Zhao H

References (71)

Title : Characterization of Thermotoga maritima Esterase Capable of Hydrolyzing Bis(2-hydroxyethyl) Terephthalate - Feng_2024_J.Agric.Food.Chem__
Author(s) : Feng S , Xue M , Xie F , Zhao H , Xue Y
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : The gene-encoding carboxylesterase (TM1022) from the hyperthermophilic bacterium Thermotoga maritima (T. maritima) was cloned and expressed in Escherichia coli Top10 and BL21 (DE3). Recombinant TM1022 showed the best activity at pH 8.0 and 85 degreesC and retained 57% activity after 8 h cultivation at 90 degreesC. TM1022 exhibited good stability at pH 6.0-9.0, maintaining 53% activity after incubation at pH 10.0 and 37 degreesC for 6 h. The esterase TM1022 exhibited the optimum thermo-alkali stability and k(cat)/K(m) (598.57 +/- 19.97 s(-1)mM(-1)) for pN-C4. TM1022 hydrolyzed poly(ethylene terephthalate) (PET) degradation intermediates, such as bis(2-hydroxyethyl) terephthalate (BHET) and mono(2-hydroxyethyl) terephthalate (MHET). The K(m), k(cat), and k(cat)/K(m) values for BHET were 0.82 +/- 0.01 mM, 2.20 +/- 0.02 s(-1), and 2.67 +/- 0.02 mM(-1) s(-1), respectively; those for MHET were 2.43 +/- 0.07 mM, 0.04 +/- 0.001 s(-1), and 0.02 +/- 0.001 mM(-1) s(-1), respectively. When purified TM1022 was added to the cutinase BhrPETase, hydrolysis of PET from drinking water bottle tops produced pure terephthalic acids (TPA) with 166% higher yield than those obtained after 72 h of incubation with BhrPETase alone as control. The above findings demonstrate that the esterase TM1022 from T. maritima has substantial potential for depolymerizing PET into monomers for reuse.
ESTHER : Feng_2024_J.Agric.Food.Chem__
PubMedSearch : Feng_2024_J.Agric.Food.Chem__
PubMedID: 38753963
Gene_locus related to this paper: 9bact-a0a2h5z9r5 , thema-ESTA

Title : A machine learning-based QSAR model reveals important molecular features for understanding the potential inhibition mechanism of ionic liquids to acetylcholinesterase - Wu_2024_Sci.Total.Environ__169974
Author(s) : Wu X , Gong J , Ren S , Tan F , Wang Y , Zhao H
Ref : Sci Total Environ , :169974 , 2024
Abstract : The broad application of ionic liquids (ILs) has been hindered by uncertainties surrounding their ecotoxicity. In this work, a Quantitative Structure-Activity Relationship (QSAR) model was devised to predict the inhibition of ILs towards the activity of AChE, employing both Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) machine learning approaches. Fourteen kings of essential molecular feature descriptors were screened from an initial roster of 244 descriptors through the application of a feature importance index and they showed a significant impact on the activity of AChE activity. The two models based solely on the 14 most critical molecular descriptors could maintain model's robustness and reliability. The correlation analysis between these 14 descriptors and the inhibition of AChE activity revealed the potential impact of the molecular characteristics on ILs toxicity. The results underscored the main influence of cations in ILs on the inhibitory activity towards the AChE enzyme. Specifically, cations exhibiting hydrophobicity properties were found to exert more potent inhibitory effects on the AChE enzyme. In addition, some other properties of the cations, such as the degree of branching, atomic weight and partial charge also modulated their inhibition potential. This study enhances the comprehension of the structure-activity relationship between ILs and AChE inhibition, providing a reference for designing safer and greener ILs.
ESTHER : Wu_2024_Sci.Total.Environ__169974
PubMedSearch : Wu_2024_Sci.Total.Environ__169974
PubMedID: 38199350

Title : Lead induced cerebellar toxicology of developmental Japanese quail (Coturnix japonica) via oxidative stress-based Nrf2\/Keap1 pathway inhibition and glutathione-mediated apoptosis signaling activation - Zhang_2024_Environ.Pollut_352_124114
Author(s) : Zhang Y , Pei X , Jing L , Zhang Q , Zhao H
Ref : Environ Pollut , 352 :124114 , 2024
Abstract : Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500 mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), gamma-Aminobutyric Acid (GABA) and Na(+)/K(+) ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.
ESTHER : Zhang_2024_Environ.Pollut_352_124114
PubMedSearch : Zhang_2024_Environ.Pollut_352_124114
PubMedID: 38718965

Title : Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids - Dong_2024_Metab.Eng__
Author(s) : Dong G , Zhao Y , Ding W , Xu S , Zhang Q , Zhao H , Shi S
Ref : Metab Eng , : , 2024
Abstract : Odd-numbered fatty acids (FAs) have been widely used in nutrition, agriculture, and chemical industries. Recently, some studies showed that they could be produced from bacteria or yeast, but the products are almost exclusively odd-numbered long-chain FAs. Here we report the design and construction of two biosynthetic pathways in Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids (OMFAs) via ricinoleic acid and 10-hydroxystearic acid, respectively. The production of OMFAs was enabled by introducing a hydroxy fatty acid cleavage pathway, including an alcohol dehydrogenase from Micrococcus luteus, a Baeyer-Villiger monooxygenase from Pseudomonas putida, and a lipase from Pseudomonas fluorescens. These OMFA biosynthetic pathways were optimized by eliminating the rate-limiting step, generating heptanoic acid, 11-hydroxyundec-9-enoic acid, nonanoic acid, and 9-hydroxynonanoic acid at 7.83 mg/L, 9.68 mg/L, 9.43 mg/L and 13.48 mg/L, respectively. This work demonstrates the biological production of OMFAs in a sustainable manner in S. cerevisiae.
ESTHER : Dong_2024_Metab.Eng__
PubMedSearch : Dong_2024_Metab.Eng__
PubMedID: 38325640

Title : Lactobacillus plantarum HF02 alleviates lipid accumulation and intestinal microbiota dysbiosis in high-fat diet-induced obese mice - Chen_2023_J.Sci.Food.Agric__
Author(s) : Chen H , Zhao H , Qi X , Sun Y , Li Q , Ma Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Obesity is closely associated with lipid accumulation and intestinal microbiota dysbiosis. It has been proved that probiotics supplement contributes to alleviate obesity. The objective of this study was to investigate the mechanism by which Lactobacillus plantarum HF02 (LP-HF02) alleviated lipid accumulation and intestinal microbiota dysbiosis in high-fat diet (HFD)-induced obese mice. RESULTS: Our results showed that LP-HF02 ameliorated body weight, dyslipidemia, liver lipid accumulation, and liver injury in obese mice. As expected, LP-HF02 inhibited pancreatic lipase activity in small intestinal contents and increased fecal triglyceride levels, thereby reducing dietary fat hydrolysis and absorption. Moreover, LP-HF02 ameliorated the intestinal microbiota composition, as evidenced by enhanced the ratio of Bacteroides to Firmicutes, decreased the abundance of pathogenic bacteria (including Bacteroides, Alistipes, Blautia, and Colidextribacter) and increased the abundance of beneficial bacteria (including Muribaculaceae, Akkermansia, Faecalibaculum, and Rikenellaceae_RC9_gut_group). LP-HF02 also increased fecal short-chain fatty acids (SCFAs) levels and colonic mucosal thickness, and subsequently decreased serum lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) levels in obese mice. Additionally, RT-qPCR and western blot results demonstrated that LP-HF02 ameliorated hepatic lipid accumulation via activating the AMP-activated protein kinase (AMPK) pathway. CONCLUSION: Therefore, our results indicated that LP-HF02 could be considered as a probiotic preparation for preventing obesity. This article is protected by copyright. All rights reserved.
ESTHER : Chen_2023_J.Sci.Food.Agric__
PubMedSearch : Chen_2023_J.Sci.Food.Agric__
PubMedID: 36866521

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

Title : Decoding transcriptomic signatures of Cysteine String Protein alpha-mediated synapse maintenance - Wang_2023_bioRxiv__
Author(s) : Wang N , Zhu B , Allnutt MA , Grijalva RM , Zhao H , Chandra SS
Ref : Biorxiv , : , 2023
Abstract : Synapse maintenance is essential for generating functional circuitry and decrement in this process is a hallmark of neurodegenerative disease. While we are beginning to understand the basis of synapse formation, much less is known about synapse maintenance in vivo . Cysteine string protein alpha (CSPalpha), encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is necessary for synapse maintenance and linked to neurodegeneration. To investigate the transcriptional changes associated with synapse maintenance, we performed single nucleus transcriptomics on the cortex of young CSPalpha knockout (KO) mice and littermate controls. Through differential expression and gene ontology analysis, we observed that both neurons and glial cells exhibit unique signatures in CSPalpha KO brain. Significantly all neurons in CSPalpha KO brains show strong signatures of repression in synaptic pathways, while upregulating autophagy related genes. Through visualization of synapses and autophagosomes by electron microscopy, we confirmed these alterations especially in inhibitory synapses. By imputing cell-cell interactions, we found that neuron-glia interactions were specifically increased in CSPalpha KO mice. This was mediated by synaptogenic adhesion molecules, including the classical Neurexin1-Neuroligin 1 pair, suggesting that communication of glial cells with neurons is strengthened in CSPalpha KO mice in an attempt to achieve synapse maintenance. Together, this study reveals unique cellular and molecular transcriptional changes in CSPalpha KO cortex and provides new insights into synapse maintenance and neurodegeneration. SIGNIFICANCE STATEMENT: Synapse maintenance is important for maintaining neuronal circuitry throughout life. However, little is known about molecules that affect synapse maintenance in vivo . CSPalpha, encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is linked to synapse maintenance and neurodegeneration. Here, we show by performing single nucleus transcriptomics of CSPalpha KO cortex that synapse instability is related to repression in synaptic pathways and elevation of autophagy in neurons. However, we find a heterogeneity of glial responses. Additionally, interactions between neurons and glia are increased in CSPalpha KO, mediated by synaptogenic adhesion molecules. This study provides a novel perspective on into synapse maintenance and reveals unique cellular and molecular transcriptional changes in CSPalpha KO brains.
ESTHER : Wang_2023_bioRxiv__
PubMedSearch : Wang_2023_bioRxiv__
PubMedID: 37873460

Title : Rapid discovery and crystallography study of highly potent and selective butylcholinesterase inhibitors based on oxime-containing libraries and conformational restriction strategies - Jing_2023_Bioorg.Chem_134_106465
Author(s) : Jing L , Wei W , Meng B , Chantegreil F , Nachon F , Martinez A , Wu G , Zhao H , Song Y , Kang D , Brazzolotto X , Zhan P , Liu X
Ref : Bioorg Chem , 134 :106465 , 2023
Abstract : Butyrylcholinesterase is regarded as a promising drug target in advanced Alzheimer's disease. In order to identify highly selective and potent BuChE inhibitors, a 53-membered compound library was constructed via the oxime-based tethering approach based on microscale synthesis. Although A2Q17 and A3Q12 exhibited higher BuChE selectivity versus acetylcholinesterase, the inhibitory activities were unsatisfactory and A3Q12 did not inhibit Abeta1-42 peptide self-induced aggregation. With A2Q17 and A3Q12 as leads, a novel series of tacrine derivatives with nitrogen-containing heterocycles were designed based on conformation restriction strategy. The results demonstrated that 39 (IC50 = 3.49 nM) and 43 (IC50 = 7.44 nM) yielded much improved hBuChE inhibitory activity compared to the lead A3Q12 (IC50 = 63 nM). Besides, the selectivity indexes (SI = AChE IC50 / BChE IC50) of 39 (SI = 33) and 43 (SI = 20) were also higher than A3Q12 (SI = 14). The results of the kinetic study showed that 39 and 43 exhibited a mixed-type inhibition against eqBuChE with respective Ki values of 1.715 nM and 0.781 nM. And 39 and 43 could inhibit Abeta1-42 peptide self-induced aggregation into fibril. X-ray crystallography structures of 39 or 43 complexes with BuChE revealed the molecular basis for their high potency. Thus, 39 and 43 are deserve for further study to develop potential drug candidates for the treatment of Alzheimer's disease.
ESTHER : Jing_2023_Bioorg.Chem_134_106465
PubMedSearch : Jing_2023_Bioorg.Chem_134_106465
PubMedID: 36933339
Gene_locus related to this paper: human-BCHE

Title : Biomimetic Metal-Pyrimidine Nanoflowers: Enzyme Immobilization Platforms with Boosted Activity - Gong_2023_Small__e2304077
Author(s) : Gong C , Wang D , Zhao H
Ref : Small , :e2304077 , 2023
Abstract : For the enzyme immobilization platform, enhancing enzyme activity retention while improving enzyme stability remains a challenge for sensitive sensing analysis. Herein, an in situ biomimetic immobilized enzyme carrier (metal-pyrimidine nanoflowers, MPNFs) synthesized by the coordination of DNA base derivative (2-aminopyrimidine) with Zn(2+) in the aqueous phase at room temperature is developed. The biocompatibility of 2-aminopyrimidine and the hydrophilicity and green synthetic conditions of MPNFs allows the immobilized enzymes to retain above 91.2% catalytic activity. On this basis, a cascade catalytic platform is constructed by simultaneously immobilizing acetylcholinesterase (AChE), choline oxidase (CHO), and horseradish peroxidase (HRP) in MPNFs (AChE/CHO/HRP@MPNFs) for organophosphorus pesticides (OPs) colorimetric biosensing detection. The assay could specifically detect parathion-methyl within 13 min with a wider linear range (0.1-1000.0 nm) and a lower limit of detection (LOD) (0.032 nm). The remarkable stability of the immobilized enzymes is also achieved under harsh environments, room temperature storage, and recycling. Furthermore, a portable and cost-effective biosensing platform is developed by integrating AChE/CHO/HRP@MPNFs with a smartphone-assisted paper device for the on-site detection of OPs. Overall, the high catalytic activity retention and the enhanced detection performance demonstrate that MPNF is a robust carrier in enzyme immobilization and holds great promise in biosensing and other field applications.
ESTHER : Gong_2023_Small__e2304077
PubMedSearch : Gong_2023_Small__e2304077
PubMedID: 37612822

Title : Characterization of caffeoyl shikimate esterase gene family identifies CsCSE5 as a positive regulator of Podosphaera xanthii and Corynespora cassiicola pathogen resistance in cucumber - Yu_2023_Plant.Cell.Rep__
Author(s) : Yu Y , He J , Liu L , Zhao H , Zhang M , Hong J , Meng X , Fan H
Ref : Plant Cell Rep , : , 2023
Abstract : CsCSE genes might be involved in the tolerance of cucumber to pathogens. Silencing of the CsCSE5 gene resulted in attenuated resistance of cucumber to Podosphaera xanthii and Corynespora cassiicola. Caffeoyl shikimate esterase (CSE), a key enzyme in the lignin biosynthetic pathway, has recently been characterized to play a key role in defense against pathogenic infection in plants. However, a systematic analysis of the CSE gene family in cucumber (Cucumis sativus) has not yet been conducted. Here, we identified eight CsCSE genes from the cucumber genome via bioinformatic analyses, and these genes were unevenly distributed on chromosomes 1, 3, 4, and 5. Results from multiple sequence alignment indicated that the CsCSE proteins had domains required for CSE activity. Phylogenetic analysis of gene structure and protein motifs revealed the conservation and diversity of the CsCSE gene family. Collinearity analysis showed that CsCSE genes had high homology with CSE genes in wax gourd (Benincasa hispida). Cis-acting element analysis of the promoters suggested that CsCSE genes might play important roles in growth, development, and stress tolerance. Expression pattern analysis indicated that CsCSE5 might be involved in regulating the resistance of cucumber to pathogens. Functional verification data confirmed that CsCSE5 positively regulates the resistance of cucumber to powdery mildew pathogen Podosphaera xanthii and target leaf spot pathogen Corynespora cassiicola. The results of our study provide information that will aid the genetic improvement of resistant cucumber varieties.
ESTHER : Yu_2023_Plant.Cell.Rep__
PubMedSearch : Yu_2023_Plant.Cell.Rep__
PubMedID: 37823975

Title : Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery - Qu_2023_Int.J.Gen.Med_16_1567
Author(s) : Qu W , Yao Y , Liu Y , Jo H , Zhang Q , Zhao H
Ref : Int J Gen Med , 16 :1567 , 2023
Abstract : PURPOSE: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. PATIENTS AND METHODS: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. RESULTS: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. CONCLUSION: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.
ESTHER : Qu_2023_Int.J.Gen.Med_16_1567
PubMedSearch : Qu_2023_Int.J.Gen.Med_16_1567
PubMedID: 37139258
Gene_locus related to this paper: human-CES2

Title : Metal-pyrimidine nanocubes immobilized enzymes with pH-switchable multienzyme-like activity for broad-pH-responsive sensing assay for organophosphorus pesticides - Gong_2023_J.Hazard.Mater_463_132849
Author(s) : Gong C , Chen B , Xing Y , Zhao H
Ref : J Hazard Mater , 463 :132849 , 2023
Abstract : Peroxidase (POD)-like can only function in acidic environments and the pH mismatch restricts the application of enzyme-nanozyme cascade catalytic sensing platforms in the broad-pH-responsive assay for organophosphorus pesticides (OPs). Herein, the metal-pyrimidine nanocubes (MPNCs) with intrinsic pH-switchable POD-like and catalase (CAT)-like properties were synthesized via the coordination of pyrimidin-2-ol with Cu(2+). Meanwhile, acetylcholinesterase (AChE) and choline oxidase (CHO) were simultaneously encapsulated in MPNCs to construct an enzyme-nanozyme cascade catalytic platform (AChE/CHO@MPNCs). AChE/CHO@MPNCs could catalyze the hydrolysis of acetylcholine to choline, which was subsequently converted to H(2)O(2). The POD-like activity of MPNCs was dominant under acidic conditions, while the CAT-like activity prevailed under neutral and alkaline conditions, which could catalyze H(2)O(2) to OH and O(2), respectively, then oxidizing dopamine (DA) to polydopamine quantum dots (PDA QDs) with different fluorescence characteristics. Consequently, OPs could be detected in a linear range from 0.05 to 1000 nM with a LOD of 0.015 nM in acidic environments and a linear range from 0.05 to 500 nM with a LOD of 0.023 nM in alkaline environments. Overall, our work expands the horizon of constructing enzyme@MOFs composites with high catalytic activity. Meanwhile, the intrinsic pH-switchable multienzyme-like property opens avenues to construct sensing platforms with broad-pH-responsive for OPs and other analytes detection.
ESTHER : Gong_2023_J.Hazard.Mater_463_132849
PubMedSearch : Gong_2023_J.Hazard.Mater_463_132849
PubMedID: 37898085

Title : Nanoclusterzyme for Dual Colorimetric Sensings: A Case Study on [Au(14) (Dppp)(5) I(4) ](2) - Zhao_2023_Small__e2207936
Author(s) : Zhao H , You Q , Zhu W , Li J , Deng H , Li MB , Zhao Y , Wu Z
Ref : Small , :e2207936 , 2023
Abstract : The enzymatic activity of atomically precise metal nanoclusters has recently been recognized; however, the number of nanoclusterzymes is very small. Besides, the applications of nanoclusterzyme wait to be explored. Herein, a novel nanoclusterzyme is synthesized and its structure is majorly resolved by single-crystal X-ray diffraction and mass spectrometry, which reveal that the nanocluster consists of an Au(13) icosahedron capped by an exterior shell including four I, three Dppp (1,3-bis(diphenylphosphino) propane) ligands, and a rarely reported Dppp-Au-Dppp handle staple, which contributes a lot to the enzyme activity of [Au(14) (Dppp)(5) I(4) ](2+) nanocluster. The as-obtained nanocluster can catalyze oxygen to O(2) (-) under visible light irradiation with a specific activity up to 0.182 U.mg(-1) and lead to the blue color of 3,3',5,5'-tetramethylbenzidine (TMB) in both solution and solid states. With the addition of acetylcholinesterase (AChE), the blue color of (Au(14) + TMB) solution system disappears due to the nanoclusterzyme activity inhibition, but the further addition of organophosphorus pesticides (OPs) into the above mixture can restore the nanoclusterzyme and recover the blue color. Based on the color turn-off and on, the various nanoclusterzyme-containing systems are used to colorimetrically sense AChE and OPs with the detection limits reaching 0.04 mU.mL(-1) and 0.02 ng.mL(-1) , respectively.
ESTHER : Zhao_2023_Small__e2207936
PubMedSearch : Zhao_2023_Small__e2207936
PubMedID: 37060229

Title : Identification of pancreatic lipase inhibitors from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Orbitrap MS and in vitro validation - Huang_2023_Food.Chem_426_136630
Author(s) : Huang H , Han MH , Gu Q , Wang JD , Zhao H , Zhai BW , Nie SM , Liu ZG , Fu YJ
Ref : Food Chem , 426 :136630 , 2023
Abstract : Pancreatic lipase inhibitors can reduce blood lipids by inactivating the catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis, which helps control some dyslipidemic diseases. The ability of Eucommia ulmoides tea to improve fat-related diseases is closely related to the natural inhibitory components of pancreatic lipase contained in the tea. In this study, fifteen pancreatic lipase inhibitors were screened and identified from Eucommia ulmoides tea by affinity-ultrafiltration combined UPLC-Q-Exactive Orbitrap/MS. Four representative components of geniposidic acid, quercetin-3-O-sambuboside, isochlorogenic acid A, and quercetin with high binding degrees were further verified by nanoscale differential scanning fluorimetry (nanoDSF) and enzyme inhibitory assays. The results of flow cytometry showed that they could significantly reduce the activity of pancreatic lipase in AR42J cells induced by palmitic acid in a concentration-dependent manner. Our findings suggest that Eucommia ulmoides tea may be a promising resource for pancreatic lipase inhibitors of natural origin.
ESTHER : Huang_2023_Food.Chem_426_136630
PubMedSearch : Huang_2023_Food.Chem_426_136630
PubMedID: 37352710

Title : The physiological, biochemical and transcriptional responses to sulfamethoxazole in the Asian clam, Corbicula fluminea (O. F. Muller, 1774) - Liu_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_260_109406
Author(s) : Liu S , Zhao H , Zheng M , Wang H , Jing C , Zhang W , Hu F
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , 260 :109406 , 2022
Abstract : Sulfamethoxazole (SMX), a broad-spectrum antibiotic, has been widely used in the treatment and prevention of infection caused by bacteria in recent years. The present study was aimed to evaluate the response mechanisms to SMX stress in gills and digestive gland of Corbicula fluminea (O. F. Mller, 1774). To this end, clams were exposed to environmentally relevant concentrations of SMX (0, 1, 10 and 100 microg/L) for 7 and 28 days, and siphon behavior, tissue-specific enzymatic and transcriptional changes were assayed. Our results showed that exposure to SMX significantly suppressed filtration rate and acetylcholinesterase (AChE) activity, activated antioxidant defense system and elevated transcription of several genes related to cell apoptosis in gills and digestive gland of clams. In general, SMX at environmentally relevant concentrations exhibited a negative impact on siphon behavior and induced neurotoxicology, oxidative stress and cell apoptosis in C. fluminea. The current study will help broaden our understanding of the ecotoxicity of SMX on freshwater bivalves.
ESTHER : Liu_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_260_109406
PubMedSearch : Liu_2022_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_260_109406
PubMedID: 35793736

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

Title : Activation and closed-state inactivation mechanisms of the human voltage-gated K(V)4 channel complexes - Ye_2022_Mol.Cell_S1097-2765_00395
Author(s) : Ye W , Zhao H , Dai Y , Wang Y , Lo YH , Jan LY , Lee CH
Ref : Mol Cell , : , 2022
Abstract : The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human K(V)4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of K(V)4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture K(V)4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the K(V)4 channel.
ESTHER : Ye_2022_Mol.Cell_S1097-2765_00395
PubMedSearch : Ye_2022_Mol.Cell_S1097-2765_00395
PubMedID: 35597238
Gene_locus related to this paper: human-DPP6

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

Title : Curcumin relieves mice gastric emptying dysfunction induced by L-arginine and atropine through interstitial cells of Cajal - Lin_2021_Exp.Ther.Med_21_548
Author(s) : Lin P , Li B , Ye J , Shang F , Zhao H , Xie J , Yu X
Ref : Exp Ther Med , 21 :548 , 2021
Abstract : Curcumin is natural polyphenol from Curcuma longa rhizomes with several biological properties. Our previous studies demonstrated that curcumin inhibited functional gastric emptying disorders induced by L-arginine, the precursor of nitric oxide (NO), and atropine, an acetylcholine receptor (AChR) blocker. However, the mechanism of action of curcumin remains unclear. In the present study, mouse models of functional gastric emptying disorders induced by L-arginine and atropine were used to examine changes in interstitial cells of Cajal (ICC) and NO- and ACh-mediated regulation of gastrointestinal motility. Curcumin pre-treatment ameliorated the gastric emptying rate in mice treated with L-arginine or atropine (P<0.01). NO content and NO synthase activity significantly increased in the stomachs of L-arginine-treated mice, compared with controls (P<0.01). Acetylcholinesterase activity (P<0.01) and mRNA expression (P<0.01), as well as AChR mRNA levels (P<0.05) significantly decreased following atropine treatment. Moreover, in both models, the levels of c-kit, anoctamin 1 and connexin 43 significantly decreased in the stomach (P<0.01). Conversely, curcumin pre-treatment inhibited the changes induced by L-arginine and atropine (P<0.01 or P<0.05). By affecting the production of exogenous NO, the effects of Ach-AchR and the biomarkers of ICC, curcumin relieves the gastric emptying dysfunction in mice.
ESTHER : Lin_2021_Exp.Ther.Med_21_548
PubMedSearch : Lin_2021_Exp.Ther.Med_21_548
PubMedID: 33850520

Title : Enhancement of Fear Extinction Memory and Resistance to Age-Related Cognitive Decline in Butyrylcholinesterase Knockout Mice and (R)-Bambuterol Treated Mice - Liu_2021_Biology.(Basel)_10_
Author(s) : Liu W , Cao Y , Lin Y , Tan KS , Zhao H , Guo H , Tan W
Ref : Biology (Basel) , 10 : , 2021
Abstract : Butyrylcholinesterase (BChE) is detected in plaques preferentially in Alzheimer's disease (AD) and may be associated with stress disorders. However, the physiological function of BChE in the central nervous system remains to be further investigated. BChE knockout (KO) mice and wild-type (WT) mice with orally or intranasal administration of (R)-bambuterol were used to explore the effect of BChE on behavior changes. (R)-bambuterol is a specific and reversible inhibitor of BChE. The behavior changes were evaluated and compared among 3-10 month old mice. Our finding showed that BChE KO and (R)-bambuterol administration enhanced episodic memory, including fear conditioning memory and fear extinction memory in fear conditioning and fear extinction test. BChE KO and (R)-bambuterol administered mice rescued age-related spatial memory and general activity in the water maze test and open field test. The brain metabolomics were imaged using a desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The image of DESI-MS demonstrated that glutamine content increased in the brain of BChE KO mice. In conclusion, this study found that inhibition of BChE ameliorated episodic and spatial memories. This study also suggested that (R)-bambuterol as a BChE inhibitor has the potential application in the treatment of post-traumatic stress disorder (PTSD) and early cognitive decline.
ESTHER : Liu_2021_Biology.(Basel)_10_
PubMedSearch : Liu_2021_Biology.(Basel)_10_
PubMedID: 34062954

Title : Clinical significance of EPHX2 deregulation in prostate cancer - Liu_2021_Asian.J.Androl_23_109
Author(s) : Liu MS , Zhao H , Xu CX , Xie PB , Wang W , Yang YY , Lee WH , Jin Y , Zhou HQ
Ref : Asian J Androl , 23 :109 , 2021
Abstract : The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.
ESTHER : Liu_2021_Asian.J.Androl_23_109
PubMedSearch : Liu_2021_Asian.J.Androl_23_109
PubMedID: 32687069

Title : Extradural Contralateral C7 Nerve Root Transfer in a Cervical Posterior Approach for Treating Spastic Limb Paralysis: A Cadaver Feasibility Study - Yang_2020_Spine.(Phila.Pa.1976)_45_E608
Author(s) : Yang K , Jiang F , Zhang S , Zhao H , Shi Z , Liu J , Cao X
Ref : Spine (Phila Pa 1976) , 45 :E608 , 2020
Abstract : STUDY DESIGN: Anatomic study in nine fresh-frozen cadavers. OBJECTIVE: To confirm the anatomical feasibility of transferring the extradural ventral roots (VRs) and dorsal roots (DRs) of contralateral C7 nerves to those of the ipsilateral C7 nerves respectively through a cervical posterior approach. SUMMARY OF BACKGROUND DATA: The contralateral C7 nerve root transfer technique makes breakthrough for treating spastic limb paralysis. However, its limitations include large surgical trauma and limited indications. METHODS: Nine fresh-frozen cadavers (four females and five males) were placed prone, and the feasibility of exposing the bilateral extradural C7 nerve roots, separation of the extradural C7 VR and DR, and transfer of the VR and DR of the contralateral C7 to those of the ipsilateral C7 on the dural mater were assessed. The pertinent distances and the myelography results of each specimen were analyzed. The acetylcholinesterase (AChE) and antineurofilament 200 (NF200) double immunofluorescent staining were preformed to determine the nerve fiber properties. RESULTS: A cervical posterior midline approach was made and the laminectomy was performed to expose the bilateral extradural C7 nerve roots. After the extradural C7 VR and DR are separated, the VR and DR of the contralateral C7 have sufficient lengths to be transferred to those of the ipsilateral C7 on the dural mater. The myelography results showed that the spinal cord is not compressed after the nerve anastomosis. The AChE and NF200 double immunofluorescent staining showed the distal ends of the contralateral C7 VRs were mostly motor nerve fibers, and the distal ends of the contralateral C7 DRs were mostly sensory nerve fibers. CONCLUSION: Extradural contralateral C7 nerve root transfer in a cervical posterior approach for treating spastic limb paralysis is anatomically feasible. LEVEL OF EVIDENCE: 5.
ESTHER : Yang_2020_Spine.(Phila.Pa.1976)_45_E608
PubMedSearch : Yang_2020_Spine.(Phila.Pa.1976)_45_E608
PubMedID: 31770316

Title : Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice - Chen_2020_Front.Psychiatry_11_564843
Author(s) : Chen S , Lin Z , Tan KL , Chen R , Su W , Zhao H , Tan Q , Tan W
Ref : Front Psychiatry , 11 :564843 , 2020
Abstract : Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.
ESTHER : Chen_2020_Front.Psychiatry_11_564843
PubMedSearch : Chen_2020_Front.Psychiatry_11_564843
PubMedID: 33061920

Title : Gene polymorphism associated with Angiotensinogen(M235T), Endothelial lipase (584C\/T) and susceptibility to coronary artery disease: A meta-analysis - Zhao_2020_Biosci.Rep__
Author(s) : Zhao H , Zhao R , Hu S , Rong J
Ref : Bioscience Reports , : , 2020
Abstract : OBJECTIVE: To explore the association between the variant M235T locus of angiotensinogen (AGT) gene, 584C/T locus of Endothelial lipase (EL) gene, and coronary artery disease (CAD) by meta-analysis. METHODS: The case-control studies on the association between AGT/EL gene polymorphism and CAD were collected through searching PubMed, EMbase, Web of Science, CNKI and Wanfang database up to March 1, 2020. Stata 15.0 software was used for analysis. RESULTS: A total of 29 articles met the inclusion criteria. After analyzing, it was found that the M235T polymorphism of AGT gene was associated with the occurrence of CAD. In the allele model (T vs. M), OR=1.38 (P < 0.05). In other heredity, there was also statistically significant. Subgroup analysis indicated that except the heterozygous genetic model of the Chinese population, other genetic models of the Caucasian and Chinese population were also statistically significant. The 584C/T polymorphism of EL gene was associated with the occurrence of CAD, with OR=0.83 (P < 0.05) in the allele model (T vs. C) and OR=0.80 (P < 0.05) in the dominant gene model. Also, in the allele model of Caucasian subgroup, OR=0.83 (P < 0.05), while in Asian subgroup, there was no statistically significant genetic model. CONCLUSION: AGT M235T and EL 584C/T polymorphisms are associated with CAD susceptibility. The genotype TT, TC or allele T of AGT M235T and genotype CC or allele C of EL 584C/T might be the genetic risk factors for the development of CAD.
ESTHER : Zhao_2020_Biosci.Rep__
PubMedSearch : Zhao_2020_Biosci.Rep__
PubMedID: 32667032

Title : Environmentally relevant concentration of cypermethrin or\/and sulfamethoxazole induce neurotoxicity of grass carp: Involvement of blood-brain barrier, oxidative stress and apoptosis - Zhao_2020_Sci.Total.Environ__143054
Author(s) : Zhao H , Wang Y , Guo M , Liu Y , Yu H , Xing M
Ref : Sci Total Environ , :143054 , 2020
Abstract : In water environment, the interaction between environmental pollutants is very complex, among which pesticides and antibiotics are dominant. However, most studies only focus on individual toxic effects, rather combined. In this study, the sub-chronic exposure effect of cypermethrin (CMN, 0.65 g/L), sulfamethoxazole (SMZ, 0.30 g/L) and their mixture on grass crap (Ctenopharyngodon idellus) was investigated. The brain tight junction, oxidative stress and apoptosis-related indices were determined after 42 days of exposure. In terms of brain function, acetyl cholinesterase (AChE) activity was significantly inhibited by CMN, SMZ and their mixtures during exposure periods. Obvious histological damage from cellular and subcellular levels were also observed, which were further confirmed by a decrease in tight junction protein levels. Malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents were significantly increased by individual compounds and mixtures, in which the content of glutathione (GSH) displayed the opposite trend. In mechanism, nuclear factor (erythrocyte derived 2) like 2(Nrf2) pathway was activated, which may trigger cellular protection to cope with CMN and SMZ exposure. However, apoptosis was also detected from the level of mRNA and histochemistry. In general, these two exogenous induced similar biological responses. The neurotoxicity of CMN was strengthened by SMZ with regard to these indices in most cases and vice versa. This study will reveal the potential co-ecological risks of pesticide and antibiotic in the aquatic organism, and provide basic data for their safety and risk assessment.
ESTHER : Zhao_2020_Sci.Total.Environ__143054
PubMedSearch : Zhao_2020_Sci.Total.Environ__143054
PubMedID: 33127128

Title : The Anti-inflammatory Effect of Soluble Epoxide Hydrolase Inhibitor and 14, 15-EET in Kawasaki Disease Through PPARgamma\/STAT1 Signaling Pathway - Dai_2020_Front.Pediatr_8_451
Author(s) : Dai N , Yang C , Fan Q , Wang M , Liu X , Zhao H , Zhao C
Ref : Front Pediatr , 8 :451 , 2020
Abstract : Soluble epoxide hydrolase (sEH) is responsible for rapid degradation of 14, 15-EET, which is one of the isomers of EETs and plays an important role in cardiovascular diseases. In this study, we investigated the mechanism by which sEH inhibitor AUDA played an anti-inflammatory effect in HCAECs. Our results indicated that AUDA treatment promoted PPARgamma expression, while knockdown of PPARgamma blocked the cell growth and STAT1 expression inhibition induced by 100 mumol/L AUDA in HCAECs. AUDA also inhibited the overexpression of TNF-alpha, IL-1 beta, and MMP-9 induced by KD sera in HCAECs. Moreover, 30 blood samples from children with Kawasaki disease (KD) were collected with 30 healthy children as the control group. QPCR and ELISA assays were used to detect the level of 14, 15-EET, TNF-alpha, IL-1beta, and MMP-9. We found that the level of 14, 15-EET was higher in peripheral blood of children with KD compared with healthy controls (P < 0.05). In comparison to KD children with non-coronary artery lesion (nCAL), the level of 14, 15-EET was higher in peripheral blood of KD children with coronary artery lesion (CAL) (P < 0.05). Compared with healthy control group, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in patients with KD were significantly up-regulated. Compared with nCAL KD children, the expression levels of TNF-alpha, IL-1beta, and MMP-9 in CAL children were abnormally high (P < 0.05). Our study indicated that AUDA played an anti-inflammatory effect in HCAECs through PPARgamma/STAT1 signaling pathway, and 14, 15-EET is up-regulated in children with KD, suggesting that 14, 15-EET involved in the progression of KD.
ESTHER : Dai_2020_Front.Pediatr_8_451
PubMedSearch : Dai_2020_Front.Pediatr_8_451
PubMedID: 32903307

Title : Chemical characterization of the main bioactive polyphenols from the roots of Morus australis (mulberry) - Guo_2019_Food.Funct_10_6915
Author(s) : Guo S , Liu L , Zhang S , Yang C , Yue W , Zhao H , Ho CT , Du J , Zhang H , Bai N
Ref : Food Funct , 10 :6915 , 2019
Abstract : Morus species, commonly known as mulberry, is widely distributed in China. The mulberry tree is a high-value plant in agriculture. Morus australis is one of the major Morus species growing in Northern China. However, the biological properties of the main constituents of M. australis roots were not well studied. In the present study, through extensive chromatographic and spectral analysis, 12 phenolic compounds were isolated and identified from the M. australis roots. Compounds 1, 2, 8, 9 and 12 were isolated from M. australis roots for the first time. Antitumor activities of these polyphenols were studied on the A549 cell line. Compounds 1, 5 and 6 exhibited cytotoxicity on A549 cells and induced apoptosis in A549 cells via the intrinsic mitochondrial pathway. They also mediated inhibition of autophagic flux contributed cell death via the PI3k/Akt/mTOR pathway. In order to explore more potential bioactivities of these isolates, alpha-glucosidase, acetylcholinesterase and tyrosinase inhibitory activities were studied, and the results demonstrated that the inhibitory activity of these polyphenols on enzymes was not defined by their basic structural skeletons, but by the substituted position.
ESTHER : Guo_2019_Food.Funct_10_6915
PubMedSearch : Guo_2019_Food.Funct_10_6915
PubMedID: 31588440

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

Title : The Effect of Protein FAM172A on Proliferation in HepG2 Cells and Investigation of the Possible Molecular Mechanism - Zhao_2019_Anal.Cell.Pathol.(Amst)_2019_5901083
Author(s) : Zhao H , Wang Y , Liu Y , Hao X , Wei H , Xie W
Ref : Anal Cell Pathol (Amst) , 2019 :5901083 , 2019
Abstract : BACKGROUND: In our previous study, we found that the FAM172A recombinant protein could promote proliferation of L02 cells. However, the underlying mechanisms are still unknown. The present study was aimed at investigating the effect of FAM172A on proliferation of HepG2 cells and exploring the possible molecular mechanisms and its role in hepatocellular carcinoma (HCC). METHODS: Cell proliferation was measured by MTT assay. Western blot test was carried out to investigate the mechanism. Rabbit antibodies against FAM172A and membrane proteins isolated from lysate of HepG2 cell were coprecipitated and the resultant precipitates were analyzed by mass spectrum. RESULTS: The MTT assay showed that recombinant protein FAM172A isoform 1 (FAM172A-1) could induce HepG2 cell proliferation at the concentration of 10-100 ng/mL, while protein FAM172A isoform 3 (FAM172A-3) was at the concentration of 80-100 ng/mL. Western blot demonstrated that both FAM172A-1 and FAM172A-3 could activate the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) pathway and the phosphatidylinositol 3-kinase/threonine-protein kinase (PI3K/Akt) pathway. Mass spectrum analysis suggested that there were some membrane proteins interacting with FAM172A. Several candidate interacting proteins might mediate proliferation signals induced by FAM172A recombinant protein, including seven membrane proteins. CONCLUSION: In conclusion, FAM172A recombinant protein could induce proliferation of HepG2 cells, in which the MAPK/ERK and PI3K/Akt signaling pathways might be involved. The role of FAM172A in HepG2 cell proliferation also indicated its possible involvement in HCC. The receptor of FAM172A on cells still needs to be exploited.
ESTHER : Zhao_2019_Anal.Cell.Pathol.(Amst)_2019_5901083
PubMedSearch : Zhao_2019_Anal.Cell.Pathol.(Amst)_2019_5901083
PubMedID: 31915594
Gene_locus related to this paper: human-f172a

Title : New phthalide derivatives from the Biscogniauxia sp. and their activities - Liu_2019_Fitoterapia__104184
Author(s) : Liu YY , Zhao H , Xie J , Zou J , Hu D , Guo LD , Chen GD , Yao XS , Gao H
Ref : Fitoterapia , :104184 , 2019
Abstract : Five new phthalide derivatives, biscogniphthalides A-D (1, 2, 3a/3b, and 4), were isolated from Biscogniauxia sp. (No. 69-8-7-1), along with one related known phthalide (5). Their structures were determined by comprehensive spectroscopic analyses, chemical derivatization, and quantum chemical ECD calculations. In addition, the anti-acetyl cholinesterase, antimicrobial, and anti-alpha-glucosidase activities of 1-5 were evaluated.
ESTHER : Liu_2019_Fitoterapia__104184
PubMedSearch : Liu_2019_Fitoterapia__104184
PubMedID: 31145983

Title : Enhancing the atypical esterase promiscuity of the gamma-lactamase Sspg from Sulfolobus solfataricus by substrate screening - Wang_2019_Appl.Microbiol.Biotechnol_103_4077
Author(s) : Wang J , Zhao H , Zhao G , Chen D , Tao Y , Wu S
Ref : Applied Microbiology & Biotechnology , 103 :4077 , 2019
Abstract : Promiscuous enzymes can be modified by protein engineering, which enables the catalysis of non-native substrates. gamma-lactamase Sspg from Sulfolobus solfataricus is an enzyme with high activity, high stability, and pronounced tolerance of high concentrations of the gamma-lactam substrate. These characteristics suggest Sspg as a robust enzymatic catalyst for the preparation of optically pure gamma-lactam. This study investigated the modification of this enzyme to expand its application toward resolving chiral esters. gamma-Lactamase-esterase conversion was performed by employing a three-step method: initial sequence alignment, followed by substrate screening, and protein engineering based on the obtained substrate-enzyme docking results. This process of fine-tuning of chemical groups on substrates has been termed "substrate screening." Steric hindrance and chemical reactivity of the substrate are major concerns during this step, since both are determining factors for the enzyme-substrate interaction. By employing this three-step method, gamma-lactamase Sspg was successfully converted into an esterase with high enantioselectivity towards phenylglycidate substrates (E value > 300). However, since both wild-type Sspg and Sspg mutants did not hydrolyze para-nitrophenyl substrates (pNPs), this esterase activity was termed "atypical esterase activity." The gamma-lactamase activity and stability of the Sspg mutants were not severely compromised. The proposed method can be applied to find novel multi-functional enzyme catalysts within existing enzyme pools.
ESTHER : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedSearch : Wang_2019_Appl.Microbiol.Biotechnol_103_4077
PubMedID: 30955078

Title : Water-like Dual-Functionalized Ionic Liquids for Enzyme Activation - Zhao_2019_ACS.Omega_4_15234
Author(s) : Zhao H , Harter GA , Martin CJ
Ref : ACS Omega , 4 :15234 , 2019
Abstract : By mimicking the water structure to improve the enzyme activity, we designed imidazolium (Im)-based ionic liquids (ILs) functionalized with both ether and tert-alcohol groups (e.g., [CH3(OCH2CH2) n -Im-t-BuOH][Tf2N]). This unique combination of the "water-like" structure enabled very high transesterification (synthetic) activities for immobilized lipase B from Candida antarctica, which are up to 2-4 folds higher than nonfunctionalized "classical" ionic liquids (such as [BMIM][Tf2N]) and up to 40-100% higher than diisopropyl ether and tert-butanol. Fluorescence emission spectra confirmed the general protein structural preservation in these tailored ionic solvents. In addition, functionalized ILs showed high thermal stabilities, which are comparable with diisopropyl ether but much higher than tert-butanol.
ESTHER : Zhao_2019_ACS.Omega_4_15234
PubMedSearch : Zhao_2019_ACS.Omega_4_15234
PubMedID: 31552369

Title : Enzymatic Ring-Opening Polymerization (ROP) of Polylactones: Roles of Non-Aqueous Solvents - Zhao_2018_J.Chem.Technol.Biotechnol_93_9
Author(s) : Zhao H
Ref : J Chem Technol Biotechnol , 93 :9 , 2018
Abstract : Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, renewable and biocompatible polymers with high potentials to replace petro-chemical-based synthetic polymers. A benign route for synthesizing these polyesters is through the enzyme-catalyzed ring-opening polymerization (ROP) reaction; this type of enzymatic process is very sensitive to reaction conditions such as solvents, water content and temperature. This review systematically discusses the crucial roles of different solvents (such as solvent-free or in bulk, organic solvents, supercritical fluids, ionic liquids, and aqueous biphasic systems) on the degree of polymerization and polydispersity. In general, many studies suggest that hydrophobic organic solvents with minimum water contents lead to efficient enzymatic polymerization and subsequently high molecular weights of polyesters; the selection of solvents is also limited by the reaction temperature, e.g. the ROP of lactide is often conducted at above 100 degreesC, therefore, the solvent typically needs to have its boiling point above this temperature. The use of supercritical fluids could be limited by its scaling-up potential, while ionic liquids have exhibited many advantages include their low-volatility, high thermal stability, controllable enzyme-compatibility, and a wide range of choices. However, the fundamental and mechanistic understanding of the specific roles of ionic liquids in enzymatic ROP reactions is still lacking. Furthermore, the lipase specificity towards l- and d-lactide is also surveyed, followed by the discussion of engineered lipases with improved enantioselectivity and thermal stability. In addition, the preparation of polyester-derived materials such as polyester-grafted cellulose by the enzymatic ROP method is briefly reviewed.
ESTHER : Zhao_2018_J.Chem.Technol.Biotechnol_93_9
PubMedSearch : Zhao_2018_J.Chem.Technol.Biotechnol_93_9
PubMedID: 31929672

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

Title : Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition - Yu_2018_Oncotarget_9_27958
Author(s) : Yu Y , Kong R , Cao H , Yin Z , Liu J , Nan X , Phan AT , Ding T , Zhao H , Wong STC
Ref : Oncotarget , 9 :27958 , 2018
Abstract : Chemotherapy-induced diarrhea (CID), with clinical high incidence, adversely affects the efficacy of cancer treatment and patients' quality of life. Our study demonstrates that the citrus flavonoid hesperetin (Hst) has a superior potential as a new agent to prevent and alleviate CID. In the animal model for irinotecan (CPT-11) induced CID, Hst could selectively inhibit intestinal carboxylesterase (CES2) and thus reduce the local conversion of CPT-11 to cytotoxic SN-38 which causes intestinal toxicity. Oral administration of Hst manifested an excellent anti-diarrhea efficacy, prohibiting 80% of severe and 100% of mild diarrhea in the CPT-11 administered tumor-bearing mice. In addition, a significant attenuation of intestinal inflammation contributed to the anti-diarrhea effect of Hst. Moreover, Hst was found to work synergistically with CPT-11 in tumor inhibition by suppressing the tumor's STAT3 activity and recruiting tumoricidal macrophages into the tumor microenvironment. The anti-intestinal inflammation and anti-STAT3 properties of Hst would contribute its broad benefits to the management of diarrhea caused by other chemo or targeted agents, and more importantly, enhance and reinforce the anti-tumor effects of these agents, to improve patient outcomes.
ESTHER : Yu_2018_Oncotarget_9_27958
PubMedSearch : Yu_2018_Oncotarget_9_27958
PubMedID: 29963254

Title : Duplication of a Pks gene cluster and subsequent functional diversification facilitate environmental adaptation in Metarhizium species - Zeng_2018_PLoS.Genet_14_e1007472
Author(s) : Zeng G , Zhang P , Zhang Q , Zhao H , Li Z , Zhang X , Wang C , Yin WB , Fang W
Ref : PLoS Genet , 14 :e1007472 , 2018
Abstract : The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection. Different upstream signaling pathways were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1-MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive selection and synthesize different secondary metabolites. PKS1 is involved in synthesis of an anthraquinone derivative, and contributes to conidial pigmentation, which plays an important role in fungal tolerance to UV radiation and extreme temperatures. Disruption of the Pks2 gene delayed formation of infectious structures and increased the time taken to kill insects, indicating that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene cluster and its subsequent functional diversification has increased the adaptive flexibility of Metarhizium species.
ESTHER : Zeng_2018_PLoS.Genet_14_e1007472
PubMedSearch : Zeng_2018_PLoS.Genet_14_e1007472
PubMedID: 29958281
Gene_locus related to this paper: metaq-pks1 , metra-pks2 , metmf-pks2 , metaf-pks1 , metbs-pks2 , metas-pks1 , metaq-pks2

Title : Bioaccumulation of sulfadiazine and subsequent enzymatic activities in Chinese mitten crab (Eriocheir sinensis) - Cheng_2017_Mar.Pollut.Bull_121_176
Author(s) : Cheng L , Chen Y , Zheng YY , Zhan Y , Zhao H , Zhou JL
Ref : Mar Pollut Bull , 121 :176 , 2017
Abstract : The bioaccumulation of sulfadiazine and subsequent enzymatic activities in Chinese mitten crab (Eriocheir sinensis) were studied in microcosms, by exposing to 50, 100, 500 and 1000ng/L of sulfadiazine for 44days. An effective method for extracting sulfadiazine in crab tissues was established by modifying the cleanup method after ultrasound extraction, with improved recoveries of 61.8%, 93.7% and 100.5% in gill, muscle and liver samples. The results showed that sulfadiazine residues were all <3ng/g dry weight in different tissues, and that sulfadiazine bioaccumulation in crab was not dose-dependent. A significantly negative correlation was observed between acetylcholinesterase activity and the residue concentration of sulfadiazine during exposure to 50ng/L and 1000ng/L, and between alkaline phosphatase and sulfadiazine residues in the 100ng/L exposure group in the gill, suggesting that the two enzymes played an important role in the metabolism of sulfadiazine in crab.
ESTHER : Cheng_2017_Mar.Pollut.Bull_121_176
PubMedSearch : Cheng_2017_Mar.Pollut.Bull_121_176
PubMedID: 28601439

Title : Genome-wide identification of pathogenicity, conidiation and colony sectorization genes in Metarhizium robertsii - Zeng_2017_Environ.Microbiol_19_3896
Author(s) : Zeng G , Chen X , Zhang X , Zhang Q , Xu C , Mi W , Guo N , Zhao H , You Y , Dryburgh FJ , Bidochka MJ , St Leger RJ , Zhang L , Fang W
Ref : Environ Microbiol , 19 :3896 , 2017
Abstract : Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. About 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi were identified. By analysing a series of conidial pigmentation mutants, a new fungal pigmentation gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA regulates expression of these pigmentation genes. During conidiation Mr-BlrA up-regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK regulates fungal conidiation by controlling the conidiation regulatory pathway, and that all three pigmentation genes exercise feedback regulation of conidiation. This work provided the foundation for deeper understanding of the genetic processes behind M. robertsii adaptive phenotypes, and advances our insights into conidiation and pigmentation in this fungus.
ESTHER : Zeng_2017_Environ.Microbiol_19_3896
PubMedSearch : Zeng_2017_Environ.Microbiol_19_3896
PubMedID: 28447400
Gene_locus related to this paper: metaf-pks1

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

Title : Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients - Zhou_2017_Sci.Rep_7_44660
Author(s) : Zhou Y , Li P , Brantner A , Wang H , Shu X , Yang J , Si N , Han L , Zhao H , Bian B
Ref : Sci Rep , 7 :44660 , 2017
Abstract : Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.
ESTHER : Zhou_2017_Sci.Rep_7_44660
PubMedSearch : Zhou_2017_Sci.Rep_7_44660
PubMedID: 28304399

Title : MAPK cascade-mediated regulation of pathogenicity, conidiation and tolerance to abiotic stresses in the entomopathogenic fungus Metarhizium robertsii - Chen_2016_Environ.Microbiol_18_1048
Author(s) : Chen X , Xu C , Qian Y , Liu R , Zhang Q , Zeng G , Zhang X , Zhao H , Fang W
Ref : Environ Microbiol , 18 :1048 , 2016
Abstract : Metarhizium robertsii has been used as a model to study fungal pathogenesis in insects, and its pathogenicity has many parallels with plant and mammal pathogenic fungi. MAPK (Mitogen-activated protein kinase) cascades play pivotal roles in cellular regulation in fungi, but their functions have not been characterized in M. robertsii. In this study, we identified the full complement of MAPK cascade components in M. robertsii and dissected their regulatory roles in pathogenesis, conidiation and stress tolerance. The nine components of the Fus3, Hog1 and Slt2-MAPK cascades are all involved in conidiation. The Fus3- and Hog1-MAPK cascades are necessary for tolerance to hyperosmotic stress, and the Slt2- and Fus3-MAPK cascades both mediate cell wall integrity. The Hog1 and Slt2-MAPK cascades contribute to pathogenicity; the Fus3-MAPK cascade is indispensable for fungal pathogenesis. During its life cycle, M. robertsii experiences multiple microenvironments as it transverses the cuticle into the haemocoel. RNA-seq analysis revealed that MAPK cascades collectively play a major role in regulating the adaptation of M. robertsii to the microenvironmental change from the cuticle to the haemolymph. The three MAPKs each regulate their own distinctive subset of genes during penetration of the cuticle and haemocoel colonization, but they function redundantly to regulate adaptation to microenvironmental change.
ESTHER : Chen_2016_Environ.Microbiol_18_1048
PubMedSearch : Chen_2016_Environ.Microbiol_18_1048
PubMedID: 26714892
Gene_locus related to this paper: metra-pks2

Title : Association Between Paraoxonase 2 Ser311Cys Polymorphism and Coronary Heart Disease Risk: A Meta-Analysis - Chen_2016_Med.Sci.Monit_22_3196
Author(s) : Chen ML , Zhao H , Liao N , Xie ZF
Ref : Med Sci Monit , 22 :3196 , 2016
Abstract : BACKGROUND The relationship between coronary heart disease (CHD) and the paraoxonase 2 (PON2) Ser311Cys polymorphism has received much attention. We conducted a meta-analysis on the results from published case-control studies examining this relation. MATERIAL AND METHODS A literature search was performed using PubMed and ISI Web of Knowledge databases until October 2015. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using Stata version 11.0 software. Data were pooled using the random-effects model. RESULTS Nine studies were eligible for statistical analysis and included a total of 5278 participants. The results did not support an association between the Ser311Cys polymorphism and CHD in the overall populations (Asians, Caucasians, and a Hispanic mixed population) under dominant (OR 1.07; 95% CI 0.91-1.28; Pz=0.413), recessive (OR 1.19; 95% CI 0.72-1.95; Pz=0.500), homozygote (OR 1.20; 95% CI 0.71-2.03; Pz=0.489), and allelic comparison (OR 1.08; 95% CI 0.91-1.28; Pz=0.390) models. However, in subgroup analysis according to ethnicity, we found that the Ser311Cys polymorphism was associated with CHD risk in Caucasians under recessive (OR 2.08; 95% CI 1.30-3.34; Pz=0.002) and homozygote (OR 2.16; 95% CI 1.33-3.50; Pz=0.002) models. Subgroup analysis indicated no significant association of this polymorphism with CHD in either Asian or Hispanic populations. CONCLUSIONS The PON2 Ser311Cys polymorphism is associated with CHD risk in Caucasians, but there is no association between this polymorphism and CHD in Asians or Hispanic populations.
ESTHER : Chen_2016_Med.Sci.Monit_22_3196
PubMedSearch : Chen_2016_Med.Sci.Monit_22_3196
PubMedID: 27609416

Title : Single and Multiple Dose Pharmacokinetics, Pharmacodynamics and Safety of the Novel Lipoprotein-Associated Phospholipase A2 Enzyme Inhibitor Darapladib in Healthy Chinese Subjects: An Open Label Phase-1 Clinical Trial - Hu_2015_PLoS.One_10_e0139862
Author(s) : Hu C , Tompson D , Magee M , Chen Q , Liu YM , Zhu W , Zhao H , Gross AS , Liu Y
Ref : PLoS ONE , 10 :e0139862 , 2015
Abstract : BACKGROUND AND OBJECTIVES: Darapladib is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. This study evaluated the pharmacokinetics, pharmacodynamics and safety of darapladib in healthy Chinese subjects.
METHODS: Twenty-four subjects received darapladib 160 mg orally, approximately 1 hour after a standard breakfast, as a single dose and once daily for 28 days. Non-compartmental methods were used to determine the single and multiple dose pharmacokinetics of darapladib and its metabolite SB-553253. Repeat dose Lp-PLA2 activity and safety were evaluated.
RESULTS: Systemic exposure (AUC(0-T), Cmax geometric mean (CVb%)) of darapladib was higher after multiple-dosing (519 ng.h/mL (33.3%), 34.4 ng/mL (49.9%)) compared to single-dose administration (153 ng.h/mL (69.0%), 17.9 ng/mL (55.2%). The steady-state accumulation ratio was less than unity (Rs = 0.80), indicating time-dependent pharmacokinetics of darapladib. Darapladib steady-state was reached by Day 14 of once daily dosing. Systemic exposure to SB-553253 was lower than darapladib with median (SB-553253: darapladib) ratios for AUC(0-tau) of 0.0786 for single dose and 0.0532 for multiple dose administration. On Day 28, pre-dose and maximum inhibition of Lp-PLA2 activity was approximately 70% and 75% relative to the baseline value, respectively and was dependent of darapladib concentration. The most common adverse events (>/= 21% subjects) were abnormal faeces, abnormal urine odour, diarrhoea and nasopharyngitis. CONCLUSION: Darapladib 160 mg single and repeat doses were profiled in healthy Chinese subjects. Single dose systemic exposure to darapladib in healthy Chinese subjects was consistent with that observed previously in Western subjects whereas steady-state systemic exposure was approximately 65% higher in Chinese than Western subjects. The Lp-PLA2 activity and adverse event profile were similar in healthy Chinese and previous reports in Western subjects. Ethnic-specific dose adjustment of darapladib is not considered necessary for the Chinese population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02000804.
ESTHER : Hu_2015_PLoS.One_10_e0139862
PubMedSearch : Hu_2015_PLoS.One_10_e0139862
PubMedID: 26465780

Title : Neuroprotective Effect of Biatractylenolide Against Memory Impairment in D-Galactose-induced Aging Mice - Ji_2015_J.Mol.Neurosci_55_678
Author(s) : Ji ZH , Liu C , Zhao H , Yu XY
Ref : Journal of Molecular Neuroscience , 55 :678 , 2015
Abstract : Biatractylenolide, a sesquiterpene lactone, which exerted the neuroprotective effect against glutamate-induced excitotoxicity, was isolated from Atractylodis macrocephala in our previous study. In this study, we evaluated the neuroprotective effect of biatractylenolide against D-galactose-induced memory impairment and explored the potential mechanism of its action. The results showed that administration of biatractylenolide could significantly improve behavioral performance of D-galactose-treated mice in passive avoidance test and spatial learning-memory test. Administration of biatractylenolide could significantly decrease the formation of reactive oxygen species (ROS), decrease the activity of acetylcholinesterase (AChE), and increase the expression of synapsin I and protein kinase C (PKC) in D-galactose-treated mice. Our findings provide first evidence for the neuroprotective effect of biatractylenolide against D-galactose-induced memory impairment. The potential mechanisms underlying the neuroprotective effect of biatractylenolide in D-galactose-treated mice might be (i) attenuating oxidative damage via decreasing ROS formation, (ii) restoring cholinergic neurotransmission via decreasing AChE activity, and (iii) increasing the expression of memory-related proteins (synapsin I and PKC). Biatractylenolide may have therapeutic potential in aging-related memory impairment.
ESTHER : Ji_2015_J.Mol.Neurosci_55_678
PubMedSearch : Ji_2015_J.Mol.Neurosci_55_678
PubMedID: 25173400

Title : An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF\/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch - Zhao_2015_J.Pharm.Biomed.Anal_120_235
Author(s) : Zhao H , Zhou S , Zhang M , Feng J , Wang S , Wang D , Geng Y , Wang X
Ref : J Pharm Biomed Anal , 120 :235 , 2015
Abstract : In this study, an in vitro acetylcholinesterase (AChE) inhibition assay based on microplate reader combined with ultrafiltration high performance liquid chromatography-electrospray quadrupole time of flight mass (UF-HPLC-ESI-Q-TOF/MS) was developed for the rapid screening and identification of acetylcholinesterase inhibitors (AChEI) from roots of Coptis chinensis Franch. Incubation conditions such as enzyme concentration, incubation time, incubation temperature and co-solvent was optimized so as to get better screening results. Five alkaloids including columbamine, jatrorrhizine, coptisine, palmatine and berberine were found with AChE inhibition activity in the 80% ethanol extract of C. chinensis Franch. The screened compounds were identified by HPLC-DAD-ESI-Q-TOF/MS compared with the reference stands and literatures. The screened results were verified by in vitro AChE inhibition assays, palmatine showed the best AChE inhibitory activities with IC50 values of 36.6muM among the five compounds. Results of the present study indicated that the combinative method using in vitro AChE inhibition assay and UF-HPLC-ESI-Q-TOF/MS could be widely applied for rapid screening and identification of AChEI from complex TCM extract.
ESTHER : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedSearch : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedID: 26760241

Title : An ultra-sensitive acetylcholinesterase biosensor based on reduced graphene oxide-Au nanoparticles-beta-cyclodextrin\/Prussian blue-chitosan nanocomposites for organophosphorus pesticides detection - Zhao_2014_Biosens.Bioelectron_65C_23
Author(s) : Zhao H , Ji X , Wang B , Wang N , Li X , Ni R , Ren J
Ref : Biosensors & Bioelectronics , 65C :23 , 2014
Abstract : This work reports a novel, ultrasensitive, and selective sensing platform based on a direct electrodeposition of electrochemical reduced graphene oxide (ERGO)-Au nanoparticles (AuNPs)-beta-cyclodextrin (beta-CD) and Prussian blue-chitosan (PB-CS) on glass carbon electrode (GCE) for efficiently fixed acetylcholinesterase (AChE) to fabricate organophosphorus pesticides (OPs) biosensor. The PB-CS not only effectively catalyzed the oxidation of thiocholine (TCh), but also shifted its oxidation potential from 0.68 to 0.2V, and accordingly the sensitivity of the biosensor was obviously improved. The synergistic effect between ERGO and AuNPs significantly promoted the electron transfer between PB and GCE, and remarkably enhanced the electrochemical oxidation of TCh. Besides, beta-CD could interact with substrate by reversible bonding, which is contribute to increase the enrichment of the substrate and improve the selectivity and sensitivity of the biosensor. The integration of ERGO-AuNPs-beta-CD with PB-CS provided an advantageous and high-performance platform for sensing applications. Based on the inhibition of OPs on AChE activity, the sensor showed wide linear ranges of 7.98-2.00x103pgmL-1 and 4.3-1.00x103pgmL-1 with low detection limits of 4.14pgmL-1 and 1.15pgmL-1 for malathion and carbaryl, respectively. The proposed biosensor exhibited short response time, good stability and high sensitivity, which can be used for direct analysis of practical samples.
ESTHER : Zhao_2014_Biosens.Bioelectron_65C_23
PubMedSearch : Zhao_2014_Biosens.Bioelectron_65C_23
PubMedID: 25461134

Title : Determination of Meserine, a new candidate for Alzheimer's disease in mice brain by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic and tissue distribution study - Zheng_2014_Anal.Bioanal.Chem_406_3451
Author(s) : Zheng Z , Tang Y , Lv H , Xu J , Zhao H , Xie Q , Qiu Z , Chen H , Wang H
Ref : Anal Bioanal Chem , 406 :3451 , 2014
Abstract : A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of Meserine ((-)-meptazinol phenylcarbamate), a novel potent inhibitor of acetylcholinesterase (AChE), was developed, validated, and applied to a pharmacokinetic study in mice brain. The lower limit of quantification (LLOQ) was 1 ng mL(-1) and the linear range was 1-1,000 ng mL(-1). The analyte was eluted on a Zorbax SB-Aq column (2.1 x 100 mm, 3.5 mum) with the mobile phase composed of methanol and water (70:30, v/v, aqueous phase contained 10 mM ammonium formate and 0.3% formic acid) using isocratic elution, and monitored by positive electrospray ionization in multiple reaction monitoring (MRM) mode. The flow rate was 0.25 mL min(-1). The injection volume was 5 muL and total run time was 4 min. The relative standard deviation (RSD) of intraday and interday variation was 2.49-7.81 and 3.01-7.67%, respectively. All analytes were stable after 4 h at room temperature and 6 h in autosampler. The extraction recoveries of Meserine in brain homogenate were over 90%. The main brain pharmacokinetic parameters obtained after intranasal administration were T max = 0.05 h, C max = 462.0 +/- 39.7 ng g(-1), T 1/2 = 0.4 h, and AUC(0-infinity) = 283.1 +/- 9.1 ng h g(-1). Moreover, Meserine was distributed rapidly and widely into brain, heart, liver, spleen, lung, and kidney tissue. The method is validated and could be applied to the pharmacokinetic and tissue distribution study of Meserine in mice.
ESTHER : Zheng_2014_Anal.Bioanal.Chem_406_3451
PubMedSearch : Zheng_2014_Anal.Bioanal.Chem_406_3451
PubMedID: 24756818

Title : Genome-wide identification of housekeeping genes in maize - Lin_2014_Plant.Mol.Biol_86_543
Author(s) : Lin F , Jiang L , Liu Y , Lv Y , Dai H , Zhao H
Ref : Plant Mol Biol , 86 :543 , 2014
Abstract : In the wake of recent progress of high throughput transcriptome profiling technologies, extensive housekeeping gene mining has been conducted in humans. However, very few studies have been reported in maize (Zea mays L.), an important crop plant, and none were conducted on a genome -wide level. In this study, we surveyed housekeeping genes throughout the maize transcriptome using RNA-seq and microarray techniques, and validated the housekeeping profile with quantitative polymerase chain reaction (qPCR) under a series of conditions including different genotypes and nitrogen supplies. Seven microarray datasets and two RNA-seq libraries representing 40 genotypes at more than 20 developmental stages were selected to screen for commonly expressed genes. A total of 1,661 genes showed constitutive expression in both microarray and RNA-seq datasets, serving as our starting housekeeping gene candidates. To determine for stably expressed housekeeping genes, NormFinder was used to select the top 20 % invariable genes to be the more likely candidates, which resulted in 48 and 489 entries from microarray and RNA-seq data, respectively. Among them, nine genes (2OG-Fe, CDK, DPP9, DUF, NAC, RPN, SGT1, UPF1 and a hypothetical protein coding gene) were expressed in all 40 maize diverse genotypes tested covering 16 tissues at more than 20 developmental stages under normal and stress conditions, implying these as being the most reliable reference genes. qPCR analysis confirmed the stable expression of selected reference gene candidates compared to two widely used housekeeping genes. All the reference gene candidates showed higher invariability than ACT and GAPDH. The hypothetical protein coding gene exhibited the most stable expression across 26 maize lines with different nitrogen treatments with qPCR, followed by CDK encoding the cyclin-dependent kinase. As the first study to systematically screen for housekeeping genes in maize, we identified candidates by examining the transcriptome atlas generated from RNA-seq and microarray technologies. The nine top-ranked qPCR-validated novel housekeeping genes provide a valuable resource of reference genes for maize gene expression analysis.
ESTHER : Lin_2014_Plant.Mol.Biol_86_543
PubMedSearch : Lin_2014_Plant.Mol.Biol_86_543
PubMedID: 25209110

Title : Aryl-aldehyde formation in fungal polyketides: discovery and characterization of a distinct biosynthetic mechanism - Wang_2014_Chem.Biol_21_257
Author(s) : Wang M , Beissner M , Zhao H
Ref : Chemical Biology , 21 :257 , 2014
Abstract : Aryl-aldehydes are a common feature in fungal polyketides, which are considered to be exclusively generated by the R domain of nonreducing polyketide synthases (NR-PKSs). However, by cloning and heterologous expression of both cryptic NR-PKS and nonribosomal peptide synthase (NRPS)-like genes from Aspergillus terreus in Saccharomyces cerevisiae, we identified a distinct mechanism for aryl-aldehyde formation in which a NRPS-like protein activates and reduces an aryl-acid produced by the accompanying NR-PKS to an aryl-aldehyde. Bioinformatics study indicates that such a mechanism may be widely used throughout the fungi kingdom.
ESTHER : Wang_2014_Chem.Biol_21_257
PubMedSearch : Wang_2014_Chem.Biol_21_257
PubMedID: 24412543
Gene_locus related to this paper: asptn-5moas , asptn-azpb5

Title : A Genetic Screen Identifies Interferon-alpha Effector Genes Required to Suppress Hepatitis C Virus Replication - Fusco_2013_Gastroenterology_144_1438
Author(s) : Fusco DN , Brisac C , John SP , Huang YW , Chin CR , Xie T , Zhao H , Jilg N , Zhang L , Chevaliez S , Wambua D , Lin W , Peng L , Chung RT , Brass AL
Ref : Gastroenterology , 144 :1438 , 2013
Abstract : BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-alpha (IFNalpha) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFNalpha (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFNalpha. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach.
METHODS: We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFNalpha and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further.
RESULTS: The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, alpha-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, beta 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, beta isoform; peroxisomal proliferator-activated receptor-gamma-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFNalpha-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFNalpha to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this screen (92%) were not transcriptionally stimulated by IFNalpha; these genes represent a heretofore unknown class of non-IFN-stimulated gene IEGs.
CONCLUSIONS: We performed a whole-genome loss-of-function screen to identify genes that mediate the effects of IFNalpha against human pathogenic viruses. We found that IFNalpha restricts HCV via actions of general and specific IEGs.
ESTHER : Fusco_2013_Gastroenterology_144_1438
PubMedSearch : Fusco_2013_Gastroenterology_144_1438
PubMedID: 23462180

Title : Contamination by metals and pharmaceuticals in northern Taihu Lake (China) and its relation to integrated biomarker response in fish - Lu_2013_Ecotoxicology_22_50
Author(s) : Lu G , Yang X , Li Z , Zhao H , Wang C
Ref : Ecotoxicology , 22 :50 , 2013
Abstract : Taihu Lake is the largest shallow freshwater lake in eastern China and is suffering not only from an increasingly serious threat of eutrophication but also potential ecological risk due to the input of emerging contaminants. Active biomonitoring was conducted in Taihu Lake using transplanted goldfish (Carassius auratus) to determine the contamination by pharmaceuticals and metals and to assess the potential ecological risk. A suite of biomarkers including acetylcholinesterase, ethoxyresorufin O-deethylase, glutathione S-transferase, glutathione peroxidase and superoxide dismutase activities in fish after 7, 14, 21 and 28 days of exposure in situ, as well as pharmaceuticals and metals in water, were determined during the field exposure period. The results indicate that pharmaceuticals exist mainly in Zhushan Bay and Meiliang Bay, while metals are present mainly in Gong Bay. An integrated biomarker response (IBR) was calculated and used to evaluate the ecological risk of the polluted area of Taihu Lake. It was found that Zhushan Bay might present higher risk to fish, followed by Meiliang Bay. IBR values were in good agreement with copper and caffeine concentrations.
ESTHER : Lu_2013_Ecotoxicology_22_50
PubMedSearch : Lu_2013_Ecotoxicology_22_50
PubMedID: 23053787

Title : Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice - Wang_2012_Exp.Neurol_236_79
Author(s) : Wang J , Chen F , Zheng P , Deng W , Yuan J , Peng B , Wang R , Liu W , Zhao H , Wang Y , Wu G
Ref : Experimental Neurology , 236 :79 , 2012
Abstract : Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-gamma and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-gamma and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology.
ESTHER : Wang_2012_Exp.Neurol_236_79
PubMedSearch : Wang_2012_Exp.Neurol_236_79
PubMedID: 22524989

Title : Constitutive expression of Yarrowia lipolytica lipase LIP2 in Pichia pastoris using GAP as promoter - Wang_2012_Appl.Biochem.Biotechnol_166_1355
Author(s) : Wang X , Sun Y , Ke F , Zhao H , Liu T , Xu L , Liu Y , Yan Y
Ref : Appl Biochem Biotechnol , 166 :1355 , 2012
Abstract : A gene encoding Yarrowia lipolytica lipase LIP2 (YlLIP2) was cloned into a constitutive expression vector pGAPZalphaA and electrotransformed into the Pichia pastoris X-33 strain. The high-yield clones obtained by high copy and enzyme activity screening were chosen as the host strains for shaking flask and fermentor culture. The results showed that glucose was the optimum carbon source for YlLIP2 production, and the maximum hydrolytic activity of recombinant YlLIP2 reached 1,315 U/ml under the flask culture at 28 degrees C, pH 7.0, for 48 h. The fed-batch fermentation was carried out in 3- and 10-l bioreactors by continuously feeding glucose into the growing medium for achieving high cell density and YlLIP2 yields. The maximum hydrolytic activity of YlLIP2 and cell density obtained in the 3-l bioreactor were 10,300 U/ml and 116 g dry cell weight (DCW)/l, respectively. The peak hydrolytic activity of YlLIP2 and cell density were further improved in the 10-l fermentor where the values respectively attained were 13,500 U/ml and 120 g DCW/l. The total protein concentration in the supernatant reached 3.3 g/l and the cell viability remained approximately 99% after 80 h of culture. Furthermore, the recombinant YlLIP2 produced in P. pastoris pGAP and pAOX1 systems have similar content of sugar (about 12%) and biochemical characteristics. The above results suggest that the GAP promoter-derived expression system of P. pastoris is effective for the expression of YlLIP2 by high cell density culture and is probably an alternative to the conventional AOX1 promoter expression system in large-scale production of industrial lipases.
ESTHER : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedSearch : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedID: 22246727

Title : Improving the thermostability of lipase Lip2 from Yarrowia lipolytica - Wen_2012_J.Biotechnol_164_248
Author(s) : Wen S , Tan T , Zhao H
Ref : J Biotechnol , 164 :248 , 2012
Abstract : Yarrowia lipolytica lipase Lip2 (YlLip2) is a highly versatile biocatalyst. However, its practical use is often hampered by its low stability. Here three complementary protein engineering strategies were used to improve the thermostability of this enzyme. The first strategy was error-prone PCR based directed evolution, which resulted in a YlLip2 variant with a 2.5-fold longer half-life of thermal inactivation at 50 degrees C compared to the wild-type enzyme. The second strategy was semi-rational design using the so-called B-factor iterative test (B-FIT), which led to the discovery of two thermostable YlLip2 variants that showed a half-life of thermal inactivation 2-fold and 5-fold longer than that of the wild-type enzyme, respectively, at 50 degrees C. The third strategy was to use site-directed mutagenesis to combinatorially combine all three thermostabilizing mutations identified in the first two strategies, which improved the half-life of thermal inactivation of YlLip2 by 7-fold compared to that of the wild-type enzyme. Such engineered lipases provide not only new insights on the protein structure and function relationship but also potentially useful catalysts for practical applications.
ESTHER : Wen_2012_J.Biotechnol_164_248
PubMedSearch : Wen_2012_J.Biotechnol_164_248
PubMedID: 22982168

Title : Complete genome sequence of the naphthalene-degrading Pseudomonas putida strain ND6 - Li_2012_J.Bacteriol_194_5154
Author(s) : Li S , Zhao H , Li Y , Niu S , Cai B
Ref : Journal of Bacteriology , 194 :5154 , 2012
Abstract : Pseudomonas putida strain ND6 is an efficient naphthalene-degrading bacterium. The complete genome of strain ND6 was sequenced and annotated. The genes encoding the enzymes involved in catechol degradation by the ortho-cleavage pathway were found in the chromosomal sequence, which indicated that strain ND6 is able to metabolize naphthalene by the catechol meta- and ortho-cleavage pathways.
ESTHER : Li_2012_J.Bacteriol_194_5154
PubMedSearch : Li_2012_J.Bacteriol_194_5154
PubMedID: 22933774
Gene_locus related to this paper: psepu-PIP , psepu-PP3943 , psepu-PP4249 , psepu-q9wwz4

Title : Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes - Morino_2012_Diabetes_61_877
Author(s) : Morino K , Petersen KF , Sono S , Choi CS , Samuel VT , Lin A , Gallo A , Zhao H , Kashiwagi A , Goldberg IJ , Wang H , Eckel RH , Maegawa H , Shulman GI
Ref : Diabetes , 61 :877 , 2012
Abstract : Recent studies reveal a strong relationship between reduced mitochondrial content and insulin resistance in human skeletal muscle, although the underlying factors responsible for this association remain unknown. To address this question, we analyzed muscle biopsy samples from young, lean, insulin resistant (IR) offspring of parents with type 2 diabetes and control subjects by microarray analyses and found significant differences in expression of ~512 probe pairs. We then screened these genes for their potential involvement in the regulation of mitochondrial biogenesis using RNA interference and found that mRNA and protein expression of lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in the IR offspring and was associated with decreased mitochondrial density. Furthermore, we show that LPL knockdown in muscle cells decreased mitochondrial content by effectively decreasing fatty acid delivery and subsequent activation of peroxisome proliferator-activated receptor (PPAR)-delta. Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-delta activation.
ESTHER : Morino_2012_Diabetes_61_877
PubMedSearch : Morino_2012_Diabetes_61_877
PubMedID: 22368174

Title : Oxidative injury in the brain of mice caused by lanthanid - Zhao_2011_Biol.Trace.Elem.Res_142_174
Author(s) : Zhao H , Cheng Z , Hu R , Chen J , Hong M , Zhou M , Gong X , Wang L , Hong F
Ref : Biol Trace Elem Res , 142 :174 , 2011
Abstract : The organ toxicity of lanthanides (Ln) on organisms had been recognized, but very little is known about the oxidative injury of brain caused by Ln. In order to study the mechanisms underlying the effects of Ln on the brain, ICR mice were injected with a single 20 mg/kg body weight dose of LaCl(3), CeCl(3), and NdCl(3) into the abdominal cavity daily for 14 days. We then examined the coefficient of the brain, the brain pathological changes and oxidative stress-mediated responses, and the accumulation of Ln and levels of neurochemicals in the brain. The results showed that CeCl(3) and NdCl(3) could induce some neurons to turn inflammatory cells and slight edema but did not observe the brain pathological changes from LaCl(3)-treated group. The concentrations of La, Ce, and Nd in the brain were significantly different and ranked in the order of Ce, Nd, and La. The injury of the brain and oxidative stress occurred as Ln appeared to trigger a cascade of reactions such as lipid peroxidation, the decreases of the total antioxidation capacity and activities of antioxidative enzymes, the excessive release of nitric oxide, the increase of glutamic acid, and the downregulated level of acetylcholinesterase activities. Furthermore, both Ce(3+) and Nd(3+) exhibited higher oxidative stress and toxicity on brain than La(3+), and Ce(3+) caused more severe brain injuries and oxidative stress than Nd(3+), implying that the differences in the brain injuries caused by Ln might be related to the number of 4f electrons of Ln.
ESTHER : Zhao_2011_Biol.Trace.Elem.Res_142_174
PubMedSearch : Zhao_2011_Biol.Trace.Elem.Res_142_174
PubMedID: 20614199

Title : [Heterologous expression and characterization of Yarrowia lipolytica lipase 4 and lipase 5 in Pichia pastoris] - Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
Author(s) : Zhao H , Xiao X , Xu L , Liu Y , Yan Y
Ref : Wei Sheng Wu Xue Bao , 51 :1374 , 2011
Abstract : OBJECTIVE: To clone cDNA sequences of lipase 4 (LIP4) and lipase 5 (LIPS), analyze gene structures and express them in Pichia pastoris so as to investigate their enzymatic characteristics. METHODS: We first cloned cDNA sequences of LIP4 and LIP5 by reverse transcription PCR and analyzed their gene structures by SignalP 3.0. Then, intracellular expression vectors pPIC3. 5K-Lip4, pPIC3. 5K-Lip5 and inducible secretion vectors pPIC9K-Lip4, pPIC9K-Lip5 were constructed. All vectors were transformed into Pichia pastoris GS115 by electroporation, resulting in a series of engineered strains. After fermentation and NTA-Ni resin purification, the enzymatic properties of LIP4 and LIP5 were examined. RESULTS: The cloned cDNA sequences revealed that there was no intron in both of Lip4 and Lip5. The two lipases both contained catalytic triads and conserved GHSLG motifs. Their optimal substrate, pH, temperature were respectively pNP-caprylate (C8), 7.0 and 40 degrees C. The activities of LIP4 and LIPS were 10.16 U/mg and 5.1 U/mg, respectively. It was found that LIP4 was more sensitive to the variations of pH and temperature than LIP5. LIP4 and LIP5 could both be stimulated by Ca2+, besides LIPS could also be activated by Mg2+. They were both strongly inhibited by Hg2+, Phenylmethanesulfonyl fluoride (PMSF) and Dithiothreitol (DTT). CONCLUSION: The cloning of Lip4 and Lip5, expression in P. pastoris and characterization of their properties would offer a solid basis for their large-scale production and future application. In addition, the results also enriched the data for a systematic research on the lipase gene family of Y. lipolytica.
ESTHER : Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
PubMedSearch : Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
PubMedID: 22233059

Title : Rare nonsynonymous variants in alpha-4 nicotinic acetylcholine receptor gene protect against nicotine dependence - Xie_2011_Biol.Psychiatry_70_528
Author(s) : Xie P , Kranzler HR , Krauthammer M , Cosgrove KP , Oslin D , Anton RF , Farrer LA , Picciotto MR , Krystal JH , Zhao H , Gelernter J
Ref : Biological Psychiatry , 70 :528 , 2011
Abstract : BACKGROUND: Several studies report association of alpha-4 nicotinic acetylcholine receptors (encoded by CHRNA4) with nicotine dependence (ND). A meta-analysis of genomewide linkage studies for ND implicated a single chromosomal region, which includes CHRNA4, as genome-wide significant.
METHODS: After establishing that common variants are unlikely to completely account for this linkage, we investigated the distribution of CHRNA4 rare variants by sequencing the coding exons and flanking intronic regions of CHRNA4 in 209 European American (EA) ND cases and 183 EA control subjects. Because most of the rare variants that we detected (and all nonsynonymous changes) were in Exon 5, we sequenced Exon 5 in an additional 1000 ND cases and 1000 non-ND comparison subjects, both of which included equal numbers of EAs and African Americans.
RESULTS: Comparison subjects had a higher frequency of rare nonsynonymous variants in the Exon 5 region (encoding the large intercellular loop of the alpha4 subunit; Fisher's Exact Test p = .009; association test p = .009, odds ratio = .43; weighted-sum method p = .014), indicating a protective effect against ND. Considering data from the two stages combined and only nonsynonymous variants predicted to alter protein function, the association was stronger (Fisher's Exact Test p = .005; association test p = .008, odds ratio = .29; weighted-sum method p = .005). Single-photon emission computed tomography imaging results were consistent with functionality.
CONCLUSIONS: CHRNA4 functional rare variants may reduce ND risk. This is the first demonstration that rare functional variants at a candidate locus protect against substance dependence to our knowledge, suggesting a novel mechanism of substance dependence heritability that is potentially of general importance.
ESTHER : Xie_2011_Biol.Psychiatry_70_528
PubMedSearch : Xie_2011_Biol.Psychiatry_70_528
PubMedID: 21683344

Title : Surface display of active lipase in Saccharomyces cerevisiae using Cwp2 as an anchor protein - Liu_2010_Biotechnol.Lett_32_255
Author(s) : Liu W , Zhao H , Jia B , Xu L , Yan Y
Ref : Biotechnol Lett , 32 :255 , 2010
Abstract : Lipase Lip2 from Yarrowia lipolytica was displayed on the cell surface of Saccharomyces cerevisiae using Cwp2 as an anchor protein. Successful display of the lipase on the cell surface was confirmed by immunofluorescence microscopy and halo assay. The length of linker sequences was further examined to confirm that the correct conformation of Lip2 was maintained. The results showed that the displayed Lip2 exhibited the highest activity at 7.6 +/- 0.4 U/g (dry cell) when using (G(4)S)(3) sequence as the linker, with an optimal temperature and pH at 40 degrees C and pH 8.0. The displayed lipase did not lose any activity after being treated with 0.1% Triton X-100 and 0.1% Tween 80 for 30 min, and it retained 92% of its original activity after incubation in 10% DMSO for 30 min. It also exhibited better thermostability than free Lip2 as reported previously.
ESTHER : Liu_2010_Biotechnol.Lett_32_255
PubMedSearch : Liu_2010_Biotechnol.Lett_32_255
PubMedID: 19821073

Title : Expression of NDRG2 in clear cell renal cell carcinoma - Ma_2008_Biol.Pharm.Bull_31_1316
Author(s) : Ma J , Jin H , Wang H , Yuan J , Bao T , Jiang X , Zhang W , Zhao H , Yao L
Ref : Biol Pharm Bull , 31 :1316 , 2008
Abstract : Clear cell renal cell carcinoma (CCRCC) is the most common pathological type of renal cell carcinoma and the main cause of renal carcinoma mortality. NDRG2, a new member of the N-Myc downstream-regulated gene (NDRG) family, is a focus for study at present. Up to now, its expression and function in carcinoma remain unclear. The aim of this study was to investigate its expression in CCRCC tissues and several renal carcinoma cell lines. The expression of NDRG2 was evaluated in renal cell carcinoma cell lines, tumor and adjacent non-tumor tissues from same clear cell renal cell carcinoma patients, by using immunohistochemistry, immunofluorescence, RT-PCR and Western blot. By immunohistochemistry and immunofluorescence we found that NDRG2 was predominantly located in the cytoplasm and membrane of renal carcinoma cancer cells, and the positive rate of NDRG2 in renal carcinoma specimens was 30.3% (40/132), which is significantly lower than 91.67% (121/132) in normal renal tissues (p<0.01). The average staining score in normal renal tissues was significantly higher than renal carcinoma (6.12+/-1.84 versus 2.65+/-1.23, p<0.01). Moreover, NDRG2 mRNA and protein were down-regulated in 6 fresh CCRCC tissues compared with their adjacent noncancerous tissues and normal tissues. Its expression was also lower in the human CCRCC-derived cell lines A-498 and 786-O than in the human proximal tubular cell lines HK-2 and HKC. These results indicated that NDRG2 might play an important role in the carcinogenesis and development of CCRCC and may function as a tumor suppressor in CCRCC.
ESTHER : Ma_2008_Biol.Pharm.Bull_31_1316
PubMedSearch : Ma_2008_Biol.Pharm.Bull_31_1316
PubMedID: 18591767

Title : [Cell surface display of Yarrowia lipolytica lipase Lip2 in Saccharomyces cerevisiae with a-agglutinin as carrier protein] - Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
Author(s) : Liu W , Xu L , Zhao H , Yang J , Yan Y
Ref : Wei Sheng Wu Xue Bao , 48 :1543 , 2008
Abstract : OBJECTIVE: In order to display extracellular.lipase Lip2 from Yarrowia lipolytica on the surface of yeast Saccharomyces cerevisiae for whole cell catalysts. METHODS: The mature Lip2 encoding fragment was amplified from Yarrowia lipolytica total DNA, and was inserted into the 3'terminal of AGA2 to give the plasmid pCTLIP2 for surface display of Lip2. Olive oil, tributyrin and p-nitrophenyl palmitate (pNPP) were used as substrates to measure lipase activity. Moreover, the characterization of displayed lipase and its free form was analyzed. RESULTS: The surface displayed lipase was confirmed to be active towards olive oil, tributyrin and p-nitrophenyl palmitate (pNPP), and reached its highest expression level at 182 U/g dry cell after induced by galactose for 72h. The optimum temperature of cell surface displayed Lip2 was 40 degrees C After incubated at 50 degrees C for 4h, the surface displayed lipase retained 23.2% of its full activity, improved a little compared to free Lip2. The surface displayed lipase showed a preference to medium-chain and long-chain fatty acids p-nitrophenyl esters (C8-C16). CONCLUSION: The cell surface display system based on a-agglutinin is an effective system for displaying Lip2, and the whole cell EBY100-pCTLIP2 will be probably suited to a different range of applications.
ESTHER : Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
PubMedSearch : Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
PubMedID: 19149173

Title : New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin - Woodyer_2007_Chem.Commun.(Camb)__359
Author(s) : Woodyer RD , Li G , Zhao H , van der Donk WA
Ref : Chem Commun (Camb) , :359 , 2007
Abstract : Hydroxyethylphosphonate is a required intermediate in fosfomycin biosynthesis.
ESTHER : Woodyer_2007_Chem.Commun.(Camb)__359
PubMedSearch : Woodyer_2007_Chem.Commun.(Camb)__359
PubMedID: 17220970

Title : Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster - Woodyer_2006_Chem.Biol_13_1171
Author(s) : Woodyer RD , Shao Z , Thomas PM , Kelleher NL , Blodgett JA , Metcalf WW , van der Donk WA , Zhao H
Ref : Chemical Biology , 13 :1171 , 2006
Abstract : Fosfomycin is a clinically utilized, highly effective antibiotic, which is active against methicillin- and vancomycin-resistant pathogens. Here we report the cloning and characterization of a complete fosfomycin biosynthetic cluster from Streptomyces fradiae and heterologous production of fosfomycin in S. lividans. Sequence analysis coupled with gene deletion and disruption revealed that the minimal cluster consists of fom1-4, fomA-D. A LuxR-type activator that was apparently required for heterologous fosfomycin production was also discovered approximately 13 kb away from the cluster and was named fomR. The genes fomE and fomF, previously thought to be involved in fosfomycin biosynthesis, were shown not to be essential by gene disruption. This work provides new insights into fosfomycin biosynthesis and opens the door for fosfomycin overproduction and creation of new analogs via biomolecular pathway engineering.
ESTHER : Woodyer_2006_Chem.Biol_13_1171
PubMedSearch : Woodyer_2006_Chem.Biol_13_1171
PubMedID: 17113999

Title : Enantioseparation of the esters of alpha-N-acetyl amino acids by lipase in ionic liquid - Malhotra_2005_Chirality_17 Suppl_S240
Author(s) : Malhotra SV , Zhao H
Ref : Chirality , 17 Suppl :S240 , 2005
Abstract : Chiral alpha-amino acids have been obtained via enzymatic resolution in ionic liquid medium. The acetyl esters of a series of amino acids were separated by enzyme porcine pancreas lipase (PPL) in an aqueous solution of N-ethyl pyridinium trifluoroacetate, [EtPy]+ [CF3OO]-. A comparative study with organic solvent acetonitrile shows that the ionic liquids provide a better medium for enzymatic resolution.
ESTHER : Malhotra_2005_Chirality_17 Suppl_S240
PubMedSearch : Malhotra_2005_Chirality_17 Suppl_S240
PubMedID: 15962281

Title : A tale of two clades: monkeypox viruses - Likos_2005_J.Gen.Virol_86_2661
Author(s) : Likos AM , Sammons SA , Olson VA , Frace AM , Li Y , Olsen-Rasmussen M , Davidson W , Galloway R , Khristova ML , Reynolds MG , Zhao H , Carroll DS , Curns A , Formenty P , Esposito JJ , Regnery RL , Damon IK
Ref : Journal of General Virology , 86 :2661 , 2005
Abstract : Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain. Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.
ESTHER : Likos_2005_J.Gen.Virol_86_2661
PubMedSearch : Likos_2005_J.Gen.Virol_86_2661
PubMedID: 16186219
Gene_locus related to this paper: cowvi-M5L

Title : Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites - Zhao_2002_Mol.Carcinog_33_99
Author(s) : Zhao H , Spitz MR , Gwyn KM , Wu X
Ref : Mol Carcinog , 33 :99 , 2002
Abstract : Microsomal epoxide hydrolase (mEPHX) is a critical metabolic enzyme involved in the activation and subsequent detoxification of specific tobacco carcinogens. mEPHX harbors polymorphisms in exon 3 and exon 4 that modulate enzymatic activity. The exon 3 polymorphism decreases mEPHX metabolic activity, whereas the exon 4 polymorphism increases activity. We hypothesized that the mEPHX polymorphisms modulate lung cancer risk. Using a case-control study design and restriction fragment length polymorphism polymerase chain reaction assay, we determined the mEPHX polymorphic genotypes of 181 lung cancer cases among non-Hispanic whites and 163 controls (matched for age, sex, ethnicity, and smoking history). Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.99-2.46). Additionally, the risk estimates were elevated significantly for younger people (<64 yr) (OR=2.27, 95% CI=1.15-4.50) and current smokers (OR=2.22, 95% CI=1.06-4.65). The variant allele of mEPHX exon 3 had no effect overall (OR=0.88, 95% CI=0.56-1.38), but there was a 53% protective effect (OR=0.47, 95% CI=0.22-0.99) in younger people. When we analyzed the exon 3 and exon 4 polymorphisms together, those people with the high enzymatic activity genotype had an elevated lung cancer risk of 1.72 (95% CI=0.90-3.29). This elevated risk was also evident only in younger people. These findings suggest that these variant alleles of exon 3 and exon 4 of mEPHX modulates lung cancer risk.
ESTHER : Zhao_2002_Mol.Carcinog_33_99
PubMedSearch : Zhao_2002_Mol.Carcinog_33_99
PubMedID: 11813302

Title : Muscarinic agonists and antagonists in the treatment of Alzheimer's disease - Greenlee_2001_Farmaco_56_247
Author(s) : Greenlee W , Clader J , Asberom T , McCombie S , Ford J , Guzik H , Kozlowski J , Li S , Liu C , Lowe D , Vice S , Zhao H , Zhou G , Billard W , Binch H , Crosby R , Duffy R , Lachowicz J , Coffin V , Watkins R , Ruperto V , Strader C , Taylor L , Cox K
Ref : Farmaco , 56 :247 , 2001
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.
ESTHER : Greenlee_2001_Farmaco_56_247
PubMedSearch : Greenlee_2001_Farmaco_56_247
PubMedID: 11421251

Title : Development of a quantitative relationship between inhibition percentage and both incubation time and inhibitor concentration for inhibition biosensors-theoretical and practical considerations - Zhang_2001_Biosens.Bioelectron_16_1119
Author(s) : Zhang S , Zhao H , John R
Ref : Biosensors & Bioelectronics , 16 :1119 , 2001
Abstract : Theoretical and practical insights into the design and development of immobilised enzyme inhibition biosensors are reported. A general mathematical expression relating the percent of enzyme inhibition (i.e. the analytical signal) to both the inhibitor concentration and the incubation time is presented. The relevant physical, chemical and biochemical parameters required by the model are developed and discussed in terms of the inhibition of acetylcholinesterase by the organophosphorous pesticide, paraoxon. A second enzyme, choline oxidase and an amperometric transducer are used to facilitate the determination acetylcholinesterase inhibitor.
ESTHER : Zhang_2001_Biosens.Bioelectron_16_1119
PubMedSearch : Zhang_2001_Biosens.Bioelectron_16_1119
PubMedID: 11679297

Title : A retrograde signal is involved in activity-dependent remodeling at a C. elegans neuromuscular junction - Zhao_2000_Development_127_1253
Author(s) : Zhao H , Nonet ML
Ref : Development , 127 :1253 , 2000
Abstract : We have characterized how perturbations of normal synaptic activity influence the morphology of cholinergic SAB motor neurons that innervate head muscle in C. elegans. Mutations disrupting components of the presynaptic release apparatus, acetylcholine (ACh) synthesis or ACh loading into synaptic vesicles each induced sprouting of SAB axonal processes. These sprouts usually arose in the middle of the normal innervation zone and terminated with a single presynaptic varicosity. Sprouting SAB neurons with a similar morphology were also observed upon reducing activity in muscle, either by using mutants lacking a functional nicotinic ACh receptor subunit or through muscle-specific expression of a gain-of-function potassium channel. Analysis of temperature-sensitive mutants in the choline acetyltransferase gene revealed that the sprouting response to inactivity was developmentally regulated; reduction of synaptic activity in early larval stages, but not in late larval stages, induced both sprouting and addition of varicosities. Our results indicate that activity levels regulate the structure of certain synaptic connections between nerve and muscle in C. elegans. One component of this regulatory machinery is a retrograde signal from the postsynaptic cell that mediates the formation of synaptic connections.
ESTHER : Zhao_2000_Development_127_1253
PubMedSearch : Zhao_2000_Development_127_1253
PubMedID: 10683178

Title : Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants - Nonet_1998_J.Neurosci_18_70
Author(s) : Nonet ML , Saifee O , Zhao H , Rand JB , Wei L
Ref : Journal of Neuroscience , 18 :70 , 1998
Abstract : Synaptobrevins are vesicle-associated proteins implicated in neurotransmitter release by both biochemical studies and perturbation experiments that use botulinum toxins. To test these models in vivo, we have isolated and characterized the first synaptobrevin mutants in metazoans and show that neurotransmission is severely disrupted in mutant animals. Mutants lacking snb-1 die just after completing embryogenesis. The dying animals retain some capability for movement, although they are extremely uncoordinated and incapable of feeding. We also have isolated and characterized several hypomorphic snb-1 mutants. Although fully viable, these mutants exhibit a variety of behavioral abnormalities that are consistent with a general defect in the efficacy of synaptic transmission. The viable mutants are resistant to the acetylcholinesterase inhibitor aldicarb, indicating that cholinergic transmission is impaired. Extracellular recordings from pharyngeal muscle also demonstrate severe defects in synaptic transmission in the mutants. The molecular lesions in the hypomorphic alleles reside on the hydrophobic face of a proposed amphipathic-helical region implicated biochemically in interacting with the t-SNAREs syntaxin and SNAP-25. Finally, we demonstrate that double mutants lacking both the v-SNAREs synaptotagmin and snb-1 are phenotypically similar to snb-1 mutants and less severe than syntaxin mutants. Our work demonstrates that synaptobrevin is essential for viability and is required for functional synaptic transmission. However, our analysis also suggests that transmitter release is not completely eliminated by removal of either one or both v-SNAREs.
ESTHER : Nonet_1998_J.Neurosci_18_70
PubMedSearch : Nonet_1998_J.Neurosci_18_70
PubMedID: 9412487