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Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental medicine 2024年第3期7卷 259-274页

作者： Huirong Xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian Qinghua Cui Kejian Li College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of chinese medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao academy of chinese Medical sciences Shandong University of Traditional Chinese MedicineQingdaoChina College of Pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： Cheng-Jin Ai Ling-Juan Chen Li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina traditional chinese medicine Regulating Metabolic Diseases Key Laboratory of sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

Cordyceps as potential therapeutic agents for atherosclerosis

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Journal of Integrative medicine 2024年第2期22卷 102-114页

作者： Yi Zhang Si-jing Liu School of Marxism Chengdu University of Traditional Chinese MedicineChengdu 61137Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Chongqing Key Laboratory of sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases with Integrated chinese and Western medicine Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina

Atherosclerosis is a leading cause of mortality and morbidity worldwide.Despite the challenges in managing atherosclerosis,researchers continue to investigate new treatments and complementary therapies.Cordyceps is a traditional chinese medicine that has recently gained attention as a potential therapeutic agent for atherosclerosis.Numerous studies have demonstrated the effectiveness of cordyceps in treating atherosclerosis through various pharmacological actions,including anti-inflammatory and antioxidant activities,lowering cholesterol,inhibiting platelet aggregation,and modulating apoptosis or autophagy in vascular endothelial cells.Notably,the current misuse of the terms cordyceps and Ophiocordyceps sinensis has caused confusion among researchers,and complicated the current academic research on cordyceps.This review focuses on the chemical composition,pharmacological actions,and underlying mechanisms contributing to the anti-atherosclerotic effects of cordyceps and the mycelium of Ophiocordyceps spp.This review provides a resource for the research on the development of new drugs for atherosclerosis from cordyceps.

关键词： Atherosclerosis Cordyceps Ophiocordyceps sinensis

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

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World Journal of Stem Cells 2024年第2期16卷 207-227页

作者： Yun Yuan Xu-Fan Zhang Yu-Chen Li Hong-Qing Chen Tian Wen Jia-Lian Zheng Zi-Yi Zhao Qiong-Ying Hu Department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of Nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Department of Hepatology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110032Liaoning ProvinceChina Hospital of Chengdu University of traditional chinese medicine Chengdu 610072Sichuan ProvinceChina traditional chinese medicine Regulating Metabolic Diseases Key Laboratory of sichuan Province Chengdu 610072Sichuan ProvinceChina

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibit

关键词： Colorectal cancer stem cells Stemness VX-509 Epithelial-mesenchymal transition Nodal

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval:A randomized controlled trial

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Journal of Integrative medicine 2024年第1期22卷 32-38页

作者： Li-ying Liu Yang Su Rong-rong Wang Yuan-yuan Lai Lei Huang Yi-ting Li Xin-yue Tao Meng-hua Su Xiao-yan Zheng Shi-chen Huang Yong-na Wu Si-yi Yu Fan-rong Liang Jie Yang Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu 610000Sichuan ProvinceChina traditional chinese medicine Department Sichuan Jinxin Xi’nan Women's and Children's HospitalChengdu 610000Sichuan ProvinceChina

Background Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure.Some research showed that transcutaneous electrical acupoint stimulation(TEAS)can relieve intraoperative pain and postoperative nausea.Objective This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval.Design,setting,participants and interventions Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group.The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval.Main outcome measures The primary outcome was the visual analog scale(VAS)pain score.Secondary outcomes were pressure pain threshold,McGill score,pain rating index(PRI),present pain intensity(PPI),VAS stress score,VAS anxiety score,and postoperative adverse symptoms.Results The baseline characteristics of the two groups were comparable(P>0.05).The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval(P0.05).The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms(P<0.05).Conclusion TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval.

关键词： Transcutaneous electrical acupoint stimulation Fertilization Embryo transfer Oocyte retrieval Pain Randomized controlled trial

Whole-genome sequencing in medicinal plants:current progress and prospect

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Science China(Life sciences) 2024年第2期67卷 258-273页

作者： Yifei Pei Liang Leng Wei Sun Baocai Liu Xue Feng Xiwen Li Shilin Chen Institute of chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Institute of Herbgenomics Chengdu University of Traditional Chinese MedicineChengdu 611137China Innovative Institute of chinese medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Institute of Agricultural Bioresource Fujian Academy of Agricultural SciencesFuzhou 350003China

Advancements in genomics have dramatically accelerated the research on medicinal plants,and the development of herbgenomics has promoted the“Project of 1K Medicinal Plant Genome”to decipher their genetic code.However,it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity.Whole genomes of 123 medicinal plants were published until September 2022.These published genome sequences were investigated in this review,covering their classification,research teams,ploidy,medicinal functions,and sequencing strategies.More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes.Diploid species account for a majority of sequenced medicinal plants.The whole genomes of plants in the Poaceae family are the most studied.Almost 40%of the published papers studied species with tonifying,replenishing,and heat-cleaning medicinal effects.Medicinal plants are still in the process of domestication as compared with crops,thereby resulting in unclear genetic backgrounds and the lack of pure lines,thus making their genomes more difficult to complete.In addition,there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome.Herein,a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants.Moreover,whole genome-based biological studies of medicinal plants,including breeding and biosynthesis,were reviewed.We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

关键词： herbgenomics whole genome high throughput sequencing research strategy model species application

Anti-inflammatory mechanism of the non-volatile ingredients performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics

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Journal of traditional chinese medicine 2024年第2期44卷 260-267页

作者： JING Wenguang LIN Xiaoyu LI Chu ZHAO Xiaoliang CHENG Xianlong WANG Penglong WEI Feng MA Shuangcheng Institute of Control of chinese traditional medicine and Ethnic medicine National Institutes for Food and Drug ControlBeijing 102629China School of traditional chinese medicine Beijing University of Chinese MedicineBeijing 102488China Beijing Key Laboratory of traditional chinese medicine Basic Research on Prevention and Treatment of Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE:To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli.METHODS:High performance liquid chromatographyheated electron spray ionization-high resolution mass spectroscope(HPLC-HESI-HRMS)was used to analyze the chemical constituents of the non-volatile ingredients of patchouli.The anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide(LPS)induced RAW264.7 cell inflammation model,and the antiinflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics.RESULTS:The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS,and 36 flavonoids and 18 other components were identified.These ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells,but also regulated the expression levels of arginine,L-leucine,cholesterol,fructose and sorbitol by down-regulating arginine metabolism,aminoacyl-tRNA biosynthesis,polyol/sorbitol pathway,so as to reduce inflammation and reduce cell damage.CONCLUSION:The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

关键词： Pogostemon non-volatile ingredients anti-inflammatory cell metabolomics

Molecular Mechanism of Polysaccharides Extracted from chinese medicine Targeting Gut Microbiota for Promoting Health

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chinese Journal of Integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China Shandong Co-innovation Center of Classic traditional chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver disease.Polysaccharides extracted from chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and anti-oxidation.The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment.In addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota.This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions

Exploring the autophagy-related pathogenesis of active ulcerative colitis

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World Journal of Clinical Cases 2024年第9期12卷 1622-1633页

作者： Zhuo-Zhi Gong Teng Li He Yan Min-Hao Xu Yue Lian Yi-Xuan Yang Wei Wei Tao Liu Wangjing Hospital China Academy of Chinese Medical SciencesBeijing 100102China College of traditional chinese medicine School of Traditional Chinese MedicineBeijing 100102China Guang’anmen Hospital China Academy of Chinese Medical SciencesBeijing 100053China

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

关键词： Ulcerative colitis Autophagy Bioinformatic Targets Pathogenesis