Wu J

General

Full name : Wu Jie

First name : Jie

Mail : Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona

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Country : USA

Email : Jie.Wu@chw.edu

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References (259)

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

Title : Alloyed Trimetallic Nanocomposite as an Efficient and Recyclable Solid Matrix for Ideonella sakaiensis Lipase Immobilization - Addai_2024_Langmuir__
Author(s) : Addai FP , Wu J , Lin F , Ma X , Han J , Liu Y , Zhou Y , Wang Y
Ref : Langmuir , : , 2024
Abstract : In this work, a trimetallic (Ni/Co/Zn) organic framework (tMOF), synthesized by a solvothermal method, was calcinated at 400 and 600 degreesC and the final products were used as a support for lipase immobilization. The material annealed at 400 degreesC (Ni-Co-Zn@400) had an improved surface area (66.01 m(2)/g) and pore volume (0.194 cm(3)/g), which showed the highest enzyme loading capacity (301 mg/g) with a specific activity of 0.196 U/mg, and could protect the enzyme against thermal denaturation at 65 degreesC. The optimal pH and temperature for the lipase were 8.0 and 45 degreesC but could tolerate pH levels 7.0-8.0 and temperatures 40-60 degreesC. Moreover, the immobilized enzyme (Ni-Co-Zn@Lipase, Ni-Co-Zn@400@Lipase, or Ni-Co-Zn@600@Lipase) could be recovered and reused for over seven cycles maintaining 80, 90, and 11% of its original activity and maintained a residual activity >90% after 40 storage days. The remarkable thermostability and storage stability of the immobilized lipase suggest that the rigid structure of the support acted as a protective shield against denaturation, while the improved pH tolerance toward the alkaline range indicates a shift in the ionization state attributed to unequal partitioning of hydroxyl and hydrogen ions within the microenvironment of the active site, suggesting that acidic residues may have been involved in forming an enzyme-support bond. The high enzyme loading capacity, specific activity, encouraging stability, and high recoverability of the tMOF@Lipase indicate that a multimetallic MOF could be a better platform for efficient enzyme immobilization.
ESTHER : Addai_2024_Langmuir__
PubMedSearch : Addai_2024_Langmuir__
PubMedID: 38626327

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 : Nanoliposome-Mediated Encapsulation of Chlorella Oil for the Development of a Controlled-Release Lipid-Lowering Formulation - Tu_2024_Foods_13_
Author(s) : Tu L , Zeng J , Bai X , Wu Z , Wu J , Xu S
Ref : Foods , 13 : , 2024
Abstract : Chlorella oil nanoliposomes (CO-NLP) were synthesized through ultrasonic injection with ethanol, and their physicochemical properties and hypolipidemic efficacy were systematically investigated. The results revealed that the mean particle size of CO-NLP was 86.90 nm and the encapsulation efficiency (EE) was 92.84%. Storage conditions at 4 degreesC were conducive to the stability of CO-NLP, maintaining an EE of approximately 90% even after 10 days of storage. The release profile of CO-NLP adhered more closely to the first-order kinetic model during in vitro assessments, exhibiting a slower release rate compared to free microalgae oil. In simulated in vitro digestion experiments, lipolytic reactions of CO-NLP were observed during intestinal digestion subsequent to nanoliposome administration. Notably, the inhibitory effect of CO-NLP on cholesterol esterase activity was measured at 85.42%. Additionally, the average fluorescence intensity of nematodes in the CO-NLP group was 52.17% lower than in the control group at a CO-NLP concentration of 500 microg/mL, which suggests a pronounced lipid-lowering effect of CO-NLP. Therefore, the CO-NLP exhibited characteristics of small and uniform particle size, elevated storage stability, gradual release during intestinal digestion, and a noteworthy hypolipidemic effect. These findings designate CO-NLP as a novel lipid-lowering active product, demonstrating potential for the development of functional foods.
ESTHER : Tu_2024_Foods_13_
PubMedSearch : Tu_2024_Foods_13_
PubMedID: 38201186

Title : Complete degradation of PET waste using a thermophilic microbe-enzyme system - Yan_2024_Int.J.Biol.Macromol__129538
Author(s) : Yan ZF , Feng CQ , Zhou JQ , Huang QS , Chen XQ , Xia W , Wu J
Ref : Int J Biol Macromol , :129538 , 2024
Abstract : Enzymatic degradation has been proposed as a suitable solution for addressing PET pollution, but approximately 10 % of PET is left as nonbiodegradable. Microbes can completely degrade PET at the gram level per year. Based on the complementary benefits of microbes and enzymes, a microbe-enzyme system was created to completely degrade PET. Here, a thermophilic microbe-enzyme (TME) system composed of Bacillus thermoamylovorans JQ3 and leaf-branch compost cutinase variant (ICCG) was used to demonstrate the synergistic degradation of PET, enabling 100 % degradation of PET waste at a high PET loading level (360 g/L). Six endogenous PET hydrolases of strain JQ3 were discovered by employing an ester bond hydrolysis function-first genome mining (EGM) strategy and first successfully expressed in E. coli. These hydrolases could release TPA as the final product from PET and preferentially degraded BHET instead of MHET. Of these, carboxylesterase 39_5 and ICCG could degrade PET in a synergistic manner to generate 50 microM of TPA, which was greater than the sum of the individual treatments. Finally, the degradation pathway of the TME system was speculated to include biofilm formation, PET degradation and utilization. The successful implementation of this study rendered a scale-up degradation feasible of PET at a lower cost.
ESTHER : Yan_2024_Int.J.Biol.Macromol__129538
PubMedSearch : Yan_2024_Int.J.Biol.Macromol__129538
PubMedID: 38246467
Gene_locus related to this paper: 9baci-a0a090kq36 , 9baci-a0a0d0eil0 , 9baci-a0a2u8ee84 , 9bact-g9by57 , 9baci-a0a0d0ejv8 , 9baci-a0a090ivg8 , 9baci-a0a090izy6

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2024_Ther.Apher.Dial_28_141
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , 28 :141 , 2024
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2024_Ther.Apher.Dial_28_141
PubMedSearch : Wan_2024_Ther.Apher.Dial_28_141
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Letter to the editor: Limitations of acetylcholinesterase inhibitor (AChEI) therapy for Alzheimer's disease -
Author(s) : Yang G , Wu J , Lei H , Hui Y
Ref : Int J Surg , : , 2024
PubMedID: 38728857

Title : A multibiomarker approach to assess the ecotoxicological effects of diclofenac on Asian clam Corbicula fluminea (O. F. Muller, 1774) - Yuan_2023_Environ.Sci.Pollut.Res.Int__
Author(s) : Yuan N , Ding J , Wu J , Bao E , Chu Y , Hu F
Ref : Environ Sci Pollut Res Int , : , 2023
Abstract : Diclofenac (DCF), one of the most current and widely used nonsteroidal anti-inflammatory drugs (NSAIDs), has been frequently detected in aquatic environments worldwide. However, the ecotoxicological effects of DCF on freshwater invertebrates remain largely unknown. In the present study, Corbicula fluminea were exposed to environmentally relevant concentrations of DCF (0, 2, 20, and 200 microg/L) for 28 days, and the potential adverse effects of DCF on siphoning behavior, antioxidant responses, and apoptosis were investigated. Our results showed that the siphon efficiencies of clams were significantly suppressed under DCF stress. DCF exerted neurotoxicity via reducing the activity of acetylcholinesterase (AChE) in gills and digestive gland of C. fluminea. Exposure to DCF induced antioxidant stress and increased malondialdehyde (MDA) levels in both gills and digestive gland of C. fluminea. Transcriptional alterations of apoptosis-related genes indicated that DCF might induce apoptosis by triggering mitochondrial apoptotic pathway. These findings can improve our understanding of the ecological risk of DCF in freshwater ecosystems.
ESTHER : Yuan_2023_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Yuan_2023_Environ.Sci.Pollut.Res.Int__
PubMedID: 37438503

Title : Design, synthesis, and biological evaluation of novel N-Benzyl piperidine derivatives as potent HDAC\/AChE inhibitors for Alzheimer's disease - Qin_2023_Bioorg.Med.Chem_80_117178
Author(s) : Qin P , Ran Y , Xie F , Liu Y , Wei C , Luan X , Wu J
Ref : Bioorganic & Medicinal Chemistry , 80 :117178 , 2023
Abstract : The multitarget-directed ligands approach represents a potential strategy to provide effective treatments for Alzheimer's disease (AD) given its multifactorial pathology. Herein, a series of N-benzyl piperidine derivatives were designed, synthesized, and biologically characterized for dual inhibitions of histone deacetylase (HDAC) and acetylcholinesterase (AChE). Among the compounds tested, d5 and d10 exhibited dual enzyme inhibitions (d5: HDAC(IC50) = 0.17 microM, AChE(IC50) = 6.89 microM, d10: HDAC(IC50) = 0.45 microM, AChE(IC50) = 3.22 microM), and both compounds showed activities on scavenging free radical, metal chelating, and inhibiting Abeta aggregations. More importantly, both compounds exhibited promising neuroprotective activities in PC-12 cells and good AChE selectivity. Collectively, the multifunctional profiles of compound d5 and d10 encourage further optimization and exploration to develop more potent analogues as potential treatments for AD.
ESTHER : Qin_2023_Bioorg.Med.Chem_80_117178
PubMedSearch : Qin_2023_Bioorg.Med.Chem_80_117178
PubMedID: 36706609

Title : Ultra-small magnetic Candida antarctica lipase B nanoreactors for enzyme synthesis of bixin-maltitol ester - Lv_2023_Food.Chem_421_136132
Author(s) : Lv D , Wang M , He W , Wu J , Liu X , Guan Y
Ref : Food Chem , 421 :136132 , 2023
Abstract : Bixin has desirable bioactivities but poor water solubility, which limits its practical applications. Enzymatic transesterification of methyl to alditol groups in bixin by Candida antarctica lipase B (CALB) improves bixin water solubility. Herein, magnetic CALB nanoreactors with diameter of 11.7 nm and CALB layer thickness of 3.5 nm were developed by covalently linking CALB onto silicon covered Fe(3)O(4) nanoparticles. The CALB loading capacity in nanoreactors achieved 30%. The Michaelis constant (Km) and maximum reaction rate of magnetic CALB nanoreactors were 56.1 mmol/L and 0.2 mmol/(L.min). Magnetic CALB nanoreactors could circularly catalyze bixin-maltitol ester synthesis and keep catalytic efficiency of 62.6% after eight repetitive enzymatic reactions. Additionally, the optimal bixin-maltitol ester synthesis procedure was heating bixin-maltitol mixture at molar ratio of 1:7 in anhydrous 2-methyl-2-butanol-dimethylsulfoxide (8:2, v/v) at 50 degreesC for 24 h. Bixin-maltitol ester showed improved water solubility at pH 5.5 and 7.0.
ESTHER : Lv_2023_Food.Chem_421_136132
PubMedSearch : Lv_2023_Food.Chem_421_136132
PubMedID: 37094396

Title : Frequency and polymorphism of acetylcholinesterase gene involved in the organophosphate resistance of Musca domestica in Guizhou Province, China - Yang_2023_Arch.Insect.Biochem.Physiol__e22045
Author(s) : Yang X , Mou R , Liang Q , Cheng J , Wu Y , Tan W , Wu J
Ref : Archives of Insect Biochemistry & Physiology , :e22045 , 2023
Abstract : Organophosphate (OP) resistance has been prevalent in Musca domestica populations worldwide since 1960s. Previous studies have demonstrated that point mutations of the acetylcholinesterase gene (Ace) are one of the important molecular mechanisms underlying OP resistance. However, few studies have investigated the molecular mechanisms of OP resistance in the past 10 years in China. In this study, we investigated the status of OP resistance and genetic diversity of Ace in the field populations of houseflies in Guizhou Province of China. The bioassays showed that the houseflies had 142-304-fold resistance to dichlorvos (DDVP) and 122-364-fold resistance to temephos, compared to the susceptible houseflies. Five nonsynonymous mutations (Y226F, V260L, G342A/V, F407Y) in Ace were detected among the 7 field populations, with an average frequency of 5.4%, 55%, 68%, 32%, and 94%, respectively, of which the Y226F mutation had not been reported previously. Eleven combinations of triple mutations (at positions 260, 342, and 407) were observed, of which the combination 260L/V+342A/V+407Y was predominant. The ZY and AS populations showed greatest diversity of allelic combination and the other five populations showed different distributions among different regions. These results indicate that the resistance to OPs is prevalent among the housefly populations and target-site insensitivity is the main cause of resistance in Guizhou Province. The difference in distribution and the allelic diversity of Ace in field populations may be due to the complexity and variability of insecticide application. It is necessary to monitor resistance to insecticides and conduct management of houseflies in Guizhou Province.
ESTHER : Yang_2023_Arch.Insect.Biochem.Physiol__e22045
PubMedSearch : Yang_2023_Arch.Insect.Biochem.Physiol__e22045
PubMedID: 37602787

Title : Carboxy-Functionalized Covalent Organic Framework as a Carrier for Lipase Immobilization and Its Application in Inhibitors Screening - Liu_2023_Appl.Biochem.Biotechnol__
Author(s) : Liu X , Wu J , Yang S , Li L , Ji Y
Ref : Appl Biochem Biotechnol , : , 2023
Abstract : Covalent organic frameworks (COFs) with large specific surface areas, high porosity, good stability, and designable structure are promising carriers for immobilized enzymes. It is important to explore lipase inhibitors from natural foods as lipase inhibitors are closely related to the treatment of obesity. In this work, a carboxyl functionalized covalent organic framework (TpBD-3COOH) was prepared by solvothermal method for covalent immobilization of porcine pancreatic lipase (PPL) and obtained the enzyme-decorated COF (PPL@COF). The immobilized lipase showed wider pH and temperature tolerance with the same optimal pH and temperature of 7.5 and 50 degC compared to free lipase. After 6 successive reuses, the PPL@COF maintained 53.0% of its original activity. Immobilized lipase also displayed enhanced storage stability (55.4% after 14 days at 4 degC). When p-nitrophenyl acetate was applied as the substrate, the calculated Michaelis constant was 3.57 mM and the half maximal inhibitory concentration of orlistat was 3.20 microM. Finally, the PPL@COF was used for enzyme inhibitors screening from natural foods combined with UV spectrophotometry, and Hawthorn was screened for excellent lipase inhibitory activity.
ESTHER : Liu_2023_Appl.Biochem.Biotechnol__
PubMedSearch : Liu_2023_Appl.Biochem.Biotechnol__
PubMedID: 37819460

Title : Novel miR-108 and miR-234 target juvenile hormone esterase to regulate the response of Plutella xylostella to Cry1Ac protoxin - Yang_2023_Ecotoxicol.Environ.Saf_254_114761
Author(s) : Yang J , Chen S , Xu X , Lin S , Wu J , Lin G , Bai J , Song Q , You M , Xie M
Ref : Ecotoxicology & Environmental Safety , 254 :114761 , 2023
Abstract : Insect hormones, such as juvenile hormone (JH), precisely regulate insect life-history traits. The regulation of JH is tightly associated with the tolerance or resistance to Bacillus thuringiensis (Bt). JH esterase (JHE) is a primary JH-specific metabolic enzyme which plays a key role in regulating JH titer. Here, we characterized a JHE gene from Plutella xylostella (PxJHE), and found it was differentially expressed in the Bt Cry1Ac resistant and susceptible strains. Suppression of PxJHE expression with RNAi increased the tolerance of P. xylostella to Cry1Ac protoxin. To investigate the regulatory mechanism of PxJHE, two target site prediction algorithms were applied to predict the putative miRNAs targeting PxJHE, and the resulting putative miRNAs were subsequently verified for their function targeting PxJHE using luciferase reporter assay and RNA immunoprecipitation. MiR-108 or miR-234 agomir delivery dramatically reduced PxJHE expression in vivo, whilst only miR-108 overexpression consequently increased the tolerance of P. xylostella larvae to Cry1Ac protoxin. By contrast, reduction of miR-108 or miR-234 dramatically increased PxJHE expression, accompanied by the decreased tolerance to Cry1Ac protoxin. Furthermore, injection of miR-108 or miR-234 led to developmental defects in P. xylostella, whilst injection of antagomir did not cause any obvious abnormal phenotypes. Our results indicated that miR-108 or miR-234 can be applied as potential molecular targets to combat P. xylostella and perhaps other lepidopteran pests, providing novel insights into miRNA-based integrated pest management.
ESTHER : Yang_2023_Ecotoxicol.Environ.Saf_254_114761
PubMedSearch : Yang_2023_Ecotoxicol.Environ.Saf_254_114761
PubMedID: 36907089

Title : Maize resistance to witchweed through changes in strigolactone biosynthesis - Li_2023_Science_379_94
Author(s) : Li C , Dong L , Durairaj J , Guan JC , Yoshimura M , Quinodoz P , Horber R , Gaus K , Li J , Setotaw YB , Qi J , De Groote H , Wang Y , Thiombiano B , Flokova K , Walmsley A , Charnikhova TV , Chojnacka A , Correia de Lemos S , Ding Y , Skibbe D , Hermann K , Screpanti C , De Mesmaeker A , Schmelz EA , Menkir A , Medema M , van Dijk ADJ , Wu J , Koch KE , Bouwmeester HJ
Ref : Science , 379 :94 , 2023
Abstract : Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga-resistant maize.
ESTHER : Li_2023_Science_379_94
PubMedSearch : Li_2023_Science_379_94
PubMedID: 36603079

Title : Glimepiride, a novel soluble epoxide hydrolase inhibitor, protects against heart failure via increasing epoxyeicosatrienoic acids - Zhao_2023_J.Mol.Cell.Cardiol_185_13
Author(s) : Zhao C , Jiang X , Peng L , Zhang Y , Li H , Zhang Q , Wang Y , Yang F , Wu J , Wen Z , He Z , Shen J , Chen C , Wang DW
Ref : Journal of Molecular & Cellular Cardiology , 185 :13 , 2023
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2(-/-) mice. Moreover, Western blot, real-time PCR, luciferase reporter, ChIP assays were employed to explore the underlying mechanism. Finally, multiple sEH inhibitors were designed, synthesized, and validated in vitro and in vivo. RESULTS: The ratios of DHETs/EETs were increased in the plasma from patients with HF. Meanwhile, the expression of sEH was upregulated in the heart of patients and mice with HF, especially in cardiomyocytes. Cardiomyocyte-specific Ephx2(-/-) mice ameliorated cardiac dysfunction induced by TAC. Consistently, Ephx2 knockdown protected Angiotensin II (AngII)-treated cardiomyocytes via increasing EETs in vitro. Mechanistically, AngII could enhance the expression of transcript factor Krppel-like factor 15 (KLF15), which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor, which benefited from the elevated EETs during HF. CONCLUSIONS: Glimepiride attenuates HF in mice in part by increasing EETs. CLINICAL TRIAL IDENTIFIER: NCT03461107 (https://clinicaltrials.gov).
ESTHER : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedSearch : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedID: 37871528

Title : Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer's disease: A systematic review and Bayesian network meta-analysis - Wei_2023_CNS.Neurosci.Ther__
Author(s) : Wei N , Liu H , Ye W , Xu S , Lu C , Dai A , Hou T , Zeng X , Wu J , Chen J
Ref : CNS Neurosci Ther , : , 2023
Abstract : BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation therapy that is primarily used to treat a variety of neuropsychiatric conditions. Recently, previous research reports stated that rTMS have the characteristics of neurorestorative in Alzheimer's disease (AD). However, the relevant clinical research evidence has not been fully summarized. METHODS: This article performed a network meta-analysis of individual participant data from eligible studies searched in PubMed, Embase, and the Cochrane Library from inception to March 31, 2022. The drug treatments involved were acetylcholinesterase inhibitors (AChEIs), N-methyl-d-aspartate (NMDA), anti-amyloid-beta (Abeta), and some new targeted therapeutic drugs. RESULTS: A total of 15, 548 individuals with AD disease in 57 randomized clinical trials (RCTs) were included in this meta-analysis. The results indicated that the patients who received rTMS treatment (standard mean difference [SMD]: 0.65; 95% confidence interval [CI]: 0.22-1.07) had a better MMSE score than placebo. Treatment outcome analysis showed that, compared with multiple pharmacological interventions, rTMS acquired the greatest probability rank with the best cognitive improvement in MMSE score [the surface under the cumulative ranking curve (SUCRA) 93.3%] and ADAS-cog score (SUCRA 86.7%). At the same time, rTMS treatment had the lowest rank in the adverse events (SUCRA 24.1%) except for the placebo group (SUCRA 19.1%). CONCLUSION: Compared with the current clinical drug treatment, rTMS demonstrated better cognitive function improvement and fewer adverse events in AD patients. Therefore, rTMS shows broad prospects in the treatment of Alzheimer's disease, and it is worth being widely popularized in clinic.
ESTHER : Wei_2023_CNS.Neurosci.Ther__
PubMedSearch : Wei_2023_CNS.Neurosci.Ther__
PubMedID: 37088953

Title : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana - Wei_2023_Org.Biomol.Chem__
Author(s) : Wei J , Li Z , Shan M , Wu F , Li L , Ma Y , Wu J , Li X , Liu Y , Hu Z , Zhang Y , Wu Z
Ref : Org Biomol Chem , : , 2023
Abstract : Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh(2)(OCOCF(3))(4)-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC(50) = 2.13 +/- 0.06 microM and K(i) = 0.058 microM), which was five times stronger than that of the positive control (rivastigmine, IC(50) = 12.46 +/- 0.82 microM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.
ESTHER : Wei_2023_Org.Biomol.Chem__
PubMedSearch : Wei_2023_Org.Biomol.Chem__
PubMedID: 37581482

Title : Rivastigmine-Bambuterol Hybrids as Selective Butyrylcholinesterase Inhibitors - Wu_2023_Molecules_29_
Author(s) : Wu J , Tan Z , Pistolozzi M , Tan W
Ref : Molecules , 29 : , 2023
Abstract : Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC(50(AChE)) > 100,000 nM, IC(50(BChE)) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer's disease.
ESTHER : Wu_2023_Molecules_29_
PubMedSearch : Wu_2023_Molecules_29_
PubMedID: 38202655

Title : A new terrein dimer and a new meroterpene from the mangrove endophytic fungus Lichtheimia sp - Ren_2023_J.Asian.Nat.Prod.Res__1
Author(s) : Ren JL , Li CM , Shen L , Wu J
Ref : J Asian Nat Prod Res , :1 , 2023
Abstract : A new terrein dimer named lichtheicol A (1) and a new meroterpene named lichtheiterpene A (2), were isolated from the mangrove endophytic fungus Lichtheimia sp. J2B1, together with 10 known compounds (3-12). The planar structures and absolute configurations of 1 and 2 were established by a combination of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 exhibited marked inhibitory effects against butyrylcholinesterase (BuChE) with IC(50) values of 0.71 and 0.53 microM, respectively.
ESTHER : Ren_2023_J.Asian.Nat.Prod.Res__1
PubMedSearch : Ren_2023_J.Asian.Nat.Prod.Res__1
PubMedID: 37042744

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2023_Ther.Apher.Dial__
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , : , 2023
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2023_Ther.Apher.Dial__
PubMedSearch : Wan_2023_Ther.Apher.Dial__
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : The FoxO1-ATGL axis alters milk lipolysis homeostasis through PI3K\/AKT signaling pathway in dairy goat mammary epithelial cells - He_2023_J.Anim.Sci__
Author(s) : He Q , GaoLiang J , Zhang F , Yao W , Wu J , Song N , Luo J , Zhang Y
Ref : J Anim Sci , : , 2023
Abstract : Goat milk is enriched in fatty acids which beneficial to human health. Previous research has revealed that 98% of milk fat is composed of triglycerides. However, the mechanisms regulating of milk fat composition remain unclear. Forkhead box protein O1 (FoxO1) is a crucial regulatory factor involved in lipid metabolism across various cell types. Chromatin immunoprecipitation sequencing (ChIP)--seq data) and RNA sequencing (RNA-seq) data revealed thathave indicated a close association between FoxO1 was closed related toand lipid metabolism during lactation in dairy goats. The objective of this study was to investigate the mechanisms by which FoxO1 regulates lipid metabolism in goat mammary epithelial cells (GMECs). FoxO1 knockdown significantly downregulated the expression of adipose triglyceride lipase (ATGL) and suppressed the activity of the ATGL promoter. Consistently, the number of lipid droplets decreased significantly in FoxO1-overexpressing cells, and increased in ATGL-knockdown cells. To further verify the effect of FoxO1 on ATGL promoter activity, cells were transfected with four promoter fragments of different lengths. We found that the core region of the ATGL promoter was located between -882 bp and -524 bp, encompassing two FoxO1 binding sites (FKH1 and FKH2). Mutations in the FoxO1 binding sites significantly downregulated ATGL promoter activity in GMECs. Luciferase reporter assays demonstrated that FoxO1 overexpression markedly enhanced ATGL promoter activity. Furthermore, site-directed mutation confirmed that FKH1 and FKH2 sites were simultaneously mutated significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activities simultaneous mutation of FKH1 and FKH2 sites significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activity. ChIP assays showed that FoxO1 directly binds to the FKH2 element located in the ATGL promoter in vivo. Finally, immunofluorescence staining revealed that insulin promotes the translocation of FoxO1 from the nucleus to the cytoplasm, thereby attenuating the FoxO1-induced activation of the ATGL promoter. Collectively, these findings uncover a novel pathway where by FoxO1 may regulate lipid metabolism in GMECs specifically by modulating the transcriptional activity of ATGL.
ESTHER : He_2023_J.Anim.Sci__
PubMedSearch : He_2023_J.Anim.Sci__
PubMedID: 37638641

Title : Genetic analysis and management of a familial hypercholesterolemia pedigree with polygenic variants: Case report - Han_2023_Medicine.(Baltimore)_102_e34534
Author(s) : Han Y , Zhang L , Tao H , Wu J , Zhai J
Ref : Medicine (Baltimore) , 102 :e34534 , 2023
Abstract : RATIONALE: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder typically caused by low density lipoprotein receptor (LDLR) gene mutation. Herein, we reported a FH pedigree with polygenic variants: LDLR, apolipoprotein B (APOB), and epoxide hydrolase 2 (EPHX2). PATIENT CONCERNS: A 10-year-old boy mainly presented multiple skin xanthomas and hypercholesterolemia. His family visited our hospital and was performed with pedigree whole exome sequencing (WES) at 20 + 3 weeks gestation of the mother's second pregnancy. DIAGNOSES: Based on the clinical features and genetic analysis, the pedigree was diagnosed with familial hypercholesterolemia. INTERVENTIONS: After genetic counseling, the couple opted to continue the pregnancy. Treatment advice and follow-up were offered to them. OUTCOMES: A novel compound heterozygous LDLR mutation: c.1009G>T and c.68-2A>G, derived from his parents respectively was revealed through pedigree WES, meanwhile, a maternal APOB gene variant: c.1670A>G and a paternal EPHX2 gene variant: c.548 dup of the proband were found together. Furthermore, the same compound heterozygous LDLR mutation as his was confirmed in his sister without APOB and EPHX2 variants in her fetal stage. LESSONS: WES combined with clinical features is essential for the diagnosis of FH, however, prenatal genetic testing results might bring more challenges to prenatal genetic counseling. Furthermore, it is more important to provide the guidance and early intervention for such families in the long run.
ESTHER : Han_2023_Medicine.(Baltimore)_102_e34534
PubMedSearch : Han_2023_Medicine.(Baltimore)_102_e34534
PubMedID: 37565868

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : Crystal structure of the GDSL family esterase EstL5 in complex with PMSF reveals a branch channel of the active site pocket - Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
Author(s) : Chen R , Gao X , Nie T , Wu J , Wang L , Osman A , Feng Y , Li X , Zhang Y
Ref : Acta Biochim Biophys Sin (Shanghai) , : , 2023
Abstract : Esterases/lipases from the GDSL family have potential applications in the hydrolysis and synthesis of important esters of pharmaceutical, food, and biotechnical interests. However, the structural and functional understanding of GDSL enzymes is still limited. Here, we report the crystal structure of the GDSL family esterase EstL5 complexed with PMSF at 2.34 A resolution. Intriguingly, the PMSF binding site is not located at the active site pocket but is situated in a surface cavity. At the active site, we note that there is a trapped crystallization solvent 1,6-hexanediol, which mimics the bound ester chain, allowing for further definition of the active site pocket of EstL5. The most striking structural feature of EstL5 is the presence of a unique channel, which extends approximately 18.9 A, with a bottleneck radius of 6.8 A, connecting the active-site pocket and the surface cavity. Replacement of Ser205 with the bulk aromatic residue Trp or Phe could partially block the channel at one end and perturb its access. Reduced enzymatic activity is found in the EstL5 S205W and EstL5 S205F mutants, suggesting the functional relevance of the channel to enzyme catalysis. Our study provides valuable information regarding the properties of the GDSL-family enzymes for designing more efficient and robust biocatalysts.
ESTHER : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedSearch : Chen_2023_Acta.Biochim.Biophys.Sin.(Shanghai)__
PubMedID: 37705347

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

Title : N-acylhomoserine lactonase-based hybrid nanoflowers: a novel and practical strategy to control plant bacterial diseases - Chen_2022_J.Nanobiotechnology_20_347
Author(s) : Chen Y , Liu P , Wu J , Yan W , Xie S , Sun X , Ye BC , Chu X
Ref : J Nanobiotechnology , 20 :347 , 2022
Abstract : BACKGROUND: The disease caused by plant pathogenic bacteria in the production, transportation, and storage of many crops has brought huge losses to agricultural production. N-acylhomoserine lactonases (AHLases) can quench quorum-sensing (QS) by hydrolyzing acylhomoserine lactones (AHLs), which makes them the promising candidates for controlling infections of QS-dependent pathogenic bacteria. Although many AHLases have been isolated and considered as a potentially effective preventive and therapeutic agents for bacterial diseases, the intrinsically poor ambient stability has seriously restricted its application. RESULTS: Herein, we showed that a spheroid enzyme-based hybrid nanoflower (EHNF), AhlX@Ni(3)(PO(4))(2), can be easily synthesized, and it exhibited 10 times AHL (3OC8-HSL) degradation activity than that with free AhlX (a thermostable AHL lactonase). In addition, it showed intriguing stability even at the working concentration, and retained ~ 100% activity after incubation at room temperature (25 degreesC) for 40 days and approximately 80% activity after incubation at 60 degreesC for 48 h. Furthermore, it exhibited better organic solvent tolerance and long-term stability in a complicated ecological environment than that of AhlX. To reduce the cost and streamline production processes, CSA@Ni(3)(PO(4))(2), which was assembled from the crude supernatants of AhlX and Ni(3)(PO(4))(2), was synthesized. Both AhlX@Ni(3)(PO(4))(2) and CSA@Ni(3)(PO(4))(2) efficiently attenuated pathogenic bacterial infection. CONCLUSIONS: In this study, we have developed N-acylhomoserine lactonase-based hybrid nanoflowers as a novel and efficient biocontrol reagent with significant control effect, outstanding environmental adaptability and tolerance. It was expected to overcome the bottlenecks of poor stability and limited environmental tolerance that have existed for over two decades and pioneered the practical application of EHNFs in the field of biological control.
ESTHER : Chen_2022_J.Nanobiotechnology_20_347
PubMedSearch : Chen_2022_J.Nanobiotechnology_20_347
PubMedID: 35883097

Title : Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population - Bai_2022_Microbiome_10_147
Author(s) : Bai X , Sun Y , Li Y , Li M , Cao Z , Huang Z , Zhang F , Yan P , Wang L , Luo J , Wu J , Fan D , Chen H , Zhi M , Lan P , Zeng Z , Wu X , Miao Y , Zuo T
Ref : Microbiome , 10 :147 , 2022
Abstract : BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.
ESTHER : Bai_2022_Microbiome_10_147
PubMedSearch : Bai_2022_Microbiome_10_147
PubMedID: 36100953

Title : The Impact of Catalpol on Proliferation, Apoptosis, Migration, and Oxidative Stress of Lung Cancer Cells Based on Nrf2\/ARE Signaling - Wang_2022_Biomed.Res.Int_2022_5621341
Author(s) : Wang H , Wu J , Fan H , Ji Y , Han C , Li C , Jiang S
Ref : Biomed Res Int , 2022 :5621341 , 2022
Abstract : The effects of catalpol on lung cancer cell proliferation, apoptosis, migration, and oxidative stress via the Nrf2/ARE signaling pathway are investigated in this work. Catalpol-12 g/mL group, catalpol-24 g/mL group, catalpol-48 g/mL group, catalpol - 48 g/mL + vector group, catalpol - 48 g/mL + Nrf2 group, si-NC group, and si-Nrf2 group were used to split lung cancer cells A549 into control groups. Proliferation was detected using the CCK-8 assay; apoptosis was detected using flow cytometry; migration was detected using the transwell chamber; ROS was distinguished using the DCFHDA method; MDA, SOD, and GSH were detected using the microvolume method; and Cleaved Caspase-3, Cleaved Caspase-9, Nrf2, HO-1, MMP-9, and MMP-2 were detected using the Western blot method. Catalpol 12 g/mL and 24 g/mL-48 g/mL treatment decreased the proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells when compared to the control group. SOD and GSH levels of lung cancer cells were decreased, and MDA and ROS levels were increased. Cleaved caspase-3, cleaved caspase-9 protein expression levels, and apoptosis were boosted (P < 0.05). The proliferation activity, migration number, and protein levels of Nrf2, HO-1, MMP-9, and MMP-2 in the catalpol - 48 g/mL + Nrf2 group were raised compared to the catalpol - 48 g/mL + vector group, whereas there was an apparent drop in the Cleaved Caspase-3, Cleaved Caspase-9, and apoptosis rate. Similarly, SOD and GSH contents increased, whereas MDA and ROS decreased (P < 0.05). The proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells in the si-Nrf2 group were all decreased when compared to the si-NC and control groups. Cleaved Caspase-3 and Cleaved Caspase-9 protein expression, on the other hand, increased as MDA and ROS levels were raised while SOD and GSH levels dropped (P < 0.05). It reveals that catalpol inhibits the Nrf2/ARE signaling pathway, which causes antiproliferation, migration, apoptosis, and oxidative stress in cancer cells of lungs. The rate of apoptosis was also lowered.
ESTHER : Wang_2022_Biomed.Res.Int_2022_5621341
PubMedSearch : Wang_2022_Biomed.Res.Int_2022_5621341
PubMedID: 35898682

Title : FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis - Du_2022_Cell.Death.Dis_13_488
Author(s) : Du Q , Liu P , Zhang C , Liu T , Wang W , Shang C , Wu J , Liao Y , Chen Y , Huang J , Tan H , Zhao Y , Xia M , Liu J , Yao S
Ref : Cell Death Dis , 13 :488 , 2022
Abstract : Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
ESTHER : Du_2022_Cell.Death.Dis_13_488
PubMedSearch : Du_2022_Cell.Death.Dis_13_488
PubMedID: 35597782

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : [Characterization of Humicola insolens cutinase-tachystatin A2 fusion protein and its application in treatment of recycled paper stickies] - Li_2022_Sheng.Wu.Gong.Cheng.Xue.Bao_38_207
Author(s) : Li G , Liu Z , Zhang Y , Wu J
Ref : Sheng Wu Gong Cheng Xue Bao , 38 :207 , 2022
Abstract : With the decrease of forest timber resources, the recycling of waste paper has received increasing attention. However, the stickies produced in the process of waste paper recycling may negatively affect the production of recycled paper. The biological decomposition of stickies, which has the advantages of high efficiency, high specificity and pollution-free, is achieved mainly through the enzymatic cleavage of the ester bond in the stickies components to prevent flocculation. Cutinase is a serine esterase that can degrade some components of the stickies. Previous research indicated that the anchor peptide tachystatin A2 (TA2) is able to bind polyurethane. In this study, the cutinase HiC derived from Humicola insolens was used to construct a fusion protein HiC-TA2 by megaprimer PCR of the whole plasmid (MEGAWHOP). The enzymatic properties and the degradation efficiency of the fusion protein on poly(ethyl acrylate) (PEA), a model substrate of stickies component, were determined. The results showed that the degradation efficiency, the size decrease of PEA particle, and the amount of ethanol produced by HiC-TA2 were 1.5 times, 6.8 times, and 1.4 times of that by HiC, respectively. These results demonstrated that TA2 improved the degradation efficiency of HiC on PEA. This study provides a useful reference for biological decomposition of stickies produced in the process of recycled paper production.
ESTHER : Li_2022_Sheng.Wu.Gong.Cheng.Xue.Bao_38_207
PubMedSearch : Li_2022_Sheng.Wu.Gong.Cheng.Xue.Bao_38_207
PubMedID: 35142131

Title : Enhanced biodegradation activity towards poly(ethyl acrylate) and poly(vinyl acetate) by anchor peptide assistant targeting - Liu_2022_J.Biotechnol__
Author(s) : Liu Z , Li G , Zhang F , Wu J
Ref : J Biotechnol , : , 2022
Abstract : The paper industry is one of the most important basic raw material pillar industries. With the decrease of forest wood resources, the recycling of wastepaper has drawn increasingly attention. However, the stickies generated in the process of wastepaper recycling will flocculate and deposite in the pulp, resulting in production accidents and inferior product quality. The biological enzymatic method, with the advantages of high efficiency, specificity, and pollution-free, can prevent the flocculation of the stickies by enzymatically hydrolyzing the ester bond of the stickies components. Previous studies have demonstrated that cutinase (EC 3.1.1.74) had the ability to degrade polyester components of stickies. Meanwhile, relevant studies have shown that anchor peptides possessed the ability to bind polyester. Herein, the cutinase from Humicola insolens (HiC) was fused with Escherichia coli anchor peptide OMP25, the enzymatic properties of the fusion protein HiC-OMP25 and its degradation efficiency of the stickies model substrate, poly(ethyl acrylate) (PEA) and poly(vinyl acetate) (PVAc), as well as stickies sediment were determined. All of the results demonstrated that OMP25 efficiently enhanced the degradation ability of HiC.
ESTHER : Liu_2022_J.Biotechnol__
PubMedSearch : Liu_2022_J.Biotechnol__
PubMedID: 35292345

Title : Polylactic acid microplastics induce higher biotoxicity of decabromodiphenyl ethane on earthworms (Eisenia fetida) compared to polyethylene and polypropylene microplastics - Han_2022_Sci.Total.Environ__160909
Author(s) : Han Y , Fu M , Wu J , Zhou S , Qiao Z , Peng C , Zhang W , Liu F , Ye C , Yang J
Ref : Sci Total Environ , :160909 , 2022
Abstract : Decabromodiphenyl ethane (DBDPE) and microplastics (MPs), such as fossil-based polymers polyethylene (PE), polypropylene (PP), and bio-based plastics polylactic acid (PLA) are abundant in e-waste dismantling areas. However, the information on the effects of DBDPE combined with MPs (DBDPE-MPs) on earthworms is still limited. In this study, we explored the impacts of DBDPE-MPs on neurotoxic biomarkers, tissue damage, and transcriptomics of Eisenia fetida by simulating different exposure patterns of 10 mg kg(-1) DBDPE and 10 mg kg(-1) DBDPE-MPs (PLA, PP, and PE). Results showed that the activities of acetylcholinesterase, Na(+)/K(+)-ATPase, Ca(2+)/Mg(2+)-ATPase, carboxylate enzyme, and the contents of calcium and glutamate were significantly stimulated. DBDPE-MP co-exposure caused more severe damage to the epidermis, muscles, and tissues. Transcriptomic analysis revealed that differentially expressed genes (DEGs) of DBDPE-MPs were mainly related to inflammation, the immune system, digestive system, endocrine system, and metabolism. DBDPE and PP-MPs had similar influences on immunity and metabolism. However, DBDPE-PLA and DBDPE-PE further affected the endocrine system and signaling pathways. Specific DEGs showed that detoxification systems in the case of MPs were significantly upregulated. The study indicated that MPs exacerbated DBDPE toxicity in the nervous system, epidermis, and gene regulation of E. fetida, helping to assess the ecological risks of e-wastes and microplastics in soil.
ESTHER : Han_2022_Sci.Total.Environ__160909
PubMedSearch : Han_2022_Sci.Total.Environ__160909
PubMedID: 36526185

Title : Enhancement of PET biodegradation by anchor peptide-cutinase fusion protein - Liu_2022_Enzyme.Microb.Technol_156_110004
Author(s) : Liu Z , Zhang Y , Wu J
Ref : Enzyme Microb Technol , 156 :110004 , 2022
Abstract : With the increasing production of polyethylene terephthalate (PET) plastic products, the problem of PET waste has become a serious threat to ecosystem. PET enzymatic biodegradation, due to its environmental friendliness and sustainability, has gradually attracted attention. As a multifunctional hydrolase, cutinase (EC 3.1.1.74) can not only degrade fatty acid esters, soluble synthetic esters, and emulsified triglycerides, but also exhibit potential for PET degradation. In order to enhance the PET degradation activity of cutinase, we functionally screened several PET binding domains, e.g. carbohydrate binding module, anchor peptide, and hydrophobin, that promote the absorption of enzyme to PET substrate, selected Dermaseptin SI (DSI) and fused it onto the N-terminus of Thermobifida fusca cutinase mutant D204C/E253C (Tfuc2), and finally achieved the PET degradation rate up to 57.9% at 70 degreesC for 96 h, which was 22.7-fold of that of Tfuc2 itself. These results indicate that the fusion of PET binding domain is a promising strategy to enhance PET enzymatic degradation.
ESTHER : Liu_2022_Enzyme.Microb.Technol_156_110004
PubMedSearch : Liu_2022_Enzyme.Microb.Technol_156_110004
PubMedID: 35217214
Gene_locus related to this paper: thefu-q6a0i3

Title : Directional-path modification strategy enhances PET hydrolase catalysis of plastic degradation - Chen_2022_J.Hazard.Mater_433_128816
Author(s) : Chen XQ , Guo ZY , Wang L , Yan ZF , Jin CX , Huang QS , Kong DM , Rao DM , Wu J
Ref : J Hazard Mater , 433 :128816 , 2022
Abstract : Poly (ethylene terephthalate) (PET) is a widely used type of general plastic that produces a significant amount of waste due to its non-degradable properties. We propose a novel directional-path modification (DPM) strategy, involving positive charge amino acid introduction and binding groove remodeling, and apply it to Thermobifida fusca cutinase to enhance PET degradation. The highest value of PET degradation (90%) was achieved in variant 4Mz (H184S/Q92G/F209I/I213K), exhibiting values almost 30-fold that of the wild-type. We employed molecular docking, molecular dynamics simulations, and QM/MM MD for the degradation process of PET, accompanied by acylation and deacylation. We found that the distance of nucleophilic attack was reduced from about 4.6 A in the wild type to 3.8 A in 4Mz, and the free energy barrier of 4Mz dropped from 14.3 kcal/mol to 7.1 kcal/mol at the acylation which was the rate-limiting step. Subsequently, the high efficiency and universality of the DPM strategy were successfully demonstrated in LCC, Est119, and BhrPETase enhancing the degradation activity of PET. Finally, the highest degradation rate of the pretreated commercial plastic bottles had reached to 73%. The present study provides insight into the molecular binding mechanism of PET into the PET hydrolases structure and proposes a novel DPM strategy that will be useful for the engineering of more efficient enzymes for PET degradation.
ESTHER : Chen_2022_J.Hazard.Mater_433_128816
PubMedSearch : Chen_2022_J.Hazard.Mater_433_128816
PubMedID: 35390614
Gene_locus related to this paper: thefu-q6a0i3

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : Synergism Between Multi-Pseudomonas and Cutinase for Biodegradation of Crude Oil-Based Derivatives - Yan_2022_Curr.Microbiol_80_30
Author(s) : Yan ZF , Xu KW , Wu J
Ref : Curr Microbiol , 80 :30 , 2022
Abstract : Polyethylene terephthalate (PET) as one of the main crude oil-based derivatives, produces a significant amount of waste that is difficult to degrade. Currently, microbial degradation of PET is an eco-friendly, efficient, and economical method. This study was conducted to propose a novel screening strategy for PET-degrading bacteria, and evaluate their degradation efficiency of PET. Two strains, Pseudomonas nitroreducens S8 and Pseudomonas monteilii S17, were isolated and could utilize PET as a carbon source by co-culture. The combined use of both bacteria gave a synergistic effect on the disruption of the PET surface through colonization behavior, which could enhance the subsequent degradation of PET. Its time of reaching a peak value of PET degradation rate (94.5% at 6 d) was 2sdays earlier than these of single bacteria. A similar synergistic effect was also observed in the metabolization of PET monomers, and the metabolic rate was expressed as 82.4% of bis (2-hydroxyethyl) terephthalate (BHET), 64.0% of mono (2-hydroxyethyl) terephthalate (MHET), and 20.0% of terephthalic acid (TPA), respectively. This study is novel in showing the degradation of PET waste by combinations of bacterial pretreatment and enzymatic treatment, which can be a promising method.
ESTHER : Yan_2022_Curr.Microbiol_80_30
PubMedSearch : Yan_2022_Curr.Microbiol_80_30
PubMedID: 36474116

Title : A novel approach for on-site screening of organophosphorus nerve agents based on DTNB modified AgNPs using surface-enhanced Raman spectrometry - Wu_2022_Anal.Methods__
Author(s) : Wu J , Zhu Y , Liu Y , Chen J , Guo L , Xie J
Ref : Anal Methods , : , 2022
Abstract : Organophosphorus nerve agents (OPNAs), such as Sarin (GB), Tabun (GA), Soman (GD) and VX, would cause tremendous harm in military and terrorist attacks, and thus the development of simple methods for the rapid and efficient detection of these hazardous substances is of great necessity. Herein, we present a novel approach for the facile, rapid and sensitive detection of real OPNAs. The detection substrate is fabricated using functionalized silver nanoparticles (AgNPs) immobilized with acetylcholinesterase (AChE) and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In the absence of OPs, AChE catalyzes the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which continues to interact quickly with DTNB to produce a very sensitive Raman probing molecule, TNB. The inhibition of the activity of AChE by OPs could induce an obvious decrease of characteristic Raman peaks of 5-thio-2-nitrobenzoic acid (TNB) at 1335 cm(-1). The introduction of DTNB as an enzyme activity indicator significantly improves the detection sensitivity with distinct characteristic Raman peaks. The LOD of GD, which is one of the most easily aged OPNAs, could reach 0.1 nM due to its strongest inhibition of AChE. Moreover, various OPNAs exhibit different SERS intensities due to their different inhibition capacities of AChE. Hence, the new strategy has great potential in public security early warning and environmental analysis.
ESTHER : Wu_2022_Anal.Methods__
PubMedSearch : Wu_2022_Anal.Methods__
PubMedID: 36285727

Title : A Simple Aptamer SERS Sensor Based on Mesoporous Silica for the Detection of Chlorpyrifos - Dong_2022_Foods_11_
Author(s) : Dong S , Shi Q , He K , Wu J , Zhu Z , Feng J
Ref : Foods , 11 : , 2022
Abstract : Chlorpyrifos is an organophosphorus insecticide, which can be used to control a variety of chewing and piercing mouthparts pests in agricultural production. It can destroy the normal nerve impulse conduction by inhibiting the activity of acetylcholinesterase or cholinesterase in the nerves, causing a series of poisoning symptoms. In order to achieve the quantitative analysis of chlorpyrifos residues in agricultural products, an aptamer-controlled signal molecule release method was developed in this study. The signal molecule 4-ATP of surface-enhanced Raman spectroscopy (SERS) was loaded into aminated mesoporous silica nanoparticles (MSNs-NH(2)) prepared by the one pot method, and then coated with an aptamer of chlorpyrifos through electrostatic interaction. The specific binding of the aptamer and chlorpyrifos led to the release of 4-ATP, and the amount of 4-ATP released was positively correlated with the amount of chlorpyrifos. Finally, the standard curve of chlorpyrifos quantitative detection based on SERS was established. Meanwhile, Ag-carrying mesoporous silica (Ag@MSNs) was prepared as the reinforcement substrate for SERS detection. The results showed that there was a good linear correlation between the Raman intensity and the concentration of chlorpyrifos at 25-250 ng/mL, and the limit of detection (LOD) was 19.87 ng/mL. The recoveries of chlorpyrifos in the apple and tomato samples were 90.08-102.2%, with RSD < 3.32%. This method has high sensitivity, specificity, reproducibility and stability, and can be used for the quantitative detection of chlorpyrifos in the environment and agricultural products.
ESTHER : Dong_2022_Foods_11_
PubMedSearch : Dong_2022_Foods_11_
PubMedID: 36359944

Title : Toxicological and Biochemical Description of Synergism of Beauveria bassiana and Emamectin Benzoate against Megalurothrips usitatus (Bagrall) - Zhang_2022_J.Fungi.(Basel)_8_
Author(s) : Zhang Y , Zhang X , Tian Q , Ali S , Tang L , Wu J
Ref : J Fungi (Basel) , 8 : , 2022
Abstract : The prophylactic application of synthetic insecticides to manage Megalurothrips usitatus (Bagrall) has resulted in insecticide resistance and negative impacts upon natural ecosystems. This has driven the need for developing alternative pest control strategies. In the present study, we investigated the synergistic interaction between the entomopathogenic fungus Beauveria bassiana and the insecticide emamectin benzoate on M. usitatus. The results of our research exhibited that higher doses of emamectin benzoate inhibited the germination rate and colony growth of B. bassiana. The percentage of M. usitatus mortality following B. bassiana and emamectin benzoate treatment indicated a dose-mortality effect. All concentrations of emamectin benzoate combined with different concentrations of B. bassiana demonstrated a synergistic effect five days post-treatment. When B. bassiana and emamectin benzoate were applied alone or in combination, antioxidant enzyme activities, including acetylcholinesterase, catalase, superoxide dismutase, and peroxidase, were significantly lower in M. usiatus than in the controls at the end of the experimental period. The findings of our study confirm the synergistic effect of B. bassiana and emamectin benzoate on M. usitatus, as well as the biochemical process that might be involved in the regulation of the synergistic effect.
ESTHER : Zhang_2022_J.Fungi.(Basel)_8_
PubMedSearch : Zhang_2022_J.Fungi.(Basel)_8_
PubMedID: 36135641

Title : From tryptamine to the discovery of efficient multi-target directed ligands against cholinesterase-associated neurodegenerative disorders - Wu_2022_Front.Pharmacol_13_1036030
Author(s) : Wu J , Zhang H , Wang Y , Yin G , Li Q , Zhuo L , Chen H , Wang Z
Ref : Front Pharmacol , 13 :1036030 , 2022
Abstract : A novel class of benzyl-free and benzyl-substituted carbamylated tryptamine derivatives (CDTs) was designed and synthesized to serve as effective building blocks for the development of novel multi-target directed ligands (MTDLs) for the treatment of neurological disorders linked to cholinesterase (ChE) activity. The majority of them endowed butyrylcholinesterase (BuChE) with more substantial inhibition potency than acetylcholinesterase (AChE), according to the full study of ChE inhibition. Particularly, hybrids with dibenzyl groups (2b-2f, 2j, 2o, and 2q) showed weak or no neuronal toxicity and hepatotoxicity and single-digit nanomolar inhibitory effects against BuChE. Through molecular docking and kinetic analyses, the potential mechanism of action on BuChE was first investigated. In vitro H(2)O(2)-induced HT-22 cells assay demonstrated the favorable neuroprotective potency of 2g, 2h, 2j, 2m, 2o, and 2p. Besides, 2g, 2h, 2j, 2m, 2o, and 2p endowed good antioxidant activities and COX-2 inhibitory effects. This study suggested that this series of hybrids can be applied to treat various ChE-associated neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as promising building blocks for further structure modification to develop efficient MTDLs.
ESTHER : Wu_2022_Front.Pharmacol_13_1036030
PubMedSearch : Wu_2022_Front.Pharmacol_13_1036030
PubMedID: 36518670

Title : Lethal and Sublethal Toxicity Assessment of Cyclosporin C (a Fungal Toxin) against Plutella xylostella (L.) - Wu_2022_Toxins.(Basel)_14_
Author(s) : Wu J , Zhang X , Bashir MH , Ali S
Ref : Toxins (Basel) , 14 : , 2022
Abstract : Secondary metabolites/toxins produced by Purpeocillium lilacinum (Hypocreales; Phiocordycipitaceae), a well-known insect pathogen, can be used for the management of different insect pests. We report the lethal and sublethal effects of cyclosporin C (a toxin produced by P. lilacinum) against a major vegetable pest, Plutella xylostella, at specific organismal (feeding rate, larval growth, adult emergence, fecundity, and adult longevity) and sub-organismal levels (changes in antioxidant and neurophysiological enzyme activities). The toxicity of cyclosporin C against different larval instars of P. xylostella increased with increasing concentrations of the toxin and the maximum percent mortality rates for different P. xylostella larval instars at different times were observed for the 300 microg/mL cyclosporin C treatment, with an average mortality rate of 100% for all larval instars. The median lethal concentrations (LC(50)) of cyclosporin C against the first, second, third, and fourth larval instars of P. xylostella 72 h post-treatment were 78.05, 60.42, 50.83, and 83.05 microg/mL, respectively. Different concentrations of cyclosporin C caused a reduction in the average leaf consumption and average larval weight. Different life history parameters, such as the pupation rate (%), adult emergence (%), female fecundity, and female longevity were also inhibited when different concentrations of cyclosporin C were applied topically. The cyclosporin C concentrations inhibited the activities of different detoxifying (glutathione S-transferase, carboxylesterase, and acetylcholinesterase) and antioxidant enzyme (superoxide dismutase, catalase, and peroxidase) activities of P. xylostella when compared to the control. These findings can serve as baseline information for the development of cyclosporin C as an insect control agent, although further work on mass production, formulation, and field application is still required.
ESTHER : Wu_2022_Toxins.(Basel)_14_
PubMedSearch : Wu_2022_Toxins.(Basel)_14_
PubMedID: 36006176

Title : Comparative Study of the Molecular Characterization, Evolution, and Structure Modeling of Digestive Lipase Genes Reveals the Different Evolutionary Selection Between Mammals and Fishes - Tang_2022_Front.Genet_13_909091
Author(s) : Tang SL , Liang XF , He S , Li L , Alam MS , Wu J
Ref : Front Genet , 13 :909091 , 2022
Abstract : Vertebrates need suitable lipases to digest lipids for the requirement of energy and essential nutrients; however, the main digestive lipase genes of fishes have certain controversies. In this study, two types of digestive lipase genes (pancreatic lipase (pl) and bile salt-activated lipase (bsal)) were identified in mammals and fishes. The neighborhood genes and key active sites of the two lipase genes were conserved in mammals and fishes. Three copies of PL genes were found in mammals, but only one copy of the pl gene was found in most of the fish species, and the pl gene was even completely absent in some fish species (e.g., zebrafish, medaka, and common carp). Additionally, the hydrophobic amino acid residues (Ile and Leu) which are important to pancreatic lipase activity were also absent in most of the fish species. The PL was the main digestive lipase gene in mammals, but the pl gene seemed not to be the main digestive lipase gene in fish due to the absence of the pl gene sequence and the important amino acid residues. In contrast, the bsal gene existed in all fish species, even two to five copies of bsal genes were found in most of the fishes, but only one copy of the BSAL gene was found in mammals. The amino acid residues of bile salt-binding sites and the three-dimensional (3D) structure modeling of Bsal proteins were conserved in most of the fish species, so bsal might be the main digestive lipase gene in fish. The phylogenetic analysis also indicated that pl or bsal showed an independent evolution between mammals and fishes. Therefore, we inferred that the evolutionary selection of the main digestive lipase genes diverged into two types between mammals and fishes. These findings will provide valuable evidence for the study of lipid digestion in fish.
ESTHER : Tang_2022_Front.Genet_13_909091
PubMedSearch : Tang_2022_Front.Genet_13_909091
PubMedID: 35991544

Title : A multifunctional anti-AD approach: Design, synthesis, X-ray crystal structure, biological evaluation and molecular docking of chrysin derivatives - Yang_2022_Eur.J.Med.Chem_233_114216
Author(s) : Yang A , Liu C , Zhang H , Wu J , Shen R , Kou X
Ref : Eur Journal of Medicinal Chemistry , 233 :114216 , 2022
Abstract : With the aging of the population intensifying, finding a cure or reasonable treatment for Alzheimer' disease (AD) has become an urgent priority. To target the multi-facets of AD, a class of chrysin derivatives (1-4) were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, which were characterized by (1)H NMR, (13)C NMR, MS and elemental analysis. 1-4 showed inhibitory activities on reactive oxygen species, Abeta(1-42) aggregation (self-, Cu(2+)-induced, AChE-induced). They were also potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with selectivity toward BuChE. Compound 1 as the most promising candidate exhibited the highest selective BuChE inhibition (SI = 15). Furthermore, the kinetic study suggested compound 1 to be a mixed type inhibitor. The results of docking study were consistent with the in vitro results. In addition, compound 1-4 showed favorable blood-brain barrier (BBB) penetration and drug-like property in silico prediction. The corresponding copper complexes of 1-4 have also been synthesized. 1-4 selectively chelated Cu(2+), Fe(2+), Zn(2+) and Al(3+) ions, while had no chelating ability to other biometals. The copper complexes also showed good AChE, BuChE and reactive oxygen species inhibitory activities. Notably, the single crystals of 1-Cu(II) complex [Cu(C(19)H(18)NO(4))(2)] were prepared for the first time and characterized by X-ray single crystal diffraction. X-ray crystallography analysis of 1-Cu(II) complex provided a reliable structure-activity insight at the molecular level about the antioxidative and Abeta(1-42) disaggregation activities. Compound 1 might be a good lead compound to develop promising candidate analogs as AD therapeutics.
ESTHER : Yang_2022_Eur.J.Med.Chem_233_114216
PubMedSearch : Yang_2022_Eur.J.Med.Chem_233_114216
PubMedID: 35227980

Title : A narrative review: The pharmaceutical evolution of phenolic syringaldehyde - Wu_2022_Biomed.Pharmacother_153_113339
Author(s) : Wu J , Fu YS , Lin K , Huang X , Chen YJ , Lai D , Kang N , Huang L , Weng CF
Ref : Biomed Pharmacother , 153 :113339 , 2022
Abstract : To better understand the pharmacological characters of syringaldehyde (SA), which is a key-odorant compound of whisky and brandy, this review article is the first to compile the published literature for molecular docking that were subsequently validated by in vitro and in vivo assays to predict and develop insights into the medicinal properties of SA in terms of anti-oxidation, anti-inflammation, and anti-diabetes. The molecular docking displayed significantly binding affinity for SA towards tumor necrosis factor-alpha, interleukin-6, and antioxidant enzymes when inflammation from myocardial infarction and spinal cord ischemia. Moreover, SA nicely docked with dipeptidyl peptidase-IV, glucagon-like peptide 1 receptor, peroxisome proliferator-activated receptor, acetylcholine M2 receptor, and acetylcholinesterase in anti-diabetes investigations. These are associated with (1) an increase glucose utilization and insulin sensitivity to an anti-hyperglycemic effect; and (2) to potentiate intestinal contractility to abolish the alpha-amylase reaction when concurrently reducing retention time and glucose absorption of the intestinal tract to achieve a glucose-lowering effect. In silico screening of multi-targets concomitantly with preclinical tests could provide a potential exploration for new indications for drug discovery and development.
ESTHER : Wu_2022_Biomed.Pharmacother_153_113339
PubMedSearch : Wu_2022_Biomed.Pharmacother_153_113339
PubMedID: 35780614

Title : Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination - Wang_2022_Curr.Drug.Metab__
Author(s) : Wang D , Zhao T , Zhao S , Chen J , Dou T , Ge G , Wang C , Sun H , Liu K , Meng Q , Wu J
Ref : Curr Drug Metab , : , 2022
Abstract : BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2.
ESTHER : Wang_2022_Curr.Drug.Metab__
PubMedSearch : Wang_2022_Curr.Drug.Metab__
PubMedID: 35114918

Title : Chain-locked precursor ion scanning based HPLC-MS\/MS for in-depth molecular analysis of lipase-catalyzed transesterification of structured phospholipids containing w-3 fatty acyl chains - Zhang_2022_Food.Chem_399_133982
Author(s) : Zhang M , Wang P , Jin D , Jian S , Wu J , Huang M , Xie H , Zhao Q , Yang H , Luo P , Yuan H , Xue J , Shen Q
Ref : Food Chem , 399 :133982 , 2022
Abstract : Lipase-catalyzed transesterification of structured phospholipids (sPLs) is a hot topic, but the structural variation of the fatty acyl chains in intact phospholipids at the molecular level remains unclear to date. The present study explored the detailed characteristics of synthesized phospholipids through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in precursor ion scan mode. The optimal conditions were in-depth inspected and determined for the reaction system, including phospholipase A1 as catalyst, 15% lipase loading, and 1% water content. The sPLs enriched with EPA/DHA were structurally and quantitatively characterized by focusing on the fragments of m/z 301.6 (eicosapentaenoic acid, EPA) and m/z 327.6 (docosahexaenoic acid, DHA), and the results were statistically analyzed using partial least squares discriminant analysis and clustered heatmap hierarchical clustering analysis. PC 38:6 (18:1/20:5), PC 38:7 (18:2/20:5), PC o-40:6 (o-18:0/22:6), and PE 40:8 (18:2/22:6) etc. were revealed as the main variables that were active in the reaction.
ESTHER : Zhang_2022_Food.Chem_399_133982
PubMedSearch : Zhang_2022_Food.Chem_399_133982
PubMedID: 36027811

Title : Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour - Chen_2022_Phytochemistry_196_113089
Author(s) : Chen SQ , Jia J , Hu JY , Wu J , Sun WT , Zheng M , Wang X , Zhu KK , Jiang CS , Yang SP , Zhang J , Wang SB , Cai YS
Ref : Phytochemistry , 196 :113089 , 2022
Abstract : Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC(50) values of 2.61, 1.19, and 1.74 microM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 microg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC(50) of 20.06 microM) and alpha-glycosidase inhibitor (IC(50) of 17.18 microM), while tabernamine, ervahanine B, and ervadivaricatine B only showed alpha-glycosidase inhibitory activities with IC(50) values in the range of 0.95-4.61 microM.
ESTHER : Chen_2022_Phytochemistry_196_113089
PubMedSearch : Chen_2022_Phytochemistry_196_113089
PubMedID: 35074605

Title : Gender Disparities in Anti-dementia Medication Use among Older Adults: Health Equity Considerations and Management of Alzheimer's Disease and Related Dementias - Lu_2021_Front.Pharmacol_12_706762
Author(s) : Lu ZK , Xiong X , Wang X , Wu J
Ref : Front Pharmacol , 12 :706762 , 2021
Abstract : Objective: The prevalence of Alzheimer's disease and related dementias (ADRD) in women is higher than men. However, the knowledge of gender disparity in ADRD treatment is limited. Therefore, this study aimed to determine the gender disparities in the receipt of anti-dementia medications among Medicare beneficiaries with ADRD in the U.S. Methods: We used data from the Medicare Current Beneficiary Survey 2016. Anti-dementia medications included cholinesterase inhibitors (ChEIs; including rivastigmine, donepezil, and galantamine) and N-methyl-D-aspartate (NMDA) receptor antagonists (including memantine). Descriptive analysis and multivariate logistic regression models were implemented to determine the possible gender disparities in the receipt of anti-dementia medications. Subgroup analyses were conducted to identify gender disparities among beneficiaries with Alzheimer's disease (AD) and those with only AD-related dementias. Results: Descriptive analyses showed there were statistically significant differences in age, marital status, and Charlson comorbidities index (CCI) between Medicare beneficiaries who received and who did not receive anti-dementia medications. After controlling for covariates, we found that female Medicare beneficiaries with ADRD were 1.7 times more likely to receive anti-dementia medications compared to their male counterparts (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.19-2.45). Specifically, among Medicare beneficiaries with AD, females were 1.2 times more likely to receive anti-dementia medications (Odds Radio: 1.20; 95% confidence interval: 0.58-2.47), and among the Medicare beneficiaries with only AD-related dementias, females were 1.9 times more likely to receive anti-dementia medications (OR: 1.90; 95% CI: 1.23-2.95). Conclusion: Healthcare providers should be aware of gender disparities in receiving anti-dementia medications among patients with ADRD, and the need to plan programs of care to support both women and men. Future approaches to finding barriers of prescribing, receiving and, adhering to anti-dementia medications by gender should include differences in longevity, biology, cognition, social roles, and environment.
ESTHER : Lu_2021_Front.Pharmacol_12_706762
PubMedSearch : Lu_2021_Front.Pharmacol_12_706762
PubMedID: 34512340

Title : Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb - Wang_2021_Fitoterapia_156_105069
Author(s) : Wang X , Wang F , Wu J , Chen SQ , Jiang CS , Yang SP , Wang C , Cai YS
Ref : Fitoterapia , 156 :105069 , 2021
Abstract : Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and alpha-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and alpha-glucosidase.
ESTHER : Wang_2021_Fitoterapia_156_105069
PubMedSearch : Wang_2021_Fitoterapia_156_105069
PubMedID: 34743932

Title : pH and Redox Dual-Response Disulfide Bond-Functionalized Red-Emitting Gold Nanoclusters for Monitoring the Contamination of Organophosphorus Pesticides in Foods - Li_2021_Anal.Chem_93_7362
Author(s) : Li Q , Wu J , Yang Q , Li H , Li F
Ref : Analytical Chemistry , 93 :7362 , 2021
Abstract : Most of the fluorescence sensors require choline oxidase or quenchers to detect organophosphorus pesticides (OPs) based on a single hydrolysate and suffer from high cost, complex procedures, weak stability, and low sensitivity. Here, we proposed a brand-new fluorescence strategy for highly sensitive detection of OPs based on both hydrolysate-response disulfide bond-functionalized gold nanoclusters (S-S-AuNCs) without additional substances. S-S-AuNCs were synthesized via a facile one-step redox reaction and emitted bright red light with ultrasmall size and high water dispersion. Interestingly, S-S-AuNCs displayed a unique response to thiol compounds and low pH values and were thus pioneered as a high-efficiency sensor for OPs based on acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine into thiocholine and CH(3)COOH and OP inhibition of AChE activity. Further, S-S-AuNCs were employed to monitor the residue, distribution, and metabolization of methidathion in pakchoi with acceptable results. We believe that this work supplies a simpler and more highly sensitive approach for OP assay than the known ones and opens a new avenue to development of multistimulus-responsive and high-performance fluorescence substances.
ESTHER : Li_2021_Anal.Chem_93_7362
PubMedSearch : Li_2021_Anal.Chem_93_7362
PubMedID: 33961403

Title : Design, synthesis and biological evaluation of naringenin carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - Wu_2021_Bioorg.Med.Chem.Lett__128316
Author(s) : Wu J , Kou X , Ju H , Zhang H , Yang A , Shen R
Ref : Bioorganic & Medicinal Chemistry Lett , :128316 , 2021
Abstract : A series of naringenin derivatives were designed and synthesized as multifunctional anti-Alzheimer's disease (AD) agents. The results showed that these derivatives displayed moderate-to-good acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities at the micromolar range (IC(50), 12.91-62.52 microM for AChE and 0.094-13.72 microM for BuChE). Specifically, compound 1 showed the highest inhibitory activity against BuChE with the IC(50) value of (0.094+/-0.0054) microM. A Lineweaver-Burk plot and molecular docking studies demonstrated that 1 targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of BuChE. Besides, all derivatives showed excellent hydroxyl free radicals (.OH) scavenging ability than vitamin C and cyclic voltammetry results displayed that 1 could effectively scavenge superoxide anion radical (.O(2)(-)). In addition, compound 1 displayed good metal chelating properties and had anti-Abeta aggregation activities. Therefore, compound 1 might be the potential anti-AD agent for further developments.
ESTHER : Wu_2021_Bioorg.Med.Chem.Lett__128316
PubMedSearch : Wu_2021_Bioorg.Med.Chem.Lett__128316
PubMedID: 34391893

Title : Application of deep eutectic solvent-based extraction coupled with an S-CQD fluorescent sensor for the determination of pirimicarb in cereals - Jing_2021_Food.Chem_370_131360
Author(s) : Jing X , Wu J , Wang H , Guo L , Zheng X , Wang X , Wang S
Ref : Food Chem , 370 :131360 , 2021
Abstract : A novel deep eutectic solvent-based extraction and sulfur-doped carbon quantum dots (S-CQDs) serving as fluorescence probes to detect pirimicarb in cereals were established. The deep eutectic solvent was synthesized using choline chloride and butanediol, achieving direct and efficient extraction of pirimicarb residue in the cereals. The fluorescence quenching of S-CQDs was caused by the electrostatic interaction between the negatively charged S-CQDs and positively charged thiocholine, which was the hydrolysate of acetylthiocholine. The fluorescence of S-CQDs was enhanced as the activity of acetylcholinesterase (AChE) was inhibited by pirimicarb, achieving the detection of pirimicarb in the cereal samples. The limit of detection (LOD) was 0.006 microg mL(-1). The recovery ranged from 96.6% to 108.2%. This extraction and detection method of pirimicarb based on an environmentally friendly DES and S-CQD fluorescent sensor maintains good stability and convenience, offering a promising strategy for extracting and testing harmful substances in food samples.
ESTHER : Jing_2021_Food.Chem_370_131360
PubMedSearch : Jing_2021_Food.Chem_370_131360
PubMedID: 34662796

Title : Synergistic biodegradation of poly(ethylene terephthalate) using Microbacterium oleivorans and Thermobifida fusca cutinase - Yan_2021_Appl.Microbiol.Biotechnol__
Author(s) : Yan ZF , Wang L , Xia W , Liu ZZ , Gu LT , Wu J
Ref : Applied Microbiology & Biotechnology , : , 2021
Abstract : Poly(ethylene terephthalate) (PET) is a major source of plastic pollution. Biodegradation technologies are of paramount interest in reducing or recycling PET waste. In particular, a synergistic microbe-enzyme treatment may prove to be a promising approach. In this study, a synergistic system composed of Microbacterium oleivorans JWG-G2 and Thermobifida fusca cutinase (referred to as TfC) was employed to degrade bis(hydroxyethyl) terephthalate (BHET) oligomers and a high crystalline PET film. A novel degradation product that was obtained by M. oleivorans JWG-G2 treatment alone was identified as ethylene glycol terephthalate (EGT). With the addition of TfC as a second biocatalyst, the highest synergy degrees for BHET oligomers and PET film degradation were 2.79 and 2.26, respectively. The largest amounts of terephthalic acid (TPA) and mono(2-hydroxyethyl) terephthalate (MHET) (47 nM and 330 nM, respectively) were detected after combined treatment of PET film with M. oleivorans JWG-G2 at 5 x 10(3) microL/cm(2) and TfC at 120 microg/cm(2), and the degree of PET film surface destruction was more significant than those produced by each treatment alone. The presence of extracellular PET hydrolases in M. oleivorans JWG-G2, including three carboxylesterases, an esterase and a lipase, was predicted by whole genome sequencing analysis, and a predicted PET degradation pathway was proposed for the synergistic microbe-enzyme treatment. The results indicated that synergistic microbe-enzyme treatment may serve as a potentially promising tool for the future development of effective PET degradation. KEY POINTS: An ecofriendly synergistic microbe-enzyme PET degradation system operating at room temperature was first introduced for degrading PET. A novel product (EGT) was first identified during PET degradation. Potential PET hydrolases in M. oleivorans JWG-G2 were predicted by whole genome sequencing analysis.
ESTHER : Yan_2021_Appl.Microbiol.Biotechnol__
PubMedSearch : Yan_2021_Appl.Microbiol.Biotechnol__
PubMedID: 34037842

Title : Detection of carboxylesterase 1 and carbamates with a novel fluorescent protein chromophore based probe - Dai_2021_Dyes.Pigments_192_109444
Author(s) : Dai J , Zhao Y , Hou Y , Zhong G , Gao R , Wu J , Shen B , Zhang X
Ref : Dyes and Pigments , 192 :109444 , 2021
Abstract : An aggregation-induced emission (AIE) fluorescent protein chromophore-based probe (CBZ-FP) for detection of human carboxylesterases (CESs) was designed and synthesized. CBZ -FP exhibited good cell permeability with a large stokes shift (116snm) and can be applied to reveal the actual activities of CES1 in living cells associated with pesticide s detoxification process. CBZ-FP can also serve as a fluorescence indicator of pesticide exposure in the way of hydrolyzing the carboxylic acid ester group in CBZ-FP. There fore, CBZ-FP has high selectivity for CESs and can detect real-time activity of CES1 in biological samples. Molecular docking study was used to explore the binding of CESs and CBZ-FP. Finding that only one specific activity site of CESs can bind with probe. In view of the fact that, the biotransformation of drugs and poisons containing ester groups can carry out normally depending on CESs, Carboxylesterase probes are expected to contribute to the characterization of relevant disease.
ESTHER : Dai_2021_Dyes.Pigments_192_109444
PubMedSearch : Dai_2021_Dyes.Pigments_192_109444
PubMedID:

Title : Two-Dimensional MnO(2) Nanozyme-Mediated Homogeneous Electrochemical Detection of Organophosphate Pesticides without the Interference of H(2)O(2) and Color - Wu_2021_Anal.Chem__
Author(s) : Wu J , Yang Q , Li Q , Li H , Li F
Ref : Analytical Chemistry , : , 2021
Abstract : Traditional peroxidase-like nanozyme-based sensors suffer from self-decomposition and high toxicity of H(2)O(2), as well as the interference of color from nanozymes themselves and testing samples. In this work, we adopt nanozymes (two-dimension (2D) MnO(2) sheets, manganese dioxide nanosheets (MnNS)) with oxidase-like and peroxidase-like properties as advanced catalysts to develop a novel homogeneous electrochemical sensor for organophosphate pesticides (OPs) using dissolved O(2) as a coreactant without the interference of H(2)O(2) and color. Owing to the large surface area and unique catalytic activity of MnNS, a large amount of tetramethylbenzidine (TMB) is catalyzed oxidation, leading to a significantly declined differential pulse voltammetry (DPV) current. Obviously, MnNS display an excellent response to thiocholine, deriving from the catalyzing hydrolysis of acetylthiocholine (ATCh) by acetylcholinesterase (AChE), which switches a homogeneous electrochemical OP detection process based on the depressing AChE activity with a limit of detection (LOD) of 0.025 ng mL(-1). The as-proposed strategy on using nanozymes with oxidase-like and peroxidase-like properties to develop a homogeneous electrochemical sensor will provide a new pathway for improving the performance of nanozyme-based sensors, and the established MnNS-based homogeneous electrochemical sensor will find more applications for OP residue determination in food samples.
ESTHER : Wu_2021_Anal.Chem__
PubMedSearch : Wu_2021_Anal.Chem__
PubMedID: 33588528

Title : Novel chrysin derivatives as hidden multifunctional agents for anti-Alzheimer's disease: design, synthesis and in vitro evaluation - Liu_2021_Eur.J.Pharm.Sci__105976
Author(s) : Liu C , Kou X , Wang X , Wu J , Yang A , Shen R
Ref : Eur J Pharm Sci , :105976 , 2021
Abstract : Alzheimer's disease (AD) is the most common type of dementia, the exact etiology of the disease has not been known yet. The use of single-target drugs limits the efficacy of drugs and has certain side effects. In this study, the 'hidden' multi-target strategy was used in combination with chrysin's metal chelating site and rivastigmine's anti-cholinesterase pharmacophore to form an ester, which improves the hydrophobicity and protects the phenolic hydroxyl group at the same time. Four derivatives (1-4) were synthesized as the hidden multifunctional agents for AD therapy. Most of the compounds displayed good activities of anti-cholinesterase, antioxidant, appropriate blood brain barrier (BBB) penetration and certain inhibitory activity of beta-amyloid (Abeta) aggregation. Compound 3 was demonstrated as the highest selective butyrylcholinesterase (BuChE) inhibitor and targeted both the catalytic active site (CAS) and the peripheral anion site (PAS). And it could be hydrolyzed by BuChE to release chrysin with good ability to chelate Cu(2+) and Fe(2+). At the same time, phenol fragment can exert its good antioxidant effect. Overall, these findings demonstrated that compound 3 might be considered as a potential hidden multifunctional candidate in the therapy of AD.
ESTHER : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedSearch : Liu_2021_Eur.J.Pharm.Sci__105976
PubMedID: 34419572

Title : Construction of a red emission fluorescent protein chromophore-based probe for detection of carboxylesterase 1 and carbamate pesticide in culture cells - Dai_2021_Talanta_223_121744
Author(s) : Dai J , Hou Y , Wu J , Zhong G , Gao R , Shen B , Huang H
Ref : Talanta , 223 :121744 , 2021
Abstract : Designing fluorescent probe for detecting carboxylesterase 1 is remains challenging. Herein, a red emission human carboxylesterase 1 (CES1) probe (CAE-FP) was synthesized based on fluorescent protein chromophore. Probe CAE-FP can specific detect human CES1 with high selectively. The fluorescence quantum yield was calucated as 0.19. The carboxylic acid ester in CAE-FP could be easily hydrolyzed by CES1 under physiological conditions, and this process could induce the obvious fluorescence signal in red emission region. The detection limit of CES1 was calculated as 84.5 ng/mL. Due to the biological detoxification mechanism of carboxylesterase and the obvious inhibitory effect of pesticides on its activity, CAE-FP was applied to detect carbamate pesticide and have achieved good application results. Since fluorescent protein chromophore has excellent biocompatibility, probe CAE-FP with good cell membrane permeable and was successfully applied to monitor the real activities of CES1 in living cells. In summary, this is one of the few reported fluorescent probes that can specific detect the real-time activity of CES1 in biological samples. Besides, we first applied the fluorescent protein chromophore to construct the specific target enzyme probe. This work would contribute to further investigate CES1-associated physiological and pathological processe.
ESTHER : Dai_2021_Talanta_223_121744
PubMedSearch : Dai_2021_Talanta_223_121744
PubMedID: 33298268

Title : Accelerated biodegradation of polyethylene terephthalate by Thermobifida fusca cutinase mediated by Stenotrophomonas pavanii - Huang_2021_Sci.Total.Environ__152107
Author(s) : Huang QS , Yan ZF , Chen XQ , Du YY , Li J , Liu ZZ , Xia W , Chen S , Wu J
Ref : Sci Total Environ , :152107 , 2021
Abstract : Polyethylene terephthalate (PET) is a general plastic that produces a significant amount of waste due to its non-degradable properties. We obtained four bacteria (Stenotrophomonas pavanii JWG-G1, Comamonas thiooxydans CG-1, Comamonas koreensis CG-2 and Fulvimonas soli GM-1) that utilize PET as a sole carbon source through a novel stepwise screening and verification strategy. PET films pretreated with S. pavanii JWG-G1 exhibited weight loss of 91.4% following subsequent degradation by Thermobifida fusca cutinase (TfC). S. pavanii JWG-G1 was able to colonize the PET surface and maintain high cell viability (over 50%) in biofilm, accelerating PET degradation. Compared with PET films with no pretreatment, pretreatment with S. pavanii JWG-G1 caused the PET surface to be significantly rougher with greater hydrophilicity (contact angle of 86.3 +/- 2 degrees vs. 96.6 +/- 2 degrees), providing better opportunities for TfC to contact and act on PET. Our study indicates that S. pavanii JWG-G1 could be used as a novel pretreatment for efficiently accelerating PET biodegradation by TfC.
ESTHER : Huang_2021_Sci.Total.Environ__152107
PubMedSearch : Huang_2021_Sci.Total.Environ__152107
PubMedID: 34864034

Title : Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 - Zhao_2021_Curr.Drug.Metab__
Author(s) : Zhao T , Wang D , Shan Z , Chen J , Dou T , Ge G , Wang C , Meng Q , Sun H , Liu K , Wu J
Ref : Curr Drug Metab , : , 2021
Abstract : BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
ESTHER : Zhao_2021_Curr.Drug.Metab__
PubMedSearch : Zhao_2021_Curr.Drug.Metab__
PubMedID: 33568030

Title : Synergistic Interaction between the Entomopathogenic Fungus Akanthomyces attenuatus (Zare & Gams) and the Botanical Insecticide Matrine against Megalurothrips usitatus (Bagrall) - Wu_2021_J.Fungi.(Basel)_7_
Author(s) : Wu J , Yang B , Zhang X , Cuthbertson AGS , Ali S
Ref : J Fungi (Basel) , 7 : , 2021
Abstract : The excessive use of synthetic chemicals for Megalurothrips usitatus (Bagrall) management has resulted in the development of insecticide resistance as well as adverse effects to the natural ecosystem. This has driven the need to develop alternative pest control strategies. This study reports a synergistic interaction between the entomopathogenic fungus Akanthomyces attenuatus (Zare & Gams) and the botanical insecticide matrine against M. usitatus. The results revealed that the germination rate and colony growth of A. attenuatus were inhibited by higher matrine concentrations. Percentage mortalities of M. usitatus following application of A. attenuatus and matrine showed a dose mortality effect. After five days of treatment, all concentrations of matrine combined with different concentrations of A. attenuatus, except one combination (matrine 0.25 mg/mL + 1 x 10(7) conidia/mL), showed synergistic effect. The activities of acetylcholinesterase and antioxidant enzymes (superoxide dismutase, catalase and peroxidase) in M. usitatus, in response to individual or combined application of A. attenuatus and matrine at the end of the experimental period, were significantly lower than controls. The findings confirm the synergistic action of A. attenuatus and matrine against M. usitatus along with the biochemical phenomenon possibly regulating the synergistic effect.
ESTHER : Wu_2021_J.Fungi.(Basel)_7_
PubMedSearch : Wu_2021_J.Fungi.(Basel)_7_
PubMedID: 34356915

Title : Detoxification II Prescription Suppresses the Th-17\/IL-17 Inflammatory Axis to Improve the Liver Function of ACLF-Rats via Inactivating the P38MAPK Pathway - Shi_2021_J.Healthc.Eng_2021_7563383
Author(s) : Shi Q , Bai W , Mao D , Chen Y , Wang K , Qiu H , Wu J
Ref : J Healthc Eng , 2021 :7563383 , 2021
Abstract : Hepatitis is a metabolic system disease which is a serious challenge to the medical and healthcare system of the world. This study attempted to investigate the therapeutic effect and illustrate the regulation pharmacological mechanism of Detoxification II Prescription on ACLF. In this study, the rats were injected with D-galactosamine to establish ACLF-rat models, and the levels of cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBiL) were measured with the related kits to reflect the liver functions of the rats. The levels of IL-17, IL-6, and IFN-gamma in the serums of the rats were detected by qRT-PCR, and the percentages of Th-17 cells in CD4(+) cells of the rats were measured by flow cytometry assay. In the results, the increased ALT, AST, TBiL, IL-6, IL-17, IFN-gamma, and percentage of Th-17 cells in CD4(+) and decreased ALB and CHE were found in the serums of the ACLF-rats, while Detoxification II Prescription could partly reverse those indexes of the ACLF-rats. Moreover, it was also found that Detoxification II Prescription could inhibit the expression of P38MAPK, and P38MAPK downregulation obviously improved the liver function indexes of the ACLF-rats including the levels of ALT, AST, TBiL, IL-6, IL-17, IFN-gamma, and percentage of Th-17 cells in CD4(+) cells. In conclusion, this study suggested that Detoxification II Prescription could suppress the Th-17/IL-17 inflammatory axis to improve the liver function of ACLF-rats via inhibiting the activity of the P38MAPK pathway.
ESTHER : Shi_2021_J.Healthc.Eng_2021_7563383
PubMedSearch : Shi_2021_J.Healthc.Eng_2021_7563383
PubMedID: 34900202

Title : Osteocyte- and late Osteoblast-derived NOTUM Reduces Cortical Bone Mass in Mice - Nilsson_2021_Am.J.Physiol.Endocrinol.Metab__
Author(s) : Nilsson KH , Henning P , El Shahawy M , Wu J , Koskela A , Tuukkanen J , Perret C , Lerner UH , Ohlsson C , Moverare-Skrtic S
Ref : American Journal of Physiology Endocrinol Metab , : , 2021
Abstract : Osteoporosis is a common skeletal disease, with increased risk of fractures. Currently available osteoporosis treatments reduce the risk of vertebral fractures, mainly dependent on trabecular bone, whereas the effect on non-vertebral fractures, mainly dependent on cortical bone, is less pronounced. WNT signaling is a crucial regulator of bone homeostasis, and the activity of WNTs is inhibited by NOTUM, a secreted WNT lipase. We previously demonstrated that conditional inactivation of NOTUM in all osteoblast lineage cells increases the cortical but not the trabecular bone mass. The aim of the present study was to determine if NOTUM increasing cortical bone is derived from osteoblast precursors/early osteoblasts or from osteocytes/late osteoblasts. First, we demonstrated Notum mRNA expression in Dmp1-expressing osteocytes and late osteoblasts in cortical bone using in situ hybridization. We then developed a mouse model with inactivation of NOTUM in Dmp1 expressing osteocytes and late osteoblasts (Dmp1-creNotum(flox/flox) mice). We observed that the Dmp1-creNotum(flox/flox) mice displayed a substantial reduction of Notum mRNA in cortical bone, resulting in increased cortical bone mass and decreased cortical porosity in femur, but no change in trabecular bone volume fraction (BV/TV) in femur or in the lumbar vertebrae L5 in Dmp1-creNotum(flox/flox) mice as compared to control mice. In conclusion, osteocytes and late osteoblasts are the principal source of NOTUM in cortical bone, and NOTUM derived from osteocytes/late osteoblasts reduces cortical bone mass. These findings demonstrate that inhibition of osteocyte/late osteoblast-derived NOTUM might be an interesting pharmacological target to increase cortical bone mass and reduce non-vertebral fracture risk.
ESTHER : Nilsson_2021_Am.J.Physiol.Endocrinol.Metab__
PubMedSearch : Nilsson_2021_Am.J.Physiol.Endocrinol.Metab__
PubMedID: 33749332
Gene_locus related to this paper: human-NOTUM , mouse-notum

Title : Inhibition of soluble epoxide hydrolase (sEH) protects hippocampal neurons and reduces cognitive decline in type 2 diabetic mice - Wu_2021_Eur.J.Neurosci__
Author(s) : Wu J , Fan Z , Zhao Y , Chen Q , Xiao Q
Ref : European Journal of Neuroscience , : , 2021
Abstract : Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury, and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t-AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein-95 (PSD95) and N-methyl-d-aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline-rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.
ESTHER : Wu_2021_Eur.J.Neurosci__
PubMedSearch : Wu_2021_Eur.J.Neurosci__
PubMedID: 33595911

Title : A review on alpha-mangostin as a potential multi-target-directed ligand for Alzheimer's disease - Yang_2021_Eur.J.Pharmacol__173950
Author(s) : Yang A , Liu C , Wu J , Kou X , Shen R
Ref : European Journal of Pharmacology , :173950 , 2021
Abstract : Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive memory loss, declining language skills and other cognitive disorders. AD has brought great mental and economic burden to patients, families and society. However due to the complexity of AD's pathology, drugs developed for the treatment of AD often fail in clinical or experimental trials. The main problems of current anti-AD drugs are low efficacy due to mono-target method or side effects, especially high hepatotoxicity. To tackle these two main problems, multi-target-directed ligand (MTDL) based on "one molecule, multiple targets" has been studied. MTDLs can regulate multiple biological targets at the same time, so it has shown higher efficacy, better safety. As a natural active small molecule, alpha-mangostin (alpha-M) has shown potential multi-factor anti-AD activities in a series of studies, furthermore it also has a certain hepatoprotective effect. The good availability of alpha-M also provides support for its application in clinical research. In this work, multiple activities of alpha-M related to AD therapy were reviewed, which included anti-cholinesterase, anti-amyloid-cascade, anti-inflammation, anti-oxidative stress, low toxicity, hepatoprotective effects and drug formulation. It shows that alpha-M is a promising candidate for the treatment of AD.
ESTHER : Yang_2021_Eur.J.Pharmacol__173950
PubMedSearch : Yang_2021_Eur.J.Pharmacol__173950
PubMedID: 33607107

Title : Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK\/HO-1 pathway - Wu_2020_Biochem.Biophys.Res.Commun__
Author(s) : Wu J , Zhao Y , Fan Z , Chen Q , Chen J , Sun Y , Jiang X , Xiao Q
Ref : Biochemical & Biophysical Research Communications , : , 2020
Abstract : Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation.
ESTHER : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedSearch : Wu_2020_Biochem.Biophys.Res.Commun__
PubMedID: 32001002

Title : Structure-guided engineering of a Thermobifida fusca cutinase for enhanced hydrolysis on natural polyester substrate - Dong_2020_Bioresour.Bioprocess_7_37
Author(s) : Dong Q , Yuan S , Wu L , Su L , Zhao Q , Wu J , Huang W , Zhou J
Ref : Bioresour. Bioprocess , 7 :37 , 2020
Abstract : Cutinases could degrade insoluble polyester, including natural cutin and synthetic plastic. However, their turnover efficiency for polyester remains too low for industrial application. Herein, we report the 1.54-A resolution X-ray crystal structure of a cutinase from Thermobifida fusca and modeling structure in complex with a cutin mimic oligo-polyester C24H42O8. These efforts subsequently guided our design of cutinase variants with less bulky residues in the vicinity of the substrate binding site. The L90A and I213A variants exhibit increased hydrolysis activity (5- and 2.4-fold, respectively) toward cutin and also showed enhanced cotton scouring efficiency compared with the wild-type enzyme.
ESTHER : Dong_2020_Bioresour.Bioprocess_7_37
PubMedSearch : Dong_2020_Bioresour.Bioprocess_7_37
PubMedID:
Gene_locus related to this paper: thefu-q6a0i4

Title : Discovery of Thai mangrove tetranortriterpenoids as agonists of human pregnane-X-receptor and inhibitors against human carboxylesterase 2 - Ren_2020_Bioorg.Chem_107_104599
Author(s) : Ren YX , Zou XP , Li WS , Wu J , Shen L
Ref : Bioorg Chem , 107 :104599 , 2020
Abstract : Human pregnane-X-receptor (hPXR) is considered to be the key target for the treatment of cholestasis and liver injury. Agonists of hPXR are potential drug leads. Potent and selective inhibitors of human carboxylesterase 2 (hCES2) could be utilized to alleviate the toxicity induced by ester drugs. In this work, fifteen new tetranortriterpenoids with structure diversity, named thaigranatins F-T (1-15), including four limonoids containing a C(1)-O-C(29) bridge (1-4), four mexicanolides (5-8), three phragmalins (9-11), two limonoids belonging to the small group of trichiliton A (12-13), and two apotirucallanes (14-15), were isolated from seeds of the Thai mangrove, Xylocarpus granatum. The structures of these compounds were established by high resolution-electrospray ionization mass spectroscopy, extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism spectra. Most notably, thaigranatins L (7) and P (11) exhibited agonistic effects on hPXR at the concentration of 10.0 microM and 10.0 nM, respectively, whereas thaigranatins J (5), M (8), and T (15) showed inhibitory activities against hCES2 with IC(50) values of 6.63, 11.35, and 5.05 microM, respectively. The 8alpha,30alpha-epoxy moiety of mexicanolide and the delta(8,14) double bond of phragmalin are pivotal for agonistic effects of these limonoids on hPXR, whereas the 6-OAc group of mexicanolide is crucial for its inhibitory activity against hCES2. Additionally, the flexible C-17-side-chain with appropriate hydroxy groups is considered to be important for the inhibitory activity of apotirucallane against hCES2.
ESTHER : Ren_2020_Bioorg.Chem_107_104599
PubMedSearch : Ren_2020_Bioorg.Chem_107_104599
PubMedID: 33421954

Title : Patatin primary structural properties and effects on lipid metabolism - Wu_2020_Food.Chem__128661
Author(s) : Wu J , Wu Q , Yang D , Zhou M , Xu J , Wen Q , Cui Y , Bai Y , Xu S , Wang Z , Wang S
Ref : Food Chem , :128661 , 2020
Abstract : Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects.
ESTHER : Wu_2020_Food.Chem__128661
PubMedSearch : Wu_2020_Food.Chem__128661
PubMedID: 33272761

Title : Biological Impact and Enzyme Activities of Spodoptera litura (Lepidoptera: Noctuidae) in Response to Synergistic Action of Matrine and Beauveria brongniartii - Wu_2020_Front.Physiol_11_584405
Author(s) : Wu J , Li J , Zhang C , Yu X , Cuthbertson AGS , Ali S
Ref : Front Physiol , 11 :584405 , 2020
Abstract : Matrine, a naturally occurring heterocyclic compound, has been shown to enhance the pathogenicity of the entomopathogenic fungus Beauveria brongniartii against Spodoptera litura. In the current study, the biological impacts and synergism activities of these two agents on nutritional efficiency and antioxidant enzymes in S. litura were explored. Our results showed a high antifeedant activity of B. brongniartii and matrine on S. litura. The S. litura larvae were unable to pupate and emerge when treated with combinations of matrine and B. brongniartii. Following on, we measured the activities of five important antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), acetylcholinesterase (AChE), and glutathione-S-transferase (GST)] when treated with B. brongniartii SB010 (1 x 10(9) spores/ml), matrine (0.5 mg/ml), and B. brongniartii SB010 (1 x 10(9) spores/ml) + matrine (0.5 mg/ml). The results indicated the detoxification activity of the five enzymes in the fat body and hemolymph of S. litura when facing a combined B. brongniartii and matrine challenge. The activities of the enzymes were significantly lower than that of the control group 7 days post-treatment, indicating the inhibitory effect of the two xenobiotics. Matrine had better inhibition effects than B. brongniartii in a majority of the trials. The improved detoxification activity of the five enzymes may be the internal mechanism of synergism of matrine on B. brongniartii.
ESTHER : Wu_2020_Front.Physiol_11_584405
PubMedSearch : Wu_2020_Front.Physiol_11_584405
PubMedID: 33224038

Title : Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry - Wan_2020_J.Virol_94_
Author(s) : Wan Y , Shang J , Sun S , Tai W , Chen J , Geng Q , He L , Chen Y , Wu J , Shi Z , Zhou Y , Du L , Li F
Ref : J Virol , 94 : , 2020
Abstract : Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.
ESTHER : Wan_2020_J.Virol_94_
PubMedSearch : Wan_2020_J.Virol_94_
PubMedID: 31826992

Title : Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation - Xu_2020_Bioorg.Chem_98_103721
Author(s) : Xu A , He F , Zhang X , Li X , Ran Y , Wei C , James Chou C , Zhang R , Wu J
Ref : Bioorg Chem , 98 :103721 , 2020
Abstract : In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Abeta1-42 self-aggregation as well as disaggregation activity on pre-formed Abeta fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics.
ESTHER : Xu_2020_Bioorg.Chem_98_103721
PubMedSearch : Xu_2020_Bioorg.Chem_98_103721
PubMedID: 32193030

Title : GDSL esterase\/lipases OsGELP34 and OsGELP110\/OsGELP115 are essential for rice pollen development - Zhang_2020_J.Integr.Plant.Biol__
Author(s) : Zhang H , Wang M , Li Y , Yan W , Chang Z , Ni H , Chen Z , Wu J , Xu C , Deng XW , Tang X
Ref : J Integr Plant Biol , : , 2020
Abstract : Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2020_J.Integr.Plant.Biol__
PubMedSearch : Zhang_2020_J.Integr.Plant.Biol__
PubMedID: 32068333

Title : Design, synthesis and biological evaluation of novel carbamates as potential inhibitors of acetylcholinesterase and butyrylcholinesterase - Wu_2020_Bioorg.Med.Chem__115324
Author(s) : Wu J , Pistolozzi M , Liu S , Tan W
Ref : Bioorganic & Medicinal Chemistry , :115324 , 2020
Abstract : Rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), has been approved by U.S. Food and Drug Administration to treat Alzheimer's disease (AD) and Parkinson's disease (PD) dementia. In the current work, a bambuterol derivative lacking one of the carbamoyloxy groups on the benzene ring (BMC-1) and its analogues were synthesized using 1-(3-hydroxyphenyl) ethan-1-one and 1-(4-hydroxyphenyl) ethan-1-one as starting materials. In-vitro cholinesterase assay established that nine compounds were more potent to inhibit both electric eel AChE and equine serum BChE than rivastigmine under the same experimental conditions. Further study confirmed that among the nine carbamates, BMC-3 (IC50(AChE) = 792 nM, IC50(BChE) = 2.2 nM) and BMC-16 (IC50(AChE) = 266 nM, IC50(BChE) = 10.6 nM) were excellent cholinesterase inhibitors with potential of permeating through the blood-brain barrier. These carbamates could be used as potential dual inhibitors of AChE and BChE and to discover novel drugs for the treatment of AD and PD dementia.
ESTHER : Wu_2020_Bioorg.Med.Chem__115324
PubMedSearch : Wu_2020_Bioorg.Med.Chem__115324
PubMedID: 32008882

Title : Prophylactic cognitive enhancers for improvement of cognitive function in patients undergoing electroconvulsive therapy: A systematic review and meta-analysis - Niu_2020_Medicine.(Baltimore)_99_e19527
Author(s) : Niu Y , Ye D , You Y , Wu J
Ref : Medicine (Baltimore) , 99 :e19527 , 2020
Abstract : OBJECTIVE: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effect for reducing post-electroconvulsive therapy (post-ECT) cognitive side effects is unclear. We conducted a systematic review and meta-analysis to assess the effectiveness of cognitive enhancers in the prevention of cognitive side effects due to ECT. METHODS: We identified relevant studies by searching electronic databases (e.g., PubMed, EMBASE, Web of Science, Cochrane Library). Only studies published up to October 2019 comparing cognitive enhancer vs placebo for cognitive function after ECT were included. The primary outcome extracted from the studies was cognitive function score. RESULTS: Five studies with 202 patients were included in this study. The cognitive enhancer group (CEG) had a significantly higher cognitive function score. Moreover, sensitivity analysis showed that no individual study had a significant impact on the overall results. CONCLUSIONS: This meta-analysis revealed that cognitive enhancers might improve cognitive function and reduce ECT-induced cognitive side effects. Nevertheless, more high-quality randomized controlled trials (RCTs) with long-term follow-up are still needed to make the final conclusion.
ESTHER : Niu_2020_Medicine.(Baltimore)_99_e19527
PubMedSearch : Niu_2020_Medicine.(Baltimore)_99_e19527
PubMedID: 32176105

Title : Relief of Cadmium-Induced Intestinal Motility Disorder in Mice by Lactobacillus plantarum CCFM8610 - Liu_2020_Front.Immunol_11_619574
Author(s) : Liu Y , Wu J , Xiao Y , Liu Q , Yu L , Tian F , Zhao J , Zhang H , Chen W , Zhai Q
Ref : Front Immunol , 11 :619574 , 2020
Abstract : Cadmium (Cd) is a toxic metal inducing a range of adverse effects on organs including liver and kidneys. However, the underlying molecular mechanisms of Cd-induced intestinal toxicity through dietary intake is poorly studied. This study evaluated the toxic effects of Cd on intestinal physiology and confirmed the effectiveness of the protective mechanism of the probiotic Lactobacillus plantarum CCFM8610 against chronic Cd toxicity. After treatment with Cd, the HT-29 cell line was subjected to iTRAQ analysis, which revealed that changes in the proteomic profiles after Cd exposure were related to pathways involved in the stress response and carbohydrate metabolism. The results of an animal trial also indicated that 10 weeks of Cd exposure decreased the fecal water content and contractile response of colonic muscle strips in mice, and delayed the excretion time of the first black feces. L. plantarum CCFM8610 treatment provided protective effects against these Cd-induced intestinal motility dysfunctions by recovering the levels of neurotransmitters, including substance P, acetyl cholinesterase, vasoactive intestinal peptide, 5-hydroxytryptamine, calcitonin gene-related peptide, and nitric oxide, and suppressing the cellular stress response in mice (e.g., the inhibition of mitogen-activated protein kinase pathways). The administration of this probiotic was also observed to reduce Cd levels in the tissues and blood of the mice. Our results suggest a newly identified protective mechanism of probiotics against Cd toxicity that involves the recovery of intestinal motility and increase in fecal cadmium excretion.
ESTHER : Liu_2020_Front.Immunol_11_619574
PubMedSearch : Liu_2020_Front.Immunol_11_619574
PubMedID: 33362802

Title : Enhanced activity towards polyacrylates and poly(vinyl acetate) by site-directed mutagenesis of Humicola insolens cutinase - Su_2020_Int.J.Biol.Macromol_162_1752
Author(s) : Su L , Hong R , Kong D , Wu J
Ref : Int J Biol Macromol , 162 :1752 , 2020
Abstract : Previous studies on the hydrolysis of polyacrylates by cutinase have found that cutinase from Humicola insolens can fulfill the requirement for a thermostable cutinase in the treatment of stickies from papermaking, but it has poor hydrolysis ability. To further improve its ability to hydrolyze the polymers in papermaking, we analyzed the structure of cutinase from H. insolens, and constructed three mutants L66A, I169A, and L66A/I169A to reduce the steric hindrance of the substrate binding region. The hydrolysis results for poly(methyl acrylate), poly(ethyl acrylate), and poly(vinyl acetate) showed the catalytic ability of the mutant L66A/I169A most significantly improved. Using polymer macroporous resin composites as substrate, the released products of L66A/I169A were 1.3-4.4 times higher than that of the wild-type enzyme. When polymer suspensions were no longer being deposited, that is, when the turbidity decrease was less than 1%, the amount of L66A/I169A added was reduced by 19%-51% compared with that of the wild-type enzyme. These results indicated that the removal of the gatekeeper structure above the substrate binding region of H. insolens cutinase enhances its ability to hydrolyze polymers, and provided a basis for the application of cutinase in the practical treatment of stickies.
ESTHER : Su_2020_Int.J.Biol.Macromol_162_1752
PubMedSearch : Su_2020_Int.J.Biol.Macromol_162_1752
PubMedID: 32771512
Gene_locus related to this paper: humin-cut

Title : In Vitro Hepatic Metabolism of Curcumin Diethyl Disuccinate by Liver S9 from Different Animal Species - Jithavech_2020_Front.Pharmacol_11_577998
Author(s) : Jithavech P , Ratnatilaka Na Bhuket P , Supasena W , Qiu G , Ye S , Wu J , Wong TW , Rojsitthisak P
Ref : Front Pharmacol , 11 :577998 , 2020
Abstract : Liver S9 (LS9) is a nearly complete collection of all hepatic drug-metabolizing enzymes. It is a low-cost model for predicting drug metabolic activity. This study aimed to identify the suitability of using LS9 of different animal sources in drug metabolism profiling with respect to the possible translation of the in vitro outcomes to clinical studies. The in vitro hepatic metabolism of curcumin diethyl disuccinate (CDD) in LS9 of rats, dogs, monkeys, and humans was evaluated. The identity of CDD metabolites and the metabolism kinetic parameters, including degradation rate constant, in vitro/in vivo intrinsic clearance, and half-life, were determined. CDD was rapidly metabolized into monoethylsuccinyl curcumin and curcumin in LS9 of all tested species mainly by carboxylesterases (CESs), including CES1 and CES2, and butyrylcholinesterase. The in vitro intrinsic clearance of CDD was in the order of human > dog > monkey > rat, whereas that of monoethylsuccinyl curcumin in the order of dog > monkey > human > rat; this parameter was not correlated with their respective in vivo clearance, which followed the order of dog > monkey > rat > human. Therefore, in vitro drug metabolism data inferred from LS9 of nonhuman origin, especially from monkeys and dogs, cannot be used as preclinical data for human trials, as humans have a smaller liver-to-body weight ratio than monkeys, dogs, and rats. The in vivo drug metabolism is dictated by the anatomical factors of the test subject.
ESTHER : Jithavech_2020_Front.Pharmacol_11_577998
PubMedSearch : Jithavech_2020_Front.Pharmacol_11_577998
PubMedID: 33312126

Title : Limonoids with diverse structures of rings-A,B from the Thai mangrove, Xylocarpus moluccensis - Shen_2020_Fitoterapia__104737
Author(s) : Shen L , Liao Q , Zhang M , Wu J
Ref : Fitoterapia , :104737 , 2020
Abstract : Nine new limonoids, named thaixylomolins S-Z (1-8) and 2-O-acetylthaixylomolin Z (9), were isolated from seeds of the mangrove, Xylocarpus moluccensis, collected in the mangrove swamp of Trang Province, Thailand. Thaixylomolin S (1) is the fourth member of the khayalactone class of limonoids containing a hexahydro-2H-2,5- propanocyclopenta[b]furan motif. Thaixylomolins T-Y (2-7) are structurally diverse mexicanolides; whereas thaixylomolin Z (8) and 2-O-acetylthaixylomolin Z (9) are phragmalin 8,9,30-orthoesters. The structures of these compounds were established by HRESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of thaixylomolins S (1), U (3), and Z (8) were unambiguously established by single-crystal X-ray diffraction analyses, conducted with Cu Kalpha radiation; whereas that of 2-O-acetylthaixylomolin Z (9) was determined to be the same as that of thaixylomolin Z (8) by the accurate fit of their experimental electronic circular dichroism spectra. Thaixylomolin S (1), featuring the presence of a 30-(2'-methyl)butyryloxy group, is the first limonoid of the khayalactone class, whose constitution and absolute configuration are unequivocally determined by X-ray crystallography. The inhibitory activities of all the compounds, except for the epimers 4, were assayed against human carboxylesterase 2. All the tested compounds exhibited inhibition rates in the range of 16-65% at the concentration of 100.0muM.
ESTHER : Shen_2020_Fitoterapia__104737
PubMedSearch : Shen_2020_Fitoterapia__104737
PubMedID: 33022332

Title : Twenty-five limonoids from the Hainan mangrove, Xylocarpus granatum - Zhang_2020_Bioorg.Chem_100_103903
Author(s) : Zhang JC , Liao Q , Shen L , Wu J
Ref : Bioorg Chem , 100 :103903 , 2020
Abstract : Twenty-four new limonoids (1-24), named hainanxylogranins A-X, were isolated from leaves and barks of the Hainan mangrove, Xylocarpus granatum, together with a known compound, tabulvelutin B (25). The structures of these compounds were established by high resolution electrospray ionization mass spectroscopy (HRESIMS), extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, the absolute configurations of seven compounds, viz., 1, 2, 6, 16, 17, 22, and 25, were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kalpha radiation. Compounds 1-4 belong to a unique group of mexicanolides containing a C3-O-C8 bridge and a C-17 substituted gamma(21)-hydroxybutenolide moiety, whereas 5-9 are mexicanolides comprising a C1-O-C8 bridge. Compounds 10-16 are typical mexicanolides, among which 14 and 15 contain a C-17 substituted gamma(23)-hydroxybutenolide moiety. Compounds 17 and 18 are phragmalin 8,9,30-orthoesters, whereas 19 and 20 are phragmalin 1,8,9-orthoesters. Compound 21 consists of a C1-O-C29 bridge, while 22-24 are derivatives of azadirone. The inhibitory activities of 1, 5-8, 11, 17, 19, 21-23, and 25 against human carboxylesterase 2 (CES2) were assayed. All the tested compounds exhibited inhibition rates of 30-64% at the concentration of 100.0 microM.
ESTHER : Zhang_2020_Bioorg.Chem_100_103903
PubMedSearch : Zhang_2020_Bioorg.Chem_100_103903
PubMedID: 32413629

Title : The toxicity assessment of extract of Peganum harmala L. seeds in Caenorhabditis elegans - Miao_2020_BMC.Complement.Med.Ther_20_256
Author(s) : Miao X , Zhang X , Yuan Y , Zhang Y , Gao J , Kang N , Liu X , Wu J , Liu Y , Tan P
Ref : BMC Complement Med Ther , 20 :256 , 2020
Abstract : BACKGROUND: Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. METHODS: In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 degC in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P < 0.01), and the mean lifespan was significantly decreased (P < 0.01). We also observed that PHS exposure could induce the toxicity on body length, brood size, and locomotion behavior. CONCLUSION: Our study shows that the ethanol extract of PHS exerts obvious toxic effects on C. elegans, which would provide new ideas and methods for the biological evaluation of the toxicity of Chinese medicinal materials.
ESTHER : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedSearch : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedID: 32807143

Title : Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing - Wu_2020_Anal.Chem__
Author(s) : Wu Y , Wu J , Jiao L , Xu W , Wang H , Wei X , Gu W , Ren G , Zhang N , Zhang Q , Huang L , Gu L , Zhu C
Ref : Analytical Chemistry , : , 2020
Abstract : Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the de-velopment of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple mod-el of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were syn-thesized through a salt-template strategy. With the densely distributed active Cu atoms (~5.1 wt%), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxi-dase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organo-phosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.
ESTHER : Wu_2020_Anal.Chem__
PubMedSearch : Wu_2020_Anal.Chem__
PubMedID: 31941278

Title : HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure - Wu_2019_J.Viral.Hepat_26_1334
Author(s) : Wu J , Guo N , Zhang X , Xiong C , Liu J , Xu Y , Fan J , Yu J , Zhao X , Liu B , Wang W , Zhang J , Cao H , Li L
Ref : J Viral Hepat , 26 :1334 , 2019
Abstract : A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.
ESTHER : Wu_2019_J.Viral.Hepat_26_1334
PubMedSearch : Wu_2019_J.Viral.Hepat_26_1334
PubMedID: 31294523

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

Title : Surface functionalization of graphene oxide by amino acids for Thermomyces lanuginosus lipase adsorption - Zhou_2019_J.Colloid.Interface.Sci_546_211
Author(s) : Zhou W , Zhuang W , Ge L , Wang Z , Wu J , Niu H , Liu D , Zhu C , Chen Y , Ying H
Ref : J Colloid Interface Sci , 546 :211 , 2019
Abstract : Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase.
ESTHER : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedSearch : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedID: 30921675

Title : High-level expression of Humicola insolens cutinase in Pichia pastoris without carbon starvation and its use in cotton fabric bioscouring - Hong_2019_J.Biotechnol_304_10
Author(s) : Hong R , Sun Y , Su L , Gu L , Wang F , Wu J
Ref : J Biotechnol , 304 :10 , 2019
Abstract : Huimcola insolens cutinase (HiC) was heterologously expressed in Pichia pastoris. To avoid a carbon starvation step, fermentation was conducted using combinations of sorbitol with glycerol and methanol in the cell growth and induction phases, respectively. The cutinase productivity (27.71 U mL(-1) h(-1)) was 9.93 U mL(-1) h(-1) greater than that achieved using traditional two-phase methods, and a cutinase activity of 2660 U mL(-1), using p-nitrophenyl butyrate as substrate, was achieved after only 96 h in a 3-L bioreactor. Subsequently, the combination of HiC with Thermobifida fusca cutinase (TfC) in cotton fabric bioscouring was evaluated by monitoring the wettability and dyeability of the fabric. Treatment with 20 U mL(-1) of HiC at 80 degrees C for 5 min followed by 30 U mL(-1) of TfC at 50 degrees C for 1 h gave the best results. The total treatment time was shorter and performance was better than those seen with the alkali method.
ESTHER : Hong_2019_J.Biotechnol_304_10
PubMedSearch : Hong_2019_J.Biotechnol_304_10
PubMedID: 31400343

Title : Assessment of phthalate ester residues and distribution patterns in Baijiu raw materials and Baijiu - Dong_2019_Food.Chem_283_508
Author(s) : Dong W , Guo R , Sun X , Li H , Zhao M , Zheng F , Sun J , Huang M , Wu J
Ref : Food Chem , 283 :508 , 2019
Abstract : Phthalate esters (PAEs) are harmful to human health and have been repeatedly identified in Baijiu samples. In our study, the distribution and degradation characteristics of 14 PAEs in Baijiu raw materials (BRMs) and Baijiu during distillation were detected using QuEChERS or vortex-assisted surfactant-enhanced-emulsification liquid-liquid micro-extraction (VSLLME) methods coupled with gas chromatography-mass spectrometry. The same five PAEs were detected in all tested samples, values ranged from 0.003 to 0.292 mg/kg; however, higher concentrations existed in BRMs compared to Baijiu samples. Using multivariate statistical analysis, detailed distinctions between different varieties of Baijiu and BRMs and separation-related PAE markers were revealed. PAEs concentration during Baijiu distillation showed a decreasing trend. The highest concentrations detected in distillate heads, were 1.6-, 2.3-, and 8.1-fold higher than those in heart1, heart2, and tail distillates, respectively. These findings revealed that PAEs may migrate from BRMs; moreover, that PAEs content can be regulated by distillation.
ESTHER : Dong_2019_Food.Chem_283_508
PubMedSearch : Dong_2019_Food.Chem_283_508
PubMedID: 30722905

Title : Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells - Wan_2019_FASEB.J__fj201802675R
Author(s) : Wan L , Xia T , Du Y , Liu J , Xie Y , Zhang Y , Guan F , Wu J , Wang X , Shi C
Ref : FASEB Journal , :fj201802675R , 2019
Abstract : The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed via electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif-1alpha was inhibited via 2-ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs, and LSECs. Disruption of Hif-1 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.-Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exomes in metabolic switch of liver nonparenchymal cells.
ESTHER : Wan_2019_FASEB.J__fj201802675R
PubMedSearch : Wan_2019_FASEB.J__fj201802675R
PubMedID: 30970216

Title : LIPG SNPs, their haplotypes and gene-environment interactions on serum lipid levels - Yang_2019_Lipids.Health.Dis_18_10
Author(s) : Yang S , Yin RX , Miao L , Zhou YG , Wu J , Zhang QH
Ref : Lipids Health Dis , 18 :10 , 2019
Abstract : BACKGROUND: Maonan nationality is a relatively conservative and isolated minority in the Southwest of China. Little is known about the association of endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. METHODS: A total of 1280 subjects of Maonan nationality and 1218 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the four LIPG SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: Several SNPs were associated with high-density lipoprotein cholesterol (rs3813082, rs2000813 and rs2097055) in the both ethnic groups; total cholesterol and apolipoprotein (Apo) A1 (rs2000813) in Han nationality; and low-density lipoprotein cholesterol, ApoB, triglyceride (rs2097055) and ApoA1 (rs3819166) in Maonan minority (P < 0.0125 for all after Bonferroni correction). The commonest haplotype was rs3813082T-rs2000813C-rs2097055T-rs3819166A (Han, 44.2% and Maonan, 48.7%). The frequencies of the T-C-T-A, T-C-T-G, T-T-C-G and G-T-C-G haplotypes were different between the Maonan and Han populations (P < 0.05-0.001). The associations between haplotypes and dyslipidemia were also different in the Han and/or Maonan populations (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid profiles between the two ethnic groups might partly be attributed to these LIPG SNPs, their haplotypes and gene-environmental interactions. TRIAL REGISTRATION: Retrospectively registered.
ESTHER : Yang_2019_Lipids.Health.Dis_18_10
PubMedSearch : Yang_2019_Lipids.Health.Dis_18_10
PubMedID: 30621702
Gene_locus related to this paper: human-LIPG

Title : A Novel Dipeptidyl Peptidase IV Inhibitory Tea Peptide Improves Pancreatic beta-Cell Function and Reduces alpha-Cell Proliferation in Streptozotocin-Induced Diabetic Mice - Lu_2019_Int.J.Mol.Sci_20_
Author(s) : Lu Y , Lu P , Wang Y , Fang X , Wu J , Wang X
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Dipeptidyl peptidase IV (DPP-IV) inhibitors occupy a growing place in the drugs used for the management of type 2 diabetes. Recently, food components, including food-derived bioactive peptides, have been suggested as sources of DPP-IV inhibitors without side effects. Chinese black tea is a traditional health beverage, and it was used for finding DPP-IV inhibitory peptides in this study. The ultra-filtrated fractions isolated from the aqueous extracts of black tea revealed DPP-IV inhibitory activity in vitro. Four peptides under 1 kDa were identified by SDS-PAGE and LC-MS/MS (Liquid Chromatography-Mass Spectrometry-Mass Spectrometry) from the ultra-filtrate. The peptide II (sequence: AGFAGDDAPR), with a molecular mass of 976 Da, showed the greatest DPP-IV inhibitory activity (in vitro) among the four peptides. After administration of peptide II (400 mg/day) for 57 days to streptozotocin (STZ)-induced hyperglycemic mice, the concentration of glucagon-like peptide-1 (GLP-1) in the blood increased from 9.85 +/- 1.96 pmol/L to 19.22 +/- 6.79 pmol/L, and the insulin level was increased 4.3-fold compared to that in STZ control mice. Immunohistochemistry revealed the improved function of pancreatic beta-cells and suppressed proliferation of pancreatic alpha-cells. This study provides new insight into the use of black tea as a potential resource of food-derived DPP-IV inhibitory peptides for the management of type 2 diabetes.
ESTHER : Lu_2019_Int.J.Mol.Sci_20_
PubMedSearch : Lu_2019_Int.J.Mol.Sci_20_
PubMedID: 30646613

Title : Association between the LIPG polymorphisms and serum lipid levels in the Maonan and Han populations - Yang_2019_J.Gene.Med__e3071
Author(s) : Yang S , Yin RX , Miao L , Zhang QH , Zhou YG , Wu J
Ref : J Gene Med , :e3071 , 2019
Abstract : BACKGROUD: Maonan nationality is a relatively isolated minority in China. Little is known about the endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. The present study was undertaken to detect the association of several LIPG SNPs and environmental factors with serum lipid levels in the Chinese Maonan and Han populations. METHODS: A total of 773 subjects of Maonan nationality and 710 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the LIPG rs2156552, rs4939883 and rs7241918 SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: The allelic (rs2156552, rs4939883 and rs7241918) and genotypic (rs2156552 and rs4939883) frequencies were different between the two ethnic groups (P < 0.05-0.01). The minor allele carriers had lower ApoA1/ApoB ratio (rs2156552 and rs7241918), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 (rs2156552) levels and higher ApoB levels (rs4939883) in Han nationality; and lower HDL-C (rs2156552, rs4939883 and rs7241918) levels in Maonan minority than the minor allele non-carriers (P < 0.0167 after the Bonferroni correction). Subgroup analyses according to sex showed that the minor allele carriers had lower ApoA1/ApoB ratio (rs2156552 and rs7241918) and higher ApoB levels (rs7241918) in Han males; and lower ApoA1 and HDL-C levels in Maonan famales than the minor allele non-carriers (P < 0.0167-0.001). CONCLUSIONS: The present study demonstrates the association between the LIPG polymorphsims and serum lipid levels in the two ethnic groups. These associations might have an ethnic-and or/sex-specificity.
ESTHER : Yang_2019_J.Gene.Med__e3071
PubMedSearch : Yang_2019_J.Gene.Med__e3071
PubMedID: 30657227

Title : Electropolymerization-Induced Positively Charged Phenothiazine Polymer Photoelectrode for Highly Sensitive Photoelectrochemical Biosensing - Wang_2019_Anal.Chem_91_13831
Author(s) : Wang J , Lv W , Wu J , Li H , Li F
Ref : Analytical Chemistry , 91 :13831 , 2019
Abstract : Exploring the fabrication of an electrode with high photoelectric conversion efficiency and abundant functional groups for ideal photoelectrochemical (PEC) sensor development is highly urgent but faces a significant challenge. Herein we report an electropolymerization strategy for the preparation of phenothiazine polymeric film on an indium tin oxide (ITO) surface (PPT/ITO), within only a few seconds, and monomers. The fabricated PPT/ITO electrode possessed excellent stability and abundant quaternary ammonium salt groups for developing a highly sensitive PEC sensor through electrostatic binding with negatively charged materials. In this context, a CdS QDs-functionalized PPT/ITO electrode (CdS/PPT/ITO) was proposed and applied to the analysis of chlorpyrifos, used as a model target organophosphorous pesticide (OP). The thiocholine generated from acetylcholinesterase (AChE)-induced catalyzed hydrolysis of acetylthiocholine (ATCh) efficiently directed CdS QDs away from PPT/ITO via electrostatic repulsion, subsequently decreasing PEC current, whereas chlorpyrifos prohibited the generation of thiocholine through inhibiting AChE activity. As compared to the case where chlorpyrifos is absent, significantly enhanced PEC current is determined and is proportional to chlorpyrifos amounts. Thus, the developed CdS/PPT/ITO-based PEC sensor achieved excellent chlorpyrifos biosensing with improved sensitivity down to approximately ng/mL level with good specificity. We envision the proposed strategy will provide a new path to conveniently fabricate photoelectrodes possessing high performance, which will have more useful applications in PEC sensing.
ESTHER : Wang_2019_Anal.Chem_91_13831
PubMedSearch : Wang_2019_Anal.Chem_91_13831
PubMedID: 31560517

Title : ACOT1 expression is associated with poor prognosis in gastric adenocarcinoma - Wang_2018_Hum.Pathol_77_35
Author(s) : Wang F , Wu J , Qiu Z , Ge X , Liu X , Zhang C , Xu W , Hua D , Qi X , Mao Y
Ref : Hum Pathol , 77 :35 , 2018
Abstract : Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. In addition, GLI3 is a major transcription factor in the regulation of hedgehog signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process. Thus, we investigated the relationship between ACOT1 expression and GLI3 in gastric adenocarcinoma. A tissue microarray was constructed from 280 cases of gastric adenocarcinoma. The immunohistochemistry method was performed on tissue sections of 4 microm from each tissue microarray block. We found a significant correlation between ACOT1 expression and poor histologic grade, a lower T category, TNM stage, and increased GLI3 expression. In addition, the survival analysis revealed that the ACOT1-positive group had significantly decreased overall survival rates compared with the ACOT1-negative group. Furthermore, GLI3 expression had a significant positive correlation with ACOT1 expression in gastric adenocarcinoma cells. In summary, these findings demonstrate that increased expression of ACOT1 is correlated with pivotal clinicopathological parameters and poor prognosis in gastric adenocarcinoma through increased expression of the potential tumor-promoting protein GLI3.
ESTHER : Wang_2018_Hum.Pathol_77_35
PubMedSearch : Wang_2018_Hum.Pathol_77_35
PubMedID: 29555575

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Proteolytic maturation of Drosophila Neuroligin 3 by tumor necrosis factor alpha-converting enzyme in the nervous system - Wu_2018_Biochim.Biophys.Acta_1862_440
Author(s) : Wu J , Tao N , Tian Y , Xing G , Lv H , Han J , Lin C , Xie W
Ref : Biochimica & Biophysica Acta , 1862 :440 , 2018
Abstract : BACKGROUND: The functions of autism-associated Neuroligins (Nlgs) are modulated by their post-translational modifications, such as proteolytic cleavage. A previous study has shown that there are different endogenous forms of DNlg3 in Drosophila, indicating it may undergo proteolytic processing. However, the molecular mechanism underlying DNlg3 proteolytic processing is unknown. Here, we report a novel proteolytic mechanism that is essential for DNlg3 maturation and function in the nervous system. METHODS: Molecular cloning, cell culture, immunohistochemistry, western blotting and genetic studies were employed to map the DNlg3 cleavage region, identify the protease and characterize the cleavage manner. Behavior analysis, immunohistochemistry and genetic manipulations were employed to study the functions of different DNlg3 forms in the nervous system and neuromuscular junction (NMJs). RESULTS: Tumor necrosis factor alpha-converting enzyme (TACE) cleaved DNlg3 exclusively at its extracellular acetylcholinesterase-like domain to generate the N-terminal fragment and the short membrane-anchored fragment (sDNlg3). DNlg3 was constitutively processed in an activity-independent manner. Interestingly, DNlg3 was cleaved intracellularly in the Golgi apparatus before it arrived at the cell surface, a unique cleavage mechanism that is distinct from 'conventional' ectodomain shedding of membrane proteins, including rodent Nlg1. Genetic studies showed that sDNlg3 was essential for maintaining proper locomotor activity in Drosophila. CONCLUSIONS: Our results revealed a unique cleavage mechanism of DNlg3 and a neuron-specific role for DNlg3 maturation which is important in locomotor activity. GENERAL SIGNIFICANCE: Our study provides a new insight into a cleavage mechanism of Nlgs maturation in the nervous system.
ESTHER : Wu_2018_Biochim.Biophys.Acta_1862_440
PubMedSearch : Wu_2018_Biochim.Biophys.Acta_1862_440
PubMedID: 29107812

Title : Psychosocial interventions for Alzheimer's disease cognitive symptoms: a Bayesian network meta-analysis - Duan_2018_BMC.Geriatr_18_175
Author(s) : Duan Y , Lu L , Chen J , Wu C , Liang J , Zheng Y , Wu J , Rong P , Tang C
Ref : BMC Geriatr , 18 :175 , 2018
Abstract : BACKGROUND: Alzheimer disease (AD) is the most common type of dementia with cognitive decline as one of the core symptoms in older adults. Numerous studies have suggested the value of psychosocial interventions to improve cognition in this population, but which one should be preferred are still matters of controversy. Consequently, we aim to compare and rank different psychosocial interventions in the management of mild to moderate AD with cognitive symptoms. METHODS: We did a network meta-analysis to identify both direct and indirect evidence in relevant studies. We searched MEDLINE, EMBASE, PsycINFO through the OVID database, CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating psychosocial interventions of cognitive symptoms in patients with Alzheimer disease, published up to August 31, 2017. We included trials of home-based exercise(HE), group exercise(GE), walking program(WP), reminiscence therapy(RT), art therapy(AT) or the combination of psychosocial interventions and acetylcholinesterase inhibitor (ChEIs). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. The outcomes investigated were Mini-Mental State Examination (MMSE) and compliance. We did a pair-wise meta-analysis using the fixed-effects model and then did a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 10 trials eligible, including 682 patients and 11 treatments. The quality of included study was rated as low in most comparison with Cochrane tools. Treatment effects from the network meta-analysis showed WP was better than control (SMD 4.89, 95% CI -0.07 to 10.00) while cognitive training and acetylcholinesterase inhibitor (CT + ChEIs) was significantly better than the other treatments, when compared with simple ChEIs treatment, assessed by MMSE. In terms of compliance, the pair-wise meta-analysis indicated that WP and HE are better than GE and AT, while CT + ChEIs, CST + ChEIs are better than other combined interventions. CONCLUSION: Our study confirmed the effectiveness of psychosocial interventions for improving cognition or slowing down the progression of cognitive impairment in AD patients and recommended several interventions for clinical practice.
ESTHER : Duan_2018_BMC.Geriatr_18_175
PubMedSearch : Duan_2018_BMC.Geriatr_18_175
PubMedID: 30086714

Title : Novel 8-hydroxyquinoline derivatives targeting beta-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease - Yang_2018_Bioorg.Med.Chem_26_3191
Author(s) : Yang X , Cai P , Liu Q , Wu J , Yin Y , Wang X , Kong L
Ref : Bioorganic & Medicinal Chemistry , 26 :3191 , 2018
Abstract : A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Abeta(1-42) aggregation and potential antioxidant properties especially compound 5b (IC(50) = 5.64 microM for self-induced Abeta aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu(2+)/Zn(2+)-induced Abeta(1-42) aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H(2)O(2) and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood-brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy.
ESTHER : Yang_2018_Bioorg.Med.Chem_26_3191
PubMedSearch : Yang_2018_Bioorg.Med.Chem_26_3191
PubMedID: 29729985

Title : Effect of food matrices on the in vitro bioavailability and oxidative damage in PC12 cells of lead - Xia_2018_Food.Chem_266_397
Author(s) : Xia J , Fang Y , Shi Y , Shen X , Wu J , Xie M , Li P , Pei F , Hu Q
Ref : Food Chem , 266 :397 , 2018
Abstract : The bioavailability and oxidative damage toxicity of lead (Pb) in seven food matrices, including rice, milk, tomato, garlic, apple, kelp and pork, were determined using an in vitro digestion/Caco-2 cell model and a rat pheochromocytoma (PC12) oxidative damage model. Results showed that Pb bioaccessibility and bioavailability in the apple and kelp groups were significantly lower than other food matrix groups, with corresponding values of 11.05-28.31% and 1.57-8.81%, respectively. Oxidative damage assays showed that digestion products of apple polyphenol extract, which was selected from seven food matrices, could increase the oxidation resistance and the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and acetyl cholinesterase (AChE) by 32.23%, 39.02%, 27.14% and 30.90%, respectively. Additionally, malondialdehyde (MDA) and reactive oxygen species (ROS) levels could be decreased by 59.66% and 40.21%, respectively. In conclusion, phenolics were an important food matrix that could decrease the bioavailability and oxidative damage of Pb.
ESTHER : Xia_2018_Food.Chem_266_397
PubMedSearch : Xia_2018_Food.Chem_266_397
PubMedID: 30381204

Title : [Effects of tenofovir and telbivudine on HBV RNA in pregnant women with different genotypes of HBeAg-positive hepatitis B in Guizhou Province] - Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
Author(s) : Zhang BF , Cheng ML , Lu S , Wu J , Wu YY , Liu Q , Zhao XK , Li YY , Hu YX , Liu W
Ref : Zhonghua Yi Xue Za Zhi , 98 :3503 , 2018
Abstract : Objective: To investigate whether HBV genotype influences HBV DNA and RNA responses to tenofovir(TDF) and telbivudine(LDT) in pregnant women with HBeAg-positive in Guizhou. Methods: This was a retrospective analysis of 75 pregnant women hepatitis B with HBsAg and HBeAg double-positive(19-38 years old, median age 26 years old), who were enrolled in the Department of Infectious Diseases and Obstetrics Clinic of the Affiliated Hospital of Guizhou Medical University from May 2016 to July 2017.Blood samples were collected at 12-24, 28-32 and 36-40 weeks of pregnancy for analyses of genotype, including hepatitis B surface antigen(HBsAg), hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA and liver function, alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBiL), total bile acids(TBA), cholinesterase(CHE), alkaline phosphatase (ALP). Continuous variable was adopted by means of mean+/-standard deviation, and categorical variables were used for statistical analysis. Results: The HBV genotype was B in 64.0%(48/75)and C in 36.0%(27/75). The TDF and LDT groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)HBV DNA and log(10)HBV RNA.TDF groups, pre-treatment: HBV DNA (4.8+/-2.0), HBV RNA (6.4+/-1.1); at 4 weeks of treatment: HBV DNA (4.0+/-0.8), HBV RNA (6.0+/-0.9); at the end of treatment: HBV DNA (3.1+/-0.7), HBV RNA (5.5+/-0.8). LDT groups, pre-treatment HBV DNA (5.1+/-2.0), HBV RNA(6.5+/-0.9); at 4 weeks of treatment: HBV DNA (4.4+/-1.2), HBV RNA(6.5+/-0.8); at the end of treatment: HBV DNA(3.5+/-1.2), HBV RNA (6.1+/-0.7). Compared with pre-treatment (12-24 weeks), the TDF and LDT group showed significant reductions in log(10)(HBV DNA) and log(10)(HBV RNA) at 36-40 weeks ( P<0.05). Under the influence of excluding other variables, the genotype had a certain influence on the HBV RNA load.That was, HBV RNA in patients with the C genome decreased by 0.54 units(log(10)) at the end of the treatment compared to patients with the B genome, and the P value was less than 0.05. Conclusion: B and C genotypes are predominant in pregnant women with hepatitis B in Guizhou Province. B-type viruses are more easily controlled when different genotypes are treated with nucleotide analogues.
ESTHER : Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
PubMedSearch : Zhang_2018_Zhonghua.Yi.Xue.Za.Zhi_98_3503
PubMedID: 30481899

Title : Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment - Tang_2018_Int.J.Mol.Med_41_251
Author(s) : Tang Y , Yu C , Wu J , Chen H , Zeng Y , Wang X , Yang L , Mei Q , Cao S , Qin D
Ref : Int J Mol Med , 41 :251 , 2018
Abstract : Lychee seed is a traditional Chinese medicine and has many beneficial effects such as modulation of blood sugar and lipids, antioxidation, antivirus and antitumor. Studies have indicated that type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) share common biological mechanisms including insulin resistance, impaired glucose metabolism, betaamyloid (Abeta) formation, oxidative stress and presence of advanced glycation end products (AGEs). The present study investigated the effects of lychee seed extract (LSE) on neuroprotection, cognitive function improvement and possible underlying mechanisms in a rat model of T2DM with cognitive impairment. We analyzed the chemical profile of LSE using a UHPLCSPD chromatogram and evaluated its effect on the improvement of spatial learning and memory of rats by a Morris water maze. The levels of glucose, insulin, Abeta, AGEs, Tau protein and acetylcholinesterase in the blood and/or hippocampus of rats were determined by bloodglucose meter, radioimmunoassay, chemical chromatometry, enzymelinked immunosorbent assay (ELISA) and immunohistochemical analysis, respectively. Results demonstrated that LSE consists of eight major and around 20 minor ingredients, and it remarkably prevents neuronal injury and improves cognitive functions in T2DM rats. The levels of glucose, insulin, Abeta, AGEs and Tau protein were significantly increased in the blood and/or hippocampus of T2DM rats, while LSE remarkably decreased their levels compared to vehicle treatment (P<0.01). The possible mechanisms may be associated with IR improvement and decreased formations of Abeta, AGEs and Tau protein in the hippocampus of T2DM rats. LSE may be developed as the agent for the treatment of T2DM and/or AD clinically.
ESTHER : Tang_2018_Int.J.Mol.Med_41_251
PubMedSearch : Tang_2018_Int.J.Mol.Med_41_251
PubMedID: 29138799

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : Sepsis decreases the activity of acetylcholinesterase by reducing its expression at the neuromuscular junction - Wu_2017_Mol.Med.Rep_16_5263
Author(s) : Wu J , Jin T , Wang H , Li ST
Ref : Mol Med Rep , 16 :5263 , 2017
Abstract : Our previous study demonstrated that sepsis may decrease the activity of acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) of the diaphragm at 24 h, and thus improve the antagonistic action of neostigmine on rocuronium. The present study aimed to determine the effects of sepsis on AChE activity over 2 weeks, which is a more clinically relevant time period. Furthermore, the present study aimed to elucidate the association between AChE activity and its expression at the NMJ during sepsis. Male adult SpragueDawley rats were randomly divided into the sham or sepsis groups. Sepsis was induced by cecal ligation and puncture. On days 1, 3, 7 and 14 after surgery, AChE activity at the NMJ of the diaphragm was detected using a modified Karnovsky and Roots method. Furthermore, AChE expression levels at the NMJ, and in the whole muscle fibers of the diaphragm, were detected by immunohistofluorescence staining and western blot analysis, respectively. AChE activity was significantly decreased in the sepsis group, with its lowest level detected on day 7; however, its activity had partially recovered on day 14 (P<0.01). AChE activity was positively correlated (r=0.975, P=0.025) with its expression at the NMJ, which showed a similar trend over 2 weeks of sepsis. The protein expression levels of AChE in the whole muscle fibers of the diaphragm were significantly decreased on days 1, 3 and 7 in the sepsis group (P<0.01), with the lowest level observed on day 3. In conclusion, sepsis decreased AChE activity by reducing its expression at the NMJ over 14 days; the reduced expression of AChE at the NMJ might be as a result of its reduced muscular production.
ESTHER : Wu_2017_Mol.Med.Rep_16_5263
PubMedSearch : Wu_2017_Mol.Med.Rep_16_5263
PubMedID: 28849127

Title : The Role of Oxidative Stress in Decreased Acetylcholinesterase Activity at the Neuromuscular Junction of the Diaphragm during Sepsis - Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
Author(s) : Liu H , Wu J , Yao JY , Wang H , Li ST
Ref : Oxid Med Cell Longev , 2017 :9718615 , 2017
Abstract : Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid-grade septic group than in the low-grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid-grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.
ESTHER : Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
PubMedSearch : Liu_2017_Oxid.Med.Cell.Longev_2017_9718615
PubMedID: 29230271

Title : Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest - Cheng_2017_Nat.Ecol.Evol_1_1747
Author(s) : Cheng T , Wu J , Wu Y , Chilukuri RV , Huang L , Yamamoto K , Feng L , Li W , Chen Z , Guo H , Liu J , Li S , Wang X , Peng L , Liu D , Guo Y , Fu B , Li Z , Liu C , Chen Y , Tomar A , Hilliou F , Montagne N , Jacquin-Joly E , d'Alencon E , Seth RK , Bhatnagar RK , Jouraku A , Shiotsuki T , Kadono-Okuda K , Promboon A , Smagghe G , Arunkumar KP , Kishino H , Goldsmith MR , Feng Q , Xia Q , Mita K
Ref : Nat Ecol Evol , 1 :1747 , 2017
Abstract : The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
ESTHER : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedSearch : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedID: 28963452

Title : A pH-responsive colorimetric strategy for DNA detection by acetylcholinesterase catalyzed hydrolysis and cascade amplification - Guo_2017_Biosens.Bioelectron_94_651
Author(s) : Guo Y , Yang K , Sun J , Wu J , Ju H
Ref : Biosensors & Bioelectronics , 94 :651 , 2017
Abstract : A pH-responsive colorimetric strategy was designed for sensitive and convenient biosensing by introducing acetylcholinesterase (AChE) catalyzed hydrolysis of acetylcholine to change solution pH and phenol red as an indicator. Using DNA as a target model, this technique was successfully employed for sensitive DNA analysis by labeling AChE to DNA. The sensitivity could be greatly improved by coupling a newly designed magnetic probe with target DNA-triggered nonenzymatic cascade amplification. In the presence of a help DNA (H) and the functional probe, the cascade assembly via toehold-mediated strand displacement released the AChE-conjugated sequence from magnetic beads, which could be simply separated from the reaction mixture to catalyze the hydrolysis of ACh in detection solution. The color change of detection solution from pink to orange-red, orange-yellow and ultimately yellow could be used for target DNA detection by naked eye and colorimetry with the absorbance ratio of detection solution at 558nm to 432nm as the signal. The nonenzymatically sensitized colorimetric strategy showed a linear range from 50pM to 50nM with a detection limit of 38pM, indicating a promising application in DNA analysis.
ESTHER : Guo_2017_Biosens.Bioelectron_94_651
PubMedSearch : Guo_2017_Biosens.Bioelectron_94_651
PubMedID: 28388529

Title : Alpha-asarone improves striatal cholinergic function and locomotor hyperactivity in Fmr1 knockout mice - Qiu_2016_Behav.Brain.Res_312_212
Author(s) : Qiu G , Chen S , Guo J , Wu J , Yi YH
Ref : Behavioural Brain Research , 312 :212 , 2016
Abstract : Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (alpha)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with alpha-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of alpha-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with alpha-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, alpha-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of alpha-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity.
ESTHER : Qiu_2016_Behav.Brain.Res_312_212
PubMedSearch : Qiu_2016_Behav.Brain.Res_312_212
PubMedID: 27316341

Title : A nano-silver enzyme electrode for organophosphorus pesticide detection - Zheng_2016_Anal.Bioanal.Chem_408_5819
Author(s) : Zheng Q , Yu Y , Fan K , Ji F , Wu J , Ying Y
Ref : Anal Bioanal Chem , 408 :5819 , 2016
Abstract : A nano-silver electrode immobilizing acetylcholinesterase (AChE) for the detection of organophosphorus (OPPs) pesticides is reported. Scanning electron microscopy (SEM) was used to characterize the surface structure of two kinds of electrodes fabricated with different sizes of silver powders and the interface between chitosan layer and nano-silver powder layer. Cyclic voltammetry was carried out to characterize the response of silver/chitosan electrode in the absence and in the presence of thiocholine (TCh). It was also used to evaluate the insulativity of the chitosan layer. An amperometric method was performed to measure the response of the electrode to TCh, which is the product of the enzymatic reaction for detecting organophosphorus pesticides indirectly. Although there are many kinds of nanoparticles, silver was chosen for its internal advantage in detecting TCh at low potential without further modification. The result shows nano-silver powder has better performance than usual silver powder, and the limit of detection of paraoxon is 4 ppb under optimized conditions. One percent (w/v) chitosan solution was used as binder for the immobilization of nano-silver powder and AChE, which made it possible for independent electrode fabrication at room temperature, whereas 3% (w/v) chitosan solution was used as insulating compound for controlling the electrode area. Unlike traditional organic insulating ink, chitosan is safe and environmentally friendly, and it is used as insulating material for the first time. The flexible nano-silver/AChE/chitosan electrode was evaluated in Chinese chives and cabbage, and the recoveries of standard addition were 105.11 and 96.41%, respectively. Owing to the antibacterial property of nano-silver and the biocompatibility, safety, and biodegradability of chitosan, the proposed method is safe, facile, environmentally friendly, and has great potential in organophosphorus pesticide detection for food safety. Graphical Abstract Current response of nano-silver electrode (a) and silver electrode (b) to thiocholine in 0.02 M PBS + KCl at 0.15 V; addition of thiocholine (0.09 mM) every 50 s ( downward arrow); inset: calibration curve of nano-silver () and silver () electrode.
ESTHER : Zheng_2016_Anal.Bioanal.Chem_408_5819
PubMedSearch : Zheng_2016_Anal.Bioanal.Chem_408_5819
PubMedID: 27342792

Title : Chemical Constituents of Plants from the Genus Phlegmariurus - Yang_2016_Chem.Biodivers_13_269
Author(s) : Yang Y , Wang Z , Wu J , Chen Y
Ref : Chem Biodivers , 13 :269 , 2016
Abstract : Phlegmariurus is a genus of ca. 200 species in the family Huperziaceae. Up to now, six species of the Phlegmariurus genus have been chemically investigated, and 89 compounds, including Lycopodium alkaloids possessing diverse structures and serratane-type triterpenes, have been isolated. These compounds show potent bioactivities, such as acetylcholinesterase inhibitory and cytotoxic activities.
ESTHER : Yang_2016_Chem.Biodivers_13_269
PubMedSearch : Yang_2016_Chem.Biodivers_13_269
PubMedID: 26916276

Title : SAR11 bacteria linked to ocean anoxia and nitrogen loss - Tsementzi_2016_Nature_536_179
Author(s) : Tsementzi D , Wu J , Deutsch S , Nath S , Rodriguez RL , Burns AS , Ranjan P , Sarode N , Malmstrom RR , Padilla CC , Stone BK , Bristow LA , Larsen M , Glass JB , Thamdrup B , Woyke T , Konstantinidis KT , Stewart FJ
Ref : Nature , 536 :179 , 2016
Abstract : Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.
ESTHER : Tsementzi_2016_Nature_536_179
PubMedSearch : Tsementzi_2016_Nature_536_179
PubMedID: 27487207
Gene_locus related to this paper: 9prot-a0a1c2agj3 , 9prot-a0a1c2azw4

Title : Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture - Wu_2016_Chin.Med.J.(Engl)_129_1477
Author(s) : Wu J , Jin T , Wang H , Li ST
Ref : Chinese Medical Journal (Engl) , 129 :1477 , 2016
Abstract : BACKGROUND: The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).
METHODS: A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 mumol/L of neostigmine on Roc (10 mumol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.
RESULTS: Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 mumol/L; P = 0.009 for 0.5 mumol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 +/- 0.045 vs. 1.047 +/- 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET).
CONCLUSIONS: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.
ESTHER : Wu_2016_Chin.Med.J.(Engl)_129_1477
PubMedSearch : Wu_2016_Chin.Med.J.(Engl)_129_1477
PubMedID: 27270546

Title : Sequence Assembly of Yarrowia lipolytica Strain W29\/CLIB89 Shows Transposable Element Diversity - Magnan_2016_PLoS.One_11_e0162363
Author(s) : Magnan C , Yu J , Chang I , Jahn E , Kanomata Y , Wu J , Zeller M , Oakes M , Baldi P , Sandmeyer S
Ref : PLoS ONE , 11 :e0162363 , 2016
Abstract : Yarrowia lipolytica, an oleaginous yeast, is capable of accumulating significant cellular mass in lipid making it an important source of biosustainable hydrocarbon-based chemicals. In spite of a similar number of protein-coding genes to that in other Hemiascomycetes, the Y. lipolytica genome is almost double that of model yeasts. Despite its economic importance and several distinct strains in common use, an independent genome assembly exists for only one strain. We report here a de novo annotated assembly of the chromosomal genome of an industrially-relevant strain, W29/CLIB89, determined by hybrid next-generation sequencing. For the first time, each Y. lipolytica chromosome is represented by a single contig. The telomeric rDNA repeats were localized by Irys long-range genome mapping and one complete copy of the rDNA sequence is reported. Two large structural variants and retroelement differences with reference strain CLIB122 including a full-length, novel Ty3/Gypsy long terminal repeat (LTR) retrotransposon and multiple LTR-like sequences are described. Strikingly, several of these are adjacent to RNA polymerase III-transcribed genes, which are almost double in number in Y. lipolytica compared to other Hemiascomycetes. In addition to previously-reported dimeric RNA polymerase III-transcribed genes, tRNA pseudogenes were identified. Multiple full-length and truncated LINE elements are also present. Therefore, although identified transposons do not constitute a significant fraction of the Y. lipolytica genome, they could have played an active role in its evolution. Differences between the sequence of this strain and of the existing reference strain underscore the utility of an additional independent genome assembly for this economically important organism.
ESTHER : Magnan_2016_PLoS.One_11_e0162363
PubMedSearch : Magnan_2016_PLoS.One_11_e0162363
PubMedID: 27603307
Gene_locus related to this paper: yarli-q6c4p0

Title : Short-chain aliphatic ester synthesis using Thermobifida fusca cutinase - Su_2016_Food.Chem_206_131
Author(s) : Su L , Hong R , Guo X , Wu J , Xia Y
Ref : Food Chem , 206 :131 , 2016
Abstract : Short-chain aliphatic esters are commonly used as fruit flavorings in the food industry. In this study, Thermobifida fusca (T. fusca) cutinase was used for the synthesis of aliphatic esters, and the maximum yield of ethyl caproate reached 99.2% at a cutinase concentration of 50U/ml, 40 degrees C, and water content of 0.5%, representing the highest ester yield to date. The cutinase-catalyzed esterification displayed strong tolerance for water content (up to 8%) and acid concentration (up to 0.8M). At substrate concentrations 0.8M, the ester yield remained above 80%. Moreover, ester yields of more than 98% and 95% were achieved for acids of C3-C8 and alcohols of C1-C6, respectively, indicating extensive chain length selectivity of the cutinase. These results demonstrate the superior ability of T. fusca cutinase to catalyze the synthesis of short-chain esters. This study provides the basis for industrial production of short-chain esters using T. fusca cutinase.
ESTHER : Su_2016_Food.Chem_206_131
PubMedSearch : Su_2016_Food.Chem_206_131
PubMedID: 27041308

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 : Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis - Wang_2015_Hepatology_61_870
Author(s) : Wang C , Zhao Y , Gao X , Li L , Yuan Y , Liu F , Zhang L , Wu J , Hu P , Zhang X , Gu Y , Xu Y , Wang Z , Li Z , Zhang H , Ye J
Ref : Hepatology , 61 :870 , 2015
Abstract : Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity.
ESTHER : Wang_2015_Hepatology_61_870
PubMedSearch : Wang_2015_Hepatology_61_870
PubMedID: 25179419

Title : Discovery and expression of a Pseudomonas sp. esterase as a novel biocatalyst for the efficient biosynthesis of a chiral intermediate of pregabalin -
Author(s) : Xu F , Chen S , Xu G , Wu J , Yang L
Ref : Biotechnol Bioprocess Eng , 20 :473 , 2015
PubMedID:

Title : Extracellular expression of natural cytosolic arginine deiminase from Pseudomonas putida and its application in the production of l-citrulline - Su_2015_Bioresour.Technol_196_176
Author(s) : Su L , Ma Y , Wu J
Ref : Bioresour Technol , 196 :176 , 2015
Abstract : The Pseudomonas putida arginine deiminase (ADI), a natural cytosolic enzyme, and Thermobifida fusca cutinase were co-expressed in Escherichia coli, and the optimized cutinase gene was used for increasing its expression level. 90.9% of the total ADI protein was released into culture medium probably through a nonspecific leaking mechanism caused by the co-expressed cutinase. The enzymatic properties of the extracellular ADI were found to be similar to those of ADI prepared by conventional cytosolic expression. Extracellular production of ADI was further scaled up in a 3-L fermentor. When the protein expression was induced by IPTG (25.0muM) and lactose (0.1gL-1h-1) at 30 degrees C, the extracellular ADI activity reached 101.2UmL-1, which represented the highest ADI production ever reported. In addition, the enzymatic synthesis of l-citrulline was performed using the extracellularly expressed ADI, and the conversion rate reached 100% with high substrate concentration at 650gL-1.
ESTHER : Su_2015_Bioresour.Technol_196_176
PubMedSearch : Su_2015_Bioresour.Technol_196_176
PubMedID: 26233330

Title : The halo-substituent effect on Pseudomonas cepacia lipase-mediated regioselective acylation of nucleosides: A comparative investigation - Wang_2015_J.Biotechnol_212_153
Author(s) : Wang ZY , Bi YH , Yang RL , Duan ZQ , Nie LH , Li XQ , Zong MH , Wu J
Ref : J Biotechnol , 212 :153 , 2015
Abstract : In this work, comparative experiments were explored to investigate the substrate specificity of Pseudomonas cepacia lipase in regioselective acylation of nucleosides carrying various substituents (such as the H, F, Cl, Br, I) at 2'- and 5-positions. Experimental data indicated that the catalytic performance of the enzyme depended very much on the halo-substituents in nucleosides. The increased bulk of 2'-substituents in ribose moiety of the nucleoside might contribute to the improved 3'-regioselectivity (90-98%, nucleosides a-d) in enzymatic decanoylation, while the enhancement of regioselectivity (93-99%) in 3'-O-acylated nucleosides e-h could be attributable to the increasing hydrophobicity of the halogen atoms at 5-positions. With regard to the chain-length selectivity, P. cepacia lipase displayed the highest 3'-regioselectivity toward the longer chain (C14) as compared to shorter (C6 and C10) ones. The position, orientation and property of the substituent, specific structure of the lipase's active site, and acyl structure could account for the diverse results.
ESTHER : Wang_2015_J.Biotechnol_212_153
PubMedSearch : Wang_2015_J.Biotechnol_212_153
PubMedID: 26325198

Title : FgRIC8 is involved in regulating vegetative growth, conidiation, deoxynivalenol production and virulence in Fusarium graminearum - Wu_2015_Fungal.Genet.Biol_83_92
Author(s) : Wu J , Liu Y , Lv W , Yue X , Que Y , Yang N , Zhang Z , Ma Z , Talbot NJ , Wang Z
Ref : Fungal Genet Biol , 83 :92 , 2015
Abstract : Proteins of the resistance to inhibitors of cholinesterase 8 (Ric8) group act as guanine nucleotide exchange factors (GEFs) and play important roles in regulating G-protein signaling in animals. In filamentous fungi, putative Ric8 orthologs have so far been identified in Magnaporthe oryzae, Neurospora crassa, Aspergillus nidulans and Aspergillus fumigatus. Here, we report the functional investigation of a potential RIC8 ortholog (FgRIC8) in the wheat head blight pathogen Fusarium graminearum. Targeted gene deletion mutants of FgRIC8 exhibited a significant reduction in vegetative growth, conidiation, pigment production as well as deoxynivalenol (DON) biosynthesis. Pathogenicity assays using a point-inoculated spikelet approach showed that the mutants were severely impaired in virulence on flowering wheat heads. Quantitative RT-PCR analysis revealed that genes encoding F. graminearum Galpha (FgGpa1 and FgGpa3), Gbeta (FgGpb1) and Ggamma (FgGpg1) subunits were significantly down-regulated in Fgric8 mutants. Moreover, we showed that FgRic8 physically interacts with both FgGpa1 and FgGpa3, but not FgGpa2, in yeast two-hybrid assays. The intracellular cAMP levels in Fgric8 mutants were significantly decreased compared to the isogenic wild-type strain. Taken together, our results indicate that FgRic8 plays critical roles in fungal development, secondary metabolism and virulence in F. graminearum and may act as a regulator of G protein alpha subunits.
ESTHER : Wu_2015_Fungal.Genet.Biol_83_92
PubMedSearch : Wu_2015_Fungal.Genet.Biol_83_92
PubMedID: 26341536

Title : Anticancer drugs induce hypomethylation of the acetylcholinesterase promoter via a phosphorylated-p38-DNMT1-AChE pathway in apoptotic hepatocellular carcinoma cells - Xi_2015_Int.J.Biochem.Cell.Biol_68_21
Author(s) : Xi Q , Gao N , Yang Y , Ye W , Zhang B , Wu J , Jiang G , Zhang X
Ref : International Journal of Biochemistryistry & Cell Biology , 68 :21 , 2015
Abstract : Apoptosis, also known as programmed cell death, plays an essential role in eliminating excessive, damaged or harmful cells. Previous work has demonstrated that anticancer drugs induce cell apoptosis by inducing cytotoxicity. In recent years, several reports demonstrated modulated expression of DNA methyltransferases 1 (DNMT1) and acetylcholinesterase (AChE) in a variety of tumors. In this study, we showed that the expression of DNMT1 was decreased and the methylation of CpGs in the promoter of AChE was reduced in anticancer drugs-induced apoptotic hepatocellular carcinoma cells. Silencing of DNMT1 expression by AZA or RNA interference (RNAi) restored AChE production and inhibition of AChE expression by RNAi protected HCC cells from anticancer drugs-induced apoptosis. Furthermore, we demonstrated that the regulation of AChE by DNMT1 was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis. In addition, immunohistochemical staining showed that P-p38, DNMT1 and AChE were aberrantly expressed in a subset of HCC tumors. Taken together, we demonstrated the regulation of AChE by DNMT1 and further, we found that this regulation was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis.
ESTHER : Xi_2015_Int.J.Biochem.Cell.Biol_68_21
PubMedSearch : Xi_2015_Int.J.Biochem.Cell.Biol_68_21
PubMedID: 26299326

Title : Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution - Li_2015_Nat.Biotechnol_33_524
Author(s) : Li F , Fan G , Lu C , Xiao G , Zou C , Kohel RJ , Ma Z , Shang H , Ma X , Wu J , Liang X , Huang G , Percy RG , Liu K , Yang W , Chen W , Du X , Shi C , Yuan Y , Ye W , Liu X , Zhang X , Liu W , Wei H , Wei S , Zhu S , Zhang H , Sun F , Wang X , Liang J , Wang J , He Q , Huang L , Cui J , Song G , Wang K , Xu X , Yu JZ , Zhu Y , Yu S
Ref : Nat Biotechnol , 33 :524 , 2015
Abstract : Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum.
ESTHER : Li_2015_Nat.Biotechnol_33_524
PubMedSearch : Li_2015_Nat.Biotechnol_33_524
PubMedID: 25893780
Gene_locus related to this paper: gosra-a0a0d2rxs2 , gosra-a0a0d2tng2 , gosra-a0a0d2twz7 , goshi-a0a1u8hr03 , gosra-a0a0d2vdc5 , goshi-a0a1u8ljh5 , gosra-a0a0d2vj24 , goshi-a0a1u8pxd3 , gosra-a0a0d2sr31 , goshi-a0a1u8knd1 , goshi-a0a1u8nhw9 , goshi-a0a1u8mt09 , goshi-a0a1u8kis4 , goshi-a0a1u8ibk3 , goshi-a0a1u8ieg2 , goshi-a0a1u8iki6 , goshi-a0a1u8jvp4 , goshi-a0a1u8jw35 , gosra-a0a0d2pzd7 , goshi-a0a1u8ied7

Title : alpha7 and beta2 Nicotinic Acetylcholine Receptor Subunits Form Heteromeric Receptor Complexes that Are Expressed in the Human Cortex and Display Distinct Pharmacological Properties - Thomsen_2015_PLoS.One_10_e0130572
Author(s) : Thomsen MS , Zwart R , Ursu D , Jensen MM , Pinborg LH , Gilmour G , Wu J , Sher E , Mikkelsen JD
Ref : PLoS ONE , 10 :e0130572 , 2015
Abstract : The existence of alpha7beta2 nicotinic acetylcholine receptors (nAChRs) has recently been demonstrated in both the rodent and human brain. Since alpha7-containing nAChRs are promising drug targets for schizophrenia and Alzheimer's disease, it is critical to determine whether alpha7beta2 nAChRs are present in the human brain, in which brain areas, and whether they differ functionally from alpha7 nAChR homomers. We used alpha-bungarotoxin to affinity purify alpha7-containing nAChRs from surgically excised human temporal cortex, and found that alpha7 subunits co-purify with beta2 subunits, indicating the presence of alpha7beta2 nAChRs in the human brain. We validated these results by demonstrating co-purification of beta2 from wild-type, but not alpha7 or beta2 knock-out mice. The pharmacology and kinetics of human alpha7beta2 nAChRs differed significantly from that of alpha7 homomers in response to nAChR agonists when expressed in Xenopus oocytes and HEK293 cells. Notably, alpha7beta2 heteromers expressed in HEK293 cells display markedly slower rise and decay phases. These results demonstrate that alpha7 subunits in the human brain form heteromeric complexes with beta2 subunits, and that human alpha7beta2 nAChR heteromers respond to nAChR agonists with a unique pharmacology and kinetic profile. alpha7beta2 nAChRs thus represent an alternative mechanism for the reported clinical efficacy of alpha7 nAChR ligands.
ESTHER : Thomsen_2015_PLoS.One_10_e0130572
PubMedSearch : Thomsen_2015_PLoS.One_10_e0130572
PubMedID: 26086615

Title : Extracellular expression of Thermobifida fusca cutinase with pelB signal peptide depends on more than type II secretion pathway in Escherichia coli - Su_2015_J.Biotechnol_204_47
Author(s) : Su L , Yu L , Xu C , Wu J
Ref : J Biotechnol , 204 :47 , 2015
Abstract : Our previous studies demonstrated that Thermobifida fusca cutinase is released into culture medium when expressed without a signal peptide in Escherichia coli, and this extracellular expression results from an enhanced membrane permeability caused by cutinase's phospholipid hydrolase activity. The present study investigated whether this phenomenon would also occur during the expression of cutinase fused to pelB signal peptide (pelB-cutinase). Secretion of fusion proteins of this type is generally believed to occur via type II secretion pathway. The results showed that when pelB-cutinase was expressed in a secB knockout strain, which has a defective type II secretion pathway, there was still a large amount of cutinase in the culture medium. Additional experiments confirmed that the periplasmic and cytoplasmic fractions of the expressing cells had hydrolytic activity toward phosphatidyl ethanolamine, and the recombinant cells showed correspondingly improved membrane permeability. All these phenomena were also observed in the parent E. coli strain. Moreover, the secretion efficiency of the inactive cutinase mutant was found to be significantly lower than that of pelB-cutinase in the parent E. coli. Based on these results, the phospholipid hydrolase activity of pelB-cutinase must play a larger role in its extracellular production than does type II secretion pathway.
ESTHER : Su_2015_J.Biotechnol_204_47
PubMedSearch : Su_2015_J.Biotechnol_204_47
PubMedID: 25863154

Title : Characterization and structure basis of Pseudomonas alcaligenes lipase's enantiopreference towards d,l-menthyl propionate - Chen_2014_J.Mol.Catal.B.Enzym_102_81
Author(s) : Chen H , Wu J , Yang L , Xu G
Ref : J Mol Catal B Enzym , 102 :81 , 2014
Abstract : In this work, a lipase from Pseudomonas alcaligenes CGMCC4405 (PaL) was cloned and expressed. It was very attractive that the recombinant PaL exhibited excellent enantioselectivity (E > 200) in the resolution of racemic d,l-menthyl propionate to produce l-menthol. The structure basis of enantiopreference is a fundamental scientific problem which needs to be resolved. In our research, molecular dynamic simulation (MD) research was employed to research the different binding modes of d and l-menthyl propionate. The results showed that when bound with slow-reacting enantiomer (d-menthyl propionate), the steric requirements of the large substituent (isopropyl) of the d-menthyl propionate force a rotation of the imidazole ring of catalytic residue His271 and further pushed the active site His271 away from its proper orientation. Moreover, the average distance between alcohol oxygen (Oalc) and HNe of catalytic His271 increased to 3.7 A, which was too far to form an essential hydrogen bond and further prevented efficient catalysis of slow enantiomer. This correlation of the distance between alcohol oxygen (Oalc) and HNe of catalytic His271 and the enantioselectivity was also confirmed by the result of site-directed mutagenesis.
ESTHER : Chen_2014_J.Mol.Catal.B.Enzym_102_81
PubMedSearch : Chen_2014_J.Mol.Catal.B.Enzym_102_81
PubMedID:
Gene_locus related to this paper: stema-s4tny8

Title : The role of synaptic activity in the regulation of amyloid beta levels in Alzheimer's disease - Cheng_2014_Neurobiol.Aging_35_1217
Author(s) : Cheng X , Wu J , Geng M , Xiong J
Ref : Neurobiology of Aging , 35 :1217 , 2014
Abstract : Alzheimer's disease (AD) is the most common form of dementia. Accumulation of amyloid-beta (Abeta) peptides is regarded as the critical component associated with AD pathogenesis, which is derived from the amyloid precursor protein (APP) cleavage. Recent studies suggest that synaptic activity is one of the most important factors that regulate Abeta levels. It has been found that synaptic activity facilitates APP internalization and influences APP cleavage. Glutamatergic, cholinergic, serotonergic, leptin, adrenergic, orexin, and gamma-amino butyric acid receptors, as well as the activity-regulated cytoskeleton-associated protein (Arc) are all involved in these processes. The present review summarizes the evidence for synaptic activity-modulated Abeta levels and the mechanisms underlying this regulation. Interestingly, the immediate early gene product Arc may also be the downstream signaling molecule of several receptors in the synaptic activity-modulated Abeta levels. Elucidating how Abeta levels are regulated by synaptic activity may provide new insights in both the understanding of the pathogenesis of AD and in the development of therapies to slow down the progression of AD.
ESTHER : Cheng_2014_Neurobiol.Aging_35_1217
PubMedSearch : Cheng_2014_Neurobiol.Aging_35_1217
PubMedID: 24368087

Title : GW1929 inhibits alpha7 nAChR expression through PPARgamma-independent activation of p38 MAPK and inactivation of PI3-K\/mTOR: The role of Egr-1 - Hahn_2014_Cell.Signal_26_730
Author(s) : Hahn SS , Tang Q , Zheng F , Zhao S , Wu J
Ref : Cell Signal , 26 :730 , 2014
Abstract : Studies demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reduce nicotine-induced non small cell lung carcinoma (NSCLC) cell growth through inhibition of nicotinic acetylcholine receptor (nAChR) mediated signaling pathways. However, the mechanisms by which PPARgamma ligands inhibited nAChR expression remain elucidated. Here, we show that GW1929, a synthetic PPARgamma ligand, not only inhibited but also antagonized the stimulatory effect of acetylcholine on NSCLC cell proliferation. Interestingly, GW1929 inhibited alpha7 nAChR expression, which was not blocked by GW9662, an antagonist of PPARgamma, or by PPARgamma siRNA, but was abrogated by the p38 MPAK inhibitor SB239063. GW1929 reduced the promoter activity of alpha7 nAChR and induced early growth response-1 (Egr-1) protein expression, which was overcame by SB239063, but enhanced by inhibitors of PI3-K and mTOR. Silencing of Egr-1 blocked, while overexpression of Egr-1 enhanced, the effect of GW1929 on alpha7 nAChR expression and promoter activity. Finally, GW1929 induced Egr-1 bound to specific DNA areas in the alpha7 nAChR gene promoter. Collectively, these results demonstrate that GW1929 not only inhibits but also antagonizes Ach-induced NSCLC cell growth by inhibition of alpha7 nAChR expression through PPARgamma-independent signals that are associated with activation of p38 MPAK and inactivation of PI3-K/mTOR, followed by inducing Egr-1 protein and Egr-1 binding activity in the alpha7 nAChR gene promoter. By downregulation of the alpha7 nAchR, GW1929 blocks cholinergic signaling and inhibits NSCLC cell growth.
ESTHER : Hahn_2014_Cell.Signal_26_730
PubMedSearch : Hahn_2014_Cell.Signal_26_730
PubMedID: 24412748

Title : Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field - Chen_2014_PLoS.One_9_e108129
Author(s) : Chen D , Feng J , Huang L , Zhang Q , Wu J , Zhu X , Duan Y , Xu Z
Ref : PLoS ONE , 9 :e108129 , 2014
Abstract : Erythromycins (Ers) are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH) and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600) in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600) in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites.
ESTHER : Chen_2014_PLoS.One_9_e108129
PubMedSearch : Chen_2014_PLoS.One_9_e108129
PubMedID: 25250723
Gene_locus related to this paper: 9acto-a0a099d7w4 , 9actn-a0a099d934

Title : In Vitro Metabolism and Drug-Drug Interaction Potential of UTL-5g, a Novel Chemo- and Radioprotective Agent - Wu_2014_Drug.Metab.Dispos_42_2058
Author(s) : Wu J , Shaw J , Dubaisi S , Valeriote F , Li J
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 42 :2058 , 2014
Abstract : N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 microM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited approximately 30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 microM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute(-1).mM(-1), respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g.
ESTHER : Wu_2014_Drug.Metab.Dispos_42_2058
PubMedSearch : Wu_2014_Drug.Metab.Dispos_42_2058
PubMedID: 25249693

Title : A natural antisense transcript regulates acetylcholinesterase gene expression via epigenetic modification in Hepatocellular Carcinoma - Xi_2014_Int.J.Biochem.Cell.Biol_55C_242
Author(s) : Xi Q , Gao N , Zhang X , Zhang B , Ye W , Wu J
Ref : International Journal of Biochemistry & Cell Biology , 55C :242 , 2014
Abstract : In recent years, widespread antisense transcripts have been identified systematically in mammalian cells and are known to regulate gene expression, although their functional significance remains largely unknown. Previous work has identified that acetylcholinesterase (AChE) is expressed aberrantly in various malignant tumors and function as a tumor growth suppressor. However, the mechanism of AChE gene regulation in tumors remains unclear. In this study, we show that the AChE antisense RNA (AChE-AS) play an important role in AChE expression regulation. An inverse relationship was identified between AChE-AS and AChE expression in hepatocellular carcinoma and hepatoma cells. The silenced AChE-AS corresponds to elevated expression of AChE. Furthermore, we demonstrated that reduced AChE-AS increased H3K4 methylation and decreased H3K9 methylation in the AChE promoter region. As expected, elevated AChE levels induced by inhibition of AChE-AS enhanced anticarcinogen-induced apoptosis. These observations demonstrated that AChE-AS modulates AChE expression and exerts an anti-apoptotic effect through direct repression of AChE expression in HCC cells. Thus, natural antisense RNA may play an important role in AChE regulation via affecting the epigenetic modification in the AChE promoter region.
ESTHER : Xi_2014_Int.J.Biochem.Cell.Biol_55C_242
PubMedSearch : Xi_2014_Int.J.Biochem.Cell.Biol_55C_242
PubMedID: 25240585

Title : Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency - Bie_2014_Nat.Neurosci_17_223
Author(s) : Bie B , Wu J , Yang H , Xu JJ , Brown DL , Naguib M
Ref : Nat Neurosci , 17 :223 , 2014
Abstract : Amyloid-induced microglial activation and neuroinflammation impair central synapses and memory function, although the mechanism remains unclear. Neuroligin 1 (NLGN1), a postsynaptic protein found in central excitatory synapses, governs excitatory synaptic efficacy and plasticity in the brain. Here we found, in rodents, that amyloid fibril-induced neuroinflammation enhanced the interaction between histone deacetylase 2 and methyl-CpG-binding protein 2, leading to suppressed histone H3 acetylation and enhanced cytosine methylation in the Nlgn1 promoter region and decreased NLGN1 expression, underlying amyloid-induced memory deficiency. Manipulation of microglia-associated neuroinflammation modulated the epigenetic modification of the Nlgn1 promoter, hippocampal glutamatergic transmission and memory function. These findings link neuroinflammation, synaptic efficacy and memory, thus providing insight into the pathogenesis of amyloid-associated diseases.
ESTHER : Bie_2014_Nat.Neurosci_17_223
PubMedSearch : Bie_2014_Nat.Neurosci_17_223
PubMedID: 24441681

Title : [(1)(2)(5)I]AT-1012, a new high affinity radioligand for the alpha3beta4 nicotinic acetylcholine receptors - Wu_2014_Neuropharmacol_77_193
Author(s) : Wu J , Perry DC , Bupp JE , Jiang F , Polgar WE , Toll L , Zaveri NT
Ref : Neuropharmacology , 77 :193 , 2014
Abstract : Recent genetic and pharmacological studies have implicated the alpha3, beta4 and alpha5 subunits of the nicotinic acetylcholine receptor (nAChR) in dependence to nicotine and other abused drugs and nicotine withdrawal. The alpha3beta4* nAChR subtype has been shown to co-assemble with the alpha5 or beta3 nAChR subunits, and is found mainly in the autonomic ganglia and select brain regions. It has been difficult to study the alpha3beta4 nAChR because there have been no selective nonpeptidic ligands available to independently examine its pharmacology. We recently reported the synthesis of a [(125)I]-radiolabeled analog of a high affinity, selective small-molecule alpha3beta4 nAChR ligand, AT-1012. We report here the vitro characterization of this radioligand in receptor binding and in vitro autoradiographic studies targeting the alpha3beta4* nAChR. Binding of [(125)I]AT-1012 was characterized at the rat alpha3beta4 and alpha4beta2 nAChR transfected into HEK cells, as well as at the human alpha3beta4alpha5 nAChR in HEK cells. Binding affinity of [(125)I]AT-1012 at the rat alpha3beta4 nAChR was 1.4 nM, with a B(max) of 10.3 pmol/mg protein, similar to what was determined for unlabeled AT-1012 using [(3)H]epibatidine. Saturation isotherms suggested that [(125)I]AT-1012 binds to a single site on the alpha3beta4 nAChR. Similar high binding affinity was also observed for [(125)I]AT-1012 at the human alpha3beta4alpha5 nAChR transfected into HEK cells. [(125)I]AT-1012 did not bind with high affinity to membranes from alpha4beta2 nAChR-transfected HEK cells. Binding studies with [(3)H]epibatidine further confirmed that AT-1012 had over 100-fold binding selectivity for alpha3beta4 over alpha4beta2 nAChR. K(i) values determined for known nAChR compounds using [(125)I]AT-1012 as radioligand were comparable to those obtained with [(3)H]epibatidine. [(125)I]AT-1012 was also used to label alpha3beta4 nAChR in rat brain slices in vitro using autoradiography, which showed highly localized binding of the radioligand in brain regions consistent with the discreet localization of the alpha3beta4 nAChR. We demonstrate that [(125)I]AT-1012 is an excellent tool for labeling the alpha3beta4 nAChR in the presence of other nAChR subtypes.
ESTHER : Wu_2014_Neuropharmacol_77_193
PubMedSearch : Wu_2014_Neuropharmacol_77_193
PubMedID: 24095990

Title : Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence - Wu_2014_Acta.Pharmacol.Sin_35_311
Author(s) : Wu J , Gao M , Taylor DH
Ref : Acta Pharmacol Sin , 35 :311 , 2014
Abstract : Neuronal nicotinic acetylcholine receptors are important targets for alcohol reward and dependence. Alcoholism is a serious public health problem and has been identified as the third major cause of preventable mortality in the world. Worldwide, about 2 billion people consume alcohol, with 76.3 million having diagnosable alcohol use disorders. Alcohol is currently responsible for the death of 4% of adults worldwide (about 2.5 million deaths each year), and this number will be significantly increased by 2020 unless effective action is taken. Alcohol is the most commonly abused substance by humans. Ethanol (EtOH) is the intoxicating agent in alcoholic drinks that can lead to abuse and dependence. Although it has been extensively studied, the mechanisms of alcohol reward and dependence are still poorly understood. The major reason is that, unlike other addictive drugs (eg, morphine, cocaine or nicotine) that have specific molecular targets, EtOH affects much wider neuronal functions. These functions include phospholipid membranes, various ion channels and receptors, synaptic and network functions, and intracellular signaling molecules. The major targets in the brain that mediate EtOH's effects remain unclear. This knowledge gap results in a therapeutic barrier in the treatment of alcoholism. Interestingly, alcohol and nicotine are often co-abused, which suggests that neuronal nicotinic acetylcholine receptors (nAChRs), the molecular targets for nicotine, may also contribute to alcohol's abusive properties. Here, we briefly summarize recent lines of evidence showing how EtOH modulates nAChRs in the mesolimbic pathway, which provides a perspective that nAChRs are important targets mediating alcohol abuse.
ESTHER : Wu_2014_Acta.Pharmacol.Sin_35_311
PubMedSearch : Wu_2014_Acta.Pharmacol.Sin_35_311
PubMedID: 24464050

Title : Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes - Biftu_2014_J.Med.Chem_57_3205
Author(s) : Biftu T , Sinha-Roy R , Chen P , Qian X , Feng D , Kuethe JT , Scapin G , Gao YD , Yan Y , Krueger D , Bak A , Eiermann G , He J , Cox J , Hicks J , Lyons K , He H , Salituro G , Tong S , Patel S , Doss G , Petrov A , Wu J , Xu SS , Sewall C , Zhang X , Zhang B , Thornberry NA , Weber AE
Ref : Journal of Medicinal Chemistry , 57 :3205 , 2014
Abstract : In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
ESTHER : Biftu_2014_J.Med.Chem_57_3205
PubMedSearch : Biftu_2014_J.Med.Chem_57_3205
PubMedID: 24660890
Gene_locus related to this paper: human-DPP4

Title : A unique mono- and diacylglycerol lipase from Penicillium cyclopium: heterologous expression, biochemical characterization and molecular basis for its substrate selectivity - Tan_2014_PLoS.One_9_e102040
Author(s) : Tan ZB , Li JF , Li XT , Gu Y , Wu MC , Wu J , Wang JQ
Ref : PLoS ONE , 9 :e102040 , 2014
Abstract : A cDNA gene encoding a mature peptide of the mono- and diacylglycerol lipase (abbreviated to PcMdl) from Penicillium cyclopium PG37 was cloned and expressed in Pichia pastoris GS115. The recombinant PcMdl (rePcMdl) with an apparent molecular weight of 39 kDa showed the highest activity (40.5 U/mL of culture supernatant) on 1,2-dibutyrin substrate at temperature 35 degrees C and pH 7.5. The rePcMdl was stable at a pH range of 6.5-9.5 and temperatures below 35 degrees C. The activity of rePcMdl was inhibited by Hg2+ and Fe3+, but not significantly affected by EDTA or the other metal ions such as Na+, K+, Li+, Mg2+, Zn2+, Ca2+, Mn2+, Cu2+, and Fe2+. PcMdl was identified to be strictly specific to mono- and diacylglycerol, but not triacylglycerol. Stereographic view of PcMdl docked with substrate (tri- or diacylglycerol) analogue indicated that the residue Phe256 plays an important role in conferring the substrate selectivity. Phe256 projects its side chain towards the substrate binding groove and makes the sn-1 moiety difficult to insert in. Furthermore, sn-1 moiety prevents the phosphorus atom (substitution of carboxyl carbon) from getting to the Ogamma of Ser145, which results in the failure of triacylglycerol hydrolysis. These results should provide a basis for molecular engineering of PcMdl and expand its applications in industries.
ESTHER : Tan_2014_PLoS.One_9_e102040
PubMedSearch : Tan_2014_PLoS.One_9_e102040
PubMedID: 25051359
Gene_locus related to this paper: penca-mdgli

Title : Hsa-miR-132 Regulates Apoptosis in Non-Small Cell Lung Cancer Independent of Acetylcholinesterase - Zhang_2014_J.Mol.Neurosci_53_335
Author(s) : Zhang B , Lu L , Zhang X , Ye W , Wu J , Xi Q
Ref : Journal of Molecular Neuroscience , 53 :335 , 2014
Abstract : MiR-132 is enriched in the central nerve system and is thought to be involved in neuronal development, maturation and function, and to be associated with several neurological disorders including Alzheimer's disease. In addition to its documented neuronal functions, an emerging role for miR-132 in tumorigenesis has been suggested. Recently, hsa-miR-132 was shown to be modulated in different tumor types. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Here, we show that hsa-miR-132 can initiate apoptosis in NSCLC cells to dramatically attenuate tumor formation in nude mice independent of its effect on the proliferation/apoptosis-associated gene, acetylcholinesterase (AChE). Interestingly, hsa-miR-132 has no pro-apoptotic effect in normal pulmonary trachea epithelium. Taken together, these results suggest that hsa-miR-132 represses NSCLC growth by inducing apoptosis independent of AChE.
ESTHER : Zhang_2014_J.Mol.Neurosci_53_335
PubMedSearch : Zhang_2014_J.Mol.Neurosci_53_335
PubMedID: 24158730

Title : Complete Genome Sequence of Acinetobacter baumannii ZW85-1 - Wang_2014_Genome.Announc_2_e01083
Author(s) : Wang X , Zhang Z , Hao Q , Wu J , Xiao J , Jing H
Ref : Genome Announc , 2 :e01083 , 2014
Abstract : Acinetobacter baumannii is an aerobic, nonmotile Gram-negative bacterium that causes nosocomial infections worldwide. Here, we report the complete genome sequence of Acinetobacter baumannii strain ZW85-1 and its two plasmids. One of the plasmids carries genes for NDM-1, which can hydrolyze a wide range of antibiotics.
ESTHER : Wang_2014_Genome.Announc_2_e01083
PubMedSearch : Wang_2014_Genome.Announc_2_e01083
PubMedID: 24459253
Gene_locus related to this paper: aciba-a0a009wzt4

Title : Cutinase: Characteristics, preparation, and application - Chen_2013_Biotechnol.Adv_31_1754
Author(s) : Chen S , Su L , Chen J , Wu J
Ref : Biotechnol Adv , 31 :1754 , 2013
Abstract : Cutinases (E.C. 3.1.1.74) belong to the alpha/beta-hydrolase superfamily. They were initially discovered because they are secreted by fungi to hydrolyze the ester bonds of the plant polymer cutin. Since then, they have been shown to catalyze the hydrolysis of a variety of polymers, insoluble triacylglycerols, and low-molecular-weight soluble esters. Cutinases are also capable of catalyzing esterification and transesterification reactions. These relatively small, versatile, secreted catalysts have shown promise in a number of industrial applications. This review begins by describing the characteristics of cutinases, pointing out key differences among cutinases, esterases and lipases, and reviewing recent progress in engineering improved cutinases. It continues with a review of the methods used to produce cutinases, with the goal of obtaining sufficient quantities of material for use in industrial processes. Finally, the uses of cutinases in the textile industry are described. The studies presented here demonstrate that the cutinases are poised to become important industrial catalysts, replacing older technologies with more environmentally friendly processes.
ESTHER : Chen_2013_Biotechnol.Adv_31_1754
PubMedSearch : Chen_2013_Biotechnol.Adv_31_1754
PubMedID: 24055682

Title : Human alpha4beta2 nicotinic acetylcholine receptor as a novel target of oligomeric alpha-synuclein - Liu_2013_PLoS.One_8_e55886
Author(s) : Liu Q , Emadi S , Shen JX , Sierks MR , Wu J
Ref : PLoS ONE , 8 :e55886 , 2013
Abstract : Cigarette smoking is associated with a decreased incidence of Parkinson disease (PD) through unknown mechanisms. Interestingly, a decrease in the numbers of alpha4beta2 nicotinic acetylcholine receptors (alpha4beta2-nAChRs) in PD patients suggests an alpha4beta2-nAChR-mediated cholinergic deficit in PD. Although oligomeric forms of alpha-synuclein have been recognized to be toxic and involved in the pathogenesis of PD, their direct effects on nAChR-mediated cholinergic signaling remains undefined. Here, we report for the first time that oligomeric alpha-synuclein selectively inhibits human alpha4beta2-nAChR-mediated currents in a dose-dependent, non-competitive and use-independent manner. We show that pre-loading cells with guanyl-5'-yl thiophosphate fails to prevent this inhibition, suggesting that the alpha-synuclein-induced inhibition of alpha4beta2-nAChR function is not mediated by nAChR internalization. By using a pharmacological approach and cultures expressing transfected human nAChRs, we have shown a clear effect of oligomeric alpha-synuclein on alpha4beta2-nAChRs, but not on alpha4beta4- or alpha7-nAChRs, suggesting nAChR subunit selectivity of oligomeric alpha-synuclein-induced inhibition. In addition, by combining the size exclusion chromatography and atomic force microscopy (AFM) analyses, we find that only large (>4 nm) oligomeric alpha-synuclein aggregates (but not monomeric, small oligomeric or fibrillar alpha-synuclein aggregates) exhibit the inhibitory effect on human alpha4beta2-nAChRs. Collectively, we have provided direct evidence that alpha4beta2-nAChR is a sensitive target to mediate oligomeric alpha-synuclein-induced modulation of cholinergic signaling, and our data imply that therapeutic strategies targeted toward alpha4beta2-nAChRs may have potential for developing new treatments for PD.
ESTHER : Liu_2013_PLoS.One_8_e55886
PubMedSearch : Liu_2013_PLoS.One_8_e55886
PubMedID: 23437071

Title : Synaptic acetylcholinesterase targeted by microRNA-212 functions as a tumor suppressor in non-small cell lung cancer - Lu_2013_Int.J.Biochem.Cell.Biol_45_2530
Author(s) : Lu L , Zhang X , Zhang B , Wu J
Ref : International Journal of Biochemistry & Cell Biology , 45 :2530 , 2013
Abstract : Acetylcholinesterase expression is modulated in various types of tumor, which suggests it is associated with tumor development; however, the mechanism of acetylcholinesterase gene regulation in tumors remains unclear. Here, we report that acetylcholinesterase is aberrantly expressed in non-small cell lung cancer and is an evolutionarily conserved functional target of miR-212. Acetylcholinesterase expression was negatively regulated by miR-212 in vitro and was inversely correlated with miR-212 expression in vivo. In addition, acetylcholinesterase levels were increased, and miR-212 levels decreased, in non-small cell lung cancer cells during cisplatin-induced apoptosis. We further determined that acetylcholinesterase acted as a pro-apoptotic gene in non-small cell lung cells; and attenuated the growth of xenografts in nude mice when upregulated. In contrast, elevated miR-212 levels preserved the protective effect of acetylcholinesterase silencing by RNA interference against cisplatin-induced apoptosis, whereas restoration of miR-212-resistant synaptic acetylcholinesterase expression inhibited the miR-212 anti-apoptotic function. The results demonstrated that miR-212 exerted an anti-apoptotic effect through direct repression of synaptic acetylcholinesterase expression in non-small cell lung cancer cells. Taken together, our study revealed that synaptic acetylcholinesterase may be a tumor suppressor and is modulated by miR-212 in non-small cell lung cancer.
ESTHER : Lu_2013_Int.J.Biochem.Cell.Biol_45_2530
PubMedSearch : Lu_2013_Int.J.Biochem.Cell.Biol_45_2530
PubMedID: 23974008

Title : Lithium treatment induces proteasomal degradation of over-expressed acetylcholinesterase (AChE-S) and inhibit GSK3beta - Jing_2013_Chem.Biol.Interact_203_309
Author(s) : Jing P , Zhang JY , Ouyang Q , Wu J , Zhang XJ
Ref : Chemico-Biological Interactions , 203 :309 , 2013
Abstract : Lithium is one of the most widely used mood-stabilizing agents for the treatment of bipolar disorder. Lithium is also a potent inhibitor of glycogen synthase kinase-3beta (GSK3beta) activity, which is linked to Alzheimer's disease (AD). In experiments with cultured HEK293T cells, we show here that GSK3beta stabilizes synaptic acetylcholinesterase (AChE-S), a critical component of AD development. Cells treated with lithium exhibited rapid proteasomal degradation of AChE-S. Furthermore treatment of the cells with MG132, an inhibitor of the 26S proteasome, prevented the destabilizing effect of lithium on AChE-S. Taken together, these findings suggest that regulation of AChE-S protein stability may be an important biological target of lithium therapy.
ESTHER : Jing_2013_Chem.Biol.Interact_203_309
PubMedSearch : Jing_2013_Chem.Biol.Interact_203_309
PubMedID: 22944069

Title : Poster: Nicotine perturbs PFC-VTA coupling: A new mechanism for nicotine addiction -
Author(s) : Gao M , Lukas RJ , Wu J
Ref : Biochemical Pharmacology , 86 :1234 , 2013
PubMedID:

Title : Fusion of binding domains to Thermobifida cellulosilytica cutinase to tune sorption characteristics and enhancing PET hydrolysis - Ribitsch_2013_Biomacromolecules_14_1769
Author(s) : Ribitsch D , Yebra AO , Zitzenbacher S , Wu J , Nowitsch S , Steinkellner G , Greimel K , Doliska A , Oberdorfer G , Gruber CC , Gruber K , Schwab H , Stana-Kleinschek K , Herrero Acero E , Guebitz GM
Ref : Biomacromolecules , 14 :1769 , 2013
Abstract : A cutinase from Thermomyces cellullosylitica (Thc_Cut1), hydrolyzing the synthetic polymer polyethylene terephthalate (PET), was fused with two different binding modules to improve sorption and thereby hydrolysis. The binding modules were from cellobiohydrolase I from Hypocrea jecorina (CBM) and from a polyhydroxyalkanoate depolymerase from Alcaligenes faecalis (PBM). Although both binding modules have a hydrophobic nature, it was possible to express the proteins in E. coli . Both fusion enzymes and the native one had comparable kcat values in the range of 311 to 342 s(-1) on pNP-butyrate, while the catalytic efficiencies kcat/Km decreased from 0.41 s(-1)/ muM (native enzyme) to 0.21 and 0.33 s(-1)/muM for Thc_Cut1+PBM and Thc_Cut1+CBM, respectively. The fusion enzymes were active both on the insoluble PET model substrate bis(benzoyloxyethyl) terephthalate (3PET) and on PET although the hydrolysis pattern was differed when compared to Thc_Cut1. Enhanced adsorption of the fusion enzymes was visible by chemiluminescence after incubation with a 6xHisTag specific horseradish peroxidase (HRP) labeled probe. Increased adsorption to PET by the fusion enzymes was confirmed with Quarz Crystal Microbalance (QCM-D) analysis and indeed resulted in enhanced hydrolysis activity (3.8x for Thc_Cut1+CBM) on PET, as quantified, based on released mono/oligomers.
ESTHER : Ribitsch_2013_Biomacromolecules_14_1769
PubMedSearch : Ribitsch_2013_Biomacromolecules_14_1769
PubMedID: 23718548
Gene_locus related to this paper: thefu-q6a0i4

Title : Extracellular location of Thermobifida fusca cutinase expressed in Escherichia coli BL21(DE3) without mediation of a signal peptide - Su_2013_Appl.Environ.Microbiol_79_4192
Author(s) : Su L , Woodard RW , Chen J , Wu J
Ref : Applied Environmental Microbiology , 79 :4192 , 2013
Abstract : Cutinase is a multifunctional esterase with potential industrial applications. In the present study, a truncated version of the extracellular Thermobifida fusca cutinase without a signal peptide (referred to as cutinase(NS)) was heterologously expressed in Escherichia coli BL21(DE3). The results showed that the majority of the cutinase activity was located in the culture medium. In a 3-liter fermentor, the cutinase activity in the culture medium reached 1,063.5 U/ml (2,380.8 mg/liter), and the productivity was 40.9 U/ml/h. Biochemical characterization of the purified cutinase(NS) showed that it has enzymatic properties similar to those of the wild-type enzyme. In addition, E. coli cells producing inactive cutinase(NS)S130A were constructed, and it was found that the majority of the inactive enzyme was located in the cytoplasm. Furthermore, T. fusca cutinase was confirmed to have hydrolytic activity toward phospholipids, an important component of the cell membrane. Compared to the cells expressing the inactive cutinase(NS)S130A, the cells expressing cutinase(NS) showed increased membrane permeability and irregular morphology. Based on these results, a hypothesis of "cell leakage induced by the limited phospholipid hydrolysis of cutinase(NS)" was proposed to explain the underlying mechanism for the extracellular release of cutinase(NS).
ESTHER : Su_2013_Appl.Environ.Microbiol_79_4192
PubMedSearch : Su_2013_Appl.Environ.Microbiol_79_4192
PubMedID: 23603671

Title : A novel strategy for enhancing extracellular secretion of recombinant proteins in Escherichia coli - Su_2013_Appl.Microbiol.Biotechnol_97_6705
Author(s) : Su L , Xu C , Woodard RW , Chen J , Wu J
Ref : Applied Microbiology & Biotechnology , 97 :6705 , 2013
Abstract : Secretion of cytoplasmic expressed proteins into culture medium has significant commercial advantages in large-scale production of proteins. Our previous study demonstrated that the membrane permeability of Escherichia coli could be significantly improved when Thermobifida fusca cutinase, without a signal peptide, was expressed in cytoplasm. This study investigated the extracellular production of other recombinant proteins, including both secretory and cytosolic proteins, with co-expression of cutinase. When the secretory enzymes, xylanase and alpha-amylase, were co-expressed with cutinase, the culture period was shortened by half, and the productivity was 7.9 and 2.0-fold to that of their individual control without co-expression, respectively. When the normally cytosolic proteins, xylose isomerase and trehalose synthase, were co-expressed with cutinase, more than half of the target proteins were "secreted" into the culture medium. Moreover, by using beta-galactosidase to detect membrane leakage, the improved secretion of the above model proteins was confirmed not to be due to cell lysis. The study provides a novel strategy for enhancing extracellular secretion of recombinant proteins in E. coli.
ESTHER : Su_2013_Appl.Microbiol.Biotechnol_97_6705
PubMedSearch : Su_2013_Appl.Microbiol.Biotechnol_97_6705
PubMedID: 23722267

Title : Enhanced activity toward PET by site-directed mutagenesis of Thermobifida fusca cutinase-CBM fusion protein - Zhang_2013_Carbohydr.Polym_97_124
Author(s) : Zhang Y , Wang L , Chen J , Wu J
Ref : Carbohydr Polym , 97 :124 , 2013
Abstract : In the present study, cutinase-CBMCenA fusion protein was genetically modified in the carbohydrate-binding module (CBM) binding sites, by site-directed mutagenesis, to enhance its activity toward polyethylene terephthalate (PET) fiber. The effects of tryptophan at particular positions of CBMCenA on the binding and hydrolysis of polyester substrate were investigated by replacing each of Trp14, Trp50 and Trp68 with leucine or tyrosine, respectively. All the mutants were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that the mutants displayed similar thermostability and pH stabilities in response to the native enzyme. Furthermore, W68L and W68Y, among all the mutants, exhibited significant improvement in binding and catalytic efficiency (1.4-1.5 fold) toward PET fiber when compared to that of the native enzyme. The enhanced binding and hydrolytic activity might be a result of creating new hydrogen bond or hydrophobic interaction between the enzyme and PET fiber.
ESTHER : Zhang_2013_Carbohydr.Polym_97_124
PubMedSearch : Zhang_2013_Carbohydr.Polym_97_124
PubMedID: 23769527

Title : Cloning of a dibutyl phthalate hydrolase gene from Acinetobacter sp. strain M673 and functional analysis of its expression product in Escherichia coli - Wu_2013_Appl.Microbiol.Biotechnol_97_2483
Author(s) : Wu J , Liao X , Yu F , Wei Z , Yang L
Ref : Applied Microbiology & Biotechnology , 97 :2483 , 2013
Abstract : A dibutyl phthalate (DBP) transforming bacterium, strain M673, was isolated and identified as Acinetobacter sp. This strain could not grow on dialkyl phthalates, including dimethyl, diethyl, dipropyl, dibutyl, dipentyl, dihexyl, di(2-ethylhexyl), di-n-octyl, and dinonyl phthalate, but suspensions of cells could transform these compounds to phthalate via corresponding monoalkyl phthalates. During growth in Luria-Bertani medium, M673 produced the high amounts of non-DBP-induced intracellular hydrolase in the stationary phase. One DBP hydrolase gene containing an open reading frame of 1,095 bp was screened from a genomic library, and its expression product hydrolyzed various dialkyl phthalates to the corresponding monoalkyl phthalates.
ESTHER : Wu_2013_Appl.Microbiol.Biotechnol_97_2483
PubMedSearch : Wu_2013_Appl.Microbiol.Biotechnol_97_2483
PubMedID: 22729233
Gene_locus related to this paper: acilw-ESTA

Title : Identification and characterization of a cold-active phthalate esters hydrolase by screening a metagenomic library derived from biofilms of a wastewater treatment plant - Jiao_2013_PLoS.One_8_e75977
Author(s) : Jiao Y , Chen X , Wang X , Liao X , Xiao L , Miao A , Wu J , Yang L
Ref : PLoS ONE , 8 :e75977 , 2013
Abstract : A cold-active phthalate esters hydrolase gene (designated dphB) was identified through functional screening of a metagenomic library derived from biofilms of a wastewater treatment plant. The enzyme specifically catalyzed the hydrolysis of dipropyl phthalate, dibutyl phthalate, and dipentyl phthalate to the corresponding monoalkyl phthalate esters at low temperatures. The catalytic triad residues of DphB were proposed to be Ser159, Asp251, and His281.
ESTHER : Jiao_2013_PLoS.One_8_e75977
PubMedSearch : Jiao_2013_PLoS.One_8_e75977
PubMedID: 24116085
Gene_locus related to this paper: acilw-ESTA , 9bact-u5qec2

Title : Cortical control of VTA function and influence on nicotine reward - Wu_2013_Biochem.Pharmacol_86(8)_1173
Author(s) : Wu J , Gao M , Shen JX , Shi WX , Oster AM , Gutkin BS
Ref : Biochemical Pharmacology , 86 :1173 , 2013
Abstract : Tobacco use is a major public health problem. Nicotine acts on widely distributed nicotinic acetylcholine receptors (nAChRs) in the brain and excites dopamine (DA) neurons in the ventral tegmental area (VTA). The elicited increase of DA neuronal activity is thought to be an important mechanism for nicotine reward and subsequently the transition to addiction. However, the current understanding of nicotine reward is based predominantly on the data accumulated from in vitro studies, often from VTA slices. Isolated VTA slices artificially terminate communications between neurons in the VTA and other brain regions that may significantly alter nicotinic effects. Consequently, the mechanisms of nicotinic excitation of VTA DA neurons under in vivo conditions have received only limited attention. Building upon the existing knowledge acquired in vitro, it is now time to elucidate the integrated mechanisms of nicotinic reward on intact systems that are more relevant to understanding the action of nicotine or other addictive drugs. In this review, we summarize recent studies that demonstrate the impact of prefrontal cortex (PFC) on the modulation of VTA DA neuronal function and nicotine reward. Based on existing evidence, we propose a new hypothesis that PFC-VTA functional coupling serves as an integration mechanism for nicotine reward. Moreover, addiction may develop due to nicotine perturbing the PFC-VTA coupling and thereby eliminating the PFC-dependent cognitive control over behavior.
ESTHER : Wu_2013_Biochem.Pharmacol_86(8)_1173
PubMedSearch : Wu_2013_Biochem.Pharmacol_86(8)_1173
PubMedID: 23933294

Title : Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson's disease - Zhang_2013_Int.J.Biochem.Cell.Biol_45_265
Author(s) : Zhang X , Lu L , Liu S , Ye W , Wu J
Ref : International Journal of Biochemistry & Cell Biology , 45 :265 , 2013
Abstract : The apoptosis pathway has been proposed to be involved in causing neuronal cell death in the pathogenesis of Parkinson's disease. However, the details of this pathway are poorly understood. Previous research has shown increased acetylcholinesterase expression during apoptosis in various cell types, which suggests that acetylcholinesterase has a potential role in neuronal cell death. In this study, we found that acetylcholinesterase protein expression increased and caspase-3 was activated in PC12 cells treated with 1-methyl-4-phenylpyridinium. Furthermore, the genetic or pharmacological inhibition of acetylcholinesterase was shown to protect PC12 cells from MPP+ induced apoptotic cell death. To study the function of acetylcholinesterase as a mechanism of neuronal cell death in vivo, we subsequently established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinson's disease mouse model utilizing acetylcholinesterase-deficient mice. Studies in these mice revealed reduced dopaminergic neuron loss and lower expression levels of apoptotic proteins in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated heterozygous mice compared to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated wild-type mice. We conclude that it is highly probable that acetylcholinesterase is involved in the pathogenesis of the neurotoxin model of Parkinson's disease via apoptosis. Specifically, a deficiency or inhibition of acetylcholinesterase can decrease apoptosis and protect dopaminergic neurons in the neurotoxin model of Parkinson's disease.
ESTHER : Zhang_2013_Int.J.Biochem.Cell.Biol_45_265
PubMedSearch : Zhang_2013_Int.J.Biochem.Cell.Biol_45_265
PubMedID: 23201480

Title : DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues - Harstad_2013_Regul.Pept_186C_26
Author(s) : Harstad EB , Rosenblum JS , Gorrell MD , Achanzar WE , Minimo L , Wu J , Rosini-Marthaler L , Gullo R , Ordway ND , Kirby MS , Chadwick KD , Cosma GN , Moyer CF
Ref : Regul Pept , 186C :26 , 2013
Abstract : Dipeptidyl peptidases (DPPs) are proteolytic enzymes that regulate many physiological systems by degrading signaling peptides. DPP8 and DPP9 are distinct from DPP4 in sequence, cellular localization and expression levels, thus implying distinct functions. However, DPP8 and DPP9 expression needs further delineation. We evaluated DPP4, DPP8 and DPP9 expression using three independent methods at the mRNA, protein, and functional levels to better understand the local physiological contribution of each enzyme. Sprague Dawley rats and cynomolgus monkeys were selected for DPP4, DPP8 and DPP9 expression profiling to represent animal species commonly utilized for drug preclinical safety evaluation. A novel Xhibit assay of DPP protease activity was applied in addition to newly available antibodies for immunohistochemical localization. This combined approach can facilitate a functional evaluation of protease expression, which is important for understanding physiological relevance. Few inter-species differences were observed. Tissue mRNA and protein levels generally correlated to functional DPP4 and DPP8/9 enzymatic activity. All three proteins were seen in epithelial cells, lymphoid cells and some endothelial and vascular smooth muscle cells. Combined DPP8/DPP9 enzymatic activity was uniformly intracellular across tissues at approximately 10-fold lower levels than non-renal DPP4. Consistent levels of each DPP were detected among most non-renal tissues in rats and monkeys. DPP4 was ubiquitous, principally detected on cell membranes of epithelial and endothelial cells and was greatest in the kidney. The expression patterns suggest that DPP8 and DPP9 may act similarly across tissues, and that their actions might in part overlap with DPP4.
ESTHER : Harstad_2013_Regul.Pept_186C_26
PubMedSearch : Harstad_2013_Regul.Pept_186C_26
PubMedID: 23850796
Gene_locus related to this paper: rat-dpp9

Title : Improvement of the Oryza sativa Nipponbare reference genome using next generation sequence and optical map data - Kawahara_2013_Rice.(N.Y)_6_4
Author(s) : Kawahara Y , de la Bastide M , Hamilton JP , Kanamori H , McCombie WR , Ouyang S , Schwartz DC , Tanaka T , Wu J , Zhou S , Childs KL , Davidson RM , Lin H , Quesada-Ocampo L , Vaillancourt B , Sakai H , Lee SS , Kim J , Numa H , Itoh T , Buell CR , Matsumoto T
Ref : Rice (N Y) , 6 :4 , 2013
Abstract : BACKGROUND: Rice research has been enabled by access to the high quality reference genome sequence generated in 2005 by the International Rice Genome Sequencing Project (IRGSP). To further facilitate genomic-enabled research, we have updated and validated the genome assembly and sequence for the Nipponbare cultivar of Oryza sativa (japonica group). RESULTS: The Nipponbare genome assembly was updated by revising and validating the minimal tiling path of clones with the optical map for rice. Sequencing errors in the revised genome assembly were identified by re-sequencing the genome of two different Nipponbare individuals using the Illumina Genome Analyzer II/IIx platform. A total of 4,886 sequencing errors were identified in 321 Mb of the assembled genome indicating an error rate in the original IRGSP assembly of only 0.15 per 10,000 nucleotides. A small number (five) of insertions/deletions were identified using longer reads generated using the Roche 454 pyrosequencing platform. As the re-sequencing data were generated from two different individuals, we were able to identify a number of allelic differences between the original individual used in the IRGSP effort and the two individuals used in the re-sequencing effort. The revised assembly, termed Os-Nipponbare-Reference-IRGSP-1.0, is now being used in updated releases of the Rice Annotation Project and the Michigan State University Rice Genome Annotation Project, thereby providing a unified set of pseudomolecules for the rice community. CONCLUSIONS: A revised, error-corrected, and validated assembly of the Nipponbare cultivar of rice was generated using optical map data, re-sequencing data, and manual curation that will facilitate on-going and future research in rice. Detection of polymorphisms between three different Nipponbare individuals highlights that allelic differences between individuals should be considered in diversity studies.
ESTHER : Kawahara_2013_Rice.(N.Y)_6_4
PubMedSearch : Kawahara_2013_Rice.(N.Y)_6_4
PubMedID: 24280374
Gene_locus related to this paper: orysa-Q0JK71 , orysj-q6yse8 , orysa-q6yzk1 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xr64 , orysj-a0a0p0y6l9 , orysj-pla4 , orysj-pla1 , orysj-q2r2z8

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Acetylcholinesterase is associated with apoptosis in beta cells and contributes to insulin-dependent diabetes mellitus pathogenesis - Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
Author(s) : Zhang B , Yang L , Yu L , Lin B , Hou Y , Wu J , Huang Q , Han Y , Guo L , Ouyang Q , Lu L , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 44 :207 , 2012
Abstract : Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic beta-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary beta cells, and apoptotic pancreatic beta cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary beta cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic beta cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.
ESTHER : Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
PubMedSearch : Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207
PubMedID: 22236578

Title : Residues and dissipation dynamics of fosthiazate in tomato and soil - Wu_2012_Bull.Environ.Contam.Toxicol_89_664
Author(s) : Wu J , Wang K , Zhang H
Ref : Bulletin of Environmental Contamination & Toxicology , 89 :664 , 2012
Abstract : Residue dynamics of fosthiazate in tomato and soil was studied in this paper utilizing liquid chromatography with tandem mass spectrometry (LC-MS/MS). The field trial was conducted in three sites: Beijing, Liaoning, Hubei in China. Fosthiazate dissipated with the half-life 0.75-2.6 days in tomato or tomato plants and 2.5-11.6 days in soil. In the terminal residue experiment, no higher residue than 0.023 mg kg(-1) in tomato and 0.27 mg kg(-1) in soil was detected. Residues of fosthiazte in tomato were far below Japan maximum residue levels (0.2 mg kg(-1)).
ESTHER : Wu_2012_Bull.Environ.Contam.Toxicol_89_664
PubMedSearch : Wu_2012_Bull.Environ.Contam.Toxicol_89_664
PubMedID: 22801926

Title : Molecular recognition of esterase plays a major role on the removal of fatty soils during detergency - Silva_2012_J.Biotechnol_161_228
Author(s) : Silva C , Azoia NG , Martins M , Matama T , Wu J , Cavaco-Paulo A
Ref : J Biotechnol , 161 :228 , 2012
Abstract : In this work it is describe for the first time the use of an esterase with null activity Tfu_0883 bacterial cutinase from Thermobifida fusca on the removal of fat from the surface of a cotton substrate Similar levels of fat removal were found for both null and wild-type proteins despite that only wild type protein yielded fatty acids Our results show that molecular recognition of esterase plays a major role on the removal of fatty soils allowing important guidelines for the design of detergent enzymes Furthermore the advantage of using null esterase enzymes lies in the avoidance of the rancid smell of short chained fatty acids typical after esterase treatment.
ESTHER : Silva_2012_J.Biotechnol_161_228
PubMedSearch : Silva_2012_J.Biotechnol_161_228
PubMedID: 22750090

Title : Functional alpha7beta2 nicotinic acetylcholine receptors expressed in hippocampal interneurons exhibit high sensitivity to pathological level of amyloid beta peptides - Liu_2012_BMC.Neurosci_13_155
Author(s) : Liu Q , Huang Y , Shen J , Steffensen S , Wu J
Ref : BMC Neurosci , 13 :155 , 2012
Abstract : BACKGROUND: beta-amyloid (Abeta) accumulation is described as a hallmark of Alzheimer's disease (AD). Abeta perturbs a number of synaptic components including nicotinic acetylcholine receptors containing alpha7 subunits (alpha7-nAChRs), which are abundantly expressed in the hippocampus and found on GABAergic interneurons. We have previously demonstrated the existence of a novel, heteromeric alpha7beta2-nAChR in basal forebrain cholinergic neurons that exhibits high sensitivity to acute Abeta exposure. To extend our previous work, we evaluated the expression and pharmacology of alpha7beta2-nAChRs in hippocampal interneurons and their sensitivity to Abeta.
RESULTS: GABAergic interneurons in the CA1 subregion of the hippocampus expressed functional alpha7beta2-nAChRs, which were characterized by relatively slow whole-cell current kinetics, pharmacological sensitivity to dihydro-beta-erythroidine (DHbetaE), a nAChR beta2* subunit selective blocker, and alpha7 and beta2 subunit interaction using immunoprecipitation assay. In addition, alpha7beta2-nAChRs were sensitive to 1 nM oligomeric Abeta. Similar effects were observed in identified hippocampal interneurons prepared from GFP-GAD mice. CONCLUSION: These findings suggest that Abeta modulation of cholinergic signaling in hippocampal GABAergic interneurons via alpha7beta2-nAChRs could be an early and critical event in Abeta-induced functional abnormalities of hippocampal function, which may be relevant to learning and memory deficits in AD.
ESTHER : Liu_2012_BMC.Neurosci_13_155
PubMedSearch : Liu_2012_BMC.Neurosci_13_155
PubMedID: 23272676

Title : alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against dopaminergic neuron loss in an MPTP mouse model via inhibition of astrocyte activation - Liu_2012_J.Neuroinflammation_9_98
Author(s) : Liu Y , Hu J , Wu J , Zhu C , Hui Y , Han Y , Huang Z , Ellsworth K , Fan W
Ref : J Neuroinflammation , 9 :98 , 2012
Abstract : BACKGROUND: Although evidence suggests that the prevalence of Parkinson's disease (PD) is lower in smokers than in non-smokers, the mechanisms of nicotine-induced neuroprotection remain unclear. Stimulation of the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) seems to be a crucial mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells, including astrocytes, and inhibition of astrocyte activation has been proposed as a novel strategy for the treatment of neurodegenerative disorders such as PD. The objective of the present study was to determine whether nicotine-induced neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model occurs via alpha7-nAChR-mediated inhibition of astrocytes.
METHODS: Both in vivo (MPTP) and in vitro (1-methyl-4-phenylpyridinium ion (MPP+) and lipopolysaccharide (LPS)) models of PD were used to investigate the role(s) of and possible mechanism(s) by which alpha7-nAChRs protect against dopaminergic neuron loss. Multiple experimental approaches, including behavioral tests, immunochemistry, and stereology experiments, astrocyte cell cultures, reverse transcriptase PCR, laser scanning confocal microscopy, tumor necrosis factor (TNF)-alpha assays, and western blotting, were used to elucidate the mechanisms of the alpha7-nAChR-mediated neuroprotection.
RESULTS: Systemic administration of nicotine alleviated MPTP-induced behavioral symptoms, improved motor coordination, and protected against dopaminergic neuron loss and the activation of astrocytes and microglia in the substantia nigra. The protective effects of nicotine were abolished by administration of the alpha7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured mouse astrocytes, pretreatment with nicotine suppressed MPP(+)-induced or LPS-induced astrocyte activation, as evidenced by both decreased production of TNF-alpha and inhibition of extracellular regulated kinase1/2 (Erk1/2) and p38 activation in astrocytes, and these effects were also reversed by MLA. CONCLUSION: Taken together, our results suggest that alpha7-nAChR-mediated inhibition of astrocyte activation is an important mechanism underlying the protective effects of nicotine.
ESTHER : Liu_2012_J.Neuroinflammation_9_98
PubMedSearch : Liu_2012_J.Neuroinflammation_9_98
PubMedID: 22624500

Title : Impact of prefrontal cortex in nicotine-induced excitation of ventral tegmental area dopamine neurons in anesthetized rats - Zhang_2012_J.Neurosci_32_12366
Author(s) : Zhang D , Gao M , Xu D , Shi WX , Gutkin BS , Steffensen SC , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 32 :12366 , 2012
Abstract : Systemic administration of nicotine increases dopaminergic (DA) neuron firing in the ventral tegmental area (VTA), which is thought to underlie nicotine reward. Here, we report that the medial prefrontal cortex (mPFC) plays a critical role in nicotine-induced excitation of VTA DA neurons. In chloral hydrate-anesthetized rats, extracellular single-unit recordings showed that VTA DA neurons exhibited two types of firing responses to systemic nicotine. After nicotine injection, the neurons with type-I response showed a biphasic early inhibition and later excitation, whereas the neurons with type-II response showed a monophasic excitation. The neurons with type-I, but not type-II, response exhibited pronounced slow oscillations (SOs) in firing. Pharmacological or structural mPFC inactivation abolished SOs and prevented systemic nicotine-induced excitation in the neurons with type-I, but not type-II, response, suggesting that these VTA DA neurons are functionally coupled to the mPFC and nicotine increases firing rate in these neurons in part through the mPFC. Systemic nicotine also increased the firing rate and SOs in mPFC pyramidal neurons. mPFC infusion of a non-alpha7 nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the excitatory effect of systemic nicotine on the VTA DA neurons with type-I response, but mPFC infusion of nicotine failed to excite these neurons. These results suggest that nAChR activation in the mPFC is necessary, but not sufficient, for systemic nicotine-induced excitation of VTA neurons. Finally, systemic injection of bicuculline prevented nicotine-induced firing alterations in the neurons with type-I response. We propose that the mPFC plays a critical role in systemic nicotine-induced excitation of VTA DA neurons.
ESTHER : Zhang_2012_J.Neurosci_32_12366
PubMedSearch : Zhang_2012_J.Neurosci_32_12366
PubMedID: 22956827

Title : Inactivation of chloramphenicol and florfenicol by a novel chloramphenicol hydrolase - Tao_2012_Appl.Environ.Microbiol_78_6295
Author(s) : Tao W , Lee MH , Wu J , Kim NH , Kim JC , Chung E , Hwang EC , Lee SW
Ref : Applied Environmental Microbiology , 78 :6295 , 2012
Abstract : Chloramphenicol and florfenicol are broad-spectrum antibiotics. Although the bacterial resistance mechanisms to these antibiotics have been well documented, hydrolysis of these antibiotics has not been reported in detail. This study reports the hydrolysis of these two antibiotics by a specific hydrolase that is encoded by a gene identified from a soil metagenome. Hydrolysis of chloramphenicol has been recognized in cell extracts of Escherichia coli expressing a chloramphenicol acetate esterase gene, estDL136. A hydrolysate of chloramphenicol was identified as p-nitrophenylserinol by liquid chromatography-mass spectroscopy and proton nuclear magnetic resonance spectroscopy. The hydrolysis of these antibiotics suggested a promiscuous amidase activity of EstDL136. When estDL136 was expressed in E. coli, EstDL136 conferred resistance to both chloramphenicol and florfenicol on E. coli, due to their inactivation. In addition, E. coli carrying estDL136 deactivated florfenicol faster than it deactivated chloramphenicol, suggesting that EstDL136 hydrolyzes florfenicol more efficiently than it hydrolyzes chloramphenicol. The nucleotide sequences flanking estDL136 encode proteins such as amidohydrolase, dehydrogenase/reductase, major facilitator transporter, esterase, and oxidase. The most closely related genes are found in the bacterial family Sphingomonadaceae, which contains many bioremediation-related strains. Whether the gene cluster with estDL136 in E. coli is involved in further chloramphenicol degradation was not clear in this study. While acetyltransferases for chloramphenicol resistance and drug exporters for chloramphenicol or florfenicol resistance are often detected in numerous microbes, this is the first report of enzymatic hydrolysis of florfenicol resulting in inactivation of the antibiotic.
ESTHER : Tao_2012_Appl.Environ.Microbiol_78_6295
PubMedSearch : Tao_2012_Appl.Environ.Microbiol_78_6295
PubMedID: 22752166
Gene_locus related to this paper: 9bact-g3cr00 , 9bact-g3cr02

Title : Extracellular overexpression of recombinant Thermobifida fusca cutinase by alpha-hemolysin secretion system in E. coli BL21(DE3) - Su_2012_Microb.Cell.Fact_11_8
Author(s) : Su L , Chen S , Yi L , Woodard RW , Chen J , Wu J
Ref : Microb Cell Fact , 11 :8 , 2012
Abstract : BACKGROUND: Extracellular expression of proteins has an absolute advantage in a large-scale industrial production. In our previous study, Thermobifida fusca cutinase, an enzyme mainly utilized in textile industry, was expressed via type II secretory system in Escherichia coli BL21(DE3), and it was found that parts of the expressed protein was accumulated in the periplasmic space. Due to the fact that alpha-hemolysin secretion system can export target proteins directly from cytoplasm across both cell membrane of E. coli to the culture medium, thus in the present study we investigated the expression of cutinase using this alpha-hemolysin secretion system. RESULTS: T. fusca cutinase was fused with the specific signal peptide of alpha-hemolysin scretion system and expressed in E. coli BL21(DE3). In addition, HlyB and HlyD, strain-specific translocation components of alpha-hemolysin secretion system, were coexpressed to facilitate the enzyme expression. The cultivation of this engineered cell showed that cutinase activity in the culture medium reached 334 U/ml, which is 2.5 times that from type II secretion pathway under the same culture condition. The recombinant cutinase was further purified. Biochemical characterization of purified enzyme, which had an alpha-hemolysin secretion pathway signal peptide attached, had substrate specificity, pH and temperature profile, as well as application capability in bioscouring similar to that of wild-type cutinase. CONCLUSIONS: In the present study, T. fusca cutinase was successfully secreted to the culture media by alpha-hemolysin secretion system. This is the first report of cutinase being efficiently secreted by this pathway. Due to the limited cases of successful expression of industrial enzyme by E. coli alpha-hemolysin secretion system, our study further explored the utilization of this pathway in industrial enzymes.
ESTHER : Su_2012_Microb.Cell.Fact_11_8
PubMedSearch : Su_2012_Microb.Cell.Fact_11_8
PubMedID: 22239833

Title : Synthesis and structure-activity relationship of (1-halo-2-naphthyl) carbamate-based inhibitors of KIAA1363 (NCEH1\/AADACL1) - Shreder_2012_Bioorg.Med.Chem.Lett_22_5748
Author(s) : Shreder KR , Lin EC , Wu J , Cajica J , Amantea CM , Hu Y , Okerberg E , Brown HE , Pham LM , Chung de M , Fraser AS , McGee E , Rosenblum JS , Kozarich JW
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :5748 , 2012
Abstract : KIAA1363 is a serine hydrolase whose activity has been shown to be positively associated with tumor cell invasiveness. Thus, inhibitors of KIAA1363 represent a novel targeted therapy approach towards cancer. AX11890 ((1-bromo-2-naphthyl) N,N-dimethylcarbamate) was identified as a KIAA1363 inhibitor with an IC(50) value of 1.2 muM and was shown using ESI-MS to carbamylate the catalytic residue Ser(191). SAR studies explored both substitution of the 1-bromo group and derivatization of the 6-position. Activity-based protein profiling demonstrated AX13057 inhibited tumor-localized KIAA1363 in SK-OV-3 xenograft-bearing mice.
ESTHER : Shreder_2012_Bioorg.Med.Chem.Lett_22_5748
PubMedSearch : Shreder_2012_Bioorg.Med.Chem.Lett_22_5748
PubMedID: 22877630
Gene_locus related to this paper: human-NCEH1

Title : alpha7beta2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their alpha7-alpha7 interfaces - Murray_2012_Mol.Pharmacol_81_175
Author(s) : Murray TA , Bertrand D , Papke RL , George AA , Pantoja R , Srinivasan R , Liu Q , Wu J , Whiteaker P , Lester HA , Lukas RJ
Ref : Molecular Pharmacology , 81 :175 , 2012
Abstract : We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of alpha7 and beta2 subunits. We measured optical and electrophysiological properties of wild-type and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged alpha7 and beta2 subunits colocalize. Forster resonance energy transfer between fluorescently tagged subunits strongly suggested that alpha7 and beta2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function alpha7 and beta2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, alpha7beta2 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-mediated, agonist-evoked currents were generally ~2-fold lower than those for alpha7 nAChRs. It is noteworthy that alpha7beta2 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro-beta-erythroidine that was not observed for alpha7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the alpha7-beta2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower alpha7beta2 nAChR current amplitudes and challenges in identifying the function of native alpha7beta2 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of beta2 subunits within the alpha7beta2 nAChRs.
ESTHER : Murray_2012_Mol.Pharmacol_81_175
PubMedSearch : Murray_2012_Mol.Pharmacol_81_175
PubMedID: 22039094

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

Title : Study on improvement of extracellular production of recombinant Thermobifida fusca cutinase by Escherichia coli - Chen_2011_Appl.Biochem.Biotechnol_165_666
Author(s) : Chen S , Liu Z , Chen J , Wu J
Ref : Appl Biochem Biotechnol , 165 :666 , 2011
Abstract : Escherichia coli is one of the most commonly used host strains for recombinant protein production. More and more research works on the production of recombinant protein indicate that extracellular production throughout a culture medium is more convenient and attractive compared to intracellular production. In present work, inducing temperature and isopropyl beta-D: -1-thiogalactopyranoside (IPTG) concentration were investigated to decrease the formation of inclusion body and increase the amount of soluble recombinant cutinase initially. Enzyme activity in the culture medium reached to 118.9 U/ml at 64 h of culture, and no inclusion body was detected in cytoplasm under the inducement condition of 0.2 mM IPTG and 30 degrees C. In addition, it was found that a large amount of cutinase had been accumulated in periplasm since 16-h cultivation under the same inducement condition. Therefore, glycine and surfactant sodium taurodeoxycholate (TDOC) were further used to promote the leakage of recombinant cutinase from periplasm. Supplied with 100 mM glycine and 1 mM TDOC, the amount of cutinase in periplasm decreased remarkably, and the activity in the culture medium reached to 146.2 and 149.2 U/ml after 54 h of culturing, respectively.
ESTHER : Chen_2011_Appl.Biochem.Biotechnol_165_666
PubMedSearch : Chen_2011_Appl.Biochem.Biotechnol_165_666
PubMedID: 21594592

Title : Functional nicotinic acetylcholine receptors containing alpha6 subunits are on GABAergic neuronal boutons adherent to ventral tegmental area dopamine neurons - Yang_2011_J.Neurosci_31_2537
Author(s) : Yang K , Buhlman L , Khan GM , Nichols RA , Jin G , McIntosh JM , Whiteaker P , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 31 :2537 , 2011
Abstract : Diverse nicotinic acetylcholine receptor (nAChR) subtypes containing different subunit combinations can be placed on nerve terminals or soma/dendrites in the ventral tegmental area (VTA). nAChR alpha6 subunit message is abundant in the VTA, but alpha6*-nAChR cellular localization, function, pharmacology, and roles in cholinergic modulation of dopaminergic (DA) neurons within the VTA are not well understood. Here, we report evidence for alpha6beta2*-nAChR expression on GABA neuronal boutons terminating on VTA DA neurons. alpha-Conotoxin (alpha-Ctx) MII labeling coupled with immunocytochemical staining localizes putative alpha6*-nAChRs to presynaptic GABAergic boutons on acutely dissociated, rat VTA DA neurons. Functionally, acetylcholine (ACh) induces increases in the frequency of bicuculline-, picrotoxin-, and 4-aminopyridine-sensitive miniature IPSCs (mIPSCs) mediated by GABA(A) receptors. These increases are abolished by alpha6*-nAChR-selective alpha-Ctx MII or alpha-Ctx PIA (1 nm) but not by alpha7 (10 nm methyllycaconitine) or alpha4* (1 mum dihydro-beta-erythroidine)-nAChR-selective antagonists. ACh also fails to increase mIPSC frequency in VTA DA neurons prepared from nAChR beta2 knock-out mice. Moreover, ACh induces an alpha-Ctx PIA-sensitive elevation in intraterminal Ca(2+) in synaptosomes prepared from the rat VTA. Subchronic exposure to 500 nm nicotine reduces ACh-induced GABA release onto the VTA DA neurons, as does 10 d of systemic nicotine exposure. Collectively, these results indicate that alpha6beta2*-nAChRs are located on presynaptic GABAergic boutons within the VTA and modulate GABA release onto DA neurons. These presynaptic alpha6beta2*-nAChRs likely play important roles in nicotinic modulation of DA neuronal activity.
ESTHER : Yang_2011_J.Neurosci_31_2537
PubMedSearch : Yang_2011_J.Neurosci_31_2537
PubMedID: 21325521

Title : Cardiac abnormalities in severe acute dichlorvos poisoning - He_2011_Crit.Care.Med_39_1906
Author(s) : He X , Li C , Wei D , Wu J , Shen L , Wang T
Ref : Critical Care Medicine , 39 :1906 , 2011
Abstract : OBJECTIVE: Patients with organophosphorus poisoning sometimes die suddenly during rigorous treatment, possibly from myocardial injury. This study sought to elucidate the mechanisms underlying organophosphorus poisoning-induced cardiotoxicity. DESIGN: Prospective observational study. SETTING: Urban, tertiary teaching hospital emergency intensive care unit with 10 beds. PATIENTS: Forty-one patients with severe acute dichlorvos poisoning were consecutively enrolled (n = 92) at emergency intensive care unit and followed for 3 months. MEASUREMENTS AND MAIN RESULTS: Levels of serum creatine kinase isoenzyme myocardium, cardiac troponin I, acetylcholinesterase, acetylcholine, epinephrine, and norepinephrine were tested on hospital days 1, 3, and 5 and on discharge day. Electrocardiography was recorded on admission and then every other day. Transthoracic echocardiography was performed at admission, in the acute phase, before discharge, and during follow-up. Technetium 99m-sestamibi myocardial single photon emission computed tomography was conducted in four patients. Thirty-seven (90.2%) patients survived and four (9.8%) patients died during treatment. We observed sinus tachycardia in 37 (90.2%) patients and ST-T changes in 33 (80.4%) patients. Creatine kinase isoenzyme myocardium and cardiac troponin I levels peaked at day 3 postadmission and then decreased to normal levels. Serum acetylcholine, epinephrine, and norepinephrine peaked at day 1 after admission and then decreased. Echocardiography revealed marked decreases in wall motion of the interventricular septum and left ventricle in the acute phase but returned to normal in the recovery phase. The left ventricular ejection fraction improved significantly from 42 +/- 5% to 59 +/- 4% (p = .001). Single photon emission computed tomography showed abnormal left ventricle perfusion. CONCLUSION: Severe acute dichlorvos poisoning is associated with reversible myocardial dysfunction, possibly through an increase in catecholamine levels.
ESTHER : He_2011_Crit.Care.Med_39_1906
PubMedSearch : He_2011_Crit.Care.Med_39_1906
PubMedID: 21516037

Title : Engineered Thermobifida fusca cutinase with increased activity on polyester substrates - Silva_2011_Biotechnol.J_6_1230
Author(s) : Silva C , Da S , Silva N , Matama T , Araujo R , Martins M , Chen S , Chen J , Wu J , Casal M , Cavaco-Paulo A
Ref : Biotechnol J , 6 :1230 , 2011
Abstract : A bacterial cutinase from Thermobifida fusca, named Tfu_0883, was genetically modified by site-directed mutagenesis to enhance its activity on poly(ethylene terephthalate) (PET). The new mutations tailored the catalytic site for PET, increasing the affinity of cutinase to this hydrophobic substrate and the ability to hydrolyze it. The mutation I218A was designed to create space and the double mutation Q132A/T101A was designed both to create space and to increase hydrophobicity. The activity of the double mutant on the soluble substrate p-nitrophenyl butyrate increased two-fold compared to wild-type cutinase, while on PET both single and double mutants exhibited considerably higher hydrolysis efficiency. The replacement of specific amino acids at the active site was an effective approach for the improvement of the Tfu_0883 cutinase capacity to hydrolyze polyester surfaces. Thus, this study provides valuable insight on how the function and stability of enzymes can be improved by molecular engineering for their application in synthetic fiber biotransformation.
ESTHER : Silva_2011_Biotechnol.J_6_1230
PubMedSearch : Silva_2011_Biotechnol.J_6_1230
PubMedID: 21751386
Gene_locus related to this paper: thefu-q6a0i4

Title : Exposure of nicotine to ventral tegmental area slices induces glutamatergic synaptic plasticity on dopamine neurons - Jin_2011_Synapse_65_332
Author(s) : Jin Y , Yang K , Wang H , Wu J
Ref : Synapse , 65 :332 , 2011
Abstract : Nicotine promotes glutamatergic synaptic plasticity in dopaminergic (DA) neurons in the ventral tegmental area (VTA), which is thought to be an important mechanism underlying nicotine reward. However, it is unclear whether exposure of nicotine alone to VTA slice is sufficient to increase glutamatergic synaptic strength on DA neurons and which nicotinic acetylcholine receptor (nAChR) subtype mediates this effect. Here, we report that the incubation of rat VTA slices with 500 nM nicotine induces glutamatergic synaptic plasticity in DA neurons. We measure the ratio of AMPA and NMDA receptor-mediated currents (AMPA/NMDA) and compare these ratios between nicotine-treated and -untreated slices. Our results demonstrate that the incubation of VTA slices with 500 nM nicotine for 1 h (but not for 10 min) significantly increases the AMPA/NMDA ratio when compared with controls. Preincubation with 10 nM of the alpha7-nAChR antagonist, methyllycaconitine (MLA) but not 1 muM alpha4-containing nAChR antagonist, dihydro-beta-erythroidine (DHbetaE) prevents nicotinic effect, suggesting that alpha7-nAChRs are mainly mediated this nicotinic effect. This finding is further supported by the disappearance of this nicotinic effect in nAChR alpha7 knockout (KO) mice. Furthermore, nicotine reduced paired-pulse ratio (PPR) of evoked excitatory postsynaptic potential (eEPSP) in the VTA slices prepared from wild-type (WT) mice but not alpha7 KO mice. Collectively, these findings suggest that exposure of smoking-relevant concentrations of nicotine to VTA slices is sufficient to increase glutamatergic synaptic strength on DA neurons and that alpha7-nAChRs likely mediate this nicotinic effect through increasing presynaptic release of glutamate.
ESTHER : Jin_2011_Synapse_65_332
PubMedSearch : Jin_2011_Synapse_65_332
PubMedID: 20730803

Title : TiO2-decorated graphene nanohybrids for fabricating an amperometric acetylcholinesterase biosensor - Wang_2011_Analyst_136_3349
Author(s) : Wang K , Li HN , Wu J , Ju C , Yan JJ , Liu Q , Qiu B
Ref : Analyst , 136 :3349 , 2011
Abstract : This work describes a highly sensitive and rapid amperometric biosensor for organophosphate compounds (OPs) based on immobilization of acetylcholinesterase (AChE) on a novel TiO(2)-decorated graphene (TiO(2)-G) nanohybrid, which was constructed by in situ growth of TiO(2) nanoparticles (NPs) on the graphene sheet. The well-dispersed TiO(2) NPs eliminated the restacking of TiO(2)-G nanohybrids. Due to the integrating of TiO(2)-G nanohybrids, the as-prepared biosensor showed high affinity to acetylthiocholine (ATCl) with a Michaelis-Menten constant (K(m)) value of 0.22 mM, and rapid inhibition time (3 min). Further, based on the inhibition of OPs on the enzymatic activity of the immobilized AChE, and using carbaryl as a model compound, the inhibition of carbaryl was proportional to its concentration ranging from 0.001 to 0.015 and 0.015 to 2 mug mL(-1) with a detection limit of 0.3 ng mL(-1) (S/N = 3). The developed biosensor exhibited a good performance for organophosphate pesticide detection, including good reproducibility and acceptable stability, which provided a new and promising tool for the analysis of enzyme inhibitors.
ESTHER : Wang_2011_Analyst_136_3349
PubMedSearch : Wang_2011_Analyst_136_3349
PubMedID: 21738917

Title : Characterization of two metagenome-derived esterases that reactivate chloramphenicol by counteracting chloramphenicol acetyltransferase - Tao_2011_J.Microbiol.Biotechnol_21_1203
Author(s) : Tao W , Lee MH , Yoon MY , Kim JC , Malhotra S , Wu J , Hwang EC , Lee SW
Ref : J Microbiol Biotechnol , 21 :1203 , 2011
Abstract : Function-driven metagenomic analysis is a powerful approach to screening for novel biocatalysts. In this study, we investigated lipolytic enzymes selected from an alluvial soil metagenomic library, and identified two novel esterases, EstDL26 and EstDL136. EstDL26 and EstDL136 reactivated chloramphenicol from its acetyl derivates by counteracting the chloramphenicol acetyltransferase (CAT) activity in Escherichia coli. These two enzymes showed only 27% identity in amino acid sequence to each other; however both preferentially hydrolyzed short-chain p-nitrophenyl esters (< or =C5) and showed mesophilic properties. In vitro, EstDL136 catalyzed the deacetylation of 1- and 3- acetyl and 1,3-diacetyl derivates; in contrast, EstDL26 was not capable of the deacetylation at C1, indicating a potential regioselectivity. EstDL26 and EstDL136 were similar to microbial hormone-sensitive lipase (HSL), and since chloramphenicol acetate esterase (CAE) activity was detected from two other soil esterases in the HSL family, this suggests a distribution of CAE among the soil microorganisms. The isolation and characterization of EstDL26 and EstDL136 in this study may be helpful in understanding the diversity of CAE enzymes and their potential role in releasing active chloramphenicol in the producing bacteria.
ESTHER : Tao_2011_J.Microbiol.Biotechnol_21_1203
PubMedSearch : Tao_2011_J.Microbiol.Biotechnol_21_1203
PubMedID: 22210605
Gene_locus related to this paper: 9bact-g3cr00 , 9bact-g3cr02

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

Title : Naturally-expressed nicotinic acetylcholine receptor subtypes - Wu_2011_Biochem.Pharmacol_82(8)_800
Author(s) : Wu J , Lukas RJ
Ref : Biochemical Pharmacology , 82 :800 , 2011
Abstract : Nicotinic acetylcholine receptors (nAChRs) warrant attention, as they play many critical roles in brain and body function and have been implicated in a number of neurological and psychiatric disorders, including nicotine dependence. nAChRs are composed as diverse subtypes containing specific combinations of genetically-distinct subunits and that have different functional properties, distributions, and pharmacological profiles. There had been confidence that the rules that define ranges of assembly partners for specific subunits were well-established, especially for the more prominent nAChR subtypes. However, we review here some newer findings indicating that nAChRs having largely the same, major subunits exist as isoforms with unexpectedly different properties. Moreover, we also summarize our own studies indicating that novel nAChR subtypes exist and/or have distributions not heretofore described. Importantly, the nAChRs that exist as new isoforms or subtypes or have interesting distributions require alteration in thinking about their roles in health and disease.
ESTHER : Wu_2011_Biochem.Pharmacol_82(8)_800
PubMedSearch : Wu_2011_Biochem.Pharmacol_82(8)_800
PubMedID: 21787755

Title : Genomic and proteomic analyses of the fungus Arthrobotrys oligospora provide insights into nematode-trap formation - Yang_2011_PLoS.Pathog_7_e1002179
Author(s) : Yang J , Wang L , Ji X , Feng Y , Li X , Zou C , Xu J , Ren Y , Mi Q , Wu J , Liu S , Liu Y , Huang X , Wang H , Niu X , Li J , Liang L , Luo Y , Ji K , Zhou W , Yu Z , Li G , Li L , Qiao M , Feng L , Zhang KQ
Ref : PLoS Pathog , 7 :e1002179 , 2011
Abstract : Nematode-trapping fungi are "carnivorous" and attack their hosts using specialized trapping devices. The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles. Here, the genome of the nematode-trapping fungus Arthrobotrys oligospora Fres. (ATCC24927) was reported. The genome contains 40.07 Mb assembled sequence with 11,479 predicted genes. Comparative analysis showed that A. oligospora shared many more genes with pathogenic fungi than with non-pathogenic fungi. Specifically, compared to several sequenced ascomycete fungi, the A. oligospora genome has a larger number of pathogenicity-related genes in the subtilisin, cellulase, cellobiohydrolase, and pectinesterase gene families. Searching against the pathogen-host interaction gene database identified 398 homologous genes involved in pathogenicity in other fungi. The analysis of repetitive sequences provided evidence for repeat-induced point mutations in A. oligospora. Proteomic and quantitative PCR (qPCR) analyses revealed that 90 genes were significantly up-regulated at the early stage of trap-formation by nematode extracts and most of these genes were involved in translation, amino acid metabolism, carbohydrate metabolism, cell wall and membrane biogenesis. Based on the combined genomic, proteomic and qPCR data, a model for the formation of nematode trapping device in this fungus was proposed. In this model, multiple fungal signal transduction pathways are activated by its nematode prey to further regulate downstream genes associated with diverse cellular processes such as energy metabolism, biosynthesis of the cell wall and adhesive proteins, cell division, glycerol accumulation and peroxisome biogenesis. This study will facilitate the identification of pathogenicity-related genes and provide a broad foundation for understanding the molecular and evolutionary mechanisms underlying fungi-nematodes interactions.
ESTHER : Yang_2011_PLoS.Pathog_7_e1002179
PubMedSearch : Yang_2011_PLoS.Pathog_7_e1002179
PubMedID: 21909256
Gene_locus related to this paper: artoa-g1wyr4 , artoa-g1x1a7 , artoa-g1x3f4 , artoa-g1x3h6 , artoa-g1x9s5 , artoa-g1x9z4 , artoa-g1xcb5 , artoa-g1xhl6 , artoa-g1xjb3 , artoa-g1xjy0 , artoa-g1xkw3 , artoa-g1xnf2 , artoa-g1xnf8 , artoa-g1xqd4 , artoa-g1xqt1 , artoa-g1xte8 , artoa-g1xu91 , artoa-g1xv59 , artoa-g1x382 , artoa-g1x3q3 , artoa-g1wxl5 , artoa-g1xj75 , artoa-g1xd25 , artoa-g1wzu7 , artoa-g1xt42 , artoa-g1xhm8 , artoa-g1wy43

Title : Isolation and characterization of a family VII esterase derived from alluvial soil metagenomic library - Tao_2011_J.Microbiol_49_178
Author(s) : Tao W , Lee MH , Wu J , Kim NH , Lee SW
Ref : J Microbiol , 49 :178 , 2011
Abstract : A novel esterase gene, estDL30, was isolated from an alluvial metagenomic library using function-driven screening. estDL30 consisted of 1,524 nucleotides and encoded a 507-amino acid protein. Sequence analysis revealed that EstDL30 is similar to many type B carboxylesterases, containing a G-E-S-A-G pentapeptide with a catalytic Ser residue. Phylogenetic analysis suggested that EstDL30 belongs to the family VII lipases, together with esterases from Bacillus subtilis (P37967), Streptomyces coelicolor A3(2) (CAA22794), and Arthrobacter oxydans (Q01470). Purified EstDL30 showed its highest catalytic efficiency toward p-nitrophenyl butyrate, with a k (cat) of 2293 s(-1) and k (cat)/K (m) of 176.4 s(-1)mM(-1); however, little activity was detected when the acyl chain length exceeded C(8). Biochemical characterization of EstDL30 revealed that it is an alkaline esterase that possesses maximal activity at pH 8 and 40 degrees C. The effects of denaturants and divalent cations were also investigated. EstDL30 tolerated well the presence of methanol and Tween 20. Its activity was strongly inhibited by 1 mM Cu(2+) and Zn(2+), but stimulated by Fe(2+). The unique properties of EstDL30, its high activity under alkaline conditions and stability in the presence of organic solvents, may render it applicable to organic synthesis.
ESTHER : Tao_2011_J.Microbiol_49_178
PubMedSearch : Tao_2011_J.Microbiol_49_178
PubMedID: 21538236
Gene_locus related to this paper: 9bact-g1ard1

Title : Complete genome sequence of Streptococcus suis serotype 14 strain JS14 - Hu_2011_J.Bacteriol_193_2375
Author(s) : Hu P , Yang M , Zhang A , Wu J , Chen B , Hua Y , Yu J , Xiao J , Jin M
Ref : Journal of Bacteriology , 193 :2375 , 2011
Abstract : Streptococcus suis is an important zoonotic agent leading to a variety of diseases in swine and can be transmitted to human beings upon close contact. Here, we report the complete genome sequence of S. suis serotype 14 strain JS14 which was isolated from a diseased pig in Jiangsu Province, China.
ESTHER : Hu_2011_J.Bacteriol_193_2375
PubMedSearch : Hu_2011_J.Bacteriol_193_2375
PubMedID: 21398551
Gene_locus related to this paper: strej-e8uk64 , strsu-a4vws4 , strsu-q673u2 , strsy-a4vus4

Title : Attenuation of CNS inflammatory responses by nicotine involves alpha7 and non-alpha7 nicotinic receptors - Hao_2011_Exp.Neurol_227_110
Author(s) : Hao J , Simard AR , Turner GH , Wu J , Whiteaker P , Lukas RJ , Shi FD
Ref : Experimental Neurology , 227 :110 , 2011
Abstract : A considerable number of in vivo studies have demonstrated that the cholinergic system can dampen the peripheral immune response, and it is thought that the alpha7-nicotinic acetylcholine receptor (nAChR) subtype is a key mediator of this process. The goal of the present study was to determine if nicotine modulates immunological mechanisms known to be involved in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for CNS autoimmune disease, via alpha7-nAChRs. Here we show that nicotine exposure attenuates EAE severity and that this effect is largely abolished in nAChR alpha7 subunit knock-out mice. However, nicotine exposure partially retains the ability to reduce lymphocyte infiltration into the CNS, inhibit auto-reactive T cell proliferation and helper T cell cytokine production, down-regulate co-stimulatory protein expression on myeloid cells, and increase the differentiation and recruitment of regulatory T cells, even in the absence of alpha7-nAChRs. Diverse effects of nicotine on effector and regulatory T cells, as well as antigen-presenting cells, may be linked to differential expression patterns of nAChR subunits across these cell types. Taken together, our data show that although alpha7-nAChRs indeed seem to play an important role in nicotine-conferred reduction of the CNS inflammatory response and protection against EAE, other nAChR subtypes also are involved in the anti-inflammatory properties of the cholinergic system.
ESTHER : Hao_2011_Exp.Neurol_227_110
PubMedSearch : Hao_2011_Exp.Neurol_227_110
PubMedID: 20932827

Title : Induction of a 55 kDa acetylcholinesterase protein during apoptosis and its negative regulation by the Akt pathway - Xie_2011_J.Mol.Cell.Biol_3_250
Author(s) : Xie J , Jiang H , Wan YH , Du AY , Guo KJ , Liu T , Ye WY , Niu X , Wu J , Dong XQ , Zhang XJ
Ref : J Molecular & Cellular Biology , 3 :250 , 2011
Abstract : Acetylcholinesterase (AChE) is emerging as an important contributor to apoptosis in various cell types. However, overexpression of AChE does not initiate apoptosis, and cells which express AChE at basal levels grow normally, suggesting that AChE may function differently between normal and apoptotic conditions. In this study, we determined that an AChE-derived protein ( approximately 55 kDa) positively correlated with cellular apoptotic levels. The 55 kDa AChE protein was not a result of a novel splice variant of the AChE primary transcript. Instead, it was determined to be a cleaved fragment of the full-length 68 kDa AChE protein that could not be inhibited by cycloheximide (CHX) but could be suppressed by caspase inhibitors in apoptotic PC-12 cells. Furthermore, activation of the Akt cascade abolished the 55 kDa protein, and both AChE protein forms (68 and 55 kDa) accumulated in the nucleus during apoptosis. In a mouse model for ischemia/reperfusion (I/R)-induced acute renal failure, the 55 kDa AChE protein was detected in the impaired organs but not in the normal ones, and its levels correlated with the genotype of the mice. In summary, a 55 kDa AChE protein resulting from the cleavage of 68 kDa AChE is induced during apoptosis, and it is negatively regulated by the Akt pathway. This study suggests that an alternative form of AChE may play a role in apoptosis.
ESTHER : Xie_2011_J.Mol.Cell.Biol_3_250
PubMedSearch : Xie_2011_J.Mol.Cell.Biol_3_250
PubMedID: 21377978

Title : Poster: Tethered pentamersLow sensitivity alpha4\/beta2-nicotinic acetylcholine receptors -
Author(s) : Lucero L , Bhakta M , Liu G , Wu J , Hauser TA , Bencherif M , Bermudez I , Whiteaker P , Lukas RJ
Ref : Biochemical Pharmacology , 82 :1025 , 2011
PubMedID:

Title : Effect of Silent Mutations in Translational Initial Region on the Production of Recombinant Cutinase in Escherichia coli - Liu_2011_Curr.Microbiol_62_1302
Author(s) : Liu ZG , Zhu L , Zhu KL , Chen S , Chen J , Wu J
Ref : Curr Microbiol , 62 :1302 , 2011
Abstract : Translational Initial Region (TIR) is the threshold of an intracellular translation process, and tiny alterations in this region are reported to intensely influence the downstream expression. Such property provides a potential utilization in extracellular production of recombinant enzyme. As an esterase, cutinase is an essential catalyst in the process of textile scouring, and has a potential application in food and chemical industry. In the present study, a bacterial cutinase (Tfu_0883) from Thermobifida fusca was expressed in Escherichia coli with pelB as its signal peptide using trc as its promoter. A subsequent TIR degeneracy mutagenesis was then carried out in the initial sequence of pelB. A fast screening method for these mutants was developed and a series of strains with different expression strengths were accordingly obtained. Among these mutants, a high cutinase production level of 38.0 U/ml was achieved, which is three times that of the control group. This study explored the potential utilization of TIR degeneracy mutagenesis in the production of industrial enzymes.
ESTHER : Liu_2011_Curr.Microbiol_62_1302
PubMedSearch : Liu_2011_Curr.Microbiol_62_1302
PubMedID: 21212953

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : Complete genome sequence of Streptococcus suis serotype 3 strain ST3 - Hu_2011_J.Bacteriol_193_3428
Author(s) : Hu P , Yang M , Zhang A , Wu J , Chen B , Hua Y , Yu J , Chen H , Xiao J , Jin M
Ref : Journal of Bacteriology , 193 :3428 , 2011
Abstract : Streptococcus suis is a zoonotic pathogen causing economic loss in the swine industry and is also a threat to human health. To date, the mechanism of pathogenesis is not fully understood. Here, we report the complete genome sequence of S. suis strain ST3 of serotype 3, which provides opportunities to reveal genetic basis of infection of S. suis non-serotype 2 strains.
ESTHER : Hu_2011_J.Bacteriol_193_3428
PubMedSearch : Hu_2011_J.Bacteriol_193_3428
PubMedID: 21572001
Gene_locus related to this paper: strsu-b9wvz1

Title : Comparative genomic analysis of Streptococcus suis reveals significant genomic diversity among different serotypes - Zhang_2011_BMC.Genomics_12_523
Author(s) : Zhang A , Yang M , Hu P , Wu J , Chen B , Hua Y , Yu J , Chen H , Xiao J , Jin M
Ref : BMC Genomics , 12 :523 , 2011
Abstract : BACKGROUND: Streptococcus suis (S. suis) is a major swine pathogen and an emerging zoonotic agent. Serotypes 1, 2, 3, 7, 9, 14 and 1/2 are the most prevalent serotypes of this pathogen. However, almost all studies were carried out on serotype 2 strains. Therefore, characterization of genomic features of other serotypes will be required to better understand their virulence potential and phylogenetic relationships among different serotypes.
RESULTS: Four Chinese S. suis strains belonging to serotypes 1, 7, 9 and 1/2 were sequenced using a rapid, high-throughput approach. Based on the 13 corresponding serotype strains, including 9 previously completed genomes of this bacterium, a full comparative genomic analysis was performed. The results provide evidence that (i) the pan-genome of this species is open and the size increases with addition of new sequenced genomes, (ii) strains of serotypes 1, 3, 7 and 9 are phylogenetically distinct from serotype 2 strains, but all serotype 2 strains, plus the serotype 1/2 and 14 strains, are very closely related. (iii) all these strains, except for the serotype 1 strain, could harbor a recombinant site for a pathogenic island (89 K) mediated by conjugal transfer, and may have the ability to gain the 89 K sequence.
CONCLUSIONS: There is significant genomic diversity among different strains in S. suis, and the gain and loss of large amount of genes are involved in shaping their genomes. This is indicated by (i) pairwise gene content comparisons between every pair of these strains, (ii) the open pan-genome of this species, (iii) the observed indels, invertions and rearrangements in the collinearity analysis. Phylogenetic relationships may be associated with serotype, as serotype 2 strains are closely related and distinct from other serotypes like 1, 3, 7 and 9, but more strains need to be sequenced to confirm this.
ESTHER : Zhang_2011_BMC.Genomics_12_523
PubMedSearch : Zhang_2011_BMC.Genomics_12_523
PubMedID: 22026465
Gene_locus related to this paper: strsu-b9wvz1

Title : Dynamic alterations of gene expression of nicotinic acetylcholine receptor alpha7, alpha4 and beta2 subunits in an acute MPTP-lesioned mouse model - Hu_2011_Neurosci.Lett_494_232
Author(s) : Hu J , Zhu C , Liu Y , Wang F , Huang Z , Fan W , Wu J
Ref : Neuroscience Letters , 494 :232 , 2011
Abstract : Epidemiologic studies show that the prevalence of Parkinson's disease (PD) is lower in smokers than in nonsmokers. Nicotine, a potent agonist of nicotinic acetylcholine receptors (nAChRs), excites midbrain dopaminergic neurons and this may contribute to the anti-parkinsonian effects. However, the alterations in gene expression of nAChR subunits using an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model remain unclear. In the present study, we profile the time course of nAChR alpha7, alpha4 and beta2 subunit expression levels using a comparative RT-PCR approach after acute MPTP injection. The results fall into four categories. (1) MPTP treatment transiently increased nAChR alpha7 (after last injection of MPTP 3 and 24 h), alpha4 and beta2 (24 h) mRNA expression in the substantia nigra (SN) and striatum. (2) Compared to cortical and hippocampal tissues, this transient increase of nAChR subunit expression specifically occurred in the SN and striatum. (3) In the acute MPTP model, time-courses of altered expression for nAChR alpha7, alpha4 and beta2 subunits closely mirrored the deficits observed in animal motor activity. (4) Stereological data showed that after administration of MPTP for 24h, there was a robust astrogliosis in the SN associated with significant dopaminergic neurodegeneration. These changes followed or paralleled MPTP-induced elevation in the levels of alpha7, alpha4 and beta2 mRNAs. Collectively, our results demonstrate that nAChRs are important targets in the MPTP neurotoxic process. These data suggest that therapeutic strategies targeted toward nAChR alpha7, alpha4 and beta2 subunits may have potential for developing new treatments for PD.
ESTHER : Hu_2011_Neurosci.Lett_494_232
PubMedSearch : Hu_2011_Neurosci.Lett_494_232
PubMedID: 21406211

Title : Poster: Acetylcholine binding protein-nicotinic receptor chimeras for delineating structure and determinants of ligand selectivity -
Author(s) : Talley TT , Nemecz A , Yamauchi JG , Wu J , Ho KY , Sankaran B , Taylor P
Ref : Biochemical Pharmacology , 82 :1028 , 2011
PubMedID:

Title : Pharmacological characterization of [(125)I]CHIBA-1006 binding, a new radioligand for alpha7 nicotinic acetylcholine receptors, to rat brain membranes - Wu_2010_Brain.Res_1360_130
Author(s) : Wu J , Toyohara J , Tanibuchi Y , Fujita Y , Zhang J , Chen H , Matsuo M , Wang RF , Hashimoto K
Ref : Brain Research , 1360 :130 , 2010
Abstract : The alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable small molecule radioligands for imaging alpha7 nAChRs in the brain. In this study, we synthesized the novel radioligand [(125)I]4-iodophenyl 1,4-diazaicyclo[3.2.2]nonane-4-carboxylate ([(125)I]CHIBA-1006), a iodine-derivative of the selective alpha7 nAChR agonist SSR180711, and studied the characterization of [(125)I]CHIBA-1006 binding to rat brain membranes. The assays of [(125)I]CHIBA-1006 binding to rat brain membranes were performed at 4 degrees C. The presence of a single saturable high-affinity binding component for [(125)I]CHIBA-1006 in the rat brain was shown. Scatchard analysis revealed an apparent equilibrium dissociation constant (K(d)) of 88.2+/-21.4nM and a maximal number of binding sites (B(max)) of 65.4+/-6.8fmol/mg protein (mean+/-SEM, n=4). The specific binding of [(125)I]CHIBA-1006 was inhibited by a number of alpha7 nAChR-selective ligands (e.g., unlabeled CHIBA-1006, SSR180711, CHIBA-1001, MG624 and A844606), suggesting a similarity among alpha7 nAChR pharmacological profiles. In contrast, alpha-bungarotoxin, MLA, and nicotine showed very weak affinity for [(125)I]CHIBA-1006 binding. The regional distribution of [(125)I]CHIBA-1006 binding to crude membranes from dissected regions of the rat brain was different from that of [(125)I]alpha-bungarotoxin binding, suggesting that [(125)I]CHIBA-1006 binding sites may not be identical to [(125)I]alpha-bungarotoxin binding sites in the rat brain. The present findings suggest that [(125)I]CHIBA-1006 would be a useful new small molecule radioligand for alpha7 nAChRs in the brain.
ESTHER : Wu_2010_Brain.Res_1360_130
PubMedSearch : Wu_2010_Brain.Res_1360_130
PubMedID: 20816767

Title : Double target concept for smoking cessation - Wu_2010_Acta.Pharmacol.Sin_31_1015
Author(s) : Wu J
Ref : Acta Pharmacol Sin , 31 :1015 , 2010
Abstract : Tobacco use is estimated to be the largest single cause of premature death in the world. Nicotine is the major addictive substance in tobacco products. After cigarette smoking, nicotine quickly acts on its target, nicotinic acetylcholine receptors (nAChRs), which are widely distributed throughout the mammalian central nervous system and are expressed as diverse subtypes on cell bodies, dendrites and/or nerve terminals. Through the nAChRs in brain reward circuits, nicotine alters dopaminergic (DA) neuronal function in the ventral tegmental area (VTA) and increases dopamine release from VTA to nuclear accumbens (NA), which leads to nicotine reward, tolerance and dependence. After quitting smoking, smokers experience withdrawal symptoms, including depression, irritability, difficulty concentrating or sleeping, headache, and tiredness. Recently, evidence has been accumulated to reveal the molecular and cellular mechanisms of nicotine reward, tolerance and dependence. The outcomes of these investigations provide pharmacological basis for smoking cessation. Here, I briefly summarize recent advancements of our understanding of nicotine reward, tolerance and dependence. Based on these understandings, I propose a double target hypothesis, in which nAChRs and dopamine release process are two important targets for smoking cessation. Dysfunction of nAChRs (antagonism or desensitization) is crucial to abolish nicotine dependence and the maintenance of an appropriate level of extracellular dopamine eliminates nicotine withdrawal syndromes. Therefore, the medications simultaneously act on these two targets should have the desired effect for smoking cessation. I discuss how to use this double target concept to interpret recent therapies and to develop new candidate compounds for smoking cessation.
ESTHER : Wu_2010_Acta.Pharmacol.Sin_31_1015
PubMedSearch : Wu_2010_Acta.Pharmacol.Sin_31_1015
PubMedID: 20711220

Title : Mechanisms involved in systemic nicotine-induced glutamatergic synaptic plasticity on dopamine neurons in the ventral tegmental area - Gao_2010_J.Neurosci_30_13814
Author(s) : Gao M , Jin Y , Yang K , Zhang D , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 30 :13814 , 2010
Abstract : Systemic exposure to nicotine induces glutamatergic synaptic plasticity on dopamine (DA) neurons in the ventral tegmental area (VTA), but mechanisms are largely unknown. Here, we report that single, systemic exposure in rats to nicotine (0.17 mg/kg free base) increases the ratio of DA neuronal currents mediated by AMPA relative to NMDA receptors (AMPA/NMDA ratio) assessed 24 h later, based on slice-patch recording. The AMPA/NMDA ratio increase is evident within 1 h and lasts for at least 72 h after nicotine exposure (and up to 8 d after repeated nicotine administration). This effect cannot be prevented by systemic injection of either alpha7-nAChR (nicotinic ACh receptor)-selective [methyllycaconitine (MLA)] or beta2*-nAChR-selective [mecamylamine (MEC)] antagonists but is prevented by coinjection of MLA and MEC. In either nAChR alpha7 or beta2 subunit knock-out mice, systemic exposure to nicotine still increases the AMPA/NMDA ratio. Preinjection in rats of a NMDA receptor antagonist MK-801((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), but neither DA receptor antagonists [SCH-23390 (R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) plus haloperidol] nor a calcineurin inhibitor (cyclosporine), prevents the nicotine-induced increase in AMPA/NMDA ratio. After systemic exposure to nicotine, glutamatergic (but not GABAergic) transmission onto rat VTA DA neuronal inputs is enhanced. Correspondingly, DA neuronal firing measured 24 h after nicotine exposure using extracellular single-unit recording in vivo is significantly faster, and there is conversion of silent to active DA neurons. Collectively, these findings demonstrate that systemic nicotine acting via either alpha7- or beta2*-nAChRs increases presynaptic and postsynaptic glutamatergic function, and consequently initiates glutamatergic synaptic plasticity, which may be an important, early neuronal adaptation in nicotine reward and reinforcement.
ESTHER : Gao_2010_J.Neurosci_30_13814
PubMedSearch : Gao_2010_J.Neurosci_30_13814
PubMedID: 20943922

Title : Biochemical characterization of the cutinases from Thermobifida fusca - Chen_2010_J.Mol.Catal.B.Enzym_63_121
Author(s) : Chen S , Su L , Billig S , Zimmermann W , Chen J , Wu J
Ref : J Mol Catal B Enzym , 63 :121 , 2010
Abstract : Thermobifida fusca produces two cutinases which share 93% identity in amino acid sequence. In the present study, we investigated the detailed biochemical properties of T. fusca cutinases for the first time. For a better comparison between bacterial and fungal cutinases, recombinant Fusarium solani pisi cutinase was subjected to the similar analysis. The results showed that both bacterial and fungal cutinases are monomeric proteins in solution. The bacterial cutinases exhibited a broad substrate specificity against plant cutin, synthetic polyesters, insoluble triglycerides, and soluble esters. In addition, the two isoenzymes of T. fusca and the F.solani pisi cutinase are similar in substrate kinetics, the lack of interfacial activation, and metal ion requirements. However, the T.fusca cutinases showed higher stability in the presence of surfactants and organic solvents. Considering the versatile hydrolytic activity, good tolerance to surfactants, superior stability in organic solvents, and thermostability demonstrated by T. fusca cutinases, they may have promising applications in related industries.
ESTHER : Chen_2010_J.Mol.Catal.B.Enzym_63_121
PubMedSearch : Chen_2010_J.Mol.Catal.B.Enzym_63_121
PubMedID:
Gene_locus related to this paper: thefu-q6a0i4 , thefu-q6a0i3

Title : The anticonvulsive drug lamotrigine blocks neuronal {alpha}4{beta}2 nicotinic acetylcholine receptors - Zheng_2010_J.Pharmacol.Exp.Ther_335_401
Author(s) : Zheng C , Yang K , Liu Q , Wang MY , Shen J , Valles AS , Lukas RJ , Barrantes FJ , Wu J
Ref : Journal of Pharmacology & Experimental Therapeutics , 335 :401 , 2010
Abstract : Lamotrigine (LTG), an anticonvulsive drug, is often used for the treatment of a variety of epilepsies. In addition to block of sodium channels, LTG may act on other targets to exert its antiepileptic effect. In the present study, we evaluated the effects of LTG on neuronal nicotinic acetylcholine receptors (nAChRs) using the patch-clamp technique on human alpha4beta2-nAChRs heterologously expressed in the SH-EP1 cell line and on native alpha4beta2-nAChRs in dopaminergic (DA) neurons in rat ventral tegmental area (VTA). In SH-EP1 cells, LTG diminished the peak and steady-state components of the inward alpha4beta2-nAChR-mediated currents. This effect exhibited concentration-, voltage- and use-dependent behavior. Nicotine dose-response curves showed that in the presence of LTG, the nicotine-induced maximal current was reduced, suggesting a noncompetitive inhibition. These findings suggest that LTG inhibits human neuronal alpha4beta2-nAChR function through an open-channel blocking mechanism. LTG-induced inhibition in alpha4beta2-nAChRs was more profound when preceded by a 2-min pretreatment, after which the nicotine-induced current was reduced even without coapplication of LTG, suggesting that LTG is also able to inhibit alpha4beta2-nAChRs without channel activation. In freshly dissociated VTA DA neurons, LTG inhibited alpha4beta2-nAChR-mediated currents but did not affect glutamate- or GABA-induced currents, indicating that LTG selectively inhibits nAChR function. Collectively, our data suggest that the neuronal alpha4beta2-nAChR is likely an important target for mediating the anticonvulsive effect of LTG and the blockade of alpha4beta2-nAChR possibly underlying the mechanism through which LTG effectively controls some types of epilepsy, such as autosomal dominant nocturnal frontal lobe epilepsy or juvenile myoclonic epilepsy.
ESTHER : Zheng_2010_J.Pharmacol.Exp.Ther_335_401
PubMedSearch : Zheng_2010_J.Pharmacol.Exp.Ther_335_401
PubMedID: 20688974

Title : AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia\/reperfusion - Ye_2010_Apoptosis_15_474
Author(s) : Ye W , Gong X , Xie J , Wu J , Zhang X , Ouyang Q , Zhao X , Shi Y
Ref : Apoptosis , 15 :474 , 2010
Abstract : We recently reported that the expression of the synaptic form of acetylcholinesterase (AChE) is induced during apoptosis in various cell types in vitro. Here, we provide evidence to confirm that AChE is expressed during ischemia-reperfusion (I/R)-induced apoptosis in vivo. Renal I/R is a major cause of acute renal failure (ARF), resulting in injury and the eventual death of renal cells due to a combination of apoptosis and necrosis. Using AChE-deficient mice and AChE inhibitors, we investigated whether AChE deficiency or inhibition can protect against apoptosis caused by I/R in a murine kidney model. Unilateral clamping of renal pedicles for 90 min followed by reperfusion for 24 h caused significant renal dysfunction and injury. Both genetic AChE deficiency and chemical inhibition of AChE (provided by huperzine A, tacrine and donepezil) significantly reduced the biochemical and histological evidence of renal dysfunction following I/R. Activation of caspases-8, -9, -12, and -3 in vivo were prevented and associated with reduced levels of cell apoptosis and cell death. A further investigation also confirmed that AChE deficiency down-regulated p53 induction and phosphorylation at serine-15, and decreased the Bax/Bcl-2 ratio during I/R. In conclusion, our study demonstrates that AChE may be a pro-apoptotic factor and the inhibition of AChE reduces renal I/R injury. These findings suggest that AChE inhibitors may represent a therapeutic strategy for protection against ischemic acute renal failure.
ESTHER : Ye_2010_Apoptosis_15_474
PubMedSearch : Ye_2010_Apoptosis_15_474
PubMedID: 20054652

Title : Comparative study of properties of immobilized lipase onto glutaraldehyde-activated amino-silica gel via different methods - Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
Author(s) : Yang G , Wu J , Xu G , Yang L
Ref : Colloids Surf B Biointerfaces , 78 :351 , 2010
Abstract : The enzyme-aggregate coating method was performed to immobilize Arthrobacter sp. lipase in order to achieve better catalytic properties comparable to the conventional covalent attachment and covalent attachment plus cross-linking. The glutaraldehyde-activated amino-silica gel which was synthesized by sol-gel technique was used as the support, and the catalytic characteristics of the lipase preparations were tested in the asymmetric acylation of 4-hydroxy-3-methyl-2-(2-propenyl)-2-cyclopenten-1-one (HMPC) in organic solvents. The results showed that the immobilized lipase by enzyme-aggregate coating possessed both higher activity and stability than those by other methods, e.g. it obtained an activity of 82.6 U/g and remained 42% and 93% of the original activity after incubation in vinyl acetate at 60 degrees C for 16 h and 9 times recycles, respectively, while the covalently attached lipase got an activity of 67.4 U/g and left 33% and 73% of the original under the same conditions, and the enzyme prepared by covalent attachment plus cross-linking exhibited the lowest activity yield. Moreover, excellent enantioselectivity (E > or =400) was achieved by all the three prepared lipases in our paper (E=85 for the free enzyme).
ESTHER : Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
PubMedSearch : Yang_2010_Colloids.Surf.B.Biointerfaces_78_351
PubMedID: 20399626

Title : Genome sequencing and analysis of the model grass Brachypodium distachyon. -
Author(s) : Vogel JP , Garvin DF , Mockler TC , Schmutz J , Rokhsar D , Bevan MW , Barry K , Lucas S , Harmon-Smith M , Lail K , Tice H , Grimwood J , McKenzie N , Huo N , Gu YQ , Lazo GR , Anderson OD , You FM , Luo MC , Dvorak J , Wright J , Febrer M , Idziak D , Hasterok R , Lindquist E , Wang M , Fox SE , Priest HD , Filichkin SA , Givan SA , Bryant DW , Chang JH , Wu H , Wu W , Hsia AP , Schnable PS , Kalyanaraman A , Barbazuk B , Michael TP , Hazen SP , Bragg JN , Laudencia-Chingcuanco D , Weng Y , Haberer G , Spannagl M , Mayer K , Rattei T , Mitros T , Lee SJ , Rose JK , Mueller LA , York TL , Wicker T , Buchmann JP , Tanskanen J , Schulman AH , Gundlach H , Bevan M , de Oliveira AC , Maia Lda C , Belknap W , Jiang N , Lai J , Zhu L , Ma J , Sun C , Pritham E , Salse J , Murat F , Abrouk M , Bruggmann R , Messing J , Fahlgren N , Sullivan CM , Carrington JC , Chapman EJ , May GD , Zhai J , Ganssmann M , Gurazada SG , German M , Meyers BC , Green PJ , Tyler L , Wu J , Thomson J , Chen S , Scheller HV , Harholt J , Ulvskov P , Kimbrel JA , Bartley LE , Cao P , Jung KH , Sharma MK , Vega-Sanchez M , Ronald P , Dardick CD , De Bodt S , Verelst W , Inz D , Heese M , Schnittger A , Yang X , Kalluri UC , Tuskan GA , Hua Z , Vierstra RD , Cui Y , Ouyang S , Sun Q , Liu Z , Yilmaz A , Grotewold E , Sibout R , Hematy K , Mouille G , Hofte H , Michael T , Pelloux J , O'Connor D , Schnable J , Rowe S , Harmon F , Cass CL , Sedbrook JC , Byrne ME , Walsh S , Higgins J , Li P , Brutnell T , Unver T , Budak H , Belcram H , Charles M , Chalhoub B , Baxter I
Ref : Nature , 463 :763 , 2010
PubMedID: 20148030
Gene_locus related to this paper: bradi-i1grm0 , bradi-i1gx82 , bradi-i1hb80 , bradi-i1hkv6 , bradi-i1hpu6 , bradi-i1i3e4 , bradi-i1i9i0 , bradi-i1i435 , bradi-i1ix93 , bradi-i1gsk6 , bradi-i1hk44 , bradi-i1hk45 , bradi-i1hnk7 , bradi-i1hsd5 , bradi-i1huy4 , bradi-i1huy9 , bradi-i1huz0 , bradi-i1gxx9 , bradi-i1hl25 , bradi-i1hcw7 , bradi-i1hyv6 , bradi-i1hyb5 , bradi-i1hvr8 , bradi-i1hmu2 , bradi-i1hf05 , bradi-i1gry7 , bradi-i1hf06 , bradi-i1i5z8 , bradi-i1icy3 , bradi-i1j1h3 , bradi-i1h1e3 , bradi-i1hvr9 , bradi-a0a0q3r7i7 , bradi-i1i377 , bradi-i1hjg5 , bradi-i1h3i9 , bradi-i1gsg5 , bradi-a0a0q3mph9 , bradi-i1h682 , bradi-a0a0q3lc91 , bradi-i1gx49 , bradi-i1i839 , bradi-a0a2k2dsp5 , bradi-i1gsb5

Title : Sequence analysis of pKF3-70 in Klebsiella pneumoniae: probable origin from R100-like plasmid of Escherichia coli - Yi_2010_PLoS.One_5_e8601
Author(s) : Yi H , Xi Y , Liu J , Wang J , Wu J , Xu T , Chen W , Chen B , Lin M , Wang H , Zhou M , Li J , Xu Z , Jin S , Bao Q
Ref : PLoS ONE , 5 :e8601 , 2010
Abstract : BACKGROUND: Klebsiella pneumoniae is a clinically significant species of bacterium which causes a variety of diseases. Clinical treatment of this bacterial infection is greatly hindered by the emergence of multidrug-resistant strains. The resistance is largely due to the acquisition of plasmids carrying drug-resistant as well as pathogenic genes, and its conjugal transfer facilitates the spread of resistant phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: The 70,057 bp plasmid pKF3-70, commonly found in Klebsiella pneumoniae, is composed of five main functional modules, including regions involved in replication, partition, conjugation, transfer leading, and variable regions. This plasmid is more similar to several Escherichia coli plasmids than any previously reported K. pneumoniae plasmids and pKF3-70 like plasmids share a common and conserved backbone sequence. The replication system of the pKF3-70 is 100% identical to that of RepFII plasmid R100 from E. coli. A beta-lactamase gene ctx-m-14 with its surrounding insertion elements (ISEcp1, truncated IS903 and a 20 bp inverted repeat sequence) may compose an active transposon which is directly bordered by two putative target repeats "ATTAC." CONCLUSIONS/SIGNIFICANCE: The K. pneumoniae plasmid pKF3-70 carries an extended-spectrum beta-lactamase gene, ctx-m-14. The conjugative characteristic makes it a widespread plasmid among genetically relevant genera which poses significant threat to public health.
ESTHER : Yi_2010_PLoS.One_5_e8601
PubMedSearch : Yi_2010_PLoS.One_5_e8601
PubMedID: 20066042

Title : Decoding state transitions in hippocampal oscillatory activity in mice - Dragomir_2010_Conf.Proc.IEEE.Eng.Med.Biol.Soc_2010_2822
Author(s) : Dragomir A , Akay YM , Wang K , Wu J , Akay M
Ref : Conf Proc IEEE Eng Med Biol Soc , 2010 :2822 , 2010
Abstract : Understanding the intricate dynamics of the hippocampal neural network, from which several types of neural oscillation rhythms arise, is an important step in uncovering the role of the hippocampus in the formation of memory. The different oscillation types commonly recorded in the hippocampus are thought to correspond to several states of neural network synchronization. Therefore, accurate segmentation and decoding of these underlying states provide useful insight on the rhythms' generation. In this study we use a framework based on Hidden Markov Models, coupled with a nonlinear dynamics method based on the Lempel-Ziv estimator. The method allows us to decode and model the neural state transitions. Network synchronization was induced by acute exposure to cholinergic agonist carbachol and oscillations were recorded from the Cornu Ammonis (CA1) region of the mouse hippocampus. Our results prove that deficits in cholinergic neuro-transmission found in triple transgenic mice (3xTG, as Alzheimer's disease animal model) lead to increased instability in the hippocampal neural network synchronization.
ESTHER : Dragomir_2010_Conf.Proc.IEEE.Eng.Med.Biol.Soc_2010_2822
PubMedSearch : Dragomir_2010_Conf.Proc.IEEE.Eng.Med.Biol.Soc_2010_2822
PubMedID: 21096221

Title : Characterization of Thermobifida fusca cutinase-carbohydrate-binding module fusion proteins and their potential application in bioscouring - Zhang_2010_Appl.Environ.Microbiol_76_6870
Author(s) : Zhang Y , Chen S , Xu M , Cavaco-Paulo A , Wu J , Chen J
Ref : Applied Environmental Microbiology , 76 :6870 , 2010
Abstract : Cutinase from Thermobifida fusca is thermally stable and has potential application in the bioscouring of cotton in the textile industry. In the present study, the carbohydrate-binding modules (CBMs) from T. fusca cellulase Cel6A (CBM(Cel6A)) and Cellulomonas fimi cellulase CenA (CBM(CenA)) were fused, separately, to the carboxyl terminus of T. fusca cutinase. Both fusion enzymes, cutinase-CBM(Cel6A) and cutinase-CBM(CenA), were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that both displayed similar catalytic properties and pH stabilities in response to T. fusca cutinase. In addition, both fusion proteins displayed an activity half-life of 53 h at their optimal temperature of 50 degrees C. Compared to T. fusca cutinase, in the absence of pectinase, the binding activity on cotton fiber was enhanced by 2% for cutinase-CBM(Cel6A) and by 28% for cutinase-CBM(CenA), whereas in the presence of pectinase, the binding activity was enhanced by 40% for the former and 45% for the latter. Notably, a dramatic increase of up to 3-fold was observed in the amount of released fatty acids from cotton fiber by both cutinase-CBM fusion proteins when acting in concert with pectinase. This is the first report of improving the scouring efficiency of cutinase by fusing it with CBM. The improvement in activity and the strong synergistic effect between the fusion proteins and pectinase suggest that they may have better applications in textile bioscouring than the native cutinase.
ESTHER : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedSearch : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedID: 20729325

Title : Characterization of [(3)H]CHIBA-1001 binding to alpha7 nicotinic acetylcholine receptors in the brain from rat, monkey, and human - Tanibuchi_2010_Brain.Res_1348_200
Author(s) : Tanibuchi Y , Wu J , Toyohara J , Fujita Y , Iyo M , Hashimoto K
Ref : Brain Research , 1348 :200 , 2010
Abstract : Accumulating evidence suggests that the alpha7 subtype of nicotinic acetylcholine receptors (nAChRs) plays a role in the pathophysiology of neuropsychiatric diseases, including schizophrenia and Alzheimer's disease. Currently, there are no suitable small molecule radioligands for alpha7 nAChRs in the brain, although [(125)I]alpha-bungarotoxin has been widely used as a radioligand for alpha7 nAChRs. In the present study, we characterized a new radioligand, 4-[(3)H]methylphenyl 2,5-diazabicyclo[3.2.2]nonane-2-carboxylate ([(3)H]CHIBA-1001), a derivative of the selective alpha7 nAChR agonist SSR180711, in brain membranes from rat, monkey, and human. Scatchard analysis revealed an apparent equilibrium dissociation constant (Kd) of 193.4nM in rat brain membranes at 4 degrees C, and the maximal number of binding sites (Bmax) was 346.2fmol/mg protein. The order of drugs for the inhibition of [(3)H]CHIBA-1001 binding to rat brain membranes is SSR180711>A-844606>MG624>epibatidine>DMAB>A-582941, suggesting a similarity of alpha7 nAChR pharmacological profiles. In contrast, alpha-bungarotoxin, MLA, and nicotine were found to be very weak. The distribution of [(3)H]CHIBA-1001 binding to crude membranes from dissected regions of rat, monkey, and human brain was different from that of [(125)I]alpha-bungarotoxin binding, suggesting that [(3)H]CHIBA-1001 binding sites may not be identical to [(125)I]alpha-bungarotoxin binding in the brain. In summary, [(3)H]CHIBA-1001 would be a useful radioligand for alpha7 nAChRs in the brains of rodents, non-human primates, and humans.
ESTHER : Tanibuchi_2010_Brain.Res_1348_200
PubMedSearch : Tanibuchi_2010_Brain.Res_1348_200
PubMedID: 20537987

Title : Understanding of nicotinic acetylcholine receptors -
Author(s) : Wu J
Ref : Acta Pharmacol Sin , 30 :653 , 2009
PubMedID: 19498413

Title : Nicotine modulates GABAergic transmission to dopaminergic neurons in substantia nigra pars compacta - Xiao_2009_Acta.Pharmacol.Sin_30_851
Author(s) : Xiao C , Yang KC , Zhou CY , Jin GZ , Wu J , Ye JH
Ref : Acta Pharmacol Sin , 30 :851 , 2009
Abstract : AIM: Dopaminergic neurons in the substantia nigra pars compacta (SNc) play important roles in motor control and drug addiction. As the major afferent, GABAergic innervation controls the activity of SNc dopaminergic neurons. Although it is clear that nicotine modulates SNc dopaminergic neurons by activating subtypes of somatodendritic nicotinic acetylcholine receptors (nAChRs), the detailed mechanisms of this activation remain to be addressed.
METHODS: In the current study, we recorded GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) from dissociated SNc dopaminergic neurons that were obtained using an enzyme-free procedure. These neurons preserved some functional terminals after isolation, including those that release GABA.
RESULTS: We found that both extra- and intra-cellular calcium modulates sIPSCs in these neurons. Furthermore, both nicotine and endogenous acetylcholine enhance the frequency of sIPSCs. Moreover, endogenous acetylcholine tonically facilitates sIPSC frequency, primarily by activating the alpha4beta2* nAChRs on the GABAergic terminals. CONCLUSION: Nicotine facilitates GABA release onto SNc dopaminergic neurons mainly via the activation of presynaptic alpha4beta2* nAChRs.
ESTHER : Xiao_2009_Acta.Pharmacol.Sin_30_851
PubMedSearch : Xiao_2009_Acta.Pharmacol.Sin_30_851
PubMedID: 19498424

Title : Impact of cigarette smoking in type 2 diabetes development - Xie_2009_Acta.Pharmacol.Sin_30_784
Author(s) : Xie XT , Liu Q , Wu J , Wakui M
Ref : Acta Pharmacol Sin , 30 :784 , 2009
Abstract : Many patients with type 2 diabetes mellitus (DM2) are at risk for micro and macro vascular complications, which could be observed in heavy smokers. Cigarette smoking increases the risk for type 2 diabetes incidence. Nicotine, acknowledged as the major pharmacologically active chemical in tobacco, is responsible for the association between cigarette smoking and development of diabetes. This minireview summarized recent studies on nicotine effects on insulin action and insulin secretion, indicating the impact of nicotine on type 2 diabetes development.
ESTHER : Xie_2009_Acta.Pharmacol.Sin_30_784
PubMedSearch : Xie_2009_Acta.Pharmacol.Sin_30_784
PubMedID: 19434055

Title : A novel nicotinic acetylcholine receptor subtype in basal forebrain cholinergic neurons with high sensitivity to amyloid peptides - Liu_2009_J.Neurosci_29_918
Author(s) : Liu Q , Huang Y , Xue F , Simard AR , DeChon J , Li G , Zhang J , Lucero L , Wang M , Sierks M , Hu G , Chang Y , Lukas RJ , Wu J
Ref : Journal of Neuroscience , 29 :918 , 2009
Abstract : Nicotinic acetylcholine receptors (nAChRs) containing alpha7 subunits are thought to assemble as homomers. alpha7-nAChR function has been implicated in learning and memory, and alterations of alpha7-nAChR have been found in patients with Alzheimer's disease (AD). Here we report findings consistent with a novel, naturally occurring nAChR subtype in rodent, basal forebrain cholinergic neurons. In these cells, alpha7 subunits are coexpressed, colocalize, and coassemble with beta2 subunit(s). Compared with homomeric alpha7-nAChRs from ventral tegmental area neurons, functional, presumably heteromeric alpha7beta2-nAChRs on cholinergic neurons freshly dissociated from medial septum/diagonal band (MS/DB) exhibit relatively slow kinetics of whole-cell current responses to nicotinic agonists and are more sensitive to the beta2 subunit-containing nAChR-selective antagonist, dihydro-beta-erythroidine (DHbetaE). Interestingly, presumed, heteromeric alpha7beta2-nAChRs are highly sensitive to functional inhibition by pathologically relevant concentrations of oligomeric, but not monomeric or fibrillar, forms of amyloid beta(1-42) (Abeta(1-42)). Slow whole-cell current kinetics, sensitivity to DHbetaE, and specific antagonism by oligomeric Abeta(1-42) also are characteristics of heteromeric alpha7beta2-nAChRs, but not of homomeric alpha7-nAChRs, heterologously expressed in Xenopus oocytes. Moreover, choline-induced currents have faster kinetics and less sensitivity to Abeta when elicited from MS/DB neurons derived from nAChR beta2 subunit knock-out mice rather than from wild-type mice. The presence of novel, functional, heteromeric alpha7beta2-nAChRs on basal forebrain cholinergic neurons and their high sensitivity to blockade by low concentrations of oligomeric Abeta(1-42) suggests possible mechanisms for deficits in cholinergic signaling that could occur early in the etiopathogenesis of AD and might be targeted by disease therapies.
ESTHER : Liu_2009_J.Neurosci_29_918
PubMedSearch : Liu_2009_J.Neurosci_29_918
PubMedID: 19176801

Title : Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons - Yang_2009_J.Physiol_587_345
Author(s) : Yang K , Hu J , Lucero L , Liu Q , Zheng C , Zhen X , Jin G , Lukas RJ , Wu J
Ref : Journal of Physiology , 587 :345 , 2009
Abstract : Dopaminergic (DAergic) neuronal activity in the ventral tegmental area (VTA) is thought to contribute generally to pleasure, reward, and drug reinforcement and has been implicated in nicotine dependence. nAChRs expressed in the VTA exhibit diverse subunit compositions, but the functional and pharmacological properties are largely unknown. Here, using patch-clamp recordings in single DAergic neurons freshly dissociated from rat VTA, we clarified three functional subtypes of nAChRs (termed ID, IID and IIID receptors) based on whole-cell current kinetics and pharmacology. Kinetic analysis demonstrated that comparing to ID, IID receptor-mediated current had faster activation and decay constant and IIID receptor-mediated current had larger current density. Pharmacologically, ID receptor-mediated current was sensitive to the alpha4beta2-nAChR agonist RJR-2403 and antagonist dihydro-beta-erythroidine (DHbetaE); IID receptor-mediated current was sensitive to the selective alpha7-nAChR agonist choline and antagonist methyllycaconitine (MLA); while IIID receptor-mediated current was sensitive to the beta4-containing nAChR agonist cytisine and antagonist mecamylamine (MEC). The agonist concentration-response relationships demonstrated that IID receptor-mediated current exhibited the highest EC(50) value compared to ID and IIID receptors, suggesting a relatively low agonist affinity of type IID receptors. These results suggest that the type ID, IID and IIID nAChR-mediated currents are predominately mediated by activation of alpha4beta2-nAChR, alpha7-nAChR and a novel nAChR subtype(s), respectively. Collectively, these findings indicate that the VTA DAergic neurons express diversity and multiplicity of functional nAChR subtypes. Interestingly, each DAergic neuron predominantly expresses only one particularly functional nAChR subtype, which may have distinct but important roles in regulation of VTA DA neuronal function, DA transmission and nicotine dependence.
ESTHER : Yang_2009_J.Physiol_587_345
PubMedSearch : Yang_2009_J.Physiol_587_345
PubMedID: 19047205

Title : Mysterious alpha6-containing nAChRs: function, pharmacology, and pathophysiology - Yang_2009_Acta.Pharmacol.Sin_30_740
Author(s) : Yang KC , Jin GZ , Wu J
Ref : Acta Pharmacol Sin , 30 :740 , 2009
Abstract : Neuronal nicotinic acetylcholine receptors (nAChRs) are the superfamily of ligand-gated ion channels and widely expressed throughout the central and peripheral nervous systems. nAChRs play crucial roles in modulating a wide range of higher cognitive functions by mediating presynaptic, postsynaptic, and extrasynaptic signaling. Thus far, nine alpha (alpha2-alpha10) and three beta (beta2, beta3, and beta4) subunits have been identified in the CNS, and these subunits assemble to form a diversity of functional nAChRs. Although alpha4beta2- and alpha7-nAChRs are the two major functional nAChR types in the CNS, alpha6*-nAChRs are abundantly expressed in the midbrain dopaminergic (DAergic) system, including mesocorticolimbic and nigrostriatal pathways, and particularly present in presynaptic nerve terminals. Recently, functional and pharmacological profiles of alpha6*-nAChRs have been assessed with the use of alpha6 subunit blockers such as alpha-conotoxin MII and PIA, and also by using alpha6 subunit knockout mice. By modulating DA release in the nucleus accumbens (NAc) and modulating GABA release onto DAergic neurons in the ventral tegmental area (VTA), alpha6*-nAChRs may play important roles in the mediation of nicotine reward and addiction. Furthermore, alpha6*-nAChRs in the nigrostriatal DAergic system may be promising targets for selective preventative treatment of Parkinson's disease (PD). Thus, alpha6*-nAChRs may hold promise for future clinical treatment of human disorders, such as nicotine addiction and PD. In this review, we mainly focus on the recent advances in the understanding of alpha6*-nAChR function, pharmacology and pathophysiology.
ESTHER : Yang_2009_Acta.Pharmacol.Sin_30_740
PubMedSearch : Yang_2009_Acta.Pharmacol.Sin_30_740
PubMedID: 19498417

Title : Kinetics of desensitization and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors stably expressed in SH-EP1 cells - Yu_2009_Acta.Pharmacol.Sin_30_805
Author(s) : Yu KD , Liu Q , Wu J , Lukas RJ
Ref : Acta Pharmacol Sin , 30 :805 , 2009
Abstract : AIM: Studies were conducted to define the kinetics of the onset of and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors (nAChR) heterologously expressed in the SH-EP1 human epithelial cell line.
METHODS: Whole-cell patch clamp recordings were performed to evaluate alpha4beta2-nAChR currents.
RESULTS: Application of 0.1 micromol/L nicotine or 1 mmol/L acetylcholine (ACh) for 1 s or longer induced two phases, with time constants of approximately 70 and approximately 700 ms, for the onset of alpha4beta2-nAChR desensitization. For a given duration of agonist exposure, recovery from desensitization induced by nicotine was slower than recovery from ACh-induced desensitization. Comparisons with published reports indicate that time constants for the recovery of alpha4beta2-nAChRs from desensitization are smaller than those for the recovery of human muscle-type nAChRs(1) from desensitization produced by the same concentrations and durations of exposure to an agonist. Moreover, the extent of human alpha4beta2-nAChR desensitization and rate of recovery are the same, regardless of whether they are measured using whole-cell recording or based on published findings(2) using isotopic ion flux assays; this equality demonstrates the equivalent legitimacy of these techniques in the evaluation of nAChR desensitization. Perhaps most significantly, recovery from desensitization also was best fit to a biphasic process. Regardless of whether it was fit to single or double exponentials, however, half-times for recovery from desensitization grew progressively longer with an increased duration of agonist exposure during the desensitizing pulse. CONCLUSION: These findings indicate the existence of alpha4beta2-nAChRs in many distinctive states of desensitization, as well as the induction of progressively deeper states of desensitization with the increased duration of agonist exposure.
ESTHER : Yu_2009_Acta.Pharmacol.Sin_30_805
PubMedSearch : Yu_2009_Acta.Pharmacol.Sin_30_805
PubMedID: 19498421

Title : U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH-EP1 cell line - Zheng_2009_J.Neurochem_108_1526
Author(s) : Zheng C , Wang MY , Liu Q , Wakui M , Whiteaker P , Lukas RJ , Wu J
Ref : Journal of Neurochemistry , 108 :1526 , 2009
Abstract : In this study, we evaluate the effects of (3beta)-3-[2-(diethylamino)ethoxy]androst-5-en-17-one dihydrochloride (U18666A), a cholesterol synthesis/transporter inhibitor, on selected human neuronal nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the SH-EP1 cell line using whole-cell patch-clamp recordings. The results indicate that with 2-min pretreatment, U18666A inhibited different nAChR subtypes with a rank-order of potency (IC(50) of whole-cell peak current): alpha4beta2 (8.0 +/- 3.0 nM) > alpha3beta2 (1.7 +/- 0.4 microM) > alpha4beta4 (26 +/- 7.2 microM) > alpha7 (> 100 microM), suggesting this compound is more selective to alpha4beta2-nAChRs. Thus, the pharmacological profiles and mechanisms of U18666A acting on alpha4beta2-nAChRs were investigated in detail. U18666A suppresses both peak and steady state components of whole-cell currents mediated by human alpha4beta2-nAChRs in response to nicotine. In nicotine-induced concentration-response curves, U18666A reduces nicotine-induced current at maximally effective agonist concentrations without influencing nicotine's EC(50) value, suggesting a non-competitive inhibition. U18666A-induced inhibition of nAChR function is concentration-, voltage-, and use-dependent, suggesting an open channel block. Taken into consideration of approximately 10 000-fold enhancement of the potency of U18666A after 2-min pre-treatment, this compound also likely inhibits alpha4beta2-nAChRs through a close channel block. In addition, the U18666A-induced inhibition in alpha4beta2-nAChRs is not mediated by either increased receptor endocytosis or altered cell cholesterol. These data indicate that U18666A is a potent antagonist of alpha4beta2-nAChRs and may be useful as a tool in the functional characterization and pharmacological profiling of nAChRs, as well as a potential candidate for smoking cessation.
ESTHER : Zheng_2009_J.Neurochem_108_1526
PubMedSearch : Zheng_2009_J.Neurochem_108_1526
PubMedID: 19183258

Title : Defining pre-synaptic nicotinic receptors regulated by beta amyloid in mouse cortex and hippocampus with receptor null mutants - Mehta_2009_J.Neurochem_109_1452
Author(s) : Mehta TK , Dougherty JJ , Wu J , Choi CH , Khan GM , Nichols RA
Ref : Journal of Neurochemistry , 109 :1452 , 2009
Abstract : Disruption of neuronal signaling by soluble beta-amyloid has been implicated in deficits in short-term recall in the early stages of Alzheimer's disease. One potential target for beta-amyloid is the synapse, with evidence for differential interaction with both pre- and post-synaptic elements. Our previous work revealed an agonist-like action of soluble beta-amyloid (pM to nM) on isolated pre-synaptic terminals to increase [Ca(2+)]i, with apparent involvement of pre-synaptic nicotinic receptors. To directly establish the role of nicotinic receptors in pre-synaptic Ca(2+) regulation, we investigated the pre-synaptic action of beta-amyloid on terminals isolated from mice harboring either beta2 or alpha7 nicotinic receptor null mutants (knockouts). Average pre-synaptic responses to beta-amyloid in hippocampal terminals of alpha7 knockout mice were unchanged, whereas responses in hippocampal terminals from beta2 knockout mice were strongly attenuated. In contrast, pre-synaptic responses to soluble beta-amyloid were strongly attenuated in cortical terminals from alpha7 knockout mice but were moderately attenuated in cortical terminals from beta2 knockout mice. The latter responses, having distinct kinetics, were completely blocked by alpha-bungarotoxin. The use of receptor null mutants thus permitted direct demonstration of the involvement of specific nicotinic receptors in pre-synaptic Ca(2+) regulation by soluble beta-amyloid, and also indicated differential neuromodulation by beta-amyloid of synapses in hippocampus and cortex.
ESTHER : Mehta_2009_J.Neurochem_109_1452
PubMedSearch : Mehta_2009_J.Neurochem_109_1452
PubMedID: 19457164

Title : Cutinase-like proteins of Mycobacterium tuberculosis: characterization of their variable enzymatic functions and active site identification - West_2009_FASEB.J_23_1694
Author(s) : West NP , Chow FM , Randall EJ , Wu J , Chen J , Ribeiro JM , Britton WJ
Ref : FASEB Journal , 23 :1694 , 2009
Abstract : Discovery and characterization of novel secreted enzymes of Mycobacterium tuberculosis are important for understanding the pathogenesis of one of the most important human bacterial pathogens. The proteome of M. tuberculosis contains over 400 potentially secreted proteins, the majority of which are uncharacterized. A family of seven cutinase-like proteins (CULPs) was identified by bioinformatic analysis, expressed and purified from Escherichia coli, and characterized in terms of their enzymatic activities. These studies revealed a functional diversity of enzyme classes based on differential preferences for substrate chain length. One member, Culp1, exhibited strong esterase activity, 40-fold higher than that of Culp6, which had strong activity as a lipase. Another, Culp4, performed moderately as an esterase and weakly as a lipase. Culp6 lipase activity was optimal above pH 7.0, and fully maintained to pH 8.5. None of the CULP members exhibited cutinase activity. Site-directed mutagenesis of each residue of the putative catalytic triad in Culp6 confirmed that each was essential for activity toward all fatty acid chain lengths of nitrophenyl esters and lipolytic function. Culp1 and Culp2 were present only in culture supernatants of M. tuberculosis, while Culp6, which is putatively essential for mycobacterial growth, was retained in the cell wall, suggesting the proteins play distinct roles in mycobacterial biology.
ESTHER : West_2009_FASEB.J_23_1694
PubMedSearch : West_2009_FASEB.J_23_1694
PubMedID: 19225166
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-RV1758 , myctu-RV3452 , myctu-RV3724 , myctu-Rv3802c

Title : An organophosphorus hapten used in the preparation of monoclonal antibody and as an active immunization vaccine in the detoxication of soman poisoning - Jia_2009_Toxicol.Lett_187_45
Author(s) : Jia P , Wang Y , Yu M , Wu J , Yang R , Zhao Y , Zhou L
Ref : Toxicol Lett , 187 :45 , 2009
Abstract : Soman is an organophosphorus neurotoxin which inhibits the activity of acetylcholinesterase (AChE). The goal of this work was to find out whether antibodies against an organophosphorus hapten could protect mice from soman toxicity. An organophosphorus hapten P6 was synthesized. Its chemical conjugates with limulus polyphemus hemocyanin and bovine serum albumin were used as immune antigen (P6-LPH) and detection antigen (P6-BSA), respectively. Eight hybridoma cell lines secreting monoclonal antibodies (Mabs) were established. The binding reactivities of Mabs with P6 and soman were determined by competitive inhibition enzyme immunoassay (CIEIA). All antibodies recognized P6 and four of them (2C10, 3G1, 3B9 and 3C11) combined with soman. The IC(50) was 10(-6.5) to 10(-5.3)mol/l for P6 and 10(-5) to 10(-3.5)mol/l for soman. Furthermore, Mab 3G1 reduced the inhibition of AChE activity by soman in vitro. When soman was pre-incubated with Mabs before being injected into mice, soman potency was reduced, indicating that Mabs could protect mice from soman toxicity. In an active immunization regimen, mice immunized with P6-LPH and challenged with 0.15mg/kg soman injected subcutaneously, had fewer signs of intoxication and a higher survival rate compared with control mice. These results demonstrate that the anti-soman antibodies have proper characteristics as scavengers in the detoxication of soman poisoning.
ESTHER : Jia_2009_Toxicol.Lett_187_45
PubMedSearch : Jia_2009_Toxicol.Lett_187_45
PubMedID: 19429243

Title : RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis - Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
Author(s) : Gong X , Ye W , Zhou H , Ren X , Li Z , Zhou W , Wu J , Gong Y , Ouyang Q , Zhao X , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :883 , 2009
Abstract : Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.
ESTHER : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedSearch : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedID: 19902122

Title : The genome of the cucumber, Cucumis sativus L - Huang_2009_Nat.Genet_41_1275
Author(s) : Huang S , Li R , Zhang Z , Li L , Gu X , Fan W , Lucas WJ , Wang X , Xie B , Ni P , Ren Y , Zhu H , Li J , Lin K , Jin W , Fei Z , Li G , Staub J , Kilian A , van der Vossen EA , Wu Y , Guo J , He J , Jia Z , Tian G , Lu Y , Ruan J , Qian W , Wang M , Huang Q , Li B , Xuan Z , Cao J , Asan , Wu Z , Zhang J , Cai Q , Bai Y , Zhao B , Han Y , Li Y , Li X , Wang S , Shi Q , Liu S , Cho WK , Kim JY , Xu Y , Heller-Uszynska K , Miao H , Cheng Z , Zhang S , Wu J , Yang Y , Kang H , Li M , Liang H , Ren X , Shi Z , Wen M , Jian M , Yang H , Zhang G , Yang Z , Chen R , Ma L , Liu H , Zhou Y , Zhao J , Fang X , Fang L , Liu D , Zheng H , Zhang Y , Qin N , Li Z , Yang G , Yang S , Bolund L , Kristiansen K , Li S , Zhang X , Wang J , Sun R , Zhang B , Jiang S , Du Y
Ref : Nat Genet , 41 :1275 , 2009
Abstract : Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.
ESTHER : Huang_2009_Nat.Genet_41_1275
PubMedSearch : Huang_2009_Nat.Genet_41_1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5 , cucsa-a0a0a0lnt6 , cucsa-a0a0a0kpn7 , cucsa-a0a0a0lvt9 , cucsa-a0a0a0kdx8 , cucsa-a0a0a0m228 , cucsa-a0a0a0kz31 , cucsa-a0a0a0k5t5 , cucsa-a0a0a0kfs7 , cucsa-a0a0a0kjj7 , cucsa-a0a0a0kzs7 , cucsa-a0a0a0l0a6 , cucsa-a0a0a0l4w4 , cucsa-a0a0a0lpz0 , cucsa-a0a0a0ls66

Title : Isolation and Characterizat