some preliminary exploration in glioma. However, there has been no bioinformatics analysis of NDRG family in glioma yet. Herein, we focused on the expression changes of NDRGs with their value in predicting patients' prognoses, upstream regulatory mechanisms (DNA mutation, DNA methylation, transcription factors, and microRNA regulation) and gene enrichment analysis based on co-expressed genes with data from public databases. Furthermore, the expression pattern of NDRGs was verified by the paired glioma and peritumoral samples in our institute. It was suggested that NDRGs were differentially expressed genes in glioma. In particular, the lower expression of NDRG2 or NDRG4 could serve as a predictor of higher grade tumor and poorer prognosis. Also, NDRGs might play a crucial role in signal transduction, energy metabolism, and cross-talk among cells in glioma, under the control of a complex regulatory network. This study enables us to better understand the role of NDRGs in glioma and with further research, it may contribute to the development of glioma treatment.
ESTHER : Tang_2021_DNA.Cell.Biol_40_949
PubMedSearch : Tang_2021_DNA.Cell.Biol_40_949
PubMedID: 34115542

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

Title : Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes - Bi_2021_Cell_184_1377
Author(s) : Bi X , Wang K , Yang L , Pan H , Jiang H , Wei Q , Fang M , Yu H , Zhu C , Cai Y , He Y , Gan X , Zeng H , Yu D , Zhu Y , Qiu Q , Yang H , Zhang YE , Wang W , Zhu M , He S , Zhang G
Ref : Cell , 184 :1377 , 2021
Abstract : Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.
ESTHER : Bi_2021_Cell_184_1377
PubMedSearch : Bi_2021_Cell_184_1377
PubMedID: 33545088
Gene_locus related to this paper: atrsp-a0a8j7tiu5

Title : Biological responses of Eisenia fetida towards the exposure and metabolism of tris (2-butoxyethyl) phosphate - Wu_2021_Sci.Total.Environ__152285
Author(s) : Wu X , Zhu Y , Yang M , Zhang J , Lin D
Ref : Sci Total Environ , :152285 , 2021
Abstract : The toxicity of various organophosphorus flame retardants (OPFRs) is of increasing concern. However, there is still a lack of research on the toxicity of OPFRs to terrestrial invertebrates and its metabolism in vivo. Herein, earthworms (Eisenia fetida) were exposed to soil spiked with 0, 0.05, 0.5, and 5 mg/kg tris(2-butoxyethyl) phosphate (TBOEP, a typical alkyl OPFRs) for 28 d to study the biological responses to the exposure and metabolism of TBOEP. TBOEP exposure inhibited the activity of acetyl-cholinesterase (64.4-68.6% of that in the control group), increased the energy consumption level, and affected calcium-dependent pathways of E. fetida, which caused a 3.6-12.4% reduction in the weight gain rate (developmental toxicity), a 10.6-69.4% reduction in the number of juveniles (reproduction toxicity), and neurotoxicity to E. fetida. The 5 mg/kg TBOEP exposure caused a significant accumulation of malondialdehyde (1.68 times higher than that in the control group) in E. fetida, which indicated that the balance of oxidation and anti-oxidation of E. fetida was broken. Meanwhile, E. fetida maintained the absorption and metabolic abilities to TBOEP under the environmental condition. The removal rate of soil TBOEP was increased by 25.1-35.5% by the presence of E. fetida. Importantly, TBOEP could accumulate in E. fetida (0.09-76.0 microg/kg) and the activation of cytochrome P450 and glutathione detoxification pathway promoted the metabolism of TBOEP in E. fetida. These findings link the biological responses and metabolic behavior of earthworms under pollution stress and provide fundamental data for the environmental risk assessment and pollution removal of OPFRs in soil.
ESTHER : Wu_2021_Sci.Total.Environ__152285
PubMedSearch : Wu_2021_Sci.Total.Environ__152285
PubMedID: 34933047

Title : Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6\/STAT3 pathway - Yang_2021_J.Obstet.Gynaecol.Res__
Author(s) : Yang X , Zhu Y , Shi Q , Zhao X , Huang Y , Yao F , Zhang Y , Wang Z
Ref : J Obstet Gynaecol Res , : , 2021
Abstract : AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling.
ESTHER : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedSearch : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedID: 33969570

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

Title : Current insights into the microbial degradation for pyrethroids: strain safety, biochemical pathway, and genetic engineering - Zhao_2021_Chemosphere_279_130542
Author(s) : Zhao T , Hu K , Li J , Zhu Y , Liu A , Yao K , Liu S
Ref : Chemosphere , 279 :130542 , 2021
Abstract : As a biologically inspired insecticide, pyrethroids (PYRs) exert evident toxic side effects on non-target organisms. PYRs and their general toxic intermediate 3-phenoxybenzoic acid (3-PBA) have shown high detection rates/levels in human beings recently, for which diet was identified as the major exposure route. Microbial mineralization has emerged as a versatile strategy in addressing such escalating concern. Herein, PYRs and 3-PBA biodegradation with regards to strain safety, application and surfactant were summarized. Numerous PYRs-degrading microbes have been reported yet with a minority focused on 3-PBA. Most isolates were from contaminated sites while several microbial food cultures (MFCs) have been investigated. MFCs such as Bacillus spp. and Aspergillus spp. that dominate in PYRs-degrading microbial pools are applicable candidates for agricultural by-products detoxification during the postharvest process. Subsequently, we discussed committed degradation steps, wherein hydrolase responsible for PYRs ester linkage cleavage and oxygenase for 3-PBA diphenyl ether bond rupture play vital roles. Finally, comprehensive information of the key enzyme genes is outlined along with methodologies concerning gene cloning. Cytochrome P450 monooxygenases (CYP) is competent for diphenyl ether scission. Newly-developed omics has become a feasible gene and enzyme mining technology. To achieve PYRs mineralization in feed and food commodities, the screening of MFCs rich in related enzymes and the construction of MFCs-derived genetically modified microbes (GMMs) exhibit great potential considering the safety issues.
ESTHER : Zhao_2021_Chemosphere_279_130542
PubMedSearch : Zhao_2021_Chemosphere_279_130542
PubMedID: 33866100

Title : Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation -
Author(s) : Cui Z , Li B , Zhang Y , He J , Shi X , Wang H , Zhao Y , Yao L , Ai D , Zhang X , Zhu Y
Ref : Hypertension , 78 :1527 , 2021
PubMedID: 34601968

Title : Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the alpha\/beta-fold epoxide hydrolase Alp1U - Zhang_2020_J.Biol.Chem_295_16987
Author(s) : Zhang L , De BC , Zhang W , Mandi A , Fang Z , Yang C , Zhu Y , Kurtan T , Zhang C
Ref : Journal of Biological Chemistry , 295 :16987 , 2020
Abstract : Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an alpha/beta-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (1), and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A W186/W187/Y247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in alpha/beta-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, while the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U, and provided a new approach for engineering regioselective epoxide hydrolases.
ESTHER : Zhang_2020_J.Biol.Chem_295_16987
PubMedSearch : Zhang_2020_J.Biol.Chem_295_16987
PubMedID: 33004437
Gene_locus related to this paper: stram-q1rqu8

Title : Computational design of new enzymes for hydrolysis and synthesis of third-generation cephalosporin antibiotics - Xue_2020_Enzyme.Microb.Technol_140_109649
Author(s) : Xue J , Wang P , Kuang J , Zhu Y
Ref : Enzyme Microb Technol , 140 :109649 , 2020
Abstract : Engineering active sites in inert scaffolds to catalyze chemical transformations with unnatural substrates is still a great challenge for enzyme catalysis. In this research, a p-nitrobenzyl esterase from Bacillus subtilis was identified from the structural database, and a double mutant E115A/E188A was designed to afford catalytic activities toward the hydrolysis of ceftizoxime. A quadruple mutant E115A/E188A/L362S/I270A with enhanced catalytic efficiency was created to catalyze the condensation reaction of ethyl-2-methoxy-amino-2-(2-aminothiazole-4-yl) acetate with 7-amino-3-nor-cephalosporanic acid to produce ceftizoxime in a fully aqueous medium. The catalytic efficiencies of the computationally designed mutants E115A/E188A/L362S/I270A and E115A/Y118 K/E188 V/I270A/L362S can be taken as starting points to further improve their properties towards the practical application in designing more ecology-friendly production of third-generation cephalosporins.
ESTHER : Xue_2020_Enzyme.Microb.Technol_140_109649
PubMedSearch : Xue_2020_Enzyme.Microb.Technol_140_109649
PubMedID: 32912699

Title : Hepatocyte-Specific Expression of Human Carboxylesterase 1 Attenuates Diet-Induced Steatohepatitis and Hyperlipidemia in Mice - Xu_2020_Hepatol.Commun_4_527
Author(s) : Xu Y , Zhu Y , Bawa FC , Hu S , Pan X , Yin L , Zhang Y
Ref : Hepatol Commun , 4 :527 , 2020
Abstract : Rodents have at least five carboxylesterase 1 (Ces1) genes, whereas there is only one CES1 gene in humans, raising the question as to whether human CES1 and mouse Ces1 genes share the same functions. In this study, we investigate the role of human CES1 in the development of steatohepatitis or dyslipidemia in C57BL/6 mice. Hepatocyte-specific expression of human CES1 prevented Western diet or alcohol-induced steatohepatitis and hyperlipidemia. Mechanistically, human CES1 induced lipolysis and fatty acid oxidation, leading to a reduction in hepatic triglyceride and free fatty acid levels. Human CES1 also reduced hepatic-free cholesterol levels and induced low-density lipoprotein receptor. In addition, human CES1 induced hepatic lipoprotein lipase and apolipoprotein C-II expression. Conclusion: Hepatocyte-specific overexpression of human CES1 attenuates diet-induced steatohepatitis and hyperlipidemia.
ESTHER : Xu_2020_Hepatol.Commun_4_527
PubMedSearch : Xu_2020_Hepatol.Commun_4_527
PubMedID: 32258948

Title : Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice - Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Xu Y , Pan X , Hu S , Zhu Y , Cassim Bawa F , Li Y , Yin L , Zhang Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2020
Abstract : Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were i.v. injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced non-alcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD.
ESTHER : Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 33325808

Title : Optimization of fermentation conditions for the production of recombinant feruloyl esterase from Burkholderia pyrrocinia B1213 - Fan_2020_3.Biotech_10_216
Author(s) : Fan G , Zhu Y , Fu Z , Sun B , Teng C , Yang R , Li X
Ref : 3 Biotech , 10 :216 , 2020
Abstract : Statistical experimental designs were used to optimize conditions for recombinant Burkholderia pyrrocinia feruloyl esterase (BpFae) production in bacteria under lactose induction. After optimization by single factor design, Plackett-Burman design, steepest ascent design and the response surface method, the optimal conditions for BpFae production were: 6 g/L lactose, pH 5.5, pre-induced period 5 h, 23 degreesC, shaker rotational speed of 240 rpm, medium volume of 50 mL/250 mL, inoculum size 0.2% (v/v), and a post-induced period of 32 h in a Luria-Bertani culture. The produced BpFae activity was 7.43 U/mL, which is 2.92 times higher than that obtained under optimal conditions using IPTG as the inducer. BpFae activity was 4.82 U/mL in a 5 L fermenter under the abovementioned optimal conditions. BpFae produced a small amount of ethyl acetate but had no effect on the synthesis of other important esters in Baijiu. The results underpin further investigations into BpFae characterization and potential applications.
ESTHER : Fan_2020_3.Biotech_10_216
PubMedSearch : Fan_2020_3.Biotech_10_216
PubMedID: 32355590
Gene_locus related to this paper: 9burk-BpFae

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

Title : Peach Carboxylesterase PpCXE1 Is Associated with Catabolism of Volatile Esters - Cao_2019_J.Agric.Food.Chem_67_5189
Author(s) : Cao X , Xie K , Duan W , Zhu Y , Liu M , Chen K , Klee H , Zhang B
Ref : Journal of Agricultural and Food Chemistry , 67 :5189 , 2019
Abstract : Peach fruit volatile acetate esters impact consumer sensory preference and contribute to defense against biotic stresses. Previous studies showed that alcohol acyltransferase (AAT) family PpAAT1 is correlated with volatile ester formation in peach fruits. However, fruits also contain carboxylesterase (CXE) enzymes that hydrolyze esters. The functions of this family with regard to volatile ester content has not been explored. Here, we observed that content of acetate ester was negatively correlated with expression of PpCXE1. Recombinant PpCXE1 protein exhibited hydrolytic activity toward acetate esters present in peach fruit. Kinetic analysis showed that PpCXE1 showed the highest catalytic activity toward E-2-hexenyl acetate. Subcellular localization demonstrated that PpCXE1 is present in the cytoplasm. Transient expression in peach fruit and stable overexpression in tomato fruit resulted in significant reduction of volatile esters in vivo. Taken together, the results indicate that PpCXE1 expression is associated with catabolism of volatile acetate esters in peach fruit.
ESTHER : Cao_2019_J.Agric.Food.Chem_67_5189
PubMedSearch : Cao_2019_J.Agric.Food.Chem_67_5189
PubMedID: 30997798
Gene_locus related to this paper: prupe-m5w2v0 , prupe-m5vkk2 , prupe-m5vq13

Title : Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Abeta1-42 Induced Cognitive Deficit Mice - Zhu_2019_Front.Pharmacol_10_258
Author(s) : Zhu Y , Shi Y , Cao C , Han Z , Liu M , Qi M , Huang R , Zhu Z , Qian D , Duan JA
Ref : Front Pharmacol , 10 :258 , 2019
Abstract : Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on beta amyloid protein 1-42 (Abeta1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Abeta1-42 injection mice. JWKXS granules significantly decreased Abeta level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Abeta production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Abeta and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Abeta levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.
ESTHER : Zhu_2019_Front.Pharmacol_10_258
PubMedSearch : Zhu_2019_Front.Pharmacol_10_258
PubMedID: 30941041

Title : The clinical parameters for the diagnosis of hepatitis B virus related acute-on-chronic liver failure with sepsis - Xue_2019_Sci.Rep_9_2558
Author(s) : Xue R , Zhu Y , Liu H , Meng Q
Ref : Sci Rep , 9 :2558 , 2019
Abstract : It is still unknown that whether sepsis with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) fit into the conventional diagnostic criteria of sepsis. Our aim was to investigate the potential clinical parameters for the diagnosis of HBV-ACLF with sepsis. A retrospective study was conducted in 43 patients with HBV-ACLF and sepsis who underwent orthotopic liver transplantation. All patients were divided into three groups according to the pathological results and laboratory test results. Immunohistochemistry (IHC) staining, hematoxylin-eosin (HE) staining and Gordon Sweet's reticulin staining were performed in this study. Alanine aminotransferase (ALT), aspartale aminotransferase (AST), total bilirubin (TBiL), cholinesterase (CHE), albumin (ALB), prothrombin activity (PTA), blood routine examination were detected. The results being chosen at admission and before transplantation were analyzed. TBiL had a significant increase (563.5 +/- 191.8 umol/L vs. 383.9 +/- 157.6 umol/L, 438.3 +/- 154.7 umol/L, P = 0.031) and ALT significantly decreased (81.6 +/- 66.4 U/L, 754.5 +/- 1084.7 U/L, 120.6 +/- 102.5 U/L, P = 0.005) in sepsis group before liver transplantation. When sepsis appeared in patients with HBV-ACLF, the ratio of PLT to WBC count before liver transplantation was much lower than it at admission (4.6 +/- 2.0 vs. 16.1 +/- 7.2, P = 0.000). In conclusion, the clinical parameters of sepsis in patients with HBV-ACLF should be reset. The ratio of PLT/WBC and (WBCBLT/WBCAA)/ (PLTBLT/PLTAA) could remind us the occurring of sepsis in patients with HBV-ACLF.
ESTHER : Xue_2019_Sci.Rep_9_2558
PubMedSearch : Xue_2019_Sci.Rep_9_2558
PubMedID: 30796255

Title : Protective role of phenylethanoid glycosides, Torenoside B and Savatiside A, in Alzheimer's disease - Ji_2019_Exp.Ther.Med_17_3755
Author(s) : Ji S , Li S , Zhao X , Kang N , Cao K , Zhu Y , Peng P , Fan J , Xu Q , Yang S , Liu Y
Ref : Exp Ther Med , 17 :3755 , 2019
Abstract : The current study assessed the efficacy of two phenylethanoid glycosides (PhGs), Torenoside B (TB) and Savatiside A (SA), in the treatment of Alzheimer's disease (AD). The effects of TB and SA compounds were first assessed following amyloid beta (Abeta)25-35 induction in SH-SY5Y cells at a range of concentrations. Their effects on cell viability and reactive oxygen species (ROS) were determined by performing MTT and dichlorofluorescin diacetate assays, respectively. The concentration of intracellular Ca(2+) was determined using Fluo-3AM to stain SH-SY5Y cells. SA and TB treatments were also assessed in Abeta25-35-induced mice. Y-maze and Morris water maze methods were utilized to assess murine learning and memory capability. The pathological changes of murine hippocampi was determined using H&E and Nissl staining. In addition, biochemical parameters associated with intracellular reactive oxygen pathways including Maleic dialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE) and Calnexin were also assessed. TB and SA treatment in Abeta25-35-induced SH-SY5Y cells resulted in the restoration of cell morphology, an increase of SOD and GSH-Px activity, a decrease in ROS, Ca(2+) and MDA content, and a decrease in Calnexin expression. Furthermore, SA or TB treatment administered to Abeta25-35-induced mice improved their spatial/non-spatial learning and memory capabilities. The efficacy of treatment was also supported by a marked change in the morphological structure of pyramidal neurons in the CA1 areas of murine hippocampi, as well as an increase of SOD and GSH-Px activity. Treatment also resulted in a decrease in MDA content, AchE activity and Calnexin expression in murine hippocampal tissue. As potential AD treatment drugs, SA and TB compounds have been demonstrated to alleviate the oxidative stress induced by Abeta25-35 via the regulation of intracellular calcium homeostasis and Calnexin, preventing AD development.
ESTHER : Ji_2019_Exp.Ther.Med_17_3755
PubMedSearch : Ji_2019_Exp.Ther.Med_17_3755
PubMedID: 30988761

Title : Evaluation of the cholinesterase activity of a potential therapeutic cocaine esterase for cocaine overdose - Hou_2019_Drug.Alcohol.Depend_202_168
Author(s) : Hou S , Zhang Y , Zhu Y , Zhang C , Kong Y , Chen X , Chen R , Yin X , Xie T
Ref : Drug Alcohol Depend , 202 :168 , 2019
Abstract : BACKGROUND: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects. METHODS: Both computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics. RESULTS: It is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (kcat/KM) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 degrees C and 37 degrees C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh. CONCLUSION: Given the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose.
ESTHER : Hou_2019_Drug.Alcohol.Depend_202_168
PubMedSearch : Hou_2019_Drug.Alcohol.Depend_202_168
PubMedID: 31352306

Title : Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice - Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
Author(s) : Yao L , Cao B , Cheng Q , Cai W , Ye C , Liang J , Liu W , Tan L , Yan M , Li B , He J , Hwang SH , Zhang X , Wang C , Ai D , Hammock BD , Zhu Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , 316 :G527 , 2019
Abstract : Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg.kg(-1).day(-1) for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.
ESTHER : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedSearch : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedID: 30789748

Title : Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice - Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
Author(s) : Zhang J , Wang J , Zhou GS , Tan YJ , Tao HJ , Chen JQ , Pu ZJ , Ma JY , She W , Kang A , Zhu Y , Liu P , Zhu ZH , Shi XQ , Tang YP , Duan JA
Ref : Oxid Med Cell Longev , 2019 :8636835 , 2019
Abstract : Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.
ESTHER : Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
PubMedSearch : Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
PubMedID: 30911351

Title : Current anti-Alzheimer's disease effect of natural products and their principal targets - Zhu_2019_J.Integr.Neurosci_18_327
Author(s) : Zhu Y , Peng L , Hu J , Chen Y , Chen F
Ref : J Integr Neurosci , 18 :327 , 2019
Abstract : Various bioactive substances isolated from natural products play a pivotal role in the prevention and cure of neurodegenerative diseases, such as Alzheimer's disease. Currently, there are many theories about the pathogenesis of this disease. In this review we discuss among them, the cholinergic hypotheses, the Abeta toxicity hypothesis, and the tau dysfunction hypothesis. Multiple potential targets are a focus for the development of anti-AD drugs. There is an urgent need to develop more effective therapies to treat and delay the onset of the disease and to find safe and effective drugs. In this review, the recent progress of anti-AD effects and their principal targets are updated.
ESTHER : Zhu_2019_J.Integr.Neurosci_18_327
PubMedSearch : Zhu_2019_J.Integr.Neurosci_18_327
PubMedID: 31601083

Title : Protective Effect of Hyperforin on beta Amyloid Protein Induced Apoptosis in PC12 Cells and Colchicine Induced Alzheimer's Disease: An Anti-oxidant and Anti-inflammatory Therapy - Jiang_2018_J.Oleo.Sci_67_1443
Author(s) : Jiang X , Kumar M , Zhu Y
Ref : J Oleo Sci , 67 :1443 , 2018
Abstract : The current investigation aimed to scrutinize the neuro-protective effect of hyperforin on betaamyloid peptide (Abeta)1-42 and H2O2 induced injury in PC12 cells and colchicine induced Alzheimer's disease (AD). PC12 cells were treated with H2O2 and (Abeta)1-42 in the presence of hyperforin. The cell viability was determined via suing the MTT assay; malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels were also scrutinized. Colchicine induced the destruction of memory and learning which was exhibited in neurobehavioral theory (passive avoidance and Morris water maze) connected with reduced activity of acetylcholinesterase (AChE). Antioxidant and inflammatory parameters also estimated. Hyperforin dose dependently increased the cell viability and reduced the MDA and LDH release via PC12 cell injured with H2O2 and (Abeta)1-42. Hyperforin treatment lead to a considerable enhance in TLT in the retention trials as comparisian to acquisition trial suggesting as boosting memory and learning in rats. Hyperforin treatments significantly increase the AChE and reduced the superoxide dismutase, glutathione, MDA, protein carbonyl, glutathione peroxdiase, catalase, NFkB and IL1beta at dose dependent manner. In summary, the model of H2O2 and (Abeta)1-42 induced PC12 cell injury was successfully developed and dose dependently treatment of hypoforin showed the neuroprotective effect against the H2O2 and (Abeta)1-42 induced cell damage. These finding clearly exhibited that hyperforin reverted the colchicine induced neurochemical and behavioural alteration via potent antiinflammatory and antioxidant activity.
ESTHER : Jiang_2018_J.Oleo.Sci_67_1443
PubMedSearch : Jiang_2018_J.Oleo.Sci_67_1443
PubMedID: 30404965

Title : Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo - Zhu_2018_Eur.J.Pharm.Sci_123_459
Author(s) : Zhu Y , Liu W , Qi S , Wang H , Wang Y , Deng G , Zhang Y , Li S , Ma C , Cheng X , Wang C
Ref : Eur J Pharm Sci , 123 :459 , 2018
Abstract : Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer's disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results, the glucuronidation metabolic rate of l-VAS was faster than d-VAS in human liver microsomes and isoenzymes tests, and it was proved that the UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B15 were the major metabolic enzymes for glucuronidation of l-VAS, while only UGT1A9 for d-VAS, which take responsibility of the significantly less metabolic affinity of d-VAS than l-VAS in HLM and rhUGT1A9. The plasma exposure of d-VAS in rats was 1.3-fold and 1.6-fold higher than that of l-VAS after intravenous and oral administration of d-VAS and l-VAS, respectively. And the plasma exposure of the major glucuronidation metabolite d-VASG was one of tenth of l-VASG or more less, no matter by intravenous or oral administration. Both d-VAS and l-VAS were exhibited promising acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and the BChE inhibitory activity of d-VAS with IC50 of 0.03+/-0.001muM was significantly stronger than that of l-VAS with IC50 of 0.98+/-0.19muM. The molecular docking results indicated that d-VAS and l-VAS could bind to the catalytic active site (CAS position) either of human AChE and BChE, and the BChE combing ability of d-VAS (the score of GBI/WAS dG -7.398) was stronger than that of l-VAS (the score of GBI/WAS dG -7.135). Both d-VAS and l-VAS could improving the learning and memory on scopolamine-induced memory deficits in mice. The content of acetylcholine (ACh) after oral administration d-VAS increased more than that of l-VAS in mice cortex, through inhibiting cholinesterase (ChE) and increasing choline acetyltransferase (ChAT). In addition, the LD50 value of d-VAS (282.51mg.kg(-1)) was slight lower than l-VAS (319.75mg.kg(-1)). These results indicated that VAS enantiomers displayed significantly stereoselective metabolic, pharmacokinetics, anti-amnesic effect and toxic properties in vitro and in vivo. The d-VAS might be the dominant configuration for treating Alzheimer's disease.
ESTHER : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedSearch : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedID: 30077712

Title : Associations between LPL gene polymorphisms and coronary artery disease: evidence based on an updated and cumulative meta-analysis - Ma_2018_Biosci.Rep_38_
Author(s) : Ma WQ , Wang Y , Han XQ , Zhu Y , Liu NF
Ref : Bioscience Reports , 38 : , 2018
Abstract : Lipoprotein lipase (LPL) is widely linked to lipid and lipoprotein metabolism, but its effects on coronary artery disease (CAD) are not clearly elucidated. The aim of this study was to clarify the association between LPL gene polymorphisms and CAD susceptibility. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the relationship between LPL gene polymorphisms and CAD risk. Comprehensive electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library, were systematically searched. A total of 45 records containing 80 eligible studies were analyzed. The results indicated an increased risk between the LPL D9N polymorphism and susceptibility to CAD in the dominant genetic model (AA + GA vs. GG: OR = 1.46, 95% CI = 1.14-1.87), whereas the LPL HindIII polymorphism showed a protective effect against CAD under all tested models (GG+GT vs. TT: OR = 0.85, 95% CI = 0.75-0.97; GG vs. TT + TG: OR = 0.62, 95% CI = 0.47-0.83; G vs. T: OR = 0.81, 95% CI = 0.71-0.92). No significant association was identified for the LPL N291S and PvuII polymorphisms. Stratification analysis by ethnicity suggested a significant correlation between the LPL S447X polymorphism and CAD susceptibility in Caucasians under the dominant and allele genetic models. In summary, our meta-analysis indicated that the LPL D9N polymorphism was associated with an increased risk of CAD, whereas the S447X and HindIII polymorphisms showed protective effects. There was no association observed between the N291S and PvuII polymorphisms and CAD risk.
ESTHER : Ma_2018_Biosci.Rep_38_
PubMedSearch : Ma_2018_Biosci.Rep_38_
PubMedID: 29459423

Title : A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study - Zhou_2018_Eur.J.Hum.Genet_26_838
Author(s) : Zhou D , Zhang D , Sun X , Li Z , Ni Y , Shan Z , Li H , Liu C , Zhang S , Liu Y , Zheng R , Pan F , Zhu Y , Shi Y , Lai M
Ref : Eur J Hum Genet , 26 :838 , 2018
Abstract : Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (Pcombined = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.
ESTHER : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedSearch : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedID: 29476167

Title : Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma - Yao_2017_Medicine.(Baltimore)_96_e6735
Author(s) : Yao Q , Bao X , Xue R , Liu H , Li J , Dong J , Duan Z , Ren M , Zhao J , Song Q , Yu H , Zhu Y , Lu J , Meng Q
Ref : Medicine (Baltimore) , 96 :e6735 , 2017
Abstract : This study aimed to determine if the immunoscore (IS) staging system would be a potential prognostic factor in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in China.IS was performed in a consecutive cohort of HBV-HCC patients (n= 92). CD3+, CD8+, and CD45RO+ T cells were quantified by immunohistochemical analyses. The patients were stratified into 5 IS groups: I0, I1, I2, I3, I4 for every 2 cell phenotypes (IS1 (CD8/CD45RO, IS2 (CD3/CD8), and IS3 (CD3/CD45RO), respectively. ImagePro Plus software was used in the calculation of the paraffin-embedded tumor sections.The staining of CD3+, CD8+, and CD45RO+ cells in the HBV-HCC tissue demonstrated that there were higher density and larger area of lymphocytes in the invasive margins (IM) region than in the center (CT). Univariate analysis showed that preoperative TNM staging (P = .01), serum gamma-glutamyl transpeptidase (GGT) level (P = .03), vascular invasion (P = .00), and density of CD3+T (CT) (P = 0.01) were correlated significantly with disease-free survival (DFS); serum alpha-fetoprotein (AFP) level (P = .02), tumor size (P = .00), serum cholinesterase (CHE) (P = .04), and GGT level (P = .01), density of CD3+T(CT) (P = .00), CD8+T(CT)(P = .00), CD45RO+T(CT) (P = .00), and CD45RO+T (IM) (P = .02) were correlated with overall survival (OS). Multivariate analysis showed that TNM staging was not an independent prognostic factor of DFS and OS. Our results showed ISs did not have a significantly correlation with DFS (P = .35, .19, and .07, respectively), but it was correlated significantly with OS (P = .00, .00, and .00, respectively). There were statistical differences among the OS of every ISs subgroup except I0 and I1 by the Cox regressions analysis.The IS staging was closely related to the outcome of patients. It can compensate the TNM tumor classification system in predicting the prognosis of HBV-HCC patients.
ESTHER : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedSearch : Yao_2017_Medicine.(Baltimore)_96_e6735
PubMedID: 28445292

Title : Characterization of the Polymyxin D Synthetase Biosynthetic Cluster and Product Profile of Paenibacillus polymyxa ATCC 10401 - Galea_2017_J.Nat.Prod_80_1264
Author(s) : Galea CA , Han M , Zhu Y , Roberts K , Wang J , Thompson PE , L J , Velkov T
Ref : Journal of Natural Products , 80 :1264 , 2017
Abstract : The increasing prevalence of polymyxin-resistant bacteria has stimulated the search for improved polymyxin lipopeptides. Here we describe the sequence and product profile for polymyxin D nonribosomal peptide synthetase from Paenibacillus polymyxa ATCC 10401. The polymyxin D synthase gene cluster comprised five genes that encoded ABC transporters (pmxC and pmxD) and enzymes responsible for the biosynthesis of polymyxin D (pmxA, pmxB, and pmxE). Unlike polymyxins B and E, polymyxin D contains d-Ser at position 3 as opposed to l-alpha,gamma-diaminobutyric acid and has an l-Thr at position 7 rather than l-Leu. Module 3 of pmxE harbored an auxiliary epimerization domain that catalyzes the conversion of l-Ser to the d-form. Structural modeling suggested that the adenylation domains of module 3 in PmxE and modules 6 and 7 in PmxA could bind amino acids with larger side chains than their preferred substrate. Feeding individual amino acids into the culture media not only affected production of polymyxins D1 and D2 but also led to the incorporation of different amino acids at positions 3, 6, and 7 of polymyxin D. Interestingly, the unnatural polymyxin analogues did not show antibiotic activity against a panel of Gram-negative clinical isolates, while the natural polymyxins D1 and D2 exhibited excellent in vitro antibacterial activity and were efficacious against Klebsiella pneumoniae and Acinetobacter baumannii in a mouse blood infection model. The results demonstrate the excellent antibacterial activity of these unusual d-Ser3 polymxyins and underscore the possibility of incorporating alternate amino acids at positions 3, 6, and 7 of polymyxin D via manipulation of the polymyxin nonribosomal biosynthetic machinery.
ESTHER : Galea_2017_J.Nat.Prod_80_1264
PubMedSearch : Galea_2017_J.Nat.Prod_80_1264
PubMedID: 28463513

Title : Functional Characterization of the Unique Terminal Thioesterase Domain from Polymyxin Synthetase - Galea_2017_Biochemistry_56_657
Author(s) : Galea CA , Roberts KD , Zhu Y , Thompson PE , Li J , Velkov T
Ref : Biochemistry , 56 :657 , 2017
Abstract : Polymyxins remain one of the few antibiotics available for treating antibiotic resistant bacteria. Here we describe polymyxin B thioesterase which performs the final step in polymyxin B biosynthesis. Isolated thioesterase catalyzed cyclization of an N-acetylcystamine polymyxin B analogue to form polymyxin B. The thioesterase contained a catalytic cysteine unlike most thioesterases which possess a serine. Supporting this, incubation of polymyxin B thioesterase with reducing agents abolished enzymatic activity, while mutation of the catalytic cysteine to serine significantly decreased activity. NMR spectroscopy demonstrated that uncyclized polymyxin B was disordered in solution, unlike other thioesterase substrates which adopt a transient structure similar to their product. Modeling showed the thioesterase substrate-binding cleft was highly negatively charged, suggesting a mechanism for the cyclization of the substrate. These studies provide new insights into the role of polymyxin thioesterase in polymyxin biosynthesis and highlight its potential use for the chemoenzymatic synthesis of polymyxin lipopeptides.
ESTHER : Galea_2017_Biochemistry_56_657
PubMedSearch : Galea_2017_Biochemistry_56_657
PubMedID: 28071053

Title : Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer's disease - Zhou_2017_Bioorg.Med.Chem.Lett_27_4180
Author(s) : Zhou LY , Zhu Y , Jiang YR , Zhao XJ , Guo D
Ref : Bioorganic & Medicinal Chemistry Lett , 27 :4180 , 2017
Abstract : With the recent research advances in molecular biology and technology, multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed; multi-target drugs have emerged as an innovative therapeutic approach for AD. Current clinical therapy for AD patients is mainly palliative treatment targeting acetylcholinesterase (AChE). Inhibition of phosphodiesterase 5A (PDE5A) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). In this work, series of new compounds were designed, synthesized and evaluated as dual cholinesterase and PDE5A inhibitor. Biological results revealed that some of these compounds display good biological activities against AChE with IC50 values about 44.67-169.80nM (donepezil IC50 50.12nM). Notably, compound 12 presented potent activities against PDE5A with IC50 values about 50muM (sildenafil IC50 12.59muM), and some of these compounds showed low cell toxicity to A549 cells in vitro.
ESTHER : Zhou_2017_Bioorg.Med.Chem.Lett_27_4180
PubMedSearch : Zhou_2017_Bioorg.Med.Chem.Lett_27_4180
PubMedID: 28751142

Title : Complex pectin metabolism by gut bacteria reveals novel catalytic functions - Ndeh_2017_Nature_544_65
Author(s) : Ndeh D , Rogowski A , Cartmell A , Luis AS , Basle A , Gray J , Venditto I , Briggs J , Zhang X , Labourel A , Terrapon N , Buffetto F , Nepogodiev S , Xiao Y , Field RA , Zhu Y , O'Neil MA , Urbanowicz BR , York WS , Davies GJ , Abbott DW , Ralet MC , Martens EC , Henrissat B , Gilbert HJ
Ref : Nature , 544 :65 , 2017
Abstract : The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.
ESTHER : Ndeh_2017_Nature_544_65
PubMedSearch : Ndeh_2017_Nature_544_65
PubMedID: 28329766

Title : Inhibition of soluble epoxide hydrolase lowers portal hypertension in cirrhotic rats by ameliorating endothelial dysfunction and liver fibrosis - Deng_2017_Prostaglandins.Other.Lipid.Mediat_131_67
Author(s) : Deng W , Zhu Y , Lin J , Zheng L , Zhang C , Luo M
Ref : Prostaglandins Other Lipid Mediat , 131 :67 , 2017
Abstract : Epoxyeicostrienoic acids (EETs) are arachidonic acid derived meditators which are catalyzed by soluble epoxide hydrolase (sEH) to less active dihydroeicostrienoics acids (DHETS). The aim of our study is to investigate the effects of sEH inhibition on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats. The sEH inhibitor,trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB) was administered to stabilize hepatic EETs by gavage at a dose of 1mg/kg/d. Our results showed that hepatic sEH expression was markedly increased in portal hypertension, and led to a lower ratio of EETs/DHETs which was effectively reversed by t-TUCB administration. t-TUCB significantly decreased portal pressure without significant changes in systemic hemodynamics, which was associated with the attenuation of intrahepatic vascular resistance (IHVR) and liver fibrosis. t-TUCB ameliorated endothelial dysfunction, increased hepatic endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. In addition, t-TUCB significantly reduced alpha-Smooth Muscle Actin (alpha-SMA) expression and liver fibrosis, which was associated with a decrease in NF-kappaB signaling. Taken together, inhibition of sEH reduces portal pressure, liver fibrosis and attenuates hepatic endothelial dysfunction in cirrhotic rats. Our results indicate that sEH inhbitors may be useful in the treatment of portal hypertension in patients with cirrhosis.
ESTHER : Deng_2017_Prostaglandins.Other.Lipid.Mediat_131_67
PubMedSearch : Deng_2017_Prostaglandins.Other.Lipid.Mediat_131_67
PubMedID: 28822809

Title : Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice - Liu_2017_J.Ethnopharmacol_204_95
Author(s) : Liu W , Zhu Y , Wang Y , Qi S , Ma C , Li S , Jiang B , Cheng X , Wang Z , Xuan Z , Wang C
Ref : J Ethnopharmacol , 204 :95 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND
METHODS: The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.
RESULTS: The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group.
CONCLUSIONS: EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
ESTHER : Liu_2017_J.Ethnopharmacol_204_95
PubMedSearch : Liu_2017_J.Ethnopharmacol_204_95
PubMedID: 28442406

Title : Multipotent AChE and BACE-1 inhibitors for the treatment of Alzheimer's disease: Design, synthesis and bio-analysis of 7-amino-1,4-dihydro-2H-isoquilin-3-one derivates - Zhao_2017_Eur.J.Med.Chem_138_738
Author(s) : Zhao XJ , Gong DM , Jiang YR , Guo D , Zhu Y , Deng YC
Ref : Eur Journal of Medicinal Chemistry , 138 :738 , 2017
Abstract : In this paper, the preparation of a new class of multi-target-directed ligands (MTDLs) based on a 7-amino-1,4-dihydro-2H-isoquilin-3-one, whose lead (compound I) showed promising properties in acetylcholinesterase (AChE) inhibitory activity [1], is described. The results of in vitro activities and molecular docking demonstrated that the target molecule (compounds 10a-n) with three parts of aromatic moieties and appropriate structural length can interact with aromatic residues in catalytic active site (CAS), peripheral anionic site (PAS) and the channel of AChE. And the introduce of connecting amide bonds, enables the target molecules provide sufficient hydrogen bond donors and acceptors to interact with the catalytic site of BACE-1. Notably, compound 10d exerted excellent AChE inhibition (IC50 = 18.93 +/- 1.02 pM, 181-fold more inhibitory effect compared with donepezil), BACE-1 inhibition (97.68 +/- 8.01% at 20 muM), and good metal chelating property, which can be chosen as lead compound for further optimization of novel small ligand for the treatment of Alzheimer's disease.
ESTHER : Zhao_2017_Eur.J.Med.Chem_138_738
PubMedSearch : Zhao_2017_Eur.J.Med.Chem_138_738
PubMedID: 28728106

Title : Computational design of cephradine synthase in a new scaffold identified from structural databases - Huang_2017_Chem.Commun.(Camb)_53_7604
Author(s) : Huang X , Xue J , Zhu Y
Ref : Chem Commun (Camb) , 53 :7604 , 2017
Abstract : Computational enzyme design exhibits excellent performance for identifying potential scaffolds from structural databases and creating new enzymatic catalysts from naught. Using the active site-matching algorithm ProdaMatch, we identified a new scaffold cocaine esterase from Rhodococcus sp. that showed modest activity (kcat/Km = 0.018 M-1 s-1) towards the hydrolysis of beta-lactam antibiotic cephradine. The identified cocaine esterase scaffold afforded low sequence identity (<30%) with the known beta-lactam synthases, such as penicillin G acylase or alpha-amino acid ester hydrolase, and was able to catalyze the condensation reaction between d-dihydrophenylglycine methyl ester and 7-aminodesacetoxycephalosporanic acid to produce cephradine via a kinetically controlled synthesis. By virtue of the computational enzyme design protocol, hundreds of sequences were predicted in the cocaine esterase scaffold to promote the catalytic activity towards the hydrolytic reaction of cephradine. Moreover, a single mutant (F261T) was experimentally confirmed to have improved the catalytic efficiency by ten times (kcat/Km = 0.193 M-1 s-1), indicating that the novel scaffold cocaine esterase may be potentially redesigned to become an industrially useful cephradine synthase.
ESTHER : Huang_2017_Chem.Commun.(Camb)_53_7604
PubMedSearch : Huang_2017_Chem.Commun.(Camb)_53_7604
PubMedID: 28639649
Gene_locus related to this paper: rhosm-cocE

Title : Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing monocyte infiltration in Ldlr(-\/-) mice - Li_2016_J.Mol.Cell.Cardiol_98_128
Author(s) : Li D , Liu Y , Zhang X , Lv H , Pang W , Sun X , Gan LM , Hammock BD , Ai D , Zhu Y
Ref : Journal of Molecular & Cellular Cardiology , 98 :128 , 2016
Abstract : RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition in atherogenesis. METHODS AND
RESULTS: Mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double-knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce arteriosclerosis. Both sEH inhibition and gene depletion decreased the WTD-induced hyperlipidemia, plaque area and macrophage infiltration in mice arterial wall. Ly6C(hi) infiltration of monocytes remained similar in blood, spleen and bone marrow of DK mice, but was decreased in aortic lesions. To further assess the role of sEH or EETs in monocyte/macrophage infiltration in atherogenesis, we transplanted DK bone marrow into Ldlr(-/-) recipients, and then fed mice the WTD. Aortic lesions and Ly6C(hi) monocyte infiltration were reduced in mice with transplanted bone marrow of DK mice without diminishing the cholesterol level. Furthermore, sEH inhibition or gene depletion increased the ratio of EETs/DHETs and diminished the expression of P-selectin glycoprotein ligand 1 (PSGL-1) in mice peripheral-blood mononuclear cells. Monocyte adhesion to P-selectin and to tumor necrosis factor alpha-activated endothelial cells was also diminished by sEH inhibition. CONCLUSION: sEH inhibition and gene depletion attenuated atherosclerosis in mice by decreasing the infiltration of monocytes into the artery wall. EET and PSGL-1 may play pivotal roles in monocyte/macrophage infiltration and atherogenesis.
ESTHER : Li_2016_J.Mol.Cell.Cardiol_98_128
PubMedSearch : Li_2016_J.Mol.Cell.Cardiol_98_128
PubMedID: 27496380

Title : A New Lycopodine-type Alkaloid from Lycopodium japonicum - Yang_2016_Nat.Prod.Res__1
Author(s) : Yang Q , Zhu Y , Peng W , Zhan R , Chen Y
Ref : Nat Prod Res , :1 , 2016
Abstract : A new lycopodine-type alkaloid, 12beta-hydroxy-acetylfawcettiine N-oxide (1), together with seven known analogues, acetyllycoposerramine M (2), lycopodine (3), lycoclavine (4), diphaladine A (5), lycoposerramine K (6), 11beta-hydroxy-12-epilycodoline (7) and fawcettiine (8), were isolated from Lycopodium japonicum. Their structures were established by mass spectrometry and 1D and 2D NMR techniques. The isolated alkaloids were assayed for their inhibition activities against acetylcholinesterase, but no inhibitory activities for the compounds were detected.
ESTHER : Yang_2016_Nat.Prod.Res__1
PubMedSearch : Yang_2016_Nat.Prod.Res__1
PubMedID: 26912449

Title : Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae - Shen_2016_Sci.Rep_6_33905
Author(s) : Shen H , Zhu Y , Wang C , Yan H , Teng M , Li X
Ref : Sci Rep , 6 :33905 , 2016
Abstract : Hda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 A. The ARB2 domain displays an alpha/beta sandwich architecture with an arm protruding outside. Two ARB2 domain molecules form a compact homo-dimer via the arm elements, and assemble as an inverse "V" shape. The pull-down and ITC results reveal that the ARB2 domain possesses the histone binding ability, recognizing both the H2A-H2B dimer and H3-H4 tetramer. Perturbation of the dimer interface abolishes the histone binding ability of the ARB2 domain, indicating that the unique dimer architecture of the ARB2 domain coincides with the function for anchoring to histone. Collectively, our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda1 HDAC complex.
ESTHER : Shen_2016_Sci.Rep_6_33905
PubMedSearch : Shen_2016_Sci.Rep_6_33905
PubMedID: 27665728
Gene_locus related to this paper: yeast-hda1

Title : Soluble epoxide hydrolase: A potential target for metabolic diseases - He_2016_J.Diabetes_8_305
Author(s) : He J , Wang C , Zhu Y , Ai D
Ref : J Diabetes , 8 :305 , 2016
Abstract : Epoxyeicosatrienoic acids (EETs), important lipid mediators derived from arachidonic acid, have many beneficial effects in metabolic diseases, including atherosclerosis, hypertension, cardiac hypertrophy, diabetes, non-alcoholic fatty liver disease, and kidney disease. Epoxyeicosatrienoic acids can be further hydrolyzed to less active diols by the enzyme soluble epoxide hydrolase (sEH). Increasing evidence suggests that inhibition of sEH increases levels of EETs, which have anti-inflammatory effects and can prevent the development of hypertension, atherosclerosis, heart failure, fatty liver, and multiple organ fibrosis. Arachidonic acid is the most abundant omega-6 polyunsaturated fatty acid (PUFA) and shares the same set of enzymes with omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid. The omega-3 PUFAs and metabolites, such as regioisomeric epoxyeicosatetraenoic acids and epoxydocosapentaenoic acids, have been reported to have strong vasodilatory and anti-inflammatory effects. Therefore, sEH may be a potential therapeutic target for metabolic disorders. In this review, we focus on our and other recent studies of the functions of sEH, including the effects of its eicosanoid products from both omega-3 and omega-6 PUFAs, in various metabolic diseases. We also discuss the possible cellular and molecular mechanisms underlying the regulation of sEH.
ESTHER : He_2016_J.Diabetes_8_305
PubMedSearch : He_2016_J.Diabetes_8_305
PubMedID: 26621325

Title : Is it possible to reverse aged acetylcholinesterase inhibited by organophosphorus compounds? Insight from the theoretical study - An_2016_Phys.Chem.Chem.Phys_18_9838
Author(s) : An Y , Zhu Y , Yao Y , Liu J
Ref : Phys Chem Chem Phys , 18 :9838 , 2016
Abstract : The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. It suffers from a competitive and irreversible aging reaction of the phosphorylated OP-AChE adduct, resulting in permanent inactivity of AChE. However, it was recently reported that N-methyl-2-methoxypyridinium species can act as methylating agents to methylate the methyl methane-phosphonate monoanion, in which the reaction mimics the reverse of the aging reaction of the phosphorylated OP-AChE adduct. If the aging reaction could be really reversed, the efficiency for the OP detoxification should be significantly improved, bringing up the possibility to develop an agent to reverse the aging process of the phosphorylated OP-AChE adduct. However, such a reaction with the N-methyl-2-methoxypyridinium species in the enzyme is still not reported so far. It is of great interest to know whether or not this reaction is observable in the enzyme, and more importantly, if it turns out to be not observable in the enzyme, why such a reaction proceeds quickly in aqueous solution but not in the enzyme. In the present study, we performed DFT calculations and quantum mechanical/molecular mechanical (QM/MM) calculations to reveal the fundamental mechanism for the methylation of both the methyl methane-phosphonate monoanion and the aged sarin-AChE adduct by N-methyl-2-methoxypyridinium species, respectively. The obtained results support the SN2 reaction mechanism, not the stepwise mechanism, for the methylation of the methyl methane-phosphonate monoanion by 9 reported N-methyl-2-methoxypyridinium compounds. The calculated free energy barriers are in good agreement with the experimental data. The methylation of the aged sarin-AChE adduct by one N-methyl-2-methoxypyridinium compound (labeled as compound 2) also employs the SN2 reaction mechanism with an extremely high free energy barrier of 30.4 +/- 3.5 (or 26.6) kcal mol(-1), implying that this reaction in the enzyme hardly occurs. Our results clearly show that compound 2 forms a strong pi-pi stacking interaction with the aromatic ring of the W86 residue of AChE, making itself unable to approach sarin for the reverse of the aging process. On the basis of the structure and mechanism, several possible strategies have been suggested for designing methylating agents with higher activity against the aged sarin-AChE adduct.
ESTHER : An_2016_Phys.Chem.Chem.Phys_18_9838
PubMedSearch : An_2016_Phys.Chem.Chem.Phys_18_9838
PubMedID: 27000635

Title : Neuroligin 1 regulates spines and synaptic plasticity via LIMK1\/cofilin-mediated actin reorganization - Liu_2016_J.Cell.Biol_212_449
Author(s) : Liu A , Zhou Z , Dang R , Zhu Y , Qi J , He G , Leung C , Pak D , Jia Z , Xie W
Ref : Journal of Cell Biology , 212 :449 , 2016
Abstract : Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C-terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase-activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin-mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function.
ESTHER : Liu_2016_J.Cell.Biol_212_449
PubMedSearch : Liu_2016_J.Cell.Biol_212_449
PubMedID: 26880202

Title : Molecular cloning and characterization of a thermostable lipase from deep-sea thermophile Geobacillus sp. EPT9 - Zhu_2015_World.J.Microbiol.Biotechnol_31_295
Author(s) : Zhu Y , Li H , Ni H , Xiao A , Li L , Cai H
Ref : World J Microbiol Biotechnol , 31 :295 , 2015
Abstract : A gene (1,254 bp) encoding a lipase was identified from a deep-sea hydrothermal field thermophile Geobacillus sp. EPT9. The open reading frame of this gene encoded 417 amino acid residues. The gene was cloned, overexpressed in Escherichia coli, and the target protein was purified to homogeneity. The purified recombinant enzyme presented a molecular mass of 44.8 kDa. When p-nitrophenyl palmitate was used as a substrate, the recombinant lipase was optimally active at 55 degrees C and pH 8.5. The recombinant enzyme retained 44 % residual activity after incubation at 80 degrees C for 1 h, which indicated that Geobacillus sp. EPT9 lipase was thermostable. Homology modeling of strain EPT9 lipase was developed with the lipase from Bacillus sp. L2 as a template. The core structure exhibits an alpha/beta-hydrolase fold and the typical catalytic triad might consist of Ser142, Asp346, and His387. The enzymatic activity of EPT9 lipase was inhibited by addition of phenylmethylsulfonyl fluoride, indicating that it contains serine residue, which plays an important role in the catalytic mechanism.
ESTHER : Zhu_2015_World.J.Microbiol.Biotechnol_31_295
PubMedSearch : Zhu_2015_World.J.Microbiol.Biotechnol_31_295
PubMedID: 25388475

Title : Outbred genome sequencing and CRISPR\/Cas9 gene editing in butterflies - Li_2015_Nat.Commun_6_8212
Author(s) : Li X , Fan D , Zhang W , Liu G , Zhang L , Zhao L , Fang X , Chen L , Dong Y , Chen Y , Ding Y , Zhao R , Feng M , Zhu Y , Feng Y , Jiang X , Zhu D , Xiang H , Feng X , Li S , Wang J , Zhang G , Kronforst MR , Wang W
Ref : Nat Commun , 6 :8212 , 2015
Abstract : Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system.
ESTHER : Li_2015_Nat.Commun_6_8212
PubMedSearch : Li_2015_Nat.Commun_6_8212
PubMedID: 26354079
Gene_locus related to this paper: papxu-a0a194pj15 , papxu-a0a194q254 , papma-a0a194rdx2 , papxu-a0a194q858 , papxu-a0a194pyl3 , papxu-a0a194q337 , papma-a0a194r1p9 , papma-a0a194r6h1 , papxu-a0a194q1w8 , papma-a0a194ql80 , papma-a0a0n1ipl3 , papma-a0a194qm14

Title : Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation - Ao_2015_PLoS.Genet_11_e1005118
Author(s) : Ao J , Mu Y , Xiang LX , Fan D , Feng M , Zhang S , Shi Q , Zhu LY , Li T , Ding Y , Nie L , Li Q , Dong WR , Jiang L , Sun B , Zhang X , Li M , Zhang HQ , Xie S , Zhu Y , Jiang X , Wang X , Mu P , Chen W , Yue Z , Wang Z , Wang J , Shao JZ , Chen X
Ref : PLoS Genet , 11 :e1005118 , 2015
Abstract : The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea.
ESTHER : Ao_2015_PLoS.Genet_11_e1005118
PubMedSearch : Ao_2015_PLoS.Genet_11_e1005118
PubMedID: 25835551
Gene_locus related to this paper: larcr-a0a0f8ay25 , larcr-a0a0f8cf53 , larcr-a0a0f8cir1 , larcr-a0a0f8d1j2 , larcr-a0a0f8alq6 , larcr-a0a0f8bdu4 , larcr-a0a0f8abw1 , larcr-a0a0f8ahh1 , larcr-a0a0f8avc6 , larcr-a0a0f8al93 , larcr-a0a0f8aed8 , larcr-a0a0f7ir14 , larcr-a0a0f8aje8 , larcr-k9lsm3 , larcr-a0a0f8but5 , larcr-a0a0f8af44

Title : Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats - Wang_2015_Mol.Med.Rep_11_775
Author(s) : Wang F , Zeng X , Zhu Y , Ning D , Liu J , Liu C , Jia X , Zhu D
Ref : Mol Med Rep , 11 :775 , 2015
Abstract : A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a signi fi cant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
ESTHER : Wang_2015_Mol.Med.Rep_11_775
PubMedSearch : Wang_2015_Mol.Med.Rep_11_775
PubMedID: 25371181

Title : Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children - Wang_2015_J.Cell.Mol.Med_19_2296
Author(s) : Wang H , Zhang D , Ling J , Lu W , Zhang S , Zhu Y , Lai M
Ref : J Cell Mol Med , 19 :2296 , 2015
Abstract : Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.
ESTHER : Wang_2015_J.Cell.Mol.Med_19_2296
PubMedSearch : Wang_2015_J.Cell.Mol.Med_19_2296
PubMedID: 26282880

Title : Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration - Wang_2015_Am.J.Physiol.Heart.Circ.Physiol__ajpheart 00289 2015
Author(s) : Wang Q , Huo L , He J , Ding W , Su H , Tian D , Welch C , Hammock B , Ai D , Zhu Y
Ref : American Journal of Physiology Heart Circ Physiol , :ajpheart 00289 2015 , 2015
Abstract : Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing biological activity. sEH inhibitors can suppress the progression of atherosclerotic lesions in animal models. However, the regulation of sEH in vascular smooth muscle cells (VSMCs) and role of sEH in patients with atherosclerosis have not been evaluated. We hypothesize that sEH in VSMC plays a pivotal role in atherosclerosis and injury-induced neointima formation. In this study, sEH expression in human autopsy atherosclerotic plaque was determined by immunohistochemistry. In cultured rat and human VSMCs, the phenotypic switching marker and sEH expression induced by platelet-derived growth factor-BB (PDGF-BB) were examined by western blot analysis. Carotid-artery balloon injury was performed after adenovirus-mediated overexpression of sEH or oral administration of a potent sEH inhibitor in Sprague-Dawley rats. sEH was highly expressed in VSMCs of the intima and media within human atherosclerotic plaque. In vitro, PDGF-BB upregulated the expression in VSMCs post-transcriptionally and promoted cell proliferation and migration, the latter effect could be largely attenuated by sEH inhibitor. Adenovirus-mediated overexpression of sEH could mimic the effect of PDGF-BB, induced VSMC proliferation and migration. In vivo, sEH inhibitor significantly decreased the injury-induced neointima formation in a rat carotid-artery injury model. These data establish the impact of sEH expression on atherosclerotic progression and vascular remodeling after injury, thus identifying a novel integrative role of sEH in VSMC phenotypic modulation and migration. Blocking sEH activity may be a potential therapeutic approach for ameliorating vascular occlusive disease.
ESTHER : Wang_2015_Am.J.Physiol.Heart.Circ.Physiol__ajpheart 00289 2015
PubMedSearch : Wang_2015_Am.J.Physiol.Heart.Circ.Physiol__ajpheart 00289 2015
PubMedID: 26453326

Title : Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution - Li_2015_Nat.Biotechnol_33_524
Author(s) : Li F , Fan G , Lu C , Xiao G , Zou C , Kohel RJ , Ma Z , Shang H , Ma X , Wu J , Liang X , Huang G , Percy RG , Liu K , Yang W , Chen W , Du X , Shi C , Yuan Y , Ye W , Liu X , Zhang X , Liu W , Wei H , Wei S , Zhu S , Zhang H , Sun F , Wang X , Liang J , Wang J , He Q , Huang L , Cui J , Song G , Wang K , Xu X , Yu JZ , Zhu Y , Yu S
Ref : Nat Biotechnol , 33 :524 , 2015
Abstract : Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
ESTHER : Li_2015_Nat.Biotechnol_33_524
PubMedSearch : Li_2015_Nat.Biotechnol_33_524
PubMedID: 25893780
Gene_locus related to this paper: gosra-a0a0d2rxs2 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , goshi-a0a1u8hr03 , gosra-a0a0d2vdc5 , goshi-a0a1u8ljh5 , gosra-a0a0d2vj24 , goshi-a0a1u8pxd3 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8mt09 , goshi-a0a1u8kis4 , goshi-a0a1u8ibk3 , goshi-a0a1u8ieg2 , goshi-a0a1u8iki6 , goshi-a0a1u8jvp4 , goshi-a0a1u8jw35 , gosra-a0a0d2pzd7 , goshi-a0a1u8ied7

Title : Molecular cloning and characterization of a new and highly thermostable esterase from Geobacillus sp. JM6 - Zhu_2015_J.Basic.Microbiol_55_1219
Author(s) : Zhu Y , Zheng W , Ni H , Liu H , Xiao A , Cai H
Ref : J Basic Microbiol , 55 :1219 , 2015
Abstract : A new lipolytic enzyme gene was cloned from a thermophile Geobacillus sp. JM6. The gene contained 750 bp and encoded a 249-amino acid protein. The recombinant enzyme was expressed and purified from Escherichia coli BL21 (DE3) with a molecular mass of 33.6 kDa. Enzyme assays using p-nitrophenyl esters with different acyl chain lengths as the substrates confirmed its esterase activity, yielding the highest activity with p-nitrophenyl butyrate. When p-nitrophenyl butyrate was used as a substrate, the optimum reaction temperature and pH for the enzyme were 60 degrees C and pH 7.5, respectively. Geobacillus sp. JM6 esterase showed excellent thermostability with 68% residual activity after incubation at 100 degrees C for 18 h. A theoretical structural model of strain JM6 esterase was developed with a monoacylglycerol lipase from Bacillus sp. H-257 as a template. The predicted core structure exhibits an alpha/beta hydrolase fold, and a putative catalytic triad (Ser97, Asp196, and His226) was identified. Inhibition assays with PMSF indicated that serine residue is involved in the catalytic activity of strain JM6 esterase. The recombinant esterase showed a relatively good tolerance to the detected detergents and denaturants, such as SDS, Chaps, Tween 20, Tween 80, Triton X-100, sodium deoxycholate, urea, and guanidine hydrochloride.
ESTHER : Zhu_2015_J.Basic.Microbiol_55_1219
PubMedSearch : Zhu_2015_J.Basic.Microbiol_55_1219
PubMedID: 26175347
Gene_locus related to this paper: 9baci-a0a0b5kth6

Title : Genome and transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. cubense causing banana vascular wilt disease - Guo_2014_PLoS.One_9_e95543
Author(s) : Guo L , Han L , Yang L , Zeng H , Fan D , Zhu Y , Feng Y , Wang G , Peng C , Jiang X , Zhou D , Ni P , Liang C , Liu L , Wang J , Mao C , Fang X , Peng M , Huang J
Ref : PLoS ONE , 9 :e95543 , 2014
Abstract : BACKGROUND: The asexual fungus Fusarium oxysporum f. sp. cubense (Foc) causing vascular wilt disease is one of the most devastating pathogens of banana (Musa spp.). To understand the molecular underpinning of pathogenicity in Foc, the genomes and transcriptomes of two Foc isolates were sequenced. METHODOLOGY/PRINCIPAL FINDINGS: Genome analysis revealed that the genome structures of race 1 and race 4 isolates were highly syntenic with those of F. oxysporum f. sp. lycopersici strain Fol4287. A large number of putative virulence associated genes were identified in both Foc genomes, including genes putatively involved in root attachment, cell degradation, detoxification of toxin, transport, secondary metabolites biosynthesis and signal transductions. Importantly, relative to the Foc race 1 isolate (Foc1), the Foc race 4 isolate (Foc4) has evolved with some expanded gene families of transporters and transcription factors for transport of toxins and nutrients that may facilitate its ability to adapt to host environments and contribute to pathogenicity to banana. Transcriptome analysis disclosed a significant difference in transcriptional responses between Foc1 and Foc4 at 48 h post inoculation to the banana 'Brazil' in comparison with the vegetative growth stage. Of particular note, more virulence-associated genes were up regulated in Foc4 than in Foc1. Several signaling pathways like the mitogen-activated protein kinase Fmk1 mediated invasion growth pathway, the FGA1-mediated G protein signaling pathway and a pathogenicity associated two-component system were activated in Foc4 rather than in Foc1. Together, these differences in gene content and transcription response between Foc1 and Foc4 might account for variation in their virulence during infection of the banana variety 'Brazil'. CONCLUSIONS/SIGNIFICANCE: Foc genome sequences will facilitate us to identify pathogenicity mechanism involved in the banana vascular wilt disease development. These will thus advance us develop effective methods for managing the banana vascular wilt disease, including improvement of disease resistance in banana.
ESTHER : Guo_2014_PLoS.One_9_e95543
PubMedSearch : Guo_2014_PLoS.One_9_e95543
PubMedID: 24743270
Gene_locus related to this paper: fusox-w9hvf0 , fusox-x0d9n6

Title : Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect - Xu_2014_BMC.Cancer_14_668
Author(s) : Xu H , Shen Z , Xiao J , Yang Y , Huang W , Zhou Z , Shen J , Zhu Y , Liu XY , Chu L
Ref : BMC Cancer , 14 :668 , 2014
Abstract : BACKGROUND: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
METHODS: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 x 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
RESULTS: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells. CONCLUSION: ZD55-AChE represented potential therapeutic effect for human gastric cancer.
ESTHER : Xu_2014_BMC.Cancer_14_668
PubMedSearch : Xu_2014_BMC.Cancer_14_668
PubMedID: 25220382

Title : Whole-genome sequence of a flatfish provides insights into ZW sex chromosome evolution and adaptation to a benthic lifestyle - Chen_2014_Nat.Genet_46_253
Author(s) : Chen S , Zhang G , Shao C , Huang Q , Liu G , Zhang P , Song W , An N , Chalopin D , Volff JN , Hong Y , Li Q , Sha Z , Zhou H , Xie M , Yu Q , Liu Y , Xiang H , Wang N , Wu K , Yang C , Zhou Q , Liao X , Yang L , Hu Q , Zhang J , Meng L , Jin L , Tian Y , Lian J , Yang J , Miao G , Liu S , Liang Z , Yan F , Li Y , Sun B , Zhang H , Zhu Y , Du M , Zhao Y , Schartl M , Tang Q , Wang J
Ref : Nat Genet , 46 :253 , 2014
Abstract : Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.
ESTHER : Chen_2014_Nat.Genet_46_253
PubMedSearch : Chen_2014_Nat.Genet_46_253
PubMedID: 24487278
Gene_locus related to this paper: cynse-a0a3p8wch2 , cynse-a0a3p8vd14 , cynse-a0a3p8w747 , cynse-a0a3p8wq40 , cynse-a0a3p8wul3 , cynse-a0a3p8vqr4 , cynse-a0a3p8vmz4

Title : Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis - Li_2014_PLoS.One_9_e94092
Author(s) : Li L , Li N , Pang W , Zhang X , Hammock BD , Ai D , Zhu Y
Ref : PLoS ONE , 9 :e94092 , 2014
Abstract : Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; manipulation of their levels is a potentially useful pharmacological strategy. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins. To better understand the phenotypic impact of sEH disruption, we compared the effect of EPHX2 gene knockout (EPHX2-/-) and sEH inhibition in mouse models. Measurement of plasma oxylipin profiles confirmed that the ratio of EETs/DHETs was increased in EPHX2-/- and sEH-inhibited mice. However, plasma concentrations of 9, 11, 15, 19-HETE were elevated in EPHX2-/- but not sEH-inhibited mice. Next, we investigated the role of this difference in cardiac dysfunction induced by Angiotensin II (AngII). Both EPHX2 gene deletion and inhibition protected against AngII-induced cardiac hypertrophy. Interestingly, cardiac dysfunction was attenuated by sEH inhibition rather than gene deletion. Histochemical staining revealed that compared with pharmacological inhibition, EPHX2 deletion aggravated AngII-induced myocardial fibrosis; the mRNA levels of fibrotic-related genes were increased. Furthermore, cardiac inflammatory response was greater in EPHX2-/- than sEH-inhibited mice with AngII treatment, as evidenced by increased macrophage infiltration and expression of MCP-1 and IL-6. In vitro, AngII-upregulated MCP-1 and IL-6 expression was significantly attenuated by sEH inhibition but promoted by EPHX2 deletion in cardiofibroblasts. Thus, compared with pharmacological inhibition of sEH, EPHX2 deletion caused the shift in arachidonic acid metabolism, which may led to pathological cardiac remodeling, especially cardiac fibrosis.
ESTHER : Li_2014_PLoS.One_9_e94092
PubMedSearch : Li_2014_PLoS.One_9_e94092
PubMedID: 24718617

Title : Swan probe: a nanoliter-scale and high-throughput sampling interface for coupling electrospray ionization mass spectrometry with microfluidic droplet array and multiwell plate - Jin_2014_Anal.Chem_86_10796
Author(s) : Jin DQ , Zhu Y , Fang Q
Ref : Analytical Chemistry , 86 :10796 , 2014
Abstract : Mass spectrometry provides a versatile detection method for high-throughput drug screening because it permits the use of native biological substrates and the direct quantification of unlabeled reaction products. This paper describes the design and application of a Swan-shaped probe for high-throughput and nanoliter-scale analysis of biological samples in both a microfluidic droplet array and a multiwell plate with electrospray ionization mass spectrometry (ESI-MS). The Swan probe is fabricated using a single capillary with quite low cost, and it consists of a U-shaped section with a micrometer-sized hole for sampling and a tapered tip for sample electrospray ionization. Continuous sample introduction was carried out under both sampling modes of push-pull and spontaneous injection by sequentially dipping the probe in the sample solutions and then removing them. High-throughput and reliable ESI-MS analysis was achieved in analyzing 256 droplets within 90 min with a peak height RSD of 12.6% (n = 256). To validate its potential in drug discovery, the present system was applied in the screening of inhibitors of acetylcholinesterase (AchE) and the measurement of the IC50 values of identified inhibitors.
ESTHER : Jin_2014_Anal.Chem_86_10796
PubMedSearch : Jin_2014_Anal.Chem_86_10796
PubMedID: 25302930

Title : Temporal specification and bilaterality of human neocortical topographic gene expression - Pletikos_2014_Neuron_81_321
Author(s) : Pletikos M , Sousa AM , Sedmak G , Meyer KA , Zhu Y , Cheng F , Li M , Kawasawa YI , Sestan N
Ref : Neuron , 81 :321 , 2014
Abstract : Transcriptional events involved in the development of human cerebral neocortex are poorly understood. Here, we analyzed the temporal dynamics and laterality of gene expression in human and macaque monkey neocortex. We found that interareal differences exhibit a temporal hourglass pattern, dividing the human neocortical development into three major phases. The first phase, corresponding to prenatal development, is characterized by the highest number of differential expressed genes among areas and gradient-like expression patterns, including those that are different between human and macaque. The second, preadolescent phase, is characterized by lesser interareal expression differences and by an increased synchronization of areal transcriptomes. During the third phase, from adolescence onward, differential expression among areas increases again driven predominantly by a subset of areas, without obvious gradient-like patterns. Analyses of left-right gene expression revealed population-level global symmetry throughout the fetal and postnatal time span. Thus, human neocortical topographic gene expression is temporally specified and globally symmetric.
ESTHER : Pletikos_2014_Neuron_81_321
PubMedSearch : Pletikos_2014_Neuron_81_321
PubMedID: 24373884

Title : Complete Genome Sequence of Neisseria meningitidis Serogroup A Strain NMA510612, Isolated from a Patient with Bacterial Meningitis in China - Zhang_2014_Genome.Announc_2_e00360
Author(s) : Zhang Y , Yang J , Xu L , Zhu Y , Liu B , Shao Z , Zhang X , Jin Q
Ref : Genome Announc , 2 :e00360 , 2014
Abstract : Serogroup A meningococcal strains have been involved in several pandemics and a series of epidemics worldwide in the past. Determination of the genome sequence of the prevalent genotype strain will help us understand the genetic background of the evolutionary and epidemiological properties of these bacteria. We sequenced the complete genome of Neisseria meningitidis NMA510612, a clinical isolate from a patient with meningococcal meningitis.
ESTHER : Zhang_2014_Genome.Announc_2_e00360
PubMedSearch : Zhang_2014_Genome.Announc_2_e00360
PubMedID: 24812217
Gene_locus related to this paper: neime-r0tza2

Title : Comparative analysis of bat genomes provides insight into the evolution of flight and immunity - Zhang_2013_Science_339_456
Author(s) : Zhang G , Cowled C , Shi Z , Huang Z , Bishop-Lilly KA , Fang X , Wynne JW , Xiong Z , Baker ML , Zhao W , Tachedjian M , Zhu Y , Zhou P , Jiang X , Ng J , Yang L , Wu L , Xiao J , Feng Y , Chen Y , Sun X , Zhang Y , Marsh GA , Crameri G , Broder CC , Frey KG , Wang LF , Wang J
Ref : Science , 339 :456 , 2013
Abstract : Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor kappaB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.
ESTHER : Zhang_2013_Science_339_456
PubMedSearch : Zhang_2013_Science_339_456
PubMedID: 23258410
Gene_locus related to this paper: myods-l5mij9 , pteal-l5k8f5 , pteal-l5kjy3 , pteal-l5k6f0 , pteal-l5kxe2 , myods-l5m0a8 , myods-l5lvb4 , pteal-l5k7h7 , myods-l5lm42 , pteal-l5jz73 , pteal-l5kvh1.1 , pteal-l5kvh1.2 , pteal-l5kw21 , myods-l5lug5 , pteal-l5kv18 , myods-l5lbf8 , pteal-l5kwh0 , myods-l5lfh8 , myods-l5lfr7 , myods-l5lu20 , pteal-l5jzi4 , pteal-l5kib7 , pteal-l5kyq5 , myods-l5lf36 , myods-l5lnh7 , myods-l5lu25 , pteal-l5k0u1 , pteal-l5k2g6 , pteal-l5l3r3 , myods-l5mdx5 , pteal-l5k220 , myolu-g1pdp2 , pteal-l5l5n3 , pteal-l5k1s7 , myolu-g1nth4 , pteal-l5l7w7 , pteal-l5l537 , myods-l5lwe4 , pteal-l5klr9 , pteal-l5k670 , pteal-l5jr94 , pteal-l5kvb4 , myolu-g1q4e3 , pteal-l5jrl1

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 : ContigScape: a Cytoscape plugin facilitating microbial genome gap closing - Tang_2013_BMC.Genomics_14_289
Author(s) : Tang B , Wang Q , Yang M , Xie F , Zhu Y , Zhuo Y , Wang S , Gao H , Ding X , Zhang L , Zhao G , Zheng H
Ref : BMC Genomics , 14 :289 , 2013
Abstract : BACKGROUND: With the emergence of next-generation sequencing, the availability of prokaryotic genome sequences is expanding rapidly. A total of 5,276 genomes have been released since 2008, yet only 1,692 genomes were complete. The final phase of microbial genome sequencing, particularly gap closing, is frequently the rate-limiting step either because of complex genomic structures that cause sequence bias even with high genomic coverage, or the presence of repeat sequences that may cause gaps in assembly.
RESULTS: We have developed a Cytoscape plugin to facilitate gap closing for high-throughput sequencing data from microbial genomes. This plugin is capable of interactively displaying the relationships among genomic contigs derived from various sequencing formats. The sequence contigs of plasmids and special repeats (IS elements, ribosomal RNAs, terminal repeats, etc.) can be displayed as well.
CONCLUSIONS: Displaying relationships between contigs using graphs in Cytoscape rather than tables provides a more straightforward visual representation. This will facilitate a faster and more precise determination of the linkages among contigs and greatly improve the efficiency of gap closing.
ESTHER : Tang_2013_BMC.Genomics_14_289
PubMedSearch : Tang_2013_BMC.Genomics_14_289
PubMedID: 23627759
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv0160c , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c , myctu-RV3452 , myctu-Rv3802c , amyor-r4tdn6 , amyor-r4sys4 , amyor-r4svp2 , amyor-r4t193 , amyor-r4t8c7 , amyor-r4t8w6 , amyor-r4t1x8 , amyor-r4stv4 , amyor-r4t7z6 , 9pseu-r4sx12

Title : Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii - Seim_2013_Nat.Commun_4_2212
Author(s) : Seim I , Fang X , Xiong Z , Lobanov AV , Huang Z , Ma S , Feng Y , Turanov AA , Zhu Y , Lenz TL , Gerashchenko MV , Fan D , Hee Yim S , Yao X , Jordan D , Xiong Y , Ma Y , Lyapunov AN , Chen G , Kulakova OI , Sun Y , Lee SG , Bronson RT , Moskalev AA , Sunyaev SR , Zhang G , Krogh A , Wang J , Gladyshev VN
Ref : Nat Commun , 4 :2212 , 2013
Abstract : Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat.
ESTHER : Seim_2013_Nat.Commun_4_2212
PubMedSearch : Seim_2013_Nat.Commun_4_2212
PubMedID: 23962925
Gene_locus related to this paper: myobr-s7mf99 , myobr-s7n4r2 , myobr-s7neb7 , myobr-s7ney7 , myobr-s7n9l2 , myobr-s7nk13 , myobr-s7mh20 , myobr-s7pbt8 , myobr-s7mux2 , myobr-s7mjb5 , myobr-s7n6x5 , myobr-s7nnt6 , myobr-s7n728.2 , myobr-s7n728.3 , myobr-s7n8d2 , myobr-s7nqw0 , myobr-s7mju4 , myolu-g1nth4 , myobr-s7mij5 , myobr-s7pr94 , myolu-g1q4e3 , myolu-g1p353

Title : Characterization of a new and thermostable esterase from a metagenomic library - Zhu_2013_Microbiol.Res_168_589
Author(s) : Zhu Y , Li J , Cai H , Ni H , Xiao A , Hou L
Ref : Microbiol Res , 168 :589 , 2013
Abstract : A new gene encoding an esterase (designated as EstEP16) was identified from a metagenomic library prepared from a sediment sample collected from a deep-sea hydrothermal field in east Pacific. The open reading frame of this gene encoded 249 amino acid residues. It was cloned, overexpressed in Escherichia coli, and the recombinant protein was purified to homogeneity. The monomeric EstEP16 presented a molecular mass of 51.7kDa. Enzyme assays using p-nitrophenyl esters with different acyl chain lengths as the substrates confirmed its esterase activity, yielding highest specific activity with p-nitrophenyl acetate. When p-nitrophenyl butyrate was used as a substrate, recombinant EstEP16 exhibited highest activity at pH 8.0 and 60 degrees C. The recombinant enzyme retained about 80% residual activity after incubation at 90 degrees C for 6h, which indicated that EstEP16 was thermostable. Homology modeling of EstEP16 was developed with the monoacylglycerol lipase from Bacillus sp. H-257 as a template. The structure showed an alpha/beta-hydrolase fold and indicated the presence of a typical catalytic triad. The activity of EstEP16 was inhibited by addition of phenylmethylsulfonyl fluoride, indicating that it contains serine residue, which plays a key role in the catalytic mechanism.
ESTHER : Zhu_2013_Microbiol.Res_168_589
PubMedSearch : Zhu_2013_Microbiol.Res_168_589
PubMedID: 23684391
Gene_locus related to this paper: 9bact-r9rev7

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice - Liu_2012_PLoS.One_7_e39165
Author(s) : Liu Y , Dang H , Li D , Pang W , Hammock BD , Zhu Y
Ref : PLoS ONE , 7 :e39165 , 2012
Abstract : Non-alcoholic fatty liver disease is associated with obesity and considered an inflammatory disease. Soluble epoxide hydrolase (sEH) is a major enzyme hydrolyzing epoxyeicosatrienoic acids and attenuates their cardiovascular protective and anti-inflammatory effects. We examined whether sEH inhibition can protect against high-fat (HF)-diet-induced fatty liver in mice and the underlying mechanism. Compared with wild-type littermates, sEH-null mice showed lower diet-induced lipid accumulation in liver, as seen by Oil-red O staining and triglycerides levels. We studied the effect of sEH inhibition on diet-induced fatty liver by feeding C57BL/6 mice an HF diet for 8 weeks (short-term) or 16 weeks (long-term) and administering t-AUCB, a selective sEH inhibitor. sEH inhibition had no effect on the HF-diet-increased body and adipose tissue weight or impaired glucose tolerance but alleviated the diet-induced hepatic steatosis. Adenovirus-mediated overexpression of sEH in liver increased the level of triglycerides in liver and the hepatic inflammatory response. Surprisingly, the induced expression of sEH in liver occurred only with the long-term but not short-term HF diet, which suggests a secondary effect of HF diet on regulating sEH expression. Furthermore, sEH inhibition attenuated the HF-diet-induced increase in plasma levels of proinflammatory cytokines and their mRNA upregulation in adipose tissue, which was accompanied by increased macrophage infiltration. Therefore, sEH inhibition could alleviate HF-diet-induced hepatic steatosis, which might involve its anti-inflammatory effect in adipose tissue and direct inhibition in liver. sEH may be a therapeutic target for HF-diet-induced hepatic steatosis in inhibiting systemic inflammation.
ESTHER : Liu_2012_PLoS.One_7_e39165
PubMedSearch : Liu_2012_PLoS.One_7_e39165
PubMedID: 22720061

Title : Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601 - Zhong_2011_Cell.Res_21_1210
Author(s) : Zhong Y , Chang X , Cao XJ , Zhang Y , Zheng H , Zhu Y , Cai C , Cui Z , Li YY , Jiang XG , Zhao GP , Wang S , Li Y , Zeng R , Li X , Guo XK
Ref : Cell Res , 21 :1210 , 2011
Abstract : The virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was derived by prolonged laboratory passage from a highly virulent ancestral strain isolated in China. We studied the genetic variations of IPAV that render it avirulent via comparative analysis against the pathogenic L. interrogans serovar Lai strain 56601. The complete genome sequence of the IPAV strain was determined and used to compare with, and then rectify and reannotate the genome sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 33 insertions, 53 deletions and 301 single-nucleotide variations (SNVs) were detected throughout the genome of IPAV directly affecting 101 genes, either in their 5' upstream region or within their coding region. Among them, the majority of the 44 functional genes are involved in signal transduction, stress response, transmembrane transport and nitrogen metabolism. Comparative proteomic analysis based on quantitative liquid chromatography (LC)-MS/MS data revealed that among 1 627 selected pairs of orthologs, 174 genes in the IPAV strain were upregulated, with enrichment mainly in classes of energy production and lipid metabolism. In contrast, 228 genes in strain 56601 were upregulated, with the majority enriched in the categories of protein translation and DNA replication/repair. The combination of genomic and proteomic approaches illustrated that altered expression or mutations in critical genes, such as those encoding a Ser/Thr kinase, carbon-starvation protein CstA, glutamine synthetase, GTP-binding protein BipA, ribonucleotide-diphosphate reductase and phosphate transporter, and alterations in the translational profile of lipoproteins or outer membrane proteins are likely to account for the virulence attenuation in strain IPAV.
ESTHER : Zhong_2011_Cell.Res_21_1210
PubMedSearch : Zhong_2011_Cell.Res_21_1210
PubMedID: 21423275
Gene_locus related to this paper: lepin-q72tt9

Title : Altered activity-rest patterns in mice with a human autosomal-dominant nocturnal frontal lobe epilepsy mutation in the beta2 nicotinic receptor - Xu_2011_Mol.Psychiatry_16_1048
Author(s) : Xu J , Cohen BN , Zhu Y , Dziewczapolski G , Panda S , Lester HA , Heinemann SF , Contractor A
Ref : Mol Psychiatry , 16 :1048 , 2011
Abstract : High-affinity nicotinic receptors containing beta2 subunits (beta2*) are widely expressed in the brain, modulating many neuronal processes and contributing to neuropathologies such as Alzheimer's disease, Parkinson's disease and epilepsy. Mutations in both the alpha4 and beta2 subunits are associated with a rare partial epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In this study, we introduced one such human missense mutation into the mouse genome to generate a knock-in strain carrying a valine-to-leucine mutation beta2V287L. beta2(V287L) mice were viable and born at an expected Mendelian ratio. Surprisingly, mice did not show an overt seizure phenotype; however, homozygous mice did show significant alterations in their activity-rest patterns. This was manifest as an increase in activity during the light cycle suggestive of disturbances in the normal sleep patterns of mice; a parallel phenotype to that found in human ADNFLE patients. Consistent with the role of nicotinic receptors in reward pathways, we found that beta2(V287L) mice did not develop a normal proclivity to voluntary wheel running, a model for natural reward. Anxiety-related behaviors were also affected by the V287L mutation. Mutant mice spent more time in the open arms on the elevated plus maze suggesting that they had reduced levels of anxiety. Together, these findings emphasize several important roles of beta2* nicotinic receptors in complex biological processes including the activity-rest cycle, natural reward and anxiety.
ESTHER : Xu_2011_Mol.Psychiatry_16_1048
PubMedSearch : Xu_2011_Mol.Psychiatry_16_1048
PubMedID: 20603624

Title : Complete genome sequence of Bacillus thuringiensis serovar finitimus strain YBT-020 - Zhu_2011_J.Bacteriol_193_2379
Author(s) : Zhu Y , Shang H , Zhu Q , Ji F , Wang P , Fu J , Deng Y , Xu C , Ye W , Zheng J , Zhu L , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2379 , 2011
Abstract : Bacillus thuringiensis is a gram-positive, spore-forming bacterium that forms parasporal crystals at the onset of the sporulation phase of its growth. Here, we report the complete genome sequence of B. thuringiensis serovar finitimus strain YBT-020, whose parasporal crystals consist of Cry26Aa and Cry28Aa crystal proteins and are located between the exosporium and the spore coat and remain adhering to the spore after sporulation.
ESTHER : Zhu_2011_J.Bacteriol_193_2379
PubMedSearch : Zhu_2011_J.Bacteriol_193_2379
PubMedID: 21398543
Gene_locus related to this paper: bacan-BA2392 , bacan-BA5009 , bacan-BA5110 , bacan-DHBF , bacce-BC2141 , bacce-BC4862 , bacce-BC5130 , bacce-BCE3188 , bacce-PHAC , bacce-q72yu1 , baccn-a7guq6 , baccr-pepx , bacce-c2qdt4

Title : Complete genome sequence of Clostridium acetobutylicum DSM 1731, a solvent-producing strain with multireplicon genome architecture - Bao_2011_J.Bacteriol_193_5007
Author(s) : Bao G , Wang R , Zhu Y , Dong H , Mao S , Zhang Y , Chen Z , Li Y , Ma Y
Ref : Journal of Bacteriology , 193 :5007 , 2011
Abstract : Clostridium acetobutylicum is an important microorganism for solvent production. We report the complete genome sequence of C. acetobutylicum DSM 1731, a genome with multireplicon architecture. Comparison with the sequenced type strain C. acetobutylicum ATCC 824, the genome of strain DSM1731 harbors a 1.7-kb insertion and a novel 11.1-kb plasmid, which might have been acquired during evolution.
ESTHER : Bao_2011_J.Bacteriol_193_5007
PubMedSearch : Bao_2011_J.Bacteriol_193_5007
PubMedID: 21742891
Gene_locus related to this paper: cloab-q97db4 , cloac-pnbae

Title : Complete genome sequence of Bacillus subtilis BSn5, an endophytic bacterium of Amorphophallus konjac with antimicrobial activity for the plant pathogen Erwinia carotovora subsp. carotovora - Deng_2011_J.Bacteriol_193_2070
Author(s) : Deng Y , Zhu Y , Wang P , Zhu L , Zheng J , Li R , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2070 , 2011
Abstract : Here, we present the complete genome sequence of Bacillus subtilis strain BSn5, isolated from Amorphophallus konjac calli tissue and showing strong inhibitory activity to Erwinia carotovora subsp. carotovora, which causes Amorphophallus soft rot disease and affects the industry development of this organism.
ESTHER : Deng_2011_J.Bacteriol_193_2070
PubMedSearch : Deng_2011_J.Bacteriol_193_2070
PubMedID: 21317323
Gene_locus related to this paper: bacpu-pnbae , bacsu-CAH , bacsu-lip , bacsu-LIPB , bacsu-PPSE , bacsu-YBAC , bacsu-YDEN , bacsu-YTPA , bacsu-ytxm , bacsu-YVAK

Title : Genome analyses of Icelandic strains of Sulfolobus islandicus, model organisms for genetic and virus-host interaction studies - Guo_2011_J.Bacteriol_193_1672
Author(s) : Guo L , Brugger K , Liu C , Shah SA , Zheng H , Zhu Y , Wang S , Lillestol RK , Chen L , Frank J , Prangishvili D , Paulin L , She Q , Huang L , Garrett RA
Ref : Journal of Bacteriology , 193 :1672 , 2011
Abstract : The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad host range for exceptional crenarchaeal viruses and conjugative plasmids and was selected for studying their life cycles and host interactions. The genomes of strains REY15A and HVE10/4 are 2.5 and 2.7 Mb, respectively, and each genome carries a variable region of 0.5 to 0.7 Mb where major differences in gene content and gene order occur. These include gene clusters involved in specific metabolic pathways, multiple copies of VapBC antitoxin-toxin gene pairs, and in strain HVE10/4, a 50-kb region rich in glycosyl transferase genes. The variable region also contains most of the insertion sequence (IS) elements and high proportions of the orphan orfB elements and SMN1 miniature inverted-repeat transposable elements (MITEs), as well as the clustered regular interspaced short palindromic repeat (CRISPR)-based immune systems, which are complex and diverse in both strains, consistent with them having been mobilized both intra- and intercellularly. In contrast, the remainder of the genomes are highly conserved in their protein and RNA gene syntenies, closely resembling those of other S. islandicus and Sulfolobus solfataricus strains, and they exhibit only minor remnants of a few genetic elements, mainly conjugative plasmids, which have integrated at a few tRNA genes lacking introns. This provides a possible rationale for the presence of the introns.
ESTHER : Guo_2011_J.Bacteriol_193_1672
PubMedSearch : Guo_2011_J.Bacteriol_193_1672
PubMedID: 21278296
Gene_locus related to this paper: sulir-f0nbu1 , sulso-APEH1 , sulso-APEH3 , sulso-dlhh , sulir-f0ndq1

Title : Genome sequencing reveals insights into physiology and longevity of the naked mole rat - Kim_2011_Nature_479_223
Author(s) : Kim EB , Fang X , Fushan AA , Huang Z , Lobanov AV , Han L , Marino SM , Sun X , Turanov AA , Yang P , Yim SH , Zhao X , Kasaikina MV , Stoletzki N , Peng C , Polak P , Xiong Z , Kiezun A , Zhu Y , Chen Y , Kryukov GV , Zhang Q , Peshkin L , Yang L , Bronson RT , Buffenstein R , Wang B , Han C , Li Q , Chen L , Zhao W , Sunyaev SR , Park TJ , Zhang G , Wang J , Gladyshev VN
Ref : Nature , 479 :223 , 2011
Abstract : The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
ESTHER : Kim_2011_Nature_479_223
PubMedSearch : Kim_2011_Nature_479_223
PubMedID: 21993625
Gene_locus related to this paper: hetga-g5amh8 , hetga-g5an68 , hetga-g5anw7 , hetga-g5as32 , hetga-g5atg6 , hetga-g5b5b7 , hetga-g5b9m6 , hetga-g5bdh8 , hetga-g5bmv3 , hetga-g5bp66 , hetga-g5bp67 , hetga-g5bp68 , hetga-g5bpp3 , hetga-g5bsd4 , hetga-g5bul0 , hetga-g5bw29 , hetga-g5bze3 , hetga-g5c6q5 , hetga-g5bfw4 , hetga-g5b832 , hetga-g5c6q8 , hetga-g5bj87 , hetga-a0a0p6jix7 , hetga-g5c108 , hetga-g5c109 , hetga-g5c110 , hetga-g5arh0 , hetga-g5aua1 , hetga-g5are8 , hetga-g5ax31 , hetga-a0a0p6jud6 , hetga-g5b7v3 , hetga-a0a0p6jw61 , hetga-a0a0p6jdl4 , hetga-g5bg83 , hetga-g5bcu5 , hetga-g5bvp0 , hetga-g5b8m7 , hetga-g5b709 , hetga-g5bt99 , hetga-g5b4q4

Title : Novel nicotinic action of the sulfoximine insecticide sulfoxaflor - Watson_2011_Insect.Biochem.Mol.Biol_41_432
Author(s) : Watson GB , Loso MR , Babcock JM , Hasler JM , Letherer TJ , Young CD , Zhu Y , Casida JE , Sparks TC
Ref : Insect Biochemistry & Molecular Biology , 41 :432 , 2011
Abstract : The novel sulfoximine insecticide sulfoxaflor is as potent or more effective than the neonicotinoids for toxicity to green peach aphids (GPA, Myzus persicae). The action of sulfoxaflor was characterized at insect nicotinic acetylcholine receptors (nAChRs) using electrophysiological and radioligand binding techniques. When tested for agonist properties on Drosophila melanogaster Dalpha2 nAChR subunit co-expressed in Xenopus laevis oocytes with the chicken beta2 subunit, sulfoxaflor elicited very high amplitude (efficacy) currents. Sulfoximine analogs of sulfoxaflor were also agonists on Dalpha2/beta2 nAChRs, but none produced maximal currents equivalent to sulfoxaflor nor were any as toxic to GPAs. Additionally, except for clothianidin, none of the neonicotinoids produced maximal currents as large as those produced by sulfoxaflor. These data suggest that the potent insecticidal activity of sulfoxaflor may be due to its very high efficacy at nAChRs. In contrast, sulfoxaflor displaced [(3)H]imidacloprid (IMI) from GPA nAChR membrane preparations with weak affinity compared to most of the neonicotinoids examined. The nature of the interaction of sulfoxaflor with nAChRs apparently differs from that of IMI and other neonicotinoids, and when coupled with other known characteristics (novel chemical structure, lack of cross-resistance, and metabolic stability), indicate that sulfoxaflor represents a significant new insecticide option for the control of sap-feeding insects.
ESTHER : Watson_2011_Insect.Biochem.Mol.Biol_41_432
PubMedSearch : Watson_2011_Insect.Biochem.Mol.Biol_41_432
PubMedID: 21296156

Title : Complete genome sequence of the neonatal-meningitis-associated Escherichia coli strain CE10 - Lu_2011_J.Bacteriol_193_7005
Author(s) : Lu S , Zhang X , Zhu Y , Kim KS , Yang J , Jin Q
Ref : Journal of Bacteriology , 193 :7005 , 2011
Abstract : Neonatal bacterial meningitis continues to be an important cause of mortality and morbidity worldwide. Escherichia coli possessing the K1 capsular polysaccharide is the most common Gram-negative pathogen causing neonatal meningitis. Here we present the complete genome sequence of neonatal meningitis-associated E. coli strain CE10, a unique K1 strain with a functional type III secretion system. Functional analysis of the genome should enhance our knowledge of the pathogenesis of neonatal E. coli K1 meningitis.
ESTHER : Lu_2011_J.Bacteriol_193_7005
PubMedSearch : Lu_2011_J.Bacteriol_193_7005
PubMedID: 22123760
Gene_locus related to this paper: ecoli-ybff , ecoli-YFBB , ecoli-yqia , ecoli-YfhR

Title : Ligustilide suppresses the biological properties of Danggui Buxue Tang: a Chinese herbal decoction composed of radix astragali and radix angelica sinensis - Zheng_2010_Planta.Med_76_439
Author(s) : Zheng YZ , Choi RC , Li J , Xie HQ , Cheung AW , Duan R , Guo AJ , Zhu JT , Chen VP , Bi CWC , Zhu Y , Lau DD , Dong TTX , Lau BW , Tsim KWK
Ref : Planta Med , 76 :439 , 2010
Abstract : Danggui Buxue Tang (DBT), a herbal decoction composed of Radix Astragali (RA) and Radix Angelica sinensis (RAS), has been used for treating menopausal irregularity in women for more than 800 years in China. According to the old tradition, RAS had to be processed with yellow wine before DBT preparation, which markedly reduced the amount of ligustilide in RAS and DBT, as well as enhanced the bioactivities of DBT. Here, we hypothesized that ligustilide would be an ingredient that possessed suppressive effects on DBT's functions. In the presence of ligustilide, the amount of astragaloside IV, calycosin, formononetin, and total polysaccharides extracted from RA were decreased. An increase of ligustilide caused a decrease of DBT's osteogenic activity in stimulating proliferation and differentiation of cultured bone cells. In addition, in the presence of a high level of ligustilide, DBT caused a side effect inducing the proliferation of breast MCF-7 cells. The current results strongly suggest that ligustilide is a negative regulator that hinders DBT to achieve its biological efficacy, which supports the traditional practice of preparing DBT using the ethanol-treated RAS.
ESTHER : Zheng_2010_Planta.Med_76_439
PubMedSearch : Zheng_2010_Planta.Med_76_439
PubMedID: 19847742

Title : Management of the diffusion of 4-methylumbelliferone across phases in microdroplet-based systems for in vitro protein evolution - Wu_2010_Electrophoresis_31_3121
Author(s) : Wu N , Courtois F , Zhu Y , Oakeshott J , Easton C , Abell C
Ref : Electrophoresis , 31 :3121 , 2010
Abstract : Fluorongenic reagents based on 4-methylumbelliferone (4-MU) have been widely used for the detection of phosphatase, sulfatase, esterase, lipase and glycosidase activities in conventionally formatted enzyme assay systems. However, the sensitivity of assays based on these substrates is also potentially very useful in the microdroplet formats now being developed for high throughput in vitro evolution experiments. In this article, we report the investigation of diffusion of 4-MU as a model dye from water-in-oil droplets and the internal aqueous phase of water-in-oil-in-water droplets in microfluidics. The effect of BSA in the aqueous phase on the diffusion of 4-MU is also discussed. Based on these results, we provided here proof-of-concept of the reaction of the enzyme OpdA with the substrate coumaphos in water-in-oil-in-water droplets. In this double-emulsion system, the reaction of OpdA and coumaphos was achieved by allowing coumaphos to diffuse from the continuous aqueous phase across the oil phase into the internal aqueous droplets.
ESTHER : Wu_2010_Electrophoresis_31_3121
PubMedSearch : Wu_2010_Electrophoresis_31_3121
PubMedID: 20803501

Title : Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism - Zhao_2010_Cell.Res_20_1096
Author(s) : Zhao W , Zhong Y , Yuan H , Wang J , Zheng H , Wang Y , Cen X , Xu F , Bai J , Han X , Lu G , Zhu Y , Shao Z , Yan H , Li C , Peng N , Zhang Z , Zhang Y , Lin W , Fan Y , Qin Z , Hu Y , Zhu B , Wang S , Ding X , Zhao GP
Ref : Cell Res , 20 :1096 , 2010
Abstract : Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimycobacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10,236,715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9,228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasi-core' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.
ESTHER : Zhao_2010_Cell.Res_20_1096
PubMedSearch : Zhao_2010_Cell.Res_20_1096
PubMedID: 20567260
Gene_locus related to this paper: amyme-ester , amymu-d8hj63 , amymu-d8hka5 , amymu-d8hl19 , amymu-d8hp99 , amymu-d8hpp2 , amymu-d8htc9 , amymu-d8hu68 , amymu-d8hu87 , amymu-d8hy40 , amymu-d8hy73 , amymu-d8i2j5 , amymu-d8i4g6 , amymu-d8i8i8 , amymu-d8hri1 , amymu-d8hsx7 , amymu-d8hzu8 , amymu-d8i5g7 , amyms-g0g7f0 , amymu-a0a0h3cwx4 , amymu-a0a0h3d2a5 , amymu-a0a0h3d6r8

Title : DNA methylation of the promoter of soluble epoxide hydrolase silences its expression by an SP-1-dependent mechanism - Zhang_2010_Biochim.Biophys.Acta_1799_659
Author(s) : Zhang D , Ai D , Tanaka H , Hammock BD , Zhu Y
Ref : Biochimica & Biophysica Acta , 1799 :659 , 2010
Abstract : Epoxyeicosatrienoic acids, derived from arachidonic acid, function as antihypertensive and antihypertrophic mediators in the cardiovascular system. They are hydrolyzed by soluble epoxide hydrolase (sEH). Pharmacological inhibition of sEH increases the level of epoxyeicosatrienoic acids, which may have a cardiovascular protective effect. However, the regulation and function of sEH in cancer are largely unknown. The present study investigated whether DNA methylation regulates the expression of sEH in carcinoma HepG2 cells. The mRNA and protein expressions of sEH in HepG2 cells were lower than those in transformed human embryonic kidney cells and in primary cultured human endothelial cells. Bioinformatic analysis revealed a putative CpG island and 5 SP-1 binding sites located in the promoter region of the sEH gene. Furthermore, the sEH expression was significantly enhanced by demethylation treatment with 5-Aza-CdR, a DNA methyltransferase inhibitor, and the sEH promoter was transformed from hypermethylation to hypomethylation as detected by methylation-specific PCR and bisulfite sequencing. Transient transfection assays showed that the activity of the human sEH promoter was increased in HepG2 cells in response to 5-Aza-CdR. Five SP-1 binding sites in the promoter region responding to treatment with 5-Aza-CdR were identified by construct deletion and mutation analysis and chromatin immunoprecipitation assay. Interestingly, adenoviral overexpression of sEH in HepG2 cells decreased cell proliferation. Thus, SP-1 is involved in the decrease in the transcription of sEH as a result of DNA methylation in HepG2 cells, which might contribute to epigenetic mechanism-induced carcinogenesis in hepatocytes.
ESTHER : Zhang_2010_Biochim.Biophys.Acta_1799_659
PubMedSearch : Zhang_2010_Biochim.Biophys.Acta_1799_659
PubMedID: 20888937

Title : Synthesis, biological assay in vitro and molecular docking studies of new imidazopyrazinone derivatives as potential dipeptidyl peptidase IV inhibitors - Zhu_2010_Eur.J.Med.Chem_45_4953
Author(s) : Zhu Y , Xia S , Zhu M , Yi W , Cheng J , Song G , Li Z , Lu P
Ref : Eur Journal of Medicinal Chemistry , 45 :4953 , 2010
Abstract : A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC(50)=78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h.
ESTHER : Zhu_2010_Eur.J.Med.Chem_45_4953
PubMedSearch : Zhu_2010_Eur.J.Med.Chem_45_4953
PubMedID: 20800322

Title : [Influence of electroacupuncture of Baihui (GV 20) and Sanyinjiao (SP 6) on hippocampal 5-HT and AChE immuno-activity in chronic depression rats] - Zhu_2009_Zhen.Ci.Yan.Jiu_34_16
Author(s) : Zhu Y , Liu QY , Zhuo LS
Ref : Zhen Ci Yan Jiu , 34 :16 , 2009
Abstract : OBJECTIVE: To investigate the influence of electroacupuncture (EA) on 5-serotonin (5-HT) and acetyl cholinesterase (AChE) activities in hippocampus tissue in chronic stressed-induced depression rats. METHODS: Thirty-two Wistar rats were randomized into normal control group (n=10), model group (n=11) and EA group (n=11). Chronic depression model was established by lonely raising, and chronic unpredictable mild stress for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Sanyinjiao" (SP 6) for 20 minutes, once daily for 14 days. 5-HT and AChE expression of hippocampal CA 4 region was detected by using immunohistochemistry, and their integrated optical density (IOD) values were determined by using image analysis system. RESULTS: Compared with normal control group, IOD values of 5-HT and AChE immuno-reaction (IR) positive neurons in hippocampal CA 4 region of model group decreased significantly (P<0.05). In comparison with model group, the IOD values of 5-HT and AChE IR positive neurons of CA 4 region in EA group increased significantly (P<0.05). No significant differences were found between EA and normal control groups in IOD values of both 5-HT and AChE IR positive neurons. CONCLUSION: EA can upregulate 5-HT and AChE expression in hippocampal CA 4 region in depression rats, which may contribute to its effect in relieving depression.
ESTHER : Zhu_2009_Zhen.Ci.Yan.Jiu_34_16
PubMedSearch : Zhu_2009_Zhen.Ci.Yan.Jiu_34_16
PubMedID: 19526802

Title : Complete genome sequence of the extremophilic Bacillus cereus strain Q1 with industrial applications - Xiong_2009_J.Bacteriol_191_1120
Author(s) : Xiong Z , Jiang Y , Qi D , Lu H , Yang F , Yang J , Chen L , Sun L , Xu X , Xue Y , Zhu Y , Jin Q
Ref : Journal of Bacteriology , 191 :1120 , 2009
Abstract : Bacillus cereus strain Q1 was isolated from a deep-subsurface oil reservoir in the Daqing oil field in northeastern China. This strain is able to produce biosurfactants and to survive in extreme environments. Here we report the finished and annotated genome sequence of this organism.
ESTHER : Xiong_2009_J.Bacteriol_191_1120
PubMedSearch : Xiong_2009_J.Bacteriol_191_1120
PubMedID: 19060151
Gene_locus related to this paper: bacah-a0rer5 , bacan-BA0954 , bacan-BA3703 , bacan-BA4338 , bacan-BA5009 , bacan-DHBF , bacc1-q73br9 , bacce-BC0192 , bacce-BC0968 , bacce-BC1788 , bacce-BC2141 , bacce-BC2171 , bacce-BC4102 , bacce-BC4854 , bacce-BC4862 , bacce-BC5130 , bacce-c2mr40 , bacce-PHAC , bacce-q72yu1 , bacce-q736x9 , baccq-b9j170 , baccr-pepx , baccz-q636u4 , bacti-q3elq7

Title : Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase - Zhu_2009_Bioorg.Med.Chem_17_1600
Author(s) : Zhu Y , Xiao K , Ma L , Xiong B , Fu Y , Yu H , Wang W , Wang X , Hu D , Peng H , Li J , Gong Q , Chai Q , Tang X , Zhang H , Shen J
Ref : Bioorganic & Medicinal Chemistry , 17 :1600 , 2009
Abstract : To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC(50)=0.567 microM; AChE: IC(50)=1.83 microM), and also showed excellent inhibitory effects on Abeta production of APP transfected HEK293 cells (IC(50)=98.7 nM) and mild protective effect against hydrogen peroxide (H(2)O(2))-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of Abeta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients.
ESTHER : Zhu_2009_Bioorg.Med.Chem_17_1600
PubMedSearch : Zhu_2009_Bioorg.Med.Chem_17_1600
PubMedID: 19162488

Title : Cordysinocan, a polysaccharide isolated from cultured Cordyceps, activates immune responses in cultured T-lymphocytes and macrophages: signaling cascade and induction of cytokines - Cheung_2009_J.Ethnopharmacol_124_61
Author(s) : Cheung JK , Li J , Cheung AW , Zhu Y , Zheng KY , Bi CWC , Duan R , Choi RC , Lau DT , Dong TTX , Lau BW , Tsim KWK
Ref : J Ethnopharmacol , 124 :61 , 2009
Abstract : Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumor, anti-oxidation and stimulating the immune response; however, the identity of active component(s) is not determined. A strain of Cordyceps sinensis, namely UST 2000, has been isolated. By using activity-guided purification, a novel polysaccharide of molecular weight approximately 82 kDa was isolated from the conditioned medium of cultured Cordyceps. The isolated exo-polysaccharide, namely cordysinocan, contains glucose, mannose, galactose in a ratio of 2.4:2:1. In cultured T-lymphocytes, application of cordysinocan induced the cell proliferation and the secretion of interleukin-2, interleukin-6 and interleukin-8. In addition, the phosphorylation of extracellular signal-regulated kinases (ERK) was induced transiently by the treatment of cordysinocan. Moreover, application of cordysinocan in cultured macrophages increased the phagocytosis activity and the enzymatic activity of acid phosphatase. These results therefore verify the important role of Cordyceps polysaccharide in triggering such immune responses.
ESTHER : Cheung_2009_J.Ethnopharmacol_124_61
PubMedSearch : Cheung_2009_J.Ethnopharmacol_124_61
PubMedID: 19446414

Title : The complete genome of Comamonas testosteroni reveals its genetic adaptations to changing environments - Ma_2009_Appl.Environ.Microbiol_75_6812
Author(s) : Ma YF , Zhang Y , Zhang JY , Chen DW , Zhu Y , Zheng H , Wang SY , Jiang CY , Zhao GP , Liu SJ
Ref : Applied Environmental Microbiology , 75 :6812 , 2009
Abstract : Members of the gram-negative, strictly aerobic genus Comamonas occur in various environments. Here we report the complete genome of Comamonas testosteroni strain CNB-2. Strain CNB-2 has a circular chromosome that is 5,373,643 bp long and has a G+C content of 61.4%. A total of 4,803 open reading frames (ORFs) were identified; 3,514 of these ORFs are functionally assigned to energy production, cell growth, signal transduction, or transportation, while 866 ORFs encode hypothetical proteins and 423 ORFs encode purely hypothetical proteins. The CNB-2 genome has many genes for transportation (22%) and signal transduction (6%), which allows the cells to respond and adapt to changing environments. Strain CNB-2 does not assimilate carbohydrates due to the lack of genes encoding proteins involved in glycolysis and pentose phosphate pathways, and it contains many genes encoding proteins involved in degradation of aromatic compounds. We identified 66 Tct and nine TRAP-T systems and a complete tricarboxylic acid cycle, which may allow CNB-2 to take up and metabolize a range of carboxylic acids. This nutritional bias for carboxylic acids and aromatic compounds enables strain CNB-2 to occupy unique niches in environments. Four different sets of terminal oxidases for the respiratory system were identified, and they putatively functioned at different oxygen concentrations. This study conclusively revealed at the genomic level that the genetic versatility of C. testosteroni is vital for competition with other bacteria in its special niches.
ESTHER : Ma_2009_Appl.Environ.Microbiol_75_6812
PubMedSearch : Ma_2009_Appl.Environ.Microbiol_75_6812
PubMedID: 19734336
Gene_locus related to this paper: comt2-d0iwv3 , comt2-d0iyk2 , comt2-d0izv6 , comt2-d0j1z3 , comt2-d0j233 , comte-b7wt77 , comte-b7wvy1 , comte-b7wwl1 , comte-b7wz02 , comte-b7x0f1 , comte-b7x2b9 , comte-b7x5l7 , comte-d8d555 , comte-TESD , comte-b7wth6 , comt2-d0j2k4

Title : Effects of galantamine on measures of attention: results from 2 clinical trials in Alzheimer disease patients with comparisons to donepezil - Galvin_2008_Alzheimer.Dis.Assoc.Disord_22_30
Author(s) : Galvin JE , Cornblatt B , Newhouse P , Ancoli-Israel S , Wesnes K , Williamson D , Zhu Y , Sorra K , Amatniek J
Ref : Alzheimer Disease & Associated Disorders , 22 :30 , 2008
Abstract : Deficits in attention are present early in the course of Alzheimer disease (AD). Acetylcholine receptors are appealing molecular targets for intervention as cholinergic pathways are involved in the neurobiology of attention. For this reason, measures of attention were included in 2 independent, multicenter, randomized, parallel, controlled trials in subjects with AD comparing the effects of galantamine, an acetylcholinesterase inhibitor and postulated nicotinic receptor modulator, and donepezil, an acetylcholinesterase inhibitor. The attention battery of the Cognitive Drug Research computerized assessment system was used in both trials. Small magnitude, positive signals were observed for simple and choice reaction times for both compounds. Attention task performance tended to improve early for galantamine-treated subjects. A consistent temporal pattern of improvement was not observed in donepezil-treated subjects. Quantitative findings appeared more pronounced in subjects with moderate AD. Galantamine's proposed action as a nicotinic receptor modulator may bear on these findings. Improved attention may have positive effects on cognitive and functional outcomes for AD patients, although this hypothesis requires further study and validation.
ESTHER : Galvin_2008_Alzheimer.Dis.Assoc.Disord_22_30
PubMedSearch : Galvin_2008_Alzheimer.Dis.Assoc.Disord_22_30
PubMedID: 18317244

Title : Construction of the pharmacophore model of acetylcholinesterase inhibitor - Zhu_2008_Yao.Xue.Xue.Bao_43_267
Author(s) : Zhu Y , Tong XY , Zhao Y , Chen H , Jiang FC
Ref : Yao Xue Xue Bao , 43 :267 , 2008
Abstract : Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.
ESTHER : Zhu_2008_Yao.Xue.Xue.Bao_43_267
PubMedSearch : Zhu_2008_Yao.Xue.Xue.Bao_43_267
PubMedID: 18630262

Title : Fluorogenic substrates for high-throughput measurements of endothelial lipase activity - Mitnaul_2007_J.Lipid.Res_48_472
Author(s) : Mitnaul LJ , Tian J , Burton C , Lam MH , Zhu Y , Olson SH , Schneeweis JE , Zuck P , Pandit S , Anderson M , Maletic MM , Waddell ST , Wright SD , Sparrow CP , Lund EG
Ref : J Lipid Res , 48 :472 , 2007
Abstract : Endothelial lipase (EL) has been shown to be a critical determinant for high density lipoprotein cholesterol levels in vivo; therefore, assays that measure EL activity have become important for the discovery of small molecule inhibitors that specifically target EL. Here, we describe fluorescent Bodipy-labeled substrates that can be used in homogeneous, ultra-high-throughput kinetic assays that measure EL phospholipase or triglyceride lipase activities. Triton X-100 detergent micelles and synthetic HDL particles containing Bodipy-labeled phospholipid or Bodipy-labeled triglyceride substrates were shown to be catalytic substrates for EL, LPL, and HL. More importantly, only synthetic HDL particles containing Bodipy-labeled triglyceride were ideal substrates for EL, LPL, and HL in the presence of high concentrations of human or mouse serum. These data suggest that substrate presentation is a critical factor when determining EL activity in the presence of serum.
ESTHER : Mitnaul_2007_J.Lipid.Res_48_472
PubMedSearch : Mitnaul_2007_J.Lipid.Res_48_472
PubMedID: 17090660
Gene_locus related to this paper: human-LIPG

Title : Enhanced cutinase production with Thermobifida fusca by two-stage pH control strategy - Du_2007_Biotechnol.J_2_365
Author(s) : Du GC , Zhang SL , Hua ZZ , Zhu Y , Chen J
Ref : Biotechnol J , 2 :365 , 2007
Abstract : A mutant of Thermobifida fusca ATCC 27730 was used for cutinase production. Acetate was the most suitable carbon source for cell growth and cutinase production compared with others. The pH was one of the most important factors affecting cutinase yield and productivity. Batch cutinase fermentations by mutant Thermobifida fusca WSH04 at various pH values ranging from 7.0 to 7.9 were studied. Based on the effects of different pH values on the specific cell growth rate and specific cutinase formation rate, a two-stage pH control strategy was developed, in which the pH was set at 7.3 for the first 20 h, and switched to 7.6 afterwards. By applying this two-stage pH control strategy for cutinase fermentation, the maximal cutinase activity reached 19.8 U/mL.
ESTHER : Du_2007_Biotechnol.J_2_365
PubMedSearch : Du_2007_Biotechnol.J_2_365
PubMedID: 17309045

Title : Expression of LPL in endothelial-intact artery results in lipid deposition and vascular cell adhesion molecule-1 upregulation in both LPL and ApoE-deficient mice - Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
Author(s) : Wang J , Xian X , Huang W , Chen L , Wu L , Zhu Y , Fan J , Ross C , Hayden MR , Liu G
Ref : Arterioscler Thromb Vasc Biol , 27 :197 , 2007
Abstract : OBJECTIVE: Overexpression of lipoprotein lipase (LPL) in deendothelialized artery led to profound localized lipid deposition. In this study the role of LPL in atherogenesis in endothelial-intact carotid arteries was assessed in genetically hyperlipidemic LPL- and ApoE-deficient mice. METHODS AND RESULTS: Human wild-type LPL (hLPLwt), catalytically inactive LPL (hLPL194), or control alkaline phosphatase (hAP) were expressed in endothelial-intact carotid arteries via adenoviral vectors. Compared with Ad-hAP, lipid deposition in the arterial wall increased 10.0- and 5.1-fold for Ad-hLPLwt and Ad-hLPL194 in LPL-deficient mice, and 10.6- and 6.2-fold in ApoE-deficient mice, respectively. Vascular cell adhesion molecule-1 (VCAM-1) was upregulated in Ad-hLPLwt and Ad-hLPL194 transferred arteries. CONCLUSIONS: Endothelial cell associated LPL, either active or inactive, in the arterial wall is a strong proatherosclerotic factor in both LPL- and ApoE-deficient mice.
ESTHER : Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
PubMedSearch : Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
PubMedID: 17038632

Title : One-step purification of a fusion protein of glucagon-like peptide-1 and human serum albumin expressed in pichia pastoris by an immunomagnetic separation technique - Chen_2007_Biosci.Biotechnol.Biochem_71_2655
Author(s) : Chen J , Bai G , Cao Y , Gao Z , Zhang Q , Zhu Y , Yang W
Ref : Biosci Biotechnol Biochem , 71 :2655 , 2007
Abstract : Glucagon-like peptide-1 (GLP-1) has great therapeutic potential to treat diabetes type 2, mainly due to its unique glucose-dependent stimulation of insulin secretion profiles, but its clinical application is limited by its short half-life in vivo, which resultes from degradation by dipeptidyl peptidase IV and/or renal clearance. Developing long-acting GLP-1 analogs is therefore an important step toward using them therapeutically. In this study, the GLP-1/human serum albumin (HSA) fusion protein gene was cloned into the secretor type expression vector pPIC9K and subsequently expressed in Pichia pastoris. The expression quantity reached 58.5 mg/l in small-scale incubation. After optimization and characterization, the GLP-1/HSA fusion protein was successfully purified from the supernatant of the broth using immunomagnetic cellulose microspheres. HPLC showed that the purified GLP-1/HSA had an overall purity of 93.9%, and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) confirmed the fusion protein exhibited the expected molecular mass of 70 kDa. Furthermore, that analysis of in vivo activity indicated that GLP-1/HSA reduced the blood glucose level after intraperitoneal administration to Chinese Kunming mice in a dose-dependent manner, and the effects held significantly 4 h after administration. Overall, this study illustrates the development of a long-acting GLP-1/HSA fusion protein expressed in Pichia pastoris.
ESTHER : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedSearch : Chen_2007_Biosci.Biotechnol.Biochem_71_2655
PubMedID: 17986790

Title : Identifying glucagon-like peptide-1 mimetics using a novel functional reporter gene high-throughput screening assay - Chen_2007_Peptides_28_928
Author(s) : Chen J , Bai G , Yang Y , Geng P , Cao Y , Zhu Y
Ref : Peptides , 28 :928 , 2007
Abstract : Glucagon-like peptide-1 (GLP-1) stimulates insulin and inhibits glucagon secretion and therefore could potentially be used to treat diabetes type II. However, its therapeutic use is limited by its short half-life in vivo, due mainly to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV). Developing GLP-1 analogs with greater bioactivity is therefore an important step toward using them therapeutically. Accordingly, we aimed to identify GLP-1 mimetic peptides by creating a high-throughput screening (HTS) assay of a phage displayed (PhD) peptide library. This assay was functionally based using the GLP-1 receptor (GLP-1R) gene. Rat GLP-1R cDNA was transfected into CHO/enhanced green fluorescent protein (EGFP) cells by lipofection. The resulting stable, recombinant cell line functionally expressed the GLP-1R and a cAMP-responsive EGFP reporter gene, to monitor receptor activation, and was used to screen a PhD dodecapeptide library. After four rounds of selection, 10 positive clones were selected based on functional evaluation and sequenced. Three sequences were obtained, corresponding to three different domains of GLP-1 (Group 1: 22-34; Group 2: 18-29; and Group 3: 6-17). The Group 3 peptide had the highest bioactivity, was synthesized, and designated KS-12. Importantly, KS-12 activated GLP-1R in vitro and reduced blood glucose levels in a dose-dependent manner when administered to Chinese Kunming mice. Although KS-12 was not as effective as GLP-1, it was significantly resistant to DPP-IV both in vitro and in vivo. Thus, this study provides a novel way to screen DPP-IV resistant agonist peptides of GLP-1 from a PhD peptide library using the functional reporter gene HTS assay.
ESTHER : Chen_2007_Peptides_28_928
PubMedSearch : Chen_2007_Peptides_28_928
PubMedID: 17267075

Title : Identification of sequence motifs that target neuronal nicotinic receptors to dendrites and axons - Xu_2006_J.Neurosci_26_9780
Author(s) : Xu J , Zhu Y , Heinemann SF
Ref : Journal of Neuroscience , 26 :9780 , 2006
Abstract : Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a family of ligand-gated ion channels that play important roles in central and peripheral nervous systems. The subcellular distribution of neuronal nAChRs has important implications for function and is not well understood. Here, we analyzed the targeting of two major types of neuronal nAChRs by expressing epitope-tagged subunits in cultured hippocampal neurons. Surprisingly, the alpha7 nAChR (alpha7) and alpha4/beta2 nAChR (alpha4beta2) displayed distinct patterns of expression, with alpha7 targeted preferentially to the somatodendritic compartments, whereas alpha4beta2 was localized to both axonal and dendritic domains. When fused to CD4 or IL2RA (interleukin 2 receptor alpha subunit) proteins, which are normally distributed ubiquitously, the M3-M4 intracellular loop from the alpha7 subunit promoted dendritic expression, whereas the homologous M3-M4 loop from the alpha4 subunit led to surface axonal expression. Systemic screening and alanine substitution further identified a 25-residue leucine motif ([DE]XXXL[LI]) containing an axonal targeting sequence within the alpha4 loop and a 48-residue dileucine and tyrosine motif (YXXO) containing a dendritic targeting sequence from the alpha7 loop. These results provide valuable information in understanding diverse roles of neuronal nAChRs in mediating and modulating synaptic transmission, synaptic plasticity, and nicotine addiction.
ESTHER : Xu_2006_J.Neurosci_26_9780
PubMedSearch : Xu_2006_J.Neurosci_26_9780
PubMedID: 16988049

Title : Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery - Yang_2005_Nucleic.Acids.Res_33_6445
Author(s) : Yang F , Yang J , Zhang X , Chen L , Jiang Y , Yan Y , Tang X , Wang J , Xiong Z , Dong J , Xue Y , Zhu Y , Xu X , Sun L , Chen S , Nie H , Peng J , Xu J , Wang Y , Yuan Z , Wen Y , Yao Z , Shen Y , Qiang B , Hou Y , Yu J , Jin Q
Ref : Nucleic Acids Research , 33 :6445 , 2005
Abstract : The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
ESTHER : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedSearch : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedID: 16275786
Gene_locus related to this paper: ecoli-yeiG , shidy-IROD , shidy-q67dv1 , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-S2753 , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YJFP , shifl-YPFH , shiss-yaim , shiss-yeiG , shiss-yqia

Title : Use of highly variable intergenic spacer sequences for multispacer typing of Rickettsia conorii strains - Fournier_2004_J.Clin.Microbiol_42_5757
Author(s) : Fournier PE , Zhu Y , Ogata H , Raoult D
Ref : J Clin Microbiol , 42 :5757 , 2004
Abstract : By use of the nearly perfectly colinear genomes of Rickettsia conorii and Rickettsia prowazekii, we compared the usefulness of three types of sequences for typing of R. conorii isolates: (i) 5 variable coding genes comprising the 16S ribosomal DNA, gltA, ompB, and sca4 (gene D) genes, which are present in both genomes, and the ompA gene, which is degraded in R. prowazekii; (ii) 28 genes degraded in R. conorii but intact in R. prowazekii, including 23 split and 5 remnant genes; and (iii) 27 conserved and 25 variable intergenic spacers. The 4 conserved and 23 split genes as well as the 27 conserved intergenic spacers each had identical sequences in 34 human and 5 tick isolates of R. conorii. Analysis of the ompA sequences identified three genotypes of R. conorii. The variable intergenic spacers were significantly more variable than conserved genes, split genes, remnant genes, and conserved spacers (P < 10(-2) in all cases). Four of the variable intergenic spacers (dksA-xerC, mppA-purC, rpmE-tRNA(fMet), and tRNA(Gly)-tRNA(Tyr)) had highly variable sequences; when they were combined for typing, multispacer typing (MST) identified 27 different genotypes in the 39 R. conorii isolates. Two batches from the same R. conorii strain, Malish (Seven), with different culture passage histories were found to exhibit the same MST type. MST was more discriminatory for strain genotyping than multiple gene sequencing (P < 10(-2)). Phylogenetic analysis based on MST sequences was concordant with the geographic origins of R. conorii isolates. Our study supports the usefulness of MST for strain genotyping. This tool may be useful for tracing a strain and identifying its source during outbreaks, including those resulting from bioterrorism.
ESTHER : Fournier_2004_J.Clin.Microbiol_42_5757
PubMedSearch : Fournier_2004_J.Clin.Microbiol_42_5757
PubMedID: 15583310

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp

Title : The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages - De Voss_2000_Proc.Natl.Acad.Sci.U.S.A_97_1252
Author(s) : De Voss JJ , Rutter K , Schroeder BG , Su H , Zhu Y , Barry CE, 3rd
Ref : Proc Natl Acad Sci U S A , 97 :1252 , 2000
Abstract : Mycobacterium tuberculosis is an important pathogen of mammals that relies on 2-hydroxyphenyloxazoline-containing siderophore molecules called mycobactins for the acquisition of iron in the restrictive environment of the mammalian macrophage. These compounds have been proposed to be biosynthesized through the action of a cluster of genes that include both nonribosomal peptide synthase and polyketide synthase components. One of these genes encodes a protein, MbtB, that putatively couples activated salicylic acid with serine or threonine and then cyclizes this precursor to the phenyloxazoline ring system. We have used gene replacement through homologous recombination to delete the mbtB gene and replace this with a hygromycin-resistance cassette in the virulent strain of M. tuberculosis H37Rv. The resulting mutant is restricted for growth in iron-limited media but grows normally in iron-replete media. Analysis of siderophore production by this organism revealed that the biosynthesis of all salicylate-derived siderophores was interrupted. The mutant was found to be impaired for growth in macrophage-like THP-1 cells, suggesting that siderophore production is required for virulence of M. tuberculosis. These results provide conclusive evidence linking this genetic locus to siderophore production.
ESTHER : De Voss_2000_Proc.Natl.Acad.Sci.U.S.A_97_1252
PubMedSearch : De Voss_2000_Proc.Natl.Acad.Sci.U.S.A_97_1252
PubMedID: 10655517
Gene_locus related to this paper: myctu-MBTB