Chen M

References (100)

Title : Upconversion fluorescence nanosensor based on enzymatic inhibited and copper-triggered o-phenylenediamine oxidation for the detection of dimethoate pesticides - Li_2024_Food.Chem_453_139666
Author(s) : Li S , Zhang S , Wu J , Khan IM , Chen M , Jiao T , Wei J , Chen X , Chen Q
Ref : Food Chem , 453 :139666 , 2024
Abstract : Pesticide residues in agricultural products pose a significant threat to human health. Herein, a sensitive fluorescence method employing upconversion nanoparticles was developed for detecting organophosphorus pesticides (OPs) based on the principle of enzyme inhibition and copper-triggered o-phenylenediamine (OPD) oxidation. Copper ions (Cu(2+)) oxidized the colorless OPD to a yellow 2,3-diaminophenazine (oxOPD). The yellow solution oxOPD quenched the fluorescence of upconversion nanoparticles due to the fluorescence resonance energy transfer. The high affinity of Cu(2+) for thiocholine reduced the level of oxOPD, resulting in almost no fluorescence quenching. The addition of dimethoate led to the inhibition of acetylcholinesterase activity and thus prevented the formation of thiocholine. Subsequently, Cu(2+) oxidized OPD to form oxOPD, which attenuated the fluorescence signal of the system. The detection system has a good linear range of 0.01 ng/mL to 50 ng/mL with a detection limit of 0.008 ng/mL, providing promising applications for rapid detection of dimethoate.
ESTHER : Li_2024_Food.Chem_453_139666
PubMedSearch : Li_2024_Food.Chem_453_139666
PubMedID: 38759443

Title : Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial - Guo_2024_Diabetes.Obes.Metab__
Author(s) : Guo L , Tian F , Liu L , Chen M , Jiang C , Li S , Liu C , Zhang Y , Qin J , Yu D , Zong Y , Dai W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
ESTHER : Guo_2024_Diabetes.Obes.Metab__
PubMedSearch : Guo_2024_Diabetes.Obes.Metab__
PubMedID: 38602409

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer - Chen_2024_J.Transl.Med_22_249
Author(s) : Chen M , Zhang C , Li H , Zheng S , Li Y , Yuan M , Chen Y , Wu J , Sun Q
Ref : J Transl Med , 22 :249 , 2024
Abstract : BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.
ESTHER : Chen_2024_J.Transl.Med_22_249
PubMedSearch : Chen_2024_J.Transl.Med_22_249
PubMedID: 38454407

Title : Metformin inhibits OCTN1- and OCTN2-mediated hepatic accumulation of doxorubicin and alleviates its hepatotoxicity in mice - Chen_2024_Toxicology__153757
Author(s) : Chen M , Yi Y , Chen B , Zhang H , Dong M , Yuan L , Zhou H , Jiang H , Ma Z
Ref : Toxicology , :153757 , 2024
Abstract : Doxorubicin (DOX) is a widely used antitumor agent; however, its clinical application is limited by dose-related organ damage. Because organic cation/carnitine transporters (OCTN1 and OCTN2), which are critical for DOX uptake, are highly expressed in hepatocytes, we aimed to elucidate the role of these transporters in hepatic DOX uptake. The results indicated that inhibitors and RNA interference both significantly reduced DOX accumulation in HepG2 and HepaRG cells, suggesting that OCTN1/2 contribute substantially to DOX uptake by hepatocytes. To determine whether metformin (MET, an inhibitor of OCTN1 and OCTN2) ameliorates DOX-induced hepatotoxicity, we conducted in vitro and in vivo studies. MET (1-100microM) inhibited DOX (500nM) accumulation and cytotoxicity in vitro in a concentration-dependent manner. Furthermore, intravenous MET administration at 250 or 500mg/kg or by gavage at 50, 100, or 200mg/kg reduced DOX (8mg/kg) accumulation in a dose-dependent manner in the mouse liver and attenuated the release of alanine aminotransferase, aspartate aminotransferase, and carboxylesterase 1. Additionally, MET reduced the distribution of DOX in the heart, liver, and kidney and enhanced the urinary elimination of DOX; however, it did not increase the nephric toxicity of DOX. In conclusion, our study demonstrated that MET alleviates DOX hepatotoxicity by inhibiting OCTN1- and OCTN2-mediated DOX uptake in vitro (mouse hepatocytes and HepaRG or HepG2 cells) and in mice.
ESTHER : Chen_2024_Toxicology__153757
PubMedSearch : Chen_2024_Toxicology__153757
PubMedID: 38364893

Title : Pyridostigmine attenuated high-fat-diet induced liver injury by the reduction of mitochondrial damage and oxidative stress via alpha7nAChR and M3AChR - Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
Author(s) : Xue R , Wu Q , Guo L , Ye D , Cao Q , Zhang M , Xian Y , Chen M , Yan K , Zheng J
Ref : J Biochem Mol Toxicol , 38 :e23671 , 2024
Abstract : Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-alpha, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H(2) O(2) levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the alpha7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via alpha7nAChR and M3AChR.
ESTHER : Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
PubMedSearch : Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
PubMedID: 38454809

Title : Immobilization of Thermomyces lanuginosus lipase in a novel polysaccharide-based hydrogel by a two-step crosslinking method and its use in the lauroylation of alpha-arbutin - Chen_2024_Bioresour.Bioprocess_11_7
Author(s) : Chen M , She W , Zhao X , Chen C , Zhu B , Sun Y , Yao Z
Ref : Bioresour Bioprocess , 11 :7 , 2024
Abstract : The Thermomyces lanuginosus lipase (TLLs) was successfully immobilized within a novel hydrogel matrix through a two-step crosslinking method. TLLs were initially crosslinked through the Schiff base reaction by oxidized carboxymethyl cellulose (OCMC). The water-soluble OCMC@TLLs complex was subsequently crosslinked by carboxymethyl chitosan (CMCSH) in a microfluidic apparatus to form the CMCHS/OCMC@TLLs microspheres. The CD (Circular Dichroism, CD) and FT-IR (Fourier Transform infrared spectroscopy, FT-IR) spectra demonstrated that the crosslinking of TLLs with OCMC resulted in a less significant impact on their structure compared to that with glutaraldehyde. CMCHS/OCMC@TLLs showed decreased catalytic performance due to the mass transfer resistance, while its thermal stability was greatly improved. The CMCHS/OCMC@TLLs were used to catalyze the lauroylation of arbutin in tetrahydrofuran. After 12 h of reaction under optimal conditions, the yield of 6'-O-lauryl arbutin reached an impressive 92.12%. The prepared 6'-O-lauryl arbutin has high lipophilicity and exhibits similar tyrosinase inhibitory activity and higher antioxidant activity compared to its parent compound.
ESTHER : Chen_2024_Bioresour.Bioprocess_11_7
PubMedSearch : Chen_2024_Bioresour.Bioprocess_11_7
PubMedID: 38647918

Title : Immobilization of Candida antarctica lipase B on ILs modified CNTs with different chain lengths: Regulation of substrate tunnel Leucine gating - Lu_2023_Int.J.Biol.Macromol_248_125894
Author(s) : Lu Z , Chen M , Jin T , Nian B , Hu Y
Ref : Int J Biol Macromol , 248 :125894 , 2023
Abstract : Ionic liquids (ILs) have been widely used as chemical modifiers to modify the carriers and thus improve the efficiency, activity and stability of the enzymes. However, as thousands of ILs have been found up to date, it's a huge work for screening and designing suitable ILs for immobilization of enzymes. Moreover, the mechanism of improving enzymes catalytic performance is still remain ambiguous. Thus, this study investigated the impact of ILs with different chain lengths on the enzymatic properties of Candida antarctica lipase B (CALB). Molecular dynamics simulations were employed to examine the interaction between ILs modified CNTs and CALB, as well as their effects on CALB's structure. The results revealed that ILs with different chain lengths significantly influenced the absorption orientation of CALB. Tunnel analysis identified a key role for Leu278 in regulating the open or closed state of Tunnel 2 during CALB's catalytic cycle. The weak interaction analysis demonstrated that ILs with suitable chain lengths provided spatial freedom and formed strong interactions with CNTs and ILs (vdW and hbond). This led to a conformational flip of Leu278, stabilizing the open state of Tunnel 2 and improving the activity and stability of immobilized CALB. This study provides novel insights into the design of new green modifiers to modulate carrier performance and obtain immobilized enzymes with better performance, and establishes a theoretical basis for the design and selection of modifiers for ILs in future work.
ESTHER : Lu_2023_Int.J.Biol.Macromol_248_125894
PubMedSearch : Lu_2023_Int.J.Biol.Macromol_248_125894
PubMedID: 37479200

Title : Heterologous Production of the C33-C45 Polyketide Fragment of Anticancer Apratoxins in a Cyanobacterial Host - Dhakal_2023_Org.Lett_25_2238
Author(s) : Dhakal D , Kallifidas D , Chen M , Kokkaliari S , Chen QY , Paul VJ , Ding Y , Luesch H
Ref : Org Lett , 25 :2238 , 2023
Abstract : A polyketide synthase subcluster of cytotoxic apratoxin A was isolated from a Moorena bouillonii environmental DNA library and engineered with a thioesterase II domain for heterologous expression in the filamentous cyanobacterium Anabaena sp. PCC7120. Further engineering with a rhamnose-inducible promoter led to the production of (2R,3R,5R,7R)-3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid, a stereogenically rich chiral building block that is important to the efficient synthesis of apratoxin analogues, representing the first synthetic biology attempt for this type of polyketide fragment.
ESTHER : Dhakal_2023_Org.Lett_25_2238
PubMedSearch : Dhakal_2023_Org.Lett_25_2238
PubMedID: 36961224

Title : Identification, expression profiles and involvement in insecticides tolerance and detoxification of carboxylesterase genes in Bactrocera dorsalis - Li_2023_Pestic.Biochem.Physiol_193_105443
Author(s) : Li Z , Chen M , Bai W , Zhang S , Meng L , Dou W , Wang J , Yuan G
Ref : Pestic Biochem Physiol , 193 :105443 , 2023
Abstract : Carboxylesterases (CarEs) are a multifunctional superfamily of enzymes and play an important role in detoxification of various insecticides in insects. The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive agricultural pests and has developed different degrees of resistance to organophosphates in field. However, the involvement of BdCarEs in tolerance or resistance to other alternative insecticides are still unclear. In the present study, 33 BdCarEs genes were identified based on the genome database of B. dorsalis. Phylogenetic analysis demonstrated that they were classified into nine clades, with abundance of alpha-esterases. Meanwhile, the sequence characterization and the chromosome distribution were also analyzed. The spatiotemporal expression analysis of BdCarEs genes suggested that the diversity of potential function in different physiological processes. With the exception of BdCarE21, all BdCarEs genes responded to at least one insecticide exposure, and BdCarE20 was found to be up-regulated after exposure to all five tested insecticides individually. Eight BdCarEs genes were overexpressed in MR strain when compared to that in SS strain. Subsequently, knockdown the expression of representative BdCarEs genes significantly increased the susceptibility of the oriental fruit fly to corresponding insecticides, which indicated that the tested BdCarEs genes contributed to one or multiple insecticide detoxification. These findings provide valuable insights into the potential role in respond to tolerance or resistance to insecticides with different mode of action, and will facilitate development of efficiency management strategy for B. dorsalis.
ESTHER : Li_2023_Pestic.Biochem.Physiol_193_105443
PubMedSearch : Li_2023_Pestic.Biochem.Physiol_193_105443
PubMedID: 37248012

Title : MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain - Gu_2023_Mol.Med.Rep_27_
Author(s) : Gu C , Chen M , Li X , Geng D , Wang C
Ref : Mol Med Rep , 27 : , 2023
Abstract : Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces antiinflammatory and antinociceptive effects. However, the potential mechanism of MAGL in OA pain remains unclear. In the present study, the synovial tissues were removed from OA patients and mice. Immunohistochemical staining and western blotting were used to detect the expression of MAGL. M1 and M2 polarization markers were detected by flow cytometry and western blotting, and the mitophagy levels were detected by the immunofluorescence staining of mitochondrial autophagosomes with lysosomes and western blotting. The OA mice were intraperitoneally injected with MJN110 to inhibit MAGL once a day for a week. Mechanical and thermal pain thresholds were detected by electronic Von Frey and hot plate methods on days 0, 3, 7, 10, 14, 17, 21, and 28. The accumulation of MAGL in the synovial tissues of OA patients and mice promoted the polarization of macrophages towards an M1 phenotype. Pharmacological inhibition and siRNA knockdown of MAGL promoted polarization of M1 macrophages towards an M2 phenotype. MAGL inhibition increased the mechanical and thermal pain thresholds of OA mice and enhanced the mitophagy levels of M1 macrophages. In conclusion, in the present study, it was shown that MAGL regulated synovial macrophage polarization by inhibiting mitophagy in OA.
ESTHER : Gu_2023_Mol.Med.Rep_27_
PubMedSearch : Gu_2023_Mol.Med.Rep_27_
PubMedID: 37144506

Title : CES1-Triggered Liver-Specific Cargo Release of CRISPR\/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration - Zhao_2023_Adv.Sci.(Weinh)__e2300502
Author(s) : Zhao Y , Li Y , Wang F , Gan X , Zheng T , Chen M , Wei L , Chen J , Yu C
Ref : Adv Sci (Weinh) , :e2300502 , 2023
Abstract : The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA). The copolymer can self-assemble with Cas9-mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG-b-P(Met/n-PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low-density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed-point release, which expand the application of CRISPR delivery systems.
ESTHER : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedSearch : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedID: 37083231

Title : Ionic liquid modification reshapes the substrate pockets of lipase to boost its stability and activity in Vitamin E succinate synthesis - Ma_2023_J.Sci.Food.Agric__
Author(s) : Ma G , Zhang Z , Chen M , Zhang Y , Nian B , Hu Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: The relative low stability, reusability and activity of enzymes made the industrial production of Vitamin E succinate (VES) can only be performed with complex processes and high cost using chemical methods. To address these issues, herein, an ionic liquids (ILs) modification strategy was developed to improve the activity and stability of lipases in VES synthesis in this study. RESULTS: The results showed that the [1-Butyl-3-Methyl Imidazole] [N-Acetyl-L-Proline] ILs modified Candida rugosa lipase (CRL) has the highest modification degree (48.28 %), activity (774 U/g), thermostability, solvent tolerance in three selected modifiers. Additionally, after reaction condition optimization, the highest yield of VES can be improved to 95.18% at 45 degreesC for 15 h, which was significantly improved compared to some previous studies. CONCLUSION: In this study, a high-efficiency VES synthesis strategy was successfully developed via modification of lipase. Moreover, the mechanism in which the ILs modification can enhance the activity and stability of lipase was investigated via both experimental and computational-aided methods. Molecular dynamics simulation suggested that ILs modification changed the geometry of Phe344 from flat to upright, which significantly reshaped and enhanced the size of substrate binding pocket of CRL. It is also agreement with our circular dichroism (CD) and fluorescence spectroscopy results which suggested that the modification changed the secondary structure of CRL to a certain extent. The larger pocket also endowed the suitable binding pose of succinate, which made the hydrogen bonds between succinate and active site Ser209 become stronger, and thus improving the yield of VES. This article is protected by copyright. All rights reserved.
ESTHER : Ma_2023_J.Sci.Food.Agric__
PubMedSearch : Ma_2023_J.Sci.Food.Agric__
PubMedID: 37994149

Title : Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling - Chen_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2304900120
Author(s) : Chen M , Shin M , Ware TB , Donvito G , Muchhala KH , Mischel R , Mustafa MA , Serbulea V , Upchurch CM , Leitinger N , Akbarali HI , Lichtman AH , Hsu KL
Ref : Proc Natl Acad Sci U S A , 120 :e2304900120 , 2023
Abstract : Diacylglycerol lipase-beta (DAGLbeta) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLbeta ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLbeta in primary macrophages leads to LKB1-AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLbeta blockade, thereby directly supporting DAGLbeta-AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.
ESTHER : Chen_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2304900120
PubMedSearch : Chen_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2304900120
PubMedID: 38109529

Title : Phytochemical Analysis, Antioxidant and Enzyme-Inhibitory Activities, and Multivariate Analysis of Insect Gall Extracts of Picea koraiensis Nakai - Wang_2023_Molecules_28_
Author(s) : Wang Y , Sun H , He X , Chen M , Zang H , Liu X , Piao H
Ref : Molecules , 28 : , 2023
Abstract : Picea koraiensis Nakai (PK) is an evergreen tree. It plays an important role in landscaping and road greening. Insect galls of PK are formed by parasitism of the adelgid Adelges laricis. Except for phenolics, other chemical constituents and biological activity of insect gall from PK are still unknown. Thus, here, we performed phytochemical and biological activity analyses of PK insect gall extracts, aiming to turn waste into treasure and serve human health. PK insect gall extracts were prepared using seven solvents. Antioxidant activities of the extracts were examined via antioxidant assays (radical and oxidizing substance quenching, metal chelating, and reducing power). The inhibitory activities of the extracts were determined toward the key human-disease-related enzymes alpha-glucosidase, alpha-amylase, cholinesterase, tyrosinase, urease, and xanthine oxidase. The content of numerous active constituents was high in the methanol and ethanol extracts of PK insect gall, and these extracts had the highest antioxidant and enzyme-inhibitory activities. They also showed excellent stability and low toxicity. These extracts have potential for use as stabilizers of olive and sunflower seed oils.
ESTHER : Wang_2023_Molecules_28_
PubMedSearch : Wang_2023_Molecules_28_
PubMedID: 37630273

Title : Responses and detoxification mechanisms of earthworm Amynthas hupeiensis to metal contaminated soils of North China - Liu_2023_Environ.Pollut__121584
Author(s) : Liu Y , Chen M , Mu X , Wang X , Zhang M , Yin Y , Wang K
Ref : Environ Pollut , :121584 , 2023
Abstract : Metal contamination is widespread, but only a few studies have evaluated the toxicological risks of metals (Cd, Cu, and Pb) in earthworms from farmlands in North China (Hebei province). Amynthas hupeiensis, the dominant species in the study area, was used to determine the responses and detoxification mechanisms of uncontaminated (CK), and low (LM)-, and high (HM)-metal-contaminated soils following 7-, 14-, and 28-days exposure. Metal toxicity in LM and HM soils inhibited the biomass of A. hupeiensis. The concentrations of Cd in A. hupeiensis bodies indicated accumulated Cd appeared to remain steady with prolonged exposure, while Cu/Pb increased significantly with soil levels. Bioaccumulation occurred in the order Cd > Pb > Cu in LM soil, and in the order Cd > Cu = Pb in HM soil, which was attributed to differences in available fractions between LM and HM soils. Physiological levels of biomarkers in A. hupeiensis were determined, including total protein (TP), glutathione (GSH), glutathione peroxidase (GPx), acetylcholinesterase (AChE), and malondialdehyde (MDA). Deviations in GSH, GPx, and AChE were considered to denote sensitive biomarkers using the IBRv2 index. Metabolomics data ((1)H nuclear magnetic resonance-based) revealed changes in metabolites following 28-days exposure to LM and HM soils. Differences in metabolism in A. hupeiensis following exposure to LM and HM were related to energy metabolism, amino acid biosynthesis, glycerophospholipid metabolism, inositol phosphate metabolism, and glutathione metabolism. Metal stress from LM and HM soils disturbed osmoregulation, resulting in oxidative stress, destruction of cell membranes and inflammation, and altered levels of amino acids required for energy by A. hupeiensis. These findings provide biochemical insights into the physiological and metabolic mechanisms underlying the ability of A. hupeiensis to resist metal stress, and for assessing the environmental risks of metal-contaminated soils in farmland in North China.
ESTHER : Liu_2023_Environ.Pollut__121584
PubMedSearch : Liu_2023_Environ.Pollut__121584
PubMedID: 37037277

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

Title : Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study - Jiang_2023_Reprod.Biol.Endocrinol_21_97
Author(s) : Jiang C , Chen M , Wu Y , Bai H , Liu X , Fan P
Ref : Reprod Biol Endocrinol , 21 :97 , 2023
Abstract : BACKGROUND: Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. METHODS: This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. RESULTS: Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. CONCLUSIONS: Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.
ESTHER : Jiang_2023_Reprod.Biol.Endocrinol_21_97
PubMedSearch : Jiang_2023_Reprod.Biol.Endocrinol_21_97
PubMedID: 37885002

Title : Brain Region Differences in alpha1- and alpha5-Subunit-Containing GABA(A) Receptor Proteomes Revealed with Affinity Purification and Blue Native PAGE Proteomics - Chen_2023_Cells_13_
Author(s) : Chen M , Koopmans F , Gonzalez-Lozano MA , Smit AB , Li KW
Ref : Cells , 13 : , 2023
Abstract : GABA(A) receptors are the major inhibitory receptors in the brain. They are hetero-pentamers with a composition of predominantly two alpha, two beta, and one gamma or delta subunit. Of the six alpha subunit genes, the alpha5 subunit displays a limited spatial expression pattern and is known to mediate both phasic and tonic inhibition. In this study, using immunoaffinity-based proteomics, we identified the alpha5 subunit containing receptor complexes in the hippocampus and olfactory bulb. The alpha1-alpha5 interaction was identified in both brain regions, albeit with significantly different stoichiometries. In line with this, reverse IPs using anti-alpha1 antibodies showed the alpha5-alpha1 co-occurrence and validated the quantitative difference. In addition, we showed that the association of Neuroligin 2 with alpha1-containing receptors was much higher in the olfactory bulb than in the hippocampus, which was confirmed using blue native gel electrophoresis and quantitative mass spectrometry. Finally, immunocytochemical staining revealed a co-localization of alpha1 and alpha5 subunits in the post-synaptic puncta in the hippocampus.
ESTHER : Chen_2023_Cells_13_
PubMedSearch : Chen_2023_Cells_13_
PubMedID: 38201218

Title : Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis - Ang_2023_Molecules_28_
Author(s) : Ang S , Liang J , Zheng W , Zhang Z , Li J , Yan Z , Wong WL , Zhang K , Chen M , Wu P
Ref : Molecules , 28 : , 2023
Abstract : A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC(50) values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 microg/mL, respectively, whereas the LC(50) value of MA was 659.34 microg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 microg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.
ESTHER : Ang_2023_Molecules_28_
PubMedSearch : Ang_2023_Molecules_28_
PubMedID: 37049799

Title : In-situ preparation of hollow CdCoS(2) heterojunction with enhanced photocurrent response for highly photoelectrochemical sensing of organophosphorus pesticides - Zheng_2022_Anal.Chim.Acta_1212_339913
Author(s) : Zheng D , Chen M , Chen Y , Gao W
Ref : Anal Chim Acta , 1212 :339913 , 2022
Abstract : In this study, a porous hollow CdCoS(2)(2) microsphere was synthesized based on the ZIF-67-S MOFs derived method of sulfurization reaction and calcination process. Under visible light irradiation, the resulting CdCoS(2)(2) composite showed a markedly enhanced photoelectrochemical (PEC) response. The photocurrent value of the CdCoS(2)(2) modified ITO electrode was 93-fold and 41-fold than that of CoS and CdS materials, respectively. Promoting the photo-absorption ability by internal multilight scattering/reflection was due to the porous and hollow nature of CdCoS(2)(2). Furthermore, obtained CdCoS(2)(2) heterostructure in-situ with a close contact interface could facilitate the separation/migration of photo-induced carriers. The CdCoS(2)(2) was also mixed with Ag nanoparticles (NPs) to further improve the PEC response. Acetylcholinesterase (AChE) as a bio-recognition molecule was immobilized on the glutaraldehyde-chitosan (GLD-CS) modified CdCoS(2)(2)@Ag electrode surface by cross-linking effect. AChE could hydrolyze the acetylcholine chloride (ATCl) to produce an electron donor of thiocholine which led to the elevated photocurrent output. When the bioactivity of AChE was inhibited by the organophosphate pesticides (chlorpyrifos as substrate), the reduced production of thiocholine resulted in a decline in photocurrent. Under optimal conditions, the structured AChE/GLD-CS/CdCoS(2)(2)@Ag/ITO sensing platform was successfully achieved for chlorpyrifos detection. The wide linear response range was from 0.001 to 270 microg mL(-1) and with a low detection limit of 0.57 ng mL(-1). The proposed PEC biosensor also exhibited excellent selectivity and good stability, demonstrating the designed porous hollow CdCoS(2)(2)@Ag heterostructured composite promised to be a great application in the PEC sensors.
ESTHER : Zheng_2022_Anal.Chim.Acta_1212_339913
PubMedSearch : Zheng_2022_Anal.Chim.Acta_1212_339913
PubMedID: 35623791

Title : Anti-human Glioma Cancer Potentials of Neobavaisoflavone as Natural Antioxidant Compound and Its Inhibition Profiles for Acetylcholinesterase and Butyrylcholinesterase Enzymes with Molecular Modeling and Spin Density Distributions Studies - Chen_2022_J.Oleo.Sci_71_277
Author(s) : Chen M , Zhao H , Cheng Y , Wang L , Alotaibi SH , Zhang Y
Ref : J Oleo Sci , 71 :277 , 2022
Abstract : In this study, the carcinogenic potential of Neobavaisoflavone as a natural antioxidant compound and the inhibitory profiles of acetylcholinesterase and butyrylcholinesterase were investigated by molecular modeling and spin density distribution studies. To evaluate the antioxidant properties of neobavaisoflavone, DPPH test was performed in the presence of butyl hydroxytoluene as a control. Neobavaisoflavone cell viability was low compared to normal human glioma cancer cell lines, namely LN-229, U-87 and A-172 cell lines, without any effect of cytotoxicity on normal cell line. Neobavaisoflavone inhibited half of DPPH at 125 microg/mL. The best effects of Neobavaisoflavone antihypertensive glioma against the above cell lines were in the LN-229 cell line. In addition, the significant anti-cancer potential of human glioma Neobavaisoflavone against the popular human glioma cancer cell lines is related in this study. IC(50) values were calculated by Neobavaisoflavone diagrams, 63.87 nM for AChE and 112.98 nM for BuChE, % Activity- [Inhibitor]. According to the above results, Neobavaisoflavone can be used to treat a variety of human glioma cancers in humans. In addition, molecular modeling calculations were performed to compare the biochemical activities of the Neobavaisoflavone molecule with enzymes. After molecular insertion calculations, ADME/T analysis was performed to investigate the properties of the neobavaisoflavone molecule, which will be used as a drug in the future. Then, different parameters for the antioxidant activity of the neobavaisoflavone molecule were calculated.
ESTHER : Chen_2022_J.Oleo.Sci_71_277
PubMedSearch : Chen_2022_J.Oleo.Sci_71_277
PubMedID: 35110469

Title : Phytochemical profiling and antioxidant, enzyme-inhibitory, and toxic activities of extracts from Adonis ramosa Franch - Guo_2022_Nat.Prod.Res__1
Author(s) : Guo X , Chen M , He X , Zhao Y , Yu J , Zhu J , Li L , Xia G , Zang H
Ref : Nat Prod Res , :1 , 2022
Abstract : This study investigated the content and biological activity of three solvent extracts of Adonis ramosa Franch (AR), which contains 12 types of phytochemicals. The overall yield and total protein content of the aqueous extract were the highest, and it exhibited the highest hydroxyl and superoxide radical-scavenging abilities, copper chelating abilities, and cupric reducing antioxidant capacity. Ethanol extract had the highest total phenolic, flavonoid, and carbohydrate contents, and it showed the highest iron chelating activity, and HClO- and nitrite-scavenging abilities. Methanol AR extract contained the highest total steroid and tannin contents; it also demonstrated high radical- and reactive oxygen species-scavenging abilities and had the best ferric reducing antioxidant power, which allowed it to effectively prevent beta-carotene bleaching. Methanol extract also showed good stability and low toxicity. All tested solvent extracts of AR exhibited weak enzyme-inhibitory activities for four enzymes (alpha-glucosidase, alpha-amylase, acetylcholinesterase and butyrylcholinesterase). Overall, AR can serve as a natural antioxidant.
ESTHER : Guo_2022_Nat.Prod.Res__1
PubMedSearch : Guo_2022_Nat.Prod.Res__1
PubMedID: 35045779

Title : Influence of ligand geometry on cholinesterase enzyme - A comparison of 1-isoindolinone based structural analog with Donepezil - Upadhyay_2022_J.Mol.Struct_1247_
Author(s) : Upadhyay SP , Singh V , Sharma R , Zhou J , Thapa P , Johnson DK , Keightley A , Chen M , Suo W , Sharma M
Ref : J Mol Struct , 1247 : , 2022
Abstract : Donepezil (DNPZ) is one of the few FDA-approved widely used medication in the clinical care of Alzheimer's disease (AD) patients. To investigate the effect of geometry and to find the significance of an enol form if any in DNPZ on acetylcholinesterase (AChE) inhibition, we changed the tetrahedral geometry of DNPZ to planar trigonal pyramidal geometry by replacing the alpha-carbon atom next to ketone functionality with a nitrogen atom. To mimic 1-indanone in DNPZ, we selected 1-isoindolinone framework to synthesize 25 new DNPZ derivatives and characterized using (1)H NMR, (13)C NMR and ESI-MS spectroscopy methods. Drug likeliness profile for each compound was predicted using Molinspiration online software following Lipinski's rule. Commercially available assay kits were used to measure AChE and butyrylcholinesterase (BuChE) inhibitory effects. NIH/3T3 mouse embryonic fibroblast cell line was used to measure cytotoxic and proliferation effects using LDH and MTT assay, respectively. Compound #20 was selected for comparative computational docking, modelling and physicochemical studies. Our results show that DNPZ with tetrahedral geometry has 3-fold higher AChE inhibition as compared to compound #20 with planar trigonal pyramidal geometry. Our approach may be useful as a novel indirect method to study the significance of the enol form in DNPZ (or similar compounds), since constant interconversion between the keto and enol forms does not permit a direct determination of the effect of the enol form of DNPZ in vivo. Overall, we conclude that the tetrahedral is a better fit and any change in geometry significantly drives down the cholinesterase inhibitory effect of DNPZ.
ESTHER : Upadhyay_2022_J.Mol.Struct_1247_
PubMedSearch : Upadhyay_2022_J.Mol.Struct_1247_
PubMedID: 34776532

Title : A new benzaldehyde from the coral-derived fungus Aspergillus terreus C23-3 and its anti-inflammatory effects via suppression of MAPK signaling pathway in RAW264.7 cells - Chen_2022_J.Zhejiang.Univ.Sci.B_23_230
Author(s) : Chen M , Liang J , Wang Y , Liu Y , Zhou C , Hong P , Zhang Y , Qian ZJ
Ref : J Zhejiang Univ Sci B , 23 :230 , 2022
Abstract : Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.
ESTHER : Chen_2022_J.Zhejiang.Univ.Sci.B_23_230
PubMedSearch : Chen_2022_J.Zhejiang.Univ.Sci.B_23_230
PubMedID: 35261218

Title : Screening models combining maternal characteristics and multiple markers for the early prediction of preeclampsia in pregnancy: a nested case-control study - Chen_2022_J.Obstet.Gynaecol__1
Author(s) : Chen L , Pi Y , Chang K , Luo S , Peng Z , Chen M , Yu L
Ref : J Obstet Gynaecol , :1 , 2022
Abstract : To identify maternal laboratory markers to predict the risk of preeclampsia (PE) in different stages of pregnancy, we analysed 67, 25, and 73, pregnancies developing PE at 11-13, 16-20, and 24-28 wks, respectively. Routine laboratory markers were measured in whole blood or serum and binary logistic regression analysis was used to identify predictive models. At 11-13 wks of gestation, patients who went on to develop PE showed significantly higher concentrations of alanine aminotransferase, aspartate aminotransferase, alpha-L-fucosidase, 5'-nucleotidase, glutamyl transpeptidase, cholinesterase, and uric acid; plateletcrit was also higher. At 16-20 wks, inhibin A concentration and plateletcrit were significantly elevated. At 24-28 wks, platelets, plateletcrit, and glucose concentration were significantly elevated. Logistic regression analysis showed that an elevation in 5'-nucleotidase was independently associated with PE at 11-13 wks. The combination of inhibin A, diastolic blood pressure, and body mass index was a significant predictor for PE at 16-20 wks, while the combination of glucose and systolic blood pressure was a significant predictor for PE at 24-28 wks. In conclusion, when combined with maternal characteristics, the measurement of 5'-nucleotidase, inhibin A, and glucose levels, represents a potentially valuable risk assessment for PE.Impact statementWhat is already known on this subject? Preeclampsia (PE) may be viewed as a spectrum of disorders with a severity that is reflected in the levels of specific biomarkers. Consequently, there is a clear need for additional biomarkers that can be used to stratify pregnancies as high or low risk soon after conception.What do the results of this study add? At 11-13 wks of gestation, maternal assays for platelets, plateletcrit, alanine aminotransferase, aspartate aminotransferase, alpha-L-fucosidase, 5'-nucleotidase, glutamyl transpeptidase, cholinesterase, and uric acid, demonstrated significantly higher values in patients with PE when compared with normal controls. Furthermore, assay results for inhibin A and platelets showed increased values at 16-20 wks of gestation. Assays performed at 24-28 wks of gestation revealed elevated levels of platelets, plateletcrit, and glucose. Our analysis indicated that increases in the levels of 5'-nucleotidase, inhibin A, and glucose, are effective and significant biomarkers that could be used in combination with maternal characteristics to screen for PE at 11-13, 16-20, and 24-28 wks of gestation, respectively. These findings provide a new basis for our understanding of the aetiology underlying PE.What are the implications of these findings for clinical practice and/or further research? Further studies that consider the entire population are now needed and should include the investigation of laboratory markers across different stages of pregnancy. Long-term follow up would also be necessary if we are to explore the full role of laboratory markers in the pathophysiology of PE.
ESTHER : Chen_2022_J.Obstet.Gynaecol__1
PubMedSearch : Chen_2022_J.Obstet.Gynaecol__1
PubMedID: 35634766

Title : A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: findings from the UK Biobank - Zhu_2022_Gene_822_146340
Author(s) : Zhu X , Li Y , Yu T , Li S , Chen M
Ref : Gene , :146340 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are protective factors against cardiovascular diseases (CVDs) because of their vasodilatory, cholesterol-lowering, and anti-inflammatory effects. Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, degrades EETs into less biologically active metabolites. EPHX2 is highly polymorphic, and genetic polymorphisms in EPHX2 have been linked to various types of CVDs, such as coronary heart disease, essential hypertension, and atrial fibrillation recurrence. METHODS: Based on a priori hypothesis that EPHX2 genetic polymorphisms play an important role in the pathogenesis of CVDs, we comprehensively investigated the associations between 210 genetic polymorphisms in the EPHX2 gene and an array of 118 diseases in the circulatory system using a large sample from the UK Biobank (N=307,516). The diseases in electronic health records were mapped to the phecode system, which was more representative of independent phenotypes. Survival analyses were employed to examine the effects of EPHX2 variants on CVD incidence, and a phenome-wide association study was conducted to study the impact of EPHX2 polymorphisms on 62 traits, including blood pressure, blood lipid levels, and inflammatory indicators. RESULTS: A novel association between the intronic variant rs116932590 and the phenotype "aneurysm and dissection of heart" was identified. In addition, the rs149467044 and rs200286838 variants showed nominal evidence of association with arterial aneurysm and cerebrovascular disease, respectively. Furthermore, the variant rs751141, which was linked with a lower hydrolase activity of sEH, was significantly associated with metabolic traits, including blood levels of triglycerides, creatinine, and urate. CONCLUSIONS: Multiple novel associations observed in the present study highlight the important role of EPHX2 genetic variation in the pathogenesis of CVDs.
ESTHER : Zhu_2022_Gene_822_146340
PubMedSearch : Zhu_2022_Gene_822_146340
PubMedID: 35183688

Title : Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots - Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
Author(s) : Chen M , Zhang J , Chang J , Li H , Zhai Y , Wang Z
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 269 :120756 , 2021
Abstract : Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay.
ESTHER : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedSearch : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedID: 34952437

Title : Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction - Zhao_2021_Chin.J.Nat.Med_19_454
Author(s) : Zhao C , Chen M , Sun SL , Wang JJ , Zhong Y , Chen HH , Li HM , Xu H , Li NG , Ma HY , Wang XL
Ref : Chin J Nat Med , 19 :454 , 2021
Abstract : Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or alpha(4)beta(2) nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.
ESTHER : Zhao_2021_Chin.J.Nat.Med_19_454
PubMedSearch : Zhao_2021_Chin.J.Nat.Med_19_454
PubMedID: 34092296

Title : Sublethal Effects of Abamectin on the Development, Reproduction, Detoxification Enzyme Activity, and Related Gene Expression of the Oriental Fruit Moth (Lepidoptera: Tortricidae) - Su_2021_J.Econ.Entomol__
Author(s) : Su S , Jian C , Zhang X , Fang S , Peng X , Pinero JC , Chen M
Ref : J Econ Entomol , : , 2021
Abstract : Grapholita molesta is one of the most important fruit pests worldwide. Abamectin is a biological pesticide frequently used to control fruit borers like G. molesta in part owing to its translaminar properties. In this study, we characterized the toxicity of abamectin to G. molesta larvae using the diet incorporation method. The sublethal effects of abamectin on the development, reproduction, detoxification enzyme activity, and related gene expression of G. molesta were assessed. The results showed that the LC20 and LC50 values of the insecticide against G. molesta 72 h post-treatment were 1.17 mg L-1 and 5.85 mg L-1, whereas the LC20 and LC50 values 96 h post-treatment were 0.34 mg L-1 and 3.63 mg L-1. When compared to the control, sublethal concentrations of abamectin 1) significantly increased the mortality of the larvae, prepupae, and pupae of G. molesta, 2) prolonged the duration of 3rd to 5th instar larva, prepupal and pupal periods, 3) shortened the longevity of adults, and 4) reduced female fecundity. The enzymatic activity of glutathione S-transferase (GST) varied significantly after exposure to sublethal concentrations of abamectin, but the cytochrome P450 monooxygenases and carboxylesterase activity were not significantly affected. Thirteen of the 25 GST genes were significantly upregulated under different sublethal concentrations of abamectin. The combined findings increase our understanding of the effects of abamectin on G. molesta and the potential role of GSTs in the metabolic interactions of abamectin in this pest, and have applications for more rational and effective use of abamectin to control G. molesta.
ESTHER : Su_2021_J.Econ.Entomol__
PubMedSearch : Su_2021_J.Econ.Entomol__
PubMedID: 34672347

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Reproductive stimulation and energy allocation variation of BDE-47 and its derivatives on Daphnia magna - Liu_2021_Chemosphere_288_132492
Author(s) : Liu Y , Chen M , Ma Y , Guo R , Yan Z , Chen J
Ref : Chemosphere , 288 :132492 , 2021
Abstract : As endocrine disrupting chemical, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is widely distributed in water environment with a high detection rate. 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) and 6-methoxy-2,2',4,4'-tetrabromodiphenyl ether (6-MeO-BDE-47) are two main derivatives of BDE-47. To explore the aquatic risk of BDE-47 and its derivatives, the effects of them and their ternary mixture on the reproduction, growth, energy allocation, and neurological and antioxidant responses of Daphnia magna were monitoring during different exposure periods, i.e., daphnids exposed to compounds for 21 days or pre-exposed to compounds for 14 days and then recovered 7 days in clean water. In general, in 21-day test, reproductive parameters of exposed daphnids were significantly stimulated, and the growth and enzymatic activities of super oxidase dimutase (SOD), glutathione peroxidase (GPx) and acetylcholinesterase (AChE) were significantly depressed by the single- or mixture compounds. In (14 + 7)-day test, the levels of body length, number of living offspring per female and the enzyme activities recovered to some degree. However, after 7 days of recovery in pollution free medium, the reproductive parameters and enzymatic activities of D. magna were unable to restore control values. These results showed that D. magna has a tendency that the energy allocated to reproduction was greater than that to grow after exposure. The energy distribution of D. magna occurred autonomously after being exposed, which can make it better adapt to environmental changes. Moreover, based on the behavioral and enzymology indicators of D. magna, the spider chart's application in the characteristic analysis of function indicators of D. magna implied that SOD, GPx and AChE could become sensitive biomarkers for different exposure periods. Those findings enable us to better understand BDE-47 and metabolites, and are conducive to better take measures to solve the pressure it brings.
ESTHER : Liu_2021_Chemosphere_288_132492
PubMedSearch : Liu_2021_Chemosphere_288_132492
PubMedID: 34626654

Title : ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis - Ding_2021_ACS.Chem.Neurosci__
Author(s) : Ding Y , Wang X , Ji J , Zhang X , Chen M , Li S , Zhang Q , Liu P
Ref : ACS Chem Neurosci , : , 2021
Abstract : Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects.
ESTHER : Ding_2021_ACS.Chem.Neurosci__
PubMedSearch : Ding_2021_ACS.Chem.Neurosci__
PubMedID: 33517657

Title : Effect of Tannic Acid on Nutrition and Activities of Detoxification Enzymes and Acetylcholinesterase of the Fall Webworm (Lepidoptera: Arctiidae) - Yuan_2020_J.Insect.Sci_20_
Author(s) : Yuan Y , Li L , Zhao J , Chen M
Ref : J Insect Sci , 20 : , 2020
Abstract : Plant tannins, polyphenolic plant secondary metabolites are involved in important chemical defense processes in plants. In this study, tannic acid was used as the standard of plant tannins to determine the effects on nutritional indices and activities of glutathione S-transferases (GSTs), cytochrome P450 monooxygenase (CYP450), carboxylesterase (CarE), and acetylcholinesterase (AChE) in fourth-instar larvae of Hyphantria cunea (Drury) by feeding on an artificial diet containing tannic acid under different treatments. We found that tannic acid significantly affected the digestive capacity and food utilization rate of H. cunea larvae. A tannic acid concentration of less than 2.0% promoted feeding and the utilization of undesirable food by H. cunea larvae, while inhibitory effects were observed at high concentrations (>2.5%). Tannic acid had a significant effect on the activity of detoxification enzymes and AChE in H. cunea larvae in concentration-dependent and time-dependent manners (P < 0.05). These results provide new insights into the potential mechanisms underlying detoxification in H. cunea larvae against tannic acid in host plants.
ESTHER : Yuan_2020_J.Insect.Sci_20_
PubMedSearch : Yuan_2020_J.Insect.Sci_20_
PubMedID: 32061083

Title : Genome-Wide Identification, Evolution, and Expression of GDSL-Type Esterase\/Lipase Gene Family in Soybean - Su_2020_Front.Plant.Sci_11_726
Author(s) : Su HG , Zhang XH , Wang TT , Wei WL , Wang YX , Chen J , Zhou YB , Chen M , Ma YZ , Xu ZS , Min DH
Ref : Front Plant Sci , 11 :726 , 2020
Abstract : GDSL-type esterase/lipase proteins (GELPs) belong to the SGNH hydrolase superfamily and contain a conserved GDSL motif at their N-terminus. GELPs are widely distributed in nature, from microbes to plants, and play crucial roles in growth and development, stress responses and pathogen defense. However, the identification and functional analysis of GELP genes are hardly explored in soybean. This study describes the identification of 194 GELP genes in the soybean genome and their phylogenetic classification into 11 subfamilies (A-K). GmGELP genes are disproportionally distributed on 20 soybean chromosomes. Large-scale WGD/segmental duplication events contribute greatly to the expansion of the soybean GDSL gene family. The Ka/Ks ratios of more than 70% of duplicated gene pairs ranged from 0.1-0.3, indicating that most GmGELP genes were under purifying selection pressure. Gene structure analysis indicate that more than 74% of GmGELP genes are interrupted by 4 introns and composed of 5 exons in their coding regions, and closer homologous genes in the phylogenetic tree often have similar exon-intron organization. Further statistics revealed that approximately 56% of subfamily K members contain more than 4 introns, and about 28% of subfamily I members consist of less than 4 introns. For this reason, the two subfamilies were used to simulate intron gain and loss events, respectively. Furthermore, a new model of intron position distribution was established in current study to explore whether the evolution of multi-gene families resulted from the diversity of gene structure. Finally, RNA-seq data were used to investigate the expression profiles of GmGELP gene under different tissues and multiple abiotic stress treatments. Subsequently, 7 stress-responsive GmGELP genes were selected to verify their expression levels by RT-qPCR, the results were consistent with RNA-seq data. Among 7 GmGELP genes, GmGELP28 was selected for further study owing to clear responses to drought, salt and ABA treatments. Transgenic Arabidopsis thaliana and soybean plants showed drought and salt tolerant phenotype. Overexpression of GmGELP28 resulted in the changes of several physiological indicators, which allowed plants to adapt adverse conditions. In all, GmGELP28 is a potential candidate gene for improving the salinity and drought tolerance of soybean.
ESTHER : Su_2020_Front.Plant.Sci_11_726
PubMedSearch : Su_2020_Front.Plant.Sci_11_726
PubMedID: 32670311

Title : Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer's Disease - Shen_2020_Front.Pharmacol_11_595254
Author(s) : Shen Y , Zhang B , Pang X , Yang R , Chen M , Zhao J , Wang J , Wang Z , Yu Z , Wang Y , Li L , Liu A , Du G
Ref : Front Pharmacol , 11 :595254 , 2020
Abstract : Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor alpha (ERalpha) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC(50) values ranging from 4.83 to 10.22 microM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.
ESTHER : Shen_2020_Front.Pharmacol_11_595254
PubMedSearch : Shen_2020_Front.Pharmacol_11_595254
PubMedID: 33390981

Title : The structure-based optimization of delta-sultone-fused pyrazoles as selective BuChE inhibitors - Zhang_2020_Eur.J.Med.Chem_201_112273
Author(s) : Zhang Z , Min J , Chen M , Jiang X , Xu Y , Qin H , Tang W
Ref : Eur Journal of Medicinal Chemistry , 201 :112273 , 2020
Abstract : Structure-based optimization was conducted to improve the potency and selectivity of BuChE inhibitors with delta-sulfonolactone-fused pyrazole scaffold. By mimicking the hydrophobic interactions of donepezil at PAS, the introduction of a tertiary benzylamine at 5-position can significantly increase BuChE inhibitory activity. Compounds C4 and C6 were identified as high selective nanomolar BuChE inhibitors (IC50 = 8.3 and 7.7 nM, respectively), which exhibited mild antioxidant capacity, nontoxicity, lipophilicity and neuroprotective activity. Kinetic studies showed that BuChE inhibition of compound C6 was mixed-type against BuChE (Ki = 24 nM) and >2000-fold selectivity for BuChE over AChE. The proposed binding mode of new inhibitors was consistent with the results of structure-activity relationship analysis.
ESTHER : Zhang_2020_Eur.J.Med.Chem_201_112273
PubMedSearch : Zhang_2020_Eur.J.Med.Chem_201_112273
PubMedID: 32569925

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 : Downregulation of carboxylesterase contributes to cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval) - Wei_2019_Pest.Manag.Sci_75_2166
Author(s) : Wei P , Chen M , Nan C , Feng K , Shen G , Cheng J , He L
Ref : Pest Manag Sci , 75 :2166 , 2019
Abstract : BACKGROUND: Increased expression or point mutations of carboxyl/cholinesterases (CCEs) have been involved in many cases of insecticide and acaricide resistance. However, it has been only rarely documented that downregulation of CCE genes is associated with resistance, although many insecticides and acaricides need hydrolytic activation in vivo. Previously, expression analysis of a laboratory-selected cyflumetofen-resistant strain of Tetranychus cinnabarinus indicated that resistance was associated with increased expression of a CCE gene of TcCCE04, but also the downregulation of two CCE genes, TcCCE12 and TcCCE23. RESULTS: Synergism experiments revealed the importance of ester hydrolysis in cyflumetofen toxicity, because treatment with S,S,S-tributylphosphorotrithioate (DEF) caused strong inhibition of cyflumetofen hydrolysis, in both the susceptible and resistant strains. Moreover, silencing expression of TcCCE12 and TcCCE23 via RNAi further decreased the susceptibility of mites to cyflumetofen significantly, suggesting that downregulated CCE genes could be involved in cyflumetofen resistance. In addition, it was shown that recombinant TcCCE12 protein could hydrolyze cyflumetofen effectively. CONCLUSION: Decreased esterase activity via downregulation of specific CCE genes most likely contributes to cyflumetofen resistance by decreased activation of cyflumetofen to its active metabolite. Mixtures of cyflumetofen and esterase-inhibition acaricides (e.g. organophosphates or carbamates) should be avoided in field applications.
ESTHER : Wei_2019_Pest.Manag.Sci_75_2166
PubMedSearch : Wei_2019_Pest.Manag.Sci_75_2166
PubMedID: 30653811
Gene_locus related to this paper: tetur-t1kth5 , tetur-t1kx09 , tetur-t1ju32 , tetur-t1jth6

Title : Large-scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH-zone-refining counter-current chromatography target-guided by ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry screening - Liu_2019_J.Sep.Sci_42_1194
Author(s) : Liu M , Liu Q , Chen M , Huang X , Chen X
Ref : J Sep Sci , 42 :1194 , 2019
Abstract : A new strategy by converging ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry and pH-zone-refining counter-current chromatography was developed for the rapid screening and separation of potential acetylcholinesterase inhibitors from the crude alkaloidals extract of Zanthoxylum nitidum. An optimized two-phase solvent system composed of chloroform/methanol/water (4:3:3, v/v) was used in this study. And, in the optimal solvent system, 45 mM hydrochloric acid was added to the aqueous stationary phase as the retainer, while 5 mM triethylamine was added to the organic mobile phase as the eluter. As a result, with the purity of over 95%, five alkaloids including jatrorrhizine (1, 340 mg), columbamine (2, 112 mg), skimmianine (3, 154 mg), palmatine (4, 226 mg), and epiberberine (5, 132 mg) were successfully purified in one step from 3.0 g crude alkaloidals extract. And their structures were identified by ultraviolet, mass spectrometry, (1) H and (13) C NMR spectroscopy. Notably, compounds 2, 4 and 5 were firstly reported in Z. nitidum. In addition, acetylcholinesterase inhibitory activities of compounds 1-5 were evaluated, and compounds 3, 4 and 5 exhibited stronger acetylcholinesterase inhibitory activity (IC50 values at 8.52 +/- 0.64, 14.82 +/- 1.21 and 3.12 +/- 0.32 mug/mL, respectively) than berberine (IC50 value at 32.86 +/- 2.14 mug/mL, positive control). The results indicated that the proposed method is an efficient technique to rapidly screen acetylcholinesterase inhibitors from complex samples, and could be served as a large-scale preparative technique for separating ionizable active compounds.
ESTHER : Liu_2019_J.Sep.Sci_42_1194
PubMedSearch : Liu_2019_J.Sep.Sci_42_1194
PubMedID: 30638299

Title : Royal Jelly Ameliorates Behavioral Deficits, Cholinergic System Deficiency, and Autonomic Nervous Dysfunction in Ovariectomized Cholesterol-Fed Rabbits - Pan_2019_Molecules_24_
Author(s) : Pan Y , Xu J , Jin P , Yang Q , Zhu K , You M , Chen M , Hu F
Ref : Molecules , 24 : , 2019
Abstract : Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer's disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Abeta), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Abeta, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Abeta deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood(-)brain barrier (BBB) permeability and restoring autonomic nervous system.
ESTHER : Pan_2019_Molecules_24_
PubMedSearch : Pan_2019_Molecules_24_
PubMedID: 30909491

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

Title : Accumulation of polystyrene microplastics in juvenile Eriocheir sinensis and oxidative stress effects in the liver - Yu_2018_Aquat.Toxicol_200_28
Author(s) : Yu P , Liu Z , Wu D , Chen M , Lv W , Zhao Y
Ref : Aquat Toxicol , 200 :28 , 2018
Abstract : As a widespread and ubiquitous pollutant of marine ecosystems, microplastic has the potential to become an emerging global threat for aquatic organisms. The present study aims to elucidate the effects of microplastics on the growth, accumulation and oxidative stress response in the liver of Eriocheir sinensis. Fluorescent microplastic particles (diameter=0.5mum) accumulated in the gill, liver and gut tissues of E. sinensis were investigated when crabs were exposed to a concentration of 40000mug/L for 7days. A 21day toxicity test suggested that the rate of weight gain, specific growth rate, and hepatosomatic index of E. sinensis decreased with increasing microplastic concentration (0mug/L, 40mug/L, 400mug/L, 4000mug/L and 40000mug/L). The activities of AChE and GPT in crabs exposed to microplastics were lower than those in control group. GOT activity increased significantly after exposure to a low concentration of microplastics and then decreased continuously with increasing microplastic concentrations. The activities of superoxide dismutase (SOD), aspartate transaminase (GOT), glutathione (GSH), and glutathione peroxidase (GPx) increased in specimens exposed to low concentrations of microplastics (40 and 400mug/L) compared to the control and decreased in organisms exposed to high concentrations (4000 and 40000mug/L). In contrast, the activities of acetylcholinesterase, catalase (CAT), and alanine aminotransferase were significantly lower in the organisms exposed to microplastics compared to control animals. Upon exposure to increasing microplastic concentrations, the expression of genes encoding the antioxidants SOD, CAT, GPx and glutathione S-transferase in the liver decreased after first increasing. Exposure to microplastics increased the expression of the gene encoding p38 in the MAPK signaling pathway and significantly decreased the expressions of genes encoding ERK, AKT, and MEK. The results of this study demonstrate that microplastics can accumulate in the tissues of E. sinensis and negatively affect growth. In addition, exposure to microplastics causes damage and induces oxidative stress in the hepatopancreas of E. sinensis. The findings provide basic biological data for environmental and human risk assessments of microplastics of high concern.
ESTHER : Yu_2018_Aquat.Toxicol_200_28
PubMedSearch : Yu_2018_Aquat.Toxicol_200_28
PubMedID: 29709883

Title : Organic matter modifies biochemical but not most behavioral responses of the clam Ruditapes philippinarum to nanosilver exposure - Zhang_2018_Mar.Environ.Res_133_105
Author(s) : Zhang T , Pan JF , Hunt DE , Chen M , Wang B
Ref : Mar Environ Research , 133 :105 , 2018
Abstract : Adsorption of dissolved organic matter (DOM) can alter the environmental fate, bioavailability and toxicity of silver nanoparticles (Ag NPs). However, a number of questions remain about DOM's ability to modify nanotoxicity. Here, we examine the impact of humic acid (HA, as a model DOM) on the toxicity of Ag NPs (10 mug L(-1)) in the marine clam Ruditapes philippinarum. Results showed that DOM additions to Ag NP treatments reduce clam silver tissue burdens and the oxidative stress response. However, HA does not significantly affect the impact of Ag NPs on clam acetylcholinesterase activity and feeding behavior (measured as filtration rate). Overall, the integrated biological response index supports the conclusion that humic acid reduces the toxicity of Ag NPs, clearly indicating the importance of considering environmental factors when assessing potential risks posed by nanomaterials in natural settings.
ESTHER : Zhang_2018_Mar.Environ.Res_133_105
PubMedSearch : Zhang_2018_Mar.Environ.Res_133_105
PubMedID: 29254654

Title : Functional Analysis of a Carboxylesterase Gene Associated With Isoprocarb and Cyhalothrin Resistance in Rhopalosiphum padi (L.) - Wang_2018_Front.Physiol_9_992
Author(s) : Wang K , Huang Y , Li X , Chen M
Ref : Front Physiol , 9 :992 , 2018
Abstract : Carboxylesterase (CarE) is an important class of detoxification enzymes involved in insecticide resistance. However, the molecular mechanism of CarE-mediated insecticide resistance in Rhopalosiphum padi, a problematic agricultural pest, remains largely unknown. In the present study, an isoprocarb-resistant (IS-R) strain and a cyhalothrin-resistant (CY-R) strain were successively selected from a susceptible (SS) strain of R. padi. The enzyme activity indicated that enhanced carboxylesterase activity contributes to isoprocarb and cyhalothrin resistance. The expression levels of putative CarE genes were examined and compared among IS-R, CY-R, and SS strains, and only the R. padi carboxylesterase gene (RpCarE) was significantly over expressed in both the IS-R and CY-R strains compared to the SS strain. The coding region of the RpCarE gene was cloned and expressed in Escherichia coli. The purified RpCarE protein was able to catalyze the model substrate, alpha-naphtyl acetate (Kcat = 5.50 s(-1); Km = 42.98 muM). HPLC assay showed that the recombinant protein had hydrolase activity against isoprocarb and cyhalothrin. The modeling and docking analyses consistently indicated these two insecticide molecules fit snugly into the catalytic pocket of RpCarE. Taken together, these findings suggest that RpCarE plays an important role in metabolic resistance to carbamates and pyrethroids in R. padi.
ESTHER : Wang_2018_Front.Physiol_9_992
PubMedSearch : Wang_2018_Front.Physiol_9_992
PubMedID: 30090072

Title : Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase - Zeng_2018_ACS.Catal_8_8856
Author(s) : Zeng S , Liu J , Anankanbil S , Chen M , Guo Z , Adams JP , Snajdrova R , Li Z
Ref : ACS Catal , 8 :8856 , 2018
Abstract : A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a-g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h-j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2-4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.
ESTHER : Zeng_2018_ACS.Catal_8_8856
PubMedSearch : Zeng_2018_ACS.Catal_8_8856
PubMedID:
Gene_locus related to this paper: sphmc-SpL

Title : Characterization of Lipophilized Monomeric and Oligomeric Grape Seed Flavan-3-ol Derivatives - Chen_2017_J.Agric.Food.Chem_65_8875
Author(s) : Chen M , Yu S
Ref : Journal of Agricultural and Food Chemistry , 65 :8875 , 2017
Abstract : Grape seed proanthocyanidins, composed of flavan-3-ols of different degrees of polymerization, are natural food antioxidants. Flavan-3-ols in grape seed are usually polyhydroxy derivatives which exhibit hydrophilic character. Monomeric and oligomeric flavan-3-ols were modified structurally to improve their lipophilicity, expand their application in lipophilic media, and enhance their cellular absorption in the body. The esterification of the water-soluble flavan-3-ols was prepared by Lipozyme TL IM with lauric acid, and their enhanced lipophilicity was confirmed by a 1-octanol/water partition coefficient. The chemical structures of monomeric and oligomeric flavan-3-ol derivatives, identified by HPLC-MS-MS and (1)H and (13)C NMR, were 3'-O-lauroyl catechin, 3'-O-lauroyl epicatechin, 3',5'-2-O-lauroyl epigallocatechin, 3',3'',5''-3-O-lauroyl epicatechin gallate, 3',3''-2-O-lauroyl procyanidin A2, 3',3''-2-O-lauroyl procyanidin B1, and 3',3'',3'''-3-O-lauroyl procyanidin C1. Flavan-3-ol derivatives exhibited the highest 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities compared to that of parent flavan-3-ols, butylated hydroxytoluene and tert-butyl hydroquinone. The results suggest that flavan-3-ol derivatives may be used as potential lipophilic antioxidants in the food industry.
ESTHER : Chen_2017_J.Agric.Food.Chem_65_8875
PubMedSearch : Chen_2017_J.Agric.Food.Chem_65_8875
PubMedID: 28936872

Title : Lipophilized Grape Seed Proanthocyanidin Derivatives as Novel Antioxidants - Chen_2017_J.Agric.Food.Chem_65_1598
Author(s) : Chen M , Yu S
Ref : Journal of Agricultural and Food Chemistry , 65 :1598 , 2017
Abstract : Grape seed proanthocyanidin (GSP) is a natural food antioxidant. Natural proanthocyanidins (PC) in grape seed are usually polyhydroxy derivatives which exhibit hydrophilic character. GSP was modified structurally to improve its lipophilicity, expand its application in lipophilic media, and enhance its cellular absorption in vivo. Esterification of the water-soluble GSP was prepared by immobilized lipase Lipozyme TL IM with lauric acid, and their enhanced lipophilicity was confirmed by the 1-octanol/water partition coefficient. The presence of mono-, di-, and trilauroylated derivatives in GSP derivatives was confirmed by HPLC-MS-MS, and four lauroylated derivatives were identified as 3',5'-2-O-lauroyl epigallocatechin, 3'-O-lauroyl catechin, 3'-O-lauroyl epicatechin, and 3',3'',5''-3-O-lauroyl epicatechin gallate by NMR. GSP derivatives exhibited the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (IC(50) of 41 g/mL) compared to that of GSP, hydroxytoluene (BHT), and tert-butyl hydroquinone (TBHQ). The results suggest that GSP derivatives may be used as potential lipophilic antioxidants in the food industry.
ESTHER : Chen_2017_J.Agric.Food.Chem_65_1598
PubMedSearch : Chen_2017_J.Agric.Food.Chem_65_1598
PubMedID: 28211691

Title : DWARF14, A Receptor Covalently Linked with the Active Form of Strigolactones, Undergoes Strigolactone-Dependent Degradation in Rice - Hu_2017_Front.Plant.Sci_8_1935
Author(s) : Hu Q , He Y , Wang L , Liu S , Meng X , Liu G , Jing Y , Chen M , Song X , Jiang L , Yu H , Wang B , Li J
Ref : Front Plant Sci , 8 :1935 , 2017
Abstract : Strigolactones (SLs) are the latest confirmed phytohormones that regulate shoot branching by inhibiting bud outgrowth in higher plants. Perception of SLs depends on a novel mechanism employing an enzyme-receptor DWARF14 (D14) that hydrolyzes SLs and becomes covalently modified. This stimulates the interaction between D14 and D3, leading to the ubiquitination and degradation of the transcriptional repressor protein D53. However, the regulation of SL perception in rice remains elusive. In this study, we provide evidences that D14 is ubiquitinated after SL treatment and degraded through the 26S proteasome system. The Lys280 site of the D14 amino acid sequence was important for SL-induced D14 degradation, but did not change the subcellular localization of D14 nor disturbed the interaction between D14 and D3, nor D53 degradation. Biochemical and genetic analysis indicated that the key amino acids in the catalytic center of D14 were essential for D14 degradation. We further showed that D14 degradation is dependent on D3 and is tightly correlated with protein levels of D53. These findings revealed that D14 degradation takes place following D53 degradation and functions as an important feedback regulation mechanism of SL perception in rice.
ESTHER : Hu_2017_Front.Plant.Sci_8_1935
PubMedSearch : Hu_2017_Front.Plant.Sci_8_1935
PubMedID: 29170677

Title : Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer - Chen_2017_Oncotarget_8_28176
Author(s) : Chen M , Li J , Zhuang C , Cai Z
Ref : Oncotarget , 8 :28176 , 2017
Abstract : Bladder cancer is one of the most common urothelial tumors worldwide. While there are some progresses on early bladder cancer detection, patients' mortalities have not been changed significantly. So it is important to get further understanding the mechanism involved in the development and progression of bladder cancer. Long non-coding RNAs play important regulatory roles in a variety of biological processes ranging from gene regulation, cellular differentiation to tumorigenesis. Previous literatures reported that lncRNA ABHD11 Antisense RNA 1 (ABHD11-AS1) (Organism: Homo sapiens) was highly expressed in gastric cancer. Inspired by these observations, we hypothesized that ABHD11-AS1 possibly plays an analogous role in human bladder cancer. We first found that ABHD11-AS1 was up-regulated in bladder cancer tissues and cell lines, and ABHD11-AS1 expression level was positively associated with clinicobiological features. Cell proliferation, cell migration and apoptosis were observed by silencing ABHD11-AS1 and overexpression ABHD11-AS1 caused contrary effects. Taken together, these data suggested that ABHD11-AS1 may be an oncogene and a therapeutic target in bladder cancer.
ESTHER : Chen_2017_Oncotarget_8_28176
PubMedSearch : Chen_2017_Oncotarget_8_28176
PubMedID: 28157695
Gene_locus related to this paper: human-ABHD11

Title : Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents - Fang_2016_Bioorg.Med.Chem_24_886
Author(s) : Fang L , Chen M , Liu Z , Fang X , Gou S , Chen L
Ref : Bioorganic & Medicinal Chemistry , 24 :886 , 2016
Abstract : In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid-carbazole hybrid compounds were designed and synthesized. Ellman's assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9muM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture.
ESTHER : Fang_2016_Bioorg.Med.Chem_24_886
PubMedSearch : Fang_2016_Bioorg.Med.Chem_24_886
PubMedID: 26795115

Title : Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population - Wang_2016_Sci.Rep_6_20691
Author(s) : Wang T , Ma X , Peng D , Zhang R , Sun X , Chen M , Yan J , Wang S , Yan D , He Z , Jiang F , Bao Y , Hu C , Jia W
Ref : Sci Rep , 6 :20691 , 2016
Abstract : Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 x 10(-5) and 6.54 x 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 x 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 x 10(-8) and 4.43 x 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 x 10(-4) and 4.65 x 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.
ESTHER : Wang_2016_Sci.Rep_6_20691
PubMedSearch : Wang_2016_Sci.Rep_6_20691
PubMedID: 26848030

Title : Discovery of Potent and Orally Active Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors as a Potential Therapy for Diabetic Macular Edema - Chen_2016_J.Med.Chem_59_2674
Author(s) : Chen X , Wang K , Xu W , Ma Q , Chen M , Du L , Mo M , Wang Y , Shen J
Ref : Journal of Medicinal Chemistry , 59 :2674 , 2016
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a promising therapeutic target for several inflammation-associated diseases. Herein, we describe the discovery of a series of pyrimidone derivatives as Lp-PLA2 inhibitors. Systematic structural modifications led to the identification of several pyrimidone compounds with promising in vitro inhibitory potency and pharmacokinetic properties. Compound 14c, selected for in vivo evaluation, demonstrated decent pharmacokinetic profiles and robust inhibitory potency against Lp-PLA2 in Sprague-Dawley (SD) rats. Furthermore, 14c significantly inhibited retinal thickening in STZ-induced diabetic SD rats as a model of diabetic macular edema (DME) after oral dosing for 4 weeks. Taken together, these results suggested that 14c can serve as a valuable lead in the search for new Lp-PLA2 inhibitors for prevention and/or treatment of DME.
ESTHER : Chen_2016_J.Med.Chem_59_2674
PubMedSearch : Chen_2016_J.Med.Chem_59_2674
PubMedID: 26927682
Gene_locus related to this paper: human-PLA2G7

Title : Targeting of cancerassociated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment - Li_2016_Mol.Med.Rep_13_2476
Author(s) : Li M , Yin T , Shi H , Wen Y , Zhang B , Chen M , Xu G , Ren K , Wei Y
Ref : Mol Med Rep , 13 :2476 , 2016
Abstract : Cancerassociated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the smallmolecule dipeptidyl peptidase inhibitor PT100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT100 contained lower numbers of tumorassociated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumorpromoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.
ESTHER : Li_2016_Mol.Med.Rep_13_2476
PubMedSearch : Li_2016_Mol.Med.Rep_13_2476
PubMedID: 26846566

Title : Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora - Zhang_2016_Sci.Rep_6_23122
Author(s) : Zhang L , Zhou Z , Guo Q , Fokkens L , Miskei M , Pocsi I , Zhang W , Chen M , Wang L , Sun Y , Donzelli BG , Gibson DM , Nelson DR , Luo JG , Rep M , Liu H , Yang S , Wang J , Krasnoff SB , Xu Y , Molnar I , Lin M
Ref : Sci Rep , 6 :23122 , 2016
Abstract : Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle.
ESTHER : Zhang_2016_Sci.Rep_6_23122
PubMedSearch : Zhang_2016_Sci.Rep_6_23122
PubMedID: 26975455
Gene_locus related to this paper: 9hypo-a0a151ga75 , 9hypo-a0a151gbh5 , 9hypo-a0a151gd50 , 9hypo-a0a151ggb9 , 9hypo-a0a151gjd5 , 9hypo-a0a151gtv2 , 9hypo-a0a151gxh2 , 9hypo-a0a151gaw8 , 9hypo-a0a151gia2

Title : Comparative Genomics Analysis of Streptomyces Species Reveals Their Adaptation to the Marine Environment and Their Diversity at the Genomic Level - Tian_2016_Front.Microbiol_7_998
Author(s) : Tian X , Zhang Z , Yang T , Chen M , Li J , Chen F , Yang J , Li W , Zhang B , Wu J , Zhang C , Long L , Xiao J
Ref : Front Microbiol , 7 :998 , 2016
Abstract : Over 200 genomes of streptomycete strains that were isolated from various environments are available from the NCBI. However, little is known about the characteristics that are linked to marine adaptation in marine-derived streptomycetes. The particularity and complexity of the marine environment suggest that marine streptomycetes are genetically diverse. Here, we sequenced nine strains from the Streptomyces genus that were isolated from different longitudes, latitudes, and depths of the South China Sea. Then we compared these strains to 22 NCBI downloaded streptomycete strains. Thirty-one streptomycete strains are clearly grouped into a marine-derived subgroup and multiple source subgroup-based phylogenetic tree. The phylogenetic analyses have revealed the dynamic process underlying streptomycete genome evolution, and lateral gene transfer is an important driving force during the process. Pan-genomics analyses have revealed that streptomycetes have an open pan-genome, which reflects the diversity of these streptomycetes and guarantees the species a quick and economical response to diverse environments. Functional and comparative genomics analyses indicate that the marine-derived streptomycetes subgroup possesses some common characteristics of marine adaptation. Our findings have expanded our knowledge of how ocean isolates of streptomycete strains adapt to marine environments. The availability of streptomycete genomes from the South China Sea will be beneficial for further analysis on marine streptomycetes and will enrich the South China Sea's genetic data sources.
ESTHER : Tian_2016_Front.Microbiol_7_998
PubMedSearch : Tian_2016_Front.Microbiol_7_998
PubMedID: 27446038
Gene_locus related to this paper: 9actn-a0a1e7k9d4 , 9actn-a0a1e7l883 , 9actn-a0a1e7kw84 , 9actn-a0a1e7kkk9 , 9actn-a0a1e7jip1 , 9actn-a0a1e7jjj1 , 9actn-a0a1e7k159 , 9actn-a0a1e7kfw2 , 9actn-a0a1e7l1n0 , 9actn-a0a1e7jf99

Title : The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration - Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
Author(s) : Xiao L , Yang G , Zhang L , Yang X , Zhao S , Ji Z , Zhou Q , Hu M , Wang Y , Chen M , Xu Y , Jin H , Xiao X , Hu G , Bao F , Hu Y , Wan P , Li L , Deng X , Kuang T , Xiang C , Zhu JK , Oliver MJ , He Y
Ref : Proc Natl Acad Sci U S A , 112 :5833 , 2015
Abstract : "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes.
ESTHER : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedSearch : Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833
PubMedID: 25902549
Gene_locus related to this paper: 9lami-a0a2z7c6k4 , 9lami-a0a2z7bgj4

Title : Plant Esterase-Chitosan\/Gold Nanoparticles-Graphene Nanosheet Composite-Based Biosensor for the Ultrasensitive Detection of Organophosphate Pesticides - Bao_2015_J.Agric.Food.Chem_63_10319
Author(s) : Bao J , Hou C , Chen M , Li J , Huo D , Yang M , Luo X , Lei Y
Ref : Journal of Agricultural and Food Chemistry , 63 :10319 , 2015
Abstract : As broad-spectrum pesticides, organophosphates (OPs) are widely used in agriculture all over the world. However, due to their neurotoxicity in humans and their increasing occurrence in the environment, there is growing interest in their sensitive and selective detection. This paper reports a new cost-effective plant esterase-chitosan/gold nanoparticles-graphene nanosheet (PLaE-CS/AuNPs-GNs) biosensor for the sensitive detection of methyl parathion and malathion. Highly pure plant esterase is produced from plants at low cost and shares the same inhibition mechanism with OPs as acetylcholinesterase, and then it was used to prepare PLaE-CS/AuNPs-GNs nanocomposites, which were systematically characterized using SEM, TEM, and UV-vis. The PLaE-CS/AuNPs-GNs composite-based biosensor measured as low as 50 ppt (0.19 nM) of methyl parathion and 0.5 ppb (1.51 nM) of malathion (S/N = 3) with a calibration curve up to 200 ppb (760 nM) and 500 ppb (1513.5 nM) for methyl parathion and malathion, respectively. There is also no interference observed from most of common species such as metal ions, inorganic ions, glucose, and citric acid. In addition, its applicability to OPs-contaminated real samples (carrot and apple) was also demonstrated with excellent response recovery. The developed simple, sensitive, and reliable PLaE-CS/AuNPs-GNs composite-based biosensor holds great potential in OPs detection for food and environmental safety.
ESTHER : Bao_2015_J.Agric.Food.Chem_63_10319
PubMedSearch : Bao_2015_J.Agric.Food.Chem_63_10319
PubMedID: 26554573

Title : Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy - Wang_2015_Ther.Clin.Risk.Manag_11_449
Author(s) : Wang ZY , Chen M , Zhu LL , Yu LS , Zeng S , Xiang MX , Zhou Q
Ref : Ther Clin Risk Manag , 11 :449 , 2015
Abstract : BACKGROUND: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug-drug interactions (DDIs) when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.
METHODS: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.
RESULTS: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John's wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C.A), species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion transporter family member 1B1. CONCLUSION: Effective and safe clopidogrel combination therapy can be achieved by increasing the awareness of potential changes in efficacy and toxicity, rationally selecting alternatives, tailoring drug therapy based on genotype, checking the appropriateness of physician orders, and performing therapeutic monitoring.
ESTHER : Wang_2015_Ther.Clin.Risk.Manag_11_449
PubMedSearch : Wang_2015_Ther.Clin.Risk.Manag_11_449
PubMedID: 25848291

Title : The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to beta-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment - Ostapchenko_2015_J.Neurosci_35_15157
Author(s) : Ostapchenko VG , Chen M , Guzman MS , Xie YF , Lavine N , Fan J , Beraldo FH , Martyn AC , Belrose JC , Mori Y , MacDonald JF , Prado VF , Prado MAM , Jackson MF
Ref : Journal of Neuroscience , 35 :15157 , 2015
Abstract : In Alzheimer's disease, accumulation of soluble oligomers of beta-amyloid peptide is known to be highly toxic, causing disturbances in synaptic activity and neuronal death. Multiple studies relate these effects to increased oxidative stress and aberrant activity of calcium-permeable cation channels leading to calcium imbalance. The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity. Here we show that the function of TRPM2 is augmented by treatment of cultured neurons with beta-amyloid oligomers. Aged APP/PS1 Alzheimer's mouse model showed increased levels of endoplasmic reticulum stress markers, protein disulfide isomerase and phosphorylated eukaryotic initiation factor 2alpha, as well as decreased levels of the presynaptic marker synaptophysin. Elimination of TRPM2 in APP/PS1 mice corrected these abnormal responses without affecting plaque burden. These effects of TRPM2 seem to be selective for beta-amyloid toxicity, as ER stress responses to thapsigargin or tunicamycin in TRPM2(-/-) neurons was identical to that of wild-type neurons. Moreover, reduced microglial activation was observed in TRPM2(-/-)/APP/PS1 hippocampus compared with APP/PS1 mice. In addition, age-dependent spatial memory deficits in APP/PS1 mice were reversed in TRPM2(-/-)/APP/PS1 mice. These results reveal the importance of TRPM2 for beta-amyloid neuronal toxicity, suggesting that TRPM2 activity could be potentially targeted to improve outcomes in Alzheimer's disease. SIGNIFICANCE STATEMENT: Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress sensing calcium-permeable channel that is thought to contribute to calcium dysregulation associated with neurodegenerative diseases, including Alzheimer's disease. Here we show that oligomeric beta-amyloid, the toxic peptide in Alzheimer's disease, facilitates TRPM2 channel activation. In mice designed to model Alzheimer's disease, genetic elimination of TRPM2 normalized deficits in synaptic markers in aged mice. Moreover, the absence of TRPM2 improved age-dependent spatial memory deficits observed in Alzheimer's mice. Our results reveal the importance of TRPM2 for neuronal toxicity and memory impairments in an Alzheimer's mouse model and suggest that TRPM2 could be targeted for the development of therapeutic agents effective in the treatment of dementia.
ESTHER : Ostapchenko_2015_J.Neurosci_35_15157
PubMedSearch : Ostapchenko_2015_J.Neurosci_35_15157
PubMedID: 26558786

Title : Whole-genome optical mapping and finished genome sequence of Sphingobacterium deserti sp. nov., a new species isolated from the Western Desert of China - Teng_2015_PLoS.One_10_e0122254
Author(s) : Teng C , Zhou Z , Molnar I , Li X , Tang R , Chen M , Wang L , Su S , Zhang W , Lin M
Ref : PLoS ONE , 10 :e0122254 , 2015
Abstract : A novel Gram-negative bacterium, designated ZWT, was isolated from a soil sample of the Western Desert of China, and its phenotypic properties and phylogenetic position were investigated using a polyphasic approach. Growth occurred on TGY medium at 5-42 degreesC with an optimum of 30 degreesC, and at pH 7.0-11.0 with an optimum of pH 9.0. The predominant cellular fatty acids were summed feature 3 (C16:1omega7c/C16:1omega6c or C16:1omega6c/C16:1omega7c) (39.22%), iso-C15:0 (27.91%), iso-C17:0 3OH (15.21%), C16:0 (4.98%), iso-C15:0 3OH (3.03%), C16:0 3OH (5.39%) and C14:0 (1.74%). The major polar lipid of strain ZWT is phosphatidylethanolamine. The only menaquinone observed was MK-7. The GC content of the DNA of strain ZWT is 44.9 mol%. rDNA phylogeny, genome relatedness and chemotaxonomic characteristics all indicate that strain ZWT represents a novel species of the genus Sphingobacterium. We propose the name S. deserti sp. nov., with ZWT (= KCTC 32092T = ACCC 05744T) as the type strain. Whole genome optical mapping and next-generation sequencing was used to derive a finished genome sequence for strain ZWT, consisting of a circular chromosome of 4,615,818 bp in size. The genome of strain ZWT features 3,391 protein-encoding and 48 tRNA-encoding genes. Comparison of the predicted proteome of ZWT with those of other sphingobacteria identified 925 species-unique proteins that may contribute to the adaptation of ZWT to its native, extremely arid and inhospitable environment. As the first finished genome sequence for any Sphingobacterium, our work will serve as a useful reference for subsequent sequencing and mapping efforts for additional strains and species within this genus.
ESTHER : Teng_2015_PLoS.One_10_e0122254
PubMedSearch : Teng_2015_PLoS.One_10_e0122254
PubMedID: 25830331
Gene_locus related to this paper: 9sphi-a0a0b8t8i3 , 9sphi-a0a0b8t3y0

Title : Draft Genome Sequence of the Filamentous Cyanobacterium Leptolyngbya sp. Strain Heron Island J, Exhibiting Chromatic Acclimation - Paul_2014_Genome.Announc_2_e01166
Author(s) : Paul R , Jinkerson RE , Buss K , Steel J , Mohr R , Hess WR , Chen M , Fromme P
Ref : Genome Announc , 2 : , 2014
Abstract : Leptolyngbya sp. strain Heron Island is a cyanobacterium exhibiting chromatic acclimation. However, this strain has strong interactions with other bacteria, making it impossible to obtain axenic cultures for sequencing. A protocol involving an analysis of tetranucleotide frequencies, G+C content, and BLAST searches has been described for separating the cyanobacterial scaffolds from those of its cooccurring bacteria.
ESTHER : Paul_2014_Genome.Announc_2_e01166
PubMedSearch : Paul_2014_Genome.Announc_2_e01166
PubMedID: 24503993
Gene_locus related to this paper: 9cyan-u9vh69

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Rational reprogramming of fungal polyketide first-ring cyclization - Xu_2013_Proc.Natl.Acad.Sci.U.S.A_110_5398
Author(s) : Xu Y , Zhou T , Zhou Z , Su S , Roberts SA , Montfort WR , Zeng J , Chen M , Zhang W , Lin M , Zhan J , Molnar I
Ref : Proc Natl Acad Sci U S A , 110 :5398 , 2013
Abstract : Resorcylic acid lactones and dihydroxyphenylacetic acid lactones represent important pharmacophores with heat shock response and immune system modulatory activities. The biosynthesis of these fungal polyketides involves a pair of collaborating iterative polyketide synthases (iPKSs): a highly reducing iPKS with product that is further elaborated by a nonreducing iPKS (nrPKS) to yield a 1,3-benzenediol moiety bridged by a macrolactone. Biosynthesis of unreduced polyketides requires the sequestration and programmed cyclization of highly reactive poly-beta-ketoacyl intermediates to channel these uncommitted, pluripotent substrates to defined subsets of the polyketide structural space. Catalyzed by product template (PT) domains of the fungal nrPKSs and discrete aromatase/cyclase enzymes in bacteria, regiospecific first-ring aldol cyclizations result in characteristically different polyketide folding modes. However, a few fungal polyketides, including the dihydroxyphenylacetic acid lactone dehydrocurvularin, derive from a folding event that is analogous to the bacterial folding mode. The structural basis of such a drastic difference in the way a PT domain acts has not been investigated until now. We report here that the fungal vs. bacterial folding mode difference is portable on creating hybrid enzymes, and we structurally characterize the resulting unnatural products. Using structure-guided active site engineering, we unravel structural contributions to regiospecific aldol condensations and show that reshaping the cyclization chamber of a PT domain by only three selected point mutations is sufficient to reprogram the dehydrocurvularin nrPKS to produce polyketides with a fungal fold. Such rational control of first-ring cyclizations will facilitate efforts to the engineered biosynthesis of novel chemical diversity from natural unreduced polyketides.
ESTHER : Xu_2013_Proc.Natl.Acad.Sci.U.S.A_110_5398
PubMedSearch : Xu_2013_Proc.Natl.Acad.Sci.U.S.A_110_5398
PubMedID: 23509261
Gene_locus related to this paper: aspte-curs2 , floch-rads2

Title : Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution - Chen_2013_Nat.Commun_4_1595
Author(s) : Chen J , Huang Q , Gao D , Wang J , Lang Y , Liu T , Li B , Bai Z , Luis Goicoechea J , Liang C , Chen C , Zhang W , Sun S , Liao Y , Zhang X , Yang L , Song C , Wang M , Shi J , Liu G , Liu J , Zhou H , Zhou W , Yu Q , An N , Chen Y , Cai Q , Wang B , Liu B , Min J , Huang Y , Wu H , Li Z , Zhang Y , Yin Y , Song W , Jiang J , Jackson SA , Wing RA , Chen M
Ref : Nat Commun , 4 :1595 , 2013
Abstract : The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza.
ESTHER : Chen_2013_Nat.Commun_4_1595
PubMedSearch : Chen_2013_Nat.Commun_4_1595
PubMedID: 23481403
Gene_locus related to this paper: orysa-Q6ZDG3 , orysa-q6h415 , orysj-q6yse8 , orysa-q33aq0 , orybr-j3l7k2 , orybr-j3m138 , orybr-j3l6m8 , orybr-j3m3b3 , orybr-j3l8d1 , orybr-j3kza5 , orybr-j3mnb5 , orybr-j3n4p4 , orybr-j3lg73 , orybr-j3l342 , orybr-j3msi2 , orybr-j3nb83 , orybr-j3mpc5

Title : Complete Genome Sequence of the Industrial Strain Gluconobacter oxydans H24 - Ge_2013_Genome.Announc_1_e00003
Author(s) : Ge X , Zhao Y , Hou W , Zhang W , Chen W , Wang J , Zhao N , Lin J , Wang W , Chen M , Wang Q , Jiao Y , Yuan Z , Xiong X
Ref : Genome Announc , 1 : , 2013
Abstract : Gluconobacter oxydans is characterized by its ability to incompletely oxidize carbohydrates and alcohols. The high yields of its oxidation products and complete secretion into the medium make it important for industrial use. We report the finished genome sequence of Gluconobacter oxydans H24, an industrial strain with high l-sorbose productivity.
ESTHER : Ge_2013_Genome.Announc_1_e00003
PubMedSearch : Ge_2013_Genome.Announc_1_e00003
PubMedID: 23472221
Gene_locus related to this paper: gluth-t1e0l0 , gluoy-k7si88 , gluoy-k7smm7

Title : Genome of Helicobacter pylori strain XZ274, an isolate from a tibetan patient with gastric cancer in China - Guo_2012_J.Bacteriol_194_4146
Author(s) : Guo Y , Wang H , Li Y , Song Y , Chen C , Liao Y , Ren L , Guo C , Tong W , Shen W , Chen M , Mao X , Guo G , Zou Q
Ref : Journal of Bacteriology , 194 :4146 , 2012
Abstract : The infection rate of Helicobacter pylori is high all over the world, especially in the Chinese Tibetan Plateau. Here, we report the genome sequence of Helicobacter pylori strain XZ274 isolated from a Tibetan patient with gastric cancer. The strain contains 1,634,138 bp with 1,654 coding sequences and a pXZ274 plasmid of 22,406 bp with 26 coding sequences. This is the first complete genome sequence of Helicobacter pylori from the Tibetan Plateau in China.
ESTHER : Guo_2012_J.Bacteriol_194_4146
PubMedSearch : Guo_2012_J.Bacteriol_194_4146
PubMedID: 22815458
Gene_locus related to this paper: helpy-o25061

Title : Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor - Lin_2012_Mol.Pharmacol_82_843
Author(s) : Lin DC , Guo Q , Luo J , Zhang J , Nguyen K , Chen M , Tran T , Dransfield PJ , Brown SP , Houze J , Vimolratana M , Jiao XY , Wang Y , Birdsall NJ , Swaminath G
Ref : Molecular Pharmacology , 82 :843 , 2012
Abstract : Activation of FFA1 (GPR40), a member of G protein-coupling receptor family A, is mediated by medium- and long-chain fatty acids and leads to amplification of glucose-stimulated insulin secretion, suggesting a potential role for free fatty acid 1 (FFA1) as a target for type 2 diabetes. It was assumed previously that there is a single binding site for fatty acids and synthetic FFA1 agonists. However, using members of two chemical series of partial and full agonists that have been identified, radioligand binding interaction studies revealed that the full agonists do not bind to the same site as the partial agonists but exhibit positive heterotropic cooperativity. Analysis of functional data reveals positive functional cooperativity between the full agonists and partial agonists in various functional assays (in vitro and ex vivo) and also in vivo. Furthermore, the endogenous fatty acid docosahexaenoic acid (DHA) shows negative or neutral cooperativity with members of both series of agonists in binding assays but displays positive cooperativity in functional assays. Another synthetic agonist is allosteric with members of both agonist series, but apparently competitive with DHA. Therefore, there appear to be three allosterically linked binding sites on FFA1 with agonists specific for each of these sites. Activation of free fatty acid 1 receptor (FFAR1) by each of these agonists is differentially affected by mutations of two arginine residues, previously found to be important for FFAR1 binding and activation. These ligands with their high potencies and strong positive functional cooperativity with endogenous fatty acids, demonstrated in vitro and in vivo, have the potential to deliver therapeutic benefits.
ESTHER : Lin_2012_Mol.Pharmacol_82_843
PubMedSearch : Lin_2012_Mol.Pharmacol_82_843
PubMedID: 22859723

Title : Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment - Li_2012_Mol.Med.Rep_6_1450
Author(s) : Li Q , Chen M , Liu H , Yang L , Yang G
Ref : Mol Med Rep , 6 :1450 , 2012
Abstract : The aim of this study was to investigate the pathological changes in a rat model of Alzheimer's disease (AD) and the effect of donepezil hydrochloride (HCl) treatment. The rat model of AD was established by the bilateral injection of amyloid beta1-40 (Abeta1-40) into the hippocampus. Changes in spatial learning and memory functions were examined using the Morris water maze test and changes in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined using chemical colorimetry. Moreover, the changes in acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) expression were analyzed using immunohistochemical staining. The mRNA expression levels of the amyloid precursor protein (APP) and beta-secreted enzyme 1 (BACE1) were evaluated using RT-PCR. The effects of donepezil HCl on the aforementioned indices were also observed. The rat memories of the platform quadrants in the blank, sham and donepezil HCl groups were improved compared with those of the rats in the model group. The ratio of swim distance in the fourth platform quadrant (l4) to the total swim distance (l total) for the model group rats (l4/l total) was significantly decreased compared with that for the blank and sham group rats. Following donepezil HCl treatment, the ratio of l4/l total significantly increased. AD modeling caused a significant decrease in the CAT and GSH-Px activities in the brain tissues of the rats. The CAT and GSH-Px activities in the AD model rats significantly increased following donepezil HCl treatment. Moreover, donepezil HCl treatment significantly decreased the AChE, APP and BACE1 mRNA expression levels and increased the ChAT expression levels. Therefore, donepezil HCl was able to significantly decrease learning and memory damage in a rat model of AD.
ESTHER : Li_2012_Mol.Med.Rep_6_1450
PubMedSearch : Li_2012_Mol.Med.Rep_6_1450
PubMedID: 23023803

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Enhanced catalytic activity of lipase encapsulated in PCL nanofibers - Song_2012_Langmuir_28_6157
Author(s) : Song J , Kahveci D , Chen M , Guo Z , Xie E , Xu X , Besenbacher F , Dong M
Ref : Langmuir , 28 :6157 , 2012
Abstract : Use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Enzyme immobilization as an effective strategy for improving the enzyme activity has emerged from developments especially in nanoscience and nanotechnology. Here, lipase from Burkholderia cepacia (LBC), as an example of the luxuriant enzymes, was successfully encapsulated in polycaprolactone (PCL) nanofibers, proven by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Evaluated in both organic and aqueous medium, the activation factor of the encapsulated enzymes in the hydrolysis reaction was generally higher than that in the transesterification reaction. Enhanced catalytic activities were found when 5-20 w/w % of LBC was loaded. The effect of different solvents pretreatment on the activity of immobilized LBC was also investigated. The highest activation factor was found up to 14 for the sample containing acetone-treated LBC/PCL (10 w/w %). The encapsulated lipase reserved 50% of its original activity after the 10th run in the transesterification reaction in hexane medium. The mechanism of activation of lipase catalytic ability based on active PCL nanofiberous matrix is proposed.
ESTHER : Song_2012_Langmuir_28_6157
PubMedSearch : Song_2012_Langmuir_28_6157
PubMedID: 22397625

Title : Genome sequence of Enterobacter sp. strain SP1, an endophytic nitrogen-fixing bacterium isolated from sugarcane - Zhu_2012_J.Bacteriol_194_6963
Author(s) : Zhu B , Chen M , Lin L , Yang L , Li Y , An Q
Ref : Journal of Bacteriology , 194 :6963 , 2012
Abstract : Enterobacter sp. strain SP1 is an endophytic nitrogen-fixing bacterium isolated from a sugarcane stem and can promote plant growth. The draft genome sequence of strain SP1 presented here will promote comparative genomic studies to determine the genetic background of interactions between endophytic enterobacteria and plants.
ESTHER : Zhu_2012_J.Bacteriol_194_6963
PubMedSearch : Zhu_2012_J.Bacteriol_194_6963
PubMedID: 23209221
Gene_locus related to this paper: 9entr-w6iyd9 , 9entr-w6j8b5 , 9entr-w6jbs2 , 9entr-w6j1u8

Title : Development of a multiplex PCR assay for detection and genogrouping of Neisseria meningitidis - Zhu_2012_J.Clin.Microbiol_50_46
Author(s) : Zhu H , Wang Q , Wen L , Xu J , Shao Z , Chen M , Reeves PR , Cao B , Wang L
Ref : J Clin Microbiol , 50 :46 , 2012
Abstract : Neisseria meningitidis is a leading pathogen of epidemic bacterial meningitis and fulminant sepsis worldwide. Twelve different N. meningitidis serogroups have been identified to date based on antigenic differences in the capsular polysaccharide. However, more than 90% of human cases of N. meningitidis meningitis are the result of infection with just five serogroups, A, B, C, W135, and Y. Efficient methods of detection and genogrouping of N. meningitidis isolates are needed, therefore, in order to monitor prevalent serogroups as a means of disease control and prevention. The capsular gene complex regions have been sequenced from only seven out of the 12 serogroups. In this study, the capsular gene complexes of the remaining five serogroups were sequenced and analyzed. Primers were designed that were specific for N. meningitidis species and for the 12 individual serogroups, and a multiplex PCR assay using these specific primers was developed for N. meningitidis detection and genogrouping. The assay was tested using 15 reference strains covering all 12 serogroups, 143 clinical isolates, and 21 strains from closely related species or from species that cause meningitis. The assay could detect N. meningitidis serogroups and was shown to be specific, with a detection sensitivity of 1 ng of genomic DNA (equivalent to -4 x 10(5) genomes) or 3 x 10(5) CFU/ml in noncultured mock cerebrospinal fluid (CSF) specimens. This study, therefore, describes for the first time the development of a molecular protocol for the detection of all N. meningitidis serogroups. This multiplex PCR-based assay may have use for the clinical diagnosis and epidemiological surveillance of N. meningitidis.
ESTHER : Zhu_2012_J.Clin.Microbiol_50_46
PubMedSearch : Zhu_2012_J.Clin.Microbiol_50_46
PubMedID: 22090406
Gene_locus related to this paper: neime-h6t5x5

Title : Genome sequence and transcriptome analysis of the radioresistant bacterium Deinococcus gobiensis: insights into the extreme environmental adaptations - Yuan_2012_PLoS.One_7_e34458
Author(s) : Yuan M , Chen M , Zhang W , Lu W , Wang J , Yang M , Zhao P , Tang R , Li X , Hao Y , Zhou Z , Zhan Y , Yu H , Teng C , Yan Y , Ping S , Wang Y , Lin M
Ref : PLoS ONE , 7 :e34458 , 2012
Abstract : The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential.
ESTHER : Yuan_2012_PLoS.One_7_e34458
PubMedSearch : Yuan_2012_PLoS.One_7_e34458
PubMedID: 22470573
Gene_locus related to this paper: deigi-h8gtt4 , deigi-h8h0j9

Title : Genome sequence of Acinetobacter calcoaceticus PHEA-2, isolated from industry wastewater - Zhan_2011_J.Bacteriol_193_2672
Author(s) : Zhan Y , Yan Y , Zhang W , Yu H , Chen M , Lu W , Ping S , Peng Z , Yuan M , Zhou Z , Elmerich C , Lin M
Ref : Journal of Bacteriology , 193 :2672 , 2011
Abstract : Genome analysis of Acinetobacter calcoaceticus PHEA-2 was undertaken because of the importance of this bacterium for bioremediation of phenol-polluted water and because of the close phylogenetic relationship of this species with the human pathogen Acinetobacter baumannii. To our knowledge, this is the first strain of A. calcoaceticus whose genome has been sequenced.
ESTHER : Zhan_2011_J.Bacteriol_193_2672
PubMedSearch : Zhan_2011_J.Bacteriol_193_2672
PubMedID: 21441526
Gene_locus related to this paper: aciad-q6fc40 , aciba-d0c992 , aciba-q76hj1 , acibt-a3m5r6 , acibt-a3m5t3 , acibt-a3m5x2 , acica-d0ryi9 , acica-d0ryx6 , acicp-f0kgu1 , acicp-f0kh68 , acicp-f0khy0 , acicp-f0kj61 , aciba-w3svn7 , aciba-a0a009wzt4

Title : Complete genome sequence of the nitrogen-fixing and rhizosphere-associated bacterium Pseudomonas stutzeri strain DSM4166 - Yu_2011_J.Bacteriol_193_3422
Author(s) : Yu H , Yuan M , Lu W , Yang J , Dai S , Li Q , Yang Z , Dong J , Sun L , Deng Z , Zhang W , Chen M , Ping S , Han Y , Zhan Y , Yan Y , Jin Q , Lin M
Ref : Journal of Bacteriology , 193 :3422 , 2011
Abstract : We present here the analysis of the whole-genome sequence of Pseudomonas stutzeri strain DSM4166, a diazotrophic isolate from the rhizosphere of a Sorghum nutans cultivar. To our knowledge, this is the second genome to be sequenced for P. stutzeri. The availability and analysis of the genome provide insight into the evolution of the nitrogen fixation property and identification of rhizosphere competence traits required in interactions with host plants.
ESTHER : Yu_2011_J.Bacteriol_193_3422
PubMedSearch : Yu_2011_J.Bacteriol_193_3422
PubMedID: 21515765
Gene_locus related to this paper: pseu5-a4vfn0 , pseu5-a4vj02 , pseu5-a4vrl9 , pseut-f8h720 , pseu5-a4vkl7 , pseu5-a4vgd4 , pseu5-a4vr33

Title : The role of GNAS and other imprinted genes in the development of obesity - Weinstein_2010_Int.J.Obes.(Lond)_34_6
Author(s) : Weinstein LS , Xie T , Qasem A , Wang J , Chen M
Ref : Int J Obes (Lond) , 34 :6 , 2010
Abstract : Genomic imprinting is an epigenetic phenomenon affecting a small number of genes, which leads to differential expression from the two parental alleles. Imprinted genes are known to regulate fetal growth and a 'kinship' or 'parental conflict' model predicts that paternally and maternally expressed imprinted genes promote and inhibit fetal growth, respectively. In this review we examine the role of imprinted genes in postnatal growth and metabolism, with an emphasis on the GNAS/Gnas locus. GNAS is a complex imprinted locus with multiple oppositely imprinted gene products, including the G-protein alpha-subunit G(s)alpha that is expressed primarily from the maternal allele in some tissues and the G(s)alpha isoform XLalphas that is expressed only from the paternal allele. Maternal, but not paternal, G(s)alpha mutations lead to obesity in Albright hereditary osteodystrophy. Mouse studies show that this phenomenon is due to G(s)alpha imprinting in the central nervous system leading to a specific defect in the ability of central melanocortins to stimulate sympathetic nervous system activity and energy expenditure. In contrast mutation of paternally expressed XLalphas leads to opposite metabolic effects in mice. Although these findings conform to the 'kinship' model, the effects of other imprinted genes on body weight regulation do not conform to this model.
ESTHER : Weinstein_2010_Int.J.Obes.(Lond)_34_6
PubMedSearch : Weinstein_2010_Int.J.Obes.(Lond)_34_6
PubMedID: 19844212

Title : Organophosphorus pesticide residues in milled rice (Oryza sativa) on the Chinese market and dietary risk assessment - Chen_2009_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess_26_340
Author(s) : Chen C , Li Y , Chen M , Chen Z , Qian Y
Ref : Food Additives & Contaminants Part A Chem Anal Control Expo Risk Assess , 26 :340 , 2009
Abstract : The present study investigates the occurrence of acetylcholinesterase (AChE)-inhibiting organophosphorus (OP) pesticide residues in milled rice samples obtained form local markets in China during the period 2004-2006 and estimates their cumulative exposure. Concentrations of OP pesticides were determined by gas chromatography with flame photometric detection (GC-FPD). The results showed that 9.3% of the samples contained detectable residues of at least one of the seven target OP pesticides (chlorpyrifos, dichlorvos, omethoate, methamidophos, parathion-methyl, parathion and triazophos) mainly used for agriculture in China, with concentrations ranging 0.011-1.756 mg kg(-1). Rice consumption data was obtained from an individual food consumption survey. Relative potency factors (RPFs) for each pesticide were calculated with methamidophos as the index compound (IC), using 1- or 2-year chronic non-observed adverse effect levels (NOAEL) for AChE inhibition, mostly in rat brain, obtained from international evaluations of pesticides. Exposure to AChE-inhibiting pesticides for the population above 7 years old at P99.9 represented 52-94.5% of the acceptable daily intake (ADI) expressed as methamidophos. Estimated exposure for children aged 2-4 and 4-7 years at P99.9 were 119 and 104.3% of the ADI level, respectively. This study suggests that a yearly monitoring program for OP pesticide residues and strict implementation of the national safety standard for milled rice is necessary.
ESTHER : Chen_2009_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess_26_340
PubMedSearch : Chen_2009_Food.Addit.Contam.Part.A.Chem.Anal.Control.Expo.Risk.Assess_26_340
PubMedID: 19680907

Title : Catalytic mechanism of SHCHC synthase in the menaquinone biosynthesis of Escherichia coli: identification and mutational analysis of the active site residues - Jiang_2009_Biochemistry_48_6921
Author(s) : Jiang M , Chen X , Wu XH , Chen M , Wu YD , Guo Z
Ref : Biochemistry , 48 :6921 , 2009
Abstract : (1R,6R)-2-Succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase (MenH) is an alpha/beta fold enzyme containing a catalytically essential serine-histidine-aspartate triad typical of serine proteases but catalyzes a pyruvate elimination reaction initiated by alpha-proton abstraction in the menaquinone biosynthetic pathway of Escherichia coli. In this study, we identify the active site residues in the synthase through sequence analysis and structural modeling and study their mechanistic roles in MenH catalysis. Steady-state kinetic characterization of site-directed mutants of the active site residues shows that three conserved arginine residues (Arg-90, Arg-124, and Arg-168) likely form ionic salt bridges with three carboxylate groups of the substrate in the Michaelis complex and that the side-chain polar groups of the conserved tyrosine (Tyr-85) and tryptophan (Trp-147) residues likely donate hydrogen bonds to form an "oxyanion hole". In addition, the pH dependence of the MenH kinetic properties reveals a catalytic base with a pK(a) highly dependent on the hydroxyl group of the triad serine residue in the enzymatic reaction. Moreover, proton inventory experiments demonstrate that the SHCHC synthase adopts one-proton catalysis like many serine proteases. These results allow the proposal of a mechanism in which the histidine residue of the MenH triad serves as a general base catalyst to deprotonate the triad seryl hydroxyl group in the alpha-proton abstraction from the substrate. As such, the MenH triad performs a simple and fundamental proton transfer reaction occurring repeatedly in the reactions catalyzed by serine proteases and alpha/beta fold hydrolases, suggesting a common evolutionary origin for all serine-histidine-aspartate triads serving different catalytic functions.
ESTHER : Jiang_2009_Biochemistry_48_6921
PubMedSearch : Jiang_2009_Biochemistry_48_6921
PubMedID: 19545176
Gene_locus related to this paper: ecoli-YFBB

Title : Identification and characterization of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase in the menaquinone biosynthesis of Escherichia coli - Jiang_2008_Biochemistry_47_3426
Author(s) : Jiang M , Chen X , Guo ZF , Cao Y , Chen M , Guo Z
Ref : Biochemistry , 47 :3426 , 2008
Abstract : Menaquinone is a lipid-soluble molecule that plays an essential role as an electron carrier in the respiratory chain of many bacteria. We have previously shown that its biosynthesis in Escherichia coli involves a new intermediate, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC), and requires an additional enzyme to convert this intermediate into (1 R,6 R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). Here, we report the identification and characterization of MenH (or YfbB), an enzyme previously proposed to catalyze a late step in menaquinone biosynthesis, as the SHCHC synthase. The synthase catalyzes a proton abstraction reaction that results in 2,5-elimination of pyruvate from SEPHCHC and the formation of SHCHC. It is an efficient enzyme ( k cat/ K M = 2.0 x 10 (7) M (-1) s (-1)) that provides a smaller transition-state stabilization than other enzymes catalyzing proton abstraction from carbon acids. Despite its lack of the proposed thioesterase activity, the SHCHC synthase is homologous to the well-characterized C-C bond hydrolase MhpC. The crystallographic structure of the Vibrio cholerae MenH protein closely resembles that of MhpC and contains a Ser-His-Asp triad typical of serine proteases. Interestingly, this triad is conserved in all MenH proteins and is essential for the SHCHC synthase activity. Mutational analysis found that the catalytic efficiency of the E. coli protein is reduced by 1.4 x 10 (3), 2.1 x 10 (5), and 9.3 x 10 (3) folds when alanine replaces serine, histidine, and aspartate of the triad, respectively. These results show that the SHCHC synthase is closely related to alpha/beta hydrolases but catalyzes a reaction mechanistically distinct from all known hydrolase reactions.
ESTHER : Jiang_2008_Biochemistry_47_3426
PubMedSearch : Jiang_2008_Biochemistry_47_3426
PubMedID: 18284213
Gene_locus related to this paper: ecoli-YFBB

Title : Dynamic evolution of oryza genomes is revealed by comparative genomic analysis of a genus-wide vertical data set - Ammiraju_2008_Plant.Cell_20_3191
Author(s) : Ammiraju JS , Lu F , Sanyal A , Yu Y , Song X , Jiang N , Pontaroli AC , Rambo T , Currie J , Collura K , Talag J , Fan C , Goicoechea JL , Zuccolo A , Chen J , Bennetzen JL , Chen M , Jackson S , Wing RA
Ref : Plant Cell , 20 :3191 , 2008
Abstract : Oryza (23 species; 10 genome types) contains the world's most important food crop - rice. Although the rice genome serves as an essential tool for biological research, little is known about the evolution of the other Oryza genome types. They contain a historical record of genomic changes that led to diversification of this genus around the world as well as an untapped reservoir of agriculturally important traits. To investigate the evolution of the collective Oryza genome, we sequenced and compared nine orthologous genomic regions encompassing the Adh1-Adh2 genes (from six diploid genome types) with the rice reference sequence. Our analysis revealed the architectural complexities and dynamic evolution of this region that have occurred over the past approximately 15 million years. Of the 46 intact genes and four pseudogenes in the japonica genome, 38 (76%) fell into eight multigene families. Analysis of the evolutionary history of each family revealed independent and lineage-specific gain and loss of gene family members as frequent causes of synteny disruption. Transposable elements were shown to mediate massive replacement of intergenic space (>95%), gene disruption, and gene/gene fragment movement. Three cases of long-range structural variation (inversions/deletions) spanning several hundred kilobases were identified that contributed significantly to genome diversification.
ESTHER : Ammiraju_2008_Plant.Cell_20_3191
PubMedSearch : Ammiraju_2008_Plant.Cell_20_3191
PubMedID: 19098269

Title : The genome of Heliobacterium modesticaldum, a phototrophic representative of the Firmicutes containing the simplest photosynthetic apparatus - Sattley_2008_J.Bacteriol_190_4687
Author(s) : Sattley WM , Madigan MT , Swingley WD , Cheung PC , Clocksin KM , Conrad AL , Dejesa LC , Honchak BM , Jung DO , Karbach LE , Kurdoglu A , Lahiri S , Mastrian SD , Page LE , Taylor HL , Wang ZT , Raymond J , Chen M , Blankenship RE , Touchman JW
Ref : Journal of Bacteriology , 190 :4687 , 2008
Abstract : Despite the fact that heliobacteria are the only phototrophic representatives of the bacterial phylum Firmicutes, genomic analyses of these organisms have yet to be reported. Here we describe the complete sequence and analysis of the genome of Heliobacterium modesticaldum, a thermophilic species belonging to this unique group of phototrophs. The genome is a single 3.1-Mb circular chromosome containing 3,138 open reading frames. As suspected from physiological studies of heliobacteria that have failed to show photoautotrophic growth, genes encoding enzymes for known autotrophic pathways in other phototrophic organisms, including ribulose bisphosphate carboxylase (Calvin cycle), citrate lyase (reverse citric acid cycle), and malyl coenzyme A lyase (3-hydroxypropionate pathway), are not present in the H. modesticaldum genome. Thus, heliobacteria appear to be the only known anaerobic anoxygenic phototrophs that are not capable of autotrophy. Although for some cellular activities, such as nitrogen fixation, there is a full complement of genes in H. modesticaldum, other processes, including carbon metabolism and endosporulation, are more genetically streamlined than they are in most other low-G+C gram-positive bacteria. Moreover, several genes encoding photosynthetic functions in phototrophic purple bacteria are not present in the heliobacteria. In contrast to the nutritional flexibility of many anoxygenic phototrophs, the complete genome sequence of H. modesticaldum reveals an organism with a notable degree of metabolic specialization and genomic reduction.
ESTHER : Sattley_2008_J.Bacteriol_190_4687
PubMedSearch : Sattley_2008_J.Bacteriol_190_4687
PubMedID: 18441057

Title : Niche adaptation and genome expansion in the chlorophyll d-producing cyanobacterium Acaryochloris marina - Swingley_2008_Proc.Natl.Acad.Sci.U.S.A_105_2005
Author(s) : Swingley WD , Chen M , Cheung PC , Conrad AL , Dejesa LC , Hao J , Honchak BM , Karbach LE , Kurdoglu A , Lahiri S , Mastrian SD , Miyashita H , Page L , Ramakrishna P , Satoh S , Sattley WM , Shimada Y , Taylor HL , Tomo T , Tsuchiya T , Wang ZT , Raymond J , Mimuro M , Blankenship RE , Touchman JW
Ref : Proc Natl Acad Sci U S A , 105 :2005 , 2008
Abstract : Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and alpha-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria.
ESTHER : Swingley_2008_Proc.Natl.Acad.Sci.U.S.A_105_2005
PubMedSearch : Swingley_2008_Proc.Natl.Acad.Sci.U.S.A_105_2005
PubMedID: 18252824
Gene_locus related to this paper: acam1-a8zmz3 , acam1-a8zp06 , acam1-b0byr5 , acam1-b0bz47 , acam1-b0bzk5 , acam1-b0bzu9 , acam1-b0c1b7 , acam1-b0c1p4 , acam1-b0c1r0 , acam1-b0c2k6 , acam1-b0c2p9 , acam1-b0c5j5 , acam1-b0c8k1 , acam1-b0c301 , acam1-b0c386 , acam1-b0c616 , acam1-b0c873 , acam1-b0c895 , acam1-b0cbs7 , acam1-b0cch0 , acam1-b0cch8 , acam1-b0ce13 , acam1-b0ce05 , acam1-b0cfu2 , acam1-a8zpc6 , acam1-b0c5g8

Title : Resistance mechanisms and associated mutations in acetylcholinesteras genes in Sitobion avenae (Fabricius) - Chen_2007_Pestic.Biochem.Physiol_87_189
Author(s) : Chen M , Han Z , Qiao X , Qu M
Ref : Pesticide Biochemistry and Physiology , 87 :189 , 2007
Abstract : Wheat aphid, Sitobion avenae (fabricius), is one of the most important wheat pests and has been reported to be resistant to commonly used insecticides in China. To determine the resistance mechanism, the resistant and susceptible strains were developed in laboratory and comparably studied. A bioassay revealed that the resistant strain showed high resistance to pirimicarb (RR: 161.8), moderate reistance to omethoate (32.5) and monocrotophos (33.5), and low resistance to deltamethrin (6.3) and thiodicarb (5.5). A biochemistry analysis showed that both strains had similar glutathione-S-transferase (GST) activity, but the resistant strain had 3.8-fold higher esterase activity, and its AChE was insensitive to this treatment. The I50 increased by 25.8-, 10.7-, and 10.4-folds for pirimicarb, omethoate, and monocrotophos, respectively, demonstrating that GST had not been involved in the resistance of S. avenae. The enhanced esterase contributed to low level resistance to all the insecticides tested, whereas higher resistance to pirimicarb, omethoate, and monocrotophos mainly depended on AChE insensitivity. However, the AChE of the resistant strain was still sensitive to thiodicarb (1.7-fold). Thus, thiodicarb could be used as substitute for control of the resistant S. avenae in this case. Furthermore, the two different AChE genes cloned from different resistant and susceptible individuals were also compared. Two mutations, L436(336)S in Sa.Ace1 and W516(435)R in Sa.Ace2, were found consistently associated with the insensitivity of AChE. They were thought to be the possible resistance mutations, but further work is needed to confirm this hypothesis.
ESTHER : Chen_2007_Pestic.Biochem.Physiol_87_189
PubMedSearch : Chen_2007_Pestic.Biochem.Physiol_87_189
PubMedID:
Gene_locus related to this paper: sitav-ACHE1 , sitav-ACHE2

Title : Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall - Wu_2006_Atherosclerosis_187_65
Author(s) : Wu X , Wang J , Fan J , Chen M , Chen L , Huang W , Liu G
Ref : Atherosclerosis , 187 :65 , 2006
Abstract : Recent studies on mice demonstrated that lipoprotein lipase (LPL) located in the arterial wall might play a pro-atherogenic role. There are major differences between humans and mice in lipoprotein metabolism and in susceptibility to atherosclerosis. We have therefore used rabbits fed normal chow diet as a model to assess such localized effects by adenovirus-mediated gene transfer of human catalytically active wild type LPL (hLPLwt) and an inactive mutant (hLPL194) to balloon-injured carotid arteries. By morphometric analysis on cryosections stained with Oil Red O (ORO) we found 7- and 4-fold increases, respectively, of lipid deposition in the arterial walls 7 days after infection with adenovirus expressing hLPLwt or hLPL194, when compared with a virus expressing human alkaline phosphatase (hAP) as control. Macrophages were detected in the arteries expressing both forms of LPL, but apoB was only found in arteries expressing hLPLwt. Expression of the LPL gene products was transient and was gone after 2 weeks, but the accumulated lipid deposits remained between the neointimal and the media layers even after 8 weeks. Our data demonstrate that expression of LPL in the arterial wall (with or without lipase activity) leads to lipid accumulation in balloon-injured rabbit arteries, and could result in enhanced formation of atherosclerotic lesions.
ESTHER : Wu_2006_Atherosclerosis_187_65
PubMedSearch : Wu_2006_Atherosclerosis_187_65
PubMedID: 16191430

Title : Cloning and sequence analysis of 2 different acetylcholinesterase genes in Rhopalosiphum padi and Sitobion avenae - Chen_2006_Genome_49_239
Author(s) : Chen M , Han Z
Ref : Genome , 49 :239 , 2006
Abstract : Two genes encoding different acetylcholinesterases (AChE) were successfully cloned from 2 species of aphid, Rhopalosiphum padi (L.) and Sitobion avenae (F.). They were named Rp.AChE1 (GenBank accession No. AY707318), Rp.AChE2 (AY667435), Sa.AChE1 (AY707319), and Sa.AChE2 (AY819704), and were 2133, 2363, 2131, and 2362 bp in length and encoded 664, 676, 664, and 676 amino acids, respectively. All of them shared the characteristics of the AChE family: catalytic tiads, 3 intra-chain disulfide bridges, an acyl pocket, and the conservative aromatic residues for the active site of the gorge. Sequence analysis revealed that Rp.AChE1 and Sa.AChE1 showed higher identity to the reported orthologous genes of Drosophila AChE, and Rp.AChE2 and Sa.AChE2 to paralogous genes. However, in each of the aphids, the 2 genes from the same species shared only 29% identity between one another. It was therefore concluded that each of the aphids has 2 different AChE genes, which are either orthologous or paralogous to Drosophila AChE. The high conservation of AChE1 and AChE2 indicated that 2 acetylcholinesterases exist popularly and that both might function in aphids.
ESTHER : Chen_2006_Genome_49_239
PubMedSearch : Chen_2006_Genome_49_239
PubMedID: 16604106
Gene_locus related to this paper: rhopd-ACHE1 , rhopd-ACHE2 , sitav-ACHE1 , sitav-ACHE2

Title : Switching From Donepezil to Rivastigmine Is Well Tolerated: Results of an Open-Label Safety and Tolerability Study - Sadowsky_2005_Prim.Care.Companion.J.Clin.Psychiatry_7_43
Author(s) : Sadowsky CH , Farlow MR , Atkinson L , Steadman J , Koumaras B , Chen M , Mirski D
Ref : Prim Care Companion J Clin Psychiatry , 7 :43 , 2005
Abstract : Background: Transitioning patients between cholinesterase inhibitors was thought to require a washout period to avoid cholinergic toxicity; however, evidence suggests that abrupt discontinuation of donepezil may lead to cognitive decline. We evaluated the safety and tolerability of an immediate switch from donepezil to rivastigmine.Method: This is an analysis of the safety and tolerability data from the first 28 days of an open-label, multicenter, prospective trial, conducted from August 2002 to August 2003, in which patients satisfying NINCDS-ADRDA criteria for probable Alzheimer's disease were administered rivastigmine 1.5 mg b.i.d. within 24 to 36 hours of donepezil discontinuation. Results are compared with adverse event rates from a retrospective analysis of a pivotal, placebo-controlled trial examining patients not previously treated with a cholinesterase inhibitor.Results: Fifty-eight of 61 patients completed the first 28 days, with no suspected drug-related discontinuations during this period. Incidence of overall gastrointestinal adverse events at day 7 was 8.2%, and at day 28 was 11.5%. The corresponding rate for rivastigmine-treated patients in the retrospective analysis of the pivotal trial for day 7 was 3.3%.Conclusion: These study results suggest that transitioning patients from donepezil to rivastigmine without a washout period is safe and well tolerated.
ESTHER : Sadowsky_2005_Prim.Care.Companion.J.Clin.Psychiatry_7_43
PubMedSearch : Sadowsky_2005_Prim.Care.Companion.J.Clin.Psychiatry_7_43
PubMedID: 15841194

Title : Presynaptic activation of silent synapses and growth of new synapses contribute to intermediate and long-term facilitation in Aplysia - Kim_2003_Neuron_40_151
Author(s) : Kim JH , Udo H , Li HL , Youn TY , Chen M , Kandel ER , Bailey CH
Ref : Neuron , 40 :151 , 2003
Abstract : The time course and functional significance of the structural changes associated with long-term facilitation of Aplysia sensory to motor neuron synaptic connections in culture were examined by time-lapse confocal imaging of individual sensory neuron varicosities labeled with three different fluorescent markers: the whole-cell marker Alexa-594 and two presynaptic marker proteins-synaptophysin-eGFP to monitor changes in synaptic vesicle distribution and synapto-PHluorin to monitor active transmitter release sites. Repeated pulses of serotonin induce two temporally, morphologically, and molecularly distinct presynaptic changes: (1) a rapid activation of silent presynaptic terminals by filling of preexisting empty varicosities with synaptic vesicles, which parallels intermediate-term facilitation, is completed within 3-6 hr and requires translation but not transcription and (2) a slower generation of new functional varicosities which occurs between 12-18 hr and requires transcription and translation. Enrichment of empty varicosities with synaptophysin accounts for 32% of the newly activated synapses at 24 hr, whereas newly formed varicosities account for 68%.
ESTHER : Kim_2003_Neuron_40_151
PubMedSearch : Kim_2003_Neuron_40_151
PubMedID: 14527440

Title : Calcitonin gene-related peptides: their binding sites and receptor accessory proteins in adult mammalian skeletal muscles - Fernandez_2003_Neurosci_119_335
Author(s) : Fernandez HL , Chen M , Nadelhaft I , Durr JA
Ref : Neuroscience , 119 :335 , 2003
Abstract : This work addresses the presence, pharmacological properties, and anatomical localization of calcitonin gene-related peptide-alpha (CGRPalpha) binding sites and the receptor's accessory proteins in endplate-enriched and non-endplate muscle membrane samples from adult rat gracilis muscles. We examined the binding of (125)I-[Tyr(0)]-CGRPalpha, the competitive binding of CGRPalpha analogs, the immunohistochemical localization of the receptor's accessory proteins, and Western blots of the receptor component protein. Results show that: (a). (125)I-[Tyr(0)]-CGRPalpha binding is saturable, specific, and consistent with the presence of a homogeneous population of binding sites (Hill coefficients=1.0) in endplate and non-endplate samples exhibiting dissociation constants of 0.39 nM and 0.38 nM, respectively; (b). the density of binding sites in the endplate samples (71.0 fmoles/mg protein) is considerably higher than that in their non-endplate counterparts (34.6 fmoles/mg protein); (c). unlabeled CGRPalpha, hCGRP8-37 and calcitonin compete with the radioligand with the same order of potency in the endplate and non-endplate samples; and (d). the localization of the receptor accessory proteins, including the receptor activity-modifying protein (RAMP1) and the receptor component protein (RCP), for the most part matches that of the motor end-plates. Thus, gracilis muscles express CGRPalpha-specific binding sites which are predominantly localized in the muscle's motor endplate regions where RAMP1, RCP, CGRPalpha, acetylcholine receptors, and acetylcholinesterase are detected in high concentrations. These findings imply that the CGRPalpha binding sites reflect the presence of physiologically functional receptors with a pharmacological profile consistent with that of the CGRPalpha receptor type 1 (CGRP1). When considered together with earlier studies on the same neuromuscular preparation, the present work further suggests that the motoneuron-dependent trophic control of acetylcholine receptors and acetylcholinesterase in skeletal muscle endplates is partly mediated by nerve-derived CGRPalpha activating specific receptors which are highly sensitive to the truncated peptide hCGRP8-37.
ESTHER : Fernandez_2003_Neurosci_119_335
PubMedSearch : Fernandez_2003_Neurosci_119_335
PubMedID: 12770550

Title : An oxidation domain in the BlmIII non-ribosomal peptide synthetase probably catalyzing thiazole formation in the biosynthesis of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003 - Du_2000_FEMS.Microbiol.Lett_189_171
Author(s) : Du L , Chen M , Sanchez C , Shen B
Ref : FEMS Microbiology Letters , 189 :171 , 2000
Abstract : We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide synthetases are involved in the formation of the bithiazole moiety of the anti-tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the identification and characterization of an oxidation domain in BlmIII. The oxidation domain shows local homology to a family of oxidoreductases and is present in all thiazole-forming non-ribosomal peptide synthetase modules known to date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to homogeneity. The oxidation domain contains one molar equivalent of non-covalently bound FMN as a prosthetic group. These results provide experimental evidence for an oxidation domain within non-ribosomal peptide synthetases, suggesting that BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin biosynthesis.
ESTHER : Du_2000_FEMS.Microbiol.Lett_189_171
PubMedSearch : Du_2000_FEMS.Microbiol.Lett_189_171
PubMedID: 10930733
Gene_locus related to this paper: strve-Q9FB36 , 9actn-q9fb38

Title : The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase - Du_2000_Chem.Biol_7_623
Author(s) : Du L , Sanchez C , Chen M , Edwards DJ , Shen B
Ref : Chemical Biology , 7 :623 , 2000
Abstract : BACKGROUND: The structural and catalytic similarities between modular nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) inspired us to search for a hybrid NRPS-PKS system. The antitumor drug bleomycin (BLM) is a natural hybrid peptide-polyketide metabolite, the biosynthesis of which provides an excellent opportunity to investigate intermodular communication between NRPS and PKS modules. Here, we report the cloning, sequencing, and characterization of the BLM biosynthetic gene cluster from Streptomyces verticillus ATCC15003. RESULTS: A set of 30 genes clustered with the previously characterized blmAB resistance genes were defined by sequencing a 85-kb contiguous region of DNA from S. verticillus ATCC15003. The sequenced gene cluster consists of 10 NRPS genes encoding nine NRPS modules, a PKS gene encoding one PKS module, five sugar biosynthesis genes, as well as genes encoding other biosynthesis, resistance, and regulatory proteins. The substrate specificities of individual NRPS and PKS modules were predicted based on sequence analysis, and the amino acid specificities of two NRPS modules were confirmed biochemically in vitro. The involvement of the cloned genes in BLM biosynthesis was demonstrated by bioconversion of the BLM aglycones into BLMs in Streptomyces lividans expressing a part of the gene cluster. CONCLUSION: The blm gene cluster is characterized by a hybrid NRPS-PKS system, supporting the wisdom of combining individual NRPS and PKS modules for combinatorial biosynthesis. The availability of the blm gene cluster has set the stage for engineering novel BLM analogs by genetic manipulation of genes governing BLM biosynthesis and for investigating the molecular basis for intermodular communication between NRPS and PKS in the biosynthesis of hybrid peptide-polyketide metabolites.
ESTHER : Du_2000_Chem.Biol_7_623
PubMedSearch : Du_2000_Chem.Biol_7_623
PubMedID: 11048953
Gene_locus related to this paper: strve-Q9FB36 , 9actn-q9fb38

Title : A novel function for serotonin-mediated short-term facilitation in aplysia: conversion of a transient, cell-wide homosynaptic hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement - Bailey_2000_Proc.Natl.Acad.Sci.U.S.A_97_11581
Author(s) : Bailey CH , Giustetto M , Zhu H , Chen M , Kandel ER
Ref : Proc Natl Acad Sci U S A , 97 :11581 , 2000
Abstract : Studies of sensitization and classical conditioning of the gill-withdrawal reflex in Aplysia have shown that the synaptic connections between identified glutamatergic sensory neurons and motor neurons can be enhanced in one of two ways: by a heterosynaptic (modulatory input-dependent) mechanism that gives rise with repetition to long-term facilitation and by a homosynaptic (activity-dependent) mechanism that gives rise with repetition to a facilitation that is partially blocked by 2-amino-5-phosphonovaleric acid and by injection of 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetate (BAPTA) into the postsynaptic cell and is similar to long-term potentiation in the hippocampus. We here have examined how these two forms of facilitation interact at the level of an individual synaptic connection by using a culture preparation consisting of a single bifurcated sensory neuron that forms independent synaptic contacts with each of two spatially separated motor neurons. We find that the homosynaptic facilitation produced by a train of action potentials is cell wide and is evident at all of the terminals of the sensory neuron. By contrast, the heterosynaptic facilitation mediated by the modulatory transmitter serotonin (5-HT) can operate at the level of a single synapse. Homosynaptic activation gives rise to only a transient facilitation lasting a few hours, even when repeated in a spaced manner. The heterosynaptic facilitation produced by a single pulse of 5-HT, applied to one terminal of the sensory neuron, also lasts only minutes. However, when one or more homosynaptic trains of spike activity are paired with even a single pulse of 5-HT applied to one of the two branches of the sensory neuron, the combined actions lead to a selective enhancement in synaptic strength only at the 5-HT-treated branch that now lasts more than a day, and thus amplifies, by more than 20-fold, the duration of the individually produced homo- and heterosynaptic facilitation. This form of synapse-specific facilitation has unusual long-term properties. It does not require protein synthesis, nor is it accompanied by synaptic growth.
ESTHER : Bailey_2000_Proc.Natl.Acad.Sci.U.S.A_97_11581
PubMedSearch : Bailey_2000_Proc.Natl.Acad.Sci.U.S.A_97_11581
PubMedID: 11027355

Title : A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis - Casadio_1999_Cell_99_221
Author(s) : Casadio A , Martin KC , Giustetto M , Zhu H , Chen M , Bartsch D , Bailey CH , Kandel ER
Ref : Cell , 99 :221 , 1999
Abstract : In a culture system where a bifurcated Aplysia sensory neuron makes synapses with two motor neurons, repeated application of serotonin (5-HT) to one synapse produces a CREB-mediated, synapse-specific, long-term facilitation, which can be captured at the opposite synapse by a single pulse of 5-HT. Repeated pulses of 5-HT applied to the cell body of the sensory neuron produce a CREB-dependent, cell-wide facilitation, which, unlike synapse-specific facilitation, is not associated with growth and does not persist beyond 48 hr. Persistent facilitation and synapse-specific growth can be induced by a single pulse of 5-HT applied to a peripheral synapse. Thus, the short-term process initiated by a single pulse of 5-HT serves not only to produce transient facilitation, but also to mark and stabilize any synapse of the neuron for long-term facilitation by means of a covalent mark and rapamycin-sensitive local protein synthesis.
ESTHER : Casadio_1999_Cell_99_221
PubMedSearch : Casadio_1999_Cell_99_221
PubMedID: 10535740

Title : Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway - Baranes_1998_Neuron_21_813
Author(s) : Baranes D , Lederfein D , Huang YY , Chen M , Bailey CH , Kandel ER
Ref : Neuron , 21 :813 , 1998
Abstract : The expression of tissue plasminogen activator (tPA) is increased during activity-dependent forms of synaptic plasticity. We have found that inhibitors of tPA inhibit the late phase of long-term potentiation (L-LTP) induced by either forskolin or tetanic stimulation in the hippocampal mossy fiber and Schaffer collateral pathways. Moreover, application of tPA enhances L-LTP induced by a single tetanus. Exposure of granule cells in culture to forskolin results in secretion of tPA, elongation of mossy fiber axons, and formation of new, active presynaptic varicosities contiguous to dendritic clusters of the glutamate receptor R1. These structural changes are blocked by tPA inhibitors and induced by application of tPA. Thus, tPA may be critically involved in the production of L-LTP and specifically in synaptic growth.
ESTHER : Baranes_1998_Neuron_21_813
PubMedSearch : Baranes_1998_Neuron_21_813
PubMedID: 9808467

Title : Synapse-specific, long-term facilitation of aplysia sensory to motor synapses: a function for local protein synthesis in memory storage - Martin_1997_Cell_91_927
Author(s) : Martin KC , Casadio A , Zhu H , Yaping E , Rose JC , Chen M , Bailey CH , Kandel ER
Ref : Cell , 91 :927 , 1997
Abstract : The requirement for transcription during long-lasting synaptic plasticity has raised the question of whether the cellular unit of synaptic plasticity is the soma and its nucleus or the synapse. To address this question, we cultured a single bifurcated Aplysia sensory neuron making synapses with two spatially separated motor neurons. By perfusing serotonin onto the synapses made onto one motor neuron, we found that a single axonal branch can undergo long-term branch-specific facilitation. This branch-specific facilitation depends on CREB-mediated transcription and involves the growth of new synaptic connections exclusively at the treated branch. Branch-specific long-term facilitation requires local protein synthesis in the presynaptic but not the postsynaptic cell. In fact, presynaptic sensory neuron axons deprived of their cell bodies are capable of protein synthesis, and this protein synthesis is stimulated 3-fold by exposure to serotonin.
ESTHER : Martin_1997_Cell_91_927
PubMedSearch : Martin_1997_Cell_91_927
PubMedID: 9428516

Title : Reconstitution of the hippocampal mossy fiber and associational-commissural pathways in a novel dissociated cell culture system - Baranes_1996_Proc.Natl.Acad.Sci.U.S.A_93_4706
Author(s) : Baranes D , Lopez-Garcia JC , Chen M , Bailey CH , Kandel ER
Ref : Proc Natl Acad Sci U S A , 93 :4706 , 1996
Abstract : Synapses of the hippocampal mossy fiber pathway exhibit several characteristic features, including a unique form of long-term potentiation that does not require activation of the N-methyl-D-aspartate receptor by glutamate, a complex postsynaptic architecture, and sprouting in response to seizures. However, these connections have proven difficult to study in hippocampal slices because of their relative paucity (<0.4%) compared to commissural-collateral synapses. To overcome this problem, we have developed a novel dissociated cell culture system in which we have enriched mossy fiber synapses by increasing the ratio of granule-to-pyramidal cells. As in vivo, mossy fiber connections are composed of large dynorphin A-positive varicosities contacting complex spines (but without a restricted localization). The elementary synaptic connections are glutamatergic, inhibited by dynorphin A, and exhibit N-methyl-D-aspartate-independent long-term potentiation. Thus, the simplicity and experimental accessibility of this enriched in vitro mossy fiber pathway provides a new perspective for studying nonassociative plasticity in the mammalian central nervous system.
ESTHER : Baranes_1996_Proc.Natl.Acad.Sci.U.S.A_93_4706
PubMedSearch : Baranes_1996_Proc.Natl.Acad.Sci.U.S.A_93_4706
PubMedID: 8643467

Title : Aplysia CREB2 represses long-term facilitation: relief of repression converts transient facilitation into long-term functional and structural change - Bartsch_1995_Cell_83_979
Author(s) : Bartsch D , Ghirardi M , Skehel PA , Karl KA , Herder SP , Chen M , Bailey CH , Kandel ER
Ref : Cell , 83 :979 , 1995
Abstract : The switch from short- to long-term facilitation induced by behavioral sensitization in Aplysia involves CREB-like proteins, as well as the immediate-early gene ApC/EBP. Using the bZIP domain of ApC/EBP in a two-hybrid system, we have cloned ApCREB2, a transcription factor constitutively expressed in sensory neurons that resembles human CREB2 and mouse ATF4. ApCREB2 represses ApCREB1-mediated transcription in F9 cells. Injection of anti-ApCREB2 antibodies into Aplysia sensory neurons causes a single pulse of serotonin (5-HT), which induces only short-term facilitation lasting minutes, to evoke facilitation lasting more than 1 day. This facilitation has the properties of long-term facilitation: it requires transcription and translation, induces the growth of new synaptic connections, and occludes further facilitation by five pulses of 5-HT.
ESTHER : Bartsch_1995_Cell_83_979
PubMedSearch : Bartsch_1995_Cell_83_979
PubMedID: 8521521

Title : Serotonin-mediated endocytosis of apCAM: an early step of learning-related synaptic growth in Aplysia - Bailey_1992_Science_256_645
Author(s) : Bailey CH , Chen M , Keller F , Kandel ER
Ref : Science , 256 :645 , 1992
Abstract : The long-term facilitation of synaptic efficacy that is induced by serotonin in dissociated cell cultures of sensory and motor neurons of Aplysia is accompanied by the growth of new synaptic connections. This growth is associated with a down-regulation in the sensory neuron of Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this down-regulation, thin-section electron microscopy was combined with immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM. Within 1 hour, serotonin led to a 50% decrease in the density of gold-labeled complexes at the surface membrane of the sensory neuron. This down-regulation was achieved by a heterologous, protein synthesis-dependent activation of the endosomal pathway, which leads to internalization and apparent degradation of apCAM. The internalization is particularly prominent at sites where the processes of the sensory neurons contact one another and may act there to destabilize process-to-process contacts that normally inhibit growth. In turn, the endocytic activation may lead to a redistribution of membrane components to sites where new synapses form.
ESTHER : Bailey_1992_Science_256_645
PubMedSearch : Bailey_1992_Science_256_645
PubMedID: 1585177

Title : Inhibitors of protein and RNA synthesis block structural changes that accompany long-term heterosynaptic plasticity in Aplysia - Bailey_1992_Neuron_9_749
Author(s) : Bailey CH , Montarolo P , Chen M , Kandel ER , Schacher S
Ref : Neuron , 9 :749 , 1992
Abstract : Synaptic connections between the sensory and motor neurons of Aplysia in culture undergo long-term facilitation in response to serotonin (5-HT) and long-term depression in response to FMRFamide. These long-term functional changes are dependent on the synthesis of macromolecules during the period in which the transmitter is applied and are accompanied by structural changes. There is an increase and a decrease, respectively, in the number of sensory neuron varicosities in response to 5-HT and FMRFamide. To determine whether macromolecular synthesis is also required for the structural changes, we examined in parallel the effects of inhibitors of protein (anisomycin) or RNA (actinomycin D) synthesis on the structural and functional changes. We have found that anisomycin and actinomycin D block both the enduring alterations in varicosity number and the long-lasting changes in synaptic potential. These results indicate that macromolecular synthesis is required for expression of the long-lasting structural changes in the sensory cells and that this synthesis is correlated with the long-term functional modulation of sensorimotor synapses.
ESTHER : Bailey_1992_Neuron_9_749
PubMedSearch : Bailey_1992_Neuron_9_749
PubMedID: 1356372

Title : Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. II. Presynaptic conductance changes caused by histamine - Kretz_1986_J.Neurophysiol_55_131
Author(s) : Kretz R , Shapiro E , Bailey CH , Chen M , Kandel ER
Ref : Journal of Neurophysiology , 55 :131 , 1986
Abstract : We have examined the morphology and pharmacology of the L32 neurons, identified cells that mediate presynaptic inhibition in the Aplysia abdominal ganglion, to gain insight into the putative transmitter released by the L32 cells. We analyzed the fine structure of the synaptic release sites of L32 cells stained with horseradish peroxidase. Each varicosity of L32 was found to contain two general classes of vesicles. One class of vesicles is large (mean long diameter of 98 nm) and contains an electron-dense core that typically filled or nearly filled each vesicle profile. The second class of vesicles is smaller (mean long diameter of 67 nm) and relatively electron lucent. The size, distribution, and morphology of the vesicle population in L32's terminals was similar to that described at the synapses of the identified histaminergic neuron C2 in Aplysia (2). These morphological observations suggested that L32 cells might be histaminergic. Among the various putative transmitters tested, histamine was most effective in mimicking the postsynaptic effects of L32 cells onto L10, and onto other follower cells of L32 in the abdominal ganglion. Histamine also caused inhibition of transmitter output from L10. Both the IPSP produced by L32 in L10 and the response of L10 to histamine could be reversibly blocked by cimetidine, a histamine antagonist in Aplysia (14). These results support, but do not establish the identification of histamine as the putative transmitter of L32 cells. Histamine mimics the action of L32 in mediating presynaptic inhibition allowing us to examine in more detail the conductance changes in L10 underlying presynaptic inhibition. Voltage-clamp analysis revealed that histamine blocked the voltage-dependent Ca2+ current and increased a voltage-dependent K+ current in L10, much as did L32. Both of these changes are likely to act synergistically to inhibit transmitter release. Reduction of Ca2+ current in L10 would directly inhibit transmitter release from L10 directly by decreasing the amount of Ca2+ entering during spike depolarization. The increase in K+ current would act indirectly to reduce transmitter release from L10, by hyperpolarizing L10 and decreasing the amplitude and duration of spikes in L10, as well as reducing the steady-state Ca2+ influx. These results support the idea that in Aplysia presynaptic inhibition is caused primarily by a direct transmitter-mediated reduction in presynaptic Ca2+ current and secondarily by a hyperpolarization of the presynaptic neuron due to a transmitter-mediated increase in a K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)
ESTHER : Kretz_1986_J.Neurophysiol_55_131
PubMedSearch : Kretz_1986_J.Neurophysiol_55_131
PubMedID: 2419525