Jiang Y

References (102)

Title : Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate Mofetil - Xie_2024_J.Microbiol.Biotechnol_34_249
Author(s) : Xie Q , Cao Z , You W , Cai X , Shen M , Yin Z , Jiang Y , Wang X , Ye S
Ref : J Microbiol Biotechnol , 34 :249 , 2024
Abstract : New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
ESTHER : Xie_2024_J.Microbiol.Biotechnol_34_249
PubMedSearch : Xie_2024_J.Microbiol.Biotechnol_34_249
PubMedID: 38419324

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

Title : Study on the Mechanism of Interaction between Dipeptidyl Peptidase 4 and Inhibitory Peptides Based on Gaussian Accelerated Molecular Dynamic Simulation - Liu_2024_Int.J.Mol.Sci_25_
Author(s) : Liu Y , Zhao W , Jiang Y , Xing S , Li W
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Dipeptidyl peptidase 4 (DPP4) inhibitors can effectively inhibit the activity of DPP4, increasing the concentrations of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which allows for them to effectively contribute to the reduction of blood sugar levels. Leu-Pro-Ala-Val-Thr-Ile-Arg (LPAVTIR) and Leu-Pro-Pro-Glu-His-Asp-Trp-Arg (LPPEHDWR) were the two peptides with the strongest inhibitory activity against DPP4 selected from silkworm pupa proteins. In this study, four systems were established: Apo (ligand-free DPP4), IPI (IPI-bound DPP4), LPAVTIR (LPAVTIR-bound DPP4), LPPEHDWR (LPPEHDWR-bound DPP4), and Gaussian accelerated molecular dynamic (GaMD) simulation was conducted to investigate the mechanism of action of two inhibitory peptides binding to DPP4. Our study revealed that the LPAVTIR peptide possessed a more stable structure and exhibited a tighter binding to the Ser630 active site in DPP4, thus exhibiting a favorable competitive inhibition effect. In contrast, the LPPEHDWR peptide caused the horizontal alpha-helix (residues 201-215) composed of Glu205 and Glu206 residues in DPP4 to disappear. The spatial arrangement of active sites Ser630 relative to Glu205 and Glu206 was disrupted, resulting in enzyme inactivation. Moreover, the size of the substrate channel and cavity volume was significantly reduced after the binding of the inhibitory peptide to the protein, which was an important factor in the inhibition of the enzyme activity. A similar effect was also found from IPI (our positive control). By stabilizing the active site of DPP4, the IPI peptide induced the disappearance of the horizontal alpha-helix and a notable reduction in the active cavity volume. In conclusion, our study provided a solid theoretical foundation for the inhibitory mechanisms of IPI, LPAVTIR, and LPPEHDWR on DPP4, offering valuable insights for advancing the development of drug targets for type 2 diabetes.
ESTHER : Liu_2024_Int.J.Mol.Sci_25_
PubMedSearch : Liu_2024_Int.J.Mol.Sci_25_
PubMedID: 38255913

Title : Characterization of a novel esterase and construction of a Rhodococcus-Burkholderia consortium capable of catabolism bis (2-hydroxyethyl) terephthalate - Jiang_2023_Environ.Res__117240
Author(s) : Jiang W , Sun J , Dong W , Zhou J , Jiang Y , Zhang W , Xin F , Jiang M
Ref : Environ Research , :117240 , 2023
Abstract : Bis (2-hydroxyethyl) terephthalate (BHET) is one of the main compounds produced by enzymatic hydrolysis or chemical depolymerization of polyethylene terephthalate (PET). However, the lack of understanding on BHET microbial metabolism is a main factor limiting the bio-upcycling of PET. In this study, BHET-degrading strains of Rhodococcus biphenylivorans GA1 and Burkholderia sp. EG1 were isolated and identified, which can grow with BHET as the sole carbon source. Furthermore, a novel esterase gene betH was cloned from strain GA1, which encodes a BHET hydrolyzing esterase with the highest activity at 30 degreesC and pH 7.0. In addition, the co-culture containing strain GA1 and strain EG1 could completely degrade high concentration of BHET, eliminating the inhibition on strain GA1 caused by the accumulation of intermediate metabolite ethylene glycol (EG). This work will provide potential strains and a feasible strategy for PET bio-upcycling.
ESTHER : Jiang_2023_Environ.Res__117240
PubMedSearch : Jiang_2023_Environ.Res__117240
PubMedID: 37783328
Gene_locus related to this paper: 9noca-h0jte1

Title : Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats - Shao_2023_J.Invest.Surg_36_1
Author(s) : Shao Y , Li C , Jiang Y , Li H , Tang X , Gao Z , Zhang D
Ref : J Invest Surg , 36 :1 , 2023
Abstract : Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-alpha, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1 and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-alpha, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.
ESTHER : Shao_2023_J.Invest.Surg_36_1
PubMedSearch : Shao_2023_J.Invest.Surg_36_1
PubMedID: 36350036

Title : A novel near-infrared fluorescent probe for high-sensitivity detection of butyrylcholinesterase in various pathological states - Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
Author(s) : Jiang Y , Cui H , Yu Q
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 308 :123801 , 2023
Abstract : Butyrylcholinesterase (BChE) is a crucial hydrolytic enzyme predominantly synthesized in the liver, playing a significant role in conditions like liver disorders, diabetes, Alzheimer's disease, and fat metabolism regulation. This study aims to address the current limitations in visualizing BChE activity in diseases at various states by introducing an ultra-sensitive near-infrared fluorescent probe, FDCM-BChE. The probe was engineered to have several properties, such as a large Stokes shift, rapid response time, high stability, excellent selectivity, and low detection limits. We validated the efficacy of FDCM-BChE in quantifying BChE activity in human serum and leveraged its low cytotoxicity for cellular imaging. The study revealed the downregulation of BChE activity in liver cancer and hepatic injury and the upregulation in diabetes. Thus, FDCM-BChE shows promise as a tool for specific applications, providing insights into diseases associated with BChE activity.
ESTHER : Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
PubMedSearch : Jiang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123801
PubMedID: 38142494

Title : Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes - Wu_2023_Diabetes.Obes.Metab__
Author(s) : Wu Y , Cheng S , Gu H , Yang K , Xu Z , Meng X , Wang Y , Jiang Y , Li H , Zhou Y
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m(2) at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m(2) or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.
ESTHER : Wu_2023_Diabetes.Obes.Metab__
PubMedSearch : Wu_2023_Diabetes.Obes.Metab__
PubMedID: 37427758

Title : (+)-\/(-)-Rutabenzofuran a and (+)-\/(-)- Rutabenzofuran b: Two unprecedented pairs of Z\/E isomeric benzofuran enantiomers from the aerial part of Ruta graveolens L - Liu_2023_Phytochemistry__113677
Author(s) : Liu Y , Peng J , Huang L , Li B , Ge C , Liu S , Jiang Y
Ref : Phytochemistry , :113677 , 2023
Abstract : Two pairs of Z/E isomeric benzofuran enantiomers possessing unprecedented carbon skeletons featuring ring cleavage and addition reactions in the alpha-pyrone ring of furocoumarin, named rutabenzofuran A [(+)-1 and (-)-1], and rutabenzofuran B [(+)-2 and (-)-2], respectively, were isolated as minor compounds from the water extract of the aerial part of Ruta graveolens L. Their structures were determined by extensive spectroscopic data analysis. The absolute configurations were assigned by comparing the optical rotation with previous research and the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra. (-)-1, (+)-2, and (-)-2 were evaluated for antibacterial, anticoagulant, anticancer, and acetylcholinesterase (AChE) inhibitory activities. No anticancer or anticoagulant activities were observed, yet (-)-2 exhibited weak antibacterial activity against Salmonella enterica subsp. Enterica. At the same time, (-)-1, (+)-2, and (-)-2 displayed weak inhibitory activity on AChE.
ESTHER : Liu_2023_Phytochemistry__113677
PubMedSearch : Liu_2023_Phytochemistry__113677
PubMedID: 37059286

Title : Eco-friendly and efficient extraction of polyphenols from Ligustrum robustum by deep eutectic solvent assisted ultrasound - Qin_2023_Food.Chem_429_136828
Author(s) : Qin G , Zhang F , Ren M , Chen X , Liu C , Li G , Gao Q , Qiao L , Jiang Y , Zhu L , Guo Y , Wang G
Ref : Food Chem , 429 :136828 , 2023
Abstract : An eco-friendly and efficient extraction method using deep eutectic solvents assisted ultrasound extraction (DESs-UAE) for the polyphenols from Ligustrum robustum was developed. Among the 34 kinds of DESs prepared, tetraethyl ammonium bromide: 1,2,4-butanol (Teab: 1,2,4-But) was proved to be a suitable extraction solvent based on the extraction efficiency. The extraction parameters including temperature, water content, liquid-solid ratio were optimized with response surface methodology (RSM). Under the optimal conditions, the total phenolic content (TPC) and total flavonoid content (TFC) were 101.46 +/- 2.96 mg GAE/g DW and 264.17 +/- 5.39 mg RE/g DW, respectively. Furthermore, the extraction mechanism of DESs-UAE was investigated by extraction kinetics, molecular dynamic simulation and theory calculations of interaction. In particular, 9 kinds of polyphenols compounds from Ligustrum robustum were firstly identified by UPLC-Q-TOF-MS. Moreover, the recovered polyphenols exhibited significant antioxidant, alpha-glucosidase inhibition, acetylcholinesterase inhibition and anticancer activity.
ESTHER : Qin_2023_Food.Chem_429_136828
PubMedSearch : Qin_2023_Food.Chem_429_136828
PubMedID: 37478601

Title : Acute toxicity of tire wear particles and leachate to Daphnia magna - Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
Author(s) : Liu J , Feng Q , Yang H , Fan X , Jiang Y , Wu T
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109713 , 2023
Abstract : Tire wear particles (TWP) are a new pollutant widely present in the environment, and have been identified as microplastics (MPs), which are receiving increasing attention due to their toxic effects on aquatic organisms. In this study, D. magna was used as test organism, and the leachate from TWP was prepared by hot water extraction for 30 (30-E) and 120 min (120-E). The acute toxic effects of particles and leachate on D. magna were studied under different exposure concentrations. The results showed that zinc and pyrene were the highest detected contaminants in the leachate. The 48 h-LC(50) values for particles and leachate were determined to be 56.99, 461.30 (30-E), and 153.00 mg/L (120-E), respectively. Following a 48 h exposure period, the immobilization of D. magna exposed to the particles and their leachate were increased with the concentration increase. The physical damage of the gut was found to be a possible mechanism for particle-induced biotoxicity. The compounds leached from TWP were responsible for the acute toxicity of leachate. Particles usually demonstrated a greater degree of toxicity in comparison to their leachate, especially at environmentally relevant concentrations. Exposure to particles and leachate resulted in the inhibition of swimming speed, swimming acceleration, filtration rate, and ingestion rate in D. magna. Furthermore, thoracic limb activity was observed to be inhibited. The heart rate of D. magna was significantly increased by the presence of particles at a concentration of 200 mg/L and leachate at concentrations of 400 and 800 mg/L (120-E). The observed alterations in behavior and physiological endpoints may be related to oxidative stress and neurotoxicity in the organism. Reduced superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities indicated that D. magna may suffer from excessive oxidative stress, whereas the increase of acetylcholinesterase (AChE) activity may serve as a biomarker of susceptibility to evaluate the environmental risks of TWP and corresponding leachates as potential aquatic pollutants.. Therefore, a more comprehensive risk assessment of TWP in the environment is necessary.
ESTHER : Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
PubMedSearch : Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
PubMedID: 37544637

Title : Identification of the first selective bioluminescent probe for real-time monitoring of carboxylesterase 2 in vitro and in vivo - Chen_2023_Analyst__
Author(s) : Chen Z , Yu J , Sun K , Song J , Chen L , Jiang Y , Wang Z , Chen Y , Zhao T , Miao Z , Huang T , Chen M , Zhao Y , Hai A , Qi Q , Feng P , Li M , Ke B
Ref : Analyst , : , 2023
Abstract : Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.
ESTHER : Chen_2023_Analyst__
PubMedSearch : Chen_2023_Analyst__
PubMedID: 36661088 || 38078792

Title : EnzyKR: a chirality-aware deep learning model for predicting the outcomes of the hydrolase-catalyzed kinetic resolution - Ran_2023_Chem.Sci_14_12073
Author(s) : Ran X , Jiang Y , Shao Q , Yang ZJ
Ref : Chem Sci , 14 :12073 , 2023
Abstract : Hydrolase-catalyzed kinetic resolution is a well-established biocatalytic process. However, the computational tools that predict favorable enzyme scaffolds for separating a racemic substrate mixture are underdeveloped. To address this challenge, we trained a deep learning framework, EnzyKR, to automate the selection of hydrolases for stereoselective biocatalysis. EnzyKR adopts a classifier-regressor architecture that first identifies the reactive binding conformer of a substrate-hydrolase complex, and then predicts its activation free energy. A structure-based encoding strategy was used to depict the chiral interactions between hydrolases and enantiomers. Different from existing models trained on protein sequences and substrate SMILES strings, EnzyKR was trained using 204 substrate-hydrolase complexes, which were constructed by docking. EnzyKR was tested using a held-out dataset of 20 complexes on the task of predicting activation free energy. EnzyKR achieved a Pearson correlation coefficient (R) of 0.72, a Spearman rank correlation coefficient (Spearman R) of 0.72, and a mean absolute error (MAE) of 1.54 kcal mol(-1) in this task. Furthermore, EnzyKR was tested on the task of predicting enantiomeric excess ratios for 28 hydrolytic kinetic resolution reactions catalyzed by fluoroacetate dehalogenase RPA1163, halohydrin HheC, A. mediolanus epoxide hydrolase, and P. fluorescens esterase. The performance of EnzyKR was compared against that of a recently developed kinetic predictor, DLKcat. EnzyKR correctly predicts the favored enantiomer and outperforms DLKcat in 18 out of 28 reactions, occupying 64% of the test cases. These results demonstrate EnzyKR to be a new approach for prediction of enantiomeric outcomes in hydrolase-catalyzed kinetic resolution reactions.
ESTHER : Ran_2023_Chem.Sci_14_12073
PubMedSearch : Ran_2023_Chem.Sci_14_12073
PubMedID: 37969577

Title : DPP4 Regulates the Th17\/IL-17 Axis and Accelerates Epithelial Mesenchymal Transition to Promote Ovalbumin-Induced Asthma in Female C57BL\/6J Mice - Li_2023_Front.Biosci.(Landmark.Ed)_28_342
Author(s) : Li L , Ling F , Li R , Jiang Y , Long H , Xiao B , Wu J , Long Z , Ma L
Ref : Front Biosci (Landmark Ed) , 28 :342 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is a transmembrane glycoprotein, prevalent across a variety of tissues and cells and can be foundin a solubilised in peripheral blood. This paper aims at determining the role of sCD26/sDPP4 in Th17 cell polarization and airway epithelial cell to epithelial mesenchymal transition (EMT) in asthma. METHODS: Female C57BL/6J mice were treated with ovalbumin to constructed asthma mice. The CD4+ T cell, and bronchial epithelial cells (BECs) were purified from the spleens and bronchus of mice. The KRT8 expression in BECs were identified by immunofluorescence (IF). Th17 cells were differentiated from a CD4+ T cell. Flow cytometry was usewd to identify and calculate the Th17 and Treg cells. Mice woth asthma were treated by DPP4 overexpressing lentivirus or DPP4 inhibitor. Histopathological modifications were assessed by hematoxylin-eosin (HE), periodic acid Schiff (PAS), and Masson staining. The total number of leucocytes was detected using a hemocytometer. For detection, quantitative Real-time PCR (qRT-PCR), western blotting (WB), and IF were used to evaluate the expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA). Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the DPP4, IL-4, IL-5, IL-13 and IL-17 levels. RESULTS: The findings suggest that sCD26/sDPP4 promote CD4+ T cells differentiation into Th17 cells in a depending on the applied dose. sCD26/sDPP4 up-regulated the expression of alpha-SMA and down-regulated the expression of E-cadherin in TGF-beta1-induced mouse BECs, which was reversed by DPP4 inhibitor. Co-culture induced a synergic effect between Th17 cells and sCD26/sDPP4 on the formation of airway EMT in BECs. Furthermore, DPP4 inhibitor prevented lung-bronchial inflammatory infiltration, mucus secretion, goblet cell hyperplasia and collagen deposition in asthma mice. Meanwhile, DPP4 inhibitor decreased the levels of DPP4, IL-4, IL-5, IL-13, IL-17 and increased the total number of leukocytes in bronchoalveolar lavage fluid of asthma mice. In addition, DPP4 inhibitor also inhibited airway EMT and Th17 cell polarization in asthma mice. CONCLUSIONS: The results in this paper show that up-regulation of DPP4 enabled airway inflammation and airway remodeling in asthmatic mice by modulating the Th17/IL-17 axis and accelerating the airway EMT, which isa therapeutic target in asthma.
ESTHER : Li_2023_Front.Biosci.(Landmark.Ed)_28_342
PubMedSearch : Li_2023_Front.Biosci.(Landmark.Ed)_28_342
PubMedID: 38179747

Title : Preclinical and randomized clinical evaluation of the p38alpha kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration - Jiang_2022_Nat.Commun_13_5308
Author(s) : Jiang Y , Alam JJ , Gomperts SN , Maruff P , Lemstra AW , Germann UA , Stavrides PH , Darji S , Malampati S , Peddy J , Bleiwas C , Pawlik M , Pensalfini A , Yang DS , Subbanna S , Basavarajappa BS , Smiley JF , Gardner A , Blackburn K , Chu HM , Prins ND , Teunissen CE , Harrison JE , Scheltens P , Nixon RA
Ref : Nat Commun , 13 :5308 , 2022
Abstract : The endosome-associated GTPase Rab5 is a central player in the molecular mechanisms leading to degeneration of basal forebrain cholinergic neurons (BFCN), a long-standing target for drug development. As p38alpha is a Rab5 activator, we hypothesized that inhibition of this kinase holds potential as an approach to treat diseases associated with BFCN loss. Herein, we report that neflamapimod (oral small molecule p38alpha inhibitor) reduces Rab5 activity, reverses endosomal pathology, and restores the numbers and morphology of BFCNs in a mouse model that develops BFCN degeneration. We also report on the results of an exploratory (hypothesis-generating) phase 2a randomized double-blind 16-week placebo-controlled clinical trial (Clinical trial registration: NCT04001517/EudraCT #2019-001566-15) of neflamapimod in mild-to-moderate dementia with Lewy bodies (DLB), a disease in which BFCN degeneration is an important driver of disease expression. A total of 91 participants, all receiving background cholinesterase inhibitor therapy, were randomized 1:1 between neflamapimod 40 mg or matching placebo capsules (taken orally twice-daily if weight <80 kg or thrice-daily if weight >80 kg). Neflamapimod does not show an effect in the clinical study on the primary endpoint, a cognitive-test battery. On two secondary endpoints, a measure of functional mobility and a dementia rating-scale, improvements were seen that are consistent with an effect on BFCN function. Neflamapimod treatment is well-tolerated with no study drug associated treatment discontinuations. The combined preclinical and clinical observations inform on the validity of the Rab5-based pathogenic model of cholinergic degeneration and provide a foundation for confirmatory (hypothesis-testing) clinical evaluation of neflamapimod in DLB.
ESTHER : Jiang_2022_Nat.Commun_13_5308
PubMedSearch : Jiang_2022_Nat.Commun_13_5308
PubMedID: 36130946

Title : Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) - Li_2022_BMC.Genomics_23_185
Author(s) : Li Z , Wu L , Wang C , Wang Y , He L , Wang Z , Ma X , Bai F , Feng G , Liu J , Jiang Y , Song F
Ref : BMC Genomics , 23 :185 , 2022
Abstract : BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
ESTHER : Li_2022_BMC.Genomics_23_185
PubMedSearch : Li_2022_BMC.Genomics_23_185
PubMedID: 35249536

Title : Engineering an Ag\/Au bimetallic nanoparticle-based acetylcholinesterase SERS biosensor for in situ sensitive detection of organophosphorus pesticide residues in food - Xu_2022_Anal.Bioanal.Chem__
Author(s) : Xu S , Li M , Li X , Jiang Y , Yu L , Zhao Y , Wen L , Xue Q
Ref : Anal Bioanal Chem , : , 2022
Abstract : Developing simple, efficient, and inexpensive method for trace amount organophosphorus pesticides' (OPs) detection with high sensitivity and specificity is of significant importance for guaranteeing food safety. Herein, an Ag/Au bimetallic nanoparticle-based acetylcholinesterase (AChE) surface-enhanced Raman scattering (SERS) biosensor was constructed for in situ simple and sensitive detection of pesticide residues in food. The principle of this biosensor exploited 4-mercaptophenylboronic acid (4-MPBA)-modified Ag/Au bimetallic nanoprobes as SERS signal probe to improve sensitivity and stability. The combination of AChE and choline oxidase (CHO) can hydrolyze acetylcholine (ATCh) to generate H(2)O(2). The product of H(2)O(2) selectively oxidizes the boronate ester of 4-MPBA, decreasing the Raman intensity of the B-O symmetric stretching. In the presence of OPs, it could inhibit the production of H(2)O(2) by destroying the AChE activity, so the reduction of the SERS signal was also alleviated. Based on the principle, an Ag/Au bimetallic nanoparticle-based AChE SERS sensor was established without any complicated pretreatments. Benefiting from the synergistic effects of Ag/Au bimetallic hybrids, a linear detection range from 5x10(-9) to 5x10(-4) M was achieved with a limit of detection down to 1.7x10(-9) M using parathion-methyl (PM) as the representative model of OPs. Moreover, the SERS biosensor uses readily available reagents and is simple to implement. Importantly, the proposed SERS biosensor was used to quantitatively analyze OP residues in apple peels. The levels of OPs detected in real samples by this method were consistent with those obtained using gas chromatography-mass spectrometry (GC-MS), suggesting the proposed assay has great potential applications for OPs in situ detection in food safety fields.
ESTHER : Xu_2022_Anal.Bioanal.Chem__
PubMedSearch : Xu_2022_Anal.Bioanal.Chem__
PubMedID: 36333614

Title : Rapid screening for acetylcholinesterase inhibitors in Selaginella doederleinii Hieron by using functionalized magnetic Fe(3)O(4) nanoparticles - Zhang_2022_Talanta_243_123284
Author(s) : Zhang F , Li S , Liu C , Fang K , Jiang Y , Zhang J , Lan J , Zhu L , Pang H , Wang G
Ref : Talanta , 243 :123284 , 2022
Abstract : Insufficient acetylcholine (ACh) can cause cognitive and memory dysfunction, clinically known as, Alzheimer's disease (AD). Acetylcholinesterase (AChE) can hydrolyze ACh into acetic acid and inactivate choline. Therefore, inhibiting the activity of AChE would help to improve the effectiveness of AD treatment. Currently, the methods for rapid screening of AChE inhibitors are limited. This study reports the application of AChE-immobilized magnetic nanoparticles as a drug screening tool to screen AChE inhibitors for natural products. First, AChE was immobilized on a surface of amino-modified magnetic nanoparticles using covalent binding and the AChE concentration, and the pH as well as time was optimized to obtain the maximum enzyme immobilization yield (61.4 microg/mg), and the kinetic model indicated that AChE-immobilized magnetic nanoparticles and the substrate had the high affinity and specificity. Then, a ligand fishing experiment was carried out using a mixed model of tacrine (an inhibitor of AChE) and caffeic acid (a non-inhibitor of AChE) to verify the specificity of the immobilized AChE, and the conditions for ligand fishing were further optimized. Finally, the optimized immobilized AChE was combined with UPLC-MS to screen for AChE inhibitors in Selaginella doederleinii Hieron extracts. Four compounds were confirmed to be potent AChE inhibitors. Among the four compounds, amentoflavone had a stronger AChE inhibitory effect than tacrine (positive control) with an IC(50) of 0.73 +/- 0.009 micromol/L. The results showed that AChE-functionalized magnetic nanoparticles can be used in the discovery of target drugs from complex matrices.
ESTHER : Zhang_2022_Talanta_243_123284
PubMedSearch : Zhang_2022_Talanta_243_123284
PubMedID: 35255433

Title : Effects of Fatty-Type and Lean-Type on Growth Performance and Lipid Droplet Metabolism in Pekin Ducks - Zhuang_2022_Animals.(Basel)_12_
Author(s) : Zhuang Z , Yang T , Jia W , Bai M , Bai H , Wang Z , Chen G , Jiang Y , Chang G
Ref : Animals (Basel) , 12 : , 2022
Abstract : The reasons for differences in lipid depositions between fatty-type (F-T) and lean-type (L-T) ducks remain unknown. The present study aimed to compare the growth performance, lipid deposition, and gene expression related to lipid droplet formation in F-T and L-T Pekin ducks. One-day-old, 140 each L-T and F-T male ducks were selected and distributed separately into 20 replicate cages. All ducks were fed commercial diets up to 35 d of age. F-T ducks had a higher average daily gain from 21 to 28 d of age. On 35-day-old, F-T ducks had higher serum levels of high- and low-density lipoprotein cholesterol, cholesterol, albumin, and hydroxybutyrate dehydrogenase activity than L-T ducks. F-T ducks had higher abdominal fat and subcutaneous fat percentages than those in L-T ducks. Liver histological examination showed that L-T ducks contained more lipid droplets in the liver, which gradually decreased with increasing age. The average adipocyte area and diameter of abdominal fat and subcutaneous fat in the F-T and L-T ducks increased with age and were higher in F-T ducks than those in L-T ducks. Furthermore, the gene expression of perilipin 1, perilipin 2, angiopoietin-like protein 4, adipose triglyceride lipase, alpha/beta-hydrolase domain-containing protein 5 (ABHD5), and serine/threonine kinase 17a in the liver, abdominal fat, and subcutaneous fat of F-T ducks was higher than that in L-T ducks, and it increased with age. Compared to L-T ducks, F-T ducks had higher expression of ABHD5 in the abdominal fat and subcutaneous fat and lower expression in the liver. Thus, F-T ducks displayed lower hepatic lipid deposition and a higher percentage of abdominal fat and subcutaneous fat, suggesting that F-T ducks had higher lipid storage capacity due to increased gene expression related to lipid droplets.
ESTHER : Zhuang_2022_Animals.(Basel)_12_
PubMedSearch : Zhuang_2022_Animals.(Basel)_12_
PubMedID: 36077988

Title : Treatment effects on event-related EEG potentials and oscillations in Alzheimer's disease - Yener_2022_Int.J.Psychophysiol__
Author(s) : Yener G , Hunerli-Gunduz D , Yildirim E , Akturk T , Basar-Eroglu C , Bonanni L , Del Percio C , Farina F , Ferri R , Guntekin B , Hajos M , Ibanez A , Jiang Y , Lizio R , Lopez S , Noce G , Parra M , Randall F , Stocchi F , Babiloni C
Ref : Int J Psychophysiol , : , 2022
Abstract : Alzheimer's disease dementia (ADD) is the most diffuse neurodegenerative disorder belonging to mild cognitive impairment (MCI) and dementia in old persons. This disease is provoked by an abnormal accumulation of amyloid-beta and tauopathy proteins in the brain. Very recently, the first disease-modifying drug has been licensed with reserve (i.e., Aducanumab). Therefore, there is a need to identify and use biomarkers probing the neurophysiological underpinnings of human cognitive functions to test the clinical efficacy of that drug. In this regard, event-related electroencephalographic potentials (ERPs) and oscillations (EROs) are promising candidates. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer's Association and Global Brain Consortium reviewed the field literature on the effects of the most used symptomatic drug against ADD (i.e., Acetylcholinesterase inhibitors) on ERPs and EROs in ADD patients with MCI and dementia at the group level. The most convincing results were found in ADD patients. In those patients, Acetylcholinesterase inhibitors partially normalized ERP P300 peak latency and amplitude in oddball paradigms using visual stimuli. In these same paradigms, those drugs partially normalize ERO phase-locking at the theta band (4-7 Hz) and spectral coherence between electrode pairs at the gamma (around 40 Hz) band. These results are of great interest and may motivate multicentric, double-blind, randomized, and placebo-controlled clinical trials in MCI and ADD patients for final cross-validation.
ESTHER : Yener_2022_Int.J.Psychophysiol__
PubMedSearch : Yener_2022_Int.J.Psychophysiol__
PubMedID: 35588964

Title : Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry - Hu_2022_Lab.Med__
Author(s) : Hu C , Zhuang X , Zhang J , Wang T , Du S , Wang J , Peng X , Cao Q , Zhang M , Jiang Y
Ref : Lab Med , : , 2022
Abstract : OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. METHODS: Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. RESULTS: A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. CONCLUSION: The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM.
ESTHER : Hu_2022_Lab.Med__
PubMedSearch : Hu_2022_Lab.Med__
PubMedID: 35075477

Title : Long non-coding RNA ABHD11-AS1 promotes colorectal cancer progression and invasion through targeting the integrin subunit alpha 5\/focal adhesion kinase\/phosphoinositide 3 kinase\/Akt signaling pathway - Luo_2021_Aging.(Albany.NY)_13_20179
Author(s) : Luo J , Jiang Y , Wu L , Zhuo D , Zhang S , Jiang X , Sun Y , Huang Y
Ref : Aging (Albany NY) , 13 :20179 , 2021
Abstract : Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.
ESTHER : Luo_2021_Aging.(Albany.NY)_13_20179
PubMedSearch : Luo_2021_Aging.(Albany.NY)_13_20179
PubMedID: 34375304
Gene_locus related to this paper: human-ABHD11

Title : Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents - Gao_2021_Bioorg.Chem_114_105149
Author(s) : Gao H , Jiang Y , Zhan J , Sun Y
Ref : Bioorg Chem , 114 :105149 , 2021
Abstract : For the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in the future. The best 3D-QSAR acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors pharmacophore hypotheses Hypo1 A and Hypo1 B were generated and validated by HypoGen program in Discovery Studio 2016 based on the training set of flavonoids, and then they were used as 3D query for screening the ZINC database. Next, the hit molecules were then subjected to the ADMET and molecular docking study to prioritize the compounds. Finally, 6 compounds showed good estimated activities and promising ADMET properties. The result of best compound ZINC08751495 with AChE estimate activity (0.028), BChE estimate activity (1.55), AChE fit value (9.369), BChE fit value (8.415), AChE -CDOCKER ENERGY (30.22), BChE -CDOCKER ENERGY (33.13) has the potential for further development as a supplement to treat Alzheimer's disease.
ESTHER : Gao_2021_Bioorg.Chem_114_105149
PubMedSearch : Gao_2021_Bioorg.Chem_114_105149
PubMedID: 34252860

Title : A pendant droplet-based sensor for the detection of acetylcholinesterase and its inhibitors - Li_2021_Chem.Commun.(Camb)_57_8909
Author(s) : Li B , Guo Y , Jiang Y , Lin JM , Hu Q , Yu L
Ref : Chem Commun (Camb) , 57 :8909 , 2021
Abstract : In this work, a pendant droplet-based sensor is developed for the rapid and label-free detection of acetylcholinesterase (AChE) and its inhibitors. The detection limit of AChE reaches 0.17 mU mL(-1). The pIC(50) values of AChE inhibitors such as neostigmine, rivastigmine and galantamine are determined to be 0.45 microM, 0.64 microM and 4.93 microM, respectively.
ESTHER : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedSearch : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedID: 35225993

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 : Poria cocos polysaccharide attenuates damage of nervus in Alzheimer's disease rat model induced by D-galactose and aluminum trichloride - Zhou_2021_Neuroreport_32_727
Author(s) : Zhou X , Zhang Y , Jiang Y , Zhou C , Ling Y
Ref : Neuroreport , 32 :727 , 2021
Abstract : Poria cocos polysaccharide (PCP) is a compound from Poria cocos, and which is used as a classical tonic agent. This article aims to investigate the effects of PCP on neuronal damage of hippocampus and cognitive function in a rat model of Alzheimer's disease induced by D-galactose and aluminum trichloride. Oxiracetam (ORC) was used as a positive drug in this experiment. The rats were treated with PCP at doses of 100, 200 and 300 mg/kg/day for 30 days and ORC at dose of 346 mg/kg/day after modeling. The results of behavioral test showed that PCP could prevent cognitive decline in Alzheimer's disease rats as assessed by Y-maze test and Morris water maze test. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with PCP. Moreover, PCP could reduce neuronal apoptosis in hippocampus of Alzheimer's disease rats. Furthermore, the activities of superoxide dismutase in the hippocampus were elevated by PCP administration, while acetyl cholinesterase, reactive oxygen, malondialdehyde and inflammatory factors levels were reduced. In addition, we found PCP could attenuate MAPK/NF-kappaB signal pathway in the hippocampus. All results illustrated that PCP could exert neuroprotective effects at least partly through alleviating oxidative stress, apoptosis, inflammation and inhibiting the MAPK/NF-kappaB pathway in Alzheimer's disease rats induced by D-galactose and aluminum trichloride.
ESTHER : Zhou_2021_Neuroreport_32_727
PubMedSearch : Zhou_2021_Neuroreport_32_727
PubMedID: 33913927

Title : A Clinical and Budgetary Impact Analysis of Introducing Sugammadex for Routine Reversal of Neuromuscular Blockade in a Hypothetical Cohort in the US - Jiang_2021_Adv.Ther__
Author(s) : Jiang Y , Bash LD , Saager L
Ref : Adv Ther , : , 2021
Abstract : INTRODUCTION: Sugammadex rapidly reverses the effects of rocuronium- and vecuronium-induced neuromuscular blockade (NMB), offering a more complete and predictable NMB recovery than cholinesterase inhibitors. Despite clinical benefits, cost pressures on hospital budgets influence the choice of the NMB reversal method. This study evaluated clinical and healthcare system payer's budget impacts associated with sugammadex in the US for routine reversal of moderate or deep rocuronium- or vecuronium-induced NMB in adults undergoing surgery. METHODS: A 1-year decision analytic model was constructed reflecting a set of procedures using rocuronium or vecuronium that resulted in moderate or deep NMB at the end of surgery. Two scenarios were considered for a hypothetical cohort of 100,000 patients: without sugammadex versus with sugammadex. Comparators included neostigmine (+glycopyrrolate) and no neuromuscular blocking agents (NMBAs). Total costs (in 2019 US dollars) to a healthcare system [net of costs of reversal agents and overall cost offsets via reduction in postoperative pulmonary complications (PPC)] were compared. RESULTS: A total of 9971 surgical procedures utilized rocuronium or vecuronium, resulting in moderate (91.0% of cases) or deep (9.0%) blockade at the end of surgeries. In the with sugammadex scenario, sugammadex replaced neostigmine in 4156 of 9585 procedures versus the without sugammadex scenario that used only neostigmine for NMB reversal. Introducing sugammadex reduced PPC events by 12% (58 cases) among the modeled procedures, leading to a budget impact of -$3,079,703 (-$309 per modeled procedure, or a 10.9% reduction in total costs). The results did not vary qualitatively in one-way sensitivity analyses. CONCLUSIONS: The additional costs of sugammadex for the reversal of rocuronium- or vecuronium-induced NMB could be offset by improved outcomes (i.e., reduced PPC events), and potentially lead to overall healthcare budgetary savings versus reversal with neostigmine or spontaneous recovery. This study provides insights into savings that can be obtained beyond the anesthesia budget, reducing the broader clinical and budgetary burden on the hospital.
ESTHER : Jiang_2021_Adv.Ther__
PubMedSearch : Jiang_2021_Adv.Ther__
PubMedID: 33871823

Title : Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt\/Beta catenin signaling pathway - Yang_2021_Arch.Oral.Biol_130_105211
Author(s) : Yang P , Li C , Kou Y , Jiang Y , Li D , Liu S , Lu Y , Hasegawa T , Li M
Ref : Archives of Oral Biology , 130 :105211 , 2021
Abstract : OBJECTIVES: The aims of this study were to explore: (i) the effect of Notum on periodontitis in vivo; (ii) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (iii) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. DESIGN: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. RESULTS: Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. CONCLUSION: These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway.
ESTHER : Yang_2021_Arch.Oral.Biol_130_105211
PubMedSearch : Yang_2021_Arch.Oral.Biol_130_105211
PubMedID: 34352447

Title : Colorimetric detection of acetylcholinesterase and its inhibitor based on thiol-regulated oxidase-like activity of 2D palladium square nanoplates on reduced graphene oxide - Yan_2021_Mikrochim.Acta_188_162
Author(s) : Yan B , Liu W , Duan G , Ni P , Jiang Y , Zhang C , Wang B , Lu Y , Chen C
Ref : Mikrochim Acta , 188 :162 , 2021
Abstract : A convenient and sensitive colorimetric assay for acetylcholinesterase (AChE) and its inhibitor has been designed based on the oxidase-like activity of {100}-faceted Pd square nanoplates which are grown in situ on reduced graphene oxide (PdSP@rGO). PdSP@rGO can effectively catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) without the assistance of H(2)O(2) to generate blue oxidized TMB (oxTMB) with a characteristic absorption peak at 652 nm. In the presence of AChE, acetylthiocholine (ATCh), a typical AChE substrate, is hydrolyzed to thiocholine (TCh). The generated TCh can effectively inhibit the PdSP@rGO-triggered chromogenic reaction of TMB via cheating with Pd, resulting in color fading and decrease in absorbance. Thus, a sensitive probe for AChE activity is constructed with a working range of 0.25-5 mU mL(-1) and a limit of detection (LOD) of 0.0625 mU mL(-1). Furthermore, because of the inhibition effect of tacrine on AChE, tacrine is also detected through the colorimetric AChE assay system within the concentrations range 0.025-0.4 microM with a LOD of 0.00229 microM. Hence, a rapid and facile colorimetric procedure to sensitively detect AChE and its inhibitor can be anticipated through modulating the oxidase-like activity of PdSP@rGO. Colorimetric method for detection of AChE and its inhibitor is established by modulating the oxidase mimetic activity of {100}-faceted Pd square nanoplates on reduced graphene oxide (PdSP@rGO).
ESTHER : Yan_2021_Mikrochim.Acta_188_162
PubMedSearch : Yan_2021_Mikrochim.Acta_188_162
PubMedID: 33839958

Title : A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase - Gao_2021_Nat.Microbiol__
Author(s) : Gao H , Bai L , Jiang Y , Huang W , Wang L , Li S , Zhu G , Wang D , Huang Z , Li X , Cao J , Jiang L , Jacobs-Lorena M , Zhan S , Wang S
Ref : Nat Microbiol , : , 2021
Abstract : The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.
ESTHER : Gao_2021_Nat.Microbiol__
PubMedSearch : Gao_2021_Nat.Microbiol__
PubMedID: 33958765

Title : Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio) - Qiao_2020_Sci.Total.Environ__143769
Author(s) : Qiao K , Hu T , Jiang Y , Huang J , Hu J , Gui W , Ye Q , Li S , Zhu G
Ref : Sci Total Environ , :143769 , 2020
Abstract : Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 g/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC(50) and LC(10) of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 g/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 g/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 g/L of chlorpyrifos induced increased free T(3) levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba, thrb, crhb, ttr, tpo, ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T(3) to the thyroid receptor beta in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T(3). Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.
ESTHER : Qiao_2020_Sci.Total.Environ__143769
PubMedSearch : Qiao_2020_Sci.Total.Environ__143769
PubMedID: 33221011
Gene_locus related to this paper: danre-ACHE

Title : Structural remodeling of active zones is associated with synaptic homeostasis - Hong_2020_J.Neurosci__
Author(s) : Hong H , Zhao K , Huang S , Yao A , Jiang Y , Sigrist S , Zhao L , Zhang YQ
Ref : Journal of Neuroscience , : , 2020
Abstract : Perturbations to postsynaptic glutamate receptors (GluRs) trigger retrograde signaling to precisely increase presynaptic neurotransmitter release, maintaining stable levels of synaptic strength, a process referred to as homeostatic regulation. However, the structural change of homeostatic regulation remains poorly defined. At wild-type Drosophila neuromuscular junction (NMJ) synapse, there is one Bruchpilot (Brp) ring detected by super-resolution microscopy at active zones (AZs). In the present study, we report multiple Brp rings, i.e., multiple T-bars seen by electron microscopy, at AZs of both male and female larvae when GluRs are reduced. At GluRIIC deficient NMJs, quantal size was reduced but quantal content was increased, indicative of homeostatic presynaptic potentiation. Consistently, multiple Brp rings at AZs were observed in the two classic synaptic homeostasis models, i.e., GluRIIA mutant and pharmacological blockade of GluRIIA activity. Furthermore, postsynaptic overexpression of the cell adhesion protein Neuroligin 1 partially rescued multiple Brp rings phenotype. Our study thus supports that the formation of multiple Brp rings at AZs might be a structural basis for synaptic homeostasis.SIGNIFICANCE STATEMENTSynaptic homeostasis is a conserved fundamental mechanism to maintain efficient neurotransmission of neural networks. Active zones (AZ) are characterized by an electron dense cytomatrix, which is largely composed of Bruchpilot (Brp) at the Drosophila neuromuscular junction (NMJ) synapses. It is not clear how the structure of AZs changes during homeostatic regulation. To address this question, we examined the structure of AZs by super-resolution microscopy and electron microscopy during homeostatic regulation. Our results reveal multiple Brp rings at AZs of glutamate receptor-deficient NMJ synapses compared with single Brp ring at AZs in wild type. We further show that Neuroligin1-mediated retrograde signaling regulates multiple Brp ring formation at glutamate receptor-deficient synapses. This study thus reveals a regulatory mechanism for synaptic homeostasis.
ESTHER : Hong_2020_J.Neurosci__
PubMedSearch : Hong_2020_J.Neurosci__
PubMedID: 32122953

Title : Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6\/JAK2\/STAT3 signaling in glioma - Zhou_2020_Cell.Oncol.(Dordr)_43_461
Author(s) : Zhou J , Jiang Y , Zhao J , Zhang H , Fu J , Luo P , Ma Y , Zou D , Gao H , Hu J , Zhang Y , Jing Z
Ref : Cell Oncol (Dordr) , 43 :461 , 2020
Abstract : PURPOSE: The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown. METHODS: Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays. RESULTS: We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling. CONCLUSIONS: Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
ESTHER : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedSearch : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedID: 32207044
Gene_locus related to this paper: human-NDRG2

Title : New biphenanthrenes with butyrylcholinesterase inhibitory activitiy from Cremastra appendiculata - Liu_2019_Nat.Prod.Res__1
Author(s) : Liu L , Yin QM , Gao Q , Li J , Jiang Y , Tu PF
Ref : Nat Prod Res , :1 , 2019
Abstract : Encouraged by the in vitro potent inhibitory activity on butyrylcholinesterase (BChE) of 95% ethanol extract of Cremastra appendiculata (D. Don) Makino tubers, a further phytochemical investigation on C. appendiculata tubers was conducted, which led to the isolation of a pair of new biphenanthrene atropisomers, namely cremaphenanthrene F-G (1-2). Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical method. It is the first time that biphenanthrene atropisomers have been isolated from the plant kingdom. Compound 1 showed potent BChE inhibitory effect with IC50 value of 14.62 +/- 2.15 muM. Compound 2 exhibited weak BChE inhibitory effect with IC50 value of 79.56 +/- 0.78 muM. Meanwhile, 1 and 2 were found to be inactive for acetylcholinesterase (AChE) inhibition. These findings suggested that compound 1 was a promising selective BChE inhibitor for AD prevention and treatment.
ESTHER : Liu_2019_Nat.Prod.Res__1
PubMedSearch : Liu_2019_Nat.Prod.Res__1
PubMedID: 31117825

Title : Compartmentalized biosynthesis of mycophenolic acid - Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
Author(s) : Zhang W , Du L , Qu Z , Zhang X , Li F , Li Z , Qi F , Wang X , Jiang Y , Men P , Sun J , Cao S , Geng C , Wan X , Liu C , Li S
Ref : Proc Natl Acad Sci U S A , 116 :13305 , 2019
Abstract : Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.
ESTHER : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedSearch : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedID: 31209052
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Molecular and functional properties of two Spodoptera exigua acetylcholinesterase genes - Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
Author(s) : Zhao J , Hao D , Xiao L , Tan Y , Jiang Y , Bai L , Wang K
Ref : Archives of Insect Biochemistry & Physiology , :e21554 , 2019
Abstract : Acetylcholinesterase (AChE) is a vital enzyme that hydrolyzes acetylcholine. Here, full-length complementary DNAs (cDNAs) of two acetylcholinesterase genes (SeAce1 and SeAce2) were obtained from Spodoptera exigua, a widespread phytophagous pest in agriculture. The complete SeAce1 cDNA comprised 5447 nucleotides including an open reading frame (ORF) encoding 694 amino acids, while SeAce2 cDNA encompassed a 1917-bp ORF which would likely yield 638 amino acids. Both SeAce1 and SeAce2 contained specific characteristics of functional AChE. A phylogenetic tree of all lepidopteran insect Aces showed S. exigua clustered with S. litura, Helicoverpa assulta, and H. armigera, all of which are Noctuidae. In S. exigua, SeAce1 gene expression levels (reverse transcription polymerase chain reaction [RT-PCR] and quantitative RT-PCR) were markedly increased compared with SeAce2 in all developmental phases and tissue types. Both genes were down regulated by inserting the corresponding dsRNAs in 5th instar larvae, which resulted in 56.7% (SeAce1) and 24.6% (SeAce2) death. Downregulation of both SeAce1 and SeAce2 significantly reduced fecundity and vitellogenin gene expression in S. exigua. These results revealed the biological functions of the two Ace genes (SeAce1 and SeAce2), providing novel insights into the development of strategies for controlling insect pests.
ESTHER : Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
PubMedSearch : Zhao_2019_Arch.Insect.Biochem.Physiol__e21554
PubMedID: 31033012
Gene_locus related to this paper: spolt-ACHE2 , spolt-ACHE1

Title : Effects of Bread Yeast Cell Wall Beta-Glucans on Mice with Loperamide-Induced Constipation - Chen_2019_J.Med.Food_22_1009
Author(s) : Chen Z , Lin S , Jiang Y , Liu L , Jiang J , Chen S , Tong Y , Wang P
Ref : J Med Food , 22 :1009 , 2019
Abstract : Constipation is a common gastrointestinal disorder characterized by changes in intestinal habits. Increasing evidence indicates that long-term use of irritant laxatives causes serious side effects. Meanwhile, more than 50% of patients are dissatisfied with sense of use of non-prescriptional laxatives. beta-glucans are natural polysaccharides widely found in yeast, fungus, and plants, which have been reported to exhibit various pharmacological effects. The aim of this study was to characterize the effect of beta-glucans extracted from the bread yeast cell wall on loperamide-induced constipation mice. Forty mice were fed with loperamide (10 mg/kg) to make the constipation model and a diet supplemented with 2.5, 5, and 10 mg/kg beta-glucan. We assessed the defecation frequency, intestinal transit function of mice, as well as used high-throughput sequencing to analyze the intestinal microbiota composition and functional biological profiles data. Meanwhile, we detected expression of neurotransmitters including acetylcholinesterase, substance P, and serotonin (5-HT) and expression of tight junction protein (TJP) including zonula occludens-1 and mucin-2 in distal colon to characterize the possible molecular mechanisms. beta-glucans significantly enhanced intestinal motility and provided a possibility to regulate the expression of neurotransmitters and TJP in mice. The intestinal microecological portion of the treatment group partially recovered and was closer to the normal group. This study showed that beta-glucans can influence the intestinal microbiota and restore microecological balance to regulate the express of neurotransmitters and TJP to recover intestinal epithelial mechanical barrier. We suggested that beta-glucans could be used as an active nutritional supplement to protect the damaged intestinal barrier and help patients who have constipation complications and dysbiosis.
ESTHER : Chen_2019_J.Med.Food_22_1009
PubMedSearch : Chen_2019_J.Med.Food_22_1009
PubMedID: 31536448

Title : Glycogen synthase kinase-3beta suppresses the expression of protein phosphatase methylesterase-1 through beta-catenin - Jin_2019_Aging.(Albany.NY)_11_9672
Author(s) : Jin N , Shi R , Jiang Y , Chu D , Gong CX , Iqbal K , Liu F
Ref : Aging (Albany NY) , 11 :9672 , 2019
Abstract : Protein phosphatase 2A (PP2A) is the major tau phosphatase. Its activity toward tau is regulated by the methylation of PP2A catalytic subunit (PP2Ac) at Leu309. Protein phosphatase methylesterase-1 (PME-1) demethylates PP2Ac and suppresses its activity. We previously found that glycogen synthase kinase-3beta (GSK-3beta) suppresses PME-1 expression. However, the underlying molecular mechanism is unknown. In the present study, we analyzed the promoter of PME-1 gene and found that human PME-1 promoter contains two lymphoid enhancer binding factor-1/T-cell factor (LEF1/TCF) cis-elements in which beta-catenin serves as a co-activator. beta-catenin acted on these two cis-elements and promoted PME-1 expression. GSK-3beta phosphorylated beta-catenin and suppressed its function in promoting PME-1 expression. Inhibition and activation of GSK-3beta by PI3K-AKT pathway promoted and suppressed, respectively, PME-1 expression in primary cultured neurons, SH-SY5Y cells and in the mouse brain. These findings suggest that GSK-3beta phosphorylates beta-catenin and suppresses its function on PME-1 expression, resulting in an increase of PP2Ac methylation.
ESTHER : Jin_2019_Aging.(Albany.NY)_11_9672
PubMedSearch : Jin_2019_Aging.(Albany.NY)_11_9672
PubMedID: 31714894
Gene_locus related to this paper: human-PPME1

Title : Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV - Jiang_2019_Viruses_11_
Author(s) : Jiang Y , Li J , Teng Y , Sun H , Tian G , He L , Li P , Chen Y , Guo Y , Zhao G , Zhou Y , Sun S
Ref : Viruses , 11 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
ESTHER : Jiang_2019_Viruses_11_
PubMedSearch : Jiang_2019_Viruses_11_
PubMedID: 30634407

Title : Genome-wide association studies reveal genetic loci associated with plasma cholinesterase activity in ducks - Xu_2019_Anim.Genet_50_287
Author(s) : Xu Y , Liu H , Jiang Y , Fan W , Hu J , Zhang Y , Guo Z , Xie M , Huang W , Liu X , Zhou Z , Hou S
Ref : Anim Genet , 50 :287 , 2019
Abstract : Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck x mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.
ESTHER : Xu_2019_Anim.Genet_50_287
PubMedSearch : Xu_2019_Anim.Genet_50_287
PubMedID: 30994195
Gene_locus related to this paper: anapl-BCHE

Title : Design, synthesis and biological Evaluation of Dual acetyl cholinesterase and beta-secretase inhibitors in treatment for alzheimer's Disease - Deng_2019_Pak.J.Pharm.Sci_32_2091
Author(s) : Deng Y , Jiang Y , Zhao X , Wang J
Ref : Pak J Pharm Sci , 32 :2091 , 2019
Abstract : With the recent research advances in molecular biology and technology multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)aceta te (1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity.
ESTHER : Deng_2019_Pak.J.Pharm.Sci_32_2091
PubMedSearch : Deng_2019_Pak.J.Pharm.Sci_32_2091
PubMedID: 31813875

Title : The Optimization Design Of Lactoferrin Loaded HupA Nanoemulsion For Targeted Drug Transport Via Intranasal Route - Jiang_2019_Int.J.Nanomedicine_14_9217
Author(s) : Jiang Y , Liu C , Zhai W , Zhuang N , Han T , Ding Z
Ref : Int J Nanomedicine , 14 :9217 , 2019
Abstract : Background: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer's disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems. Purpose: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration. Methods: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency. Results: Optimized HupA-NE had a particle size of 15.24+/-0.67 nm, polydispersity index (PDI) of 0.128+/-0.025, and zeta potential of -4.48+/-0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2+/-0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE. Conclusion: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.
ESTHER : Jiang_2019_Int.J.Nanomedicine_14_9217
PubMedSearch : Jiang_2019_Int.J.Nanomedicine_14_9217
PubMedID: 31819426

Title : Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining - Ling_2019_Clin.Neurol.Neurosurg_189_105620
Author(s) : Ling L , Liu Y , Sun Y , Cai Y , Jiang Y , Chen L , He L , Xue J
Ref : Clin Neurol Neurosurg , 189 :105620 , 2019
Abstract : OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage.
ESTHER : Ling_2019_Clin.Neurol.Neurosurg_189_105620
PubMedSearch : Ling_2019_Clin.Neurol.Neurosurg_189_105620
PubMedID: 31812030

Title : Hierarchical nanocomposites with an N-doped carbon shell and bimetal core: Novel enzyme nanocarriers for electrochemical pesticide detection - Ma_2018_Biosens.Bioelectron_121_166
Author(s) : Ma L , Zhou L , He Y , Wang L , Huang Z , Jiang Y , Gao J
Ref : Biosensors & Bioelectronics , 121 :166 , 2018
Abstract : Core-shell structured nanocomposites (named PtPd@NCS) with N-doped carbon shell and bimetal core (Pt and Pd) were fabricated through a facile strategy for the first time. The PtPd@NCS nanocomposites were obtained through reduction of K2PtCl4, H2PtCl6 and Na2PdCl4 species, self-polymerization of dopamine (DA) and co-assembly of Pluronic F127 using a one-pot approach. DA serves as a reductant, as well as a carbon and nitrogen source. The core-shell structure of the PtPd@NCS nanocomposites was characterized and the result indicated that Pt-Pd nanoparticle core with a diameter of approximately 15nm was encased in the N-doped carbon shells with a thickness of approximately 35nm. The PtPd@NCS nanocomposites were used as an electrode material to prepare acetylcholinesterase (AChE) biosensors for detecting organophosphate pesticides. The obtained AChE biosensor exhibited a linear range of 1x10(-14) to 1x10(-10) M and 1x10(-9) to 1x10(-5) M within the detection limit of 7.9x10(-15) M for malathion, 1x10(-13) to 1x10(-6) within the detection limit of 7.1x10(-14) M for chlopyrifos, and 1x10(-14) to 1x10(-11) M and 1x10(-10) to 1x10(-5) M within the detection limit of 8.6x10(-15) M for parathion methyl. The proposed biosensor also exhibited high selectivity, reproducibility and stability. The AChE biosensor was also applied in real samples for detecting organophosphate pesticides and exhibited acceptable recovery. This work demonstrated that the PtPd@NCS had great potential in constructing biosensors to detect organophosphate pesticides and other analytes.
ESTHER : Ma_2018_Biosens.Bioelectron_121_166
PubMedSearch : Ma_2018_Biosens.Bioelectron_121_166
PubMedID: 30218924

Title : Preparation of Margarine Stock Rich in Naturally Bioactive Components by Enzymatic Interesterification - Yu_2018_J.Oleo.Sci_67_29
Author(s) : Yu D , Qi X , Jiang Y , Zou D , Wang L , Jiang L , Qin L
Ref : J Oleo Sci , 67 :29 , 2018
Abstract : Fully hydrogenated expanded press soybean oil (FHEPSO) rich in naturally bioactive components was prepared using Palladium on Carbon (Pd/C) catalyst. Interesterified fat was prepared from binary blends of FHEPSO and cold press corn oil (CPCO) with FHEPSO/CPCO mass ratios of 50:50, 40:60 and 30:70. Lipozyme RM IM (6 wt% of total substrate) was used in a supercritical CO(2) system to catalyze the transesterification. The fatty acid compositions had no significant changes in the fats before and after interesterification, and trans-fatty acid (TFA) was not detected. The fatty acid compositions within triacylglycerol (TAG) were rearranged, and the amounts of trisaturated and triunsaturated TAG decreased, whereas that of mixed TAG increased as a result of interesterification. The enzymatic interesterified fats (EIEF) had a lower solid fat content (SFC), broader melting and plasticity ranges compared to the noninteresterified blend (NIB). According to X-ray diffraction (XRD), the predominant crystal form had changed from beta to beta'. EIEF contained 0.33-0.51 g/100 g phospholipids, 88.6-105.6 mg/100 g total tocopherols, and 916-1053 mg/100 g total phytosterols, which could confer health benefits. The results indicated that EIEF may have a potential use in trans-free margarine stock preparation.
ESTHER : Yu_2018_J.Oleo.Sci_67_29
PubMedSearch : Yu_2018_J.Oleo.Sci_67_29
PubMedID: 29238024

Title : Pharmacophore-based drug design for the identification of novel butyrylcholinesterase inhibitors against Alzheimer's disease - Jiang_2018_Phytomedicine_54_278
Author(s) : Jiang Y , Gao H
Ref : Phytomedicine , 54 :278 , 2018
Abstract : BACKGROUND: Alzheimer's disease is a severe neurodegenerative disease of the central nervous system in the elderly. HYPOTHESIS/PURPOSE: In our study, we aimed to find the best potential small molecule for AD treatment. STUDY DESIGN: We used many models in Discovery Studio 2016 to find new potential inhibitors of butyrylcholinesterase (BChE), including pharmacophore model, virtual screening model, molecular docking model, de novo evolution model. METHODS: Ligand-based pharmacophore models were used to identify the critical chemical features of BChE inhibitors using the module of 3D QSAR Pharmacophore Generation in Discovery Studio 2016. The best pharmacophore model was then validated by cost analysis, Fischer's randomization method, 3D-QSAR Method of the training set and test set. The compounds that match the best pharmacophore model with the predicted activity <1muM filtered by Lipinski's rule of five were subjected to molecular docking. RESULT: After virtual screening, 35 compounds filtered by Lipinski's rule of five and ADMET analysis were subjected to molecular docking and then the number were narrowed down on 10 compounds based on -CDOCKER_ENERGY. Finally, we obtained and modified the best potential candidate ENA739155. CONCLUSION: Ultimately, ENA739155_Evo with -CDOCKER_ENERGY of 47.12, estimate activity of 0.012, fit value of 10.02 could be further subjected to drug development and forwarded as better alternatives to the current batch of medicines used for the treatment of AD.
ESTHER : Jiang_2018_Phytomedicine_54_278
PubMedSearch : Jiang_2018_Phytomedicine_54_278
PubMedID: 30668379

Title : Biphasic Alteration of Butyrylcholinesterase (BChE) During Prostate Cancer Development - Gu_2018_Transl.Oncol_11_1012
Author(s) : Gu Y , Chow MJ , Kapoor A , Mei W , Jiang Y , Yan J , De Melo J , Seliman M , Yang H , Cutz JC , Bonert M , Major P , Tang D
Ref : Transl Oncol , 11 :1012 , 2018
Abstract : Butyrylcholinesterase (BChE) is a plasma enzyme that hydrolyzes ghrelin and bioactive esters, suggesting a role in modulating metabolism. Serum BChE is reduced in cancer patients. In prostate cancer (PC), the down-regulation is associated with disease recurrence. Nonetheless, how BChE is expressed in PC and its impact on PC remain unclear. We report here the biphasic changes of BChE expression in PC. In vitro, BChE expression was decreased in more tumorigenic PC stem-like cells (PCSLCs), DU145, and PC3 cells compared to less tumorigenic non-stem PCs and LNCaP cells. On the other hand, BChE was expressed at a higher level in LNCaP cells than immortalized but non-tumorigenic prostate epithelial BPH-1 cells. In vivo, BChE expression was up-regulated in DU145 xenografts compared to LNCaP xenografts; DU145 cell-derived lung metastases displayed comparable levels of BChE as subcutaneous tumors. Furthermore, LNCaP xenografts produced in castrated mice exhibited a significant increase of BChE expression compared to xenografts generated in intact mice. In patients, BChE expression was down-regulated in PCs (n = 340) compared to prostate tissues (n = 86). In two independent PC populations MSKCC (n = 130) and TCGA Provisional (n = 490), BChE mRNA levels were reduced from World Health Organization grade group 1 (WHOGG 1) PCs to WHOGG 3 PCs, followed by a significant increase in WHOGG 5 PCs. The up-regulation was associated with a reduction in disease-free survival (P = .008). Collectively, we demonstrated for the first time a biphasic alteration of BChE, its down-regulation at early stage of PC and its up-regulation at advanced PC.
ESTHER : Gu_2018_Transl.Oncol_11_1012
PubMedSearch : Gu_2018_Transl.Oncol_11_1012
PubMedID: 29966864

Title : Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV - Jiang_2018_Emerg.Microbes.Infect_7_77
Author(s) : Jiang Y , Zhao G , Song N , Li P , Chen Y , Guo Y , Li J , Du L , Jiang S , Guo R , Sun S , Zhou Y
Ref : Emerg Microbes Infect , 7 :77 , 2018
Abstract : The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
ESTHER : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedSearch : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedID: 29691378

Title : Discovery of the leinamycin family of natural products by mining actinobacterial genomes - Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
Author(s) : Pan G , Xu Z , Guo Z , Hindra , Ma M , Yang D , Zhou H , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Cheng J , Van Nieuwerburgh F , Suh JW , Duan Y , Shen B
Ref : Proc Natl Acad Sci U S A , 114 :E11131 , 2017
Abstract : Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.
ESTHER : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedSearch : Pan_2017_Proc.Natl.Acad.Sci.U.S.A_114_E11131
PubMedID: 29229819
Gene_locus related to this paper: 9actn-a0a2m9jcs9 , 9actn-a0a2m9ijf7 , 9actn-a0a2m9iy91 , 9actn-a0a2m9k146 , 9actn-a0a2m9m5n6 , 9actn-a0a2m9ifq0 , 9actn-a0a1c4rpf7

Title : Pharmacophore-based drug design for potential AChE inhibitors from Traditional Chinese Medicine Database - Jiang_2017_Bioorg.Chem_76_400
Author(s) : Jiang Y , Gao H
Ref : Bioorg Chem , 76 :400 , 2017
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder. Substrate-specific Acetylcholinesterase (AChE) plays a vital role in the AD treatment. Flavonoids with AChE inhibitory activities and low toxicity are used to developing new anti-AD agents. In this study, the best 3D QSAR pharmacophore model Hypo1 was generated by HypoGen program in Discovery Studio2016 based on the training set of flavonoids. We performed a virtual screening from Traditional Chinese Medicine (TCM), Druglike and MiniMaybridge databases using Hypo1. From docking analyses, we got the top 10 AChE inhibitors which were further evaluated by 8 different scoring functions. De Novo Evolution designed the top 10 derivatives, and three potential AChE inhibitor candidates were obtained eventually.
ESTHER : Jiang_2017_Bioorg.Chem_76_400
PubMedSearch : Jiang_2017_Bioorg.Chem_76_400
PubMedID: 29258018

Title : Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer's disease: A review - Jiang_2017_Bioorg.Chem_75_50
Author(s) : Jiang Y , Gao H , Turdu G
Ref : Bioorg Chem , 75 :50 , 2017
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting 25 million people worldwide, and cholinergic hypothesis is considered as an important hypotheses in the processes of improving cognitive function and recognition skills in recent years. For the long-term treatment of AD, traditional Chinese medicine are particularly suitable for drug discovery. In this review, we sum up six traditional Chinese medicinal herbs concerned with development of AChEIs, including Herba Epimedii, Coptis Chinensis Franch, Rhizoma Curcumae Longae, Green tea, Ganoderma, Panax Ginseng. The listed compounds based on these herbs are belonging to six classes Flavonoids, Alkaloids, Ketones, Polyphenols, Terpenoid and Saponins, respectively. These compounds could be very promising agents in the search for potent anti-Alzheimer's drugs.
ESTHER : Jiang_2017_Bioorg.Chem_75_50
PubMedSearch : Jiang_2017_Bioorg.Chem_75_50
PubMedID: 28915465

Title : Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin - Yang_2017_PLoS.One_12_e0184581
Author(s) : Yang Z , Zhang Y , Jiang Y , Zhu F , Zeng L , Wang Y , Lei X , Yao Y , Hou Y , Xu L , Xiong C , Yang X , Hu K
Ref : PLoS ONE , 12 :e0184581 , 2017
Abstract : Deltamethrin is an important pesticide widely used against ectoparasites. Deltamethrin contamination has resulted in a threat to the healthy breeding of the Chinese mitten crab, Eriocheir sinensis. In this study, we investigated transcriptional responses in the hepatopancreas of E. sinensis exposed to deltamethrin. We obtained 99,087,448, 89,086,478, and 100,117,958 raw sequence reads from control 1, control 2, and control 3 groups, and 92,094,972, 92,883,894, and 92,500,828 raw sequence reads from test 1, test 2, and test 3 groups, respectively. After filtering and quality checking of the raw sequence reads, our analysis yielded 79,228,354, 72,336,470, 81,859,826, 77,649,400, 77,194,276, and 75,697,016 clean reads with a mean length of 150 bp from the control and test groups. After deltamethrin treatment, a total of 160 and 167 genes were significantly upregulated and downregulated, respectively. Gene ontology terms "biological process," "cellular component," and "molecular function" were enriched with respect to cell killing, cellular process, other organism part, cell part, binding, and catalytic. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes showed that the metabolic pathways were significantly enriched. We found that the CYP450 enzyme system, carboxylesterase, glutathione-S-transferase, and material (including carbohydrate, lipid, protein, and other substances) metabolism played important roles in the metabolism of deltamethrin in the hepatopancreas of E. sinensis. This study revealed differentially expressed genes related to insecticide metabolism and detoxification in E. sinensis for the first time and will help in understanding the toxicity and molecular metabolic mechanisms of deltamethrin in E. sinensis.
ESTHER : Yang_2017_PLoS.One_12_e0184581
PubMedSearch : Yang_2017_PLoS.One_12_e0184581
PubMedID: 28910412

Title : Enhancement of methanol resistance of Yarrowia lipolytica lipase 2 using beta-cyclodextrin as an additive: Insights from experiments and molecular dynamics simulation - Cao_2017_Enzyme.Microb.Technol_96_157
Author(s) : Cao H , Jiang Y , Zhang H , Nie K , Lei M , Deng L , Wang F , Tan T
Ref : Enzyme Microb Technol , 96 :157 , 2017
Abstract : The methanol resistance of lipase is a critical parameter in enzymatic biodiesel production. In the present work, the methanol resistance of Yarrowia lipolytica Lipase 2 (YLLIP2) was significantly improved using beta-cyclodextrin (beta-CD) as an additive. According to the results, YLLIP2 with beta-CD exhibited approximately 7000U/mg specific activity in 30wt% methanol for 60min compared with no activity without beta-CD under the same conditions. Molecular dynamics (MD) simulation results indicated that the beta-CD molecules weakened the conformational change of YLLIP2 and maintained a semi-open state of the lid by overcoming the interference caused by methanol molecules. Furthermore, the beta-CD molecule could directly stabilize "pathway" regions (e.g., Asp61-Asp67) and indirectly stabilize "pathway" regions (e.g., Gly44-Phe50) by forming hydrogen bonds with "pathway" regions and nearby "pathway" regions, respectively. The regions stabilized by the beta-CD molecule then prevented the closure of active pockets, thus retaining the enzymatic activity of YLLIP2 with beta-CD in methanol solvent.
ESTHER : Cao_2017_Enzyme.Microb.Technol_96_157
PubMedSearch : Cao_2017_Enzyme.Microb.Technol_96_157
PubMedID: 27871377

Title : Synthesis and characterization of biodegradable poly(ether-ester) urethane acrylates for controlled drug release - Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
Author(s) : Feng X , Wang G , Neumann K , Yao W , Ding L , Li S , Sheng Y , Jiang Y , Bradley M , Zhang R
Ref : Mater Sci Eng C Mater Biol Appl , 74 :270 , 2017
Abstract : Three polyether-ester triblock diols, with various molecular weights, were synthesized from sigma-caprolactone and polyethylene glycol and used, with diisocyanates, as soft segments for the preparation of polyurethane acrylate oligomers. The polyurethane acrylates were used to generate cross-linked polyurethane films via UV initiated polymerization with and without cargo incorporation. Degradation experiment indicated that in PBS/H(2)O(2)/CoCl(2) the films degraded rapidly compared to PBS alone or with lipase. The polyurethane membrane loaded with the antibiotic tetracycline, demonstrated prolonged release over 200h, suggesting that the polymers could be used as an implant coating for controlled drug release.
ESTHER : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedSearch : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedID: 28254295

Title : Preparation of Diacylglycerol-enriched Rice Bran Oil by Lipase-catalyzed Deacidification in Packed-bed Reactors by Continuous Dehydration - Lu_2016_J.Oleo.Sci_65_151
Author(s) : Lu Y , Zou X , Han W , Jiang Y , Jin Q , Li L , Xu X , Wang X
Ref : J Oleo Sci , 65 :151 , 2016
Abstract : Diacylglycerol-enriched rice bran oil (RBO-DAG) was produced by deacidification of high-acid rice bran oil (RBO) with glycerol (Gly) using Lipozyme RM IM by continuous dehydration by combination of two enzyme columns (column 1 and 3, used for deacidification) with one molecular sieves column (column 2, used for dehydration). The conditions for three columns were respectively optimized. Response surface methodology (RSM) was used to optimize the conditions of column 1. The content of DAG and conversion of free fatty acid (FFA) were used as indicators and the effects of the enzyme load (8-12 g), flow rate (0.3-0.6 mL/min), substrate molar ratio (4-6) and reaction temperature (55-75 degC) were investigated. The content of DAG and conversion of FFA were significantly correlated to the flow rate and substrate molar ratio. Most desirable conditions of the reaction with respect to the maximal DAG content and FFA conversion was attained under the residence time of 40 min, substrate molar ratio of 5.52 (Gly: RBO) and temperature of 66 degC. The conditions for column 2 were investigated by varying molecular sieves load and flow rate, and the maximal dehydration rate of 85.22% was obtained under the optimal conditions. For column 3, the optimum conditions were obtained as: flow rate, 0.2mL/min; temperature, 65 degC, and the content of DAG and FFA were 38.99% and 3.04%, respectively under these conditions. The catalytic activity of the lipase was stable in twelve continuous operations with 83.22% of its original ability, demonstrating its potential in the continuous packed-bed reactors (PBRs) system. These results showed that packed-bed reactors combined with continuous deacidification and dehydration in one system had great value in industrial production for high-acid RBO with the improved conversion rate.
ESTHER : Lu_2016_J.Oleo.Sci_65_151
PubMedSearch : Lu_2016_J.Oleo.Sci_65_151
PubMedID: 26833284

Title : Strain Prioritization and Genome Mining for Enediyne Natural Products - Yan_2016_MBio_7_e02104
Author(s) : Yan X , Ge H , Huang T , Hindra , Yang D , Teng Q , Crnovcic I , Li X , Rudolf JD , Lohman JR , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Van Nieuwerburgh F , Rader C , Duan Y , Shen B
Ref : MBio , 7 : , 2016
Abstract : The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE: Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.
ESTHER : Yan_2016_MBio_7_e02104
PubMedSearch : Yan_2016_MBio_7_e02104
PubMedID: 27999165
Gene_locus related to this paper: 9actn-a0a1q5ckn8 , 9actn-a0a1q5j3v0 , 9actn-a0a1q5kj90 , 9actn-a0a1q5jti2 , 9actn-a0a1q5luf4 , 9actn-a0a1q4w3c8 , 9actn-a0a1q4wvf2 , 9actn-a0a1q4yuw0 , 9actn-a0a1q5diu2 , 9actn-a0a1q5dxi1 , 9actn-a0a1q5ftj7 , 9actn-a0a1q5h9t1 , 9actn-a0a1q5k3r2 , 9actn-a0a1q5l4j4 , 9actn-a0a1q5l7v2 , 9actn-a0a1q5ltu8 , 9actn-a0a1q5m0p6 , 9actn-a0a1q5mza2 , 9pseu-a0a1q4yle9 , 9pseu-a0a1q4ylg6 , 9actn-a0a1q5hn40 , 9actn-a0a1q4zi93 , 9actn-a0a1q5d7w2 , 9actn-a0a1q5mn15 , 9pseu-a0a1q4xtq2 , 9actn-a0a1q5le62 , 9actn-a0a1q5fgx4 , strsp-TnmK1 , strsp-TnmK2 , strun-UcmK2 , 9actn-a0a1q4w6n9 , 9actn-a0a1q4yc91 , 9actn-a0a1q4yun2 , 9actn-a0a1q5g588 , 9actn-a0a1q5h571 , 9actn-a0a1q5kh06 , 9actn-a0a1q5lnf3 , 9actn-a0a1q5n7d1 , 9actn-a0a1q5n4g6

Title : Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells - Yao_2016_Bioorg.Chem_68_112
Author(s) : Yao D , Wang J , Wang G , Jiang Y , Shang L , Zhao Y , Huang J , Yang S , Yu Y
Ref : Bioorg Chem , 68 :112 , 2016
Abstract : A novel series of coumarin derivatives were designed, synthesized and investigated for inhibition of cholinesterase, including acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE). This biological study showed that these compounds containing piperazine ring had significant inhibition activities on AChE rather than BuChE. Further study suggested that 9x, as one of this kind of structure derivative, showed the strongest inhibition activity on AChE with an IC50 value of 34nM. Moreover, molecular docking, flow cytometry (FCM), and western blot assay suggested that 9x could induce cytoprotective autophagy to attenuate H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. These findings highlight a new approach for the development of a novel potential neuroprotective compound targeting AChE with autophagy-inducing activity in future Alzheimer's disease (AD) therapy.
ESTHER : Yao_2016_Bioorg.Chem_68_112
PubMedSearch : Yao_2016_Bioorg.Chem_68_112
PubMedID: 27479541

Title : Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3 - Zhao_2015_Cell.Res_25_1219
Author(s) : Zhao LH , Zhou XE , Yi W , Wu Z , Liu Y , Kang Y , Hou L , de Waal PW , Li S , Jiang Y , Scaffidi A , Flematti GR , Smith SM , Lam VQ , Griffin PR , Wang Y , Li J , Melcher K , Xu HE
Ref : Cell Res , 25 :1219 , 2015
Abstract : Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the alpha/beta-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCF(D3) that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process.
ESTHER : Zhao_2015_Cell.Res_25_1219
PubMedSearch : Zhao_2015_Cell.Res_25_1219
PubMedID: 26470846
Gene_locus related to this paper: orysj-Q10QA5

Title : Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits - Xu_2015_Gene_557_146
Author(s) : Xu H , Tao X , Wei Y , Chen J , Xing S , Cen W , Wen A , Zhu L , Tang G , Li M , Jiang A , Jiang Y , Li X
Ref : Gene , 557 :146 , 2015
Abstract : Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits.
ESTHER : Xu_2015_Gene_557_146
PubMedSearch : Xu_2015_Gene_557_146
PubMedID: 25498336

Title : Butyrylcholinesterase K Variant and Alzheimer's Disease Risk: A Meta-Analysis - Wang_2015_Med.Sci.Monit_21_1408
Author(s) : Wang Z , Jiang Y , Wang X , Du Y , Xiao D , Deng Y , Wang J
Ref : Med Sci Monit , 21 :1408 , 2015
Abstract : Background Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. Material and Methods We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE epsilon4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE epsilon4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). Conclusions The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.
ESTHER : Wang_2015_Med.Sci.Monit_21_1408
PubMedSearch : Wang_2015_Med.Sci.Monit_21_1408
PubMedID: 25978873

Title : ATRX promotes gene expression by facilitating transcriptional elongation through guanine-rich coding regions - Levy_2015_Hum.Mol.Genet_24_1824
Author(s) : Levy MA , Kernohan KD , Jiang Y , Berube NG
Ref : Hum Mol Genet , 24 :1824 , 2015
Abstract : ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a set of genes, including the autism susceptibility gene Neuroligin 4 (Nlgn4), that exhibit decreased expression in ATRX-null cells to investigate the mechanisms used by ATRX to promote gene transcription. Overall TERRA levels, as well as DNA methylation and histone modifications at ATRX target genes are not altered and thus cannot explain transcriptional dysregulation. We found that ATRX does not associate with the promoter of these genes, but rather binds within regions of the gene body corresponding to high H3.3 occupancy. These intragenic regions consist of guanine-rich DNA sequences predicted to form non-B DNA structures called G-quadruplexes during transcriptional elongation. We demonstrate that ATRX deficiency corresponds to reduced H3.3 incorporation and stalling of RNA polymerase II at these G-rich intragenic sites. These findings suggest that ATRX promotes the incorporation of histone H3.3 at particular transcribed genes and facilitates transcriptional elongation through G-rich sequences. The inability to transcribe genes such as Nlgn4 could cause deficits in neuronal connectivity and cognition associated with ATRX mutations in humans.
ESTHER : Levy_2015_Hum.Mol.Genet_24_1824
PubMedSearch : Levy_2015_Hum.Mol.Genet_24_1824
PubMedID: 25452430

Title : Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus - Zhao_2015_PLoS.One_10_e0145561
Author(s) : Zhao G , Jiang Y , Qiu H , Gao T , Zeng Y , Guo Y , Yu H , Li J , Kou Z , Du L , Tan W , Jiang S , Sun S , Zhou Y
Ref : PLoS ONE , 10 :e0145561 , 2015
Abstract : The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.
ESTHER : Zhao_2015_PLoS.One_10_e0145561
PubMedSearch : Zhao_2015_PLoS.One_10_e0145561
PubMedID: 26701103

Title : Theoretical and Experimental Studies on Activity of Yarrowia lipolytica Lipase in Methanol\/Water Mixtures - Li_2014_J.Phys.Chem.B_118_1976
Author(s) : Li L , Jiang Y , Zhang H , Feng W , Chen B , Tan T
Ref : J Phys Chem B , 118 :1976 , 2014
Abstract : Methanol is regularly used as a substrate for biodiesel synthesis. Excess methanol can however inhibit the lipase activity. In the present work, the activity and conformational changes of Yarrowia lipolytica lipase (LIP2) at different concentrations of methanol were investigated by measuring fluorescence, UV-vis spectra, and molecular dynamics simulations. The lipase tended to expand at higher concentrations of methanol, and the methanol molecules were able to enter into the LIP2, leading to microenvironment changes around the aromatic amino acids. More hydrophobic groups were exposed to the solvents at high methanol concentrations, and the original hydrophobic interaction in the protein was destroyed, thus resulting in the tertiary structure change of the lipase.
ESTHER : Li_2014_J.Phys.Chem.B_118_1976
PubMedSearch : Li_2014_J.Phys.Chem.B_118_1976
PubMedID: 24520949

Title : Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection - Ross_2014_HIV.Med_15_537
Author(s) : Ross Eckard A , Longenecker CT , Jiang Y , Debanne SM , Labbato D , Storer N , McComsey GA
Ref : HIV Med , 15 :537 , 2014
Abstract : OBJECTIVES: HIV-infected patients on antiretroviral therapy (ART) have an increased cardiovascular disease (CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. METHODS: One hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. RESULTS: The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor-II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P < 0.01), and negatively correlated with coagulation markers (D-dimer and fibrinogen; both R = -0.2; P < 0.04). Lp-PLA2 was not correlated with lipids, coronary artery calcium score, or flow-mediated vasodilation, but trended towards a significant correlation with carotid intima-media thickness (R = 0.2; P = 0.05). CONCLUSIONS: In this population with stable ART and normal LDL cholesterol, Lp-PLA2 was in the high CVD risk category in the majority of subjects. Lp-PLA2 appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA2 may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected.
ESTHER : Ross_2014_HIV.Med_15_537
PubMedSearch : Ross_2014_HIV.Med_15_537
PubMedID: 24650269

Title : Lid closure mechanism of Yarrowia lipolytica lipase in methanol investigated by molecular dynamics simulation - Jiang_2014_J.Chem.Inf.Model_54_2033
Author(s) : Jiang Y , Li L , Zhang H , Feng W , Tan T
Ref : J Chem Inf Model , 54 :2033 , 2014
Abstract : In nonaqueous organic solvents, lipases can catalyze esterification reactions, which increase their application value. Yarrowia lipolytica Lipase (Lip2) possesses potential values in medicine and industrial production. In order to investigate its lid closure mechanism in methanol we performed molecular dynamics (MD) simulations of the open conformation of Lip2 in methanol and hexane, respectively. Simulation results indicated that Lip2 undergoes a greater conformational change in methanol. Principle component analysis showed Lip2 has "double-domain" and "torsion" motion modes in hexane and methanol. By analyzing B-factor and dynamical cross-correlation, region Ser274-Asn288, region Thr106-His126, and region Asp61-Asp67 were found to interact with the lid region (Thr88-Leu105). Furthermore, local restricted MD simulations showed that closure mechanism of Lip2 is "double-lid movement" which is also observed in Pseudomonas aeruginosa Lipase (PAL), and we detected two interaction propagation pathways in Lip2 driven by the interaction between Ser274-Asn288 and methanol.
ESTHER : Jiang_2014_J.Chem.Inf.Model_54_2033
PubMedSearch : Jiang_2014_J.Chem.Inf.Model_54_2033
PubMedID: 24954406

Title : Genome Sequence of a Promising Hydrogen-Producing Facultative Anaerobic Bacterium, Brevundimonas naejangsanensis Strain B1 - Su_2014_Genome.Announc_2_e00542
Author(s) : Su H , Zhang T , Bao M , Jiang Y , Wang Y , Tan T
Ref : Genome Announc , 2 : , 2014
Abstract : Brevundimonas naejangsanensis strain B1 is a newly isolated, facultative anaerobic bacterium capable of producing hydrogen with high efficiency. Here, we present a 2.94-Mb assembly of the genome sequence of strain B1, which may provide further insights into the molecular mechanism of hydrogen production from bioresource.
ESTHER : Su_2014_Genome.Announc_2_e00542
PubMedSearch : Su_2014_Genome.Announc_2_e00542
PubMedID: 24903872
Gene_locus related to this paper: 9caul-a0a172y535 , 9caul-a0a172y4n5

Title : Identification of differentially expressed proteins related to organophosphorus-induced delayed neuropathy in the brains of hens - Jiang_2014_J.Appl.Toxicol_34_1352
Author(s) : Jiang Y , Liu X , Li S , Zhang Y , Piao F , Sun X
Ref : J Appl Toxicol , 34 :1352 , 2014
Abstract : Some organophosphorus compounds can cause organophosphate-induced delayed neuropathy (OPIDN). Incidents have been documented for decades, however, little is known about which proteins contribute to the initiation, progression and development of OPIDN. In this study, 51 hens were divided into three groups. The tri-ortho-cresyl-phosphate (TOCP) group was treated with 1000 mg kg(-1) TOCP whereas the control group was treated with an equivalent volume of vehicle. The PMSF + TOCP group was treated subcutaneously with 40 mg kg(-1) phenylmethylsulfonyl fluoride (PMSF), followed by 1000 mg kg(-1) TOCP 24 h later. Proteins in the brains of hens were separated by two-dimensional polyacrylamide gel electrophoresis on day 5 after TOCP administration. Mass spectrometry identified eight differentially expressed proteins. Among these proteins, downregulated expression of glutamine synthetase (GS) in the brains of hens after TOCP treatment was further confirmed by real time RT-PCR and ELISA. Moreover, the brains of hens exposed to TOCP exhibited increased levels of glutamate (Glu) and cytosolic calcium concentration ([Ca(2+) ]i ), and a decreased level of glutamine (Gln). However, there were no significant differences in GS expression or levels of Glu, Gln, and [Ca(2+) ]i in the brains of hens among the groups on day 21 after TOCP administration. These results indicate that TOCP exposure downregulates GS expression in the brains of hens, and that downregulation of GS is accompanied by increased levels of Glu and [Ca(2+) ]i in the early stage after TOCP administration. It is also suggested that the downregulated expression of GS might be associated with OPIDN through the disruption of homeostasis of the Glu-Gln cycle and [Ca(2+) ]i . Copyright (c) 2013 John Wiley & Sons, Ltd.
ESTHER : Jiang_2014_J.Appl.Toxicol_34_1352
PubMedSearch : Jiang_2014_J.Appl.Toxicol_34_1352
PubMedID: 24338829

Title : Optimal dose of zinc supplementation for preventing aluminum-induced neurotoxicity in rats - Lu_2013_Neural.Regen.Res_8_2754
Author(s) : Lu H , Hu J , Li J , Pang W , Hu Y , Yang H , Li W , Huang C , Zhang M , Jiang Y
Ref : Neural Regen Res , 8 :2754 , 2013
Abstract : Zinc supplementation can help maintain learning and memory function in rodents. In this study, we hypothesized that zinc supplementation could antagonize the neurotoxicity induced by aluminum in rats. Animals were fed a diet containing different doses of zinc (50, 100, 200 mg/kg) for 9 weeks, and orally administered aluminum chloride (300 mg/kg daily) from the third week for 7 consecutive weeks. Open-field behavioral test results showed that the number of rearings in the group given the 100 mg/kg zinc supplement was significantly increased compared with the group given the 50 mg/kg zinc supplement. Malondialdehyde content in the cerebrum was significantly decreased, while dopamine and 5-hydroxytryptamine levels were increased in the groups given the diet supplemented with 100 and 200 mg/kg zinc, compared with the group given the diet supplemented with 50 mg/kg zinc. The acetylcholinesterase activity in the cerebrum was significantly decreased in the group given the 100 mg/kg zinc supplement. Hematoxylin-eosin staining revealed evident pathological damage in the hippocampus of rats in the group given the diet supplemented with 50 mg/kg zinc, but the damage was attenuated in the groups given the diet supplemented with 100 and 200 mg/kg zinc. Our findings suggest that zinc is a potential neuroprotective agent against aluminum-induced neurotoxicity in rats, and the optimal dosages are 100 and 200 mg/kg.
ESTHER : Lu_2013_Neural.Regen.Res_8_2754
PubMedSearch : Lu_2013_Neural.Regen.Res_8_2754
PubMedID: 25206586

Title : Evaluation of novel carbamate insecticides for neurotoxicity to non-target species - Jiang_2013_Pestic.Biochem.Physiol_106_156
Author(s) : Jiang Y , Swale D , Carlier PR , Hartsel JA , Ma M , Ekstrom F , Bloomquist JR
Ref : Pesticide Biochemistry and Physiology , 106 :156 , 2013
Abstract : Malaria is an urgent world health concern and vector control is one important option for reducing disease prevalence. Increased reports of pyrethroid-resistant mosquito strains have amplified the need for new vector-control chemicals. We compared three commercially available carbamate insecticides (carbofuran, bendiocarb, and propoxur) to eight experimental compounds 1-8 for activity against Anopheles gambiae acetylcholinesterase, as well as enzymes from mammalian, avian, and aquatic species. The experimental compounds (except 7) were less potent than the commercial inhibitors against the mosquito enzyme, but had higher selectivity values (up to near 600-fold, IC50 of non-target species/IC50 An. gambiae) because of their low potency for acetylcholinesterases from nontarget species. Neurotoxic esterase assay showed that none of the experimental carbamates (1 mM) displayed NTE inhibition, while bendiocarb did (24% inhibition at 1 mM), although the effect was much less than that of mipafox. In vivo bioassays using Daphnia magna showed that all novel carbamates were of similar killing potency as bendiocarb (24 h LC50 = 611 nM), with the exception of experimental compound 1 (LC50 = 172 nM). Overall, the results suggested that the novel carbamate insecticides 4-8 presented in this study were safer to mammals than the commercial compounds and were promising insecticides for malaria vector control usage on bednets or indoor residual sprays.
ESTHER : Jiang_2013_Pestic.Biochem.Physiol_106_156
PubMedSearch : Jiang_2013_Pestic.Biochem.Physiol_106_156

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL\/6 mice - Jiang_2013_Neuropharmacol_73C_415
Author(s) : Jiang Y , Zou Y , Chen S , Zhu C , Wu A , Liu Y , Ma L , Zhu D , Ma X , Liu M , Kang Z , Pi R , Peng F , Wang Q , Chen X
Ref : Neuropharmacology , 73C :415 , 2013
Abstract : Donepezil is a potent and selective acetylcholinesterase inhibitor. It has been reported to restore cognitive performance in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) mice, an established model of MS. However, there are no reports about the anti-inflammatory effects of donepezil on EAE. In this study, the donepezil treatments on EAE mice were initiated at day 7 post immunization (7 p.i., subclinical periods, early donepezil treatment) and day 13 p.i. (clinical periods, late donepezil treatment) with the dosage of 1, 2 and 4 mg/kg/d respectively and the treatments persisted throughout the experiments. Blood-brain barrier (BBB) permeability was detected by Evan's blue content, the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, Akt and phosphorylated Akt (p-Akt) as well as nerve growth factor (NGF) and its precursor form (proNGF) in the brains of EAE mice were detected by Western blot, and the levels of interferon-gamma and interleukin-4 in the splenocytes culture supernatants and brains of EAE mice were evaluated by ELISA. The results showed that the 2 mg/kg/d late donepezil treatment was the optimal dosage and could ameliorate clinical and pathological parameters, improve magnetic resonance imaging outcomes, reduce the permeability of BBB, inhibit the production of MMP-2 and MMP-9, modulate the expression of NGF and proNGF, increase Th2 bias and the phosphorylation of Akt in the brains of EAE mice. Our data suggested that the anti-inflammatory effects of donepezil may be a novel mechanism on treating EAE and provided further insights to understand the donepezil's neuroprotective activities in MS.
ESTHER : Jiang_2013_Neuropharmacol_73C_415
PubMedSearch : Jiang_2013_Neuropharmacol_73C_415
PubMedID: 23831366

Title : Description and nomenclature of Neisseria meningitidis capsule locus - Harrison_2013_Emerg.Infect.Dis_19_566
Author(s) : Harrison OB , Claus H , Jiang Y , Bennett JS , Bratcher HB , Jolley KA , Corton C , Care R , Poolman JT , Zollinger WD , Frasch CE , Stephens DS , Feavers I , Frosch M , Parkhill J , Vogel U , Quail MA , Bentley SD , Maiden MC
Ref : Emerg Infect Dis , 19 :566 , 2013
Abstract : Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.
ESTHER : Harrison_2013_Emerg.Infect.Dis_19_566
PubMedSearch : Harrison_2013_Emerg.Infect.Dis_19_566
PubMedID: 23628376
Gene_locus related to this paper: neime-h6t5x5

Title : Mutualistic co-evolution of type III effector genes in Sinorhizobium fredii and Bradyrhizobium japonicum - Kimbrel_2013_PLoS.Pathog_9_e1003204
Author(s) : Kimbrel JA , Thomas WJ , Jiang Y , Creason AL , Thireault CA , Sachs JL , Chang JH
Ref : PLoS Pathog , 9 :e1003204 , 2013
Abstract : Two diametric paradigms have been proposed to model the molecular co-evolution of microbial mutualists and their eukaryotic hosts. In one, mutualist and host exhibit an antagonistic arms race and each partner evolves rapidly to maximize their own fitness from the interaction at potential expense of the other. In the opposing model, conflicts between mutualist and host are largely resolved and the interaction is characterized by evolutionary stasis. We tested these opposing frameworks in two lineages of mutualistic rhizobia, Sinorhizobium fredii and Bradyrhizobium japonicum. To examine genes demonstrably important for host-interactions we coupled the mining of genome sequences to a comprehensive functional screen for type III effector genes, which are necessary for many Gram-negative pathogens to infect their hosts. We demonstrate that the rhizobial type III effector genes exhibit a surprisingly high degree of conservation in content and sequence that is in contrast to those of a well characterized plant pathogenic species. This type III effector gene conservation is particularly striking in the context of the relatively high genome-wide diversity of rhizobia. The evolution of rhizobial type III effectors is inconsistent with the molecular arms race paradigm. Instead, our results reveal that these loci are relatively static in rhizobial lineages and suggest that fitness conflicts between rhizobia mutualists and their host plants have been largely resolved.
ESTHER : Kimbrel_2013_PLoS.Pathog_9_e1003204
PubMedSearch : Kimbrel_2013_PLoS.Pathog_9_e1003204
PubMedID: 23468637
Gene_locus related to this paper: brajp-g7daf5 , brajp-m4ps52

Title : Genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from a patient before and after treatment with tigecycline - Hua_2012_J.Bacteriol_194_6979
Author(s) : Hua X , Zhou H , Jiang Y , Feng Y , Chen Q , Ruan Z , Yu Y
Ref : Journal of Bacteriology , 194 :6979 , 2012
Abstract : Acinetobacter baumannii is a Gram-negative bacterium which emerged as a significant nosocomial pathogen worldwide. To investigate the molecular basis of the tigecycline-resistant mechanism, we determined the genome sequences of two multidrug-resistant A. baumannii strains isolated from a patient before and after treatment with tigecycline.
ESTHER : Hua_2012_J.Bacteriol_194_6979
PubMedSearch : Hua_2012_J.Bacteriol_194_6979
PubMedID: 23209232
Gene_locus related to this paper: aciba-f5iht4 , aciba-a0a009wzt4

Title : Efficient assembly and annotation of the transcriptome of catfish by RNA-Seq analysis of a doubled haploid homozygote - Liu_2012_BMC.Genomics_13_595
Author(s) : Liu S , Zhang Y , Zhou Z , Waldbieser G , Sun F , Lu J , Zhang J , Jiang Y , Zhang H , Wang X , Rajendran KV , Khoo L , Kucuktas H , Peatman E , Liu Z
Ref : BMC Genomics , 13 :595 , 2012
Abstract : BACKGROUND: Upon the completion of whole genome sequencing, thorough genome annotation that associates genome sequences with biological meanings is essential. Genome annotation depends on the availability of transcript information as well as orthology information. In teleost fish, genome annotation is seriously hindered by genome duplication. Because of gene duplications, one cannot establish orthologies simply by homology comparisons. Rather intense phylogenetic analysis or structural analysis of orthologies is required for the identification of genes. To conduct phylogenetic analysis and orthology analysis, full-length transcripts are essential. Generation of large numbers of full-length transcripts using traditional transcript sequencing is very difficult and extremely costly.
RESULTS: In this work, we took advantage of a doubled haploid catfish, which has two sets of identical chromosomes and in theory there should be no allelic variations. As such, transcript sequences generated from next-generation sequencing can be favorably assembled into full-length transcripts. Deep sequencing of the doubled haploid channel catfish transcriptome was performed using Illumina HiSeq 2000 platform, yielding over 300 million high-quality trimmed reads totaling 27 Gbp. Assembly of these reads generated 370,798 non-redundant transcript-derived contigs. Functional annotation of the assembly allowed identification of 25,144 unique protein-encoding genes. A total of 2,659 unique genes were identified as putative duplicated genes in the catfish genome because the assembly of the corresponding transcripts harbored PSVs or MSVs (in the form of pseudo-SNPs in the assembly). Of the 25,144 contigs with unique protein hits, around 20,000 contigs matched 50% length of reference proteins, and over 14,000 transcripts were identified as full-length with complete open reading frames. The characterization of consensus sequences surrounding start codon and the stop codon confirmed the correct assembly of the full-length transcripts.
CONCLUSIONS: The large set of transcripts assembled in this study is the most comprehensive set of genome resources ever developed from catfish, which will provide the much needed resources for functional genome research in catfish, serving as a reference transcriptome for genome annotation, analysis of gene duplication, gene family structures, and digital gene expression analysis. The putative set of duplicated genes provide a starting point for genome scale analysis of gene duplication in the catfish genome, and should be a valuable resource for comparative genome analysis, genome evolution, and genome function studies.
ESTHER : Liu_2012_BMC.Genomics_13_595
PubMedSearch : Liu_2012_BMC.Genomics_13_595
PubMedID: 23127152
Gene_locus related to this paper: ictpu-w5u6j2 , ictpu-w5ub99 , ictpu-w5uc03 , ictpu-w5utq3 , ictpu-w5u610 , ictpu-w5ui62 , ictpu-w5uj33 , ictpu-w5u9s1 , ictpu-a0a2d0rtv8 , ictpu-w5uf93 , ictpu-w5u6h4 , ictpu-a0a2d0qam4 , ictpu-w5u7r0 , ictpu-w5ugq3

Title : Lipases as biocatalysts for the synthesis of structured lipids - Jala_2012_Methods.Mol.Biol_861_403
Author(s) : Jala RC , Hu P , Yang T , Jiang Y , Zheng Y , Xu X
Ref : Methods Mol Biol , 861 :403 , 2012
Abstract : Structured lipids (SL) are broadly referred to as modified or synthetic oils and fats or lipids with functional or pharmaceutical applications. Some structured lipids, such as triglycerides that contain both long-chain (mainly essential) fatty acids and medium- or short-chain fatty acids and also artificial products that mimic the structure of natural materials, namely human milk fat substitutes and cocoa butter equivalents, have been discussed. Further, other modified or synthetic lipids, such as structured phospholipids and synthetic phenolic lipids are also included in this chapter. For all the products described in this chapter, enzymatic production in industry has been already conducted in one way or another. Cocoa butter equivalents, healthy oil containing medium-chain fatty acids, phosphatidyl serine, and phenol lipids from enzyme technology have been reported for commercial operation. As the demand for better quality functional lipids is increasing, the production of structured lipids becomes an interesting area. Thus, in this chapter we have discussed latest developments as well as present industrial situation of all commercially important structured lipids.
ESTHER : Jala_2012_Methods.Mol.Biol_861_403
PubMedSearch : Jala_2012_Methods.Mol.Biol_861_403
PubMedID: 22426731

Title : Different active-site loop orientation in serine hydrolases versus acyltransferases - Jiang_2011_Chembiochem_12_768
Author(s) : Jiang Y , Morley KL , Schrag JD , Kazlauskas RJ
Ref : Chembiochem , 12 :768 , 2011
Abstract : Acyl transfer is a key reaction in biosynthesis, including synthesis of antibiotics and polyesters. Although researchers have long recognized the similar protein fold and catalytic machinery in acyltransferases and hydrolases, the molecular basis for the different reactivity has been a long-standing mystery. By comparison of X-ray structures, we identified a different oxyanion-loop orientation in the active site. In esterases/lipases a carbonyl oxygen points toward the active site, whereas in acyltransferases a NH of the main-chain amide points toward the active site. Amino acid sequence comparisons alone cannot identify such a difference in the main-chain orientation. To identify how this difference might change the reaction mechanism, we solved the X-ray crystal structure of Pseudomonas fluorescens esterase containing a sulfonate transition-state analogue bound to the active-site serine. This structure mimics the transition state for the attack of water on the acyl-enzyme and shows a bridging water molecule between the carbonyl oxygen mentioned above and the sulfonyl oxygen that mimics the attacking water. A possible mechanistic role for this bridging water molecule is to position and activate the attacking water molecule in hydrolases, but to deactivate the attacking water molecule in acyl transferases.
ESTHER : Jiang_2011_Chembiochem_12_768
PubMedSearch : Jiang_2011_Chembiochem_12_768
PubMedID: 21351219
Gene_locus related to this paper: psefl-este

Title : [Construction of Aspergillus niger lipase mutants with oil-water interface independence] - Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
Author(s) : Chen D , Shu Z , Xue L , Lin R , Wu J , Jiang Y , Li X , Lin Y , Huang J
Ref : Sheng Wu Gong Cheng Xue Bao , 27 :860 , 2011
Abstract : Based on previous bioinformational analysis results, two Aspergillus niger lipase (ANL) mutants, ANL-Ser84Gly and ANL-Asp99Pro were constructed to screen ANL mutants with oil-water interface independence. ANL-Ser84Gly still displayed a pronounced interfacial activation, while ANL-Asp99Pro displayed no interfacial activation. The specific activity of ANL-Ser84Gly towards p-nitrophenyl palmitate (-myristate, -laurate and -decanoate) decreased by 29.8% (53.1, 60.1 and 77.1, respectively) than that of ANL, while the specific activity of ANL-Asp99Pro towards p-nitrophenyl palmitate increased by 2.2-fold. The mutation in the hinge region at both sides of the lid domain also destabilized various secondary structure factors of ANL-S84G and ANL-D99P, which resulted in a substantial decrease in thermostability. The achievement to construct oil-water interface-independent ANL mutants would help to further understand lipase interfacial activation mechanism.
ESTHER : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedSearch : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedID: 22034814

Title : Construction of Aspergillus niger lipase mutants with oil-water interface independence - Shu_2011_Enzyme.Microb.Technol_48_129
Author(s) : Shu Z , Wu J , Xue L , Lin R , Jiang Y , Tang L , Li X , Huang J
Ref : Enzyme Microb Technol , 48 :129 , 2011
Abstract : Based on previous bioinformational analytical results [Shu ZY, et al. Biotechnol Prog 2009;25:409-16], four A. niger lipase (ANL) mutants, ANL-Ser84Gly, ANL-Asp99Pro, ANL-Lys108Glu and ANL-EalphaH (obtained by replacing the lid domain of ANL with the corresponding domain from A. niger feruloyl esterase), were constructed to screen out ANL mutants with oil-water interface independence. ANL-S84G displayed a pronounced interfacial activation, while ANL-D99P and ANL-K108E displayed no interfacial activation. The specific activity of ANL-S84G towards p-nitrophenyl esters decreased from 29.8% to 76.5% compared with that of ANL, while the specific activity of ANL-D99P towards p-nitrophenyl palmitate increased 2.2-fold. The thermostability of ANL-K108E was almost unchanged, while the thermostability of ANL-S84G and ANL-D99P significantly decreased compared with that of ANL. The construction of oil-water interface-independent ANL mutants would help to further understand the mechanism of lipase interfacial activation.
ESTHER : Shu_2011_Enzyme.Microb.Technol_48_129
PubMedSearch : Shu_2011_Enzyme.Microb.Technol_48_129
PubMedID: 22112821

Title : [The effects of soluble epoxide hydrolase inhibitors on cholesterol efflux in adipocytes] - Jiang_2011_Zhonghua.Nei.Ke.Za.Zhi_50_235
Author(s) : Jiang Y , Xu DY , Zhao SP , Liu YW , Zhao TT , Du JQ
Ref : Zhonghua Nei Ke Za Zhi , 50 :235 , 2011
Abstract : OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes.
METHODS: 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimulated with 100 microg/L LPS after starved for 24 hours, then tAUCB in various concentrations (1, 10, 50, 100 micromol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARgamma) antagonist GW9662 (5 micromol/L). 0 micromol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARgamma and adenosine triphosphate binding cassette transporter A1(ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARgamma and ABCA1 in cells were detected by Western blot, the efflux rates of (3)H-cholesterol in cells were detected by means of liquid scintillation counter.
RESULTS: tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10, 50, 100 micromol/L tAUCB, cholesterol efflux rates were (5.93 +/- 0.66)%, (7.40 +/- 0.43)%, (8.30 +/- 0.34)%, (9.77 +/- 0.42)% respectively, there were significant difference after treated by 10 - 100 micromol/L tAUCB compared with control (5.67 +/- 0.17)% (P < 0.05).With the concentration of tAUCB increased, ABCA1, PPARgamma mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARgamma and ABCA1 in adipocytes.
CONCLUSIONS: tAUCB could up-regulate PPARgamma expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.
ESTHER : Jiang_2011_Zhonghua.Nei.Ke.Za.Zhi_50_235
PubMedSearch : Jiang_2011_Zhonghua.Nei.Ke.Za.Zhi_50_235
PubMedID: 21600089

Title : [Effects of soluble epoxide hydrolase inhibitors on lipid metabolism and secretive functions of adipocytes] - Jiang_2011_Zhonghua.Yi.Xue.Za.Zhi_91_111
Author(s) : Jiang Y , Xu DY , Zhao TT , Du JQ , Peng DQ , Zhao SP
Ref : Zhonghua Yi Xue Za Zhi , 91 :111 , 2011
Abstract : OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitors-tAUCB on the uptake and degradation of ox-LDL in adipocytes.
METHODS: 3T3-L1 preadipocytes were induced into differentiation and maturation. After a 24-hour starvation, the cells were stimulated with 100 ng/ml LPS and then tAUCB at various concentrations (0 - 100 micromol/L)were added for 24 h, or preincubated with the PPARgamma (peroxisome proliferators activated receptor gamma) antagonist GW9662 (5 micromol/L). And the 0 micromol/L tAUCB-treated group was taken as the blank control group. Then the uptake and degradation of ox-LDL in cells were measured by radioligand assay. The mRNA expressions of PPARgamma and CD36 were detected by real-time PCR (polymerase chain reaction). And the intracellular levels of protein expression of PPARgamma and CD36 were detected by Western blot. While ADP and TNF-alpha in supernatant were detected by ELISA.
RESULTS: tAUCB could dose-dependently increase the uptake and degradation of ox-LDL in adipocytes. When stimulated with 10, 50, 100 micromol/L tAUCB, the uptake levels of ox-LDL were (35.6 +/- 1.1)ng/mg, (39.8 +/- 1.6) ng/mg, (42.6 +/- 1.4) ng/mg cell protein and the degradation levels of ox-LDL (2879 +/- 54) ng/mg, (3082 +/- 56) ng/mg, (3226 +/- 68) ng/mg cell protein. And they were significantly higher than those of the control group (28.9 +/- 1.2) ng/mg, (2791 +/- 54) ng/mg respectively (all P < 0.05). However, after preincubation of GW9662, the uptake of ox-LDL were decreased to (30.6 +/- 1.3) ng/mg, (31.1 +/- 1.7) ng/mg, (32.1 +/- 1.8) ng/mg cell protein whereas the degradation of ox-LDL decreased to (2788 +/- 53) ng/mg, (2824 +/- 70) ng/mg, (2874 +/- 70) ng/mg cell protein. And the difference was statistically significant when it was compared with the corresponding tAUCB-treated group. With the rising concentration of tAUCB, tAUCB could dose-dependently increase the mRNA and protein expression of CD36 and PPARgamma. tAUCB could dose-dependently decrease the levels of TNF-alpha and increase the levels of ADP in adipocytes. GW9662 could significantly inhibit those effects of tAUCB and reduce the uptake and degradation of ox-LDL and the expression of PPARgamma and CD36 in adipocytes. CONCLUSION: tAUCB can up-regulate the PPARgamma expression in adipocytes and promote the uptake and degradation of ox-LDL in adipocytes via PPARgamma-CD36 pathway. Meanwhile, the levels of ADP and TNF-alpha may be mediated through the activation of PPARgamma.
ESTHER : Jiang_2011_Zhonghua.Yi.Xue.Za.Zhi_91_111
PubMedSearch : Jiang_2011_Zhonghua.Yi.Xue.Za.Zhi_91_111
PubMedID: 21418994

Title : Natural variation in GS5 plays an important role in regulating grain size and yield in rice - Li_2011_Nat.Genet_43_1266
Author(s) : Li Y , Fan C , Xing Y , Jiang Y , Luo L , Sun L , Shao D , Xu C , Li X , Xiao J , He Y , Zhang Q
Ref : Nat Genet , 43 :1266 , 2011
Abstract : Increasing crop yield is one of the most important goals of plant science research. Grain size is a major determinant of grain yield in cereals and is a target trait for both domestication and artificial breeding(1). We showed that the quantitative trait locus (QTL) GS5 in rice controls grain size by regulating grain width, filling and weight. GS5 encodes a putative serine carboxypeptidase and functions as a positive regulator of grain size, such that higher expression of GS5 is correlated with larger grain size. Sequencing of the promoter region in 51 rice accessions from a wide geographic range identified three haplotypes that seem to be associated with grain width. The results suggest that natural variation in GS5 contributes to grain size diversity in rice and may be useful in improving yield in rice and, potentially, other crops(2).
ESTHER : Li_2011_Nat.Genet_43_1266
PubMedSearch : Li_2011_Nat.Genet_43_1266
PubMedID: 22019783
Gene_locus related to this paper: orysa-q5w727

Title : Effects of farnesoid X receptor on the expression of the fatty acid synthetase and hepatic lipase - Shen_2011_Mol.Biol.Rep_38_553
Author(s) : Shen LL , Liu H , Peng J , Gan L , Lu L , Zhang Q , Li L , He F , Jiang Y
Ref : Mol Biol Rep , 38 :553 , 2011
Abstract : The farnesoid X receptor (FXR) is a nuclear receptor that regulates gene expression in response to bile acids (BAs). FXR plays an important role in the homeostasis of bile acid, cholesterol, lipoprotein and triglyceride. In this report, we identified fatty acid synthase (FAS) and hepatic lipase (HL) genes as novel target genes of FXR. Human hepatoma HepG2 cells were treated with chenodeoxycholic acid, the natural FXR ligand, and the messenger RNA and protein levels of FAS and HL were determined by RT-PCR and Western blot analysis, respectively. Chenodeoxycholic acid (CDCA) down-regulated the expression of FAS and HL genes in a dose and time-dependent manner in human hepatoma HepG2 cells. In addition, treatment of mice with CDCA significantly decreased the expression of FAS and HL in mouse liver and the activity of HL. These results demonstrated that FAS and HL might be FXR-regulated genes in liver cells. In view of the role of FAS and HL in lipogenesis and plasma lipoprotein metabolism, our results further support the central role of FXR in the homeostasis of fatty acid and lipid.
ESTHER : Shen_2011_Mol.Biol.Rep_38_553
PubMedSearch : Shen_2011_Mol.Biol.Rep_38_553
PubMedID: 20373033

Title : The complete genome sequence of Mycoplasma bovis strain Hubei-1 - Li_2011_PLoS.One_6_e20999
Author(s) : Li Y , Zheng H , Liu Y , Jiang Y , Xin J , Chen W , Song Z
Ref : PLoS ONE , 6 :e20999 , 2011
Abstract : Infection by Mycoplasma bovis (M. bovis) can induce diseases, such as pneumonia and otitis media in young calves and mastitis and arthritis in older animals. Here, we report the finished and annotated genome sequence of M. bovis strain Hubei-1, a strain isolated in 2008 that caused calf pneumonia on a Chinese farm. The genome of M. bovis strain Hubei-1 contains a single circular chromosome of 953,114 bp with a 29.37% GC content. We identified 803 open reading frames (ORFs) that occupy 89.5% of the genome. While 34 ORFs were Hubei-1 specific, 662 ORFs had orthologs in the M. bovis type strain PG45 genome. Genome analysis validated lateral gene transfer between M. bovis and the Mycoplasma mycoides subspecies mycoides, while phylogenetic analysis found that the closest M. bovis neighbor is Mycoplasma agalactiae. Glycerol may be the main carbon and energy source of M. bovis, and most of the biosynthesis pathways were incomplete. We report that 47 lipoproteins, 12 extracellular proteins and 18 transmembrane proteins are phase-variable and may help M. bovis escape the immune response. Besides lipoproteins and phase-variable proteins, genomic analysis found two possible pathogenicity islands, which consist of four genes and 11 genes each, and several other virulence factors including hemolysin, lipoate protein ligase, dihydrolipoamide dehydrogenase, extracellular cysteine protease and 5'-nucleotidase.
ESTHER : Li_2011_PLoS.One_6_e20999
PubMedSearch : Li_2011_PLoS.One_6_e20999
PubMedID: 21731639

Title : Switching catalysis from hydrolysis to perhydrolysis in Pseudomonas fluorescens esterase - Yin_2010_Biochemistry_49_1931
Author(s) : Yin DL , Bernhardt P , Morley KL , Jiang Y , Cheeseman JD , Purpero V , Schrag JD , Kazlauskas RJ
Ref : Biochemistry , 49 :1931 , 2010
Abstract : Many serine hydrolases catalyze perhydrolysis, the reversible formation of peracids from carboxylic acids and hydrogen peroxide. Recently, we showed that a single amino acid substitution in the alcohol binding pocket, L29P, in Pseudomonas fluorescens (SIK WI) aryl esterase (PFE) increased the specificity constant of PFE for peracetic acid formation >100-fold [Bernhardt et al. (2005) Angew. Chem., Int. Ed. 44, 2742]. In this paper, we extend this work to address the three following questions. First, what is the molecular basis of the increase in perhydrolysis activity? We previously proposed that the L29P substitution creates a hydrogen bond between the enzyme and hydrogen peroxide in the transition state. Here we report two X-ray structures of L29P PFE that support this proposal. Both structures show a main chain carbonyl oxygen closer to the active site serine as expected. One structure further shows acetate in the active site in an orientation consistent with reaction by an acyl-enzyme mechanism. We also detected an acyl-enzyme intermediate in the hydrolysis of epsilon-caprolactone by mass spectrometry. Second, can we further increase perhydrolysis activity? We discovered that the reverse reaction, hydrolysis of peracetic acid to acetic acid and hydrogen peroxide, occurs at nearly the diffusion limited rate. Since the reverse reaction cannot increase further, neither can the forward reaction. Consistent with this prediction, two variants with additional amino acid substitutions showed 2-fold higher k(cat), but K(m) also increased so the specificity constant, k(cat)/K(m), remained similar. Third, how does the L29P substitution change the esterase activity? Ester hydrolysis decreased for most esters (75-fold for ethyl acetate) but not for methyl esters. In contrast, L29P PFE catalyzed hydrolysis of epsilon-caprolactone five times more efficiently than wild-type PFE. Molecular modeling suggests that moving the carbonyl group closer to the active site blocks access for larger alcohol moieties but binds epsilon-caprolactone more tightly. These results are consistent with the natural function of perhydrolases being either hydrolysis of peroxycarboxylic acids or hydrolysis of lactones.
ESTHER : Yin_2010_Biochemistry_49_1931
PubMedSearch : Yin_2010_Biochemistry_49_1931
PubMedID: 20112920
Gene_locus related to this paper: psefl-este

Title : Immobilization of Candida antarctica lipase B by adsorption in organic medium - Sun_2010_N.Biotechnol_27_53
Author(s) : Sun J , Jiang Y , Zhou L , Gao J
Ref : N Biotechnol , 27 :53 , 2010
Abstract : Candida antarctica lipase B (CALB) was immobilized on the macroporous resin by physical adsorption in organic medium. The immobilization was performed in 5 mL isooctane, and the immobilization conditions were optimized. The results were achieved with the mass ratio of lipase to support 1:80, the buffer of pH 6.0, initial addition of PBS 75 microL, and immobilization time of two hours at 30 degrees C. Under the optimal conditions, the activity recovery was 83.3%. IM-CALB presented enhanced pH and thermal stability compared to the free lipase, and showed comparable stability with the commercial Novozym 435, after 7 times repeated use for catalyzing the synthesis of ethyl lactate, 56.9% of its initial activity was retained, and only 24.7% was retained when used for catalyzing the hydrolysis of olive oil.
ESTHER : Sun_2010_N.Biotechnol_27_53
PubMedSearch : Sun_2010_N.Biotechnol_27_53
PubMedID: 20004754

Title : Identification and characterization of full-length cDNAs in channel catfish (Ictalurus punctatus) and blue catfish (Ictalurus furcatus) - Chen_2010_PLoS.One_5_e11546
Author(s) : Chen F , Lee Y , Jiang Y , Wang S , Peatman E , Abernathy J , Liu H , Liu S , Kucuktas H , Ke C , Liu Z
Ref : PLoS ONE , 5 :e11546 , 2010
Abstract : BACKGROUND: Genome annotation projects, gene functional studies, and phylogenetic analyses for a given organism all greatly benefit from access to a validated full-length cDNA resource. While increasingly common in model species, full-length cDNA resources in aquaculture species are scarce. METHODOLOGY AND PRINCIPAL FINDINGS: Through in silico analysis of catfish (Ictalurus spp.) ESTs, a total of 10,037 channel catfish and 7,382 blue catfish cDNA clones were identified as potentially encoding full-length cDNAs. Of this set, a total of 1,169 channel catfish and 933 blue catfish full-length cDNA clones were selected for re-sequencing to provide additional coverage and ensure sequence accuracy. A total of 1,745 unique gene transcripts were identified from the full-length cDNA set, including 1,064 gene transcripts from channel catfish and 681 gene transcripts from blue catfish, with 416 transcripts shared between the two closely related species. Full-length sequence characteristics (ortholog conservation, UTR length, Kozak sequence, and conserved motifs) of the channel and blue catfish were examined in detail. Comparison of gene ontology composition between full-length cDNAs and all catfish ESTs revealed that the full-length cDNA set is representative of the gene diversity encoded in the catfish transcriptome.
CONCLUSIONS: This study describes the first catfish full-length cDNA set constructed from several cDNA libraries. The catfish full-length cDNA sequences, and data gleaned from sequence characteristics analysis, will be a valuable resource for ongoing catfish whole-genome sequencing and future gene-based studies of function and evolution in teleost fishes.
ESTHER : Chen_2010_PLoS.One_5_e11546
PubMedSearch : Chen_2010_PLoS.One_5_e11546
PubMedID: 20634964
Gene_locus related to this paper: ictpu-e3teh0 , ictpu-e3tfr7 , ictpu-a0a2d0pnc6

Title : [Immobilized lipase-catalyzed synthesis of biodiesel from crude cottonseed oil] - Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
Author(s) : Liu W , Zhou L , Jiang Y , Gao J
Ref : Sheng Wu Gong Cheng Xue Bao , 25 :1996 , 2009
Abstract : We investigated the transesterification of crude cottonseed oil with methyl acetate to biodiesel, by using Lipozyme TL IM and Novozym 435 as catalysts. Results showed that the biodiesel yield significantly increased with the addition of methanol into the reaction system, and the highest biodiesel yield of 91.83% was achieved with the optimum conditions as follows: n-hexane as solvent, molar ratio of methyl acetate to oil 9:1, 3% methanol based on the oil mass to inhibit the creation of acetic acid, 10% Lipozyme TL IM and 5% Novozym 435 as catalyst based on the oil mass, reaction temperature 55 degrees C and reaction time 8 h. Additionally, we explored the kinetics of lipase-catalyzed crude cottonseed oil to biodiesel, and proposed a kinetic model.
ESTHER : Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
PubMedSearch : Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
PubMedID: 20352980

Title : Age- and sex-related expression and activity of carboxylesterase 1 and 2 in mouse and human liver - Zhu_2009_Drug.Metab.Dispos_37_1819
Author(s) : Zhu HJ , Appel DI , Jiang Y , Markowitz JS
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 37 :1819 , 2009
Abstract : Carboxylesterase (CES) 1 and CES2 are two major hepatic hydrolases responsible for the metabolism of numerous endogenous and exogenous compounds. In this study, age- and sex-dependent expression and activity of CES1 and CES2 were investigated using both animal models and individual human liver s9 samples. The expression and activity of mouse CES1 (mCES1) and mCES2 in the liver were markedly lower in newborns relative to adults and increased gradually with age, approximating levels of adult animals by age 2 to 4 weeks. Likewise, the average human CES1 (hCES1) expression in the subjects <1 year of age was significantly lower than that of pooled samples. In particular, hCES1 expression in the 13-day and 1-month-old subjects was just 20.3 and 11.1%, respectively, of the pooled sample values. In addition, the subjects <1 year of age exhibited a trend suggestive of low hCES2 expression, but this difference failed to reach statistical significance because of large interindividual variability. The expression and activity of mCES1 and mCES2 were not significantly altered after the animals were treated with human growth hormone, indicating growth hormone may not be associated with the low level of CES expression during early developmental stages. No significant differences of the expression and activity of mCES1 and mCES2 were observed between sexually mature male and female mice. In conclusion, the expression and activity of CES1 and CES2 are age-related but independent of growth hormone level. Sex seems to be an unlikely factor contributing to the regulation of CES1 and CES2.
ESTHER : Zhu_2009_Drug.Metab.Dispos_37_1819
PubMedSearch : Zhu_2009_Drug.Metab.Dispos_37_1819
PubMedID: 19487248

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

Title : Two-dimensional turbulent flow chromatography coupled on-line to liquid chromatography-mass spectrometry for solution-based ligand screening against multiple proteins - Zhou_2009_J.Chromatogr.A_1216_2394
Author(s) : Zhou JL , An JJ , Li P , Li HJ , Jiang Y , Cheng JF
Ref : Journal of Chromatography A , 1216 :2394 , 2009
Abstract : We present herein a novel bioseparation/chemical analysis strategy for protein-ligand screening and affinity ranking in compound mixtures, designed to increase screening rates and improve sensitivity and ruggedness in performance. The strategy is carried out by combining on-line two-dimensional turbulent flow chromatography (2D-TFC) with liquid chromatography-mass spectrometry (LC-MS), and accomplished through the following steps: (1) a reversed-phase TFC stage to separate the protein/ligand complex from the unbound free molecules, (2) an on-line dissociation process to release the bound ligands from the complexes, and (3) a second mixed-mode cation-exchange/reversed-phase TFC stage to trap the bound ligands and to remove the proteins and salts, followed by LC-MS analysis for identification and determination of the binding affinities. The technique can implement an ultra-fast isolation of protein/ligand complex with the retention time of a complex peak in about 5s, and on-line prepare the "clean" sample to be directly compatible with the LC-MS analysis. The improvement in performance of this 2D-TFC/LC-MS approach over the conventional approach has been demonstrated by determining affinity-selected ligands of the target proteins acetylcholinesterase and butyrylcholinesterase from a small library with known binding affinities and a steroidal alkaloid library composed of structurally similar compounds. Our results show that 2D-TFC/LC-MS is a generic and efficient tool for high-throughput screening of ligands with low-to-high binding affinities, and structure-activity relationship evaluation.
ESTHER : Zhou_2009_J.Chromatogr.A_1216_2394
PubMedSearch : Zhou_2009_J.Chromatogr.A_1216_2394
PubMedID: 19203758

Title : Characterization of ST-4821 complex, a unique Neisseria meningitidis clone - Peng_2008_Genomics_91_78
Author(s) : Peng J , Yang L , Yang F , Yang J , Yan Y , Nie H , Zhang X , Xiong Z , Jiang Y , Cheng F , Xu X , Chen S , Sun L , Li W , Shen Y , Shao Z , Liang X , Xu J , Jin Q
Ref : Genomics , 91 :78 , 2008
Abstract : Ten outbreaks of a new serogroup C meningococcal disease emerged during 2003-2005 in China. The multilocus sequence typing results indicated that unique sequence type 4821 clone meningococci were responsible for these outbreaks. Herein, we determined the entire genomic DNA sequence of serogroup C isolate 053442, which belongs to ST-4821. Comparison of 053442 gene contents with other meningococcal genomes shows that they have similar characteristics, including thousands of repetitive elements and simple sequence repeats, numerous phase-variable genes, and similar virulence-related factors. However, many strain-specific regions were found in each genome. We also present the results of a genomic comparison of 28 ST-4821 complex isolates that were isolated from different serogroups using comparative genomic hybridization analysis. Genome comparison between the newly emerged hyperinvasive isolates belonging to different serogroups will further our understanding of their respective pathogenetic mechanisms.
ESTHER : Peng_2008_Genomics_91_78
PubMedSearch : Peng_2008_Genomics_91_78
PubMedID: 18031983
Gene_locus related to this paper: neigo-pip , neima-metx , neimb-q9k0t9 , neime-ESD , neime-NMA2216 , neime-NMB0276 , neime-NMB1877

Title : A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates - Chen_2007_PLoS.One_2_e315
Author(s) : Chen C , Tang J , Dong W , Wang C , Feng Y , Wang J , Zheng F , Pan X , Liu D , Li M , Song Y , Zhu X , Sun H , Feng T , Guo Z , Ju A , Ge J , Dong Y , Sun W , Jiang Y , Yan J , Yang H , Wang X , Gao GF , Yang R , Yu J
Ref : PLoS ONE , 2 :e315 , 2007
Abstract : BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.
ESTHER : Chen_2007_PLoS.One_2_e315
PubMedSearch : Chen_2007_PLoS.One_2_e315
PubMedID: 17375201
Gene_locus related to this paper: strsu-a4vws4 , strsu-q302y4 , strsy-a4vus4 , strsy-a4vwf6

Title : Inhibitors of acetylcholine esterase in vitro--screening of steroidal alkaloids from Fritillaria species - Lin_2006_Planta.Med_72_814
Author(s) : Lin BQ , Ji H , Li P , Fang W , Jiang Y
Ref : Planta Med , 72 :814 , 2006
Abstract : 18 alkaloids were successfully isolated from five Fritillaria species and 5 derivatives were synthesized. Their effects on the bioactivity of human whole blood cholinesterase (ChE) were assessed. The results showed that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone inhibited the bioactivity of human whole blood ChE at the concentration of 1.0 x 10 ( - 4) M, with the inhibitory effects of 55.5 +/- 2.7 %, 66.8 +/- 2.0 %, 69.0 +/- 1.7 %, 71.2 +/- 1.8 % and 70.7 +/- 3.3 %, respectively. The effects of the five alkaloids on human red blood cell (RBC) acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BChE) were further studied, and their IC (50) values for human RBC AChE were 6.4 +/- 0.003 microM, 16.9 +/- 0.018 microM, 5.7 +/- 0.004 microM, 6.5 +/- 0.013 microM and 7.7 +/- 0.001 microM, respectively, and the IC50 values for human plasma BChE were 12.5 +/- 0.026 microM, 2.1 +/- 0.005 microM, 5.2 +/- 0.002 microM, 7.3 +/- 0.005 microM and 0.7 +/- 0.001 microM, respectively. These data suggest, therefore, that N-demethylpuqietinone, hupeheninoside, ebeiedinone, yibeinoside A and chuanbeinone have both anti-RBC AChE and anti-plasma BChE activities, N-demethylpuqietinone is a selective inhibitor of AChE, whereas hupeheninoside and chuanbeinone are the selective inhibitors of BChE.
ESTHER : Lin_2006_Planta.Med_72_814
PubMedSearch : Lin_2006_Planta.Med_72_814
PubMedID: 16881015

Title : Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors - Sheng_2005_Bioorg.Med.Chem.Lett_15_3834
Author(s) : Sheng R , Lin X , Li J , Jiang Y , Shang Z , Hu Y
Ref : Bioorganic & Medicinal Chemistry Lett , 15 :3834 , 2005
Abstract : A series of 2-phenoxy-indan-1-one derivatives have been designed, synthesized, and tested as acetylcholinesterase inhibitors. The most potent compound exhibited high AChE inhibitory activity (IC50 = 50 nM), and the molecular docking study indicated that it was nicely accommodated by AChE.
ESTHER : Sheng_2005_Bioorg.Med.Chem.Lett_15_3834
PubMedSearch : Sheng_2005_Bioorg.Med.Chem.Lett_15_3834
PubMedID: 15993600

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

Title : Cloning and expression of the polyhydroxyalkanote depolymerase gene from Pseudomonas putida, and characterization of the gene product - Jiang_2004_Biotechnol.Lett_26_1585
Author(s) : Jiang Y , Ye J , Wu H , Zhang H
Ref : Biotechnol Lett , 26 :1585 , 2004
Abstract : A polyhydroxyalkanote (PHA) depolymerase gene ( pha Z) was cloned by PCR from Pseudomonas putida and over-expressed in Escherichia coli as inclusion bodies. Nucleotide sequence analysis predicted an 852 bp open reading frame encoding a protein of 283 amino acids with a predicted molecular weight of 31283 Da. The deduced amino acid sequence had at least 80% homology to the PHA depolymerase from other Pseudomonas strains and consisted a conserved lipase box-like sequence (G-X-S(102)-X-G). The inclusion bodies were refolded and biochemically characterized. The depolymerase activity was optimal at 40 degrees C and pH 8.
ESTHER : Jiang_2004_Biotechnol.Lett_26_1585
PubMedSearch : Jiang_2004_Biotechnol.Lett_26_1585
PubMedID: 15604801

Title : Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen encephalitis - Watson_2004_Neurology_63_43
Author(s) : Watson R , Jiang Y , Bermudez I , Houlihan LM , Clover L , McKnight K , Cross JH , Hart IK , Roubertie A , Valmier J , Hart Y , Palace J , Beeson D , Vincent A , Lang B
Ref : Neurology , 63 :43 , 2004
Abstract : OBJECTIVE: To determine the prevalence of serum antibodies to the ionotropic glutamate receptor 3 (GluR3) in patients with Rasmussen encephalitis (RE), a severe epileptic disorder, and to compare with serum from control subjects and patients with intractable epilepsy (IE).
METHODS: The authors looked for serum immunoglobulin (Ig) G antibodies to GluR3 in 30 patients with RE, including two patients who had plasma exchange and 12 who had been treated with IV Igs with varying results, and 49 patients with IE and 23 healthy individuals, using ELISA with GluR3B peptide, Western blot analysis of recombinant full-length GluR3, immunoprecipitation of [35S]- and [125I]-labeled GluR3 extracellular domains, immunohistochemistry on rat brain sections, and electrophysiology of GluR3 expressed in Xenopus oocytes.
RESULTS: Low levels of antibodies to the GluR3B peptide were detected using ELISA in only 4 of the 79 patients with epilepsy (2 with RE and 2 with IE); binding to GluR3B in other sera was shown to be nonspecific. One other patient with IE had antibodies to recombinant GluR3 on Western blot analysis. However, none of the sera tested precipitated either the [35S]- or the [125I]-labeled GluR3 domains; none bound to rat brain sections in a manner similar to rabbit antibodies to GluR3; and none of the nine sera tested affected the electrophysiologic function of GluR3.
CONCLUSIONS: GluR3 antibodies were only infrequently found in Rasmussen encephalitis or intractable epilepsy.
ESTHER : Watson_2004_Neurology_63_43
PubMedSearch : Watson_2004_Neurology_63_43
PubMedID: 15249609

Title : Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate - Singh_2003_Toxicol.Ind.Health_19_93
Author(s) : Singh AK , Jiang Y
Ref : Toxicol Ind Health , 19 :93 , 2003
Abstract : Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1beta (IL1beta), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (INTgamma), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1beta, TNFalpha and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhi IgDhi, IgMlo IgDlo and CD8+ CD45RA- CCR7+ cells were elevated, while IgMlo IgDhi, IgMhi IgDlo, IgMin IgDlo, CD8+ CD45RA+ CCR7+ and CD8+ CD45RA- CCR7 cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.
ESTHER : Singh_2003_Toxicol.Ind.Health_19_93
PubMedSearch : Singh_2003_Toxicol.Ind.Health_19_93
PubMedID: 15697179

Title : Simultaneous determination of N-butyramide-tacrine and tacrine in mouse plasma and brain homogenate by high-performance liquid chromatography with a simple gradient solvent system - Jiang_2003_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_791_285
Author(s) : Jiang Y , Zhang Y , Zhang ZR
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 791 :285 , 2003
Abstract : A novel reversed-phase HPLC method was developed for the simultaneous determination of tacrine (THA) and the newly synthesized prodrug (N-butyramide-THA, BTHA) in mouse plasma and brain homogenate. The assay involves deproteinisation and subsequent detection at 240 nm with a gradient solvent system. Retention times were 18.5 and 9.3 min for BTHA and THA, respectively. Average recoveries for the analytes were 80.7% (BTHA) and 76.6% (THA) from plasma, and 75.0% (BTHA) and 68.4% (THA) from brain homogenate. Linear responses were observed over a wide range (0.25-20 microg/ml for BTHA in plasma and in brain homogenate, 0.025-20 microg/ml for THA in both matrices). Both BTHA and THA degraded from the prodrug can be detected even 12 h after intravenous administration of BTHA, indicating that BTHA is a promising prodrug for brain targeting.
ESTHER : Jiang_2003_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_791_285
PubMedSearch : Jiang_2003_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_791_285
PubMedID: 12798188

Title : Apolipoprotein E4 inhibits, and apolipoprotein E3 promotes neurite outgrowth in cultured adult mouse cortical neurons through the low-density lipoprotein receptor-related protein - Nathan_2002_Brain.Res_928_96
Author(s) : Nathan BP , Jiang Y , Wong GK , Shen F , Brewer GJ , Struble RG
Ref : Brain Research , 928 :96 , 2002
Abstract : The apolipoprotein E4 (apoE4) genotype is a major risk factor for Alzheimer's disease (AD); however, the mechanism is unknown. We previously demonstrated that apoE isoforms differentially modulated neurite outgrowth in embryonic neurons and in neuronal cell lines. ApoE3 increased neurite outgrowth whereas apoE4 decreased outgrowth, suggesting that apoE4 may directly affect neurons in the brain. In the present study we examined the effects of apoE on neurite outgrowth from cultured adult mouse cortical neurons to examine if adult neurons respond the same way that embryonic cells do. The results from this study demonstrated that (1) cortical neurons derived from adult apoE-gene knockout (apoE KO) mice have significantly shorter neurites than neurons from adult wild-type (WT) mice; (2) incubation of cortical neurons from adult apoE KO mice with human apoE3 increased neurite outgrowth, whereas human apoE4 decreased outgrowth in a dose-dependent fashion; (3) the isoform specific effects were abolished by incubation of the neurons with either receptor associated protein (RAP) or lactoferrin, both of which block the interaction of apoE-containing lipoproteins with the low-density lipoprotein receptor-related protein (LRP). These data suggest a potential mechanism whereby apoE4 may play a role in regenerative failure and accelerate the development of AD.
ESTHER : Nathan_2002_Brain.Res_928_96
PubMedSearch : Nathan_2002_Brain.Res_928_96
PubMedID: 11844476

Title : Immunotoxicity of acute acephate exposure in control or IL-1-challenged rats: correlation between the immune cell composition and corticosteroid concentration in blood - Singh_2002_J.Appl.Toxicol_22_279
Author(s) : Singh AK , Jiang Y
Ref : Journal of Applied Toxicology , 22 :279 , 2002
Abstract : Corticosterone concentration and the immune cell composition were measured in rats exposed by intraperitoneal (i.p.) injection to different doses (10-500 mg kg(-1)) of acephate (Ace) and 250 micro g kg(-1) of interleukin 1 (IL-1), either alone or in combination. Two different combination protocols were used: IL-1 and Ace were administered simultaneously; and IL-1 was injected 60 min after Ace administration (sequential exposure). Ace, in a dose- and time-dependent manner, inhibited blood and brain acetylcholinesterase (AChE) activities, increased blood corticosterone concentrations, suppressed blood CD4, CD8, B cell and monocyte contents and increased blood neutrophil counts. The Ace-induced changes lasted for up to 24 h after Ace exposure. Interleukin 1 increased blood corticosterone concentrations without affecting blood or brain AChE activities. The IL-1-induced corticosterone concentration returned to the basal level within 3-10 h after IL-1 exposure. The CD4, CD8, B cell and monocyte counts increased significantly at 10 min after IL-1 exposure. The cell counts decreased gradually thereafter and returned to the basal level within 30 min after IL-1 exposure. Simultaneous exposure of rats to Ace and IL-1 partially suppressed the IL-1-induced increase in the immune cell counts and decreased the immune cell numbers below the basal values. Sequential injection of Ace and IL-1 blocked the IL-1-induced increase in the immune cell numbers. Thus, Ace exposure would impair the normal distribution of immune cells and deregulate the IL-1 response in rats. This study therefore suggests that Ace would suppress the immune cell numbers in blood, thus decreasing an organism's immunity. Ace exposure occurring concurrent with injury would augment the acute-phase response, which would augment the toxic effects of IL-1 and other cytokines, and Ace exposure occurring prior to the injury would suppress or abolish the initial stimulatory effects of IL-1, which would decrease an organism's ability to combat infection or injury.
ESTHER : Singh_2002_J.Appl.Toxicol_22_279
PubMedSearch : Singh_2002_J.Appl.Toxicol_22_279
PubMedID: 12355557

Title : Physicochemical, molecular-orbital and electronic properties of acephate and methamidophos - Singh_1998_Comp.Biochem.Physiol.C.Pharmacol.Toxicol.Endocrinol_119_107
Author(s) : Singh AK , White T , Spassova D , Jiang Y
Ref : Comparative Biochemistry & Physiology C Pharmacology Toxicology & Endocrinology , 119 :107 , 1998
Abstract : Methamidophos (Me) and its N-acetylated derivative, acephate (Ac), are water soluble insecticides that have similar insecticidal potency, but different mammalian toxicity. Me is a potent inhibitor, while Ac is a poor inhibitor of mammalian AChE (mAChE). At physiological pH, both insecticides exhibit similar accumulation in RBC, while Ac exhibits greater binding to plasma proteins than Me. These differential effects of Ac and Me are attributed to the differences in their physicochemical, molecular-orbital and electronic properties. Ac and Me are freely soluble in aqueous solution, moderately soluble in ethyl-acetate (EtAct) and insoluble in n-hexane. The solubility of these insecticides in aqueous solution and the partitioning of these insecticides from aqueous solution into EtAct are independent of the pH of the aqueous solution. At pH 8, Me did not react with o-phthalaldehyde (a NH2 selective dye), but gamma-amino-butyric acid (pKa 10) did. Thus, despite the presence of an amino group, Ac and Me do not exhibit pH dependent solubility in aqueous and in organic solvents. Ac has two O atoms with non-bonding electrons (P = O delta- and C = O delta-) where P = O and C = O point in opposite directions. Me has only one O atom with non-bonding electrons (P = O delta-). However, because of charge translocation, the C = O group of Ac exists as C = O- and the P-NH3+ group of Me exists as P = NH2+ at a pH lower than their pKa. The P-N bond of Me, but not of Ac, is hydrolyzed at pH 2. Thus, the presence of an electron rich domain stabilizes Ac's P-N bond. The CH3S-P bond of both insecticides is similarly hydrolyzed at pH 11. This indicates that the two compounds are considerably similar except that Ac has an additional electron rich domain. At physiological pH, therefore, the functional differences between these insecticides may be due to the differences in their electronic structure. We propose that, similar to a previous model for cationic inhibitors of AChE (13), the P = O delta- group of Me forms hydrogen bonds within the oxyanion-hole causing the leaving group (-SCH3) to orient towards the "gorge" opening. This orientation allows the P atom of Me to interact with Ser200, resulting in the phosphorylation of the enzyme. For acephate, either P = O or C = O, but not both, interact within the oxyanion-hole. This destabilizes the binding of Ac to the active center, resulting in reduced AChE phosphorylation.
ESTHER : Singh_1998_Comp.Biochem.Physiol.C.Pharmacol.Toxicol.Endocrinol_119_107
PubMedSearch : Singh_1998_Comp.Biochem.Physiol.C.Pharmacol.Toxicol.Endocrinol_119_107
PubMedID: 9568380