Lu X

References (76)

Title : Comprehensive analysis of the immune implication of EPHX4 gene in laryngeal squamous cell carcinoma - Shen_2024_Braz.J.Otorhinolaryngol_90_101411
Author(s) : Shen N , Gao G , Lu X , Jin J , Lin L , Qian M , Qin Y
Ref : Braz J Otorhinolaryngol , 90 :101411 , 2024
Abstract : OBJECTIVES: The role of Epoxide Hydrolase-4 (EPHX4), a member of epoxide hydrolase family, has not been investigated in cancer. The purpose of this article is to explore the application value of EPHX4 in laryngeal cancer and its relationship with immune infiltration. METHODS: We observed that EPHX4 expression and its survival assays in laryngeal cancer specimens based on The Cancer Genome Atlas (TCGA) cohorts. We also analyzed the correlation between immune cell infiltration levels and EPHX4 gene copy number in laryngeal cancer. Finally, we conducted in vitro assay to evaluate the functions of EPHX4 in laryngeal cancer cell line. RESULTS: EPHX4 is highly expressed in laryngeal cancer specimens and has a poor prognosis. EPHX4 related immune cell analysis showed that it participated in NK Natural killer cell mediated cytotoxicity. Finally, Cell experiments indicate that EPHX4 could promote laryngeal cancer cell line proliferation, colony formation and invasion. CONCLUSIONS: Our research results suggest that EPHX4 may be a potential immunotherapy target for laryngeal cancer. The nominated immune signature is a helpful and promising prognostic indicator in laryngeal cancer. LEVELS OF EVIDENCE: Level 3.
ESTHER : Shen_2024_Braz.J.Otorhinolaryngol_90_101411
PubMedSearch : Shen_2024_Braz.J.Otorhinolaryngol_90_101411
PubMedID: 38663041

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

Title : Discovery, Structure-Based Modification, In Vitro, In Vivo, and In Silico Exploration of m-Sulfamoyl Benzoamide Derivatives as Selective Butyrylcholinesterase Inhibitors for Treating Alzheimer's Disease - Lu_2024_ACS.Chem.Neurosci__
Author(s) : Lu X , Li Y , Guan Q , Yang H , Liu Y , Du C , Wang L , Wang Q , Pei Y , Wu L , Sun H , Chen Y
Ref : ACS Chem Neurosci , : , 2024
Abstract : For the potential therapy of Alzheimer's disease (AD), butyrylcholinesterase (BChE) has gradually gained worldwide interest in the progression of AD. This study used a pharmacophore-based virtual screening (VS) approach to identify Z32439948 as a new BChE inhibitor. Aiding by molecular docking and molecular dynamics, essential binding information was disclosed. Specifically, a subpocket was found and structure-guided design of a series of novel compounds was conducted. Derivatives were evaluated in vitro for cholinesterase inhibition and physicochemical properties (BBB, log P, and solubility). The investigation involved docking, molecular dynamics, enzyme kinetics, and surface plasmon resonance as well. The study highlighted compounds 27a (hBChE IC(50) = 0.078 +/- 0.03 microM) and (R)-37a (hBChE IC(50) = 0.005 +/- 0.001 microM) as the top-ranked BChE inhibitors. These compounds showed anti-inflammatory activity and no apparent cytotoxicity against the human neuroblastoma (SH-SY5Y) and mouse microglia (BV2) cell lines. The most active compounds exhibited the ability to improve cognition in both scopolamine- and Abeta(1-42) peptide-induced cognitive deficit models. They can be promising lead compounds with potential implications for treating the late stage of AD.
ESTHER : Lu_2024_ACS.Chem.Neurosci__
PubMedSearch : Lu_2024_ACS.Chem.Neurosci__
PubMedID: 38453668

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

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

Title : Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections - Xiao_2024_J.Control.Release_369_39
Author(s) : Xiao J , Yin M , Yang M , Ren J , Liu C , Lian J , Lu X , Jiang Y , Yao Y , Luo J
Ref : J Control Release , 369 :39 , 2024
Abstract : The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.
ESTHER : Xiao_2024_J.Control.Release_369_39
PubMedSearch : Xiao_2024_J.Control.Release_369_39
PubMedID: 38508523

Title : Discovery of 4-benzylpiperazinequinoline BChE inhibitor that suppresses neuroinflammation for the treatment of Alzheimer's disease - Chen_2024_Eur.J.Med.Chem_272_116463
Author(s) : Chen Y , Zhang W , Li Q , Xie H , Xing S , Lu X , Lyu W , Xiong B , Wang Y , Qu W , Liu W , Chi H , Zhang X , Feng F , Sun H
Ref : Eur Journal of Medicinal Chemistry , 272 :116463 , 2024
Abstract : Butyrylcholinesterase (BChE) has attracted wide interest as a promising target in Alzheimer's disease (AD) investigation. BChE is considered to play a compensable role of hydrolyzing acetylcholine (ACh), and its positive correlation with beta-amyloid (Abeta) deposition also promotes disease progression. Herein, we uncovered a selective potent BChE inhibitor S21-1011 (eqBChE IC(50) = 0.059 +/- 0.006 microM, hBChE IC(50) = 0.162 +/- 0.069 microM), which presented satisfactory druggability and therapeutic efficacy in AD models. In pharmacokinetics (PK) studies, S21-1011 showed excellent blood-brain barrier (BBB) permeability, metabolism stability and high oral-bioavailability. In pharmacodynamic (PD) studies, it protected neural cells from toxicity and inflammation stimulation in vitro. Besides, it also exerted anti-inflammatory effect and alleviated cognitive impairment in mice models induced by lipopolysaccharides (LPS) and Abeta. Generally, this compound has been confirmed to function as a neuroprotector and cognition improver in various AD pathology-like models. Therefore, S21-1011, a novel potent BChE inhibitor, could be considered as a potential anti-AD candidate worthy of more profound investigation.
ESTHER : Chen_2024_Eur.J.Med.Chem_272_116463
PubMedSearch : Chen_2024_Eur.J.Med.Chem_272_116463
PubMedID: 38704944

Title : In-situ growth of SnO(2) nanoparticles on Nb(2)CT(x) nanosheets as highly sensitive electrochemical sensing platform for organophosphorus pesticide detection - Guo_2023_Colloids.Surf.B.Biointerfaces_224_113238
Author(s) : Guo W , Liang L , Zhao Y , Zhao C , Lu X , Cao Y , Gao F
Ref : Colloids Surf B Biointerfaces , 224 :113238 , 2023
Abstract : In this study, the SnO(2)/Nb(2)CT(x) MXene nanocomposite containing 0D/2D interfaces was prepared by situ growth strategy of one-step hydrothermal method. A SnO(2)/Nb(2)CT(x) MXene based acetylcholinesterase (AChE) biosensor was constructed for pesticide detection. Highly conductive Nb(2)CT(x) MXene, acting as substrate material, restrained the agglomeration of nanoparticles (NPs) and accelerated electron migration due to the confinement effect and well-known accordion-like layered structure. In addition, SnO(2) anchored on both sides of the Nb(2)CT(x) MXene nanosheets effectively provided a large surface area, abundant surface groups and active sites, which preserved numbers of electrons at the interface of the heterojunction. The SnO(2)/Nb(2)CT(x) MXene hybrids with outstanding conductivity, good biocompatibility and structural stability were beneficial for AChE immobilization. Under the optimized conditions, as-fabricated electrochemical biosensor demonstrated superior performance with linear detection range of 5.1 x 10(-14) - 5.1 x 10(-7) M for chlorpyrifos, along with the limit of detection (LOD) down to 5.1 x 10(-14) M (calculated for 10% inhibition). Furthermore, it is highly expected that this biosensor can be applied for the detection of other organophosphorus pesticides in the environment, providing an effective nanoplatform in biosensing field.
ESTHER : Guo_2023_Colloids.Surf.B.Biointerfaces_224_113238
PubMedSearch : Guo_2023_Colloids.Surf.B.Biointerfaces_224_113238
PubMedID: 36870270

Title : Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients - Liu_2023_Front.Med.(Lausanne)_10_1175089
Author(s) : Liu J , Shao T , Chen H , Ma C , Lu X , Yang X , Song K , Wang L , Lei S , Wang D
Ref : Front Med (Lausanne) , 10 :1175089 , 2023
Abstract : AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.
ESTHER : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedSearch : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedID: 37502364

Title : Inside Out Computational Redesign of Cavities for Improving Thermostability and Catalytic Activity of Rhizomucor Miehei Lipase - Zhang_2023_Appl.Environ.Microbiol__e0217222
Author(s) : Zhang Z , Long M , Zheng N , Lu X , Zhu C , Osire T , Xia X
Ref : Applied Environmental Microbiology , :e0217222 , 2023
Abstract : Cavities are created by hydrophobic interactions between residue side chain atoms during the folding of enzymes. Redesigning cavities can improve the thermostability and catalytic activity of the enzyme; however, the synergistic effect of cavities remains unclear. In this study, Rhizomucor miehei lipase (RML) was used as a model to explore volume fluctuation and spatial distribution changes of the internal cavities, which could reveal the roles of internal cavities in the thermostability and catalytic activity. We present an inside out cavity engineering (CE) strategy based on computational techniques to explore how changes in the volumes and spatial distribution of cavities affect the thermostability and catalytic activity of the enzyme. We obtained 12 single-point mutants, among which the melting temperatures (T(m)) of 8 mutants showed an increase of more than 2 degreesC. Sixteen multipoint mutations were further designed by spatial distribution rearrangement of internal cavities. The T(m) of the most stable triple variant, with mutations including T21V (a change of T to V at position 21), S27A, and T198L (T21V/S27A/T198L), was elevated by 11.0 degreesC, together with a 28.7-fold increase in the half-life at 65 degreesC and a specific activity increase of 9.9-fold (up to 5,828 U mg(-1)), one of the highest lipase activities reported. The possible mechanism of decreased volumes and spatial rearrangement of the internal cavities improved the stability of the enzyme, optimizing the outer substrate tunnel to improve the catalytic efficiency. Overall, the inside out computational redesign of cavities method could help to deeply understand the effect of cavities on enzymatic stability and activity, which would be beneficial for protein engineering efforts to optimize natural enzymes. IMPORTANCE In the present study, R. miehei lipase, which is widely used in various industries, provides an opportunity to explore the effects of internal cavities on the thermostability and catalytic activity of enzymes. Here, we execute high hydrostatic pressure molecular dynamics (HP-MD) simulations to screen the critical internal cavity and reshape the internal cavities through site-directed mutation. We show that as the global internal cavity volume decreases, cavity rearrangement can improve the stability of the protein while optimizing the substrate channel to improve the catalytic efficiency. Our results provide significant insights into understanding the mechanism of action of the internal cavity. Our strategy is expected to be applied to other enzymes to promote increases in thermostability and catalytic activity.
ESTHER : Zhang_2023_Appl.Environ.Microbiol__e0217222
PubMedSearch : Zhang_2023_Appl.Environ.Microbiol__e0217222
PubMedID: 36912632

Title : Diketopyrrolopyrrole-based fluorescent probe for visualizing over-expressed carboxylesterase in fever via ratiometric imaging - Zhang_2023_Talanta_266_124971
Author(s) : Zhang B , Qin S , Wang N , Lu X , Jiao J , Zhang J , Zhao W
Ref : Talanta , 266 :124971 , 2023
Abstract : Fever is the result of inflammation and the innate self-defense response of organisms, can cause abnormal changes in the activity of many enzymes in organisms, including the important carboxylesterase (CE). Monitoring the activity changes of CE in vivo during a fever will help to understand heat-related pathological mechanisms. In this paper, we designed diketopyrrolopyrrole-based ratiometric fluorescent probes DPP-FBC-P and DPP-FBO-P containing alkyl chain and diethylene glycol monomethyl ether chain respective for detection of CE. Both probes could realized fast response to CE and displayed good selectivity and high sensitivity. Compared with DPP-FBO-P, DPP-FBC-P had better biocompatibility, larger signal to noise ratio (225-fold vs 125-fold) and lower detection limit (1.6 x 10(-5) U/mL vs 4.2 x 10(-5) U/mL). Moreover, the probe DPP-FBC-P had been successfully applied to image the endogenous CE in HepG2 cells and solid tumors, and also visualized the over expressed CE in fever cells. Most importantly, the changes of CE level in the liver of fever mice model induced by LPS were monitored with the assistance of DPP-FBC-Pvia dual channel ratio imaging for the first time. In addition, fluorescence color signal in solution was captured by smart phone, and the linear relationship between RGB ratio (G/R) and CE concentration was established. This work will provide a potential approach for investigating the physiological and pathological processes of heat related diseases.
ESTHER : Zhang_2023_Talanta_266_124971
PubMedSearch : Zhang_2023_Talanta_266_124971
PubMedID: 37480822

Title : Synthesis, Bioactivity and Molecular Docking of Nereistoxin Derivatives Containing Phosphonate - Yan_2023_Molecules_28_
Author(s) : Yan Q , Lu X , Zhang Z , Jin Q , Gao R , Li L , Wang H
Ref : Molecules , 28 : , 2023
Abstract : Novel nereistoxin derivatives containing phosphonate were synthesized and characterized via (31)P, (1)H and (13)C NMR and HRMS. The anticholinesterase activity of the synthesized compounds was evaluated on human acetylcholinesterase (AChE) using the in vitro Ellman method. Most of the compounds exhibited good inhibition of acetylcholinesterase. All of these compounds were selected to assess their insecticidal activity (in vivo) against Mythimna separata Walker, Myzus persicae Sulzer and Rhopalosiphum padi. Most of the tested compounds displayed potent insecticidal activity against these three species. Compound 7f displayed good activity against all three insect species, showing LC(50) values of 136.86 microg/mL for M. separata, 138.37 microg/mL for M. persicae and 131.64 microg/mL for R. padi. Compound 7b had the highest activity against M. persicae and R. padi, with LC(50) values of 42.93 microg/mL and 58.19 microg/mL, respectively. Docking studies were performed to speculate the possible binding sites of the compounds and explain the reasons for the activity of the compounds. The results showed that the compounds had lower binding energies with AChE than with the acetylcholine receptor (AchR), suggesting that compounds are more easily bound with AChE.
ESTHER : Yan_2023_Molecules_28_
PubMedSearch : Yan_2023_Molecules_28_
PubMedID: 37375402

Title : The porous hollow cobalt-based oxides encapsulated with bimetallic PdAu Nanoparticles of electrochemical biosensor for highly sensitive pesticides detection - Zhao_2023_Nanotechnology__
Author(s) : Zhao Y , Liang L , Guo W , Lu X , Zhao C , Gao F
Ref : Nanotechnology , : , 2023
Abstract : Efficient and portable electrochemical biosensors are received to evaluation of pesticides in the environment, which can make great significance for food safety. In this study, the Co-based oxides with a kind of hierarchical porous hollow and nanocages were constructed, in which the materials (Co3O4-NC) were encapsulated with PdAu nanoparticles (NPs). Due to the unique porous structure, the changeable valence state of cobalt and the synergistic effect of bimetallic PdAuNPs, PdAu@Co3O4-NC possessed excellent electron pathways, and showed more exposed active sites. Accordingly, the porous Co-based oxides have been applied to construct an acetylcholinesterase (AChE) electrochemical biosensor, which showed good performance for organophosphorus pesticides (OPs) detection. The optimum biosensing platform based on nanocomposites was applied to exhibit highly sensitive determination of omethoate and chlorpyrifos, with the relative low detection limit of 6.125 x 10-15 M and 5.10 x 10-13 M, respectively. And a wide detection range of 6.125 x 10-15 ~ 6.125 x 10-6 M and 5.10 x 10-13 ~ 5.10 x 10-6 M for these two pesticides were achieved. Therefore, the PdAu@Co3O4-NC may represent a powerful tool for ultrasensitive sensing of OPs, and have great potential application.
ESTHER : Zhao_2023_Nanotechnology__
PubMedSearch : Zhao_2023_Nanotechnology__
PubMedID: 37054697

Title : Core-shell ZnO@CoO nitrogen doped nano-composites as highly sensitive electrochemical sensor for organophosphate pesticides detection - Li_2023_Anal.Biochem__115422
Author(s) : Li Z , Lu X , Liu G , Yang L , Gao F
Ref : Analytical Biochemistry , :115422 , 2023
Abstract : Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 x 10(-13) M for chlorpyrifos and 7.6 x 10(-15) M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.
ESTHER : Li_2023_Anal.Biochem__115422
PubMedSearch : Li_2023_Anal.Biochem__115422
PubMedID: 38070664

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

Title : N-Benzyl Benzamide Derivatives as Selective Sub-Nanomolar Butyrylcholinesterase Inhibitors for Possible Treatment in Advanced Alzheimer's Disease - Du_2022_J.Med.Chem__
Author(s) : Du C , Wang L , Guan Q , Yang H , Chen T , Liu Y , Li Q , Lyu W , Lu X , Chen Y , Liu H , Feng F , Liu W , Liu Z , Li W , Sun H
Ref : Journal of Medicinal Chemistry , : , 2022
Abstract : Herein, we report a series of selective sub-nanomolar inhibitors against butyrylcholinesterase (BChE). These compounds, bearing a novel N-benzyl benzamide scaffold, inhibited BChE with IC(50) from picomolar to nanomolar. The inhibitory activity was confirmed by the surface plasmon resonance assay, showing a sub-nanomolar K(D) value, which revealed that the compounds exert the inhibitory effect through directly binding to BChE. Several compounds showed neuroprotective effects verified by the oxidative damage model. Furthermore, the safety of S11-1014 and S11-1033 was demonstrated by the in vivo acute toxicity test. In the behavior study, 0.5 mg/kg S11-1014 or S11-1033 exhibited a marked therapeutic effect, which was almost equal to the treatment with 1 mg/kg rivastigmine, against the cognitive impairment induced by Abeta(1-42). The pharmacokinetics studies characterized the metabolic stability of S11-1014. Thus, N-benzyl benzamide inhibitors are promising compounds with drug-like properties for improving cognitive dysfunction, providing a potential strategy for the treatment of Alzheimer's disease.
ESTHER : Du_2022_J.Med.Chem__
PubMedSearch : Du_2022_J.Med.Chem__
PubMedID: 35969197

Title : A stable enzyme sensor via embedding enzymes into zeolitic imidazolate frameworks for pesticide determination - Zhao_2022_Anal.Biochem__114628
Author(s) : Zhao Y , Lu X , Gao F
Ref : Analytical Biochemistry , :114628 , 2022
Abstract : The stability of biosensors is of significant importance for practical applications, and the natural biomineralization processes in living organisms have inspired us from a new perspective. In this work, acetylcholinesterase (AChE) was embedded into zeolitic imidazolate framework-8 carriers (with negligible cytotoxicity) via biomimetic mineralization, being demonstrated to be a stable strategy for enzyme immobilization. When further coupled with the conductive and catalytic Au nanoparticles, the biocomposites were explored as electrochemical pesticide detection biosensor, which showed favorable analytical performance, and improved stability comparing with other biosensors. This work provides a new strategy for the reasonable design of stable biosensors for different analytes monitoring.
ESTHER : Zhao_2022_Anal.Biochem__114628
PubMedSearch : Zhao_2022_Anal.Biochem__114628
PubMedID: 35257680

Title : Promising candidates from drug clinical trials: Implications for clinical treatment of Alzheimer's disease in China - Cao_2022_Front.Neurol_13_1034243
Author(s) : Cao Y , Yu F , Lyu Y , Lu X
Ref : Front Neurol , 13 :1034243 , 2022
Abstract : Alzheimer's disease is the most common neurodegenerative disease. Prior to 2017, National Medical Products Administration approved only four drugs to treat Alzheimer's disease, including three cholinesterase inhibitors and one N-methyl-D-aspartate receptor antagonist. We queried ClinicalTrials.gov to better understand Alzheimer's drug development over the past 5 years and found 16 promising candidates that have entered late-stage trials and analyzed their impact on clinical treatment of Alzheimer's disease in China. The 16 compounds selected include disease-modifying therapies and symptomatic therapies. The research and development pipeline now focuses on disease-modifying therapies such as gantenerumab, aducanumab, ALZ-801, ALZT-OP1, donanemab, lecanemab, simufilam, NE3107, semaglutide, and GV-971, which could put an end to the situation where Alzheimer's patients in China have no effective treatment alternatives. The reuse of drugs or combinations currently under investigation for the psychiatric treatment of Alzheimer's disease, including AXS-05, AVP-786, nabilone, brexpiprazole, methylphenidate, and pimavanserin, could provide physicians with additional treatment options. Although most of these drugs have not been explored in China yet, due to the current development trend in this field in China, it is expected that China will be involved in research on these drugs in the future.
ESTHER : Cao_2022_Front.Neurol_13_1034243
PubMedSearch : Cao_2022_Front.Neurol_13_1034243
PubMedID: 36457865

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

Title : Design, synthesis, and biological evaluation of aromatic tertiary amine derivatives as selective butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease - Lu_2022_Eur.J.Med.Chem_243_114729
Author(s) : Lu X , Qin N , Liu Y , Du C , Feng F , Liu W , Chen Y , Sun H
Ref : Eur Journal of Medicinal Chemistry , 243 :114729 , 2022
Abstract : Butyrylcholinesterase (BChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD), the development of selective BChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Previously, an aromatic tertiary amine derivative (S17-1001) was screened and validated as a selective BChE inhibitor. Structured-based molecular modification guided the synthesis of 43 analogs. Biological test of cholinesterase inhibition, in vitro blood brain barrier permeation assay, neurotoxicity assay and neuroprotective effects assay indicated two optimal compounds 17c and 19c. Both compounds showed selective BChE inhibitory (hBChE < 20 nM, eeAChE > 10 microM), good BBB permeation and primary cell safety. Besides, 17c can dose-response protect cell from Abeta(1-42) induced damage. It also demonstrated that 17c and 19c were able to restore cognitive impairment in vivo test. These data suggest that 17c and 19c represent promising candidate for follow-up in the drug-discovery process against AD.
ESTHER : Lu_2022_Eur.J.Med.Chem_243_114729
PubMedSearch : Lu_2022_Eur.J.Med.Chem_243_114729
PubMedID: 36084535

Title : Synthesis and activity of miconazole derivatives as dual BChE\/IDO1 inhibitors for the treatment of Alzheimer's disease - Lu_2021_Future.Med.Chem_13_1105
Author(s) : Lu X , Liu Y , Qin N , Yang H , Qiao Y , Jiang X , Chen Y , Feng F , Liu W , Zhou Y , Sun H
Ref : Future Med Chem , 13 :1105 , 2021
Abstract : Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.
ESTHER : Lu_2021_Future.Med.Chem_13_1105
PubMedSearch : Lu_2021_Future.Med.Chem_13_1105
PubMedID: 33960203

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

Title : LIPG: an inflammation and cancer modulator - Hong_2021_Cancer.Gene.Ther_28_27
Author(s) : Hong C , Deng R , Wang P , Lu X , Zhao X , Wang X , Cai R , Lin J
Ref : Cancer Gene Therapy , 28 :27 , 2021
Abstract : Endothelial lipase (LIPG/EL) performs fundamental and vital roles in the human body, including cell composition, cytokine expression, and energy provision. Since LIPG predominantly functions as a phospholipase as well as presents low levels of triglyceride lipase activity, it plays an essential role in lipoprotein metabolism, and involves in the metabolic syndromes such as inflammatory response and atherosclerosis. Cytokines significantly affect LIPG expression in endothelial cells in many diseases. Recently, it is suggested that LIPG contributes to cancer initiation and progression, and LIPG attached increasing importance to its potential for future targeted therapy.
ESTHER : Hong_2021_Cancer.Gene.Ther_28_27
PubMedSearch : Hong_2021_Cancer.Gene.Ther_28_27
PubMedID: 32572177
Gene_locus related to this paper: human-LIPG

Title : Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining - Tang_2020_J.Nat.Prod_83_473
Author(s) : Tang S , Zhang W , Li Z , Li H , Geng C , Huang X , Lu X
Ref : Journal of Natural Products , 83 :473 , 2020
Abstract : Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids have been characterized to produce polyketide-amino acid compounds with striking structural features and biological activities. In this study, a PKS-NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS-NRPS gene cluster was successfully activated and ten products (1-10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS-NRPS hybrid identified in A. terreus.
ESTHER : Tang_2020_J.Nat.Prod_83_473
PubMedSearch : Tang_2020_J.Nat.Prod_83_473
PubMedID: 32077283
Gene_locus related to this paper: asptn-pytb , aspte-pyti

Title : Role of penehyclidine in acute organophosphorus pesticide poisoning - Yu_2020_World.J.Emerg.Med_11_37
Author(s) : Yu SY , Gao YX , Walline J , Lu X , Zhao LN , Huang YX , Tao J , Yu AY , Ta N , Xiao RJ , Li Y
Ref : World J Emerg Med , 11 :37 , 2020
Abstract : BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). RESULTS: Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine- or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. CONCLUSION: Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.
ESTHER : Yu_2020_World.J.Emerg.Med_11_37
PubMedSearch : Yu_2020_World.J.Emerg.Med_11_37
PubMedID: 31893002

Title : Biology and applications of Clonostachys rosea - Sun_2020_J.Appl.Microbiol__
Author(s) : Sun ZB , Li SD , Ren Q , Xu JL , Lu X , Sun MH
Ref : J Appl Microbiol , : , 2020
Abstract : Clonostachys rosea is a promising saprophytic filamentous fungus that belongs to phylum Ascomycota. Clonostachys rosea is widespread around the world and exists in many kinds of habitats, with the highest frequency in soil. As an excellent mycoparasite, C. rosea exhibits strong biological control ability against numerous fungal plant pathogens, nematodes and insects. These behaviours are based on the activation of multiple mechanisms such as secreted cell-wall-degrading enzymes, production of antifungal secondary metabolites and induction of plant defence systems. Besides having significant biocontrol activity, C. rosea also functions in the biodegradation of plastic waste, biotransformation of bioactive compounds, as a bioenergy sources and in fermentation. This mini review summarizes information about the biology and various applications of C. rosea and expands on its possible uses.
ESTHER : Sun_2020_J.Appl.Microbiol__
PubMedSearch : Sun_2020_J.Appl.Microbiol__
PubMedID: 32115828

Title : Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure - Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
Author(s) : Fu F , Liu H , Lu X , Zhang R , Li L , Gao R , Xie J , Wang H , Pei C
Ref : Rapid Commun Mass Spectrom , :e8721 , 2020
Abstract : RATIONALE: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. METHODS: After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. RESULTS: The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman, and V-type nerve agents) were shown to bind more readily to K414 on the peptide. CONCLUSIONS: This research revealed the new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from nerve agents and providing an important tool for identification of sarin or cyclosarin in terrorist attacks.
ESTHER : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedSearch : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedID: 31899842

Title : Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish - Ma_2020_ACS.Sens_5_83
Author(s) : Ma J , Si T , Yan C , Li Y , Li Q , Lu X , Guo Y
Ref : ACS Sens , 5 :83 , 2020
Abstract : Acetylcholinesterase (AChE) plays crucial roles in numerous physiological processes such as cell differentiation, cell apoptosis, and nerve tissue developments. Hence, it is highly necessary to design a fluorescent probe for monitoring AChE activity in complex living organisms. In this work, a near-infrared (NIR) off-on probe (CyN) was developed for AChE detection. CyN was exactly synthesized by introducing an N,N-dimethyl carbamyl moiety to hemicyanine (CyOH). AChE can "light up" strong NIR fluorescence through a cleavage special ester bond and transform CyN into CyOH. Moreover, CyN was qualified for imaging the dynamic change of AChE activity in PC12 cells with retinoic acid or hypoxia stimulation. In particular, the probe has been successfully applied for in situ tracing the intact distribution of AChE in living zebrafish. The observations indicate that major occurrence sites of endogenic AChE on zebrafish are the yolk sac and neuromasts. Overall, CyN shows great potential for use in AChE-related physiological studies.
ESTHER : Ma_2020_ACS.Sens_5_83
PubMedSearch : Ma_2020_ACS.Sens_5_83
PubMedID: 31875385
Gene_locus related to this paper: danre-ACHE

Title : Rational design of a near-infrared fluorescence probe for highly selective sensing butyrylcholinesterase (BChE) and its bioimaging applications in living cell - Ma_2020_Talanta_219_121278
Author(s) : Ma J , Lu X , Zhai H , Li Q , Qiao L , Guo Y
Ref : Talanta , 219 :121278 , 2020
Abstract : In the current work, a near-infrared (NIR) fluorescent probe (CyClCP) was developed for fast (35 min), highly sensitive (LOD of 3.75 U/L) and selective response to BChE in vitro and in vivo. Upon the addition of BChE, CyClCP could be efficiently activated with remarkable NIR ((em) = 708 nm) fluorescence enhancement and obvious absorbance red shift (581 nm-687 nm). Specifically, according to the subtle differences structural features and substrate preference between BChE and its sister enzyme AChE, CyClCP was constructed by introducing chlorine atom at the ortho-position of the phenolic hydroxyl in the previous reported probe (CyCP). Fortunately, CyClCP exhibited better selectivity towards BChE over AChE compared with CyCP. This molecular design strategy was further rationalized by docking molecular of fluorescence probes (CyClCP and CyCP) and enzymes (BChE and AChE). Finally, CyClCP was membrane permeable and successfully applied to image endogenous BChE level in HepG2 and LO2 cells. Therefore, CyClCP could serve as a promising tool for BChE-related physiological function studies in complex biological systems.
ESTHER : Ma_2020_Talanta_219_121278
PubMedSearch : Ma_2020_Talanta_219_121278
PubMedID: 32887168

Title : Correction to Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish -
Author(s) : Ma J , Si T , Yan C , Li Y , Li Q , Lu X , Guo Y
Ref : ACS Sens , : , 2020
PubMedID: 32196313
Gene_locus related to this paper: danre-ACHE

Title : Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway - Zhang_2020_Exp.Cell.Res__111856
Author(s) : Zhang Y , Sun L , Sun Y , Chen Y , Wang X , Xu M , Chi P , Xu Z , Lu X
Ref : Experimental Cell Research , :111856 , 2020
Abstract : CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (P<0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment.
ESTHER : Zhang_2020_Exp.Cell.Res__111856
PubMedSearch : Zhang_2020_Exp.Cell.Res__111856
PubMedID: 31981591
Gene_locus related to this paper: human-CES2

Title : Structural insights into the catalytic mechanism of lovastatin hydrolase - Liang_2020_J.Biol.Chem_295_1047
Author(s) : Liang Y , Lu X
Ref : Journal of Biological Chemistry , 295 :1047 , 2020
Abstract : The lovastatin hydrolase PcEST from the fungus Penicillium chrysogenum exhibits enormous potential for industrial-scale applications in single-step production of monacolin J, the key precursor for synthesis of the cholesterol-lowering drug simvastatin. This enzyme specifically and efficiently catalyzes the conversion of lovastatin to monacolin J but cannot hydrolyze simvastatin. Understanding the catalytic mechanism and the structure-function relationship of PcEST is therefore important for further lovastatin hydrolase screening, engineering, and commercial applications. Here, we solved four X-ray crystal structures, including apo PcEST (2.3 A), PcEST in complex with monacolin J (2.48 A), PcEST complexed with the substrate analog simvastatin (2.4 A), and an inactivated PcEST variant (S57A) with the lovastatin substrate (2.3 A). Structure-based biochemical analyses and mutagenesis assays revealed that the Ser(57) (nucleophile)-Tyr(170) (general base)-Lys(60) (general acid) catalytic triad, the hydrogen-bond network (Trp(344) and Tyr(127)) around the active site, and the specific substrate-binding tunnel together determine efficient and specific lovastatin hydrolysis by PcEST. Moreover, steric effects on nucleophilic attack caused by the 2',2-dimethybutyryl group of simvastatin resulted in no activity of PcEST on simvastatin. On the basis of structural comparisons, we propose several indicators to define lovastatin esterases. Furthermore, using structure-guided enzyme engineering, we developed a PcEST variant, D106A, having improved solubility and thermostability, suggesting a promising application of this variant in industrial processes. To our knowledge, this is the first report describing the mechanism and structure-function relationship of lovastatin hydrolase and providing insights that may guide rapid screening and engineering of additional lovastatin esterase variants.
ESTHER : Liang_2020_J.Biol.Chem_295_1047
PubMedSearch : Liang_2020_J.Biol.Chem_295_1047
PubMedID: 31839596

Title : Collaborative Biosynthesis of a Class of Bioactive Azaphilones by Two Separate Gene Clusters Containing Four PKS\/NRPSs with Transcriptional Crosstalk in Fungi - Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
Author(s) : Huang X , Zhang W , Tang S , Wei S , Lu X
Ref : Angew Chem Int Ed Engl , 59 :4349 , 2020
Abstract : Azaphilones are a family of fungal polyketide metabolites with diverse chemical structures and biological activities with a highly oxygenated pyranoquinone bicyclic core. Here, a class of azaphilones possessing a 6/6/6/6 tetracyclic ring system was identified in Aspergillus terreus, and exhibited potential anticancer activities. The gene deletions and biochemical investigations demonstrated that these azaphilones were collaboratively synthesized by two separate clusters containing four core-enzymes, two nonreducing PKSs, one highly reducing PKS, and one NRPS-like. More interestingly, we found that the biosynthesis is coordinately regulated by a crosstalk mechanism between these two gene clusters based on three transcriptional factors. This is a meaningful mechanism of fungal secondary metabolism, which allows fungi to synthesize more complex compounds and gain new physiological functions. The results provide a new insight into fungal natural product biosynthesis.
ESTHER : Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
PubMedSearch : Huang_2020_Angew.Chem.Int.Ed.Engl_59_4349
PubMedID: 31908094
Gene_locus related to this paper: asptn-5moas , asptn-azpb5

Title : Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies - Zhou_2020_Bioorg.Med.Chem.Lett__127756
Author(s) : Zhou Y , Lu X , Du C , Liu Y , Wang Y , Ho Hong K , Chen Y , Sun H
Ref : Bioorganic & Medicinal Chemistry Lett , :127756 , 2020
Abstract : In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
ESTHER : Zhou_2020_Bioorg.Med.Chem.Lett__127756
PubMedSearch : Zhou_2020_Bioorg.Med.Chem.Lett__127756
PubMedID: 33359445

Title : Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring - Zhou_2020_Dose.Response_18_1559325820938526
Author(s) : Zhou Y , Hu Y , Lu X , Yang H , Li Q , Du C , Chen Y , Hong KH , Sun H
Ref : Dose Response , 18 :1559325820938526 , 2020
Abstract : Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC50 = 1.4 muM). The binding mode prediction and kinetic analysis were performed to obtain detailed information about compound 5. Besides, a preliminary structure-activity relationship investigation of compound 5 was carried out for further development of the series. The present results provided a valuable chemical template with a novel scaffold for the development of selective BChE inhibitors.
ESTHER : Zhou_2020_Dose.Response_18_1559325820938526
PubMedSearch : Zhou_2020_Dose.Response_18_1559325820938526
PubMedID: 32636723

Title : Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease - Bai_2019_Eur.J.Med.Chem_183_111737
Author(s) : Bai P , Wang K , Zhang P , Shi J , Cheng X , Zhang Q , Zheng C , Cheng Y , Yang J , Lu X , Sang Z
Ref : Eur Journal of Medicinal Chemistry , 183 :111737 , 2019
Abstract : A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50=1.3+/-0.01muM) and butyrylcholinesterase (IC50=1.2+/-0.09muM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57+/-0.01muM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Abeta1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu(2+)-induced Abeta1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Abeta1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.
ESTHER : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedSearch : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedID: 31581002

Title : Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations - Zhou_2019_Molecules_24_
Author(s) : Zhou Y , Lu X , Yang H , Chen Y , Wang F , Li J , Tang Z , Cheng X , Yang Y , Xu L , Xia Q
Ref : Molecules , 24 : , 2019
Abstract : As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 muM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.
ESTHER : Zhou_2019_Molecules_24_
PubMedSearch : Zhou_2019_Molecules_24_
PubMedID: 31757047

Title : Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin - Fu_2019_Toxicology_430_152346
Author(s) : Fu F , Chen J , Zhao P , Lu X , Gao R , Chen D , Liu H , Wang H , Pei C
Ref : Toxicology , 430 :152346 , 2019
Abstract : V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2-(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans.
ESTHER : Fu_2019_Toxicology_430_152346
PubMedSearch : Fu_2019_Toxicology_430_152346
PubMedID: 31857189

Title : Discovery, molecular dynamic simulation and biological evaluation of structurally diverse cholinesterase inhibitors with new scaffold through shape-based pharmacophore virtual screening - Yang_2019_Bioorg.Chem_92_103294
Author(s) : Yang H , Du C , Li Q , Chen T , Lu X , Feng F , Chen Y , Liu W , Sun H
Ref : Bioorg Chem , 92 :103294 , 2019
Abstract : Designing small molecule inhibitors targeting cholinesterases (ChEs) is considered as an efficient strategy for the treatment of Alzheimer's disease (AD). In the present study, based on a shaped-based pharmacophore (SBP) model that we reported previously, virtual screening was performed on four commercial compound databases, from which eight small molecules containing new structurally scaffolds were retained and evaluated. In general, six of these potential hits were identified to be selective ChEs inhibitors. Three compounds exhibited IC50 values and Ki values in micromolar range on acetylcholinesterase (AChE), the most active compound 4 showed IC50 value of 6.31+/-2.68muM and Ki value of 4.76muM. Other three compounds displayed IC50 values and Ki values in micromolar range on butyrylcholinesterase (BChE) with high target selectivity, the most active compound 1 showed IC50 value of 3.87+/-2.48muM and Ki value of 1.52muM. Multiple biological evaluations were performed to determine their cytotoxicity, cyto-protective effects, antioxidant effect as well as druglike properties. These compounds provide new cores for the further design and optimization, with the aim to discover new ChEs inhibitors for the treatment of AD.
ESTHER : Yang_2019_Bioorg.Chem_92_103294
PubMedSearch : Yang_2019_Bioorg.Chem_92_103294
PubMedID: 31557623

Title : Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis - Yu_2019_Am.J.Emerg.Med_37_1611
Author(s) : Yu S , Zhang L , Gao Y , Walline J , Lu X , Ma Y , Zhu H , Yu X , Li Y
Ref : Am J Emerg Med , 37 :1611 , 2019
Abstract : OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR=2.54, 95% CI (1.33, 4.86), p=0.005] and lower the mortality rate [OR=0.31, 95% CI (0.13, 0.74), p=0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD=-1.52, 95% CI (-2.64, 0.40), p=0.008; AST, SMD=-1.66, 95% CI (-3.15, 0.16), p=0.03; TBIL, SMD=-1.26, 95% CI (-2.32, 0.20), p=0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD=2.15, 95% CI (1.60, 2.71), p<0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR=0.19, 95% CI (0.05, 0.71), p=0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended.
ESTHER : Yu_2019_Am.J.Emerg.Med_37_1611
PubMedSearch : Yu_2019_Am.J.Emerg.Med_37_1611
PubMedID: 30527914

Title : Epigenetic mechanisms underlying the effects of triptolide and tripchlorolide on the expression of neuroligin-1 in the hippocampus of APP\/PS1 transgenic mice - Lu_2019_Pharm.Biol_57_453
Author(s) : Lu X , Yang B , Yu H , Hu X , Nie J , Wan B , Zhang M , Lu C
Ref : Pharm Biol , 57 :453 , 2019
Abstract : Context: Neuroligin-1 (NLGN1) is a cell adhesion protein located on the excitatory postsynaptic membrane. beta-Amyloid (Abeta)-induced neuroinflammation decreases NLGN1 expression through epigenetic mechanisms. Triptolide (T10) and tripchlorolide (T4) exert protective effects on synapses in Alzheimer's disease (AD) mice, but the mechanisms remain unclear. Objective: The effects of T10 and T4 on hippocampal NLGN1 expression in AD mice and the epigenetic mechanisms were assessed using chromatin immunoprecipitation and methylated DNA immunoprecipitation. Materials and methods: Sixty APP/PS1 transgenic mice were randomly divided into an AD model group, a T10-treated group and a T4-treated group (n = 20); 20 wild-type littermates served as the control group. APP/PS1 transgenic mice were intraperitoneally injected with T10 (0.1 mg/kg) and T4 (25 mug/kg) once per day for 60 days. NLGN1 expression was examined using western blotting and quantitative PCR. Results: T10 and T4 increased the levels of the NLGN1 protein and mRNA in hippocampus of AD mice. T10 and T4 inhibited the binding of HDAC2 (p< 0.01) and MeCP2 (p< 0.01 and p< 0.05, respectively) to the NLGN1 promoter, and cytosine methylation (1.2305 +/- 0.1482/1.2554 +/- 0.3570 vs. 1.6578 +/- 0.1818, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. T10 and T4 increased the level of acetylated histone H3 (0.7733 +/- 0.1611/0.8241 +/- 0.0964 vs. 0.5587 +/- 0.0925, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. Conclusions: T10 and T4 may increase hippocampal NLGN1 expression in AD mice through epigenetic mechanisms, providing a new explanation for the mechanism underlying the protective effects of T10 and T4 on synapses.
ESTHER : Lu_2019_Pharm.Biol_57_453
PubMedSearch : Lu_2019_Pharm.Biol_57_453
PubMedID: 31311385

Title : Expansion of the scaffold diversity for the development of highly selective butyrylcholinesterase (BChE) inhibitors: Discovery of new hits through the pharmacophore model generation, virtual screening and molecular dynamics simulation - Lu_2019_Bioorg.Chem_85_117
Author(s) : Lu X , Yang H , Li Q , Chen Y , Zhou Y , Feng F , Liu W , Guo Q , Sun H
Ref : Bioorg Chem , 85 :117 , 2018 || 2019
Abstract : Butyrylcholinesterase (BChE) is recently considered as a new target for the treatment of Alzheimer's disease (AD). There is an increasing interest in the development of BChE inhibitors. In the present study, a set of pharmacophore models for BChE was developed and validated. Based on the models, virtual screening was performed on five compound collections, from which seventeen potential hits were retained for biological investigation. In total, eight of these seventeen potential hits showed selective BChE inhibitory activity. Moreover, four compounds displayed IC50 values in sub-micromolar range on eqBChE and three displayed IC50 values <2muM on huBChE. The diverse scaffolds of the active compounds provided good starting point further development of selective BChE inhibitors. As far as we concerned, here we disclose the first selective pharmacophore model targeting BChE. The high rate of the model in the identification of active hits indicates it is a valuable tool for the development of selective BChE inhibitors, which may benefit the treatment of AD.
ESTHER : Lu_2019_Bioorg.Chem_85_117
PubMedSearch : Lu_2019_Bioorg.Chem_85_117
PubMedID: 30605885

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Detection of vapor-phase organophosphate threats using wearable conformable integrated epidermal and textile wireless biosensor systems - Mishra_2018_Biosens.Bioelectron_101_227
Author(s) : Mishra RK , Martin A , Nakagawa T , Barfidokht A , Lu X , Sempionatto JR , Lyu KM , Karajic A , Musameh MM , Kyratzis IL , Wang J
Ref : Biosensors & Bioelectronics , 101 :227 , 2018
Abstract : Flexible epidermal tattoo and textile-based electrochemical biosensors have been developed for vapor-phase detection of organophosphorus (OP) nerve agents. These new wearable sensors, based on stretchable organophosphorus hydrolase (OPH) enzyme electrodes, are coupled with a fully integrated conformal flexible electronic interface that offers rapid and selective square-wave voltammetric detection of OP vapor threats and wireless data transmission to a mobile device. The epidermal tattoo and textile sensors display a good reproducibility (with RSD of 2.5% and 4.2%, respectively), along with good discrimination against potential interferences and linearity over the 90-300mg/L range, with a sensitivity of 10.7microAcm3mg-1 (R2 = 0.983) and detection limit of 12mg/L in terms of OP air density. Stress-enduring inks, used for printing the electrode transducers, ensure resilience against mechanical deformations associated with textile and skin-based on-body sensing operations. Theoretical simulations are used to estimate the OP air density over the sensor surface. These fully integrated wearable wireless tattoo and textile-based nerve-agent vapor biosensor systems offer considerable promise for rapid warning regarding personal exposure to OP nerve-agent vapors in variety of decentralized security applications.
ESTHER : Mishra_2018_Biosens.Bioelectron_101_227
PubMedSearch : Mishra_2018_Biosens.Bioelectron_101_227
PubMedID: 29096360

Title : Ultra-thin bimetallic alloy nanowires with porous architecture\/monolayer MoS2 nanosheet as a highly sensitive platform for the electrochemical assay of hazardous omethoate pollutant - Song_2018_J.Hazard.Mater_357_466
Author(s) : Song D , Li Q , Lu X , Li Y , Wang Y , Gao F
Ref : J Hazard Mater , 357 :466 , 2018
Abstract : A novel electrochemical biosensor was designed for sensitive detection of organophosphate pesticides based on three-dimensional porous bimetallic alloy architecture with ultrathin nanowires (PdCo NWs, PdCu NWs, PdNi NWs) and monolayer MoS2 nanosheet (m-MoS2). The bimetallic alloy NWs/m-MoS2 nanomaterials were used as a sensing platform for electrochemical analysis of omethoate, a representative organophosphate pesticide, via acetylcholinesterase inhibition pathway. We demonstrated that all three bimetallic alloy NWs enhanced electrochemical responses of enzymatic biosensor, benefited from bimetallic synergistic action and porous structure. In particular, PdNi NWs outperformed other two bimetallic alloy. Moreover, PdNi NWs/m-MoS2 as an electronic transducer is superior to the corresponding biosensor in the absence of monolayer MoS2 nanosheet, which arise from synergistic signal amplification effect between different components. Under optimized conditions, the developed biosensor on the basis of PdNi NWs/m-MoS2 shows outstanding performance for the electrochemical assay of omethoate, such as a wide linear range (10(-13) M approximately 10(-7) M), a low detection limit of 0.05pM at a signal-to-noise ratio of 3, high sensitivity and long-time stability. The results demonstrate that bimetallic alloy NWs/m-MoS2 nanocomposites could be excellent transducers to promote electron transfer for the electrochemical reactions, holding great potentials in the construction of current and future biosensing devices.
ESTHER : Song_2018_J.Hazard.Mater_357_466
PubMedSearch : Song_2018_J.Hazard.Mater_357_466
PubMedID: 29935459

Title : Investigation of multi-target-directed ligands (MTDLs) with butyrylcholinesterase (BuChE) and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition: The design, synthesis of miconazole analogues targeting Alzheimer's disease - Lu_2018_Bioorg.Med.Chem_26_1665
Author(s) : Lu X , He SY , Li Q , Yang H , Jiang X , Lin H , Chen Y , Qu W , Feng F , Bian Y , Zhou Y , Sun H
Ref : Bioorganic & Medicinal Chemistry , 26 :1665 , 2018
Abstract : In our endeavor towards the development of potent multi-target ligands for the treatment of Alzheimer's disease, miconazole was identified to show BuChE-IDO1 dual-target inhibitory effects. Morris water maze test indicated that miconazole obviously ameliorated the cognitive function impaired by scopolamine. Furthermore, it showed good safety in primary hepatotoxicity evaluation. Based on these results, we designed, synthesized, and evaluated a series of miconazole derivatives as BuChE-IDO1 dual-target inhibitors. Out of the 12 compounds, 5i and 5j exhibited the best potency in enzymatic evaluation, thus were selected for subsequent behavioral study, in which the two compounds exerted much improved effect than tacrine. Meanwhile, 5i and 5j displayed no apparent hepatotoxicity. The results suggest that miconazole analogue offers an attractive starting point for further development of new BuChE-IDO1 dual-target inhibitors against Alzheimer's disease.
ESTHER : Lu_2018_Bioorg.Med.Chem_26_1665
PubMedSearch : Lu_2018_Bioorg.Med.Chem_26_1665
PubMedID: 29475581

Title : Amorphous metal boride as a novel platform for acetylcholinesterase biosensor development and detection of organophosphate pesticides - Lu_2018_Nanotechnology_30_055501
Author(s) : Lu X , Li Y , Tao L , Song D , Wang Y , Gao F
Ref : Nanotechnology , 30 :055501 , 2018
Abstract : The exploration of new materials for modifying electrodes is important to advance electrochemical biosensors. Herein, we demonstrated that amorphous bimetallic boride material (Co-2Ni-B) prepared by a simple and facile aqueous reaction is an efficient matrix to immobilize acetylcholinesterase (AChE) to construct a biosensor for the determination of organophosphate pesticides. The effects of different composition and crystallinity on its electrochemical performance are investigated, and the optimization studies of the biological transducer were also discussed. Under optimal conditions, the fabricated sensor showed good analytical performance for the determination of chlorpyrifos with a low limit of detection (2.83 pM) and a wide linear range (3 pM-300 nM). The proposed biosensor also demonstrated high reproducibility, stability and accuracy. The impressive performance was due to the excellent conductivity and the unique amorphous bimetal-metalloid complex nanostructure. These results introduce a new class of promising materials as a robust platform for biosensor applications.
ESTHER : Lu_2018_Nanotechnology_30_055501
PubMedSearch : Lu_2018_Nanotechnology_30_055501
PubMedID: 30499458

Title : Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease - Agostini_2018_mBio_9_
Author(s) : Agostini ML , Andres EL , Sims AC , Graham RL , Sheahan TP , Lu X , Smith EC , Case JB , Feng JY , Jordan R , Ray AS , Cihlar T , Siegel D , Mackman RL , Clarke MO , Baric RS , Denison MR
Ref : MBio , 9 : , 2018
Abstract : Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC(50)) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC(50) The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same in vitro resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.IMPORTANCE Coronaviruses (CoVs) cause severe human infections, but there are no approved antivirals to treat these infections. Development of nucleoside-based therapeutics for CoV infections has been hampered by the presence of a proofreading exoribonuclease. Here, we expand the known efficacy of the nucleotide prodrug remdesivir (GS-5734) to include a group beta-2a CoV. Further, GS-5734 potently inhibits CoVs with intact proofreading. Following selection with the GS-5734 parent nucleoside, 2 amino acid substitutions in the nsp12 polymerase at residues that are identical across CoVs provide low-level resistance to GS-5734. The resistance mutations decrease viral fitness of MHV in vitro and attenuate pathogenesis in a SARS-CoV animal model of infection. Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.
ESTHER : Agostini_2018_mBio_9_
PubMedSearch : Agostini_2018_mBio_9_
PubMedID: 29511076

Title : Isosteroidal alkaloids as potent dual-binding site inhibitors of both acetylcholinesterase and butyrylcholinesterase from the bulbs of Fritillaria walujewii - Liu_2017_Eur.J.Med.Chem_137_280
Author(s) : Liu YM , Feng YD , Lu X , Nie JB , Li W , Wang LN , Tian LJ , Liu QH
Ref : Eur Journal of Medicinal Chemistry , 137 :280 , 2017
Abstract : Five new isosteroidal alkaloids, walujewine A (1), walujewine B (4), walujewine C (5), walujewine D (6), walujewine E (10) were isolated from the bulbs of Fritillaria walujewii together with seven known isosteroidal alkaloids (2, 3, 7-9, 11, 12). Their structures were elucidated on the basis of IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses and single-crystal X-ray diffraction. All the isolates were tested for ChE inhibiting activity by the Ellman's method. Compounds 3-5 and 8-10 were potent dual AChE-BChE inhibitors, and compound 1 showed highly selective AChE inhibition. The structure-activity relationship of compounds 1-12 was discussed in details. And kinetic analysis showed that compounds 1, 3-5, and 8-10 were mixed-type reversible inhibitors of AChE, simultaneously binding to the catalytic and peripheral anionic sites, which was verified by in silico docking studies. The docking simulation also showed that active compound 3 and 8 created many interactions with the CAS and PAS gorges of BChE, revealing their mixed-type inhibition. ADMET analysis further confirmed the therapeutic potential of some isosteroidal alkaloids based on their high BBB-penetration.
ESTHER : Liu_2017_Eur.J.Med.Chem_137_280
PubMedSearch : Liu_2017_Eur.J.Med.Chem_137_280
PubMedID: 28605675

Title : Dietary phosphatidylcholine impacts on growth performance and lipid metabolism in adult Genetically Improved Farmed Tilapia (GIFT) strain of Nile tilapia Oreochromis niloticus - Tian_2017_Br.J.Nutr__1
Author(s) : Tian J , Wen H , Lu X , Liu W , Wu F , Yang CG , Jiang M , Yu LJ
Ref : British Journal of Nutrition , :1 , 2017
Abstract : This study aimed to determine the effects of supplementing the diet of adult Nile tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth performance, body composition, fatty acid composition and gene expression. Genetically Improved Farmed Tilapia fish with an initial body weight of 83.1 (sd 2.9) g were divided into six groups. Each group was hand-fed a semi-purified diet containing 1.7 (control diet), 4.0, 6.5, 11.5, 21.3 or 41.0 g PC/kg diet for 68 d. Supplemental PC improved the feed efficiency rate, which was highest in the 11.5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary PC increased PC content in the liver and decreased crude fat content in the liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with increasing dietary PC. Cytoplasmic phospholipase A 2 and secreted phospholipase A 2 mRNA expression were up-regulated in the brain and heart in PC-supplemented fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral tissue but increased expression in muscle. Hormone-sensitive lipase and lipoprotein lipase expression increased in the liver with increasing dietary PC. Growth hormone mRNA expression was reduced in the brain and insulin-like growth factor-1 mRNA expression in liver reduced with PC above 6.5 g/kg. Our results demonstrate that dietary supplementation with PC improves feed efficiency and reduces liver fat in adult Nile tilapia, without increasing weight gain, representing a novel dietary approach to reduce feed requirements and improve the health of Nile tilapia.
ESTHER : Tian_2017_Br.J.Nutr__1
PubMedSearch : Tian_2017_Br.J.Nutr__1
PubMedID: 29227215

Title : Palladium-copper nanowires-based biosensor for the ultrasensitive detection of organophosphate pesticides - Song_2017_Anal.Chim.Acta_982_168
Author(s) : Song D , Li Y , Lu X , Sun M , Liu H , Yu G , Gao F
Ref : Anal Chim Acta , 982 :168 , 2017
Abstract : A highly sensitive acetylcholinesterase (AChE) electrochemical biosensor for the quantitative determination of organophosphate pesticides (OPs) in vegetables and fruits based on palladium-copper nanowires (Pd-Cu NWs) was reported. AChE immobilized on the modified electrode could catalyze hydrolysis of acetylthiocholine chloride (ATCl), generating an irreversible oxidation peak. When exposed to the OPs, the activity of the AChE was inhibited and the current significantly decreased. The detection mechanism is based on the inhibition of AChE. The Pd-Cu NWs not only provide a large active surface area (0.268 +/- 0.01) cm2 for the immobilization of AChE, which was approximately 3.8 times higher than the bare glass carbon electrode, but also exhibit excellent electro-catalytic activity and remarkable electron mobility. The biosensor modified with Pd-Cu NWs displayed a good affinity to ATCl and catalyzed hydrolysis of ATCl, with a low Michaelis-Menten constant (KM) of 50.56 muM. Under optimized conditions, the AChE-Cs/Pd-Cu NWs/GCE biosensor detected malathion with wide linear ranges of 5-1000 ppt and 500-3000 ppb, and the low detection limit was 1.5 ppt (4.5 pM). In addition, the OPs biosensor has been applied to the analysis of malathion in commercial vegetable and fruit samples, with excellent recoveries in the range of 98.5%-113.5%. This work provides a simple, sensitive and effective platform for biosensors and exhibits future potential in practical application for the OPs assay.
ESTHER : Song_2017_Anal.Chim.Acta_982_168
PubMedSearch : Song_2017_Anal.Chim.Acta_982_168
PubMedID: 28734356

Title : Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer - Yang_2016_Tumour.Biol_37_1183
Author(s) : Yang Y , Shao Y , Zhu M , Li Q , Yang F , Lu X , Xu C , Xiao B , Sun Y , Guo J
Ref : Tumour Biol , 37 :1183 , 2016
Abstract : Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.
ESTHER : Yang_2016_Tumour.Biol_37_1183
PubMedSearch : Yang_2016_Tumour.Biol_37_1183
PubMedID: 26280398
Gene_locus related to this paper: human-ABHD11

Title : Comparative genomics of Steinernema reveals deeply conserved gene regulatory networks - Dillman_2015_Genome.Biol_16_200
Author(s) : Dillman AR , Macchietto M , Porter CF , Rogers A , Williams B , Antoshechkin I , Lee MM , Goodwin Z , Lu X , Lewis EE , Goodrich-Blair H , Stock SP , Adams BJ , Sternberg PW , Mortazavi A
Ref : Genome Biol , 16 :200 , 2015
Abstract : BACKGROUND: Parasitism is a major ecological niche for a variety of nematodes. Multiple nematode lineages have specialized as pathogens, including deadly parasites of insects that are used in biological control. We have sequenced and analyzed the draft genomes and transcriptomes of the entomopathogenic nematode Steinernema carpocapsae and four congeners (S. scapterisci, S. monticolum, S. feltiae, and S. glaseri).
RESULTS: We used these genomes to establish phylogenetic relationships, explore gene conservation across species, and identify genes uniquely expanded in insect parasites. Protein domain analysis in Steinernema revealed a striking expansion of numerous putative parasitism genes, including certain protease and protease inhibitor families, as well as fatty acid- and retinol-binding proteins. Stage-specific gene expression of some of these expanded families further supports the notion that they are involved in insect parasitism by Steinernema. We show that sets of novel conserved non-coding regulatory motifs are associated with orthologous genes in Steinernema and Caenorhabditis.
CONCLUSIONS: We have identified a set of expanded gene families that are likely to be involved in parasitism. We have also identified a set of non-coding motifs associated with groups of orthologous genes in Steinernema and Caenorhabditis involved in neurogenesis and embryonic development that are likely part of conserved protein-DNA relationships shared between these two genera.
ESTHER : Dillman_2015_Genome.Biol_16_200
PubMedSearch : Dillman_2015_Genome.Biol_16_200
PubMedID: 26392177
Gene_locus related to this paper: 9bila-a0a1i7y7c9 , 9bila-a0a1i8a8u4 , 9bila-a0a1i7yci6 , 9bila-a0a1i7ys27 , 9bila-a0a1i7y373

Title : Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population - Hong_2015_Mamm.Genome_26_191
Author(s) : Hong M , Zhang M , Lu X
Ref : Mamm Genome , 26 :191 , 2015
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy-Weinberg equilibrium). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 x 10(-3) and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.
ESTHER : Hong_2015_Mamm.Genome_26_191
PubMedSearch : Hong_2015_Mamm.Genome_26_191
PubMedID: 25690150
Gene_locus related to this paper: human-PLA2G7

Title : Whole Genome Sequence of the Probiotic Strain Lactobacillus paracasei N1115, Isolated from Traditional Chinese Fermented Milk - Wang_2014_Genome.Announc_2_e00059
Author(s) : Wang S , Zhu H , He F , Luo Y , Kang Z , Lu C , Feng L , Lu X , Xue Y , Wang H
Ref : Genome Announc , 2 : , 2014
Abstract : Lactobacillus paracasei N1115 is a new strain with probiotic properties isolated from traditional homemade dairy products in Inner Mongolia, China. Here, we report the complete genome sequence of L. paracasei N1115, which shows high similarity to the well-studied probiotic Lactobacillus rhamnosus GG, and 3 structures turned out to be inversions, according to the colinearity analysis of the BLAST alignment.
ESTHER : Wang_2014_Genome.Announc_2_e00059
PubMedSearch : Wang_2014_Genome.Announc_2_e00059
PubMedID: 24625864
Gene_locus related to this paper: lacc3-q03b36 , lacrh-pepr , lacca-b5qt93 , lacca-k0n1x0 , lacpa-s2ter8 , lacpa-s2rz88

Title : Genome Sequence of Mycoplasma columbinum Strain SF7 - Guo_2013_Genome.Announc_1_e0015713
Author(s) : Guo Z , Xu X , Zheng Q , Li T , Kuang S , Zhang Z , Chen Y , Lu X , Zhou R , Bi D , Jin H
Ref : Genome Announc , 1 :e0015713 , 2013
Abstract : Mycoplasma columbinum is a member of nonglycolytic Mycoplasma species which can hydrolyze arginine. Increasingly research has revealed that M. columbinum is associated with respiratory disease of pigeons and that the respiratory disease symptoms could be eliminated via the use of mycoplasma treatment medicine. Here we report the genome sequence of M. columbinum strain SF7, which is the first genome report for M. columbinum.
ESTHER : Guo_2013_Genome.Announc_1_e0015713
PubMedSearch : Guo_2013_Genome.Announc_1_e0015713
PubMedID: 23599295

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

Title : 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism - Zhang_2013_Biomaterials_34_7552
Author(s) : Zhang J , Cao Q , Li S , Lu X , Zhao Y , Guan JS , Chen JC , Wu Q , Chen GQ
Ref : Biomaterials , 34 :7552 , 2013
Abstract : Alzheimer's disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-beta deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages.
ESTHER : Zhang_2013_Biomaterials_34_7552
PubMedSearch : Zhang_2013_Biomaterials_34_7552
PubMedID: 23849878

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

Title : Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups - Tu_2012_Bioorg.Med.Chem_20_4422
Author(s) : Tu Z , Wang W , Cui J , Zhang X , Lu X , Xu J , Parsons SM
Ref : Bioorganic & Medicinal Chemistry , 20 :4422 , 2012
Abstract : To identify selective high-affinity ligands for the vesicular acetylcholine transporter (VAChT), we have incorporated a carbonyl group into the structures of trozamicol and prezamicol scaffolds, and also converted the secondary amines of the piperidines of trozamicols and prezamicols into amides. Of 18 new racemic compounds, 4 compounds displayed high affinity for VAChT (K(i)=10-20 nM) and greater than 300-fold selectivity for VAChT over sigma(1) and sigma(2) receptors, namely (4-(4-fluorobenzoyl)-4'-hydroxy-[1,3'-bipiperidin]-1'-yl)(3-methylthiophen-2-yl)m ethanone oxalate (9g) (K(i-VAChT)=11.4 nM, VAChT/sigma(1)=1063, VAChT/sigma(2)=370), (1'-benzoyl-4'-hydroxy-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10c) (K(i-VAChT)=15.4 nM, VAChT/sigma(1)=374, VAChT/sigma(2)=315), (4'-hydroxy-1'-(thiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)me thanone oxalate (10e) (K(i-VAChT)=19.0 nM, VAChT/sigma(1)=1787, VAChT/sigma(2)=335), and (4'-hydroxy-1'-(3-methylthiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyp henyl)methanone oxalate (10g) (K(i-VAChT)=10.2 nM, VAChT/sigma(1)=1500, VAChT/sigma(2)=2030). These four compounds can be radiosynthesized with C-11 or F-18 to validate their possibilities of serving as PET probes for quantifying the levels of VAChT in vivo.
ESTHER : Tu_2012_Bioorg.Med.Chem_20_4422
PubMedSearch : Tu_2012_Bioorg.Med.Chem_20_4422
PubMedID: 22739089

Title : The yak genome and adaptation to life at high altitude - Qiu_2012_Nat.Genet_44_946
Author(s) : Qiu Q , Zhang G , Ma T , Qian W , Wang J , Ye Z , Cao C , Hu Q , Kim J , Larkin DM , Auvil L , Capitanu B , Ma J , Lewin HA , Qian X , Lang Y , Zhou R , Wang L , Wang K , Xia J , Liao S , Pan S , Lu X , Hou H , Wang Y , Zang X , Yin Y , Ma H , Zhang J , Wang Z , Zhang Y , Zhang D , Yonezawa T , Hasegawa M , Zhong Y , Liu W , Huang Z , Zhang S , Long R , Yang H , Lenstra JA , Cooper DN , Wu Y , Shi P , Liu J
Ref : Nat Genet , 44 :946 , 2012
Abstract : Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.
ESTHER : Qiu_2012_Nat.Genet_44_946
PubMedSearch : Qiu_2012_Nat.Genet_44_946
PubMedID: 22751099
Gene_locus related to this paper: bosmu-l8ic43 , bovin-2neur , bovin-balip , bovin-BCHE , bovin-e1bbv2 , bovin-e1bn79 , bovin-est8 , bovin-f1mi11 , bovin-f1n385 , bovin-g3mxp5 , bovin-lipli , bovin-lipr2 , bovin-q2kj30 , bovin-q3sz79 , bovin-q3t0r6 , bovin-ABHDA , bovin-q08dw9 , bovin-ABHD16B , bovin-SPG21 , bovin-TEX30 , 9ceta-l8iwv2 , 9ceta-l8idy3 , 9ceta-l8hsi3 , bovin-e1bjq9 , bovin-f1mc21 , 9ceta-l8hyl8 , bovin-LIPG , bovin-a0a3q1nm09 , bovin-f1n2i5

Title : Carboxylesterase-Triggered Hydrolysis of Nanoparticle PEGylating Agents - Howard_2012_Langmuir_28_12030
Author(s) : Howard MD , Lu X , Rinehart JJ , Jay M , Dziubla TD
Ref : Langmuir , 28 :12030 , 2012
Abstract : Despite the importance of PEGylation in achieving long nanoparticle circulation times, many nanoparticles are coated with PEGylating agents susceptible to enzymatic degradation. In this study, solid lipid nanoparticles (SLNs) prepared with ester-containing compounds were evaluated for their stability in the presence of carboxylesterase. SLN suspensions became turbid within 30 min of enzymatic exposure, indicating possible disassociation of a portion of the nanoparticles. The particle size of SLNs incubated with the enzyme was smaller than the size of controls, although their morphologies appeared similar in transmission electron microscopy images. Although SLNs offered some protection over micelles, PEG6000 monostearate was rapidly degraded within 15 min. Hydrolysis of polysorbate 60 was much slower, reaching only 36% in 2 h. These studies reveal the importance of confirming the stability of PEG surface coatings prior to undertaking in vivo experiments in small animal models, which can have considerably higher plasma esterase activity than humans.
ESTHER : Howard_2012_Langmuir_28_12030
PubMedSearch : Howard_2012_Langmuir_28_12030
PubMedID: 22830432

Title : The entomopathogenic bacterial endosymbionts Xenorhabdus and Photorhabdus: convergent lifestyles from divergent genomes - Chaston_2011_PLoS.One_6_e27909
Author(s) : Chaston JM , Suen G , Tucker SL , Andersen AW , Bhasin A , Bode E , Bode HB , Brachmann AO , Cowles CE , Cowles KN , Darby C , de Leon L , Drace K , Du Z , Givaudan A , Herbert Tran EE , Jewell KA , Knack JJ , Krasomil-Osterfeld KC , Kukor R , Lanois A , Latreille P , Leimgruber NK , Lipke CM , Liu R , Lu X , Martens EC , Marri PR , Medigue C , Menard ML , Miller NM , Morales-Soto N , Norton S , Ogier JC , Orchard SS , Park D , Park Y , Qurollo BA , Sugar DR , Richards GR , Rouy Z , Slominski B , Slominski K , Snyder H , Tjaden BC , van der Hoeven R , Welch RD , Wheeler C , Xiang B , Barbazuk B , Gaudriault S , Goodner B , Slater SC , Forst S , Goldman BS , Goodrich-Blair H
Ref : PLoS ONE , 6 :e27909 , 2011
Abstract : Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points.
ESTHER : Chaston_2011_PLoS.One_6_e27909
PubMedSearch : Chaston_2011_PLoS.One_6_e27909
PubMedID: 22125637
Gene_locus related to this paper: xenna-d3vdr8 , xenne-n1nl20 , xenbs-d3v2h2

Title : Synthesis and in vitro biological evaluation of carbonyl group-containing analogues for sigma1 receptors - Wang_2011_J.Med.Chem_54_5362
Author(s) : Wang W , Cui J , Lu X , Padakanti PK , Xu J , Parsons SM , Luedtke RR , Rath NP , Tu Z
Ref : Journal of Medicinal Chemistry , 54 :5362 , 2011
Abstract : To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1) (K(i) = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K(i) > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K(i) = 44.2 nM). The compound [1'-(4-fluorobenzyl)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanon e (14a) displayed very high affinity and selectivity for sigma(1) receptor (K(i) = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.
ESTHER : Wang_2011_J.Med.Chem_54_5362
PubMedSearch : Wang_2011_J.Med.Chem_54_5362
PubMedID: 21732626

Title : Correlation between carboxylesterase alleles and insecticide resistance in Culex pipiens complex from China - Liu_2011_Parasit.Vectors_4_236
Author(s) : Liu Y , Zhang H , Qiao C , Lu X , Cui F
Ref : Parasit Vectors , 4 :236 , 2011
Abstract : BACKGROUND: In China, large amounts of chemical insecticides are applied in fields or indoors every year, directly or indirectly bringing selection pressure on vector mosquitoes. Culex pipiens complex has evolved to be resistant to all types of chemical insecticides, especially organophosphates, through carboxylesterases. Six resistant carboxylesterase alleles (Ester) were recorded previously and sometimes co-existed in one field population, representing a complex situation for the evolution of Ester genes. RESULTS: In order to explore the evolutionary scenario, we analyzed the data from an historical record in 2003 and a recent investigation on five Culex pipiens pallens populations sampled from north China in 2010. Insecticide bioassays showed that these five populations had high resistance to pyrethroids, medium resistance to organophosphates, and low resistance to carbamates. Six types of Ester alleles, EsterB1, Ester2, Ester8, Ester9, EsterB10, and Ester11 were identified, and the overall pattern of their frequencies in geographic distribution was consistent with the report seven years prior to this study. Statistical correlation analysis indicated that Ester8 and Ester9 positively correlated with resistance to four insecticides, and EsterB10 to one insecticide. The occurrences of these three alleles were positively correlated, while the occurrence of EsterB1 was negatively correlated with Ester8, indicating an allelic competition. CONCLUSION: Our analysis suggests that one insecticide can select multiple Ester alleles and one Ester allele can work on multiple insecticides. The evolutionary scenario of carboxylesterases under insecticide selection is possibly "one to many".
ESTHER : Liu_2011_Parasit.Vectors_4_236
PubMedSearch : Liu_2011_Parasit.Vectors_4_236
PubMedID: 22177233

Title : Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in extreme parasitism - Spanu_2010_Science_330_1543
Author(s) : Spanu PD , Abbott JC , Amselem J , Burgis TA , Soanes DM , Stuber K , Ver Loren van Themaat E , Brown JK , Butcher SA , Gurr SJ , Lebrun MH , Ridout CJ , Schulze-Lefert P , Talbot NJ , Ahmadinejad N , Ametz C , Barton GR , Benjdia M , Bidzinski P , Bindschedler LV , Both M , Brewer MT , Cadle-Davidson L , Cadle-Davidson MM , Collemare J , Cramer R , Frenkel O , Godfrey D , Harriman J , Hoede C , King BC , Klages S , Kleemann J , Knoll D , Koti PS , Kreplak J , Lopez-Ruiz FJ , Lu X , Maekawa T , Mahanil S , Micali C , Milgroom MG , Montana G , Noir S , O'Connell RJ , Oberhaensli S , Parlange F , Pedersen C , Quesneville H , Reinhardt R , Rott M , Sacristan S , Schmidt SM , Schon M , Skamnioti P , Sommer H , Stephens A , Takahara H , Thordal-Christensen H , Vigouroux M , Wessling R , Wicker T , Panstruga R
Ref : Science , 330 :1543 , 2010
Abstract : Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei (Blumeria), as well as a comparison with the analysis of two powdery mildews pathogenic on dicotyledonous plants. These genomes display massive retrotransposon proliferation, genome-size expansion, and gene losses. The missing genes encode enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, probably reflecting their redundancy in an exclusively biotrophic life-style. Among the 248 candidate effectors of pathogenesis identified in the Blumeria genome, very few (less than 10) define a core set conserved in all three mildews, suggesting that most effectors represent species-specific adaptations.
ESTHER : Spanu_2010_Science_330_1543
PubMedSearch : Spanu_2010_Science_330_1543
PubMedID: 21148392
Gene_locus related to this paper: blugr-d2cql4 , blug1-n1jlh9 , blug1-n1j5n4 , blug1-n1j9r9 , blug1-n1je34 , blug1-n1jkm5 , blug1-n1jhv6 , blug1-n1j8l0 , blug1-n1jqj7 , blug1-n1j543

Title : PLA2G7 gene polymorphisms and coronary heart disease risk: a meta-analysis - Wang_2010_Thromb.Res_126_498
Author(s) : Wang Q , Hao Y , Mo X , Wang L , Lu X , Huang J , Cao J , Li H , Gu D
Ref : Thromb Res , 126 :498 , 2010
Abstract : INTRODUCTION: Variants of PLA2G7 gene have been reported to be associated with coronary heart disease (CHD) since ten years ago, but the available data on this relationship are inconsistent. A meta-analysis was conducted to assess the effect of PLA2G7 gene on CHD. MATERIALS AND METHODS: Association studies were identified from the databases of PubMed, EMbase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang by two investigators and pooled effects (odds ratio (OR), together with 95% confidence interval (CI)) were calculated. RESULTS: 14 association studies focusing on three polymorphisms (A379V, V279F and R92H) in PLA2G7 gene and risk of CHD were included in meta-analysis, covering a total of 8,280 cases and 5,656 controls. Concerning R92H, a significantly increased CHD risk was observed in recessive model, with an OR of 1.31(1.02, 1.68). Nevertheless, combined analyses of studies of the A379V and V279F variants showed no significant overall association with CHD, yielding ORs of 0.99(0.85, 1.15) and 1.09(0.88, 1.35) in allelic analysis, with strong evidence of heterogeneity. Similar results were also obtained in dominant and recessive models. CONCLUSIONS: The results indicate 92H allele had probably increased the risk of CHD, while the hypothesized effects of A379V and V279F polymorphisms on CHD cannot be confirmed in present data. However, given the limited number of studies and the potential biases, the influence of these polymorphisms on CHD risk needs further investigation.
ESTHER : Wang_2010_Thromb.Res_126_498
PubMedSearch : Wang_2010_Thromb.Res_126_498
PubMedID: 20926117
Gene_locus related to this paper: human-PLA2G7

Title : Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2 - Lu_2010_Cell.Cycle_9_2719
Author(s) : Lu X , Yang X , Liu J
Ref : Cell Cycle , 9 :2719 , 2010
Abstract : Lipid droplets (LDs) are intracellular storage sites for triacylglyerols (TAGs)and steryl esters, and play essential roles in energy metabolism and membrane biosynthesis. Adipose triglyceride lipase (ATGL) is the key enzyme for TAG hydrolysis (lipolysis) in adipocytes and LD degradation in nonadipocyte cells. Lipase activity of ATGL in vivo largely depends on its C-terminal sequence as well as coactivation by CGI-58. Here we demonstrate that the C-terminal hydrophobic domain in ATGL is required for LD targeting and CGI-58-independent LD degradation. Overexpression of wild type ATGL causes a dramatic decrease in LD size and number, whereas a mutant lacking the hydrophobic domain fails to localize to LDs and to affect their morphology. Interestingly, coexpression of CGI-58 is able to promote LD turnover mediated by this ATGL mutant. Recently we have discovered that G0S2 acts as an inhibitor of ATGL activity and ATGL-mediated lipolysis. Here we show that G0S2 binds to ATGL irrelevantly of its activity state or the presence of CGI-58. In G0S2-expressing cells, the combined expression of CGI-58 and ATGL is incapable of stimulating LD turnover. We propose that CGI-58 and G0S2 regulate ATGL via non-competing mechanisms.
ESTHER : Lu_2010_Cell.Cycle_9_2719
PubMedSearch : Lu_2010_Cell.Cycle_9_2719
PubMedID: 20676045

Title : Identification of a novel splicing isoform of murine CGI-58 - Yang_2010_FEBS.Lett_584_903
Author(s) : Yang X , Lu X , Liu J
Ref : FEBS Letters , 584 :903 , 2010
Abstract : The comparative gene identification-58 (CGI-58) gene, mutations of which are linked to Chanarin-Dorfman syndrome, encodes a protein of the alpha/beta hydrolase domain subfamily. We report here a new alternative splicing isoform of the murine CGI-58 gene, termed mCGI-58S. Sequence comparison indicates the lack of second and third exons in this cDNA variant. While the full-length protein displayed perilipin-dependent localization to lipid droplets, mCGI-58S showed a predominant cytoplasmic staining when expressed in cells. mCGI-58S was incapable of activating adipose triglyceride lipase but retained the capacity to acylate lysophosphatidic acid. Overexpression of mCGI-58S failed to promote lipid droplet turnover and loss of intracellular triacylglycerols. These results suggest that this splicing event may be involved in the regulation of lipid homeostasis.
ESTHER : Yang_2010_FEBS.Lett_584_903
PubMedSearch : Yang_2010_FEBS.Lett_584_903
PubMedID: 20083112
Gene_locus related to this paper: mouse-abhd5

Title : The G(0)\/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase - Yang_2010_Cell.Metab_11_194
Author(s) : Yang X , Lu X , Lombes M , Rha GB , Chi YI , Guerin TM , Smart EJ , Liu J
Ref : Cell Metab , 11 :194 , 2010
Abstract : Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G(0)/G(1) switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.
ESTHER : Yang_2010_Cell.Metab_11_194
PubMedSearch : Yang_2010_Cell.Metab_11_194
PubMedID: 20197052

Title : Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants II: role of plasma esterases in drug release -
Author(s) : Lu X , Howard MD , Talbert DR , Rinehart JJ , Potter PM , Jay M , Leggas M
Ref : AAPS J , 11 :120 , 2009
PubMedID: 19225893

Title : Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study - Hou_2009_Hum.Genet_125_11
Author(s) : Hou L , Chen S , Yu H , Lu X , Chen J , Wang L , Huang J , Fan Z , Gu D
Ref : Hum Genet , 125 :11 , 2009
Abstract : The human PLA2G7 gene encodes lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA(2) activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA(2) activity in CHD and MI cases was significantly higher (233.42+/-57.66 and 234.27+/-59.51 nmol ml(-1) min(-1), respectively) than in controls (211.47+/-58.61 nmol ml(-1) min(-1)). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA(2) activity were 1.27 (95% CI, 1.07-1.50) and 1.27 (95% CI, 1.05-1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA(2) activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA(2) activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA(2), only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA(2) activity appears to influence the CHD and MI risk in Chinese Han population.
ESTHER : Hou_2009_Hum.Genet_125_11
PubMedSearch : Hou_2009_Hum.Genet_125_11
PubMedID: 19034521
Gene_locus related to this paper: human-PLA2G7

Title : Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88 - Pel_2007_Nat.Biotechnol_25_221
Author(s) : Pel HJ , de Winde JH , Archer DB , Dyer PS , Hofmann G , Schaap PJ , Turner G , de Vries RP , Albang R , Albermann K , Andersen MR , Bendtsen JD , Benen JA , van den Berg M , Breestraat S , Caddick MX , Contreras R , Cornell M , Coutinho PM , Danchin EG , Debets AJ , Dekker P , van Dijck PW , van Dijk A , Dijkhuizen L , Driessen AJ , d'Enfert C , Geysens S , Goosen C , Groot GS , de Groot PW , Guillemette T , Henrissat B , Herweijer M , van den Hombergh JP , van den Hondel CA , van der Heijden RT , van der Kaaij RM , Klis FM , Kools HJ , Kubicek CP , van Kuyk PA , Lauber J , Lu X , van der Maarel MJ , Meulenberg R , Menke H , Mortimer MA , Nielsen J , Oliver SG , Olsthoorn M , Pal K , van Peij NN , Ram AF , Rinas U , Roubos JA , Sagt CM , Schmoll M , Sun J , Ussery D , Varga J , Vervecken W , van de Vondervoort PJ , Wedler H , Wosten HA , Zeng AP , van Ooyen AJ , Visser J , Stam H
Ref : Nat Biotechnol , 25 :221 , 2007
Abstract : The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.
ESTHER : Pel_2007_Nat.Biotechnol_25_221
PubMedSearch : Pel_2007_Nat.Biotechnol_25_221
PubMedID: 17259976
Gene_locus related to this paper: aspna-g3yal2 , aspnc-a2q8r7 , aspnc-a2q814 , aspnc-a2qb93 , aspnc-a2qbd3 , aspnc-a2qbh3 , aspnc-a2qbx7 , aspnc-a2qdj6 , aspnc-a2qe77 , aspnc-a2qf54 , aspnc-a2qfe9 , aspnc-a2qg33 , aspnc-a2qgj6 , aspnc-a2qgm6 , aspnc-a2qh52 , aspnc-a2qh76 , aspnc-a2qh85 , aspnc-a2qhe2 , aspnc-a2qi32 , aspnc-a2qib2 , aspnc-a2qk14 , aspnc-a2ql23 , aspnc-a2ql89 , aspnc-a2ql90 , aspnc-a2qla0 , aspnc-a2qlz0 , aspnc-a2qm14 , aspnc-a2qmk5 , aspnc-a2qms0 , aspnc-a2qn29 , aspnc-a2qn56 , aspnc-a2qn70 , aspnc-a2qnw9 , aspnc-a2qr21 , aspnc-a2qs22 , aspnc-a2qt50 , aspnc-a2qti9 , aspnc-a2qtz0 , aspnc-a2quc1 , aspnc-a2qw06 , aspnc-a2qwz6 , aspnc-a2qx92 , aspnc-a2qyf0 , aspnc-a2qys7 , aspnc-a2qz72 , aspnc-a2qzn6 , aspnc-a2qzr0 , aspnc-a2qzs1 , aspnc-a2qzx0 , aspnc-a2qzx4 , aspnc-a2r0p4 , aspnc-a2r0u0 , aspnc-a2r1p3 , aspnc-a2r1r5 , aspnc-a2r2i5 , aspnc-a2r2l0 , aspnc-a2r3s8 , aspnc-a2r4c0 , aspnc-a2r4j8 , aspnc-a2r5r4 , aspnc-a2r6g3 , aspnc-a2r6h5 , aspnc-a2r6h8 , aspnc-a2r7q1 , aspnc-a2r8r3 , aspnc-a2r8z3 , aspnc-a2r9y8 , aspnc-a2r032 , aspnc-a2r040 , aspnc-a2r273 , aspnc-a2r496 , aspnc-a2r502 , aspnc-a2ra07 , aspnc-a2rap4 , aspnc-a2raq2 , aspnc-a2rav1 , aspnc-a5aaf4 , aspnc-a5ab63 , aspnc-a5abc6 , aspnc-a5abe5 , aspnc-a5abe8 , aspnc-a5abf0 , aspnc-a5abh9 , aspnc-a5abk1 , aspnc-a5abt2 , aspnc-a5abz1 , aspnc-atg15 , aspnc-axe1 , aspnc-cuti1 , aspnc-cuti2 , aspnc-faec , aspng-a2q8w0 , aspng-a2qs46 , aspng-a2qst4 , aspng-a2qv27 , aspng-a2qzk9 , aspng-a2r0p8 , aspng-a2r225 , aspng-DAPB , aspng-DPP5 , aspng-faeb , aspni-APSC , aspni-EstA , aspni-FAEA , aspni-PAPA , aspkw-g7y0v7 , aspnc-a2qt47 , aspnc-a2qt66 , aspnc-a2r199 , aspnc-a2r871 , aspnc-a2qbp6 , aspnc-a2qqa1 , aspnc-a2qt70 , aspna-g3y5a6 , aspna-g3xpw9 , aspnc-a2qw57 , aspaw-a0a401kcz4 , aspna-alba , aspnc-kex1 , aspnc-cbpya , aspnc-a2qbg8

Title : Molecular cloning and functional analysis of two polyhydroxyalkanoate synthases from two strains of Aeromonas hydrophila spp - Lu_2005_FEMS.Microbiol.Lett_243_149
Author(s) : Lu X , Zhang W , Jian J , Wu Q , Chen GQ
Ref : FEMS Microbiology Letters , 243 :149 , 2005
Abstract : Polyhydroxyalkanoate (PHA) synthase genes (phaC) were cloned from two Aeromonas hydrophila strains named WQ and 4AK5, respectively. Both strains are able to produce PHBHHx copolyesters consisting of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx). Sequence analysis showed that there was only 2 bp difference between these two PHA synthase genes, corresponding to two-amino acid difference at positions of 437 and 458 of the two synthases. PHA productivity and its monomer content produced by A. hydrophila WQ and A. hydrophila 4AK5 were quite different. A. hydrophila WQ accumulated 33% PHBHHx of its cell dry weight (CDW) with 5 mol% 3HHx in the copolyester when cultured in lauric acid for 48 h. Yet A. hydrophila 4AK5 was able to produce 43% PHBHHx of the CDW with 14 mol% 3HHx under the same condition. Hetero-expression of PHA synthase genes of A. hydrophila WQ and A. hydrophila 4AK5, respectively, in Escherichia coli XL1-Blue led to PHBHHx accumulation of 24% and 39% of the CDW and the 3HHx content in PHBHHx were 6 and 15 mol%, respectively. This indicated that the function of these two PHA synthases were different due to these two different residues at positions of 437 and 458. Site specific mutation was carried out to change these two amino acid residues. Results showed that the changes on either of the two amino acids negatively affected the PHA productivity.
ESTHER : Lu_2005_FEMS.Microbiol.Lett_243_149
PubMedSearch : Lu_2005_FEMS.Microbiol.Lett_243_149
PubMedID: 15668013
Gene_locus related to this paper: aerhy-PHAC

Title : The strength of dehalogenase-substrate hydrogen bonding correlates with the rate of Meisenheimer intermediate formation - Dong_2003_Biochemistry_42_9482
Author(s) : Dong J , Lu X , Wei Y , Luo L , Dunaway-Mariano D , Carey PR
Ref : Biochemistry , 42 :9482 , 2003
Abstract : 4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolytic dehalogenation of 4-CBA-CoA to 4-hydroxybenzoyl-CoA by using an active site aspartate as the nucleophile. Formation of the corresponding Meisenheimer complex (EMc) is followed by chloride ion expulsion which forms the arylated intermediate (EAr). This is then hydrolyzed to the product. In this paper, we explore the relationship between active site polarizing forces acting on the benzoyl carbonyl and the rate of formation of the Meisenheimer complex. The polarizing forces at the C[double bond]O group were modulated by introducing site-selected mutations (A112V, Y65D, G113A, G113S, G113N, and F64P), near the C[double bond]O binding site. Using either the substrate, 4-CBA-CoA, or the substrate analogue, 4-methylbenzoyl-CoA (4-MBA-CoA), Raman difference spectroscopy provided the position of the C[double bond]O stretching frequency (nu(C)[double bond](O)) for a total of 10 enzyme-ligand complexes. In turn, the values of the C[double bond]O frequencies could be converted to differences in effective hydrogen bonding strengths between members of the series, based on earlier model studies [Clarkson, J., Tonge, P. J., Taylor, K. L., Dunaway-Mariano, D., and Carey, P. (1997) Biochemistry 36, 10192-10199]. Catalysis in the F64P, G113A, G113S, and G113N dehalogenase mutants was very slow with k(cat) values ranging from 8 x 10(-3) to 7.6 x 10(-6) s(-1). The EAr intermediate did not accumulate to a detectable level on these enzymes during a single turnover. Catalysis in the Y65D and A112V dehalogenase mutants were almost as efficient as catalysis in wild-type dehalogenase with k(cat) values of 0.1-0.6 s(-1). In wild-type dehalogenase, 22% of the bound substrate accumulated as the EAr intermediate during a single turnover (k(obs) for EAr formation = 24 s(-(1)); in the Y65D mutant, the level of accumulation is 17% (k(obs) for EAr formation = 3 s(-1)), and in the A112V mutant, the level is 23% (k(obs) for EAr formation = 17 s(-1)). The k(obs) for EAr formation in wild-type dehalogenase and the more active dehalogenase mutants (Y65D and A112V) was taken to be an estimate of the k for EMc formation, and the k(obs) for EP formation in a single turnover was taken to be an estimate of the k for EMc formation in the severely impaired mutants (F64P, G113A, G113S, and G113N). A plot of the log k(obs) for EMc formation versus the C[double bond]O stretching frequency of bound 4-CBA-CoA (or 4-MBA-CoA) is a straight line (R(2) = 0.9584). Throughout the series, nu(C)[double bond](O) varied by 61 cm(-1), corresponding to the change in hydrogen bonding enthalpy of 67 kJ/mol. The results show that changes in polarizing forces at the benzoyl carbonyl are transmitted to the benzoyl (4) position and correlate with the rate of aromatic nucleophilic addition five chemical bonds away. Interestingly, the relationship between effective polarizing forces and reactivity seen here for dehalogenase is similar to that reported for the addition-elimination reaction involving the hydrolysis of a series of acyl serine proteases.
ESTHER : Dong_2003_Biochemistry_42_9482
PubMedSearch : Dong_2003_Biochemistry_42_9482
PubMedID: 12899635

Title : Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences - Strausberg_2002_Proc.Natl.Acad.Sci.U.S.A_99_16899
Author(s) : Strausberg RL , Feingold EA , Grouse LH , Derge JG , Klausner RD , Collins FS , Wagner L , Shenmen CM , Schuler GD , Altschul SF , Zeeberg B , Buetow KH , Schaefer CF , Bhat NK , Hopkins RF , Jordan H , Moore T , Max SI , Wang J , Hsieh F , Diatchenko L , Marusina K , Farmer AA , Rubin GM , Hong L , Stapleton M , Soares MB , Bonaldo MF , Casavant TL , Scheetz TE , Brownstein MJ , Usdin TB , Toshiyuki S , Carninci P , Prange C , Raha SS , Loquellano NA , Peters GJ , Abramson RD , Mullahy SJ , Bosak SA , McEwan PJ , McKernan KJ , Malek JA , Gunaratne PH , Richards S , Worley KC , Hale S , Garcia AM , Gay LJ , Hulyk SW , Villalon DK , Muzny DM , Sodergren EJ , Lu X , Gibbs RA , Fahey J , Helton E , Ketteman M , Madan A , Rodrigues S , Sanchez A , Whiting M , Young AC , Shevchenko Y , Bouffard GG , Blakesley RW , Touchman JW , Green ED , Dickson MC , Rodriguez AC , Grimwood J , Schmutz J , Myers RM , Butterfield YS , Krzywinski MI , Skalska U , Smailus DE , Schnerch A , Schein JE , Jones SJ , Marra MA
Ref : Proc Natl Acad Sci U S A , 99 :16899 , 2002
Abstract : The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence a cDNA clone containing a complete ORF for each human and mouse gene. ESTs were generated from libraries enriched for full-length cDNAs and analyzed to identify candidate full-ORF clones, which then were sequenced to high accuracy. The MGC has currently sequenced and verified the full ORF for a nonredundant set of >9,000 human and >6,000 mouse genes. Candidate full-ORF clones for an additional 7,800 human and 3,500 mouse genes also have been identified. All MGC sequences and clones are available without restriction through public databases and clone distribution networks (see http:mgc.nci.nih.gov).
ESTHER : Strausberg_2002_Proc.Natl.Acad.Sci.U.S.A_99_16899
PubMedSearch : Strausberg_2002_Proc.Natl.Acad.Sci.U.S.A_99_16899
PubMedID: 12477932
Gene_locus related to this paper: bovin-q3zcj6 , danre-OVCA2 , danre-q4qrh4 , danre-q4v960 , danre-q32ls6 , danre-q503e2 , ratno-CPVL , ratno-q3mhs0 , ratno-q4qr68 , ratno-q5fvr5 , ratno-q32q55 , xenla-a2bd54 , xenla-q2tap9 , xenla-q3kq37 , xenla-q3kq76 , xenla-q4klb6 , xenla-q32n48 , xenla-q32ns5 , xenla-q52l41 , xentr-q4va73 , danre-a7mbu9