Deng Y

References (65)

Title : Aquatic photolysis of high-risk fluorinated liquid crystal monomers: Kinetics, toxicity evaluation, and mechanisms - Wu_2024_Water.Res_255_121510
Author(s) : Wu J , Ye W , Feng Y , Lao W , Li J , Lu H , Liu G , Su G , Deng Y
Ref : Water Res , 255 :121510 , 2024
Abstract : Despite the frequent detection of fluorinated liquid-crystal monomers (FLCMs) in the environment, the level of understanding of their fate, toxicity, and transformation remains insufficient. Herein, we investigated the degradation kinetics and mechanism of an FLCM (4-cyano-3-fluorophenyl 4-ethylbenzoate, CEB-F) under ultraviolet (UV) photolysis in aquatic environment. Our findings demonstrated that the UV photolysis of CEB-F followed first-order kinetics. Photodegradation products were identified using liquid chromatography with mass spectrometry, and detailed reaction pathways were proposed. It is postulated that through the attack of reactive oxygen species, hydroxylation, and CO/C-F bond cleavage, CEB-F gradually degraded into small molecular compounds, releasing fluorine ions. Acute immobilization tests with Daphnia magna (D. magna) revealed significant acute toxicity of CEB-F, with LC(50) values ranging from 1.023 to 0.0536 microM over 24 to 96 h, emphasizing the potential high risk of FLCMs in aquatic ecosystems if inadvertently discharged. Interestingly, we found that the toxicity of CEB-F photolysis reaction solutions was effectively reduced. Through catalase and acetylcholinesterase activities analysis along with molecular docking simulation, we proposed differences in the underlying toxicity mechanisms of CEB-F and its photolysis products to D. magna. These findings highlight the potential harmful effects of FLCMs on aquatic ecosystems and enrich our understanding of the photolysis behavior of FLCMs.
ESTHER : Wu_2024_Water.Res_255_121510
PubMedSearch : Wu_2024_Water.Res_255_121510
PubMedID: 38555780

Title : Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles - Tang_2024_Mater.Today.Bio_25_100988
Author(s) : Tang X , Zhang J , Sui D , Xu Z , Yang Q , Wang T , Li X , Liu X , Deng Y , Song Y
Ref : Mater Today Bio , 25 :100988 , 2024
Abstract : The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.
ESTHER : Tang_2024_Mater.Today.Bio_25_100988
PubMedSearch : Tang_2024_Mater.Today.Bio_25_100988
PubMedID: 38379935

Title : Kinetic and thermodynamic-based studies on the interaction mechanism of novel R. roxburghii seed peptides against pancreatic lipase and cholesterol esterase - Yin_2024_Food.Chem_447_139006
Author(s) : Yin H , Zhu J , Zhong Y , Wang D , Deng Y
Ref : Food Chem , 447 :139006 , 2024
Abstract : Pancreatic lipase (PL) and cholesterol esterase (CE) are vital digestive enzymes that regulate lipid digestion. Three bioactive peptides (LFCMH, RIPAGSPF, YFRPR), possessing enzyme inhibitory activities, were identified in the seed proteins of R. roxburghii. It is hypothesized that these peptides could inhibit the activities of these enzymes by binding to their active sites or altering their conformation. The results showed that LFCMH exhibited superior inhibitory activity against these enzymes compared to the other peptides. The inhibition mechanisms of the three peptides were identified as either competitive or mixed, according to inhibition models. Further studies have shown that peptides could bind to the active sites of enzymes, thus affecting their spatial conformation and restricting substrate entry into the active site. Molecular simulation further proved that hydrogen bonds and hydrophobic interactions played a vital role in the binding of peptides to enzymes. This study enriches our understanding of interaction mechanisms of peptides on PL and CE.
ESTHER : Yin_2024_Food.Chem_447_139006
PubMedSearch : Yin_2024_Food.Chem_447_139006
PubMedID: 38492305

Title : Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING - Fan_2024_Int.Immunopharmacol_131_111904
Author(s) : Fan C , Du J , Yu Z , Wang J , Yao L , Ji Z , He W , Deng Y , Geng D , Wu X , Mao H
Ref : Int Immunopharmacol , 131 :111904 , 2024
Abstract : Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4alpha. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-beta-gal-positive cells and hindered the manifestation of p16INK4alpha and the inflammatory factor IL-1beta in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.
ESTHER : Fan_2024_Int.Immunopharmacol_131_111904
PubMedSearch : Fan_2024_Int.Immunopharmacol_131_111904
PubMedID: 38518595

Title : Tabersonine Induces the Apoptosis of Human Hepatocellular Carcinoma In vitro and In vivo - Li_2024_Anticancer.Agents.Med.Chem__
Author(s) : Li X , Chen L , Deng Y , Zheng Z , Ming Y
Ref : Anticancer Agents Med Chem , : , 2024
Abstract : BACKGROUND: Tabersonine, a natural indole alkaloid derived from Apocynaceae plants, exhibits antiinflammatory and acetylcholinesterase inhibitory activities, among other pharmacological effects. However, its anti-tumor properties and the underlying molecular mechanisms remain underexplored. OBJECTIVE: The present study aims to investigate the anti-tumor effects of tabersonine and its mechanisms in inducing apoptosis in hepatocellular carcinoma. METHODS: The inhibitory effects of tabersonine on the viability and proliferation of liver cancer cells were evaluated using MTT assay and colony formation assay. AO/EB, Hoechst, and Annexin V-FITC/ PI staining techniques were employed to observe cell damage and apoptosis. JC-1 staining was used to detect changes in mitochondrial membrane potential. Western blot analysis was conducted to study the anti-tumor mechanism of tabersonine on liver cancer cells. Additionally, a xenograft model using mice hepatoma HepG2 cells was established to assess the anti-tumor potency of tabersonine in vivo. RESULTS AND DISCUSSION: Our findings revealed that tabersonine significantly inhibited cell viability and proliferation, inducing apoptosis in liver cancer cells. Treatment with tabersonine inhibited Akt phosphorylation, reduced mitochondrial membrane potential, promoted cytochrome c release from mitochondria to the cytoplasm, and increased the ratio of Bax to Bcl-2. These findings suggested that tabersonine induces apoptosis in liver cancer cells through the mitochondrial pathway. Furthermore, tabersonine treatment activated the death receptor pathway of apoptosis. In vivo studies demonstrated that tabersonine significantly inhibited xenograft tumor growth. CONCLUSION: Our study is the first to demonstrate that tabersonine induces apoptosis in HepG2 cells through both mitochondrial and death receptor apoptotic pathways, suggesting its potential as a therapeutic agent candidate for hepatic cancer.
ESTHER : Li_2024_Anticancer.Agents.Med.Chem__
PubMedSearch : Li_2024_Anticancer.Agents.Med.Chem__
PubMedID: 38465429

Title : Benzofuran Derivatives from Cortex Mori Radicis and Their Cholinesterase-Inhibitory Activity - Cui_2024_Molecules_29_
Author(s) : Cui X , Huang Z , Deng S , Zhang Y , Li G , Wang L , Deng Y , Wu C
Ref : Molecules , 29 : , 2024
Abstract : The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone (1) and four ring-opening derivatives (2-5) named albaphenol A-E, as well as nigranol A (6), together with ten 2-arylbenzofuran derivatives (7-16). The characterization of the structures of the new compounds and the structural revision of nigranol A (6) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1-16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC(50) 45.5 and 61.0 microM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC(50) 2.5-32.8 microM) than the positive control galantamine (IC(50) 35.3 microM), while being inactive or weakly inhibitory toward AChE. Cathafuran C (14) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 microM. The structure-activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor-enzyme complex.
ESTHER : Cui_2024_Molecules_29_
PubMedSearch : Cui_2024_Molecules_29_
PubMedID: 38257228

Title : ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque - Zhang_2024_J.Adv.Res__
Author(s) : Zhang Y , Yan C , Dong Y , Zhao J , Yang X , Deng Y , Su L , Yin J , Sun F , Feng Y
Ref : J Adv Res , : , 2024
Abstract : INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin alphavbeta3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin alphavbeta3 for atherosclerosis progression. METHODS: Ldlr(-/-) mice on a high-fat diet and ApoE(-/-) mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE(-/-) mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3(-/-)ApoE(-/-) mice and ApoE(-/-) littermates. THP-1 cells were exposed to 0 or 50 microg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin beta3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68(+) macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG(+) cells were identified in plaque of gene transferred ApoE(-/-) mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1beta and tumour necrosis factor-alpha in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin beta3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-kappaB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.
ESTHER : Zhang_2024_J.Adv.Res__
PubMedSearch : Zhang_2024_J.Adv.Res__
PubMedID: 38740260

Title : Efficient decolorization of melanoidin in raw molasses wastewater by thermophilic esterase in actual extreme conditions - Zhang_2023_Bioresour.Technol_382_129191
Author(s) : Zhang Z , Hu W , Xie Q , Shi Y , Zhao Y , Deng Y , He J , Wu X , Zhang Y , Zhang W , Liu P , Yang H , Wang W
Ref : Bioresour Technol , 382 :129191 , 2023
Abstract : This work was developed to explore the versatility of thermophilic esterase for decolorizing raw molasses wastewater at high temperature and acidic pH. Combining covalent crosslinking method with deep eutectic solvent, a thermophilic esterase from Pyrobaculum calidifontis was immobilized on chitosan/macroporous resin composite carrier. The application of this immobilized thermophilic esterase eliminated 92.35% of colorants in raw molasses wastewater, achieving maximal decolorization efficiency across all the enzymes tested. Strikingly, this immobilized thermophilic esterase was capable of engaging in continuous activity for a 5-day period while removing 76.23% of pigments from samples. It effectively and continuously eliminated BOD(5) and COD, effectively and directly facilitating raw molasses wastewater decolorization under extreme conditions more readily than control group. In addition, this thermophilic esterase was believed to achieve decolorization through an addition reaction that disrupted conjugated system of melanoidins. Together, these results highlight an efficient and practical means of achieving enzyme-based molasses wastewater decolorization.
ESTHER : Zhang_2023_Bioresour.Technol_382_129191
PubMedSearch : Zhang_2023_Bioresour.Technol_382_129191
PubMedID: 37196742

Title : Alzheimer's disease with frailty: Prevalence, screening, assessment, intervention strategies and challenges - Deng_2023_Biosci.Trends__
Author(s) : Deng Y , Wang H , Gu K , Song P
Ref : Biosci Trends , : , 2023
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions worldwide and is expected to surge in prevalence due to aging populations. Frailty, characterized by muscle function decline, becomes more prevalent with age, imposing substantial burdens on patients and caregivers. This paper aimed to comprehensively review the current literature on AD coupled with frailty, encompassing prevalence, screening, assessment, and treatment while delving into the field's challenges and future trajectories. Frailty and AD coexist in more than 30% of cases, with hazard ratios above 120% indicating a mutually detrimental association.Various screening tools have emerged for both frailty and AD, including the Fried Frailty Phenotype (FP), FRAIL scale, Edmonton Frailty Scale (EFS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Drawing Test (CDT), and General Practitioner Assessment of Cognition (GPCOG). However, none has solidified its role as the definitive gold standard. The convergence of electronic health records and brain aging biomarkers heralds a new era in AD with frailty screening and assessment. In terms of intervention, non-pharmacological strategies spanning nutrition, horticulture, exercise, and social interaction, along with pharmacological approaches involving acetylcholinesterase inhibitors (AChEIs), N-methyl-D-aspartate (NMDA) receptor antagonists, and anti-amyloid beta-protein medications, constituted cornerstones for treating AD coupled with frailty. Technological interventions like repetitive transcranial magnetic stimulation (rTMS) also entered the fold. Notably, multi-domain non-pharmacological interventions wield considerable potential in enhancing cognition and mitigating disability. However, the long-term efficacy and safety of pharmacological interventions necessitate further validation. Diagnosing and managing AD with frailty present several daunting challenges, encompassing low rates of early co-diagnosis, limited clinical trial evidence, and scarce integrated, pioneering service delivery models. These challenges demand heightened attention through robust research and pragmatic implementation.
ESTHER : Deng_2023_Biosci.Trends__
PubMedSearch : Deng_2023_Biosci.Trends__
PubMedID: 37612122

Title : Construction and Manipulation of Serial Gradient Dilution Array on a Microfluidic Slipchip for Screening and Characterizing Inhibitors against Human Pancreatic Lipase - Yang_2023_Biosensors.(Basel)_13_
Author(s) : Yang J , Deng Y , Zhang M , Feng S , Peng S , Yang S , Liu P , Cai G , Ge G
Ref : Biosensors (Basel) , 13 : , 2023
Abstract : Obesity is one of the foremost public health concerns. Human pancreatic lipase (hPL), a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, has been validated as an important therapeutic target for preventing and treating obesity. The serial dilution technique is commonly used to generate solutions with different concentrations and can be easily modified for drug screening. Conventional serial gradient dilution is often performed with tedious multiple manual pipetting steps, where it is difficult to precisely control fluidic volumes at low microliter levels. Herein, we presented a microfluidic SlipChip that enabled formation and manipulation of serial dilution array in an instrument-free manner. With simple slipping steps, the compound solution could be diluted to seven gradients with the dilution ratio of 1:1 and co-incubated with the enzyme (hPL)-substrate system for screening the anti-hPL potentials. To ensure complete mixing of solution and diluent during continuous dilution, we established a numerical simulation model and conducted an ink mixing experiment to determine the mixing time. Furthermore, we also demonstrated the serial dilution ability of the proposed SlipChip using standard fluorescent dye. As a proof of concept, we tested this microfluidic SlipChip using one marketed anti-obesity drug (Orlistat) and two natural products (1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (PGG) and sciadopitysin) with anti-hPL potentials. The IC(50) values of these agents were calculated as 11.69 nM, 8.22 nM and 0.80 microM, for Orlistat, PGG and sciadopitysin, respectively, which were consistent with the results obtained by conventional biochemical assay.
ESTHER : Yang_2023_Biosensors.(Basel)_13_
PubMedSearch : Yang_2023_Biosensors.(Basel)_13_
PubMedID: 36832040

Title : Development of novel 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as balanced multifunctional agents against Alzheimer's disease - Shi_2022_Eur.J.Med.Chem_230_114098
Author(s) : Shi Y , Zhang H , Song Q , Yu G , Liu Z , Zhong F , Tan Z , Liu X , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 230 :114098 , 2022
Abstract : Based on multitarget-directed ligands approach, through two rounds of screening, a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives were designed, synthesized and evaluated as innovative multifunctional agents against Alzheimer's disease. In vitro biological assays indicated that most of the hybrids were endowed with great AChE inhibitory activity, excellent antioxidant activity and moderate Abeta(1-42) aggregation inhibition. Taken both efficacy and balance into account, 12a was identified as the optimal multifunctional ligand with significant inhibition of AChE (EeAChE, IC(50) = 0.20 microM; HuAChE, IC(50) = 37.02 nM) and anti-Abeta activity (IC(50) = 1.92 microM for self-induced Abeta(1-42) aggregation; IC(50) = 1.80 microM for disaggregation of Abeta(1-42) fibrils; IC(50) = 2.18 microM for Cu(2+)-induced Abeta(1-42) aggregation; IC(50) = 1.17 microM for disaggregation of Cu(2+)-induced Abeta(1-42) fibrils; 81.7% for HuAChE-induced Abeta(1-40) aggregation). Moreover, it was equipped with the potential to serve as antioxidant (3.03 Trolox equivalents), metals chelator and anti-neuroinflammation agent for synergetic treatment. Finally, in vivo study demonstrated that 12a, with suitable BBB permeability (log BB = -0.61), could efficaciously ameliorate cognitive dysfunction on scopolamine-treated mice by regulating cholinergic system and oxidative stress simultaneously. Altogether, these results highlight the potential of 12a as an innovative balanced multifunctional candidate for Alzheimer's disease treatment.
ESTHER : Shi_2022_Eur.J.Med.Chem_230_114098
PubMedSearch : Shi_2022_Eur.J.Med.Chem_230_114098
PubMedID: 35026532

Title : Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer's disease - Liu_2022_Bioorg.Med.Chem_58_116660
Author(s) : Liu Z , Shi Y , Zhang X , Yu G , Li J , Cong S , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 58 :116660 , 2022
Abstract : Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC(50) = 0.087 microM), HuAChE (IC(50) = 0.041 microM) and MAO-B (IC(50) = 0.30 microM). Furthermore, molecular docking studies were conducted to investigate the interaction mode with enzymes. Besides, 7d also possessed good effects of Cu(2+) chelation, ameliorate oxidative stress, and anti-neuroinflammation, desirable BBB permeability and eligible drug-like properties. Altogether, the multifunctional profiles of 7d prove that it deserves further investigation as a novel drug candidate for AD treatment.
ESTHER : Liu_2022_Bioorg.Med.Chem_58_116660
PubMedSearch : Liu_2022_Bioorg.Med.Chem_58_116660
PubMedID: 35183029

Title : Butenolide derivatives from Aspergillus terreus selectively inhibit butyrylcholinesterase - Cui_2022_Front.Chem_10_1063284
Author(s) : Cui X , Deng S , Li G , Zhang Y , Wang L , Wu C , Deng Y
Ref : Front Chem , 10 :1063284 , 2022
Abstract : Two undescribed butenolide derivatives, asperteretal J (1) and K (2), together with 13 known ones (3-15) were isolated from an endophytic fungus Aspergillus terreus SGP-1, the fermentation product of which exhibited selective inhibitory activity toward butyrylcholinesterase. The structures of the new compounds were elucidated based on HRMS and NMR data, and the absolute configurations were determined by specific optical rotation comparison. All compounds were evaluated for cholinesterase inhibitory effects with galantamine as a positive control. Compounds 4-8 selectively inhibited butyrylcholinesterase with IC(50) values of 18.4-45.8smicroM in a competitive manner, with Ki values of 12.3-38.2smicroM. The structure-activity relationship was discussed. Molecular docking and dynamic simulation of the inhibitor-enzyme complex were performed to better understand the interactions.
ESTHER : Cui_2022_Front.Chem_10_1063284
PubMedSearch : Cui_2022_Front.Chem_10_1063284
PubMedID: 36618870

Title : The Cell-Cell Communication Signal Indole Controls the Physiology and Interspecies Communication of Acinetobacter baumannii - Cui_2022_Microbiol.Spectr__e0102722
Author(s) : Cui B , Chen X , Guo Q , Song S , Wang M , Liu J , Deng Y
Ref : Microbiol Spectr , :e0102722 , 2022
Abstract : Many bacteria utilize quorum sensing (QS) to control group behavior in a cell density-dependent manner. Previous studies have demonstrated that Acinetobacter baumannii employs an N-acyl-L-homoserine lactone (AHL)-based QS system to control biological functions and virulence. Here, we report that indole controls biological functions, virulence and AHL signal production in A. baumannii. The biosynthesis of indole is performed by A1S_3160 (AbiS, Acinetobacter baumannii indole synthase), which is a novel indole synthase annotated as an alpha/beta hydrolase in A. baumannii. Heterologous expression of AbiS in an Escherichia coli indole-deficient mutant also rescued the production of indole by using a distinct biosynthetic pathway from the tryptophanase TnaA, which produces indole directly from tryptophan in E. coli. Moreover, we revealed that indole from A. baumannii reduced the competitive fitness of Pseudomonas aeruginosa by inhibiting its QS systems and type III secretion system (T3SS). As A. baumannii and P. aeruginosa usually coexist in human lungs, our results suggest the crucial roles of indole in both the bacterial physiology and interspecies communication. IMPORTANCE Acinetobacter baumannii is an important human opportunistic pathogen that usually causes high morbidity and mortality. It employs the N-acyl-L-homoserine lactone (AHL)-type quorum sensing (QS) system, AbaI/AbaR, to regulate biological functions and virulence. In this study, we found that A. baumannii utilizes another QS signal, indole, to modulate biological functions and virulence. It was further revealed that indole positively controls the production of AHL signals by regulating abaI expression at the transcriptional levels. Furthermore, indole represses the QS systems and type III secretion system (T3SS) of P. aeruginosa and enhances the competitive ability of A. baumannii. Together, our work describes a QS signaling network where a pathogen uses to control the bacterial physiology and pathogenesis, and the competitive ability in microbial community.
ESTHER : Cui_2022_Microbiol.Spectr__e0102722
PubMedSearch : Cui_2022_Microbiol.Spectr__e0102722
PubMedID: 35862954
Gene_locus related to this paper: acicp-AbiS

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

Title : Phthalimide-(N-alkylbenzylamine) cysteamide hybrids as multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Zhang_2021_Chem.Biol.Drug.Des__
Author(s) : Zhang H , Song Q , Yu G , Cao Z , Qiang X , Liu X , Deng Y
Ref : Chemical Biology Drug Des , : , 2021
Abstract : The complex pathogenesis of Alzheimer's disease (AD) calls for multi-target approach for disease treatment. Herein, based on the MTDLs strategy, a series of phthalimide-(N-alkylbenzylamine) cysteamide hybrids were designed, synthesized and investigated in vitro for the purpose. Most of the target compounds were found to be potential multi-target agents. In vitro results showed that compound 9e was the representative compound in this series, endowed with high EeAChE and HuAChE inhibitory potency (IC(50) = 1.55microM and 2.23 microM, respectively), good inhibitory activity against self-induced Abeta(1-42) aggregation (36.08% at 25 microM) and moderate antioxidant capacity (ORAC-FL value was 0.68 Trolox equivalents). Molecular docking studies rationalized the binding mode of 9e in both PAS and CAS of AChE. Moreover, 9e displayed excellent ability to against H(2) O(2) -induced PC12 cell injury and penetrate BBB. Overall, these results highlighted that compound 9e was an effective and promising multi-target agent for further anti-AD drug development.
ESTHER : Zhang_2021_Chem.Biol.Drug.Des__
PubMedSearch : Zhang_2021_Chem.Biol.Drug.Des__
PubMedID: 34143938

Title : Novel 3-benzylidene\/benzylphthalide Mannich base derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - Cao_2021_Bioorg.Med.Chem_35_116074
Author(s) : Cao Z , Song Q , Yu G , Liu Z , Cong S , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 35 :116074 , 2021
Abstract : To discover novel multifunctional agents for the treatment of Alzheimer's disease, a series of 3-benzylidene/benzylphthalide Mannich base derivatives were designed, synthesized and evaluated. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound (Z)-13c raised particular interest because of its excellent multifunctional bioactivities. It displayed excellent EeAChE and HuAChE inhibition (IC(50) = 9.18 x 10(-5) and 6.16 x 10(-4) microM, respectively), good MAO-B inhibitory activity (IC(50) = 5.88 microM) and high antioxidant activity (ORAC =2.05 Trolox equivalents). Additionally, it also exhibited good antiplatelet aggregation activity, moderate self- and Cu(2+)-induced Abeta(1-42) aggregation inhibitory potency, disaggregation ability on Abeta(1-42) fibrils, biometal chelating ability, appropriate BBB permeability and significant neuroprotective effect. Furthermore, (Z)-13c can also ameliorate the learning and memory impairment induced by scopolamine in mice. These multifunctional properties highlight compound (Z)-13c as a promising candidate for further development of multifunctional drug against AD.
ESTHER : Cao_2021_Bioorg.Med.Chem_35_116074
PubMedSearch : Cao_2021_Bioorg.Med.Chem_35_116074
PubMedID: 33640707

Title : Chlorogenic acid alleviates thioacetamide-induced toxicity and promotes liver development in zebrafish (Danio rerio) through the Wnt signaling pathway - Liu_2021_Aquat.Toxicol_242_106039
Author(s) : Liu Y , Guo J , Zhang J , Deng Y , Xiong G , Fu J , Wei L , Lu H
Ref : Aquat Toxicol , 242 :106039 , 2021
Abstract : Chlorogenic acid (CGA) is a phenylpropanoid compound that is well known to improve the antioxidant capacity and other biological activities. However, the roles of CGA in the liver development of organisms are unclear. In the present study, we aimed to investigate the function of CGA in the hepatic development in thioacetamide (TAA)-induced zebrafish embryos. We found that CGA exerted certain beneficial effects on zebrafish larvae from TAA-exposed zebrafish embryos, such as increasing the liver size, body length, heart rate, acetylcholinesterase activity, and motor ability. In addition, CGA displayed an antioxidant effect on TAA-induced zebrafish embryos by enhancing the activities of superoxide dismutase (SOD), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH), and decreasing of the contents of malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO). The results of western blotting analysis showed that CGA inhibited cell apoptosis by increasing the levels of Bcl2 apoptosis regulator and decreasing the levels of Bcl2 associated X (Bax), apoptosis regulator and tumor protein P53. Moreover, CGA promoted cell proliferation in TAA-induced zebrafish larvae, as detected using proliferating cell nuclear antigen fluorescence immunostaining. In addition, CGA inhibited the expression of Wnt signaling pathway genes Dkk1 (encoding Dickkopf Wnt signaling pathway inhibitors), and promoted the expression of Lef1 (encoding lymphoid enhancer binding factor 1) and Wnt2bb (encoding wingless-type MMTV integration site family, member 2Bb). When the Wnt signal inhibitor IWR-1 was added, there was no significant change in liver development in the IWR-1 + TAA group compared with the IWR-1 + TAA + CGA group (p <0.05), which suggested that CGA regulates liver development via Wnt signaling pathway. Overall, our results suggested that CGA might alleviate TAA-induced toxicity in zebrafish and promote liver development through the Wnt signaling pathway, which provides a basis for the therapeutic effect of CGA on liver dysplasia.
ESTHER : Liu_2021_Aquat.Toxicol_242_106039
PubMedSearch : Liu_2021_Aquat.Toxicol_242_106039
PubMedID: 34856462

Title : Design, synthesis, and in vitro evaluation of 4-aminoalkyl-1(2H)-phthalazinones as potential multifunctional anti-Alzheimer's disease agents - Ye_2021_Bioorg.Chem_111_104895
Author(s) : Ye C , Xu R , Cao Z , Song Q , Yu G , Shi Y , Liu Z , Liu X , Deng Y
Ref : Bioorg Chem , 111 :104895 , 2021
Abstract : A series of 4-aminoalkyl-1(2H)-phthalazinone derivatives was designed and synthesized as potential multifunctional agents for Alzheimer's disease (AD) treatment. In vitro biological assay results demonstrated that most synthesized compounds exhibited significant AChE inhibition, moderate to high MAOs inhibitory potencies and good anti-platelet aggregation abilities. Among them, compound 15b exhibited the highest inhibitory potencies towards MAO-B and MAO-A (IC(50) = 0.7 microM and 6.4 microM respectively), moderate inhibition towards AChE (IC(50) = 8.2 microM), and good activities against self- and Cu(2+)-induced Abeta(1-42) aggregation and platelet aggregation. Moreover, 15b also displayed antioxidant capacity, neuroprotective potency, anti-neuroinflammation and BBB permeability. These excellent results indicated that compound 15b could be worthy of further studies to be considered as a promising multifunctional candidate for the treatment of AD.
ESTHER : Ye_2021_Bioorg.Chem_111_104895
PubMedSearch : Ye_2021_Bioorg.Chem_111_104895
PubMedID: 33887586

Title : Lipolytic Activity of a Carboxylesterase from Bumblebee (Bombus ignitus) Venom - Deng_2021_Toxins.(Basel)_13_
Author(s) : Deng Y , Kim BY , Lee KY , Yoon HJ , Wan H , Li J , Lee KS , Jin BR
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Bee venom is a complex mixture composed of peptides, proteins with enzymatic properties, and low-molecular-weight compounds. Although the carboxylesterase in bee venom has been identified as an allergen, the enzyme's role as a venom component has not been previously elucidated. Here, we show the lipolytic activity of a bumblebee (Bombus ignitus) venom carboxylesterase (BivCaE). The presence of BivCaE in the venom secreted by B. ignitus worker bees was confirmed using an anti-BivCaE antibody raised against a recombinant BivCaE protein produced in baculovirus-infected insect cells. The enzymatic activity of the recombinant BivCaE protein was optimal at 40 degreesC and pH 8.5. Recombinant BivCaE protein degrades triglycerides and exhibits high lipolytic activity toward long-chain triglycerides, defining the role of BivCaE as a lipolytic agent. Bee venom phospholipase A(2) binds to mammalian cells and induces apoptosis, whereas BivCaE does not affect mammalian cells. Collectively, our data demonstrate that BivCaE functions as a lipolytic agent in bee venom, suggesting that BivCaE will be involved in distributing the venom via degradation of blood triglycerides.
ESTHER : Deng_2021_Toxins.(Basel)_13_
PubMedSearch : Deng_2021_Toxins.(Basel)_13_
PubMedID: 33810599

Title : Effect of Selenium on Brain Injury in Chickens with Subacute Arsenic Poisoning - Ren_2021_Biol.Trace.Elem.Res__
Author(s) : Ren Z , Deng H , Wu Q , Jia G , Wen N , Deng Y , Zhu L , Zuo Z , Deng J
Ref : Biol Trace Elem Res , : , 2021
Abstract : The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage.
ESTHER : Ren_2021_Biol.Trace.Elem.Res__
PubMedSearch : Ren_2021_Biol.Trace.Elem.Res__
PubMedID: 33594525

Title : Design, synthesis and evaluation of phthalide alkyl tertiary amine derivatives as promising acetylcholinesterase inhibitors with high potency and selectivity against Alzheimer's disease - Luo_2020_Bioorg.Med.Chem__115400
Author(s) : Luo L , Song Q , Li Y , Cao Z , Qiang X , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , :115400 , 2020
Abstract : A series of phthalide alkyl tertiary amine derivatives were designed, synthesized and evaluated as potential multi-target agents against Alzheimer's disease (AD). The results indicated that almost all the compounds displayed significant AChE inhibitory and selective activities. Besides, most of the derivatives exhibited increased self-induced Abeta1-42 aggregation inhibitory activity compared to the lead compound dl-NBP, and some compounds also exerted good antioxidant activity. Specifically, compound I-8 showed the highest inhibitory potency toward AChE (IC50=2.66nM), which was significantly better than Donepezil (IC50=26.4nM). Moreover, molecular docking studies revealed that compound I-8 could bind to both the catalytic active site and peripheral anionic site of AChE. Furthermore, compound I-8 displayed excellent BBB permeability in vitro. Importantly, the step-down passive avoidance test indicated that I-8 significantly reversed scopolamine-induced memory deficit in mice. Collectively, these results suggested that I-8 might be a potent and selective AChE inhibitor for further anti-AD drug development.
ESTHER : Luo_2020_Bioorg.Med.Chem__115400
PubMedSearch : Luo_2020_Bioorg.Med.Chem__115400
PubMedID: 32146060

Title : A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer's Disease - Wu_2020_Int.J.Mol.Sci_21_
Author(s) : Wu W , Zhang Z , Li F , Deng Y , Lei M , Long H , Hou J
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein-protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids' anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer's disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.
ESTHER : Wu_2020_Int.J.Mol.Sci_21_
PubMedSearch : Wu_2020_Int.J.Mol.Sci_21_
PubMedID: 32143538

Title : miR-132 improves the cognitive function of rats with Alzheimer's disease by inhibiting the MAPK1 signal pathway - Deng_2020_Exp.Ther.Med_20_159
Author(s) : Deng Y , Zhang J , Sun X , Ma G , Luo G , Miao Z , Song L
Ref : Exp Ther Med , 20 :159 , 2020
Abstract : Alzheimer's disease (AD) is a common worldwide progressive neurodegenerative disease. The dysregulation of miRNA is crucial in neurodegenerative diseases and neuron apoptosis during AD and is closely associated with the MAPK pathway. By bioinformatic website, we found that there was target inhibiting relationship between microRNA (miR)-132 and MAPK1. Therefore, the current study speculated that miR-132 could improve the cognitive function of rats with AD by inhibiting MAPK1 expression. To verify our hypothesis, 10 normal rats and 60 rats with AD were selected and divided into model, Ad-miR-132 negative control (NC), Ad-miR-132, Ad-small interfering (si)MAPK1 NC, Ad-siMAPK1 and Ad-miR-132 + Ad-MAPK1 groups. Rats were evaluated for learning by performing morris water maze tests and pathological changes of the hippocampus were assessed via HE staining. Additionally, hippocampus cell apoptosis was determined using a TUNEL assay and levels of acetylcholinesterase (AChE), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in sera via ELISA. The mRNA and protein expression of miR-132, iNOS, MAPK1 and phosphorylated (p)-MAPK1 was determined in hippocampus tissues via reverse transcription-quantitative PCR and western blotting, respectively. Compared with normal mice, rats with AD had significantly decreased learning abilities, increased cell apoptosis rates, increased levels of AChE, iNOS, ROS, MDA, MAPK1 and p-MAPK1 and decreased levels of SOD, GSH-Px and miR-132. Upregulation of miR-132 group improved the above indictors and silencing MAKP1 worsened the condition of rats. miR-132 upregulation therefore reversed the negative effects caused by MAPK1 silencing in rats with AD. In conclusion, miR-132 inhibited hippocampal iNOS expression and oxidative stress by inhibiting MAPK1expression to improve the cognitive function of rats with AD.
ESTHER : Deng_2020_Exp.Ther.Med_20_159
PubMedSearch : Deng_2020_Exp.Ther.Med_20_159
PubMedID: 33093897

Title : A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review - Li_2019_Gene_704_113
Author(s) : Li T , Feng Y , Liu Y , He C , Liu J , Chen H , Deng Y , Li M , Li W , Song J , Niu Z , Sang S , Wen J , Men M , Chen X , Li J , Liu X , Ling J
Ref : Gene , 704 :113 , 2019
Abstract : Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.
ESTHER : Li_2019_Gene_704_113
PubMedSearch : Li_2019_Gene_704_113
PubMedID: 30974196
Gene_locus related to this paper: human-ABHD12

Title : The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure - Tao_2019_Medicine.(Baltimore)_98_e16556
Author(s) : Tao J , Li N , Liu Z , Deng Y , Li X , Chen M , Yu J , Zhu J , Yu P , Wang Y
Ref : Medicine (Baltimore) , 98 :e16556 , 2019
Abstract : Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.
ESTHER : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedSearch : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedID: 31348278

Title : Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation - Tian_2019_Bioorg.Chem__103477
Author(s) : Tian C , Qiang X , Song Q , Cao Z , Ye C , He Y , Deng Y , Zhang L
Ref : Bioorg Chem , :103477 , 2019
Abstract : The complex pathogenesis of Alzheimer's disease (AD) calls for multitarget approach for disease management. Herein, a series of novel flurbiprofen-chalcone hybrid Mannich base derivatives were designed and synthesized. The biological screening results indicated that most of the derivatives exhibited potent multi-target effects involved in AD. In particular, compound 6c bearing a pyrrolidine group showed the highest activities against self- and Cu(2+)-induced Abeta1-42 aggregation (70.65% and 54.89% at 25.0 microM, respectively), highly selective inhibition towards AChE and MAO-B (IC50 = 7.15 muM and 0.43 muM respectively), good antioxidant ability and metal-chelating property. Moreover, 6c displayed excellent anti-neuroinflammatory activity and appropriate BBB permeability in vitro. These outstanding results qualified compound 6c as a promising multifunctional agent for further development of disease-modifying treatment of AD.
ESTHER : Tian_2019_Bioorg.Chem__103477
PubMedSearch : Tian_2019_Bioorg.Chem__103477
PubMedID: 31818478

Title : Design, synthesis and evaluation of chalcone Mannich base derivatives as multifunctional agents for the potential treatment of Alzheimer's disease - Zhang_2019_Bioorg.Chem_87_395
Author(s) : Zhang X , Song Q , Cao Z , Li Y , Tian C , Yang Z , Zhang H , Deng Y
Ref : Bioorg Chem , 87 :395 , 2019
Abstract : A series of chalcone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease based on the multi-target directed ligands design strategy. In vitro assays demonstrated that most of the derivatives exerted potent selective inhibitory potency on AChE with good multifunctional properties. Among them, representative compound 7c exhibited moderate inhibitory potency for EeAChE (IC50=0.44muM) and MAO-B inhibition (IC50=1.21muM), good inhibitory effect on self-induced Abeta1-42 aggregation (55.0%, at 25muM), biometal chelating property, moderate antioxidant activity with a value 1.93-fold of Trolox. Moreover, both kinetic analysis of AChE inhibition and molecular modeling study revealed that 7c showed a mixed-type inhibition, binding simultaneously to CAS and PAS of AChE. In addition, 7c also displayed high BBB permeability. These properties indicated 7c may be a promising multifunctional agent for the treatment of AD.
ESTHER : Zhang_2019_Bioorg.Chem_87_395
PubMedSearch : Zhang_2019_Bioorg.Chem_87_395
PubMedID: 30921741

Title : Syndecan-1 Mediates Sorting of Soluble Lipoprotein Lipase with Sphingomyelin-Rich Membrane in the Golgi Apparatus - Sundberg_2019_Dev.Cell_51_387
Author(s) : Sundberg EL , Deng Y , Burd CG
Ref : Dev Cell , 51 :387 , 2019
Abstract : In the secretory pathway, budding of vesicular transport carriers from the trans-Golgi network (TGN) must coordinate specification of lipid composition with selection of secreted proteins. We elucidate a mechanism of soluble protein cargo sorting into secretory vesicles with a sphingomyelin-rich membrane; the integral membrane proteoglycan Syndecan-1 (SDC1) acts as a sorting receptor, capturing the soluble enzyme lipoprotein lipase (LPL) during export from the TGN. Sorting of LPL requires bivalent interactions between LPL and SDC1-linked heparan sulfate chains and between LPL and the Golgi membrane. Physical features of the SDC1 transmembrane domain, rather than a specific sequence, confer targeting of SDC1 and bound LPL into the sphingomyelin secretion pathway. This study establishes that physicochemical properties of a protein transmembrane domain that drive lateral heterogeneity of the plasma membrane also operate at the TGN to confer sorting of an integral membrane protein and its ligand within the biosynthetic secretory pathway.
ESTHER : Sundberg_2019_Dev.Cell_51_387
PubMedSearch : Sundberg_2019_Dev.Cell_51_387
PubMedID: 31543446

Title : Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium - Zhang_2019_Chemosphere_226_817
Author(s) : Zhang L , Chen L , Meng Z , Zhang W , Xu X , Wang Z , Qin Y , Deng Y , Liu R , Zhou Z , Diao J
Ref : Chemosphere , 226 :817 , 2019
Abstract : Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance.
ESTHER : Zhang_2019_Chemosphere_226_817
PubMedSearch : Zhang_2019_Chemosphere_226_817
PubMedID: 30965253

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 : Design, synthesis and evaluation of pterostilbene beta-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment - Zheng_2018_Bioorg.Chem_78_298
Author(s) : Zheng Y , Qiang X , Xu R , Song Q , Tian C , Liu H , Li W , Tan Z , Deng Y
Ref : Bioorg Chem , 78 :298 , 2018
Abstract : A series of pterostilbene beta-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50=24.04muM), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced Abeta1-42 aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Zheng_2018_Bioorg.Chem_78_298
PubMedSearch : Zheng_2018_Bioorg.Chem_78_298
PubMedID: 29625269

Title : Discovery of novel 2,5-dihydroxyterephthalamide derivatives as multifunctional agents for the treatment of Alzheimer's disease - Song_2018_Bioorg.Med.Chem_26_6115
Author(s) : Song Q , Li Y , Cao Z , Liu H , Tian C , Yang Z , Qiang X , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 26 :6115 , 2018
Abstract : A series of 2,5-dihydroxyterephthalamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives exhibited good multifunctional activities. Among them, compound 9d showed the best inhibitory activity against both RatAChE and EeAChE (IC50=0.56muM and 5.12muM, respectively). Moreover, 9d exhibited excellent inhibitory effects on self-induced Abeta1-42 aggregation (IC50=3.05muM) and Cu(2+)-induced Abeta1-42 aggregation (71.7% at 25.0muM), and displayed significant disaggregation ability to self- and Cu(2+)-induced Abeta1-42 aggregation fibrils (75.2% and 77.2% at 25.0muM, respectively). Furthermore, 9d also showed biometal chelating abilities, antioxidant activity, anti-neuroinflammatory activities and appropriate BBB permeability. These multifunctional properties highlight 9d as promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Song_2018_Bioorg.Med.Chem_26_6115
PubMedSearch : Song_2018_Bioorg.Med.Chem_26_6115
PubMedID: 30470598

Title : Evidence that microplastics aggravate the toxicity of organophosphorus flame retardants in mice (Mus musculus) - Deng_2018_J.Hazard.Mater_357_348
Author(s) : Deng Y , Zhang Y , Qiao R , Bonilla MM , Yang X , Ren H , Lemos B
Ref : J Hazard Mater , 357 :348 , 2018
Abstract : This study was performed to reveal the health risks of co-exposure to organophosphorus flame retardants (OPFRs) and microplastics (MPs). We exposed mice to polyethylene (PE) and polystyrene (PS) MPs and OPFRs [tris (2-chloroethy) phosphate (TCEP) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP)] for 90 days. Biochemical markers and metabolomics were used to determine whether MPs could enhance the toxicity of OPFRs. Superoxide dismutase (SOD) and catalase (CAT) increased (p<0.05) by 21% and 26% respectively in 10mug/L TDCPP+PE group compared to TDCPP group. Lactate dehydrogenase (LDH) in TDCPP+MPs groups were higher (18%-30%) than that in TDCPP groups (p<0.05). Acetylcholinesterase (AChE) in TCEP+PE groups were lower (10%-19%) than those in TCEP groups (p<0.05). These results suggested that OPFR co-exposure with MPs induced more toxicity than OPFR exposure alone. Finally, in comparison to controls we observed that 29, 41, 41, 26, 40 and 37 metabolites changed significantly (p<0.05; fold-change>1.2) in TCEP, TCEP+PS, TCEP+PE, TDCPP, TDCPP+PS and TDCPP+PE groups, respectively. Most of these metabolites are related to pathways of amino acid and energy metabolism. Our results indicate that MPs aggravate the toxicity of OPFRs and highlight the health risks of MP co-exposure with other pollutants.
ESTHER : Deng_2018_J.Hazard.Mater_357_348
PubMedSearch : Deng_2018_J.Hazard.Mater_357_348
PubMedID: 29908513

Title : Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease - Xu_2018_Bioorg.Med.Chem_26_1885
Author(s) : Xu R , Xiao G , Li Y , Liu H , Song Q , Zhang X , Yang Z , Zheng Y , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 26 :1885 , 2018
Abstract : A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50=0.29+/-0.01muM and 0.46+/-0.02muM, respectively), MAO-A (IC50=8.2+/-0.08muM and 7.9+/-0.07muM, respectively) and MAO-B (IC50=20.1+/-0.16muM and 43.8+/-2.0% at 10muM, respectively) inhibitory activities, moderate self-induced Abeta1-42 aggregation inhibitory potency (35.4+/-0.42% and 48.0+/-1.53% at 25muM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD.
ESTHER : Xu_2018_Bioorg.Med.Chem_26_1885
PubMedSearch : Xu_2018_Bioorg.Med.Chem_26_1885
PubMedID: 29500132

Title : Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation - Song_2018_Bioorg.Chem_84_137
Author(s) : Song Q , Li Y , Cao Z , Qiang X , Tan Z , Deng Y
Ref : Bioorg Chem , 84 :137 , 2018
Abstract : A series of salicylamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors. They showed good inhibitory activities of self- and Cu(2+)-induced Abeta1-42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4muM and 15.2muM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu(2+)-induced Abeta1-42 aggregation inhibitory potency (42.5% and 31.4% at 25.0muM, respectively) and moderate disaggregation ability to self- and Cu(2+)-induced Abeta1-42 aggregation fibrils (23.4% and 27.0% at 25muM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment.
ESTHER : Song_2018_Bioorg.Chem_84_137
PubMedSearch : Song_2018_Bioorg.Chem_84_137
PubMedID: 30500523

Title : Molecular cloning, characterization and expression analysis of two juvenile hormone esterase-like carboxylesterase cDNAs in Chinese mitten crab, Eriocheir sinensis - Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
Author(s) : Xu Y , Zhao M , Deng Y , Yang Y , Li X , Lu Q , Ge J , Pan J , Xu Z
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 205 :46 , 2017
Abstract : Precise regulation of methyl farnesoate (MF) titer is of prime importance throughout the crustacean life-cycle. Although the synthetic pathway of MF is well-documented, little is known about its degradation and recycling in crustaceans. Juvenile hormone esterase-like (JHE-like) carboxylesterase (CXE) is a key enzyme in MF degradation, thus playing a significant role in regulating the MF titer. We identified and characterized two cDNAs, Es-CXE1 and Es-CXE2, encoding JHE-like CXEs in Chinese mitten crab. Full-length cDNAs of Es-CXE1 and Es-CXE2 encode proteins composed of 584 and 597 amino acids, respectively, both of which contain a typical carboxylesterase domain. Alignment and phylogenetic analyses revealed that the Es-CXEs are highly similar to those of other crustaceans. To further validate their functions, we evaluated the mRNA expression patterns of the Es-CXEs in various tissues and in different physiological conditions. Tissue-specific expression analysis showed that the two Es-CXEs were predominantly expressed in the hepatopancreas and ovaries, which are the major tissues for MF metabolism. Es-CXE2 expression levels in the hepatopancreas and ovaries were about 100 and 25-fold higher, than the respective Es-CXE1 expressions. During ovarian rapid development stage, the global expressions of Es-CXEs were up-regulated in the hepatopancreas and down-regulated in the ovaries. After eyestalk ablation (ESA), the mRNA expressions of the two Es-CXEs were up-regulated in the hepatopancreas, further indicating their potential in degrading MF. Taken together, our results suggest that Es-CXEs, the key component of the juvenile hormone degradation pathway, may play vital roles in the development and reproduction of the Chinese mitten crab.
ESTHER : Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
PubMedSearch : Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
PubMedID: 28077333
Gene_locus related to this paper: erisi-a0a1l5jht6

Title : Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease - Sang_2017_Eur.J.Med.Chem_135_307
Author(s) : Sang Z , Qiang X , Li Y , Xu R , Cao Z , Song Q , Wang T , Zhang X , Liu H , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 135 :307 , 2017
Abstract : A series of scutellarein-O-acetamidoalkylbenzylamines derivatives were designed based on a multitarget-directed ligands strategy for the treatment of Alzheimer's disease. Among these compounds, compound T-22 demonstrated excellent acetylcholinesterase inhibitory, moderate inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils, and also acted as potential antioxidant and biometals chelator. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that T-22 interacted with both the catalytic active site and peripheral anionic site of AChE. Moreover, compound T-22 showed a good neuroprotective effect against H2O2-induced PC12 cell injury and low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated T-22 significantly reversed scopolamine-induced memory deficit in mice. Taken together, the data showed that T-22 was an interesting multifunctional lead compound worthy of further study for AD.
ESTHER : Sang_2017_Eur.J.Med.Chem_135_307
PubMedSearch : Sang_2017_Eur.J.Med.Chem_135_307
PubMedID: 28458136

Title : Multifunctional thioxanthone derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease - Luo_2017_Bioorg.Med.Chem_25_1997
Author(s) : Luo L , Li Y , Qiang X , Cao Z , Xu R , Yang X , Xiao G , Song Q , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 25 :1997 , 2017
Abstract : A series of 1-hydroxyl-3-aminoalkoxy-thioxanthone derivatives were designed, synthesized and evaluated as potential multifunctional agents against Alzheimer's disease (AD). The results indicated that most of these compounds exhibited good AChE and MAOs inhibitory activities, significant inhibition of self- and Cu2+-induced Abeta1-42 aggregation, and moderate to good antioxidant activities. Specifically, compound 9e displayed high inhibitory potency toward AChE (IC50=0.59+/-0.02muM), MAO-A and MAO-B (IC50=1.01+/-0.02muM and 0.90+/-0.01muM respectively), excellent efficiency to block both self- and Cu2+-induced Abeta1-42 aggregation (74.8+/-1.2% and 87.7+/-1.9% at 25muM, respectively), good metal-chelating property and a low toxicity in SH-SY5Y cells. Furthermore, kinetic and molecular modeling studies revealed that compound 9e binds simultaneously to the catalytic active site and peripheral anionic site of AChE, and could penetrate the BBB. Collectively, these results suggested that 9e might be a potential multifunctional agent for further development in the treatment of AD.
ESTHER : Luo_2017_Bioorg.Med.Chem_25_1997
PubMedSearch : Luo_2017_Bioorg.Med.Chem_25_1997
PubMedID: 28237559

Title : Multitarget drug design strategy against Alzheimer's disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties - Li_2017_Bioorg.Med.Chem_25_714
Author(s) : Li Y , Qiang X , Luo L , Yang X , Xiao G , Zheng Y , Cao Z , Sang Z , Su F , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 25 :714 , 2017
Abstract : A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC50=2.49+/-0.08nM and 1.74+/-0.0581muM, respectively), good self- and Cu2+-induced Abeta1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD.
ESTHER : Li_2017_Bioorg.Med.Chem_25_714
PubMedSearch : Li_2017_Bioorg.Med.Chem_25_714
PubMedID: 27923535

Title : Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer's disease - Yang_2017_Bioorg.Chem_71_305
Author(s) : Yang X , Qiang X , Li Y , Luo L , Xu R , Zheng Y , Cao Z , Tan Z , Deng Y
Ref : Bioorg Chem , 71 :305 , 2017
Abstract : A series of pyridoxine-resveratrol hybrids Mannich base derivatives as multifunctional agents have been designed, synthesized and evaluated for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activity. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and metal-chelating properties were also tested. The results showed that most of these compounds could selectively inhibit acetylcholinesterase (AChE) and MAO-B. Among them, compounds 7d and 8b exhibited the highest potency for AChE inhibition with IC50 values of 2.11muM and 1.56muM, respectively, and compound 7e exhibited the highest MAO-B inhibition with an IC50 value of 2.68muM. The inhibition kinetic analysis revealed that compound 7d showed a mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. Molecular modeling study was also performed to investigate the binding mode of these hybrids with MAO-B. In addition, all target compounds displayed good antioxidant and metal-chelating properties. Taken together, these preliminary findings can be a new starting point for further development of multifunctional agents for Alzheimer's disease.
ESTHER : Yang_2017_Bioorg.Chem_71_305
PubMedSearch : Yang_2017_Bioorg.Chem_71_305
PubMedID: 28267984

Title : Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Xiao_2017_Bioorg.Med.Chem_25_1030
Author(s) : Xiao G , Li Y , Qiang X , Xu R , Zheng Y , Cao Z , Luo L , Yang X , Sang Z , Su F , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 25 :1030 , 2017
Abstract : A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC50=4.91muM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Abeta1-42 aggregation and Cu2+-induced Abeta1-42 aggregation by 89.5% and 79.7% at 25muM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC50=0.29muM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease.
ESTHER : Xiao_2017_Bioorg.Med.Chem_25_1030
PubMedSearch : Xiao_2017_Bioorg.Med.Chem_25_1030
PubMedID: 28011206

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

Title : Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro - Bai_2016_Int.J.Biol.Macromol_96_214
Author(s) : Bai Y , Liu L , Zhang R , Huang F , Deng Y , Zhang M
Ref : Int J Biol Macromol , 96 :214 , 2016
Abstract : An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by beta-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function.
ESTHER : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedSearch : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedID: 27908719

Title : Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-beta-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease - Li_2016_Bioorg.Med.Chem.Lett_26_2035
Author(s) : Li Y , Qiang X , Yang X , Luo L , Xiao G , Cao Z , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :2035 , 2016
Abstract : A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Abeta1-42 aggregation and HuAChE-induced Abeta1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50=0.06muM) and good inhibition of BuChE (IC50=28.04muM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Abeta aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease.
ESTHER : Li_2016_Bioorg.Med.Chem.Lett_26_2035
PubMedSearch : Li_2016_Bioorg.Med.Chem.Lett_26_2035
PubMedID: 26947607

Title : Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-beta-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease - Li_2016_Eur.J.Med.Chem_126_762
Author(s) : Li Y , Qiang X , Luo L , Yang X , Xiao G , Liu Q , Ai J , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 126 :762 , 2016
Abstract : A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 +/- 0.0002 muM, 0.0212 +/- 0.006 muM and 0.0371 +/- 0.004 muM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Abeta1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.
ESTHER : Li_2016_Eur.J.Med.Chem_126_762
PubMedSearch : Li_2016_Eur.J.Med.Chem_126_762
PubMedID: 27951485

Title : Design, synthesis and evaluation of scutellarein-O-alkylamines as multifunctional agents for the treatment of Alzheimer's disease - Sang_2015_Eur.J.Med.Chem_94_348
Author(s) : Sang Z , Qiang X , Li Y , Yuan W , Liu Q , Shi Y , Ang W , Luo Y , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 94 :348 , 2015
Abstract : A series of scutellarein-O-alkylamine derivatives were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 16d demonstrated significant metal chelating properties, moderate acetylcholinesterase (AChE) inhibitory and anti-oxidative activity, and excellent inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that 16d binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Moreover, compound 16d showed a good protective effect against H2O2-induced PC12 cell injury, with low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Thus, 16d was shown to be an interesting multifunctional lead compound worthy of further study.
ESTHER : Sang_2015_Eur.J.Med.Chem_94_348
PubMedSearch : Sang_2015_Eur.J.Med.Chem_94_348
PubMedID: 25778991

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 : Design, synthesis and evaluation of chromone-2-carboxamido-alkylbenzylamines as multifunctional agents for the treatment of Alzheimer's disease - Liu_2015_Bioorg.Med.Chem_23_911
Author(s) : Liu Q , Qiang X , Li Y , Sang Z , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 23 :911 , 2015
Abstract : A series of chromone-2-carboxamido-alkylbenzylamines were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 49 displayed excellent inhibitory potency toward acetylcholinesterase (AChE), moderate anti-oxidative activity, selective biometal chelating, and possessed good inhibitory effects on self-induced and Cu(2+)-induced Abeta aggregation. Both kinetic analysis of AChE inhibition and molecular modeling study indicated that 49 was a mixed-type inhibitor, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. These results suggested that 49 might be a potential multifunctional agent for AD treatment.
ESTHER : Liu_2015_Bioorg.Med.Chem_23_911
PubMedSearch : Liu_2015_Bioorg.Med.Chem_23_911
PubMedID: 25678013

Title : Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease - Sang_2015_Chem.Biol.Drug.Des_86_1168
Author(s) : Sang ZP , Qiang XM , Li Y , Wu B , Zhang H , Zhao MG , Deng Y
Ref : Chemical Biology Drug Des , 86 :1168 , 2015
Abstract : A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 +/- 0.03 mum and 22.1 +/- 0.15 mum, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step-down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.
ESTHER : Sang_2015_Chem.Biol.Drug.Des_86_1168
PubMedSearch : Sang_2015_Chem.Biol.Drug.Des_86_1168
PubMedID: 25941042

Title : Association of endothelial lipase gene-384A\/C with coronary artery disease in Han Chinese people - Xie_2015_BMJ.Open_5_e007621
Author(s) : Xie L , Sun Y , Tong Y , Liu Y , Deng Y
Ref : BMJ Open , 5 :e007621 , 2015
Abstract : OBJECTIVES: The endothelial lipase gene (LIPG) is one of the important genes in the metabolism of high-density lipoprotein cholesterol (HDL-C) and may be involved in the pathogenesis of coronary artery disease (CAD). MATERIALS AND
METHODS: To investigate the relationship between the common single nucleotide polymorphisms (SNPs) 584C/T (rs2000813) and -384A/C (rs3813082) in the LIPG gene and CAD, allele and genotype frequencies of the two SNPs were analysed in 287 Chinese patients with CAD and 367 controls by the high-resolution melting curve (HRM) method.
RESULTS: For 584C/T, no significant difference in polymorphic distribution was observed between patients and controls. However, the frequencies of allele C (20.2% vs 15%, p=0.013, OR=1.437, 95% CI 1.078 to 1.915) at -384A/C were significantly increased in patients compared with controls. Haplotype analysis also showed that haplotype CT (12.37% vs 8.72%, p=0.035, OR=1.478, 95% CI 1.034 to 2.112) was significantly higher in patients compared with controls.
CONCLUSIONS: These results suggested that the SNP -384A/C in the LIPG gene may be associated with risk for CAD and the LIPG gene may play a role in CAD in the Han Chinese.
ESTHER : Xie_2015_BMJ.Open_5_e007621
PubMedSearch : Xie_2015_BMJ.Open_5_e007621
PubMedID: 26124511
Gene_locus related to this paper: human-LIPG

Title : Multifunctional scutellarin-rivastigmine hybrids with cholinergic, antioxidant, biometal chelating and neuroprotective properties for the treatment of Alzheimer's disease - Sang_2015_Bioorg.Med.Chem_23_668
Author(s) : Sang Z , Li Y , Qiang X , Xiao G , Liu Q , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , 23 :668 , 2015
Abstract : To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed ligand strategy. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metal-chelating properties and neuroprotective effects against hydrogen peroxide induced PC12 cell injury were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good multifunctional activities. In particular, compound 15c exhibited dual inhibitory potency on acetylcholinesterase and butyrylcholinesterase with IC50 values of 0.57 and 22.6muM, respectively, and good antioxidative activity, with a value 1.3-fold of Trolox. In addition, 15c acted as a selective biometal chelator and possessed neuroprotective effects. Furthermore, 15c could cross the blood-brain barrier (BBB) in vitro and had significant neuroprotective effects in scopolamine-induced cognitive impairment in mice. Taken together, these results suggest that compound 15c might be a potential multifunctional agent for the treatment of AD.
ESTHER : Sang_2015_Bioorg.Med.Chem_23_668
PubMedSearch : Sang_2015_Bioorg.Med.Chem_23_668
PubMedID: 25614117

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease - Qiang_2014_Eur.J.Med.Chem_76_314
Author(s) : Qiang X , Sang Z , Yuan W , Li Y , Liu Q , Bai P , Shi Y , Ang W , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 76C :314 , 2014
Abstract : A series of genistein derivatives with carbon spacer-linked alkylbenzylamines were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to-good anti-oxidative activity. Specifically, compounds 10b, 19d and 25d exhibited significant inhibition of beta-amyloid (Abeta) aggregation and exhibited metal chelating properties. In particular, 25d inhibited: self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, and human AChE-induced Abeta1-40 aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic analysis of AChE inhibition and the molecular modeling study suggested that 25d binds simultaneously to catalytic active site and peripheral anionic site of AChE. More importantly, compound 25d disassembled the well-structured Abeta fibrils generated by Cu2+-induced Abeta aggregation by 72.1%. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. These results suggest that 25d may be a promising multifunctional agent for AD treatment.
ESTHER : Qiang_2014_Eur.J.Med.Chem_76_314
PubMedSearch : Qiang_2014_Eur.J.Med.Chem_76_314
PubMedID: 24589487

Title : Isoflurane prevents neurocognitive dysfunction after cardiopulmonary bypass in rats - Li_2013_J.Cardiothorac.Vasc.Anesth_27_502
Author(s) : Li W , Zheng B , Xu H , Deng Y , Wang S , Wang X , Su D
Ref : J Cardiothorac Vasc Anesth , 27 :502 , 2013
Abstract : OBJECTIVE: Postoperative cognitive dysfunction occurs frequently after cardiac surgeries with cardiopulmonary bypass (CPB). Available data from rat CPB models are conflicting. However, none of them was designed to investigate the role of isoflurane (the main anesthetic in all of these studies) in the neurocognitive dysfunction after CPB. Isoflurane has documented neuroprotective effects so the present authors hypothesized that isoflurane prevents the neurocognitive dysfunction in rats after CPB. DESIGN: A prospective, interventional study. SETTING: A university research laboratory. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Male Sprague-Dawley rats were divided into 5 groups: the isoflurane CPB group, the animals were anesthetized with isoflurane and underwent 60 minutes of normothermic CPB; the chloral hydrate CPB group, the animals were anesthetized with chloral hydrate and underwent 60 minutes of normothermic CPB; the isoflurane sham group, the animals were subjected only to cannulation and the same duration of anesthesia but no CPB; the chloral hydrate sham group, the animals received only cannulation and the same duration of anesthesia but no CPB; and the naive group, the animals received no treatment. The neurocognitive function of all rats was measured on days 4 to 6 (short-term) and 31 to 33 after CPB (long-term). After the behavior tests, the animals were sacrificed, and the brain was harvested for the measurement of acetylcholinesterase (AChE) and choline acetyltransferase protein levels. MEASUREMENTS AND MAIN
RESULTS: Short-term (days 4-6 after CPB) learning and memory were impaired after CPB when the animals were anesthetized with chloral hydrate. When isoflurane was used, the learning and memory did not change after CPB. No long-term (days 31-33 after CPB) neurocognitive changes were found after CPB. AChE decreased significantly after isoflurane anesthesia regardless of whether CPB was performed.
CONCLUSIONS: Isoflurane prevented the neurocognitive dysfunction induced by CPB, which might involve the cerebral cholinergic system.
ESTHER : Li_2013_J.Cardiothorac.Vasc.Anesth_27_502
PubMedSearch : Li_2013_J.Cardiothorac.Vasc.Anesth_27_502
PubMedID: 23141628

Title : Complete genome sequence of Bacillus thuringiensis serovar finitimus strain YBT-020 - Zhu_2011_J.Bacteriol_193_2379
Author(s) : Zhu Y , Shang H , Zhu Q , Ji F , Wang P , Fu J , Deng Y , Xu C , Ye W , Zheng J , Zhu L , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2379 , 2011
Abstract : Bacillus thuringiensis is a gram-positive, spore-forming bacterium that forms parasporal crystals at the onset of the sporulation phase of its growth. Here, we report the complete genome sequence of B. thuringiensis serovar finitimus strain YBT-020, whose parasporal crystals consist of Cry26Aa and Cry28Aa crystal proteins and are located between the exosporium and the spore coat and remain adhering to the spore after sporulation.
ESTHER : Zhu_2011_J.Bacteriol_193_2379
PubMedSearch : Zhu_2011_J.Bacteriol_193_2379
PubMedID: 21398543
Gene_locus related to this paper: bacan-BA2392 , bacan-BA5009 , bacan-BA5110 , bacan-DHBF , bacce-BC2141 , bacce-BC4862 , bacce-BC5130 , bacce-BCE3188 , bacce-PHAC , bacce-q72yu1 , baccn-a7guq6 , baccr-pepx , bacce-c2qdt4

Title : Complete genome sequence of Bacillus subtilis BSn5, an endophytic bacterium of Amorphophallus konjac with antimicrobial activity for the plant pathogen Erwinia carotovora subsp. carotovora - Deng_2011_J.Bacteriol_193_2070
Author(s) : Deng Y , Zhu Y , Wang P , Zhu L , Zheng J , Li R , Ruan L , Peng D , Sun M
Ref : Journal of Bacteriology , 193 :2070 , 2011
Abstract : Here, we present the complete genome sequence of Bacillus subtilis strain BSn5, isolated from Amorphophallus konjac calli tissue and showing strong inhibitory activity to Erwinia carotovora subsp. carotovora, which causes Amorphophallus soft rot disease and affects the industry development of this organism.
ESTHER : Deng_2011_J.Bacteriol_193_2070
PubMedSearch : Deng_2011_J.Bacteriol_193_2070
PubMedID: 21317323
Gene_locus related to this paper: bacpu-pnbae , bacsu-CAH , bacsu-lip , bacsu-LIPB , bacsu-PPSE , bacsu-YBAC , bacsu-YDEN , bacsu-YTPA , bacsu-ytxm , bacsu-YVAK

Title : Integrated transcriptional and proteomic analysis with in vitro biochemical assay reveal the important role of CYP3A46 in T-2 toxin hydroxylation in porcine primary hepatocytes - Wang_2011_Mol.Cell.Proteomics_10_M111 008748
Author(s) : Wang J , Jiang J , Zhang H , Cai H , Li C , Li K , Liu J , Guo X , Zou G , Wang D , Deng Y , Dai J
Ref : Mol Cell Proteomics , 10 :M111 008748 , 2011
Abstract : Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3'-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions.
ESTHER : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedSearch : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedID: 21685020

Title : Cytokine modulation of muscarinic receptors in the murine intestine - Akiho_2007_Am.J.Physiol.Gastrointest.Liver.Physiol_293_G250
Author(s) : Akiho H , Khan WI , Al-Kaabi A , Blennerhassett P , Deng Y , Collins SM
Ref : American Journal of Physiology Gastrointest Liver Physiol , 293 :G250 , 2007
Abstract : The extent to which gut motility and smooth muscle contractility are altered by intestinal inflammation depends on the nature of the underlying immune activation. The muscarinic receptor on smooth muscle plays a critical role in mediating acetylcholine-driven motor function. We examined the ability of cytokines to influence muscarinic receptor characteristics on intestinal longitudinal muscle and related the findings to studies on carbachol-induced contraction. Cells were isolated from longitudinal muscle myenteric plexus (LMMP). Cytokine receptor expression, muscle contractility, and muscarinic agonist receptor characteristics were examined by agonist displacement of [N-methyl-(3)H]scopolamine ([(3)H]NMS) binding. The TGF-beta1 receptor (543 bp) and the IFN-gamma receptor 1 (660 bp) were identified on smooth muscle cells. Scatchard analysis revealed dissociation constant and maximum binding values for [(3)H]NMS of 2.6 nM and 2.4 x 10(4) sites/cell, respectively, in control cells. Nematode infection was accompanied by a reduction in inhibitory constant of the high-affinity sites (K(H)), and this was independent of signal transduction and activator of transcription 6. Preincubation with TGF-beta1 enhanced longitudinal muscle contractility and decreased the K(H) to 2.2 pM (increased muscarinic receptor affinity), whereas preincubation with IFN-gamma increased the K(H) to 0.4 muM (decreased muscarinic receptor affinity) and decreased longitudinal muscle contractility. Preincubation of LMMP with IL-13 decreased the K(H) to 0.2 nM. Cytokines exert differential effects on the muscarinic receptor on intestinal longitudinal smooth muscle. These findings explain the basis for altered muscle contractility observed in Th1 and Th2 models of inflammation, as well as in the post-nematode-infected state.
ESTHER : Akiho_2007_Am.J.Physiol.Gastrointest.Liver.Physiol_293_G250
PubMedSearch : Akiho_2007_Am.J.Physiol.Gastrointest.Liver.Physiol_293_G250
PubMedID: 17431212

Title : The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter - Zhang_2006_J.Biol.Chem_281_39159
Author(s) : Zhang J , Li F , Liu X , Shen L , Liu J , Su J , Zhang W , Deng Y , Wang L , Liu N , Han W , Ji S , Yang A , Han H , Yao L
Ref : Journal of Biological Chemistry , 281 :39159 , 2006
Abstract : The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.
ESTHER : Zhang_2006_J.Biol.Chem_281_39159
PubMedSearch : Zhang_2006_J.Biol.Chem_281_39159
PubMedID: 17050536

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Mechanisms underlying the maintenance of muscle hypercontractility in a model of postinfective gut dysfunction - Akiho_2005_Gastroenterology_129_131
Author(s) : Akiho H , Deng Y , Blennerhassett P , Kanbayashi H , Collins SM
Ref : Gastroenterology , 129 :131 , 2005
Abstract : BACKGROUND & AIMS: Acute gastroenteritis is a strong risk factor for the development of irritable bowel syndrome (IBS). We have developed an animal model in which transient acute infection leads to persistent muscle hypercontractility. Here, we investigate the mechanisms underlying the maintenance of this hypercontractility in the postinfective (PI) state.
METHODS: Muscle contraction and messenger RNA (mRNA) or protein expression of cytokines were examined from jejunal longitudinal muscle cells of NIH Swiss mice infected with Trichinella spiralis or incubated with or without cytokines.
RESULTS: During acute infection, interleukin (IL)-4 or IL-13, transforming growth factor (TGF)-beta1, and cyclooxygenase (COX)-2 were increased in the muscle layer ( P < .05). In the PI phase of the model, T helper (Th)2 cytokines returned to normal, but TGF-beta1 remained in the muscle ( P < .05). Exposure of muscle cells to IL-4 or IL-13 increased TGF-beta1 ( P < .01), COX-2 protein, and prostaglandin (PG)E 2 . Exposure of muscle cells to TGF-beta1 increased PGE 2 ( P < .05) and COX-2 protein. Incubation of tissue with IL-4, IL-13, TGF-beta1, or PGE 2 enhanced carbachol-induced muscle cell contractility ( P < .05). COX-2 inhibitor attenuated TGF-beta1-induced muscle hypercontractility ( P < .05).
CONCLUSIONS: These results support the hypothesis that Th2 cytokines induce muscle hypercontractility during infection by a direct action on smooth muscle. The maintenance of hypercontractility results from Th2 cytokine-induced expression of TGF-beta1 and the subsequent up-regulation of COX-2 and PGE 2 at the level of the smooth muscle cell. We propose that PI gut dysfunction reflects mediator production in the neuromuscular tissues and that this may occur in PI-IBS.
ESTHER : Akiho_2005_Gastroenterology_129_131
PubMedSearch : Akiho_2005_Gastroenterology_129_131
PubMedID: 16012943

Title : Interleukin-4- and -13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease - Akiho_2005_Am.J.Physiol.Gastrointest.Liver.Physiol_288_G609
Author(s) : Akiho H , Lovato P , Deng Y , Ceponis PJ , Blennerhassett P , Collins SM
Ref : American Journal of Physiology Gastrointest Liver Physiol , 288 :G609 , 2005
Abstract : Crohn's disease is an idiopathic inflammatory condition. However, little is known about the changes that occur in the muscularis externa, despite the fact that this tissue contributes to motility changes and stricture formation. We characterized immune activity in the muscularis externa from intestinal segments of Crohn's disease patients and evaluated the role of IL-4 and -13 as well as signal transducer and activator of transcription (STAT)6 in the contractility of the cultured human intestinal smooth muscle cells. CD3+ve cells (P < 0.01) and IL-4 protein (P < 0.01) were significantly increased in the muscularis externa of Crohn's disease patients compared with noninflamed controls. Preincubation of human cultured smooth muscle cells with IL-4 (P < 0.001) or IL-13 (P < 0.05) significantly enhanced carbachol-induced contraction, and this was significantly inhibited by the STAT6 inhibitor leflunomide (P < 0.0001). A similar profile was observed in muscle cells isolated from Crohn's disease patients. Both IL-4 and IL-13 increased specific STAT6-DNA binding in control cells, and this was inhibited by anti-STAT6 Ab (P < 0.05) or leflunomide (P < 0.05). IL-4 and IL-13 mediate the hypercontractility of intestinal muscle via a STAT6 pathway at the level of the smooth muscle cell. The STAT6 pathway may contribute to the hypercontractility of intestinal muscle in Crohn's disease.
ESTHER : Akiho_2005_Am.J.Physiol.Gastrointest.Liver.Physiol_288_G609
PubMedSearch : Akiho_2005_Am.J.Physiol.Gastrointest.Liver.Physiol_288_G609
PubMedID: 15528258

Title : Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells - Akiho_2002_Am.J.Physiol.Gastrointest.Liver.Physiol_282_G226
Author(s) : Akiho H , Blennerhassett P , Deng Y , Collins SM
Ref : American Journal of Physiology Gastrointest Liver Physiol , 282 :G226 , 2002
Abstract : T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 -/- mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 -/- mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (R(max) 26.7 +/- 1.9%). Cells from T. spiralis-infected STAT6 -/- mice showed the hypertrophy (cell lengths 41.4 +/- 0.8 to 89.0 +/- 8.7 microm) and hypercontractility (R(max) 37.5 +/- 1.3%) induced by infection. IL-4Ralpha mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (R(max) 35.5 +/- 1.9 and 32.4 +/- 2.9%, respectively). Incubation of LMMP from STAT6 -/- mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 -/- mice (P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.
ESTHER : Akiho_2002_Am.J.Physiol.Gastrointest.Liver.Physiol_282_G226
PubMedSearch : Akiho_2002_Am.J.Physiol.Gastrointest.Liver.Physiol_282_G226
PubMedID: 11804843

Title : IL-5 contributes to worm expulsion and muscle hypercontractility in a primary T. spiralis infection - Vallance_1999_Am.J.Physiol_277_G400
Author(s) : Vallance BA , Blennerhassett PA , Deng Y , Matthaei KI , Young IG , Collins SM
Ref : American Journal of Physiology , 277 :G400 , 1999
Abstract : Enteric nematode infections lead to increased interleukin (IL)-5 expression, eosinophilic inflammation, and intestinal smooth muscle hypercontractility. Although eosinophils release inflammatory mediators that cause smooth muscle contraction, the role of IL-5 and eosinophils in enteric smooth muscle hypercontractility is unclear. IL-5-deficient mice and their wild-type controls were infected with the nematode Trichinella spiralis. Intestinal parasites and eosinophils were counted, and jejunal longitudinal muscle contractility was assessed. During infection, IL-5 gene expression increased significantly in wild-type mice and was accompanied by significant intestinal eosinophilia in wild-type but not IL-5-deficient mice. Although both strains developed increased muscle contractility during infection, contraction was significantly less in the IL-5-deficient mice at days 16 and 21 postinfection. In addition, parasite expulsion was transiently delayed at day 16 in IL-5-deficient mice. Thus, in the nematode-infected mouse, IL-5 appears essential for intestinal eosinophilia and contributes to, but is not essential for, the development of muscle hypercontractility. IL-5 also appears to play a minor role in expelling a primary T. spiralis infection from the gut.
ESTHER : Vallance_1999_Am.J.Physiol_277_G400
PubMedSearch : Vallance_1999_Am.J.Physiol_277_G400
PubMedID: 10444455