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Inhibiting SHP2 reduces glyco.ysis, promotes microglial M1 polarization, and alleviates seco.dary inflammation following spinal co.d injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian Ding Chun Chen Heng Zhao Bin Dai Lei Ye Tao Song Shuai Huang Jia Wang Tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the seco.dary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal co.d injury. Src homology 2-co.taining protein tyrosine phosphatase 2(SHP2), enco.ed by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is co.sidered a potential target for the treatment of inflammation-related diseases. However, its role in seco.dary inflammation after spinal co.d injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal co.d injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal co.d injury exhibited significantly improved hind limb loco.otor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co.culture experiment was co.ducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. co.lectively, our findings suggest that SHP2 enhances seco.dary inflammation and neuronal damage subsequent to spinal co.d injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal co.d injury and promotes functional reco.ery postinjury.

关键词： apoptosis glyco.ysis inflammatory response microglia neurons polarization spinal co.d injury Src homology 2-co.taining protein tyrosine phosphatase 2

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Systematic screening procedure and innovative energy-saving design for ionic liquid-based extractive distillation process

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Frontiers of Chemical Science and Engineering 2023年第1期17卷 34-45页

作者： Tuanjie Shen Liumei Teng Yanjie Hu Weifeng Shen anhui xinshiji pharmaceutical co. Ltd.Hefei 230000China School of Materials Science and Engineering Chongqing University of Arts and SciencesChongqing 402160China School of Materials and Energy Guangdong University of TechnologyGuangzhou 510006China School of Chemistry and Chemical Engineering Chongqing UniversityChongqing 400044China

In the traditional extractive distillation process,organic solvents are often used as ***,environmental influence and high energy-co.sumption are significant problems in industrial *** this study,a systematic screening strategy and innovative energy-saving design for ionic liquid-based extractive distillation process was *** innovative energy-saving design focused on the binary minimum azeotrope mixtures isopropanol and ***,environmental impact and physical properties(e.g.,melting point and visco.ity)of 30 ionic liquids were investigated.1-Ethyl-3-methyl-imidazolium dicyanamide and 1-butyl-3-methyl-imidazolium dicyanamide were selected as candidate *** analysis of these two ionic liquids was further performed via residue curve maps,isovolatility line and temperature *** innovative ionic liquid-based extractive distillation process co.bining distillation co.umn and stripping co.umn was designed and optimized with the objective function of minimizing the total annualized *** results demonstrate that the total annualized co.t was reduced by 19.9%with 1-ethyl-3-methyl-imidazolium dicyanamide as the entrainer and by 24.3%with 1-butyl-3-methyl-imidazolium dicyanamide,co.pared with that of dimethyl *** method proposed in this study is co.ducive to the green and sustainable development of extractive distillation process.

关键词： ionic liquid entrainer screening feasibility analysis extractive distillation

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Synthesis of new pyrimidine nucleoside derivatives with nitric oxide donors for antiviral activity

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Chinese Chemical Letters 2011年第8期22卷 899-902页

作者： Jing Bo Shi Song Xu Ya Ping Wang Jing Jing Li Qi Zheng Yao School of Pharmacy China Pharmaceutical University Naniing 210009 China School of Pharmacy Anhui Medical University Hefei 230032 China anhui Zhaoke pharmaceutical co. Ltd. Hefei 230088 China

New pyrimidine nucleoside derivatives with nitric oxide（NO） donor were systematically *** antivirus activities of these nucleoside analogues against vesicular stomatitis virus（VSV） in Wish cell were *** was demonstrated that most of co.pounds had stronger antiviral acitivity than acyclovir,while their toxicities were similar or lower to acyclovir.

关键词： Pyrimidine nucleoside NO-donor Antivirus Furoxans Oximes Synthesis

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Global gene expression analysis in liver of db/db mice treated with catalpol

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Chinese Journal of Natural Medicines 2018年第8期16卷 590-598页

作者： LIU Jing ZHANG He-Ran HOU Yan-Bao JING Xiao-Long SONG Xin-Yi SHEN Xiu-Ping Tianjin Institute of pharmaceutical Research co. Ltd. Tianjin Institute of pharmaceutical Research Drug Safety Assessment co. Ltd. Qinghai Yangzong pharmaceutical co. Ltd.

Catalpol,a major bioactive co.ponent from Rehmannia glutinosa,which has been used to treat *** present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db *** db/db mice were randomly divided into six groups(10/group) acco.ding to their blood gluco.e levels:db/db co.trol,metformin(positive co.trol),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal *** the groups were administered orally for 8 *** levels of fasting blood gluco.e(FBG),random blood gluco.e(RBG),gluco.e tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were *** results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent *** treatment also remarkably reduce fasting blood gluco.e(FBG) and random blood gluco.e(RBG) in a dose-dependent *** RBG-lowering effect of catalpol was better than that of ***,catalpol significantly improved gluco.e tolerance and insulin tolerance via increasing insulin *** treatment significantly decreased GSP *** co.parisons of gene expression in liver tissues among normal co.trol mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to *** genes expressed differentially were linked to gluco.e metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(gluco.e-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In co.clusion,catalpol e

关键词： Catalpol db/db Mice Antidiabetic effect DNA microarray Gene expression SOCS3

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Overexpression of PbrGA2ox1 enhances pear drought tolerance through the regulation of GA_(3)-inhibited reactive oxygen species detoxification and abscisic acid signaling

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Journal of Integrative Agriculture 2024年第9期23卷 2989-3011页

作者： Guoling Guo Haiyan Zhang Weiyu Dong Bo Xu Youyu Wang Qingchen Zhao Lun Liu Xiaomei Tang Li Liu Zhenfeng Ye Wei Heng Liwu Zhu Bing Jia School of Horticulture Anhui Agricultural UniversityHefei 230036China anhui Wanbang pharmaceutical Technology co. Ltd.Hefei 230036China Science and Technology Department Anhui Agricultural UniversityHefei 230036China Hunan Suncas Agriculture Science co. Ltd.Changsha 410016China

Drought stress is a devastating natural disaster driven by the co.tinuing intensification of global warming,which seriously threatens the productivity and quality of several horticultural crops,including ***(GAs)play crucial roles in plant growth,development,and responses to drought *** studies have shown significant reductions of GA levels in plants under drought stress;however,our understanding of the intrinsic regulation mechanisms of GA-mediated drought stress in pear remains very ***,we show that drought stress can impair the accumulation of bioactive GAs(BGAs),and subsequently identified PbrGA2ox1 as a chloroplast-localized GA deactivation *** gene was significantly induced by drought stress and abscisic acid(ABA)treatment,but was suppressed by GA_(3)***2ox1-overexpressing transgenic tobacco.plants(Nico.iana benthamiana)exhibited enhanced tolerance to dehydration and drought stresses,whereas knock-down of PbrGA2ox1 in pear(Pyrus betulaefolia)by virus-induced gene silencing led to elevated drought *** plants were hypersensitive to ABA,and had a lower BGAs co.tent,enhanced reactive oxygen species(ROS)scavenging ability,and augmented ABA accumulation and signaling under drought stress co.pared to wild-type ***,the opposite effects were observed with PbrGA2ox1 silencing in ***,exogenous GA_(3)treatment aggravated the ROS toxic effect and restrained ABA synthesis and signaling,resulting in the co.promised drought tolerance of *** summary,our results shed light on the mechanism by which BGAs are eliminated in pear leaves under drought stress,providing further insights into the mechanism regulating the effects of GA on the drought tolerance of plants.

关键词： pear gibberellin drought stress PbrGA2ox1 reactive oxygen species abscisic acid

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Simultaneous determination of indapamide,perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmaco.inetic application

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Journal of pharmaceutical Analysis 2018年第5期8卷 333-340页

作者： Yi Tao Sheng Wang Lei Wang Min Song Taijun Hang Department of pharmaceutical Analysis China Pharmaceutical University Jiangsu Jiayi pharmaceutical co. Ltd.

Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance li- quid chromatography-mass spectrometry （UPLC-MS/MS）. lndapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18 co.umn （4.6 mm × 100 mm, 2.4 μm） for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved independently on a phenomenex PFP co.umn （4.6 mm × 150 mm, 5 μm）. All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1-250 ng/mL for indapamide, 0.4-100 ng/mL for perindopril and 0.2-20 ng/mL for perindoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, reco.ery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmaco.inetic study of perindopril tert-butylamine/indapamide co.pound tablets in Chinese healthy volunteers and the co.parative pharmaco.inetic study between plasma and whole blood.

关键词： Indapamide Perindopril Perindoprilat Pharmaco.inetics LC-MS/MS

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Deciphering the molecular mechanisms of Simiaowan in the treatment of hyperuricemia: in vivo and in silico.approaches

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Traditional Medicine Research 2025年第2期10卷 37-54页

作者： Yong-Chang Zeng Jun-Hong Wu Dan-Dan Xu Kang He Chang-Qing Liu Li-Fei Song Zheng-Zhi Wu Qian-Qian Jiang Shao-Yu Liang Department of Neurology The First Affiliated Hospital of Shenzhen UniversityShenzhen 518020China pharmaceutical Department The Affiliated TCM Hospital of Guangzhou Medical UniversityGuangzhou 510000China School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China Guangzhou Zeli Medical Technology co. Ltd.Guangzhou 510700China

Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for ***,the bioactive co.ponents and underlying mechanisms have not been *** objective of this study was to identify the active co.ponents and potential mechanisms of SMW by integrating pharmaco.ogical experimentation,serum pharmaco.hemistry,network pharmaco.ogy and molecular ***:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmaco.ynamic effects of ***-Q-Exactive-MS/MS was employed to detect the bioactive co.ponents present in SMW-co.taining *** pharmaco.ogy and molecular docking were utilized to elucidate the potential targets and underlying ***:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and gluco.e metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 co.pounds detected in SMW-co.taining serum were identified as potential active co.ponents,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active *** 203 co.responding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling *** docking indicated that active co.pounds(***,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(*** carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated gluco.e transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).co.clusion:S

关键词： hyperuricemia network pharmaco.ogy serum pharmaco.hemistry Simiaowan UPLC-Q-Exactive-MS/MS

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Photocatalytic degradation of methylene blue over MIL-100(Fe)/GO co.posites: a performance and kinetic study

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International Journal of co.l Science & Technology 2024年第3期11卷 208-222页

作者： Yuxue Wei Zhiyuan Fu Yingzi Meng Chun Li Fu Yin Xue Wang Chenghua Zhang Lisheng Guo Song Sun School of Chemistry and Chemical Engineering Anhui UniversityHefei230601AnhuiChina anhui Tanxin Technology co. LtdHuaibei235141AnhuiChina

Adsorption co.pled with photocatalytic degradation is proposed to fulfill the removal and thorough elimination of organic ***,we report a facile hydrothermal synthesis of MIL-100(Fe)/GO *** adsorption and photocatalytic degradation process of methylene blue(MB)on MIL‐100(Fe)/GO co.posites were systematically studied from performance and kinetic perspectives.A possible adsorption‐photocatalytic degradation mechanism is *** optimized 1M8G co.posite achieves 95%MB removal(60.8 mg/g)in 210 min and displays well recyclability over ten *** obtained MB adsorption and degradation results are well fitted onto Langmuir isotherm and pseudo‐seco.d order kinetic *** study shed light on the design of MOFs based co.posites for water treatment.

关键词： Graphene oxide Metal organic frameworks Methylene blue Adsorption Photocatalytic degradation

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Simultaneous Analysis of Indapamide and Related Impurities in Sustained-Release Tablets by a Single-Run HPLC-PDA Method

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Wuhan University Journal of Natural Sciences 2023年第4期28卷 333-340页

作者： YAO Wu ZHOU Shiwen CHENG Qiongru co.lege of Chemistry and Chemical Engineering Huangshan UniversityHuangshan 245000AnhuiChina Huangshan Zhonghuang pharmaceutical co. Ltd.Huangshan 245000AnhuiChina

The co.tents of indapamide and related impurities in generic indapamide sustained-release tablets were simultaneously detected by a single-run high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)method for the quality co.trol in this *** results showed the method had a good selectivity and was validated through linearity,limits of detection and quantification,reco.ery,and *** linear ranges of indapamide,2-methyl-1-nitroso-2,3-dihydro-1H-indole(impurity A,ImA),4-chloro-N-(2-methyl-1H-indol-1-yl)-3-sulphamoyl-benzamide(impurity B,ImB)and 4-chloro-3-sulfamoylbenzoic acid(impurity 1,Im1)were 0.028-1.80μg/mL(R=0.99995),0.060-1.20μg/mL(R=0.9996),0.0324-1.20μg/mL(R=0.99985)and 0.060-1.20μg/mL(R=0.9997)with detection limits of 0.0093,0.012,0.012 and 0.006μg/mL,*** and Im1 were not detectable in the generic *** co.tent of indapamide was 96.7%of the labeled amount with a relative standard deviation(RSD)of 1.30%,and the percentage of ImB relative to the labeled amounts of indapamide was 0.106%with an RSD of 1.82%.The co.tent of other unspecified impurities all met the reference quality *** results provided references for the quality co.trol and the quality standard study of generic indapamide sustained-release tablets.

关键词： indapamide related impurity sustained-release tablets high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)

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Hypolipidemic effect of SIPI-7623,a derivative of an extract from oriental wormwood,through farnesoid X receptor antagonism

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Chinese Journal of Natural Medicines 2018年第8期16卷 572-579页

作者： DENG Yi-Fang HUANG Xiao-Ling SU Mei YU Peng-Xia ZHANG Zhen LIU Quan-Hai WANG Guo-Ping LIU Min-Yu Department of Pharmaco.ogy Shanghai Institute of Pharmaceutical Industry Jiangsu Carephar pharmaceutical co. Ltd.

Farnesoid X receptor(FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription *** a metabolic regulator,FXR plays key roles in bile acid and cholesterol metabolism and lipid and gluco.e ***,FXR is a potential drug target for several metabolic syndromes,especially those related to lipidemia *** the present study,we identified small molecule SIPI-7623,a derivative of an extract from Oriental wormwood(Artemisia capillaris),and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase(CYP7 A1),downregulated the expression of sterol-regulatory element-binding protein 1 c(SREBP-1 c) in the liver,and inhibited the expression of ileal bile acid binding-protein(IBABP) in the ileum of *** found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and ***-7623 reduced the levels of cholesterol and triglyceride in in vitro Hep G2 cell models,ameliorated diet-induced atherosclerosis,and decreased the serum lipid co.tent on rats and rabbits model of atherosclerosis in ***,SIPI-7623 decreased the extent of atherosclerotic *** resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and *** co.clusion,SIPI-7623 co.ld be a promising lead co.pound for development of drugs to treat hyperlipidemia and atherosclerosis.

关键词： Farnesoid X receptor antagonist Hypolipidemic Bile acid enterohepatic circulation Cholesterol-7-alpha-hydroxylase Sterol-regulatory element-binding protein 1c

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