Wei X

References (51)

Title : Penicilloneines A and B, Quinolone-Citrinin Hybrids from a Starfish-Derived Penicillium sp - Fan_2024_J.Nat.Prod__
Author(s) : Fan H , Shao XH , Zhang ZK , Ni C , Feng C , Wei X , Zhu JQ , Li XH , Zhang CX
Ref : Journal of Natural Products , : , 2024
Abstract : Penicilloneines A (1) and B (2) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A (1) and B (2) share a common 4-hydroxy-1-methyl-2(1H)-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A (1) and B (2) exhibited antifungal activities against Colletotrichum gloeosporioides, with lethal concentration 50 values of 0.02 and 1.51 microg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.
ESTHER : Fan_2024_J.Nat.Prod__
PubMedSearch : Fan_2024_J.Nat.Prod__
PubMedID: 38547118

Title : SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma - Zhou_2024_Cell.Oncol.(Dordr)__
Author(s) : Zhou P , Yao W , Liu L , Yan Q , Chen X , Wei X , Ding S , Lv Z , Zhu F
Ref : Cell Oncol (Dordr) , : , 2024
Abstract : PURPOSE: Chronic hepatitis B virus (HBV) infection is the primary risk factor for the malignant progression of hepatocellular carcinoma (HCC). It has been reported that HBV X protein (HBx) possesses oncogenic properties, promoting hepatocarcinogenesis and chemoresistance. However, the detailed molecular mechanisms are not fully understood. Here, we aim to investigate the effects of miR-128-3p/SPG21 axis on HBx-induced hepatocarcinogenesis and chemoresistance. METHODS: The expression of SPG21 in HCC was determined using bioinformatics analysis, quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC). The roles of SPG21 in HCC were elucidated through a series of in vitro and in vivo experiments, including real-time cellular analysis (RTCA), matrigel invasion assay, and xenograft mouse model. Pharmacologic treatment and flow cytometry were performed to demonstrate the potential mechanism of SPG21 in HCC. RESULTS: SPG21 expression was elevated in HCC tissues compared to adjacent non-tumor tissues (NTs). Moreover, higher SPG21 expression correlated with poor overall survival. Functional assays revealed that SPG21 fostered HCC tumorigenesis and invasion. MiR-128-3p, which targeted SPG21, was downregulated in HCC tissues. Subsequent analyses showed that HBx amplified TRPM7-mediated calcium influx via miR-128-3p/SPG21, thereby activating the c-Jun N-terminal kinase (JNK) pathway. Furthermore, HBx inhibited doxorubicin-induced apoptosis by engaging the JNK pathway through miR-128-3p/SPG21. CONCLUSION: The study suggested that SPG21, targeted by miR-128-3p, might be involved in enhancing HBx-induced carcinogenesis and doxorubicin resistance in HCC via the TRPM7/Ca(2+)/JNK signaling pathway. This insight suggested that SPG21 could be recognized as a potential oncogene, offering a novel perspective on its role as a prognostic factor and a therapeutic target in the context of HCC.
ESTHER : Zhou_2024_Cell.Oncol.(Dordr)__
PubMedSearch : Zhou_2024_Cell.Oncol.(Dordr)__
PubMedID: 38753154
Gene_locus related to this paper: human-SPG21

Title : Dual-Mode Ratiometric Electrochemical and Turn-On Fluorescent Detection of Butyrylcholinesterase Utilizing a Single Probe for the Diagnosis of Alzheimer's Disease - Dong_2023_Anal.Chem_95_8340
Author(s) : Dong H , Zhao L , Wang T , Chen Y , Hao W , Zhang Z , Hao Y , Zhang C , Wei X , Zhang Y , Zhou Y , Xu M
Ref : Analytical Chemistry , 95 :8340 , 2023
Abstract : Biomarkers detection in blood with high accuracy is crucial for the diagnosis and treatment of many diseases. In this study, the proof-of-concept fabrication of a dual-mode sensor based on a single probe (Re-BChE) using a dual-signaling electrochemical ratiometric strategy and a "turn-on" fluorescent method is presented. The probe Re-BChE was synthesized in a single step and demonstrated dual mode response toward butyrylcholinesterase (BChE), a promising biomarker of Alzheimer's disease (AD). Due to the specific hydrolysis reaction, the probe Re-BChE demonstrated a turn-on current response for BChE at -0.28 V, followed by a turn-off current response at -0.18 V, while the fluorescence spectrum demonstrated a turn-on response with an emission wavelength of 600 nm. The developed ratiometric electrochemical sensor and fluorescence detection demonstrated high sensitivity with BChE concentrations with a low detection limit of 0.08 microg mL(-1) and 0.05 microg mL(-1), respectively. Importantly, the dual-mode sensor presents the following advantages: (1) dual-mode readout can correct the impact of systematic or background error, thereby achieving more accurate results; (2) the responses of dual-mode readout originate from two distinct mechanisms and relatively independent signal transduction, in which there is no interference between two signaling routes. Additionally, compared with the reported single-signal electrochemical assays for BChE, both redox potential signals were detected in the absence of biological interference within a negative potential window. Furthermore, it was discovered that the outcomes of direct dual-mode electrochemical and fluorescence quantifications of the level of BChE in serum were in agreement with those obtained from the use of commercially available assay kits for BChE sensing. This method has the potential to serve as a useful point-of-care tool for the early detection of AD.
ESTHER : Dong_2023_Anal.Chem_95_8340
PubMedSearch : Dong_2023_Anal.Chem_95_8340
PubMedID: 37192372

Title : Hyperglycemia disrupted the integrity of the blood-brain barrier following diffuse axonal injury through the sEH\/NF-B pathway - Wei_2023_Immun.Inflamm.Dis_11_e1105
Author(s) : Wei X , Xing Z , Huang T , Zhang M , Song J , Zhao Y
Ref : Immun Inflamm Dis , 11 :e1105 , 2023
Abstract : OBJECTIVES: We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced-disruption of blood-brain barrier (BBB) integrity after diffuse axonal injury (DAI). METHODS: Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium-binding adapter molecule-1, beta-amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. The permeability of blood-brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the nuclear transcription factor kappa B (NF-kappaB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol-12-myristate-13-acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF-kappaB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF-kappaB pathway abrogated the protective effects of TPPU on BBB integrity in vitro. CONCLUSIONS: sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF-kappaB pathway.
ESTHER : Wei_2023_Immun.Inflamm.Dis_11_e1105
PubMedSearch : Wei_2023_Immun.Inflamm.Dis_11_e1105
PubMedID: 38156378

Title : Structural insights into the oligomeric effects on catalytic activity of a decameric feruloyl esterase and its application in ferulic acid production - Du_2023_Int.J.Biol.Macromol__126540
Author(s) : Du G , Wang Y , Zhang Y , Yu H , Liu S , Ma X , Cao H , Wei X , Wen B , Li Z , Fan S , Zhou H , Xin F
Ref : Int J Biol Macromol , :126540 , 2023
Abstract : Oligomeric feruloyl esterase (FAE) has great application prospect in industry due to its potentially high stability and fine-tuned activity. However, the relationship between catalytic capability and oligomeric structure remains undetermined. Here we identified and characterized a novel, cold-adapted FAE (BtFae) derived from Bacteroides thetaiotaomicron. Structural studies unraveled that BtFae adopts a barrel-like decameric architecture unique in esterase families. By disrupting the interface, the monomeric variant exhibited significantly reduced catalytic activity and stability toward methyl ferulate, potentially due to its impact on the flexibility of the catalytic triad. Additionally, our results also showed that the monomerization of BtFae severely decreased the ferulic acid release from de-starched wheat bran and insoluble wheat arabinoxylan by 75 % and 80 %, respectively. Collectively, this study revealed novel connections between oligomerization and FAE catalytic function, which will benefit for further protein engineering of FAEs at the quaternary structure level for improved industrial applications.
ESTHER : Du_2023_Int.J.Biol.Macromol__126540
PubMedSearch : Du_2023_Int.J.Biol.Macromol__126540
PubMedID: 37634773
Gene_locus related to this paper: bactn-BT4077

Title : Monitoring acetylcholinesterase level changes under oxidative stress through ESIPT-ICT-based near-infrared fluorescent probe - Wei_2023_Sens.Actuators.B.Chem_380_133392
Author(s) : Wei X , Zhu T , Ma Y , Sun J , Zheng G , Ma T , Yang X , Song Z , Lv Y , Zhang J , Yan M
Ref : Sensors and Actuators B: Chemical , 380 :133392 , 2023
Abstract : Oxidative stress plays an important role in pathology, and contributes to a variety of diseases, including inflammation, neurodegenerative diseases, and cancer. Research studies have shown that acetylcholinesterase (AChE) plays a key role in regulating oxidative stress. However, an effective analytical method for real-time monitoring of AChE under oxidative stress is still lacking. Currently, fluorescent probes based on dual sensing mechanisms have attracted great attention by combining and amplifying the advantages of both mechanisms. In this work, two NIR fluorescent probes (SNCN-AE and SNC-AE) that combined ESIPT and ICT processes were designed and synthesized for accurate detection of AChE activity. After the probes reacted with AChE, the strong electron push-pull effect enhanced the ICT process, which further synergized with the ESIPT effect, resulting in a distinct NIR fluorescence signal accompanied by a large Stokes shift. In particular, SNCN-AE showed better detection performance of fast response, good photostability and low cytotoxicity, which was highly suitable for imaging of endogenous AChE in living system. Importantly, SNCN-AE had been successfully applied for monitoring AChE under oxidative stress in PC12 cells and zebrafish model. These excellent properties made probes the promising tools for studying oxidative stress and related diseases.
ESTHER : Wei_2023_Sens.Actuators.B.Chem_380_133392
PubMedSearch : Wei_2023_Sens.Actuators.B.Chem_380_133392

Title : Soluble Epoxide Hydrolase Inhibitor TPPU Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain via Suppressing NF-B Signalling in the Spinal Cord of a Rat - Wei_2023_Pain.Res.Manag_2023_9058774
Author(s) : Wei X , Jia L , Zhou Y , Li W , Shan C , Zhang S , Zhao Y
Ref : Pain Res Manag , 2023 :9058774 , 2023
Abstract : OBJECTIVE: Paclitaxel-induced peripheral neuropathy (PIPN) is a debilitating and difficult-to-treat side effect of paclitaxel. Soluble epoxide hydrolase (sEH) can rapidly metabolize the endogenous anti-inflammatory mediators' epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. This study aimed to assess whether the sEH inhibitor N-(1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy) phenyl)-urea (TPPU) plays a critical role in PIPN of rats and provides a new target for treatment. METHODS: A Sprague-Dawley male rat model of PIPN induced by nab-paclitaxel was established. Rats were randomly divided into a control group, nab-paclitaxel group, and nab-paclitaxel + TPPU (sEH inhibitor) group, with 36 rats in each group. The effects of the sEH inhibitor TPPU on behavioural assays, apoptosis, glial activation, axonal injury, microstructure, and permeability of the blood-spinal cord barrier were detected, and the underlying mechanisms were explored by examining the expression of NF-kappaB signalling pathways, inflammatory cytokines, and oxidative stress. RESULTS: The results showed that the mechanical and thermal pain thresholds of rats were decreased after nab-paclitaxel treatment, accompanied by an increased expression of axonal injury-related proteins, enhanced cell apoptosis, aggravated destruction of vascular permeability, intense glial responses, and elevated inflammatory cytokines and oxidative stress in the L4-L6 spinal cord. TPPU restored the mechanical and thermal thresholds, decreased cell apoptosis, alleviated axonal injury and glial responses, and protected vascular permeability by increasing the expression of tight junction proteins. TPPU relieved PIPN by inhibiting the activation of the sEH and NF-kappaB signalling pathways by decreasing the levels of inflammatory cytokines and oxidative stress. CONCLUSION: These findings support a role for sEH in PIPN and suggest that the inhibition of sEH represents a potential new therapeutic target for PIPN.
ESTHER : Wei_2023_Pain.Res.Manag_2023_9058774
PubMedSearch : Wei_2023_Pain.Res.Manag_2023_9058774
PubMedID: 36819745

Title : The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes - Wu_2023_Nat.Commun_14_3132
Author(s) : Wu SA , Shen C , Wei X , Zhang X , Wang S , Chen X , Torres M , Lu Y , Lin LL , Wang HH , Hunter AH , Fang D , Sun S , Ivanova MI , Lin Y , Qi L
Ref : Nat Commun , 14 :3132 , 2023
Abstract : Endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-phagy are two principal degradative mechanisms for ER proteins and aggregates, respectively; however, the crosstalk between these two pathways under physiological settings remains unexplored. Using adipocytes as a model system, here we report that SEL1L-HRD1 protein complex of ERAD degrades misfolded ER proteins and limits ER-phagy and that, only when SEL1L-HRD1 ERAD is impaired, the ER becomes fragmented and cleared by ER-phagy. When both are compromised, ER fragments containing misfolded proteins spatially coalesce into a distinct architecture termed Coalescence of ER Fragments (CERFs), consisted of lipoprotein lipase (LPL, a key lipolytic enzyme and an endogenous SEL1L-HRD1 substrate) and certain ER chaperones. CERFs enlarge and become increasingly insoluble with age. Finally, we reconstitute the CERFs through LPL and BiP phase separation in vitro, a process influenced by both redox environment and C-terminal tryptophan loop of LPL. Hence, our findings demonstrate a sequence of events centered around SEL1L-HRD1 ERAD to dispose of misfolded proteins in the ER of adipocytes, highlighting the profound cellular adaptability to misfolded proteins in the ER in vivo.
ESTHER : Wu_2023_Nat.Commun_14_3132
PubMedSearch : Wu_2023_Nat.Commun_14_3132
PubMedID: 37253728

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

Title : Neurexin and neuroligins jointly regulate synaptic degeneration at the Drosophila neuromuscular junction based on TEM studies - Guangming_2023_Front.Cell.Neurosci_17_1257347
Author(s) : Guangming G , Mei C , Qinfeng Y , Xiang G , Chenchen Z , Qingyuan S , Wei X , Junhua G
Ref : Front Cell Neurosci , 17 :1257347 , 2023
Abstract : The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx(273), Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx(83);dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration.
ESTHER : Guangming_2023_Front.Cell.Neurosci_17_1257347
PubMedSearch : Guangming_2023_Front.Cell.Neurosci_17_1257347
PubMedID: 38026694

Title : Genome-Wide Identification and Analysis of Lipases in Fig Wasps (Chalcidoidea, Hymenoptera) - Wei_2022_Insects_13_
Author(s) : Wei X , Li J , Wang T , Xiao J , Huang D
Ref : Insects , 13 : , 2022
Abstract : Lipases are the main enzymes involved in lipid metabolism. However, the characteristics of lipases in insects were scarcely investigated. Here, we screened the recently sequenced genomes of 12 fig wasp species consisting of seven pollinator fig wasps (PFWs) and five non-pollinating fig wasps (NPFWs) for the six major lipase gene families. In total, 481 lipase genes were identified, and the two most numerous families were the neutral and acid lipases. Tandem duplication accounted for the expansion of the gene family. NPFWs had significantly more lipases than PFWs. A significant gene family contraction occurred in the clade of PFWs. The difference of lipases between NPFWs and PFWs might contribute to their distinction in life histories and feeding regimes. Phylogenetic analysis showed that the lipase genes of each fig wasp species was almost equally distributed in each clade, indicating that the lipase genes were conserved. The gene structures were similar within each clade, while they were different among clades. Most of the neutral and acid lipases were signal peptides and located extracellularly. The pathways of lipases involved were predicted. This genome-wide study provides a systematic analysis of lipase gene families in 12 hymenopteran insects and further insights towards understanding the potential functions of lipases.
ESTHER : Wei_2022_Insects_13_
PubMedSearch : Wei_2022_Insects_13_
PubMedID: 35621743

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

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

Title : Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense - Hu_2022_J.Org.Chem__
Author(s) : Hu XY , Zhu SJ , Meng XH , Yu HF , Liu X , Zhang LY , Wei Y , Lei CW , Wei X , Zhou Y
Ref : J Org Chem , : , 2022
Abstract : Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (+/-)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.
ESTHER : Hu_2022_J.Org.Chem__
PubMedSearch : Hu_2022_J.Org.Chem__
PubMedID: 36354352

Title : Structurally diverse steroids from an endophyte of Aspergillus tennesseensis 1022LEF attenuates LPS-induced inflammatory response through the cholinergic anti-inflammatory pathway - Su_2022_Chem.Biol.Interact_362_109998
Author(s) : Su JC , Pan Q , Xu X , Wei X , Lei X , Zhang P
Ref : Chemico-Biological Interactions , 362 :109998 , 2022
Abstract : The emerging cholinergic anti-inflammatory pathway plays a key role in regulating inflammation. Steroids are known to possess remarkable anti-inflammatory activity. However, the links between steroids and the cholinergic anti-inflammatory pathway remain unidentified. In this study, eight steroids (1-8) featuring five different structural types were characterized from an endophytic fungus Aspergillus tennesseensis 1022LEF, and were subsequently evaluated for their potential role in regulating the cholinergic anti-inflammatory pathway. As a result, compound 8, with the best potency, showed remarkable anti-inflammatory activity at the nanomolar to low micromolar level. Further pharmacological study indicated that 8 notably increased alpha7nAchR expression and inhibited the activation of its down-stream signaling pathways. Collectively, the present study not only highlighted the potential correlation between steroids and the cholinergic anti-inflammatory pathway, but also identified 8 as a dual-functional modulator via directly inhibition to acetylcholinesterase as well as up-regulation of alpha7nAchR expression.
ESTHER : Su_2022_Chem.Biol.Interact_362_109998
PubMedSearch : Su_2022_Chem.Biol.Interact_362_109998
PubMedID: 35649461

Title : Directed evolution of feruloyl esterase from Lactobacillus acidophilus and its application for ferulic acid production - Liu_2021_Bioresour.Technol_332_124967
Author(s) : Liu S , Soomro L , Wei X , Yuan X , Gu T , Li Z , Wang Y , Bao Y , Wang F , Wen B , Xin F
Ref : Bioresour Technol , 332 :124967 , 2021
Abstract : Producing ferulic acid (FA) from the natural substrate with feruloyl esterase is promising in industries, screening and engineering new enzymes with high efficiency to increase the FA yield is of great concern. Here, the feruloyl esterase of Lactobacillus acidophilus (FAELac) was heterologous expressed and the FAELac with different oligomerization states was separated. Interestingly, the activity of dimer was 37-fold higher than high-polymer. To further enhance the efficiency of FAELac, eight mutants were generated based on the simulated structure, of which Q198A, Q134T enhanced the catalytic efficiency by 5.4- and 4.3-fold in comparison with the wild type. Moreover, higher yields of FA (2.21, 6.60, and 1.67 mg/g substrate, respectively) were released by the mutants from de-starched wheat bran, insoluble wheat arabinoxylan, and steam-exploded corn stover. These results indicated that improving the purification process, engineering new FAELac and substrates bias studies hold great potential for increasing FA production yield.
ESTHER : Liu_2021_Bioresour.Technol_332_124967
PubMedSearch : Liu_2021_Bioresour.Technol_332_124967
PubMedID: 33845316
Gene_locus related to this paper: lacac-q5fi30

Title : A reverse catalytic triad Asp containing loop shaping a wide substrate binding pocket of a feruloyl esterase from Lactobacillus plantarum - Zhang_2021_Int.J.Biol.Macromol_184_92
Author(s) : Zhang H , Wen B , Liu Y , Du G , Wei X , Khandaker S , Zhou H , Fan S , Wang F , Wang Y , Xin F
Ref : Int J Biol Macromol , 184 :92 , 2021
Abstract : Feruloyl esterase is an indispensable biocatalyst in food processing, pesticide and pharmaceutical industries, catalyzing the cleavage of the ester bond cross-linked between the polysaccharide side chain of hemicellulose and ferulic acid in plant cell walls. LP_0796 from Lactobacillus plantarum was identified as a feruloyl esterase that may have potential applications in the food industry, but the lack of the substrate recognition and catalytic mechanisms limits its application. Here, LP_0796 showed the highest activity towards methyl caffeate at pH 6.6 and 40 degreesC. The crystal structure of LP_0796 was determined at 2.5 A resolution and featured a catalytic triad Asp195-containing loop facing the opposite direction, thus forming a wider substrate binding pocket. Molecular docking simulation and site-directed mutagenesis studies further demonstrated that in addition to the catalytic triad (Ser94, Asp195, His225), Arg125 and Val128 played essential roles in the function of the active site. Our data also showed that Asp mutation of Ala23 and Ile198 increased the catalytic efficiency to 4- and 5-fold, respectively. Collectively, this work provided a better understanding of the substrate recognition and catalytic mechanisms of LP_0796 and may facilitate the future protein design of this important feruloyl esterase.
ESTHER : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedSearch : Zhang_2021_Int.J.Biol.Macromol_184_92
PubMedID: 34116094
Gene_locus related to this paper: lacpl-LP.0796

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

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

Title : Liamocins biosynthesis, its regulation in Aureobasidium spp., and their bioactivities - Kang_2021_Crit.Rev.Biotechnol__1
Author(s) : Kang XX , Jia SL , Wei X , Zhang M , Liu GL , Hu Z , Chi Z , Chi ZM
Ref : Critical Reviews in Biotechnology , :1 , 2021
Abstract : Liamocins synthesized by Aureobasidium spp. are glycolipids composed of a single mannitol or arabitol headgroup linked to either three, four or even six 3,5-dihydroxydecanoic ester tail-groups. The highest titer of liamocin achieved was over 40.0 g/L. The substrates for liamocins synthesis include glucose, sucrose, xylose, mannitol, and others. The Pks1 is responsible for the biosynthesis of the tail-group 3,5-dihydroxydecanoic acid, both mannitol dehydrogenase (MDH) and mannitol 1-phosphate 5-dehydrogenase (MPDH) catalyze the mannitol biosynthesis and the arabitol biosynthesis is controlled by arabitol dehydrogenase (ArDH). The ester bond formation between 3,5-dihydroxydecanoic acid and mannitol or arabitol is catalyzed by the esterase (Est1). Liamocin biosynthesis is regulated by the specific transcriptional activator (Gal1), global transcriptional activator (Msn2), various signaling pathways, acetyl-CoA flux while Pks1 activity is controlled by PPTase activity. The synthesized liamocins have high bioactivity against the pathogenic bacteria Streptococcus spp. and some kinds of cancer cells while Massoia lactone released liamocins which exhibited obvious antifungal and anticancer activities. Therefore, liamocins and Massoia lactone have many applications in various sectors of biotechnology.
ESTHER : Kang_2021_Crit.Rev.Biotechnol__1
PubMedSearch : Kang_2021_Crit.Rev.Biotechnol__1
PubMedID: 34154468

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

Title : Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease - Wei_2020_Circ.Res_127_249
Author(s) : Wei X , Adak S , Zayed M , Yin L , Feng C , Speck SL , Kathayat RS , Zhang Q , Dickinson BC , Semenkovich CF
Ref : Circulation Research , 127 :249 , 2020
Abstract : RATIONALE: Peripheral artery disease, common in metabolic syndrome and diabetes mellitus, responds poorly to medical interventions and is characterized by chronic vessel immaturity leading to lower extremity amputations. OBJECTIVE: To define the role of reversible palmitoylation at the endothelium in the maintenance of vascular maturity. METHODS AND RESULTS: Endothelial knockout of the depalmitoylation enzyme APT-1 (acyl-protein thioesterase 1) in mice impaired recovery from chronic hindlimb ischemia, a model of peripheral artery disease. Endothelial APT-1 deficiency decreased fibronectin processing, disrupted adherens junctions, and inhibited in vitro lumen formation. In an unbiased palmitoylation proteomic screen of endothelial cells from genetically modified mice, R-Ras, known to promote vessel maturation, was preferentially affected by APT-1 deficiency. R-Ras was validated as an APT-1 substrate, and click chemistry analyses demonstrated increased R-Ras palmitoylation in cells with APT-1 deficiency. APT-1 enzyme activity was decreased in endothelial cells from db/db mice. Hyperglycemia decreased APT-1 activity in human umbilical vein endothelial cells, due, in part, to altered acetylation of the APT-1 protein. Click chemistry analyses demonstrated increased R-Ras palmitoylation in the setting of hyperglycemia. Altered R-Ras trafficking, increased R-Ras palmitoylation, and fibronectin retention were found in diabetes mellitus models. Loss of R-Ras depalmitoylation caused by APT-1 deficiency constrained R-Ras membrane trafficking, as shown by total internal reflection fluorescence imaging. To rescue cellular phenotypes, we generated an R-Ras molecule with an inserted hydrophilic domain to circumvent membrane rigidity caused by defective palmitoylation turnover. This modification corrected R-Ras membrane trafficking, restored fibronectin processing, increased adherens junctions, and rescued defective lumen formation induced by APT-1 deficiency. CONCLUSIONS: These results suggest that endothelial depalmitoylation is regulated by the metabolic milieu and controls plasma membrane partitioning to maintain vascular homeostasis.
ESTHER : Wei_2020_Circ.Res_127_249
PubMedSearch : Wei_2020_Circ.Res_127_249
PubMedID: 32233916

Title : Discovery of Pyranoviolin A and Its Biosynthetic Gene Cluster in Aspergillus violaceofuscus - Wei_2020_Front.Microbiol_11_562063
Author(s) : Wei X , Chen L , Tang JW , Matsuda Y
Ref : Front Microbiol , 11 :562063 , 2020
Abstract : A new polyketide-non-ribosomal peptide hybrid molecule, pyranoviolin A (1), was discovered from the genome-sequenced fungus Aspergillus violaceofuscus CBS 115571 and was characterized to be the first pyranonigrin analog harboring the C-3 methoxy group. Examination of the genome sequence of the fungus identified a putative biosynthetic gene cluster of 1, which was designated as the pyv cluster. The gene deletion experiment of the polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) hybrid gene in the cluster confirmed the involvement of the pyv cluster in the pyranoviolin A biosynthesis. Finally, a plausible biosynthetic route leading to 1 has been proposed based on the bioinformatic analysis. Our study indicates that metabolite analysis of genome-sequenced microorganisms whose metabolites have been largely unexplored facilitates the discovery of new secondary metabolites along with their biosynthetic gene clusters.
ESTHER : Wei_2020_Front.Microbiol_11_562063
PubMedSearch : Wei_2020_Front.Microbiol_11_562063
PubMedID: 33117309
Gene_locus related to this paper: aspv1-pyvd

Title : Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing - Wu_2020_Anal.Chem__
Author(s) : Wu Y , Wu J , Jiao L , Xu W , Wang H , Wei X , Gu W , Ren G , Zhang N , Zhang Q , Huang L , Gu L , Zhu C
Ref : Analytical Chemistry , : , 2020
Abstract : Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the de-velopment of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple mod-el of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were syn-thesized through a salt-template strategy. With the densely distributed active Cu atoms (~5.1 wt%), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxi-dase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organo-phosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.
ESTHER : Wu_2020_Anal.Chem__
PubMedSearch : Wu_2020_Anal.Chem__
PubMedID: 31941278

Title : Biomarker Effects in Carassius auratus Exposure to Ofloxacin, Sulfamethoxazole and Ibuprofen - Yang_2019_Int.J.Environ.Res.Public.Health_16_
Author(s) : Yang X , Xu X , Wei X , Wan J , Zhang Y
Ref : Int J Environ Research Public Health , 16 : , 2019
Abstract : Ofloxacin, sulfamethoxazole and ibuprofen are three commonly used drugs which can be detected in aquatic environments. To assess their ecotoxicity, the effects of these three pharmaceuticals and their mixture on AChE (acetylcholinesterase) activity in the brain, and EROD (7-ethoxyresorufin-O-deethylase) and SOD (superoxide dismutase) activities in the liver of the freshwater crucian carp Carassius auratus were tested after exposure for 1, 2, 4 and 7 days. The results showed that treatments with 0.002(-)0.01 mg/L ofloxacin and 0.0008(-)0.004 mg/L sulfamethoxazole did not significantly change AChE, EROD and SOD activities. AChE activity was significantly inhibited in response to treatment with 0.05mg/L ofloxacin and 0.02mg/L sulfamethoxazole. All three biomarkers were induced significantly in treatments with ibuprofen and the mixture of the three pharmaceuticals at all the tested concentrations. The combined effects of ofloxacin, sulfamethoxazole and ibuprofen were compared with their isolated effects on the three biomarkers, and the results indicated that exposure to ibuprofen and the mixture at environmentally relevant concentrations could trigger adverse impacts on Carassius auratus. The hazard quotient (HQ) index also demonstrated a high risk for ibuprofen. Moreover, the present study showed that the effects of ofloxacin, sulfamethoxazole and ibuprofen might be additive on the physiological indices of Carassius auratus.
ESTHER : Yang_2019_Int.J.Environ.Res.Public.Health_16_
PubMedSearch : Yang_2019_Int.J.Environ.Res.Public.Health_16_
PubMedID: 31075982

Title : Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity - Wu_2019_Small__e1903108
Author(s) : Wu Y , Jiao L , Luo X , Xu W , Wei X , Wang H , Yan H , Gu W , Xu BZ , Du D , Lin Y , Zhu C
Ref : Small , :e1903108 , 2019
Abstract : Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2 (-) * radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.
ESTHER : Wu_2019_Small__e1903108
PubMedSearch : Wu_2019_Small__e1903108
PubMedID: 31482681

Title : Colletotryptins A-F, new dimeric tryptophol derivatives from the endophytic fungus Colletotrichum sp. SC1355 - Shao_2019_Fitoterapia__104465
Author(s) : Shao L , Wu P , Xu L , Xue J , Li H , Wei X
Ref : Fitoterapia , :104465 , 2019
Abstract : Seven new dimeric tryptophol-related alkaloids (1-4, 5a, 5b, and 6) were isolated from solid cultures of the endophytic fungus Colletotrichum sp. SC1355. The structures and absolute configurations of these compounds were determined by NMR spectroscopic analyses in combination with quantum chemical calculations of NMR (GIAO) shifts and ECD spectra. This is the first report of fungus-derived tryptophol dimers. In addition, the isolated compounds were evaluated for acetylcholinesterase (AchE) inhibitory activity.
ESTHER : Shao_2019_Fitoterapia__104465
PubMedSearch : Shao_2019_Fitoterapia__104465
PubMedID: 31870947

Title : Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing Aerobic Glycolysis and Epithelial-Mesenchymal Transition -
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 24 :2795 , 2018
PubMedID: 30184511
Gene_locus related to this paper: human-ABHD5

Title : Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage - Zou_2018_Aging.Dis_9_51
Author(s) : Zou J , Chen Z , Liang C , Fu Y , Wei X , Lu J , Pan M , Guo Y , Liao X , Xie H , Wu D , Li M , Liang L , Wang P , Wang Q
Ref : Aging Dis , 9 :51 , 2018
Abstract : Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.
ESTHER : Zou_2018_Aging.Dis_9_51
PubMedSearch : Zou_2018_Aging.Dis_9_51
PubMedID: 29392081

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 : miR27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker - Liu_2017_Oncol.Rep_37_3554
Author(s) : Liu W , Qian K , Wei X , Deng H , Zhao B , Chen Q , Zhang J , Liu H
Ref : Oncol Rep , 37 :3554 , 2017
Abstract : Accumulating evidence shows that mircroRNAs (miRNAs) play a crucial role in the development of colorectal cancer. In our previous study, FAM172A was demonstrated to be a novel tumor suppressor gene in CRC. Therefore, the aim of the present study was to identify whether the miR27a could be a diagnostic and prognostic marker and the regulatory relationships between miR27a and FAM172A. We demonstrated high levels of miR27a expression in tissues of patients with CRC as well as in CRC cell lines. There was a positive correlation between the levels of miR27a and the poor overall survival of patients with CRC. Furthermore, elevated levels of miR27a expression were associated with TNM stage and distant metastasis. Increased expression or inhibition of miR27a promoted or inhibited the metastasis of CRC cell lines, respectively. Moreover, we showed that miR27a directly targets the 3'-untranslated region of FAM172A mRNA by using a dual-luciferase assay. Increased or decreased expression of FAM172A expression was observed when miR27a expression was inhibited or elevated in the CRC cells, respectively. In summary, our study showed that miR27a expression is a diagnostic and prognostic marker and correlates with overall survival of patients with CRC. Therefore, it may be a therapeutic approach for preventing metastasis of CRC to inhibit expression of miR27a or increase expression of FAM172A.
ESTHER : Liu_2017_Oncol.Rep_37_3554
PubMedSearch : Liu_2017_Oncol.Rep_37_3554
PubMedID: 28440497
Gene_locus related to this paper: human-f172a

Title : Study of acetylcholinesterase activity and apoptosis in SH-SY5Y cells and mice exposed to ethanol - Sun_2017_Toxicology_384_33
Author(s) : Sun W , Chen L , Zheng W , Wei X , Wu W , Duysen EG , Jiang W
Ref : Toxicology , 384 :33 , 2017
Abstract : Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol. For this purpose, in vitro and in vivo experiments were performed. AChE activity was quantified by spectrophotometry and apoptosis by flow cytometer in SH-SY5Y cells exposed to ethanol. The results showed that cells treated with 500mM ethanol for 24h had a 9-fold increase in apoptotic cells and a 6-fold increase in AChE activity compared with controls. Mice exposed acutely to 200mul of 20% ethanol daily on days 1-4 had elevated AChE activity in plasma on days 3-7. On day 4, plasma AChE activity was 2.4-fold higher than pretreatment activity. More apoptotic cells were found in the brains of treated mice compared to controls. Cells in brain sections that were positive in the TUNEL assay stained for AChE activity. In conclusion, AChE activity and apoptosis were induced in SH-SY5Y cells and mice treated with ethanol, which may indicate that increased AChE may related to apoptosis induced by ethanol. Unusually high AChE activity may be an effect marker of exposure to ethanol. The relationship between AChE and apoptosis might represent a novel mechanism of ethanol-associated neuronal injury.
ESTHER : Sun_2017_Toxicology_384_33
PubMedSearch : Sun_2017_Toxicology_384_33
PubMedID: 28427893

Title : Sunitinib, a Clinically Used Anticancer Drug, Is a Potent AChE Inhibitor and Attenuates Cognitive Impairments in Mice - Huang_2016_ACS.Chem.Neurosci_7_1047
Author(s) : Huang L , Lin J , Xiang S , Zhao K , Yu J , Zheng J , Xu D , Mak SH , Hu S , Nirasha S , Wang C , Chen X , Zhang J , Xu S , Wei X , Zhang Z , Zhou D , Zhou W , Cui W , Han YF , Hu Z , Wang Q
Ref : ACS Chem Neurosci , 7 :1047 , 2016
Abstract : Sunitinib, a tyrosine kinase inhibitor, is clinically used for the treatment of cancer. In this study, we found for the first time that sunitinib inhibits acetylcholinesterase (AChE) at submicromolar concentrations in vitro. In addition, sunitinib dramatically decreased the hippocampal and cortical activity of AChE in a time-dependent manner in mice. Molecular docking analysis further demonstrates that sunitinib might interact with both the catalytic anion and peripheral anionic sites within AChE, which is in accordance with enzymatic activity results showing that sunitinib inhibits AChE in a mixed pattern. Most importantly, we evaluated the effects of sunitinib on scopolamine-induced cognitive impairments in mice by using novel object recognition and Morris water maze tests. Surprisingly, sunitinib could attenuate cognitive impairments to a similar extent as donepezil, a marketed AChE inhibitor used for the treatment of Alzheimer's disease. In summary, our results have shown that sunitinib could potently inhibit AChE and attenuate cognitive impairments in mice.
ESTHER : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedSearch : Huang_2016_ACS.Chem.Neurosci_7_1047
PubMedID: 27046396

Title : Surrogate markers of the kidney and liver in the assessment of gestational diabetes mellitus and fetal outcome - Liu_2015_J.Clin.Diagn.Res_9_OC14
Author(s) : Liu H , Shao-Gang M , Liang C , Feng B , Wei X
Ref : J Clin Diagn Res , 9 :OC14 , 2015
Abstract : INTRODUCTION: To investigate whether serum levels of butyrylcho-linesterase activity, cystatin C, and pre-albumin has the potential value as gamma-glutamyl transferase in reflecting gestational diabetes mellitus and its fetal outcome. MATERIALS AND
METHODS: Seventy-six gestational diabetes mellitus women and 76 pregnancies with normal glucose tolerance in the second trimester were enrolled. Maternal serum parameters of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, and pre-albumin were detected and evaluated. The pregnant complications and fetal outcome were also evaluated.
RESULTS: Levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C, pre-albumin and glycemic variables were higher in the gestational diabetes mellitus patients than in the controls. Levels of butyrylcholinesterase activity were significantly correlated to the levels of fasting plasma glucose, cystatin C, and gamma- glutamyl transferase (p < 0.05) in the gestational diabetes mellitus group. There were statistical differences in cases of preterm delivery, preeclampsia and postpartum hemorrhage. Higher levels of gamma-glutamyl transferase and pre-albumin were risk markers for gestational diabetes mellitus (p < 0.05). The diagnosis curve demonstrated that gamma-glutamyl transferase had a significant advantage over other markers (p < 0.001) but no significance compared with pre-albumin (p = 0.096). None of the detected markers showed predictive value for fetal outcome. CONCLUSION: Serum levels of butyrylcholinesterase activity, gamma-glutamyl transferase, cystatin C and pre-albumin were correlated with gestational diabetes mellitus status but not with the fetal outcome. Pre-albumin can be equivalent as gamma-glutamyl transferase in reflecting the presence of gestational diabetes mellitus.
ESTHER : Liu_2015_J.Clin.Diagn.Res_9_OC14
PubMedSearch : Liu_2015_J.Clin.Diagn.Res_9_OC14
PubMedID: 25738017

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

Title : Efficient immobilization of acetylcholinesterase onto amino functionalized carbon nanotubes for the fabrication of high sensitive organophosphorus pesticides biosensors - Yu_2015_Biosens.Bioelectron_68C_288
Author(s) : Yu G , Wu W , Zhao Q , Wei X , Lu Q
Ref : Biosensors & Bioelectronics , 68C :288 , 2015
Abstract : This work introduced an efficient immobilization of acetylcholinesterase (AChE) onto amino functionalized carbon nanotubes (CNT-NH2), in order to fabricate high sensitive and practical organophosphorus pesticide (OPs) biosensors. Compared with the pristine, -COOH and -OH decorated CNTs, there were larger amount of enzymes adsorbed on the surface of CNT-NH2 with a favorable orientation and the best amperometric response was obtained on the AChE/CNT-NH2/GC electrode. Furthermore, the biosensor modified with CNT-NH2 showed a high affinity to acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with an apparent Michaelis-Menten constant (Km) value of 67.4microM. Using paraoxon as a model compound, wide linear ranges from 0.2nM to 1nM and 1nM to 30nM, and a low detection limit of 0.08nM were obtained with satisfactory reproducibility and stability. Moreover, the biosensor had also been successfully employed for the determination of low concentrations of pesticides in real vegetable samples. This method could be extended to other functionalized nano-materials for their application in constructing biosensors.
ESTHER : Yu_2015_Biosens.Bioelectron_68C_288
PubMedSearch : Yu_2015_Biosens.Bioelectron_68C_288
PubMedID: 25594160

Title : Contribution of carboxylesterase and cytochrome p450 to the bioactivation and detoxification of isocarbophos and its enantiomers in human liver microsomes - Zhuang_2014_Toxicol.Sci_140_40
Author(s) : Zhuang XM , Wei X , Tan Y , Xiao WB , Yang HY , Xie JW , Lu C , Li H
Ref : Toxicol Sci , 140 :40 , 2014
Abstract : Organophosphorus pesticides are the most widely used pesticides in modern agricultural systems to ensure good harvests. Isocarbophos (ICP), with a potent acetylcholinesterase inhibitory effect is widely utilized to control a variety of leaf-eating and soil insects. However, the characteristics of the bioactivation and detoxification of ICP in humans remain unclear. In this study, the oxidative metabolism, esterase hydrolysis, and chiral inversion of ICP in human liver microsomes (HLMs) were investigated with the aid of a stereoselective LC/MS/MS method. The depletion of ICP in HLMs was faster in the absence of carboxylesterase inhibitor (BNPP) than in the presence of NADPH and BNPP, with t1/2 of 5.2 and 90 min, respectively. Carboxylesterase was found to be responsible for the hydrolysis of ICP, the major metabolic pathway. CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19 were all involved in the secondary metabolism pathway of desulfuration of ICP. Flavin-containing monooxygenase (FMO) did not contribute to the clearance of ICP. The hydrolysis and desulfuration of (+/-)ICP, (+)ICP, and (-)ICP in HLMs follow Michaelis-Menten kinetics. Individual enantiomers of ICP and its oxidative desulfuration metabolite isocarbophos oxon (ICPO) were found to be inhibitors of acetylcholinesterases at different extents. For example, (+/-)ICPO is more potent than ICP (IC50 0.031muM vs. 192muM), whereas (+)ICPO is more potent than (-)ICPO (IC50 0.017muM vs. 1.55muM). Given the finding of rapid hydrolysis of ICP and low abundance of oxidative metabolites presence in human liver, the current study highlights that human liver has a greater capacity for detoxification of ICP.
ESTHER : Zhuang_2014_Toxicol.Sci_140_40
PubMedSearch : Zhuang_2014_Toxicol.Sci_140_40
PubMedID: 24752505

Title : Elevated 14,15- epoxyeicosatrienoic acid by increasing of cytochrome P450 2C8, 2C9 and 2J2 and decreasing of soluble epoxide hydrolase associated with aggressiveness of human breast cancer - Wei_2014_BMC.Cancer_14_841
Author(s) : Wei X , Zhang D , Dou X , Niu N , Huang W , Bai J , Zhang G
Ref : BMC Cancer , 14 :841 , 2014
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid by cytochrome P450 (CYP) and metabolized by soluble epoxide hydrolase (sEH). EETs have been associated with cardiovascular disease, diabetes and several cancer diseases. However, the distribution in tissue and role of CYP2C8, 2C9, 2J2 and sEH in human breast carcinogenesis remains uncertain. METHODS: Breast cancer (BC) and adjacent noncancerous tissue was obtained from 40 breast cancer patients in the Chaoshan region in China from 2010 to 2012. The level of 14,15-EET/14,15-DHET in BC patients was detected by ELISA; the expression and distribution of CYP2C8, 2C9, 2J2 and sEH was determined by quantitative RT-PCR and immunohistochemical staining; and cell proliferation and migration was analyzed by MTT and transwell assays, respectively. RESULTS: The median 14,15-EET and 14,15-EET/DHET level was 2.5-fold higher in BC than noncancerous tissue. The mRNA and protein levels of CYP2C8, 2C9 and 2J2 were higher, and sEH was lower in BC than noncancerous tissue. Furthermore, CYP2C8 and 2C9 protein levels positively correlated with Ki67 status, and CYP2J2 levels positively correlated with histological grade and tumor size. The sEH protein level negatively correlated with tumor size, estrogen receptors and Ki67. In MDA-MB-231 cells, siRNA knockdown of CYP2C8, 2C9 or 2J2 reduced cell proliferation, by 24.5%, 29.13%, or 22.7% and decreased cell migration by 49.1%, 44.9%, and 50.9%, respectively. Similarly, with adenovirus overexpression of sEH, both cell proliferation and migration rates were reduced by 31.4% and 45.8%, respectively. CONCLUSIONS: The present study shows that elevated EET levels in BC tissues are associated with upregulation of CYP2C8, 2C9, and 2J2, and downregulation of sEH, and are also associated with aggressive cell behavior in BC patients.
ESTHER : Wei_2014_BMC.Cancer_14_841
PubMedSearch : Wei_2014_BMC.Cancer_14_841
PubMedID: 25406731

Title : Simvastatin reverses the downregulation of M1\/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory - Wang_2014_Neurosci_267_57
Author(s) : Wang Q , Wei X , Gao H , Li J , Liao J , Liu X , Qin B , Yu Y , Deng C , Tang B , Huang XF
Ref : Neuroscience , 267 :57 , 2014
Abstract : BACKGROUND: It is believed that muscarinic M1/4 receptors are closely correlated to the dopaminergic system and are strongly involved in the pathogenesis of Parkinson's disease (PD). In addition to regulating lipid metabolism and protection from stroke, statins have been used to regulate the declined cognition. We aimed to explore the regional changes in M1/4 receptors in the 6-hydroxydopamine (6-OHDA)-lesioned rat brain.
METHODS: PD rat model was set up by injecting 6-OHDA into the unilateral medial forebrain bundle; while simvastatin (10mg/kg/day) or saline was orally administrated for 3weeks, respectively. Long-term memory was measured using the Morris water maze. [(3)H]pirenzepine binding autoradiography was applied to investigate the alterations of M1/4 receptors in the PD rat brains.
RESULTS: 6-OHDA induced long-term memory deficits along with downregulation of M1/4 receptors in the hippocampus, the medial amygdala, the posteromedial cortical and the piriform cortex; simvastatin administration significantly ameliorated the impaired memory and reversed the downregulation of M1/4 receptors in the examined brain regions. Profound positive correlations were verified between the decline in long-term memory activity and the restoration of M1/4 receptors in different brain regions after simvastatin treatment. CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence that M1/4 receptor modulation after simvastatin administration did, at least partially, contribute to the improvement in the long-term memory in 6-OHDA-induced PD rats. These results provide a possible mechanism for simvastatin treatment in psycho-neurological diseases such as PD via M1/4 receptors.
ESTHER : Wang_2014_Neurosci_267_57
PubMedSearch : Wang_2014_Neurosci_267_57
PubMedID: 24613723

Title : Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition - Ou_2014_Cell.Rep_9_1798
Author(s) : Ou J , Miao H , Ma Y , Guo F , Deng J , Wei X , Zhou J , Xie G , Shi H , Xue B , Liang H , Yu L
Ref : Cell Rep , 9 :1798 , 2014
Abstract : How cancer cells shift metabolism to aerobic glycolysis is largely unknown. Here, we show that deficiency of alpha/beta-hydrolase domain-containing 5 (Abhd5), an intracellular lipolytic activator that is also known as comparative gene identification 58 (CGI-58), promotes this metabolic shift and enhances malignancies of colorectal carcinomas (CRCs). Silencing of Abhd5 in normal fibroblasts induces malignant transformation. Intestine-specific knockout of Abhd5 in Apc(Min/+) mice robustly increases tumorigenesis and malignant transformation of adenomatous polyps. In colon cancer cells, Abhd5 deficiency induces epithelial-mesenchymal transition by suppressing the AMPKalpha-p53 pathway, which is attributable to increased aerobic glycolysis. In human CRCs, Abhd5 expression falls substantially and correlates negatively with malignant features. Our findings link Abhd5 to CRC pathogenesis and suggest that cancer cells develop aerobic glycolysis by suppressing Abhd5-mediated intracellular lipolysis.
ESTHER : Ou_2014_Cell.Rep_9_1798
PubMedSearch : Ou_2014_Cell.Rep_9_1798
PubMedID: 25482557
Gene_locus related to this paper: human-ABHD5

Title : Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens - Liu_2013_PLoS.One_8_e55185
Author(s) : Liu G , Zhang L , Wei X , Zou G , Qin Y , Ma L , Li J , Zheng H , Wang S , Wang C , Xun L , Zhao GP , Zhou Z , Qu Y
Ref : PLoS ONE , 8 :e55185 , 2013
Abstract : Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.
ESTHER : Liu_2013_PLoS.One_8_e55185
PubMedSearch : Liu_2013_PLoS.One_8_e55185
PubMedID: 23383313
Gene_locus related to this paper: peno1-s7zjd1 , peno1-s8aym9 , peno1-s7zcd7 , peno1-s8aui7 , peno1-s7zba9 , peno1-s7z7w2 , peno1-s7zkn6 , peno1-s8ak78 , peno1-s7z721 , peno1-s8ajn6 , peno1-s7zqw4 , peno1-s8bba0 , peno1-s8b4w2 , peno1-s7zta4 , peno1-s8a1h3 , peno1-s8aiq5 , peno1-s8ba66 , peno1-s7zxp5 , penox-poxo

Title : Association of LIPC and advanced age-related macular degeneration - Lee_2013_Eye.(Lond)_27_265
Author(s) : Lee J , Zeng J , Hughes G , Chen Y , Grob S , Zhao L , Lee C , Krupa M , Quach J , Luo J , Wei X , Zhang X , Zhu J , Duan Y , Ferreyra H , Goldbaum M , Haw W , Shaw PX , Tang L , Zhang K
Ref : Eye (Lond) , 27 :265 , 2013
Abstract : PURPOSE: To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts.
METHODS: A discovery cohort of 1626 patients with advanced AMD and 859 normal controls and a replication cohort of 2159 cases and 1150 controls were genotyped for two single-nucleotide polymorphisms (SNPs) in the promoter region of LIPC. The associations between the SNPs and AMD were examined by chi(2) tests.
RESULTS: In the discovery cohort, rs493258 and rs10468017 were both associated with advanced AMD (P=9.63E-3 and P=0.048, respectively). The association was corroborated in the replication cohort (P=4.48E-03 for rs493258 and P=0.015 for rs10468017). Combined analysis resulted in even more significant associations (P=1.21E-04 for rs493258 and P=1.67E-03 for rs10468017). CONCLUSION: The LIPC promoter variants rs493258 and rs10468017 were associated with advanced AMD in two independent Caucasian populations, confirming that LIPC polymorphisms may be a genetic risk factor for AMD in the Caucasian population.
ESTHER : Lee_2013_Eye.(Lond)_27_265
PubMedSearch : Lee_2013_Eye.(Lond)_27_265
PubMedID: 23348725

Title : Cloning, expression and characterization of a new enantioselective esterase from a marine bacterium Pelagibacterium halotolerans B2T - Wei_2013_J.Mol.Catal.B.Enzym_97_270
Author(s) : Wei X , Jiang X , Ye L , Yuan S , Chen Z , Wu M , Yu H
Ref : J Mol Catal B Enzym , 97 :270 , 2013
Abstract : An esterase, designated as PE8 (219 aa, 23.19 kDa), was cloned from a marine bacterium Pelagibacterium halotolerans B2T and overexpressed in Escherichia coli Rosetta, resulting an active, soluble protein which constituted 23.1% of the total cell protein content. Phylogenetic analysis of the protein showed it was a new member of family VI lipolytic enzymes. Biochemical characterization analysis showed that PE8 preferred short chain p-nitrophenyl esters (C2-C6), exhibited maximum activity toward p-nitrophenyl acetate, and was not a metalloenzyme. PE8 was an alkaline esterase with an optimal pH of 9.5 and an optimal temperature of 45 C toward p-nitrophenyl acetate. Furthermore, it was found that PE8 exhibited activity and enantioselectivity in the synthesis of methyl (R)-3-(4-fluorophenyl)glutarate ((R)-3-MFG) from the prochiral dimethyl 3-(4-fluorophenyl)glutarate (3-DFG). (R)-3-MFG was obtained in 71.6% ee and 73.2% yield after 36 h reaction under optimized conditions (0.6 M phosphate buffer (pH 8.0) containing 17.5% 1,4-dioxane under 30C). In addition, PE8 was tolerant to extremely strong basic and high ionic strength solutions as it exhibited high activity even at pH 11.0 in 1 M phosphate buffer. Given its highly soluble expression, alkalitolerance, halotolerance and enantioselectivity, PE8 could be a promising candidate for the production of (R)-3-MFG in industry. The results also demonstrate the potential of the marine environment as a source of useful biocatalysts.
ESTHER : Wei_2013_J.Mol.Catal.B.Enzym_97_270
PubMedSearch : Wei_2013_J.Mol.Catal.B.Enzym_97_270
Gene_locus related to this paper: pelhb-g4rfi7

Title : Examining the interactome of huperzine A by magnetic biopanning - Guo_2012_PLoS.One_7_e37098
Author(s) : Guo W , Liu S , Peng J , Wei X , Sun Y , Qiu Y , Gao G , Wang P , Xu Y
Ref : PLoS ONE , 7 :e37098 , 2012
Abstract : Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules.
ESTHER : Guo_2012_PLoS.One_7_e37098
PubMedSearch : Guo_2012_PLoS.One_7_e37098
PubMedID: 22615909

Title : Genomic analysis and temperature-dependent transcriptome profiles of the rhizosphere originating strain Pseudomonas aeruginosa M18 - Wu_2011_BMC.Genomics_12_438
Author(s) : Wu DQ , Ye J , Ou HY , Wei X , Huang X , He YW , Xu Y
Ref : BMC Genomics , 12 :438 , 2011
Abstract : BACKGROUND: Our previously published reports have described an effective biocontrol agent named Pseudomonas sp. M18 as its 16S rDNA sequence and several regulator genes share homologous sequences with those of P. aeruginosa, but there are several unusual phenotypic features. This study aims to explore its strain specific genomic features and gene expression patterns at different temperatures.
RESULTS: The complete M18 genome is composed of a single chromosome of 6,327,754 base pairs containing 5684 open reading frames. Seven genomic islands, including two novel prophages and five specific non-phage islands were identified besides the conserved P. aeruginosa core genome. Each prophage contains a putative chitinase coding gene, and the prophage II contains a capB gene encoding a putative cold stress protein. The non-phage genomic islands contain genes responsible for pyoluteorin biosynthesis, environmental substance degradation and type I and III restriction-modification systems. Compared with other P. aeruginosa strains, the fewest number (3) of insertion sequences and the most number (3) of clustered regularly interspaced short palindromic repeats in M18 genome may contribute to the relative genome stability. Although the M18 genome is most closely related to that of P. aeruginosa strain LESB58, the strain M18 is more susceptible to several antimicrobial agents and easier to be erased in a mouse acute lung infection model than the strain LESB58. The whole M18 transcriptomic analysis indicated that 10.6% of the expressed genes are temperature-dependent, with 22 genes up-regulated at 28 degrees C in three non-phage genomic islands and one prophage but none at 37 degrees C.
CONCLUSIONS: The P. aeruginosa strain M18 has evolved its specific genomic structures and temperature dependent expression patterns to meet the requirement of its fitness and competitiveness under selective pressures imposed on the strain in rhizosphere niche.
ESTHER : Wu_2011_BMC.Genomics_12_438
PubMedSearch : Wu_2011_BMC.Genomics_12_438
PubMedID: 21884571
Gene_locus related to this paper: pseae-PA1558 , pseae-PA2927 , pseae-PA2949 , pseae-PA3695 , pseae-PA5080 , pseae-q9i252

Title : Stage-dependent tolerance of the German cockroach, Blattella germanica for dichlorvos and propoxur - Qian_2010_J.Insect.Sci_10_201
Author(s) : Qian K , Wei X , Zeng X , Liu T , Gao X
Ref : J Insect Sci , 10 :201 , 2010
Abstract : tage-dependent dichlorvos and propoxur tolerance in a field population of the German cockroach, Blattella germanica Linnaeus (Blatodea: Blattellidae), was investigated in the laboratory using a topical application bioassay. The results showed the 6 week-old nymphs were more tolerant to dichlorvos and propoxur than the other ages tested. LD(5)(0) values of dichlorvos and propoxur for the 6 week-old nymphs were 2.003 microg per insect and 5.296 microg per insect, respectively. Tolerance ratios of 18.55-fold and 4.98-fold for LD(5)(0) were obtained from 6-week-old nymphs compared to 4 week-old nymphs. The specific activity of acetylcholinesterase (AChE) from 1 week-old nymphs was the highest among all tested developmental stages of nymphs and adult males and females. The specific activity of AChE decreased significantly with increasing age. The sensitivity of AChE to dichlorvos was the highest with a k(i) value of 3.12 x 10(4) mol(-)(1)min(-)(1) in the last nymphal stage of B. germanica (about 6 weeks-old). The AChE from 4 week-old nymphs was the most sensitive to propoxur, with the highest k(i) value being 2.63 x 10(5) mol(-)(1) min(-)(1). These results indicated that the different developmental stages and sexes of B. germanica affected the inhibition of AChE by dichlorvos and propoxur.
ESTHER : Qian_2010_J.Insect.Sci_10_201
PubMedSearch : Qian_2010_J.Insect.Sci_10_201
PubMedID: 21268698

Title : Whole-genome analysis of the ammonia-oxidizing bacterium, Nitrosomonas eutropha C91: implications for niche adaptation - Stein_2007_Environ.Microbiol_9_2993
Author(s) : Stein LY , Arp DJ , Berube PM , Chain PS , Hauser L , Jetten MS , Klotz MG , Larimer FW , Norton JM , Op den Camp HJ , Shin M , Wei X
Ref : Environ Microbiol , 9 :2993 , 2007
Abstract : Analysis of the structure and inventory of the genome of Nitrosomonas eutropha C91 revealed distinctive features that may explain the adaptation of N. eutropha-like bacteria to N-saturated ecosystems. Multiple gene-shuffling events are apparent, including mobilized and replicated transposition, as well as plasmid or phage integration events into the 2.66 Mbp chromosome and two plasmids (65 and 56 kbp) of N. eutropha C91. A 117 kbp genomic island encodes multiple genes for heavy metal resistance, including clusters for copper and mercury transport, which are absent from the genomes of other ammonia-oxidizing bacteria (AOB). Whereas the sequences of the two ammonia monooxygenase and three hydroxylamine oxidoreductase gene clusters in N. eutropha C91 are highly similar to those of Nitrosomonas europaea ATCC 19718, a break of synteny in the regions flanking these clusters in each genome is evident. Nitrosomonas eutropha C91 encodes four gene clusters for distinct classes of haem-copper oxidases, two of which are not found in other aerobic AOB. This diversity of terminal oxidases may explain the adaptation of N. eutropha to environments with variable O(2) concentrations and/or high concentrations of nitrogen oxides. As with N. europaea, the N. eutropha genome lacks genes for urease metabolism, likely disadvantaging nitrosomonads in low-nitrogen or acidic ecosystems. Taken together, this analysis revealed significant genomic variation between N. eutropha C91 and other AOB, even the closely related N. europaea, and several distinctive properties of the N. eutropha genome that are supportive of niche specialization.
ESTHER : Stein_2007_Environ.Microbiol_9_2993
PubMedSearch : Stein_2007_Environ.Microbiol_9_2993
PubMedID: 17991028
Gene_locus related to this paper: nitec-metx , nitec-q0ae77 , nitec-q0ag98 , nitec-q0ahg3 , nitec-q0aix1 , nitec-q0ajy0 , nitec-q0aea2 , nitec-q0aea3

Title : Complete genomic characterization of a pathogenic A.II strain of Francisella tularensis subspecies tularensis - Beckstrom-Sternberg_2007_PLoS.One_2_e947
Author(s) : Beckstrom-Sternberg SM , Auerbach RK , Godbole S , Pearson JV , Beckstrom-Sternberg JS , Deng Z , Munk C , Kubota K , Zhou Y , Bruce D , Noronha J , Scheuermann RH , Wang A , Wei X , Wang J , Hao J , Wagner DM , Brettin TS , Brown N , Gilna P , Keim PS
Ref : PLoS ONE , 2 :e947 , 2007
Abstract : Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I - A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between "WY96" and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis.
ESTHER : Beckstrom-Sternberg_2007_PLoS.One_2_e947
PubMedSearch : Beckstrom-Sternberg_2007_PLoS.One_2_e947
PubMedID: 17895988
Gene_locus related to this paper: fratt-q5ngu5

Title : Identification and synthesis of novel alkaloids from the root system of Nicotiana tabacum: affinity for neuronal nicotinic acetylcholine receptors - Wei_2005_Life.Sci_78_495
Author(s) : Wei X , Sumithran SP , Deaciuc AG , Burton HR , Bush LP , Dwoskin LP , Crooks PA
Ref : Life Sciences , 78 :495 , 2005
Abstract : A novel pyridine derivative, 3,5-bis-(1-methyl-pyrrolidin-2-yl)-pyridine, and a pair of diastereomers of 1,1'-dimethyl-[2,3']bipyrrolidinyl were isolated from the root of Nicotiana tabacum plants and identified as novel alkaloids by GC-MS analysis. The structures of these new alkaloids were confirmed by total synthesis. The affinities of these novel alkaloids, and other structurally related compounds for alpha4beta2*, alpha7* neuronal nicotinic acetylcholine receptors (nAChRs), and for nAChRs mediating nicotine-evoked dopamine release from rat striatum were also assessed. The results indicate that these compounds do not interact with alpha7* nAChRs, but inhibit [3H]nicotine binding to the alpha4beta2* nAChR subtype. The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum.
ESTHER : Wei_2005_Life.Sci_78_495
PubMedSearch : Wei_2005_Life.Sci_78_495
PubMedID: 16197964

Title : Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases - Wadkins_2005_J.Med.Chem_48_2906
Author(s) : Wadkins RM , Hyatt JL , Wei X , Yoon KJ , Wierdl M , Edwards CC , Morton CL , Obenauer JC , Damodaran K , Beroza P , Danks MK , Potter PM
Ref : Journal of Medicinal Chemistry , 48 :2906 , 2005
Abstract : Carboxylesterases (CE) are ubiquitous enzymes responsible for the metabolism of xenobiotics. Because the structural and amino acid homology among esterases of different classes, the identification of selective inhibitors of these proteins has proved problematic. Using Telik's target-related affinity profiling (TRAP) technology, we have identified a class of compounds based on benzil (1,2-diphenylethane-1,2-dione) that are potent CE inhibitors, with K(i) values in the low nanomolar range. Benzil and 30 analogues demonstrated selective inhibition of CEs, with no inhibitory activity toward human acetylcholinesterase or butyrylcholinesterase. Analysis of structurally related compounds indicated that the ethane-1,2-dione moiety was essential for enzyme inhibition and that potency was dependent on the presence of, and substitution within, the benzene ring. 3D-QSAR analyses of these benzil analogues for three different mammalian CEs demonstrated excellent correlations of observed versus predicted K(i) (r(2) > 0.91), with cross-validation coefficients (q(2)) of 0.9. Overall, these results suggest that selective inhibitors of CEs with potential for use in clinical applications can be designed.
ESTHER : Wadkins_2005_J.Med.Chem_48_2906
PubMedSearch : Wadkins_2005_J.Med.Chem_48_2906
PubMedID: 15828829

Title : The DNA sequence of the human X chromosome - Ross_2005_Nature_434_325
Author(s) : Ross MT , Grafham DV , Coffey AJ , Scherer S , McLay K , Muzny D , Platzer M , Howell GR , Burrows C , Bird CP , Frankish A , Lovell FL , Howe KL , Ashurst JL , Fulton RS , Sudbrak R , Wen G , Jones MC , Hurles ME , Andrews TD , Scott CE , Searle S , Ramser J , Whittaker A , Deadman R , Carter NP , Hunt SE , Chen R , Cree A , Gunaratne P , Havlak P , Hodgson A , Metzker ML , Richards S , Scott G , Steffen D , Sodergren E , Wheeler DA , Worley KC , Ainscough R , Ambrose KD , Ansari-Lari MA , Aradhya S , Ashwell RI , Babbage AK , Bagguley CL , Ballabio A , Banerjee R , Barker GE , Barlow KF , Barrett IP , Bates KN , Beare DM , Beasley H , Beasley O , Beck A , Bethel G , Blechschmidt K , Brady N , Bray-Allen S , Bridgeman AM , Brown AJ , Brown MJ , Bonnin D , Bruford EA , Buhay C , Burch P , Burford D , Burgess J , Burrill W , Burton J , Bye JM , Carder C , Carrel L , Chako J , Chapman JC , Chavez D , Chen E , Chen G , Chen Y , Chen Z , Chinault C , Ciccodicola A , Clark SY , Clarke G , Clee CM , Clegg S , Clerc-Blankenburg K , Clifford K , Cobley V , Cole CG , Conquer JS , Corby N , Connor RE , David R , Davies J , Davis C , Davis J , Delgado O , Deshazo D , Dhami P , Ding Y , Dinh H , Dodsworth S , Draper H , Dugan-Rocha S , Dunham A , Dunn M , Durbin KJ , Dutta I , Eades T , Ellwood M , Emery-Cohen A , Errington H , Evans KL , Faulkner L , Francis F , Frankland J , Fraser AE , Galgoczy P , Gilbert J , Gill R , Glockner G , Gregory SG , Gribble S , Griffiths C , Grocock R , Gu Y , Gwilliam R , Hamilton C , Hart EA , Hawes A , Heath PD , Heitmann K , Hennig S , Hernandez J , Hinzmann B , Ho S , Hoffs M , Howden PJ , Huckle EJ , Hume J , Hunt PJ , Hunt AR , Isherwood J , Jacob L , Johnson D , Jones S , de Jong PJ , Joseph SS , Keenan S , Kelly S , Kershaw JK , Khan Z , Kioschis P , Klages S , Knights AJ , Kosiura A , Kovar-Smith C , Laird GK , Langford C , Lawlor S , Leversha M , Lewis L , Liu W , Lloyd C , Lloyd DM , Loulseged H , Loveland JE , Lovell JD , Lozado R , Lu J , Lyne R , Ma J , Maheshwari M , Matthews LH , McDowall J , Mclaren S , McMurray A , Meidl P , Meitinger T , Milne S , Miner G , Mistry SL , Morgan M , Morris S , Muller I , Mullikin JC , Nguyen N , Nordsiek G , Nyakatura G , O'Dell CN , Okwuonu G , Palmer S , Pandian R , Parker D , Parrish J , Pasternak S , Patel D , Pearce AV , Pearson DM , Pelan SE , Perez L , Porter KM , Ramsey Y , Reichwald K , Rhodes S , Ridler KA , Schlessinger D , Schueler MG , Sehra HK , Shaw-Smith C , Shen H , Sheridan EM , Shownkeen R , Skuce CD , Smith ML , Sotheran EC , Steingruber HE , Steward CA , Storey R , Swann RM , Swarbreck D , Tabor PE , Taudien S , Taylor T , Teague B , Thomas K , Thorpe A , Timms K , Tracey A , Trevanion S , Tromans AC , d'Urso M , Verduzco D , Villasana D , Waldron L , Wall M , Wang Q , Warren J , Warry GL , Wei X , West A , Whitehead SL , Whiteley MN , Wilkinson JE , Willey DL , Williams G , Williams L , Williamson A , Williamson H , Wilming L , Woodmansey RL , Wray PW , Yen J , Zhang J , Zhou J , Zoghbi H , Zorilla S , Buck D , Reinhardt R , Poustka A , Rosenthal A , Lehrach H , Meindl A , Minx PJ , Hillier LW , Willard HF , Wilson RK , Waterston RH , Rice CM , Vaudin M , Coulson A , Nelson DL , Weinstock G , Sulston JE , Durbin R , Hubbard T , Gibbs RA , Beck S , Rogers J , Bentley DR
Ref : Nature , 434 :325 , 2005
Abstract : The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
ESTHER : Ross_2005_Nature_434_325
PubMedSearch : Ross_2005_Nature_434_325
PubMedID: 15772651
Gene_locus related to this paper: human-NLGN3 , human-NLGN4X