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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： ying xia Ming Sun Hai Huang Wei-Lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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Modulation of starch synthesis in Arabidopsis via phytochrome B-mediated light signal

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Journal of Integrative Plant Biology 2024年第5期66卷 973-985页

作者： Qingbiao Shi ying xia Na Xue Qibin Wang Qing Tao Mingjing Li Di Xu xiaofei Wang Fanying Kong Haisen Zhang Gang Li National Key Laboratory of Wheat Improvement College of Life SciencesShandong Agricultural UniversityTai'an 271018China National Key Laboratory of Wheat Improvement College of AgronomyShandong Agricultural UniversityTai'an 271018China

Starch is a major storage carbohydrate in plants and is critical in crop yield and quality.Starch synthesis is intricately regulated by internal metabolic processes and external environmental cues;however,the precise molecular mechanisms governing this process remain largely unknown.In this study,we revealed that high red to far-red(high R:FR)light significantly induces the synthesis of leaf starch and the expression of synthesis-related genes,whereas low R:FR light suppress these processes.Arabidopsis phytochrome B(phyB),the primary R and FR photoreceptor,was identified as a critical positive regulator in this process.Downstream of phyB,basic leucine zipper transcription factor ELONGATED HYPOCOTYL5(HY5)was found to enhance starch synthesis,whereas the basic helix-loop-helix transcription factors PHYTOCHROME INTERACTING FACTORs(PIF3,PIF4,and PIF5)inhibit starch synthesis in Arabidopsis leaves.Notably,HY5 and PIFs directly compete for binding to a shared G-box cis-element in the promoter region of genes encoding starch synthases GBSS,SS3,and SS4,which leads to antagonistic regulation of their expression and,consequently,starch synthesis.Our findings highlight the vital role of phyB in enhancing starch synthesis by stabilizing HY5 and facilitating PIFs degradation under high R:FR light conditions.Conversely,under low R:FR light,PIFs predominantly inhibit starch synthesis.This study provides insight into the physiological and molecular functions of phyB and its downstream transcription factors HY5 and PIFs in starch synthesis regulation,shedding light on the regulatory mechanism by which plants synchronize dynamic light signals with metabolic cues to module starch synthesis.

关键词： Arabidopsis thaliana HY5 light signal phyB PIFs starch synthesis

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Lycorine derivative effectively inhibits the replication of coronaviruses both in vitro and in vivo

hLife

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hLife 2024年第2期2卷 75-87页

作者： Liang Shen Jianzhong Zhao ying xia Junjie Lu Jiali Sun Jian Tang Hui Xing Lijuan Yin Yang Yang Chunhua Wang Department of Clinical Laboratory Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceHubeiChina Shenzhen Key Laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyGuangdongChina Department of Clinical Laboratory Xiangyang No.1 People’s HospitalHubei University of MedicineHubeiChina State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&TechnologyTianjinChina

The established and ongoing prevalence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and seasonal human coronaviruses(HCoV)like HCoV-OC43,HCoV-NL63,and HCoV-229E,pose a continuous threat to public health.Therefore,it is urgently needed to explore antiviral drugs with broad-spectrum anti-coronavirus activity.Our previous studies have revealed that lycorine is a potent broad-spectrum anti-coronavirus drug,a natural alkaloid extracted from Amaryllidaceae with various pharmacological and microbiological effects.However,it is unsafe to directly use lycorine as a clinical antiviral drug due to the cytotoxicity and induction of cell apoptosis.In this study,a series of lycorine derivatives were designed and synthesized.One of them,named Ly-8,was found to effectively inhibit the replication of different coronavirus strains in vitro,including SARS-CoV-2.Moreover,Ly-8 was also shown to effectively inhibit HCoVOC43 replication in the central nervous system,and provide effective protection against HCoV-OC43 infection in mice with low drug toxicity.Furthermore,Ly-8-resistant mutants were not observed during the 30 times sequential passages in cell culture.Collectively,these findings suggest that Ly-8 may be a potential candidate drug for the future development of broad-spectrum anti-coronavirus drugs.

关键词： broad-spectrum antiviral drug lycorine derivative Ly-8

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Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第2期30卷 152-162页

作者： YANG ying QU Jin-yu GUO Hua ZHOU Hai-ying RUAN xia PENG ying-chun SHEN Xue-fang XIONG Jin WANG Yi-li School of Clinical Medicine Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation Medicine the First Affliated Hospital of Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation Medicine West China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu(610041)China Department of Neurology the First Affiliated Hospital of Chengdu Medical CollegeChengdu(610500)China

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis model.Twelve rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were determined.Rats were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no treatment.Acupuncture was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive days.GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days.Mechanical sensitivity was assessed with von Frey filaments.Body weight and disease activity index(DAI) scores of rats were determined.Hematoxylin and eosin staining was performed to observe colon histopathology.SSC was analyzed by immunofluorescence staining.Immunohistochemical staining was performed to detect 5-HT and substance P(SP) expressions.The calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western blot.The levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 15 acupoint was used as a non-sensitized acupoint

关键词： electroacupuncture sensitized acupoints sympathetic-sensory coupling 5-hydroxytryptamine neurogenic inflammation somaticreferredpain

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Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

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Chinese Journal of Integrative Medicine 2024年第5期30卷 421-432页

作者： YUE Tong-tong CAO ying-jie CAO Ya-xuan LI Wei-xia WANG xiao-yan SI Chun-ying xia Han ZHU Ming-jun TANG Jin-fa WANG He The First Clinical Medical College of Henan University of Chinese Medicine Zhengzhou 450046China Department of Pharmacy the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China Department of Cardiovascular Diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was closely related to SXNI treatment of MIRI. In v

关键词： myocardial ischemia reperfusion injury PI3K/AKT signaling pathway Shuxuening Injection apoptosis Ginkgo biloba leaves

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