Wang R

References (84)

Title : DPP8\/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathway - Li_2024_Toxicol.Lett__
Author(s) : Li K , Zhang Y , Zhao W , Wang R , Li Y , Wei L , Wang L , Chen X , Chen Z , Liu P , Nie N , Tian X , Fu R
Ref : Toxicol Lett , : , 2024
Abstract : The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9 involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgAN patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-beta1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen , collagen , fibronectin, MMP2, in TGF-beta1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-beta1 via suppressing TGF-beta1/Smad and AKT signaling pathway.
ESTHER : Li_2024_Toxicol.Lett__
PubMedSearch : Li_2024_Toxicol.Lett__
PubMedID: 38458339

Title : Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors - Wang_2024_J.Org.Chem__
Author(s) : Wang K , Wang R , Yan Z , Li Y , Shi Y , Ge JY , Bai Y , Chen Z , Zhang L
Ref : J Org Chem , : , 2024
Abstract : Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.
ESTHER : Wang_2024_J.Org.Chem__
PubMedSearch : Wang_2024_J.Org.Chem__
PubMedID: 38720168

Title : Annexin A6 mitigates neurological deficit in ischemia\/reperfusion injury by promoting synaptic plasticity - Wang_2024_CNS.Neurosci.Ther_30_e14639
Author(s) : Wang Y , Yang Z , Wang R , Zheng Y , Han Z , Fan J , Yan F , Liu P , Luo Y
Ref : CNS Neurosci Ther , 30 :e14639 , 2024
Abstract : AIMS: Alleviating neurological dysfunction caused by acute ischemic stroke (AIS) remains intractable. Given Annexin A6 (ANXA6)'s potential in promoting axon branching and repairing cell membranes, the study aimed to explore ANXA6's potential in alleviating AIS-induced neurological dysfunction. METHODS: A mouse middle cerebral artery occlusion model was established. Brain and plasma ANXA6 levels were detected at different timepoints post ischemia/reperfusion (I/R). We overexpressed and down-regulated brain ANXA6 and evaluated infarction volume, neurological function, and synaptic plasticity-related proteins post I/R. Plasma ANXA6 levels were measured in patients with AIS and healthy controls, investigating ANXA6 expression's clinical significance. RESULTS: Brain ANXA6 levels initially decreased, gradually returning to normal post I/R; plasma ANXA6 levels showed an opposite trend. ANXA6 overexpression significantly decreased the modified neurological severity score (p = 0.0109) 1 day post I/R and the infarction area at 1 day (p = 0.0008) and 7 day (p = 0.0013) post I/R, and vice versa. ANXA6 positively influenced synaptic plasticity, upregulating synaptophysin (p = 0.006), myelin basic protein (p = 0.010), neuroligin (p = 0.078), and tropomyosin-related kinase B (p = 0.150). Plasma ANXA6 levels were higher in patients with AIS (1.969 [1.228-3.086]) compared to healthy controls (1.249 [0.757-2.226]) (p < 0.001), that served as an independent risk factor for poor AIS outcomes (2.120 [1.563-3.023], p < 0.001). CONCLUSIONS: This study is the first to suggest that ANXA6 enhances synaptic plasticity and protects against transient cerebral ischemia.
ESTHER : Wang_2024_CNS.Neurosci.Ther_30_e14639
PubMedSearch : Wang_2024_CNS.Neurosci.Ther_30_e14639
PubMedID: 38380783

Title : Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish: Effects on neurobehaviors and multiple biomarkers - Zhang_2024_J.Environ.Sci.(China)_143_138
Author(s) : Zhang R , Wang R , Chang J , Sheng GD , Yin D
Ref : J Environ Sci (China) , 143 :138 , 2024
Abstract : Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA(+)) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA(+) exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA(+) evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA(+) exposure than larval zebrafish.
ESTHER : Zhang_2024_J.Environ.Sci.(China)_143_138
PubMedSearch : Zhang_2024_J.Environ.Sci.(China)_143_138
PubMedID: 38644012

Title : Identification and characterization of novel carboxyl ester lipase gene variants in patients with different subtypes of diabetes - Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
Author(s) : Wu H , Shu M , Liu C , Zhao W , Li Q , Song Y , Zhang T , Chen X , Shi Y , Shi P , Fang L , Wang R , Xu C
Ref : BMJ Open Diabetes Res Care , 11 : , 2023
Abstract : INTRODUCTION: Mutations of CEL gene were first reported to cause a new type of maturity-onset diabetes of the young (MODY) denoted as MODY8 and then were also found in patients with type 1 (T1D) and type 2 diabetes (T2D). However, its genotype-phenotype relationship has not been fully determined and how carboxyl ester lipase (CEL) variants result in diabetes remains unclear. The aim of our study was to identify pathogenic variants of CEL in patients with diabetes and confirm their pathogenicity. RESEARCH DESIGN AND METHODS: All five patients enrolled in our study were admitted to Shandong Provincial Hospital and diagnosed with diabetes in the past year. Whole-exome sequencing was performed to identify pathogenic variants in three patients with MODY-like diabetes, one newborn baby with T1D and one patient with atypical T2D, as well as their immediate family members. Then the consequences of the identified variants were predicted by bioinformatic analysis. Furthermore, pathogenic effects of two novel CEL variants were evaluated in HEK293 cells transfected with wild-type and mutant plasmids. Finally, we summarized all CEL gene variants recorded in Human Gene Mutation Database and analyzed the mutation distribution of CEL. RESULTS: Five novel heterozygous variants were identified in CEL gene and they were predicted to be pathogenic by bioinformatic analysis. Moreover, in vitro studies indicated that the expression of CEL(R540C) was remarkably increased, while p.G729_T739del variant did not significantly affect the expression of CEL. Both novel variants obviously abrogated the secretion of CEL. Furthermore, we summarized all reported CEL variants and found that 74.3% of missense mutations were located in exons 1, 3, 4, 10 and 11 and most missense variants clustered near catalytic triad, Arg-83 and Arg-443. CONCLUSION: Our study identified five novel CEL variants in patients with different subtypes of diabetes, expanding the gene mutation spectrum of CEL and confirmed the pathogenicity of several novel variants.
ESTHER : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedSearch : Wu_2023_BMJ.Open.Diabetes.Res.Care_11_e003127
PubMedID: 36634979
Gene_locus related to this paper: human-CEL

Title : The effect of chlorogenic acid, a potential botanical insecticide, on gene transcription and protein expression of carboxylesterases in the armyworm (Mythimna separata) - Lin_2023_Pestic.Biochem.Physiol_195_105575
Author(s) : Lin DJ , Zhang YX , Fang Y , Gao SJ , Wang R , Wang JD
Ref : Pestic Biochem Physiol , 195 :105575 , 2023
Abstract : Chlorogenic acid (CGA) is a potential botanical insecticide metabolite that naturally occurs in various plants. Our previous studies revealed CGA is sufficient to control the armyworm Mythimna separata. In this study, we conducted a proteomic analysis of saliva collected from M. separata following exposure to CGA and found that differentially expressed proteins (DEPs) treated with CGA for 6 h and 24 h were primarily enriched in glutathione metabolism and the pentose phosphate pathway. Notably, we observed six carboxylesterase (CarE) proteins that were enriched at both time points. Additionally, these corresponding genes were expressed at levels 5.05 to 130.25 times higher in our laboratory-selected resistance strains. We also noted a significant increase in the enzyme activity of carboxylesterase following treatments with varying CGA concentrations. Finally, we confirmed that knockdown of MsCarE14, MsCarE28, and MsCCE001h decreased the susceptibility to CGA in resistance strain, indicating three CarE genes play crucial roles in CGA detoxification. This study presents the first report on the salivary proteomics of M. separata, offering valuable insights into the role of salivary proteins. Moreover, the determination of CarE mediated susceptibility change to CGA provides new targets for agricultural pest control and highlights the potential insecticide resistance mechanism for pest resistance management.
ESTHER : Lin_2023_Pestic.Biochem.Physiol_195_105575
PubMedSearch : Lin_2023_Pestic.Biochem.Physiol_195_105575
PubMedID: 37666601

Title : Preparation, structural properties, and in vitro and in vivo activities of peptides against dipeptidyl peptidase IV (DPP-IV) and alpha-glucosidase: a general review - Mu_2023_Crit.Rev.Food.Sci.Nutr__1
Author(s) : Mu X , Wang R , Cheng C , Ma Y , Zhang Y , Lu W
Ref : Crit Rev Food Sci Nutr , :1 , 2023
Abstract : Diabetes is one of the fastest-growing and most widespread diseases worldwide. Approximately 90% of diabetic patients have type 2 diabetes. In 2019, there were about 463 million diabetic patients worldwide. Inhibiting the dipeptidyl peptidase IV (DPP-IV) and alpha-glucosidase activity is an effective strategy for the treatment of type 2 diabetes. Currently, various anti-diabetic bioactive peptides have been isolated and identified. This review summarizes the preparation methods, structure-effect relationships, molecular binding sites, and effectiveness validation of DPP-IV and alpha-glucosidase inhibitory peptides in cellular and animal models. The analysis of peptides shows that the DPP-IV inhibitory peptides, containing 2-8 amino acids and having proline, leucine, and valine at their N-terminal and C-terminal, are the highly active peptides. The more active alpha-glucosidase inhibitory peptides contain 2-9 amino acids and have valine, isoleucine, and proline at the N-terminal and proline, alanine, and serine at the C-terminal.
ESTHER : Mu_2023_Crit.Rev.Food.Sci.Nutr__1
PubMedSearch : Mu_2023_Crit.Rev.Food.Sci.Nutr__1
PubMedID: 37310013

Title : Aerobic exercise-induced decrease of chemerin improved glucose and lipid metabolism and fatty liver of diabetes mice through key metabolism enzymes and proteins - Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
Author(s) : Lin X , Qu J , Yin L , Wang R , Wang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159409 , 2023
Abstract : Our previous studies have implicated an important role of adipokine chemerin in exercise-induced improvements of glycolipid metabolism and fatty liver in diabetes rat, but the underlying mechanisms remain unknown. This study first used an exogenous chemerin supplement to clarify the roles of decreased chemerin in exercised diabetes mice and possible mechanisms of glucose and lipid metabolism key enzymes and proteins [such as adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 4 (GLUT4)]. In addition, two kinds of adipose-specific chemerin knockout mice were generated to demonstrate the regulation of chemerin on glucose and lipid metabolism enzymes and proteins. We found that in diabetes mice, exercise-induced improvements of glucose and lipid metabolism and fatty liver, and exercise-induced increases of ATGL, LPL, and GLUT4 in liver, gastrocnemius and fat were reversed by exogenous chemerin. Furthermore, in chemerin knockdown mice, chemerin(-/-)adiponectin mice had lower body fat mass, improved blood glucose and lipid, and no fatty liver; while chemerin(-/-)fabp4 mice had hyperlipemia and unchanged body fat mass. Peroxisome proliferator-activated receptor gamma (PPARgamma), ATGL, LPL, GLUT4 and PEPCK in the liver and gastrocnemius had improve changes in chemerin(-/-).adiponectin mice while deteriorated alterations in chemerin(-/-).fabp4 mice, although PPARgamma, ATGL, LPL, and GLUT4 increased in the fat of two kinds of chemerin(-/-) mice. CONCLUSIONS: Decreased chemerin exerts an important role in exercise-induced improvements of glucose and lipid metabolism and fatty liver in diabetes mice, which was likely to be through PPARgamma mediating elevations of ATGL, LPL and GLUT4 in peripheral metabolic organs.
ESTHER : Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
PubMedSearch : Lin_2023_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159409
PubMedID: 37871796

Title : Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency - Xia_2023_J.Clin.Lipidol__
Author(s) : Xia Y , Zheng W , Du T , Gong Z , Liang L , Wang R , Yang Y , Zhang K , Lu D , Chen X , Sun Y , Xiao B , Qiu W
Ref : J Clin Lipidol , : , 2023
Abstract : BACKGROUND: Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. OBJECTIVE: To describe the manifestations and management of 19 pediatric patients with LPL-FCS. METHODS: LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. RESULTS: Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. CONCLUSIONS: This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy.
ESTHER : Xia_2023_J.Clin.Lipidol__
PubMedSearch : Xia_2023_J.Clin.Lipidol__
PubMedID: 37858495
Gene_locus related to this paper: human-LPL

Title : Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles - Wu_2022_Heliyon_8_e11751
Author(s) : Wu MY , Shi XC , Shan J , Wang R , Wang Y , Li J , Tian DN , Xu HM
Ref : Heliyon , 8 :e11751 , 2022
Abstract : OBJECTIVE: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. METHODS: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-alpha), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. RESULTS: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-alpha increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (++), CHRM5 (++), CHRNA5 (++), CHRNA7 (++), CHRNA9 (- +), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. CONCLUSION: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.
ESTHER : Wu_2022_Heliyon_8_e11751
PubMedSearch : Wu_2022_Heliyon_8_e11751
PubMedID: 36468138

Title : Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes - Xie_2022_Biochem.Biophys.Res.Commun_641_93
Author(s) : Xie H , Liu S , Fu Y , Cheng Q , Wang P , Bi CL , Wang R , Chen MM , Fang M
Ref : Biochemical & Biophysical Research Communications , 641 :93 , 2022
Abstract : Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.
ESTHER : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedSearch : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedID: 36525929

Title : Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster - Zhu_2022_Theor.Appl.Genet__
Author(s) : Zhu K , Li M , Wu H , Zhang D , Dong L , Wu Q , Chen Y , Xie J , Lu P , Guo G , Zhang H , Zhang P , Li B , Li W , Wang Q , Zhu J , Hu W , Guo L , Wang R , Yuan C , Li H , Liu Z , Hua W
Ref : Theor Appl Genet , : , 2022
Abstract : Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.
ESTHER : Zhu_2022_Theor.Appl.Genet__
PubMedSearch : Zhu_2022_Theor.Appl.Genet__
PubMedID: 35006335

Title : Impact of amyloid PET in the clinical care of veterans in a tertiary memory disorders clinic - Vives-Rodriguez_2022_Alzheimers.Dement.(N.Y)_8_e12320
Author(s) : Vives-Rodriguez AL , Schiloski KA , Marin A , Wang R , Hajos GP , Powsner R , DeCaro R , Budson AE , Turk KW
Ref : Alzheimers Dement (N Y) , 8 :e12320 , 2022
Abstract : INTRODUCTION: We aimed to characterize the clinical impact of amyloid PET (APET) in a veteran population with cognitive decline by comparing differences in management between those who did and did not have an APET. METHODS: This was a retrospective observational study. Poisson regressions and logistic regression were used for comparisons. RESULTS: Out of 565 veterans, 197 underwent APET; positivity rate was 36.55%. Having an APET was associated with longer follow-up, and increased diagnostic variability; it was not associated with number of additional studies, cholinesterase inhibitors prescription, or referrals to research. A positive APET was associated with less diagnostic variability, fewer additional tests, greater cholinesterase inhibitor prescriptions, and more research referrals. DISCUSSION: In a medically complex, real-world population, APET yielded lower positivity rates and was not associated with classical clinical utility variables when comparing patients with and without an APET. APET may be used more to "rule out" rather than to confirm Alzheimer's disease. HIGHLIGHTS: Amyloid PET was associated with longer follow-up, and higher diagnostic variability.No association was seen with cholinesterase inhibitors prescription, or referrals to research.In complex patients, expected amyloid PET positivity rates are lower than previously described.Amyloid PETs were used to "rule out" AD than to confirm the diagnosis of AD.
ESTHER : Vives-Rodriguez_2022_Alzheimers.Dement.(N.Y)_8_e12320
PubMedSearch : Vives-Rodriguez_2022_Alzheimers.Dement.(N.Y)_8_e12320
PubMedID: 35992216

Title : Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects - Wang_2022_Front.Neurol_13_933217
Author(s) : Wang R , Gao H , Xie H , Jia Z , Chen Q
Ref : Front Neurol , 13 :933217 , 2022
Abstract : Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with (18)F-flortaucipir and (11)C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the (11)C-DOPA and (11)C-CFT in PET and the (123)I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the (11)C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the (11)C-DAA1106 and (11)C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. (18)F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.
ESTHER : Wang_2022_Front.Neurol_13_933217
PubMedSearch : Wang_2022_Front.Neurol_13_933217
PubMedID: 36051222

Title : Enantioselective bioaccumulation and toxicity of rac-sulfoxaflor in zebrafish (Danio rerio) - Deng_2022_Sci.Total.Environ_817_153007
Author(s) : Deng Y , Wang R , Song B , Yang Y , Hu D , Xiao X , Chen X , Lu P
Ref : Sci Total Environ , 817 :153007 , 2022
Abstract : Sulfoxaflor is a fourth-generation neonicotinoid insecticide mainly used to control sap-feeding pests. In this study, four stereoisomers of sulfoxaflor were separated using HPLC, and the absolute configurations of three stereoisomers were identified via single-crystal X-ray diffraction. First, the stability and isomerization of the four enantiomers and rac-sulfoxaflor in water and seven organic solvents were investigated. All enantiomers were extremely unstable in water with isomerization rates above 20%. The racemate did not isomerize in any of the solutions and was stable in water (degradation rate less than 7%). Therefore, we studied the acute toxicity, enantioselective behavior, and enzymatic activities of rac-sulfoxaflor in zebrafish. The bioaccumulation experiment demonstrated that the bioconcentration of sulfoxaflor in zebrafish was enantioselective, and the four enantiomers accumulated in zebrafish in the order (+)-2S,3S-sulfoxaflor > (-)-2R,3R-sulfoxaflor > (+)-2R,3S-sulfoxaflor > (-)-2S,3R-sulfoxaflor. The effect of rac-sulfoxaflor on the enzymatic activities of zebrafish showed that superoxide dismutase and glutathione-S-transferase activities and malondialdehyde content were significantly enhanced as compared to those in control, whereas acetylcholinesterase was significantly reduced in the sulfoxaflor exposure treatment (p < 0.05), indicating that sulfoxaflor caused oxidative lesions and induced enzymatic activity in zebrafish. This study provides important information on the enantioselective behavior and toxic effects of sulfoxaflor, which can help assess the potential ecological risk of chiral pesticides to aquatic organisms.
ESTHER : Deng_2022_Sci.Total.Environ_817_153007
PubMedSearch : Deng_2022_Sci.Total.Environ_817_153007
PubMedID: 35026276

Title : Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1H)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease - Guo_2022_Drug.Des.Devel.Ther_16_1495
Author(s) : Guo J , Xu A , Cheng M , Wan Y , Wang R , Fang Y , Jin Y , Xie SS , Liu J
Ref : Drug Des Devel Ther , 16 :1495 , 2022
Abstract : BACKGROUND: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports. PURPOSE: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate. METHODS: All compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo. RESULTS: Most compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC(50)=0.28 microM to eeAChE; IC(50)=0.34 microM to hAChE; IC(50)=2.81 microM to hMAO-B; IC(50)=0.91 microM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 microM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.). CONCLUSION: This work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.
ESTHER : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedSearch : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedID: 35611357

Title : A Valuable Product of Microbial Cell Factories: Microbial Lipase - Yao_2021_Front.Microbiol_12_743377
Author(s) : Yao W , Liu K , Liu H , Jiang Y , Wang R , Wang W , Wang T
Ref : Front Microbiol , 12 :743377 , 2021
Abstract : As a powerful factory, microbial cells produce a variety of enzymes, such as lipase. Lipase has a wide range of actions and participates in multiple reactions, and they can catalyze the hydrolysis of triacylglycerol into its component free fatty acids and glycerol backbone. Lipase exists widely in nature, most prominently in plants, animals and microorganisms, among which microorganisms are the most important source of lipase. Microbial lipases have been adapted for numerous industrial applications due to their substrate specificity, heterogeneous patterns of expression and versatility (i.e., capacity to catalyze reactions at the extremes of pH and temperature as well as in the presence of metal ions and organic solvents). Now they have been introduced into applications involving the production and processing of food, pharmaceutics, paper making, detergents, biodiesel fuels, and so on. In this mini-review, we will focus on the most up-to-date research on microbial lipases and their commercial and industrial applications. We will also discuss and predict future applications of these important technologies.
ESTHER : Yao_2021_Front.Microbiol_12_743377
PubMedSearch : Yao_2021_Front.Microbiol_12_743377
PubMedID: 34616387

Title : Rational Design of Highly Selective Near-Infrared Two-Photon Fluorogenic Probe for Imaging Orthotopic Hepatocellular Carcinoma Chemotherapy - Wu_2021_Angew.Chem.Int.Ed.Engl__
Author(s) : Wu X , Wang R , Qi S , Kwon N , Han J , Kim H , Li H , Yu F , Yoon J
Ref : Angew Chem Int Ed Engl , : , 2021
Abstract : Selective fluorescence imaging of biomarker in vivo and in situ for evaluating orthotopic hepatocellular carcinoma (HCC) chemotherapy remains a great challenge due to current imaging agents suffering from the potential interferences of other hydrolases. Herein, we observed that carbamate unit showed a high selectivity toward HCC-related biomarker (carboxylesterase, CE) for evaluation of treatment. A near-infrared two-photon fluorescent probe was developed to not only specially image CE activity in vivo and in situ but also target orthotopic liver tumor after systemic administration. In vivo signals of probe correlating well with tumor apoptosis make it possible to evaluate the status of treatment. Excellent property of probe enables the first imaging of CE activity in situ with high resolution three-dimensional view. This study may promote advancements in optical imaging approach for precise imaging-guided diagnosis of HCC in situ and its evaluation of treatment.
ESTHER : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedID: 33942436

Title : Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia - Yang_2021_Bioorg.Med.Chem_37_116109
Author(s) : Yang GX , Sun JM , Zheng LL , Zhang L , Li J , Gan HX , Huang Y , Huang J , Diao XX , Tang Y , Wang R , Ma L
Ref : Bioorganic & Medicinal Chemistry , 37 :116109 , 2021
Abstract : A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment.
ESTHER : Yang_2021_Bioorg.Med.Chem_37_116109
PubMedSearch : Yang_2021_Bioorg.Med.Chem_37_116109
PubMedID: 33780813

Title : Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhang_2021_Eur.J.Med.Chem_213_113154
Author(s) : Zhang Z , Guo J , Cheng M , Zhou W , Wan Y , Wang R , Fang Y , Jin Y , Liu J , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 213 :113154 , 2021
Abstract : In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC(50) values 0.85 microM and 0.59 microM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu(2+) and Al(3+) at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedSearch : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedID: 33476932

Title : An Evolving Technology That Integrates Classical Methods with Continuous Technological Developments: Thin-Layer Chromatography Bioautography - Wang_2021_Molecules_26_
Author(s) : Wang M , Zhang Y , Wang R , Wang Z , Yang B , Kuang H
Ref : Molecules , 26 : , 2021
Abstract : Thin-layer chromatography (TLC) bioautography is an evolving technology that integrates the separation and analysis technology of TLC with biological activity detection technology, which has shown a steep rise in popularity over the past few decades. It connects TLC with convenient, economic and intuitive features and bioautography with high levels of sensitivity and specificity. In this study, we discuss the research progress of TLC bioautography and then establish a definite timeline to introduce it. This review summarizes known TLC bioautography types and practical applications for determining antibacterial, antifungal, antitumor and antioxidant compounds and for inhibiting glucosidase, pancreatic lipase, tyrosinase and cholinesterase activity constitutes. Nowadays, especially during the COVID-19 pandemic, it is important to identify original, natural products with anti-COVID potential compounds from Chinese traditional medicine and natural medicinal plants. We also give an account of detection techniques, including in situ and ex situ techniques; even in situ ion sources represent a major reform. Considering the current technical innovations, we propose that the technology will make more progress in TLC plates with higher separation and detection technology with a more portable and extensive scope of application. We believe this technology will be diffusely applied in medicine, biology, agriculture, animal husbandry, garden forestry, environmental management and other fields in the future.
ESTHER : Wang_2021_Molecules_26_
PubMedSearch : Wang_2021_Molecules_26_
PubMedID: 34361800

Title : Chemical Constituents and their Antioxidant, Anti-Inflammatory and Anti-Acetylcholinesterase Activities from Pholidota cantonensis - Liu_2021_Plant.Foods.Hum.Nutr_76_105
Author(s) : Liu L , Zou M , Zeng K , Ye X , Wang R , Wang W , Zhang X
Ref : Plant Foods Hum Nutr , 76 :105 , 2021
Abstract : Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC(50) = 0.72 +/- 0.08 microM) than the positive control quercetin (IC(50) = 12.94 +/- 0.08 microM). Compound 13 also had a higher inhibitory rate (99.59 +/- 0.43%) on AChE than that of the positive control galantamine (78.32 +/- 1.16%) at the concentrate of 50 microg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs.
ESTHER : Liu_2021_Plant.Foods.Hum.Nutr_76_105
PubMedSearch : Liu_2021_Plant.Foods.Hum.Nutr_76_105
PubMedID: 33620638

Title : Characterization of the insecticide detoxification carboxylesterase Boest1 from Bradysia odoriphaga Yang et Zhang (Diptera:Sciaridae) - Ding_2021_Pest.Manag.Sci__
Author(s) : Ding Q , Xu X , Sang Z , Wang R , Ullah F , Gao X , Song D
Ref : Pest Manag Sci , : , 2021
Abstract : BACKGROUND: In insects, carboxylesterases (CarEs) are enzymes involved in the detoxification of insecticides. However, the molecular mechanism of CarE-mediated insecticide metabolism in Bradysia odoriphaga, a serious agricultural pest, remains unclear. The aim of this study is to investigate the detoxification process of malathion, bifenthrin, and imidacloprid by B. odoriphaga carboxylesterase (Boest1). RESULTS: An alpha class CarE gene Boest1 was cloned from B. odoriphaga. The results of real-time quantitative PCR showed that Boest1 is up-regulated with age during the larval stage, and the level of transcription of Boest1 is higher in the midgut and Malpighian tubule than in other tissues. The expression level of Boest1 was significantly increased after exposure to malathion and bifenthrin. Recombinant BoEST1 expressed in vitro showed high catalytic activity toward alpha-naphthyl acetate, which was substantially inhibited by malathion and triphenyl phosphate. The in vitro metabolism assays showed that BoEST1 demonstrates hydrolytic capacity toward malathion and bifenthrin but not imidacloprid. The binding free energy analysis indicates that BoEST1 has a higher affinity for malathion and bifenthrin than imidacloprid. CONCLUSION: These results suggest that BoEST1 plays a role in the breakdown of insecticides and may be involved in the development of resistance in the Chinese chive pest B. odoriphaga; our findings also provide data for better pest management and perspectives for new pesticides development. This article is protected by copyright. All rights reserved.
ESTHER : Ding_2021_Pest.Manag.Sci__
PubMedSearch : Ding_2021_Pest.Manag.Sci__
PubMedID: 34596943
Gene_locus related to this paper: 9dipt-Boest1 , braco-est1

Title : Design, synthesis and evaluation of diosgenin carbamate derivatives as multitarget anti-Alzheimer's disease agents - Yang_2020_Eur.J.Med.Chem_187_111913
Author(s) : Yang GX , Huang Y , Zheng LL , Zhang L , Su L , Wu YH , Li J , Zhou LC , Huang J , Tang Y , Wang R , Ma L
Ref : Eur Journal of Medicinal Chemistry , 187 :111913 , 2020
Abstract : In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Abeta activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 +/- 2.2%,10 muM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 +/- 3.4%, 10 muM) or Abeta (astrocytes protection = 70.2 +/- 6.5%, 10 muM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Abeta42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1beta, IL-6 and TNF-alpha level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Abeta activities.
ESTHER : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedSearch : Yang_2020_Eur.J.Med.Chem_187_111913
PubMedID: 31837501

Title : Scocycamides, a Pair of Macrocyclic Dicaffeoylspermidines with Butyrylcholinesterase Inhibition and Antioxidation Activity from the Roots of Scopolia tangutica - Wang_2020_Org.Lett_22_8240
Author(s) : Wang JX , Zhao YP , Du NN , Han Y , Li H , Wang R , Xu Y , Liu YF , Liang XM
Ref : Org Lett , 22 :8240 , 2020
Abstract : A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.
ESTHER : Wang_2020_Org.Lett_22_8240
PubMedSearch : Wang_2020_Org.Lett_22_8240
PubMedID: 33021797

Title : Monitoring insecticide resistance and diagnostics of resistance mechanisms in Bemisia tabaci Mediterranean (Q biotype) in China - Wang_2020_Pestic.Biochem.Physiol_163_117
Author(s) : Wang R , Che W , Wang J , Luo C
Ref : Pestic Biochem Physiol , 163 :117 , 2020
Abstract : Bemisia tabaci is one of notorious agricultural insect pests in China, and the strategies of management largely depend on application of insecticides. In order to assess levels of resistance in field populations of B. tabaci to six insecticides including abamectin, cyantraniliprole, pymetrozine, imidacloprid, chlorpyrifos and bifenthrin, we monitored the susceptibility to all tested insecticides in five field populations across China and the results indicated that field populations of B. tabaci have developed various levels of resistance to each chemical agent. Furthermore, para-type voltage gated sodium channel mutations (L925I and T929V) and acetylcholinesterase ace1 mutation (F331W) were confirmed, and expression levels of CYP6CM1, CYP4C64, GSTd7 and ABCG3 were detected for investigating mechanisms of imidacloprid resistance in the five field-collected populations. The results showed that, in all tested populations, frequencies of F331W were 100%, and the frequencies of the L925I and T929V were in the range of 28.5 to 47.0% and 11.0 to 53.5%, respectively. Moreover, CYP6CM1 and CYP4C64 were significantly overexpressed in two tested populations, respectively, and GSTd7 was significantly overexpressed in one population. No overexpression of ABCG3 was observed in all the populations. Above results provided valuable insight into the current status of insecticide resistance and could be contributed to design strategies of management for B. tabaci.
ESTHER : Wang_2020_Pestic.Biochem.Physiol_163_117
PubMedSearch : Wang_2020_Pestic.Biochem.Physiol_163_117
PubMedID: 31973847

Title : Engineering of a thermo-alkali-stable lipase from Rhizopus chinensis by rational design of a buried disulfide bond and combinatorial mutagenesis - Wang_2020_J.Ind.Microbiol.Biotechnol_47_1019
Author(s) : Wang R , Wang S , Xu Y , Yu X
Ref : J Ind Microbiol Biotechnol , 47 :1019 , 2020
Abstract : To improve the thermostability of the lipase (r27RCL) from Rhizopus chinensis through rational design, a newly introduced buried disulfide bond F223C/G247C was proved to be beneficial to thermostability. Interestingly, F223C/G247C was also found to improve the alkali tolerance of the lipase. Subsequently, six other thermostabilizing mutations from our previous work were integrated into the mutant F223C/G247C, leading to a thermo-alkali-stable mutant m32. Compared to the wild-type lipase, the associative effect of the beneficial mutations showed significant improvements on the thermostability of m32, with a 74.7-fold increase in half-life at 60 degreesC, a 21.2 degreesC higher [Formula: see text] value and a 10 degreesC elevation in optimum temperature. The mutated m32 was also found stable at pH 9.0-10.0. Furthermore, the molecular dynamics simulations of m32 indicated that its rigidity was enhanced due to the decreased solvent-accessible surface area, a newly formed salt bridge, and the increased deltadeltaG values.
ESTHER : Wang_2020_J.Ind.Microbiol.Biotechnol_47_1019
PubMedSearch : Wang_2020_J.Ind.Microbiol.Biotechnol_47_1019
PubMedID: 33070231
Gene_locus related to this paper: rhich-a3fm73

Title : Enhancing the thermostability of Rhizopus chinensis lipase by rational design and MD simulations - Wang_2020_Int.J.Biol.Macromol_60_1189
Author(s) : Wang R , Wang S , Xu Y , Yu X
Ref : Int J Biol Macromol , 60 :1189 , 2020
Abstract : To improve the thermostability of r27RCL from Rhizopus chinensis and broaden its industrial applications, we used rational design (FoldX) according to DeltaDeltaG calculation to predict mutations. Four thermostable variants S142A, D217V, Q239F, and S250Y were screened out and then combined together to generate a quadruple-mutation (S142A/D217V/Q239F/S250Y) variant, called m31. m31 exhibited enhanced thermostability with a 41.7-fold longer half-life at 60 degrees C, a 5 degrees C higher of topt, and 15.8 degrees C higher of T30 50 compared to that of r27RCL expressed in P. pastoris. Molecular dynamics simulations were conducted to analyze the mechanism of the thermostable mutant. The results indicated that the rigidity of m31 was improved due to the decreased solvent accessible surface area, a newly formed salt bridge of Glu292:His171, and the increased DeltaDeltaG of m31. According to the root-mean-square-fluctuation analysis, three positive mutations S142A, D217V, and Q239F located in the thermal weak regions and greatly decreased the distribution of thermal-fluctuated regions of m31, compared to that of r27RCL. These results suggested that to simultaneously implement MD simulations and DeltaDeltaG-based rational approaches will be more accurate and efficient for the improvement of enzyme thermostability.
ESTHER : Wang_2020_Int.J.Biol.Macromol_60_1189
PubMedSearch : Wang_2020_Int.J.Biol.Macromol_60_1189
PubMedID: 32485250
Gene_locus related to this paper: rhich-a3fm73

Title : Biochemical Mechanisms, Cross-resistance and Stability of Resistance to Metaflumizone in Plutella xylostella - Shen_2020_Insects_11_
Author(s) : Shen J , Li Z , Li D , Wang R , Zhang S , You H , Li J
Ref : Insects , 11 : , 2020
Abstract : The diamondback moth, Plutella xylostella (L.) is an important pest of cruciferous crops worldwide. It has developed resistance to many conventional and novel insecticide classes. Metaflumizone belongs to the new chemical class of semicarbazone insecticides. To delay the development of metaflumizone resistance in P. xylostella and to guide insecticide use in the field, the biochemical mechanisms, cross-resistance spectrum, and stability of resistance to metaflumizone were studied in a laboratory-selected resistant strain (metaflu-SEL). Synergism tests with the carboxylesterase inhibitor triphenyl phosphate (TPP), the glutathione S-transferase depletor diethyl maleate (DEM), and the P450 inhibitor piperonyl butoxide(PBO) had no obvious effect on metaflumizone in the metaflu-SEL strain and the susceptible strain (SS) of P. xylostella, with synergism ratios that ranged from 1.02 to 1.86. Biochemical studies revealed that the cytochrome P450-dependent monooxygenase increased only 1.13-fold in the metaflu-SEL strain compared with the UNSEL stain; meanwhile, carboxylesterase and glutathione S-transferase activity showed no difference. These results suggest that these detoxification enzymes may be not actively involved in metaflumizone resistance. Furthermore, the metaflu-SEL population showed a moderate level of cross-resistance to indoxacarb (11.63-fold), but only very low cross-resistance to spinosad (1.75-fold), spinetoram (3.52-fold), abamectin (2.81-fold), beta-cypermethrin (0.71-fold), diafenthiuron (0.79-fold), chlorantraniliprole (2.16-fold), BT (WG-001) (3.34-fold), chlorfenapyr (0.49-fold), and chlorfluazuron (0.97-fold). Moreover, metaflumizone resistance decreased from 1087.85- to 1.23-fold in the metaflu-SEL strain after 12 generations without exposure to metaflumizone. These results are useful for formulating insecticide resistance management strategies to control P. xylostella and to delay the development of metaflumizone resistance in the field.
ESTHER : Shen_2020_Insects_11_
PubMedSearch : Shen_2020_Insects_11_
PubMedID: 32429053

Title : Neuroprotective potential of ketamine prevents developing brain structure impairment and alteration of neurocognitive function induced via isoflurane through the PI3K\/AKT\/GSK-3beta pathway - Wang_2019_Drug.Des.Devel.Ther_13_501
Author(s) : Wang R , Zhang Z , Kumar M , Xu G , Zhang M
Ref : Drug Des Devel Ther , 13 :501 , 2019
Abstract : Background: The aim of the current experimental study was to scrutinize the neuroprotective effect of ketamine on the isoflurane (iso)-induced cognitive dysfunction in rats via phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3beta (GSK-3beta) pathway. Materials and methods: Sprague-Dawley rats were used for the current experimental study. The rats were divided into six groups and rats were treated with ketamine and memantine. For the estimation of cognitive function study, we used the Morris water test. Pro-inflammatory cytokines such as IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and caspase-6; the antioxidant parameters malondialdehyde, glutathione, superoxide dismutase, catalase, and protein carbonyl; acetylcholinesterase, amyloid beta, and brain-derived neurotrophic factor were estimated, respectively. The protein expression of AKT, GSK-3beta, p21WAF1/CIP1, and p53 was also estimated, respectively. Results: Ketamine significantly enhanced cognitive function and showed anti-inflammatory and antioxidant effects, and exhibited the neuroprotective effect of ketamine against the isoflurane-induced cognitive impairment. Additionally, ketamine significantly (P<0.005) suppressed IL-1beta, TNF-alpha, IL-6, caspase-6 and p21WAF1/CIP1, p53 expression and up-regulated the PI3K/AKT/GSK-3beta expression in the group of iso-induced rats. Conclusion: We can conclude that ketamine prevented the cognitive impairment induced by isoflurane anesthesia through anti-apoptotic, anti-inflammatory, and antioxidant effects via the PI3K/AKT/GSK-3beta pathway.
ESTHER : Wang_2019_Drug.Des.Devel.Ther_13_501
PubMedSearch : Wang_2019_Drug.Des.Devel.Ther_13_501
PubMedID: 30787593

Title : Mori Ramulus (Chin.Ph.)-the Dried Twigs of Morus alba L.\/Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract - Yao_2019_Molecules_24_
Author(s) : Yao J , He H , Xue J , Wang J , Jin H , Wu J , Hu J , Wang R , Kuchta K
Ref : Molecules , 24 : , 2019
Abstract : In Traditional Chinese Medicine (TCM), Mori ramulus (Chin.Ph.)-the dried twigs of Morus alba L.-is extensively used as an antirheumatic agent and also finds additional use in asthma therapy. As a pathological high xanthine oxidase (XO, EC 1.1.3.22) activity is strongly correlated to hyperuricemy and gout, standard anti-hyperuremic therapy typically involves XO inhibitors like allopurinol, which often cause adverse effects by inhibiting other enzymes involved in purine metabolism. Mori ramulus may therefore be a promissing source for the development of new antirheumatic therapeutics with less side effects. Coumarins, one of the dominant groups of bioactive constituents of M. alba, have been demonstrated to possess anti-inflammatory, antiplatelet aggregation, antitumor, and acetylcholinesterase (AChE) inhibitory activities. The combination of HPLC (DAD) and Q-TOF technique could give excellent separating and good structural characterization abilities which make it suitable to analyze complex multi-herbal extracts in TCM. The aim of this study was to develop a HPLC (DAD)/ESI-Q-TOF-MS/MS method for the identification and profiling of pharmacologically active coumarin glycosides in Mori ramulus refined extracts for used in TCM. This HPLC (DAD)/ESI-Q-TOF-MS/MS method provided a rapid and accurate method for identification of coumarin glycosides-including new natural products described here for the first time-in the crude extract of M. alba L. In the course of this project, two novel natural products moriramulosid A (umbelliferone-6-beta-d-apiofuranosyl-(1-->6)-beta-d-glucopyranoside) and moriramulosid B (6-[[6-O-(6-deoxy-alpha-l-mannopyranosyl)-beta-d-glucopyranosyl]oxy]-2H-1-benzopy ran-1-one) were newly discovered and the known natural product Scopolin was identified in M. alba L. for the first time.
ESTHER : Yao_2019_Molecules_24_
PubMedSearch : Yao_2019_Molecules_24_
PubMedID: 30754654

Title : Clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning - Jiang_2019_Saudi.J.Biol.Sci_26_2018
Author(s) : Jiang SZ , Ma BE , Liu C , Wang R
Ref : Saudi J Biol Sci , 26 :2018 , 2019
Abstract : Objective: To observe the clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning patients, and investigate the potential mechanism. Methods: In this study, we enrolled 136 organophosphorus poisoning patients who received treatment in this hospital between January 2009 and December 2017, and they were divided into three groups according to the clinical treatment methods, i.e. Group A (comprehensive treatment with HP, n=47), Group B (continuous intravenous infusion of atropine with micropump, n=43) and Group C (regular intravenous infusion of atropine, n=46). In addition to the close monitoring of vital signs, we recorded the atropinization time (min), cholinesterase reactivation time (h), total dose of atropine, recurrence, incidence rate of atropine poisoning (%), hospitalization time (d) and cure rate (%). Results: In comparison with Group C, patients in Group A and B manifested more stable vital signs with lower total dose of atropine and incidence rate of atropine poisoning and shorter cholinesterase reactivation time, while the cure rate was remarkably increased (p<0.05), and no significant differences were observed in atropinization time among three groups (p>0.05). Compared to Group B and C, total dose of atropine in Group A was significantly decreased with obvious excellence in hospitalization time, reduction of complications and increases in cure rates (p<0.05). Moreover, patients in Group A had the lowest mortality rate among three groups. Conclusion: In treatment of organophosphorus poisoning patients, HP and continuous intravenous infusion of atropine using micropump can elevate the survival rate, reduce the incidence of adverse reaction, shorten the reactivation time of cholinesterase and decrease the incidence rate of complications, which are superior to the traditional treatment method.
ESTHER : Jiang_2019_Saudi.J.Biol.Sci_26_2018
PubMedSearch : Jiang_2019_Saudi.J.Biol.Sci_26_2018
PubMedID: 31889787

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

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

Title : Multiple site-directed mutagenesis of a Phaseolus vulgaris epoxide hydrolase to improve its catalytic performance towards p-chlorostyrene oxide based on the computer-aided re-design - Li_2019_Int.J.Biol.Macromol_121_326
Author(s) : Li C , Zhao J , Hu D , Hu BC , Wang R , Zang J , Wu MC
Ref : Int J Biol Macromol , 121 :326 , 2019
Abstract : To improve the activity and regioselectivity of a Phaseolus vulgaris epoxide hydrolase (PvEH3) towards p-chlorostyrene oxide (pCSO), the site-directed mutagenesis was conducted based on the computer-aided re-design. Firstly, seven single-site variants of a PvEH3-encoding gene (pveh3) were constructed as designed theoretically and expressed in E. coli BL21(DE3), respectively. One transformant, E. coli/pveh3(G170E), had the higher EH activity towards racemic pCSO, while both E. coli/pveh3(F187L) and /pveh3(P237L) with enhanced regioselectivity coefficient alphaS values. Secondly, to combine their respective merits, the double- and triple-site variants, pveh3(G170E/F187L), pveh3(G170E/P237L) and pveh3(G170E/F187L/P237L), were also constructed. Among all E. coli transformants, E. coli/pveh3(G170E/F187L/P237L) simultaneously had the highest EH activity of 20.3U/g wet cell and alphaS value of 95.2%, by which the hydrolysis of rac-pCSO enantioconvergently produced (R)-p-chlorophenylethane-1,2-diol with an enantiomeric excess of 93.2%. Furthermore, PvEH3(G170E/F187L/P237L) expressed in E. coli/pveh3(G170E/F187L/P237L) was purified. Its specific activity and catalytic efficiency towards rac-pCSO were 4.1U/mg protein and 1.81mM(-1)s(-1), which were 3.0- and 3.1-fold those of PvEH3. Finally, the molecular docking simulation analysis indicated that PvEH3(G170E/F187L/P237L) preferentially attacks the more hindered benzylic carbon of (S)-pCSO over PvEH3, which was consistent with their alphaS values measured experimentally.
ESTHER : Li_2019_Int.J.Biol.Macromol_121_326
PubMedSearch : Li_2019_Int.J.Biol.Macromol_121_326
PubMedID: 30308283
Gene_locus related to this paper: phavu-PvEH3

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

Title : Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides - Li_2018_Nat.Commun_9_4951
Author(s) : Li C , Cao YX , Wang R , Wang YN , Lan Q , Wang XS
Ref : Nat Commun , 9 :4951 , 2018
Abstract : The selective incorporation of gem-difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp(3))-CF2 bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer's disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery.
ESTHER : Li_2018_Nat.Commun_9_4951
PubMedSearch : Li_2018_Nat.Commun_9_4951
PubMedID: 30470757

Title : Response of detoxification and immune genes and of transcriptome expression in Mythimna separata following chlorantraniliprole exposure - Wang_2018_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_28_90
Author(s) : Wang JD , Wang WZ , Wang YR , Gao SJ , Elzaki M , Wang R , Wu M
Ref : Comparative Biochemistry & Physiology Part D Genomics Proteomics , 28 :90 , 2018
Abstract : The oriental armyworm Mythimna separata is a serious polyphagous pest in China and there are major efforts to control this pest. In the present study, an RNA-Seq method was used to explore transcriptome data of M. separata and identify the responses of genes to chlorantraniliprole. Sequencing and de novo assembly yielded 134,533 transcripts that were further assembled into 77,628 unigenes with an N50 length of 2165bp. A total of 76 unigenes encoding insecticide targets were identified. Furthermore, 62 cytochrome P450s, 34 glutathione S-transferase (GSTs)and 64 carboxylesterase (CCEs) were curated to construct phylogenetic trees. In addition, we identified 647 the differentially expressed genes following treatment with chlorantraniliprole. The pathways of calcium signaling was identified as response to the pesticide The transcriptome data we generated represents a comprehensive genomic resource for further studies focused on control of M. separata. The response of genes to chlorantraniliprole treatment will elucidate the molecular mechanisms of insecticide resistance and allow for the development of new chemical pesticides to control this pest.
ESTHER : Wang_2018_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_28_90
PubMedSearch : Wang_2018_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_28_90
PubMedID: 30005390

Title : Biotransformation enzyme activities and phase I metabolites analysis in Litopenaeus vannamei following intramuscular administration of T-2 toxin - Deng_2017_Drug.Chem.Toxicol__1
Author(s) : Deng Y , Wang Y , Sun L , Lu P , Wang R , Ye L , Xu D , Ye R , Liu Y , Bi S , Gooneratne R
Ref : Drug & Chemical Toxicology , :1 , 2017
Abstract : T-2 toxin (T-2) is a type-A trichothecene produced by Fusarium that causes toxicity to animals. T-2 contamination of grain-based aquatic feed is a concern for the industries related to edible aquatic crustacean species such as the shrimp industry because it can lead to serious food safety issues. T-2, its metabolites, and selected phase I (EROD, CarE) and phase II (GST, UGT, SULT) detoxification enzymes in hemolymph and tissues were monitored at 0, 5, 10 15, 30, 45, and 60 min following T-2 intramuscular administration (3 mg/kg bw) in shrimp (Litopenaeus vannamei). Marked increases of EROD activity in hepatopancreas and CarE activity in hemolymph, gill, hepatopancreas and intestine were observed followed by increases in phase II enzymes (GST, UGT, SULT) in hepatopancreas, hemolymph, intestine and gill, which remained elevated for an extended period. Time-dependent decrease in shrimp tissue T-2 concentration was observed. HT-2 increased up to 15 min. Most other T-2 metabolites were detected but not T-2 tetraol. Enzyme responses on exposure to T-2 were tissue-specific and time-dependent. Detection results indicated that HT-2 may not be the only important metabolite in aquatic crustacean species. Further investigation into T-2 metabolite toxicity is needed to fully understand the food safety issues related to T-2.
ESTHER : Deng_2017_Drug.Chem.Toxicol__1
PubMedSearch : Deng_2017_Drug.Chem.Toxicol__1
PubMedID: 28482697

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Enantioconvergent hydrolysis of racemic styrene oxide at high concentration by a pair of novel epoxide hydrolases into (R)-phenyl-1,2-ethanediol - Wang_2017_Biotechnol.Lett_39_1917
Author(s) : Wang R , Hu D , Zong X , Li J , Ding L , Wu M
Ref : Biotechnol Lett , 39 :1917 , 2017
Abstract : OBJECTIVES: To prepare (R)-phenyl-1,2-ethanediol ((R)-PED) with high enantiomeric excess (ee p) and yield from racemic styrene oxide (rac-SO) at high concentration by bi-enzymatic catalysis.
RESULTS: The bi-enzymatic catalysis was designed for enantioconvergent hydrolysis of rac-SO by a pair of novel epoxide hydrolases (EHs), a Vigna radiata EH3 (VrEH3) and a variant (AuEH2A250I) of Aspergillus usamii EH2. The simultaneous addition mode of VrEH3 and AuEH2A250I, exhibiting the highest average turnover frequency (aTOF) of 0.12 g h-1 g-1, was selected, by which rac-SO (10 mM) was converted into (R)-PED with 92.6% ee p and 96.3% yield. Under the optimized reaction conditions: dry weight ratio 14:1 of VrEH3-expressing E. coli/vreh3 to AuEH2A250I-expressing E. coli/Aueh2 A250I and reaction at 20 degrees C, rac-SO (10 mM) was completely hydrolyzed in 2.3 h, affording (R)-PED with 98% ee p. At the weight ratio 0.8:1 of rac-SO to two mixed dry cells, (R)-PED with 97.4% ee p and 98.7% yield was produced from 200 mM (24 mg/ml) rac-SO in 10.5 h.
CONCLUSIONS: Enantioconvergent hydrolysis of rac-SO at high concentration catalyzed by both VrEH3 and AuEH2A250I is an effective method for preparing (R)-PED with high ee p and yield.
ESTHER : Wang_2017_Biotechnol.Lett_39_1917
PubMedSearch : Wang_2017_Biotechnol.Lett_39_1917
PubMedID: 28875350
Gene_locus related to this paper: vigra-Vreh3 , aspng-q1ktb5

Title : Kinetic resolution of racemic styrene oxide at a high concentration by recombinant Aspergillus usamii epoxide hydrolase in an n-hexanol\/buffer biphasic system - Hu_2016_J.Biotechnol_236_152
Author(s) : Hu D , Wang R , Shi XL , Ye HH , Wu Q , Wu MC , Chu JJ
Ref : J Biotechnol , 236 :152 , 2016
Abstract : Using the cell-free extract of engineered E. coli/Aueh2, expressing the recombinant Aspergillus usamii epoxide hydrolase (reAuEH2), as a biocatalyst, the kinetic resolution technique of racemic styrene oxide (rac-SO) was examined. In a phosphate buffer system (50mM, pH 7.0), 200mM rac-SO was efficiently resolved, obtaining (S)-SO with 98.1% enantiomeric excess (e.e.), whereas (S)-SO only with 45.2% e.e. was obtained from 750mM rac-SO. The analytical results verified that reAuEH2 shows tolerance towards high substrate concentration but is inactivated at a product concentration of 300mM. To produce (S)-SO with the high concentration, e.e. and volumetric productivity, n-hexanol was selected from a variety of water-miscible and water-immiscible organic solvents to construct an n-hexanol/buffer biphasic system. The optimal phase volume ratio, substrate over enzyme ratio and temperature were 1:1 (v/v), 6:1 (w/w) and 25 degrees C, respectively. In an optimized biocatalytic system, a gram-scale resolution of rac-SO at a high concentration of 1M (120g/L) was performed at 25 degrees C for 2h, obtaining (S)-SO with 98.2% e.e., 34.3% yield (maximum yield of 50%). The substrate concentration and volumetric productivity (1M, 20.6g/L/h) in a biphasic system significantly increased compared with those (0.2M, 3.1g/L/h) in a phosphate buffer system. The efficient resolution of rac-SO at a high concentration in a biphasic system makes it a promising technique for preparing a highly value-added enantiopure (S)-SO with high volumetric productivity.
ESTHER : Hu_2016_J.Biotechnol_236_152
PubMedSearch : Hu_2016_J.Biotechnol_236_152
PubMedID: 27546798
Gene_locus related to this paper: aspng-q1ktb5

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Expanding the Toolkit for the Serine Hydrolases - Ross_2015_Chem.Biol_22_808
Author(s) : Ross MK , Wang R
Ref : Chemical Biology , 22 :808 , 2015
Abstract : In this issue of Chemistry & Biology, Cognetta et al. (2015) describe new pharmacological tools, including N-hydroxyhydantoin-containing carbamate inhibitors and an activity-based probe, for palmitoyl protein thioesterase 1 and alpha, beta-hydrolase domain-4 that expand the toolkit for the serine hydrolases.
ESTHER : Ross_2015_Chem.Biol_22_808
PubMedSearch : Ross_2015_Chem.Biol_22_808
PubMedID: 26207294

Title : Effects of electroacupuncture on recovery of the electrophysiological properties of the rabbit gastrocnemius after contusion: an in vivo animal study - Liu_2015_BMC.Complement.Altern.Med_15_69
Author(s) : Liu S , Wang R , Luo D , Xu Q , Xiao C , Lin P , Yu Z , Zhao X , Cai R , Ma J , Zhang Q , Wang Y
Ref : BMC Complement Altern Med , 15 :69 , 2015
Abstract : BACKGROUND: Our preliminary studies indicated that electroacupuncture (EA) at the ST36 and Ashi acupoints could promote regeneration of the rabbit gastrocnemius (GM) by improving microcirculation perfusion, promoting the recovery of myofiber structures, and inhibiting excessive fibrosis. However, the effects of EA on recovery of the electrophysiological properties of the GM after contusion are not yet clear. Thus, the purpose of this study was to investigate the effects of EA at the Zusanli (ST36) and Ashi acupoints with regard to recovery of the electrophysiological properties of the rabbit GM after contusion.
METHODS: Forty-five rabbits were randomly divided into three groups: normal, contusion, and EA. After an acute GM contusion was produced (in rabbits in the contusion and EA groups), rabbits in the EA group were treated with electrostimulation at the ST36 and Ashi acupoints with 0.4 mA (2 Hz) for 15 min. The contusion group received no EA treatment. At different time points (7, 14, and 28 days) after contusion, we performed surface electromyography (EMG) and measured the nerve conduction velocity (NCV) of the GM and the GM branch of the tibial nerve. We also examined acetylcholinesterase (AchE) and Agrin expression in the neuromuscular junction (NMJ) via immunohistochemistry.
RESULTS: Compared with the contusion group, the EMG amplitude and NCV in rabbits in the EA group were significantly higher at all time points after contusion. AchE and Agrin expression in the EA group were significantly higher than those in the contusion group.
CONCLUSIONS: Our results showed that EA at the ST36 and Ashi acupoints effectively promoted recovery of the electrophysiological properties of the rabbit GM after contusion. The effects of EA were realized by promotion of the regeneration of myofibers and nerve fibers, as well as acceleration of NMJ reconstruction by upregulation of AchE and Agrin expression in the motor endplate area.
ESTHER : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedSearch : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedID: 25887510

Title : Preventive effect of Wall. ex Lindl. on activated carbon-induced constipation in mice - Wang_2015_Exp.Ther.Med_9_563
Author(s) : Wang R , Sun P , Zhou Y , Zhao X
Ref : Exp Ther Med , 9 :563 , 2015
Abstract : The aim of this study was to investigate the effects of Dendrobium candidum Wall. ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered D. candidum for 9 days. Body weight, defecation status, gastrointestinal (GI) transit and defecation times, in addition to the levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were used to evaluate the preventive effects of D. candidum on constipation. The laxative drug bisacodyl acted as a positive control. The time to the first defecation of a black stool for the normal, control, bisacodyl-treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126, 161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D. candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and 90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with D. candidum compared with those in the untreated control mice (P<0.05). These results demonstrate that D. candidum has preventive effects on constipation in mice, and a greater functional activity was observed when a higher concentration was administered.
ESTHER : Wang_2015_Exp.Ther.Med_9_563
PubMedSearch : Wang_2015_Exp.Ther.Med_9_563
PubMedID: 25574235

Title : Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic pemphigus and their correlations with symptoms and prognosis - Wang_2015_Br.J.Dermatol_172_968
Author(s) : Wang R , Li J , Wang M , Hao H , Chen X , Li R , Zhu X
Ref : Br J Dermatol , 172 :968 , 2015
Abstract : BACKGROUND: Paraneoplastic pemphigus (PNP) involves multiple organs, but little is known about its neurological involvement. OBJECTIVES: To investigate the symptoms, prognosis and profiles of associated autoantibodies in myasthenia gravis (MG), and their correlations in patients with PNP.
METHODS: Fifty-eight patients with PNP were assessed for myasthenic symptoms and laboratory evidence. Serum autoantibodies against acetylcholine receptor (AChR), acetylcholinesterase (AChE), titin, ryanodine receptor (RyR) and muscle-specific kinase (MuSK) were measured by enzyme-linked immunosorbent assay. Patients with pemphigus vulgaris (PV), pemphigus foliaceus (PF), connective tissue disease (CTD) and non-PNP MG (NP-MG), and healthy donors, served as controls. These autoantibodies in PNP were also compared in the presence or absence of dyspnoea or muscle weakness. Cox regression and log-rank tests were used for survival analysis.
RESULTS: Overall 39% of patients with PNP experienced muscle weakness, and 35% were diagnosed with MG. Moreover, 35% had positive anti-AChR and 28% had anti-AChE antibodies, similarly to NP-MG (33% and 17%, respectively, P > 0.05). However, both were negative in all patients with PV, PF and CTD and healthy donors (P < 0.005). No other antibodies showed significant differences among groups. Anti-AChR and anti-AChE antibody levels were significantly increased in patients with PNP with dyspnoea, while anti-AChR, anti-titin and anti-RyR were significantly increased in patients with PNP with muscle weakness (P < 0.05). Nevertheless, levels and positive rates of these autoantibodies showed no significant differences between PNP with Castleman disease and thymoma. Although anti-AChE levels impacted survival duration (P = 0.027, odds ratio 3.14), MG complications did not affect the overall survival percentage in PNP.
CONCLUSIONS: MG is a complication of PNP. Anti-AChR and anti-AChE antibodies are prominent in patients with PNP, especially those with dyspnoea.
ESTHER : Wang_2015_Br.J.Dermatol_172_968
PubMedSearch : Wang_2015_Br.J.Dermatol_172_968
PubMedID: 25388377

Title : Inhibiting beta-Amyloid-Associated Alzheimer's Pathogenesis In Vitro and In Vivo by a Multifunctional Dimeric Bis(12)-hupyridone Derived from Its Natural Analogue - Hu_2015_J.Mol.Neurosci_55_1014
Author(s) : Hu S , Wang R , Cui W , Zhang Z , Mak SH , Xu D , Choi C , Tsim KWK , Carlier PR , Lee M , Han Y
Ref : Journal of Molecular Neuroscience , 55 :1014 , 2015
Abstract : Fibrillar aggregates of beta-amyloid protein (Abeta) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit the formation of Abeta fibrils and block Abeta fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China. In the current study, the inhibitory effect of B12H on the formation of Abeta fibrils and their associated toxicity was investigated both in vitro and in vivo. By using Thioflavin T fluorescence assay, we found that B12H (0.3-3 muM) directly inhibited Abeta fibrils formation following co-incubation of B12H and Abeta1-40 at 37 degrees C for 6 days in vitro. However, huperzine A, at the same concentrations, did not show significant inhibitory effect on Abeta1-40 fibrils formation. Moreover, B12H markedly reduced Abeta1-40-induced cytotoxicity in cultured SH-SY5Y cells, as evidenced by the increase in cell viability, the decrease in lactate dehydrogenase release, and the reduction of apoptotic nuclei. Most importantly, B12H (0.2 and 0.4 mg/kg) reduced intracerebroventricular Abeta1-40 infusion-induced cognitive and memory impairments in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with increasing choline acetyltransferase activity and decreasing acetylcholinesterase activity. Collectively, our study provided novel sights into the potential application of B12H in AD treatment.
ESTHER : Hu_2015_J.Mol.Neurosci_55_1014
PubMedSearch : Hu_2015_J.Mol.Neurosci_55_1014
PubMedID: 25407821

Title : Dimeric bis (heptyl)-Cognitin Blocks Alzheimer's beta-Amyloid Neurotoxicity Via the Inhibition of Abeta Fibrils Formation and Disaggregation of Preformed Fibrils - Hu_2015_CNS.Neurosci.Ther_21_953
Author(s) : Hu SQ , Wang R , Cui W , Mak SH , Li G , Hu YJ , Lee MY , Pang YP , Han YF
Ref : CNS Neurosci Ther , 21 :953 , 2015
Abstract : AIMS: Fibrillar aggregates of beta-amyloid protein (Abeta) are the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit Abeta fibrils formation, disaggregate preformed Abeta fibrils as well as reduce their associated neurotoxicity might have therapeutic values for treating AD. In this study, the inhibitory effects of bis (heptyl)-cognitin (B7C), a multifunctional dimer derived from tacrine, on aggregation and neurotoxicity of Abeta1-40 were evaluated both in vitro and in vivo.
METHODS: Thioflavin T fluorescence assay was carried out to evaluate Abeta aggregation, MTT and Hoechst-staining assays were performed to investigate Abeta-associated neurotoxicity. Fluorescent probe DCFH-DA was used to estimate the accumulation of intracellular reactive oxygen stress (ROS). Morris water maze was applied to determine learning and memory deficits induced by intracerebroventricular infusion of Abeta in rats.
RESULTS: B7C (0.1-10 muM), but not tacrine, effectively inhibited Abeta fibrils formation and disaggregated preformed Abeta fibrils following co-incubation of B7C and Abeta monomers or preformed fibrils, respectively. In addition, B7C markedly reduced Abeta fibrils-associated neurotoxicity in SH-SY5Y cell line, as evidenced by the increase in cell survival, the decrease in Hoechst-stained nuclei and in intracellular ROS. Most encouragingly, B7C (0.1 and 0.2 mg/kg), 10 times more potently than tacrine (1 and 2 mg/kg), inhibited memory impairments after intracerebroventricular infusion of Abeta in rats, as evidenced by the decrease in escape latency and the increase in the spatial bias in Morris water maze test along with upregulation of choline acetyltransferase activity and downregulation of acetylcholinesterase activity. CONCLUSION: These findings provide not only novel molecular insight into the potential application of B7C in treating AD, but also an effective approach for screening anti-AD agents.
ESTHER : Hu_2015_CNS.Neurosci.Ther_21_953
PubMedSearch : Hu_2015_CNS.Neurosci.Ther_21_953
PubMedID: 26507365

Title : A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 - Wang_2014_Appl.Environ.Microbiol_80_3811
Author(s) : Wang C , Chen Q , Wang R , Shi C , Yan X , He J , Hong Q , Li S
Ref : Applied Environmental Microbiology , 80 :3811 , 2014
Abstract : Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.
ESTHER : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedSearch : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedID: 24747891
Gene_locus related to this paper: 9sphn-q0kjt3 , sphwj-a0a059u2z8

Title : Characterization of QmnD3\/QmnD4 for double bond formation in quartromicin biosynthesis - Wu_2014_Org.Lett_16_1578
Author(s) : Wu LF , He HY , Pan HX , Han L , Wang R , Tang GL
Ref : Org Lett , 16 :1578 , 2014
Abstract : In this work, two enzymes responsible for the biogenesis of possible [4 + 2] reaction precursors in the quartromicin biosynthetic pathway were characterized: acetylation of 1 to yield 2 was catalyzed by QmnD3, and subsequent acetic acid elimination of 2 to form double bond product 3 was catalyzed by QmnD4. Site-directed mutagenesis assay of QmnD3 and QmnD4 was investigated, and a general base-catalyzed mechanism for QmnD4 is proposed.
ESTHER : Wu_2014_Org.Lett_16_1578
PubMedSearch : Wu_2014_Org.Lett_16_1578
PubMedID: 24580034

Title : Effects of toxicologically relevant xenobiotics and the lipid-derived electrophile 4-hydroxynonenal on macrophage cholesterol efflux: silencing carboxylesterase 1 has paradoxical effects on cholesterol uptake and efflux - Ross_2014_Chem.Res.Toxicol_27_1743
Author(s) : Ross MK , Borazjani A , Mangum LC , Wang R , Crow JA
Ref : Chemical Research in Toxicology , 27 :1743 , 2014
Abstract : Cholesterol cycles between free cholesterol (unesterified) found predominantly in membranes and cholesteryl esters (CEs) stored in cytoplasmic lipid droplets. Only free cholesterol is effluxed from macrophages via ATP-binding cassette (ABC) transporters to extracellular acceptors. Carboxylesterase 1 (CES1), proposed to hydrolyze CEs, is inactivated by oxon metabolites of organophosphorus pesticides and by the lipid electrophile 4-hydroxynonenal (HNE). We assessed the ability of these compounds to reduce cholesterol efflux from foam cells. Human THP-1 macrophages were loaded with [(3)H]-cholesterol/acetylated LDL and then allowed to equilibrate to enable [(3)H]-cholesterol to distribute into its various cellular pools. The cholesterol-engorged cells were then treated with toxicants in the absence of cholesterol acceptors for 24 h, followed by a 24 h efflux period in the presence of toxicant. A concentration-dependent reduction in [(3)H]-cholesterol efflux via ABCA1 (up to 50%) was found for paraoxon (0.1-10 muM), whereas treatment with HNE had no effect. A modest reduction in [(3)H]-cholesterol efflux via ABCG1 (25%) was found after treatment with either paraoxon or chlorpyrifos oxon (10 muM each) but not HNE. No difference in efflux rates was found after treatments with either paraoxon or HNE when the universal cholesterol acceptor 10% (v/v) fetal bovine serum was used. When the re-esterification arm of the CE cycle was disabled in foam cells, paraoxon treatment increased CE levels, suggesting the neutral CE hydrolysis arm of the cycle had been inhibited by the toxicant. However, paraoxon also partially inhibited lysosomal acid lipase, which generates cholesterol for efflux, and reduced the expression of ABCA1 protein. Paradoxically, silencing CES1 expression in macrophages did not affect the percent of [(3)H]-cholesterol efflux. However, CES1 mRNA knockdown markedly reduced cholesterol uptake by macrophages, with SR-A and CD36 mRNA reduced 3- and 4-fold, respectively. Immunoblots confirmed SR-A and CD36 protein downregulation. Together, these results suggest that toxicants, e.g., oxons, may interfere with macrophage cholesterol homeostasis/metabolism.
ESTHER : Ross_2014_Chem.Res.Toxicol_27_1743
PubMedSearch : Ross_2014_Chem.Res.Toxicol_27_1743
PubMedID: 25250848

Title : The future potential for cocaine vaccines - Orson_2014_Expert.Opin.Biol.Ther_14_1271
Author(s) : Orson FM , Wang R , Brimijoin S , Kinsey BM , Singh RA , Ramakrishnan M , Wang HY , Kosten TR
Ref : Expert Opin Biol Ther , 14 :1271 , 2014
Abstract : INTRODUCTION: Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine's pharmacodynamic effects. AREAS COVERED: This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness. EXPERT OPINION: Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes.
ESTHER : Orson_2014_Expert.Opin.Biol.Ther_14_1271
PubMedSearch : Orson_2014_Expert.Opin.Biol.Ther_14_1271
PubMedID: 24835496

Title : Identification of palmitoyl protein thioesterase 1 in human THP1 monocytes and macrophages and characterization of unique biochemical activities for this enzyme - Wang_2013_Biochemistry_52_7559
Author(s) : Wang R , Borazjani A , Matthews AT , Mangum LC , Edelmann MJ , Ross MK
Ref : Biochemistry , 52 :7559 , 2013
Abstract : The profiles of serine hydrolases in human and mouse macrophages are similar yet different. For instance, human macrophages express high levels of carboxylesterase 1 (CES1), whereas mouse macrophages have minimal amounts of the orthologous murine CES1. On the other hand, macrophages from both species exhibit limited expression of the canonical 2-arachidonoylglycerol (2-AG) hydrolytic enzyme, MAGL. Our previous study showed CES1 was partly responsible for the hydrolysis of 2-AG (50%) and prostaglandin glyceryl esters (PG-Gs) (80-95%) in human THP1 monocytes and macrophages. However, MAGL and other endocannabinoid hydrolases, FAAH, ABHD6, and ABHD12, did not have a role because of limited expression or no expression. Thus, another enzyme was hypothesized to be responsible for the remaining 2-AG hydrolysis activity following chemical inhibition and immunodepletion of CES1 (previous study) or CES1 gene knockdown (this study). Here we identified two candidate serine hydrolases in THP1 cell lysates by activity-based protein profiling (ABPP)-MUDPIT and Western blotting: cathepsin G and palmitoyl protein thioesterase 1 (PPT1). Both proteins exhibited electrophoretic properties similar to those of a serine hydrolase in THP1 cells detected by gel-based ABPP at 31-32 kDa; however, only PPT1 exhibited lipolytic activity and hydrolyzed 2-AG in vitro. Interestingly, PPT1 was strongly expressed in THP1 cells but was significantly less reactive than cathepsin G toward the activity-based probe, fluorophosphonate-biotin. KIAA1363, another serine hydrolase, was also identified in THP1 cells but did not have significant lipolytic activity. On the basis of chemoproteomic profiling, immunodepletion studies, and chemical inhibitor profiles, we estimated that PPT1 contributed 32-40% of 2-AG hydrolysis activity in the THP1 cell line. In addition, pure recombinant PPT1 catalyzed the hydrolysis of 2-AG, PGE2-G, and PGF2alpha-G, although the catalytic efficiency of hydrolysis of 2-AG by PPT1 was ~10-fold lower than that of CES1. PPT1 was also insensitive to several chemical inhibitors that potently inhibit CES1, such as organophosphate poisons and JZL184. This is the first report to document the expression of PPT1 in a human monocyte and macrophage cell line and to show PPT1 can hydrolyze the natural substrates 2-AG and PG-Gs. These findings suggest that PPT1 may participate in endocannabinoid metabolism within specific cellular contexts and highlights the functional redundancy often exhibited by enzymes involved in lipid metabolism.
ESTHER : Wang_2013_Biochemistry_52_7559
PubMedSearch : Wang_2013_Biochemistry_52_7559
PubMedID: 24083319
Gene_locus related to this paper: human-PPT1

Title : [Enhanced thermostability of Rhizopus chinensis lipase by error-prone PCR] - Wang_2013_Sheng.Wu.Gong.Cheng.Xue.Bao_29_1753
Author(s) : Wang R , Yu X , Xu Y
Ref : Sheng Wu Gong Cheng Xue Bao , 29 :1753 , 2013
Abstract : Directed evolution was conducted to improve the thermostability of lipase from Rhizopus chinensis CCTCC M201021. Mutations were introduced by two rounds of error-prone PCR and mutant lipase was selected by fast-blue RR top agar screening. Two positive variants were selected in the first-round and four in the second-round screening process. Ep2-4 was proved as the most thermostable lipase and its DNA sequencing revealed three amino acid substitutions: A129S, P168L and V329A. Compared with the parent, its half-life at 60 degrees C was 5.4- times longer and T50 was 7.8 degrees higher. Purified lipase of Ep2-4 was characterized and the result shows that its thermostability improved without compromising enzyme activity. According to the mimicked protein structure, mutation A129S formed a hydrogen bond with Gln133 and improved the thermostability by increasing the hydrophilicity and polarity of protein; mutation P168L by forming a hydrophobic bond with the nearby Leu164.
ESTHER : Wang_2013_Sheng.Wu.Gong.Cheng.Xue.Bao_29_1753
PubMedSearch : Wang_2013_Sheng.Wu.Gong.Cheng.Xue.Bao_29_1753
PubMedID: 24660623

Title : Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens - Condon_2013_PLoS.Genet_9_e1003233
Author(s) : Condon BJ , Leng Y , Wu D , Bushley KE , Ohm RA , Otillar R , Martin J , Schackwitz W , Grimwood J , MohdZainudin N , Xue C , Wang R , Manning VA , Dhillon B , Tu ZJ , Steffenson BJ , Salamov A , Sun H , Lowry S , LaButti K , Han J , Copeland A , Lindquist E , Barry K , Schmutz J , Baker SE , Ciuffetti LM , Grigoriev IV , Zhong S , Turgeon BG
Ref : PLoS Genet , 9 :e1003233 , 2013
Abstract : The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25x higher than those between inbred lines and 50x lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence.
ESTHER : Condon_2013_PLoS.Genet_9_e1003233
PubMedSearch : Condon_2013_PLoS.Genet_9_e1003233
PubMedID: 23357949
Gene_locus related to this paper: cocsn-m2rnc6 , coch5-m2tnl8 , coch4-n4xap8 , sett2-r0j560 , cocsn-m2thl9 , coch5-m2v1s2 , coch4-n4xzy1 , cocsn-m2sqr3 , cocsn-m2rnk8 , coch4-n4xdv7 , coch5-m2uds0 , coch5-m2um94 , sett2-r0i8c5 , coch4-n4wlc8 , coch4-n4x9p3 , cocsn-m2rh47 , cocsn-m2qz08 , sett2-r0jqq6 , sett2-r0imb6 , coch4-n4x7u3 , cocsn-m2rv02 , cocsn-m2sy95 , coch5-m2ubd5 , cocsn-m2t3d2 , sett2-r0kl84 , sett2-r0jts7 , coch4-n4x2h3 , sett2-r0jxt9 , coch4-n4x7r9 , cocsn-m2sh75 , cocsn-m2t5z2 , coch5-m2ucf6 , sett2-r0k664 , cocsn-m2t3q1 , sett2-r0k4b4 , cocsn-m2t4i1 , coch5-m2th93 , cocsn-m2svm8 , cocsn-m2s6q4 , cocsn-m2s5h5 , coch4-n4xf94 , sett2-r0kdl8 , cocsn-m2qvi9 , sett2-r0kfg6 , cocsn-m2szq4 , sett2-r0j437 , coch4-n4x7j4 , coch5-m2twk3 , coch5-m2usf2 , sett2-r0kjt7 , sett2-r0k7y2 , cocsn-m2th03 , sett2-r0iy92 , sett2-r0kbr9 , sett2-r0k997 , coch5-m2sik6 , sett2-r0jzj5 , cocsn-m2r0j6 , coch4-n4x6a4 , cocsn-m2s7a5 , cocsn-m2sv79 , sett2-r0knx4 , sett2-r0ksh8 , sett2-r0ip86 , cocmi-w6yyy3 , cocsn-m2sqe4 , coch4-n4xzc8 , cocvi-w7eyp1 , cocmi-w6zf65 , cocvi-w7er28 , cocca-w6yw25 , cocvi-w7e2g6 , cocmi-w6z7k5 , cocca-w6ys73 , cocca-w6ydq2 , cocca-w6y7i5 , cocmi-w6yyr0 , cocca-w6yh47 , cocmi-w6zju4 , cocca-w6ynq5 , cocmi-w6zm44 , cocca-w6xx85 , cocmi-w6z011 , cocca-w6yre4 , cocmi-w6z9l3 , cocca-w6yfp7 , cocmi-w6zlc2 , cocca-w6yar2 , cocmi-w6yjr7 , cocca-w6yhs1 , cocca-w6xux8 , cocmi-w6z9s8 , cocca-w6yq27 , cocmi-w6zqk9 , cocca-w6xq19 , cocca-w6y1r6 , cocca-w6ygj2 , cocmi-w6zgn4 , cocca-w6ybh2 , cocmi-w6z710 , cocca-w6yk86 , cocmi-w6zjz2 , cocmi-w6z7f2 , cocca-w6xn57 , cocca-w6ybq4 , cocmi-w6yxn5 , cocmi-w6zf08 , cocsn-m2rtg8 , cocmi-w6zuj7 , cocca-w6xtb2 , cocca-w6yk97 , coch5-m2t2x3 , cocmi-w6z646 , cocsn-m2sze4 , sett2-r0kjg6 , cocmi-w6yrn5 , sett2-r0k5q0 , cocvi-w7ezb7 , sett2-r0jtm1 , cocmi-w6ywa1 , cocsn-m2t3e8 , coch5-m2ulw5 , coch5-m2urw9 , sett2-r0knn5 , cocmi-w6ysb2 , cocvi-w7eag7 , cocca-w6y1v2 , sett2-r0i9k2 , coch5-m2uul8 , cocsn-m2sl21

Title : Molecular cloning and expression in vitro of a carboxylesterase gene from the Glanville fritillary butterfly (Melitaea cinxia) - Luo_2013_Gene_524_275
Author(s) : Luo S , Shu C , Xu C , Wang R
Ref : Gene , 524 :275 , 2013
Abstract : Carboxylesterase (EC 3.1.1.1) is a member of the carboxyl/cholinesterase (CCE) superfamily, which is widely distributed in animals, plants and microorganisms. This enzyme has been known to be associated with insecticide resistance and detoxification. Although CCEs have been extensively studied in insects, including lepidopterans, the research on butterflies, a major subgroup in Lepidoptera, is still poor. In the present study, we cloned a CCE gene (McCCE1) from the Glanville fritillary butterfly (Melitaea cinxia, Lepidoptera: Nymphalidae). The full-length cDNA encoding McCCE1 was 1786 bp, containing a 1641 bp open reading frame encoding 546 amino acids, a 38 bp 5'-untranslated region (5'-UTR), and a 107 bp 3'-UTR with a poly(A) tail. The functionally conserved amino acids in McCCE1 shared the 55% identity with the cytoplasmic esterase CCE017a in Helicoverpa armigera (Lepidoptera: Noctuidae), which has been associated with detoxification. Assays in vitro showed that the recombinant McCCE1 could hydrolyze alpha- and beta-naphthyl acetate. Thus, the present study adds to the body of knowledge concerning the detoxification of pesticides by lepidopterans.
ESTHER : Luo_2013_Gene_524_275
PubMedSearch : Luo_2013_Gene_524_275
PubMedID: 23603019
Gene_locus related to this paper: melcn-f8v329

Title : Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins - Han_2012_Brain.Res_1470_59
Author(s) : Han RW , Zhang RS , Chang M , Peng YL , Wang P , Hu SQ , Choi CL , Yin M , Wang R , Han YF
Ref : Brain Research , 1470 :59 , 2012
Abstract : Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 mumol/kg), B7C (0.4-0.6 mumol/kg) or tacrine (8-12 mumol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations.
ESTHER : Han_2012_Brain.Res_1470_59
PubMedSearch : Han_2012_Brain.Res_1470_59
PubMedID: 22750583

Title : [A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis] - Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
Author(s) : Ma JL , Wang R , Zhang FK , Jia JD , Ou XJ , Zhang T , Wang Y , Duan WJ , Zhao XY , You H , Ma H
Ref : Zhonghua Nei Ke Za Zhi , 51 :618 , 2012
Abstract : OBJECTIVE To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis PBC based on conventional laboratory markers METHODS Seventy-three patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital Capital Medical University were recruited in this study Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis RESULTS The predictive model H index consisting of five conventional laboratory markers i.e platelet count serum cholinesterase albumin HDL-C and prothrombin time activity could predict advanced fibrosis stages III-IV with an AUC(ROC of 0.861 The sensitivity of predicting the absence of advanced fibrosis using H index 2.20 was 96.6 and the specificity of predicting the presence of advanced fibrosis using H index 0.41 was 93.2 CONCLUSION The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC stages I-II from advanced stage PBC stages III-IV).
ESTHER : Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
PubMedSearch : Ma_2012_Zhonghua.Nei.Ke.Za.Zhi_51_618
PubMedID: 23158860

Title : The protection of acetylcholinesterase inhibitor on beta-amyloid-induced the injury of neurite outgrowth via regulating axon guidance related genes expression in neuronal cells - Shen_2012_Int.J.Clin.Exp.Pathol_5_900
Author(s) : Shen JN , Wang DS , Wang R
Ref : Int J Clin Exp Pathol , 5 :900 , 2012
Abstract : Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss The Rho family of small GTPases including Rho Rac and Cdc42 has a central role in cellular motility and cytokinesis Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries Present studies examined if the effect of HupA on neurite outgrowth in Abeta-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Abeta and HupA's effects The effects of Abeta and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining Abeta up-regulated the mRNA expressions of NFAT5 LIMK1 EPHA1 NTN4 and RAC2 markedly in SH-SY5Y cells Co-incubation of Abeta and HupA reversed or decreased the changes of NFAT5 NTN4 RAC2 CDC42 and SEMA4F HupA treated alone increased NFAT5 LIMK1 NTN4 significantly Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not The morphological results confirmed that HupA improved or partly reversed the Abeta-induced damage of neurite outgrowth The protective effect of HupA from Abeta induced morphological injury might be correlative to at least partially regulating the network of neurite outgrowth related genes.
ESTHER : Shen_2012_Int.J.Clin.Exp.Pathol_5_900
PubMedSearch : Shen_2012_Int.J.Clin.Exp.Pathol_5_900
PubMedID: 23119107

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

Title : Enhanced thermostability of a Rhizopus chinensis lipase by in vivo recombination in Pichia pastoris - Yu_2012_Microb.Cell.Fact_11_102
Author(s) : Yu XW , Wang R , Zhang M , Xu Y , Xiao R
Ref : Microb Cell Fact , 11 :102 , 2012
Abstract : BACKGROUND: Lipase from Rhizopus chinensis is a versatile biocatalyst for various bioconversions and has been expressed at high-level in Pichia pastoris. However, the use of R. chinensis lipase in industrial applications is restricted by its low thermostability. Directed evolution has been proven to be a powerful and efficient protein engineering tool for improvement of biocatalysts. The present work describes improvement of the thermostability of R. chinensis lipase by directed evolution using P. pastoris as the host. RESULTS: An efficient, fast and highly simplified method was developed to create a mutant gene library in P. pastoris based on in vivo recombination, whose recombination efficiency could reach 2.3 x 10/microg DNA. The thermostability of r27RCL was improved significantly by two rounds of error-prone PCR and two rounds of DNA shuffling in P. pastoris. The S4-3 variant was found to be the most thermostable lipase, under the conditions tested. Compared with the parent, the optimum temperature of S4-3 was two degrees higher, Tm was 22 degrees higher and half-lives at 60 degreesC and 65 degreesC were 46- and 23- times longer. Moreover, the catalytic efficiency kcat/Km of S4-3 was comparable to the parent. Stabilizing mutations probably increased thermostability by increasing the hydrophilicity and polarity of the protein surface and creating hydrophobic contacts inside the protein. CONCLUSIONS: P. pastoris was shown to be a valuable cell factory to improve thermostability of enzymes by directed evolution and it also could be used for improving other properties of enzymes. In this study, by using P. pastoris as a host to build mutant pool, we succeeded in obtaining a thermostable variant S4-3 without compromising enzyme activity and making it a highly promising candidate for future applications at high temperatures.
ESTHER : Yu_2012_Microb.Cell.Fact_11_102
PubMedSearch : Yu_2012_Microb.Cell.Fact_11_102
PubMedID: 22866667
Gene_locus related to this paper: rhich-a3fm73

Title : Examination of the carboxylesterase phenotype in human liver - Ross_2012_Arch.Biochem.Biophys_522_44
Author(s) : Ross MK , Borazjani A , Wang R , Crow JA , Xie S
Ref : Archives of Biochemistry & Biophysics , 522 :44 , 2012
Abstract : Carboxylesterases (CES) metabolize esters. Two CES isoforms are expressed in human liver (CES1 and CES2) and liver extracts are used in reaction phenotyping studies to discern interindividual metabolic variation. We tested the hypothesis that an individual's CES phenotype can be characterized by reporter substrates/probes that interrogate native CES1 and CES2 activities in liver and immunoblotting methods. We obtained 25 livers and found that CES1 is the main hydrolytic enzyme. Moreover, although CES1 protein levels were similar, we observed large interindividual variation in bioresmethrin hydrolysis rates (17-fold), a pyrethroid metabolized by CES1 but not CES2. Bioresmethrin hydrolysis rates did not correlate with CES1 protein levels. In contrast, procaine hydrolysis rates, a drug metabolized by CES2 but not CES1, were much less variant (3-fold). Using activity-based fluorophosphonate probes (FP-biotin), which covalently reacts with active serine hydrolases, CES1 protein was the most active enzyme in the livers. Finally, using bioorthogonal probes and click chemistry methodology, the half-life of CES 1 and 2 in cultured HepG2 cells was estimated at 96 h. The cause of the differential CES1 activities is unknown, but the underlying factors will be important to understand because several carboxylic acid ester drugs and environmental toxicants are metabolized by this enzyme.
ESTHER : Ross_2012_Arch.Biochem.Biophys_522_44
PubMedSearch : Ross_2012_Arch.Biochem.Biophys_522_44
PubMedID: 22525521

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

Title : The pharmacokinetics of PF-734200, a DPP-IV inhibitor, in subjects with renal insufficiency - Dai_2011_Br.J.Clin.Pharmacol_72_85
Author(s) : Dai H , Johnson SL , Terra SG , Marbury TC , Smith WB , Alcorn H , Boyd RA , Wang R , Nguyen TT
Ref : British Journal of Clinical Pharmacology , 72 :85 , 2011
Abstract : AIMS: PF-734200 is a potent, selective inhibitor of DPP-IV. This two-part study evaluated the pharmacokinetics (PK) of oral 20mg PF-734200 in subjects with varying degrees of renal insufficiency or with end-stage renal disease (ESRD) requiring chronic haemodialysis (HD). The study also assessed the HD clearance of PF-734200 in ESRD. METHODS: Part 1 included subjects with normal renal function or renal insufficiency but not on HD. Subjects received a single dose of 20mg PF-734200 while fasting and serum and urine samples were collected. In part 2, period 1, 1h after HD, a single 20-mg dose was given to subjects with ESRD and serum samples were collected. After a 7-day washout, subjects received another dose followed by collection of serum samples (period 2), during which HD was initiated 4h after dosing. Dialysate samples were collected to quantify amount of drug removed, from which HD clearance was calculated. The fraction of drug dialysed was calculated using an AUC-based method. RESULTS: Systemic exposures of PF-734200 increased approximately 1.5-, 2.2-, 2.1- and 2.8-fold in subjects with mild, moderate, or severe renal insufficiency or ESRD, respectively, compared with subjects with normal renal function. The terminal half-life increased from 16.2h in subjects with normal renal function to 36.6h in subjects with ESRD. Approximately, 29% of PF-734200 in the body after a single-dose administration was dialysed by 4h HD. CONCLUSIONS: Systemic exposure of PF-734200 increases with decreasing renal function. The effect of HD on drug removal is modest.
ESTHER : Dai_2011_Br.J.Clin.Pharmacol_72_85
PubMedSearch : Dai_2011_Br.J.Clin.Pharmacol_72_85
PubMedID: 21366665

Title : DWARF27, an iron-containing protein required for the biosynthesis of strigolactones, regulates rice tiller bud outgrowth - Lin_2009_Plant.Cell_21_1512
Author(s) : Lin H , Wang R , Qian Q , Yan M , Meng X , Fu Z , Yan C , Jiang B , Su Z , Li J , Wang Y
Ref : Plant Cell , 21 :1512 , 2009
Abstract : Tillering in rice (Oryza sativa) is one of the most important agronomic traits that determine grain yields. Previous studies on rice tillering mutants have shown that the outgrowth of tiller buds in rice is regulated by a carotenoid-derived MAX/RMS/D (more axillary branching) pathway, which may be conserved in higher plants. Strigolactones, a group of terpenoid lactones, have been recently identified as products of the MAX/RMS/D pathway that inhibits axillary bud outgrowth. We report here the molecular genetic characterization of d27, a classic rice mutant exhibiting increased tillers and reduced plant height. D27 encodes a novel iron-containing protein that localizes in chloroplasts and is expressed mainly in vascular cells of shoots and roots. The phenotype of d27 is correlated with enhanced polar auxin transport. The phenotypes of the d27 d10 double mutant are similar to those of d10, a mutant defective in the ortholog of MAX4/RMS1 in rice. In addition, 2'-epi-5-deoxystrigol, an identified strigolactone in root exudates of rice seedlings, was undetectable in d27, and the phenotypes of d27 could be rescued by supplementation with GR24, a synthetic strigolactone analog. Our results demonstrate that D27 is involved in the MAX/RMS/D pathway, in which D27 acts as a new member participating in the biosynthesis of strigolactones.
ESTHER : Lin_2009_Plant.Cell_21_1512
PubMedSearch : Lin_2009_Plant.Cell_21_1512
PubMedID: 19470589

Title : Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice - Chen_2008_Pharmacol.Biochem.Behav_90_441
Author(s) : Chen J , Long Y , Han M , Wang T , Chen Q , Wang R
Ref : Pharmacol Biochem Behav , 90 :441 , 2008
Abstract : The water-soluble derivative of propolis (WSDP) was prepared from fresh Chinese propolis. Its major constituents were identified by high performance liquid chromatography (HPLC) analysis. It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now. Thus, this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice. WSDP (50 mg/kg, 100 mg/kg) was given by intragastric administration (i.g.) 40 min prior to the intraperitoneal (i.p.) injection of scopolamine (1 mg/kg). The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test. The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice. Furthermore, WSDP's effect on the acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus was also assayed. As a result, WSDP (100 mg/kg) significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice. These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus, which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease (AD) and other neurodegenerative diseases.
ESTHER : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedSearch : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedID: 18485465

Title : Prognostic factors for chronic severe hepatitis and construction of a prognostic model - Li_2008_Hepatobiliary.Pancreat.Dis.Int_7_40
Author(s) : Li Q , Yuan GY , Tang KC , Liu GW , Wang R , Cao WK
Ref : Hepatobiliary Pancreat Dis Int , 7 :40 , 2008
Abstract : BACKGROUND: Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model.
METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis.
RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were significantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P) =1.573XAge+1.338XHE-1.608XCHO+0.011XCr-0.109XNa+1.298XINR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score.
CONCLUSIONS: Multivariate analysis excels univariate analysis in the prognosis of chronic severe hepatitis, and the regression model is of significant value in the prognosis of this disease.
ESTHER : Li_2008_Hepatobiliary.Pancreat.Dis.Int_7_40
PubMedSearch : Li_2008_Hepatobiliary.Pancreat.Dis.Int_7_40
PubMedID: 18234637

Title : Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine - Wang_2006_Acta.Pharmacol.Sin_27_1
Author(s) : Wang R , Yan H , Tang XC
Ref : Acta Pharmacol Sin , 27 :1 , 2006
Abstract : Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase(AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.
ESTHER : Wang_2006_Acta.Pharmacol.Sin_27_1
PubMedSearch : Wang_2006_Acta.Pharmacol.Sin_27_1
PubMedID: 16364207

Title : Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets - Ito_2005_Arch.Toxicol_79_147
Author(s) : Ito Y , Yokota H , Wang R , Yamanoshita O , Ichihara G , Wang H , Kurata Y , Takagi K , Nakajima T
Ref : Archives of Toxicology , 79 :147 , 2005
Abstract : To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague-Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6-3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2-14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor alpha involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.
ESTHER : Ito_2005_Arch.Toxicol_79_147
PubMedSearch : Ito_2005_Arch.Toxicol_79_147
PubMedID: 15798888

Title : Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease - Wang_2005_Neurosignals_14_71
Author(s) : Wang R , Tang XC
Ref : Neurosignals , 14 :71 , 2005
Abstract : Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase. It has been found to reverse or attenuate cognitive deficits in a broad range of animal models. Clinical trials in China have demonstrated that HupA significantly relieves memory deficits in aged subjects, patients with benign senescent forgetfulness, Alzheimer's disease (AD) and vascular dementia (VD), with minimal peripheral cholinergic side effects compared with other AChEIs in use. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53 and caspase-3, protect mitochondria, and interfere with APP metabolism. Antagonizing effects on NMDA receptors and potassium currents may contribute to the neuroprotection as well. It is also possible that the non-catalytic function of AChE is involved in neuroprotective effects of HupA. The therapeutic effects of HupA on AD or VD are probably exerted via a multi-target mechanism.
ESTHER : Wang_2005_Neurosignals_14_71
PubMedSearch : Wang_2005_Neurosignals_14_71
PubMedID: 15956816

Title : Huperzine A protects SHSY5Y neuroblastoma cells against oxidative stress damage via nerve growth factor production - Tang_2005_Eur.J.Pharmacol_519_9
Author(s) : Tang LL , Wang R , Tang XC
Ref : European Journal of Pharmacology , 519 :9 , 2005
Abstract : Our previous study demonstrated that huperzine A, a selective acetylcholinesterase inhibitor, stimulates the synthesis of nerve growth factor (NGF) in cultured rat cortical astrocytes. The present studies are designed to examine if huperzine A exerts its neuroprotective activity against oxidative stress damage through increasing the synthesis of NGF in SHSY5Y neuroblastoma cells. Transient exposure of the cells to 200 microM H2O2 triggered a significant reduction of cell viability and decreased the mRNA and protein levels of NGF, neurotrophin receptor P75 (P75NTR) receptor and tyrosine kinase A (TrkA) receptor. Incubation of cells with 10 microM huperzine A prior to H2O2 exposure significantly elevated their survival and restored the mRNA and protein levels of NGF, P75NTR receptor and TrkA receptor. These neuroprotective effects of huperzine A on H2O2-induced cytotoxicity were blocked by the TrkA receptor phosphorylation inhibitor K252alpha, and were antagonized by the mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) inhibitor, PD98059. The present results indicate that the cytoprotective effect of huperzine A is mediated at least partly by up-regulated NGF and NGF receptors. The results also show that the MAP/ERK kinase signal pathway is crucial for huperzine A to protect against H2O2-induced damage in SHSY5Y cells.
ESTHER : Tang_2005_Eur.J.Pharmacol_519_9
PubMedSearch : Tang_2005_Eur.J.Pharmacol_519_9
PubMedID: 16111675

Title : Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes - Brasaemle_2004_J.Biol.Chem_279_46835
Author(s) : Brasaemle DL , Dolios G , Shapiro L , Wang R
Ref : Journal of Biological Chemistry , 279 :46835 , 2004
Abstract : Adipocytes hold the body's major energy reserve as triacylglycerols packaged in large lipid droplets. Perilipins, the most abundant proteins on these lipid droplets, play a critical role in facilitating both triacylglycerol storage and hydrolysis. The stimulation of lipolysis by beta-adrenergic agonists triggers rapid phosphorylation of perilipin and translocation of hormone-sensitive lipase to the surfaces of lipid droplets and more gradual fragmentation and dispersion of micro-lipid droplets. Because few lipid droplet-associated proteins have been identified in adipocytes, we isolated lipid droplets from basal and lipolytically stimulated 3T3-L1 adipocytes and identified the component proteins by mass spectrometry. Structural proteins identified in both preparations include perilipin, S3-12, vimentin, and TIP47; in contrast, adipophilin, caveolin-1, and tubulin selectively localized to droplets in lipolytically stimulated cells. Lipid metabolic enzymes identified in both preparations include hormone-sensitive lipase, lanosterol synthase, NAD(P)-dependent steroid dehydrogenase-like protein, acyl-CoA synthetase, long chain family member (ACSL) 1, and CGI-58. 17-beta-Hydroxysteroid dehydrogenase, type 7, was identified only in basal preparations, whereas ACSL3 and 4 and two short-chain reductase/dehydrogenases were identified on droplets from lipolytically stimulated cells. Additionally, both preparations contained FSP27, ribophorin I, EHD2, diaphorase I, and ancient ubiquitous protein. Basal preparations contained CGI-49, whereas lipid droplets from lipolytically stimulated cells contained several Rab GTPases and tumor protein D54. A close association of mitochondria with lipid droplets was suggested by the identification of pyruvate carboxylase, prohibitin, and a subunit of ATP synthase in the preparations. Thus, adipocyte lipid droplets contain specific structural proteins as well as lipid metabolic enzymes; the structural reorganization of lipid droplets in response to the hormonal stimulation of lipolysis is accompanied by increases in the relative mass of several proteins and the recruitment of additional proteins.
ESTHER : Brasaemle_2004_J.Biol.Chem_279_46835
PubMedSearch : Brasaemle_2004_J.Biol.Chem_279_46835
PubMedID: 15337753

Title : Presenilin 1 familial Alzheimer's disease mutation leads to defective associative learning and impaired adult neurogenesis - Wang_2004_Neurosci_126_305
Author(s) : Wang R , Dineley KT , Sweatt JD , Zheng H
Ref : Neuroscience , 126 :305 , 2004
Abstract : Alzheimer's disease is a learning and memory disorder pathologically characterized by the deposition of beta-amyloid plaques and loss of neurons and synapses in affected areas of the brain. Mutations in presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease (FAD), and are associated with accelerated plaque deposition. However, since the function of PS1 is pleiotropic, we reasoned that the FAD mutations may alter multiple PS1-mediated pathways, and the combination of which may account for the early onset nature of the disease phenotype. Using the PS1M146V knockin mice in which the M146V mutation was incorporated into the endogenous mouse PS1 gene, we report here that the FAD mutation results in impaired hippocampus-dependent associative learning, as measured by a contextual fear conditioning paradigm, at 3 months of age. This is correlated with reduced adult neurogenesis in the dentate gyrus. However, short-term and long-term synaptic plasticity in both area CA1 and dentate gyrus are not affected. Our results suggest that impaired adult neurogenesis may contribute to the memory deficit associated with FAD.
ESTHER : Wang_2004_Neurosci_126_305
PubMedSearch : Wang_2004_Neurosci_126_305
PubMedID: 15207348

Title : Adolescent development of forebrain stimulant responsiveness: insights from animal studies - Leslie_2004_Ann.N.Y.Acad.Sci_1021_148
Author(s) : Leslie FM , Loughlin SE , Wang R , Perez L , Lotfipour S , Belluzzia JD
Ref : Annals of the New York Academy of Sciences , 1021 :148 , 2004
Abstract : Although initiation of drug abuse occurs primarily during adolescence, little is known about the central effects of nicotine and other abused drugs during this developmental period. Here evidence, derived from studies in rodents, is presented that suggests that tobacco use initiation during early adolescence results from a higher reward value of nicotine. The developmental profiles of the rewarding effects of other abused drugs, such as cocaine, differ from that of nicotine. Using in situ hybridization to quantify mRNA levels of the immediate early gene, cfos, the neuronal activating effects of nicotine in limbic and sensory cortices at different developmental stages are evaluated. Significant age changes in basal levels of cfos mRNA expression in cortical regions are observed, with a peak of responding of limbic cortices during early adolescence. A changing pattern of nicotine-induced neuronal activation is seen across the developmental spectrum, with unique differences in both limbic and sensory cortex responding during adolescence. An attentional set-shifting task was also used to evaluate whether the observed differences during adolescence reflect early functional immaturity of prefrontal cortices that regulate motivated behavior and psychostimulant responding. The finding of significantly better responding during adolescence suggests apparent functional maturity of prefrontal circuits and greater cognitive flexibility at younger ages. These findings in rodent models suggest that adolescence is a period of altered sensitivity to environmental stimuli, including abused drugs. Further efforts are required to overcome technical challenges in order to evaluate drug effects systematically in this age group.
ESTHER : Leslie_2004_Ann.N.Y.Acad.Sci_1021_148
PubMedSearch : Leslie_2004_Ann.N.Y.Acad.Sci_1021_148
PubMedID: 15251884

Title : Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes - Subramanian_2004_J.Biol.Chem_279_42062
Author(s) : Subramanian V , Rothenberg A , Gomez C , Cohen AW , Garcia A , Bhattacharyya S , Shapiro L , Dolios G , Wang R , Lisanti MP , Brasaemle DL
Ref : Journal of Biological Chemistry , 279 :42062 , 2004
Abstract : Perilipins, the major structural proteins coating the surfaces of mature lipid droplets of adipocytes, play an important role in the regulation of triacylglycerol storage and hydrolysis. We have used proteomic analysis to identify CGI-58, a member of the alpha/beta-hydrolase fold family of enzymes, as a component of lipid droplets of 3T3-L1 adipocytes. CGI-58 mRNA is highly expressed in adipose tissue and testes, tissues that also express perilipins, and at lower levels in liver, skin, kidney, and heart. Both endogenous CGI-58 and an ectopic CGI-58-GFP chimera show diffuse cytoplasmic localization in 3T3-L1 preadipocytes, but localize almost exclusively to the surfaces of lipid droplets in differentiated 3T3-L1 adipocytes. The localization of endogenous CGI-58 was investigated in 3T3-L1 cells stably expressing mutated forms of perilipin using microscopy. CGI-58 binds to lipid droplets coated with perilipin A or mutated forms of perilipin with an intact C-terminal sequence from amino acid 382 to 429, but not to lipid droplets coated with perilipin B or mutated perilipin A lacking this sequence. Immunoprecipitation studies confirmed these findings, but also showed co-precipitation of perilipin B and CGI-58. Remarkably, activation of cAMP-dependent protein kinase by the incubation of 3T3-L1 adipocytes with isoproterenol and isobutylmethylxanthine disperses CGI-58 from the surfaces of lipid droplets to a cytoplasmic distribution. This shift in subcellular localization can be reversed by the addition of propanolol to the culture medium. Thus, CGI-58 binds to perilipin A-coated lipid droplets in a manner that is dependent upon the metabolic status of the adipocyte and the activity of cAMP-dependent protein kinase.
ESTHER : Subramanian_2004_J.Biol.Chem_279_42062
PubMedSearch : Subramanian_2004_J.Biol.Chem_279_42062
PubMedID: 15292255
Gene_locus related to this paper: mouse-abhd5

Title : Epoxide hydrolase Tyr113His polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma in population of North China - Zhang_2003_World.J.Gastroenterol_9_2654
Author(s) : Zhang JH , Jin X , Li Y , Wang R , Guo W , Wang N , Wen DG , Chen ZF , Kuang G , Wei LZ , Wang SJ
Ref : World J Gastroenterol , 9 :2654 , 2003
Abstract : AIM To investigate the possible association of microsomal epoxide hydrolase (mEH) Tyr113His polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) in a population of North China. METHODS: The mEH Tyr113His genotypes were determined by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 257 patients with esophageal squamous cell carcinoma (ESCC) and 252 healthy subjects as a control group. RESULTS: The frequencies for Tyr and His alleles were 44.2%, 55.8% in ESCC patients, and 44.0% and 56.0% in healthy subjects, respectively. No statistic difference in allele distribution was observed between ESCC patients and controls (chi2=0.008, P=0.929). The overall genotype distribution difference was not observed between cancer cases and controls (chi2=2.116, P=0.347). Compared with Tyr/Tyr genotype, neither His/His genotype nor in combination with Tyr/His genotype significantly modified the risk of the development of ESCC, the adjusted odds ratio was 1.076 (95% CI=0.850-1.361) and 0.756 (95% CI=0.493-1.157), respectively. When stratified for sex, age, smoking status and family history of upper gastrointestinal cancer, His/His genotype alone or in combination with Tyr/His genotype also did not show any significant influence on the risk of developing ESCC. CONCLUSION: MEH Tyr113His polymorphism may not be used as a stratification marker in screening individuals at a high risk of ESCC.
ESTHER : Zhang_2003_World.J.Gastroenterol_9_2654
PubMedSearch : Zhang_2003_World.J.Gastroenterol_9_2654
PubMedID: 14669306

Title : Genetic loci affecting resistance to human malaria parasites in a West African mosquito vector population - Niare_2002_Science_298_213
Author(s) : Niare O , Markianos K , Volz J , Oduol F , Toure A , Bagayoko M , Sangare D , Traore SF , Wang R , Blass C , Dolo G , Bouare M , Kafatos FC , Kruglyak L , Toure YT , Vernick KD
Ref : Science , 298 :213 , 2002
Abstract : Successful propagation of the malaria parasite Plasmodium falciparum within a susceptible mosquito vector is a prerequisite for the transmission of malaria. A field-based genetic analysis of the major human malaria vector, Anopheles gambiae, has revealed natural factors that reduce the transmission of P. falciparum. Differences in P. falciparum oocyst numbers between mosquito isofemale families fed on the same infected blood indicated a large genetic component affecting resistance to the parasite, and genome-wide scanning in pedigrees of wild mosquitoes detected segregating resistance alleles. The apparently high natural frequency of resistance alleles suggests that malaria parasites (or a similar pathogen) exert a significant selective pressure on vector populations.
ESTHER : Niare_2002_Science_298_213
PubMedSearch : Niare_2002_Science_298_213
PubMedID: 12364806

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells - Wang_2002_Brain.Res.Mol.Brain.Res_107_1
Author(s) : Wang R , Zhou J , Tang XC
Ref : Brain Research Mol Brain Res , 107 :1 , 2002
Abstract : The present studies investigated the effects of tacrine, a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H(2)O(2))-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H(2)O(2) (100 microM) triggered typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed upregulated p53 and bax mRNA levels with H(2)O(2) treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with tacrine significantly attenuated H(2)O(2)-induced injury, prevented the cells from apoptosis and attenuated H(2)O(2)-induced overexpression of bax and p53. The present findings suggest that tacrine exert significant protection against H(2)O(2)-induced apoptosis possibly through inhibiting expression of pro-apoptosis genes.
ESTHER : Wang_2002_Brain.Res.Mol.Brain.Res_107_1
PubMedSearch : Wang_2002_Brain.Res.Mol.Brain.Res_107_1
PubMedID: 12414117

Title : Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells - Wang_2001_Neuroreport_12_2629
Author(s) : Wang R , Xiao XQ , Tang XC
Ref : Neuroreport , 12 :2629 , 2001
Abstract : The present studies investigated effects of huperzine A (HupA), a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on hydrogen peroxide (H2O2)-induced apoptosis and the expression of apoptosis-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H2O2 (100 microM) triggered a typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies showed up-regulated p53 and Bax but lowered Bcl-2 mRNA levels with H2O2 treatment. The results were further confirmed at protein levels by immunocytochemistry with specific antibodies. Preincubation with HupA (1 microM) significantly prevented the cells from apoptosis, attenuated H2O2-induced over-expression of Bax and p53, and rehabilitated the level of Bcl-2. The present findings suggest that HupA exerts significant protection against H2O2-induced apoptosis, possibly through improving expression of apoptosis-related genes.
ESTHER : Wang_2001_Neuroreport_12_2629
PubMedSearch : Wang_2001_Neuroreport_12_2629
PubMedID: 11522938

Title : Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury - Xiao_2000_J.Neurosci.Res_61_564
Author(s) : Xiao XQ , Wang R , Tang XC
Ref : Journal of Neuroscience Research , 61 :564 , 2000
Abstract : Increased oxidative stress resulting from free radical damage to cellular function is associated with a number of neurodegenerative diseases, in particular with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (Abeta), the major pathological hallmark for AD, has been suggested as the central disease-causing and disease-promoting event for the disease, and the pathological role of Abeta was partially mediated by oxidative stress. Here we compared the effects of huperzine A (HupA) and tacrine, two acetylcholinesterase (AChE) inhibitors available for AD, on Abeta-induced cell lesion, level of lipid peroxidation, and antioxidant enzyme activities in rat PC12 and primary cultured cortical neurons. Following exposure of both cells to different concentrations of an active fragment of Abeta, a marked reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MDA) and superoxide dismutase (SOD), were observed. Pretreatment of the cells with HupA or tacrine (0.1-10 microM) prior to Abeta exposure significantly elevated the cell survival and GSH-Px and CAT activities and decreased the level of MDA. Both drugs have similar protection against Abeta insult. Our results indicate that HupA and tacrine exert neuroprotective effects against Abeta toxicity, which might be of importance and might contribute to their clinical efficacy for the treatment of AD.
ESTHER : Xiao_2000_J.Neurosci.Res_61_564
PubMedSearch : Xiao_2000_J.Neurosci.Res_61_564
PubMedID: 10956426

Title : Protective effects of huperzine A on beta-amyloid(25-35) induced oxidative injury in rat pheochromocytoma cells - Xiao_2000_Neurosci.Lett_286_155
Author(s) : Xiao XQ , Wang R , Han YF , Tang XC
Ref : Neuroscience Letters , 286 :155 , 2000
Abstract : The effects of huperzine A (HupA), a novel acetylcholinesterase inhibitor, on Abeta(25-35)-induced cell lesion, level of lipid peroxidation, antioxidant enzyme activities were investigated in the rat pheochromocytoma line PC12. Following a 48 h exposure of the cells to Abeta(25-35), a significant reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MDA) and superoxide dismutase (SOD) were observed. Preincubation of the cells with HupA prior to Abeta(25-35) exposure elevated the cell survival and GSH-Px and CAT activities, and decreased the level of MDA and SOD activity. The results indicate that HupA has protective effects against Abeta-induced cell toxicity, which might be beneficial for the treatment of Alzheimer's disease.
ESTHER : Xiao_2000_Neurosci.Lett_286_155
PubMedSearch : Xiao_2000_Neurosci.Lett_286_155
PubMedID: 10832008

Title : Beta-amyloid precursor protein-like immunoreactivity is upregulated during olfactory nerve regeneration in adult rats - Struble_1998_Brain.Res_780_129
Author(s) : Struble RG , Dhanraj DN , Mei Y , Wilson M , Wang R , Ramkumar V
Ref : Brain Research , 780 :129 , 1998
Abstract : Beta-amyloid precursor protein (APP) is the source of beta-amyloid, which forms the cores of senile plaques in Alzheimer's Disease. However, the function of this precursor protein is currently unknown and an adult animal in which this protein varied substantially would be valuable. We used subcutaneous diethyldithiocarbamate to reversibly lesion the olfactory epithelium in adult rats and found that whole-bulb levels of APP-like immunoreactivity significantly decreased after the lesion, then increased reaching almost five-fold normal levels six weeks after treatment. Growth cone associated protein (GAP43) decreased when the nerve degenerated, then increased, replicating previous studies of olfactory nerve regeneration. Immunocytochemical techniques identified APP immunoreactive perikarya and fibers in and around glomeruli at three days to one week post-lesion and upregulation of APP-like immunoreactivity in mitral cells and dendrites at five weeks. Olfactory nerve regeneration appears to be a useful in vivo model system to understand the regulation of APP-like proteins.
ESTHER : Struble_1998_Brain.Res_780_129
PubMedSearch : Struble_1998_Brain.Res_780_129
PubMedID: 9473628