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Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

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Journal of Traditional chinese medicine 2024年第2期44卷 303-314页

作者： REN Li HAI Yang YANG Xue LUO Xianqin Chongqing Key Laboratory of Traditional chinese medicine for Prevention and Cure of Metabolic Diseases College of Traditional Chinese MedicineChongqing Medical UniversityChongqing 400016China college of basic medicine Chongqing Medical UniversityChongqing 400016China

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in ***:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry ***,HEL was found to suppress LPS-induced ALI in ***-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)*** model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI *** counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and ***,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal ***:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora *** study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung *** addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturban

关键词： Yemazhui(Herba Eupatorii Lindleyani) acute lung injury anti-inflammation toll-like receptor 4 nuclear factor kappa-B nod-like receptor family pyrin domain-containing 3 protein signal transduction gastrointestinal microbiome

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Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells

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Journal of Pharmaceutical Analysis 2024年第6期14卷 889-901页

作者： Shaowei Huang Xueqian Xie Bo Xu Zengfeng Pan Junjie Liang Meiling Zhang Simin Pan Xiaojing Wang Meng Zhao Qing Wang Jinyan Chen Yanyang Li Lian Zhou Xia Luo School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine510006China School of basic medicine Guangzhou University of Chinese Medicine510006China First Clinical medical college Guangzhou University of Chinese Medicine510000China

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains *** this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG *** detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,***,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for *** results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal ***,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune *** additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via *** conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

关键词： Paeoniflorin Ulcerative colitis Intestinal mucosal barrier DR3 signaling pathway Group 3 innate lymphoid cells

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

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chinese Journal of Natural medicines 2024年第1期22卷 62-74页

作者： GUO Qiru LI Jiali WANG Zheng WU Xiao JIN Zhong ZHU Song LI Hongfei ZHANG Delai HU Wangming XU Huan YANG Lan SHI Liangqin WANG Yong college of basic medicine Chengdu University of Traditional Chinese MedicineChengdu 610000China Chengdu university of Traditional chinese medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610000China

Pathological vascular remodeling is a hallmark of various vascular *** research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular *** dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral *** study investigates the potential of PDA in regulating pathological vascular *** effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 *** approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein *** results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima *** treatment significantly increased the proliferation and migration of *** mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular *** findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

关键词： Potassium dehydroandrographolide succinate Smooth muscle cell Myeloid differentiation factor 88 T-cadherin Pathological vascular remodeling

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions

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chinese Journal of Integrative medicine 2024年第6期30卷 565-576页

作者： KE Jun-yu SONG Jin-bin LI Long HE Zhen-fan HUANG Zhuo-jian LIU Zheng-lin CHEN Gui-rong WANG Hai-yan WEN Su-ru ZHOU Heng-li MA Hui-lin DU Qun WU Yong-qiang LI Yan-wu CHEN Xin-lin School of basic medical Sciences Guangzhou University of Chinese MedicineGuangzhou510006China Department of Surgery II Gaozhou Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese MedicineGaozhou525200China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou510405China The First Clinical medical college of Guangzhou university of Traditional chinese medicine Guangzhou510405China

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

关键词： macrophage ulcerative colitis colon cancer chinese medicine

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Brain Pathology in COVID-19:Clinical Manifestations and Potential Mechanisms

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Neuroscience Bulletin 2024年第3期40卷 383-400页

作者： Zhixing Xu Hui Wang Siya Jiang Jiao Teng Dongxu Zhou Zhong Chen Chengping Wen Zhenghao Xu First School of Clinical medicine Zhejiang Chinese Medical UniversityHangzhou 310053China School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Second School of Clinical medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Afliated Lin’an People’s Hospital of Hangzhou medical college First People’s Hospital of Hangzhou Lin’an DistrictLin’anHangzhou 311300China School of Life Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and Translational medicine of Zhejiang Province College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Laboratory of Rheumatology and Institute of TCM Clinical basic medicine College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in *** though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is *** than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging *** this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza *** also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 *** addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment *** review may offer new insights into preventing or treating brain damage in COVID-19.

关键词： COVID-19 SARS-CoV-2 Brain Neurological pathology

Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve

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chinese Journal of Integrative medicine 2024年第8期30卷 729-741页

作者： WANG Yuan ZHENG A-ni YANG Huan WANG Qiang DAI Biao WANG Jia-ju WAN Yi-tong LIU Zhi-bin LIU Si-yang college of Acu-moxibustion and Massage Shaanxi University of Chinese MedicineXianyangShaanxi Province712046China Shaanxi Key Laboratory of Acupuncture and medicine Shaanxi University of Chinese MedicineXianyangShaanxi Province712046China The Second Affiliated Hospital of Shaanxi university of chinese medicine XianyangShaanxi Province712000China Department of Traditional chinese medicine Baotou Medical CollegeBaotouInner Mongolia Autonomous Region014040China School of basic medical Sciences Xi’an Medical UniversityXi’an710021China

Objective To investigate the effects and mechanisms of olfactory three-needle(OTN)electroacupuncture(EA)stimulation of the olfactory system on cognitive dysfunction,synaptic plasticity,and the gut microbiota in senescence-accelerated mouse prone 8(SAMP8)*** Thirty-six SAMP8 mice were randomly divided into the SAMP8(P8),SAMP8+OTN(P8-OT),and SAMP8+nerve transection+OTN(P8-N-OT)groups according to a random number table(n=12 per group),and 12 accelerated senescence-resistant(SAMR1)mice were used as the control(R1)*** was performed at the Yintang(GV 29)and bilateral Yingxiang(LI 20)acupoints of SAMP8 mice for 4 *** Morris water maze test,transmission electron microscopy,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,Nissl staining,Golgi staining,Western blot,and 16S rRNA sequencing were performed,*** Compared with the P8 group,OTN improved the cognitive behavior of SAMP8 mice,inhibited neuronal apoptosis,increased neuronal activity,and attenuated hippocampal synaptic dysfunction(P<0.05 or P<0.01).Moreover,the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1(NMDAR1),NMDAR2B,synaptophysin(SYN),and postsynaptic density protein-95(PSD95)in hippocampus were increased by OTN treatment(P<0.05 or P<0.01).Furthermore,OTN greatly enhanced the brain-derived neurotrophic factor(BDNF)/cAMP-response element binding(CREB)signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling compared with the P8 group(P<0.05 or P<0.01).However,the neuroprotective effect of OTN was attenuated by olfactory nerve *** with the P8 group,OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice,while specifically increased the genera Oscillospira and Sutterella(P<0.05).Interestingly,the P8-N-OT group showed an abnormal fecal microbiota with higher microbialα-diversity,Firmicutes/Bacter

关键词： Alzheimer's disease olfactory threeneedle electroacupuncture olfactory nerve synaptic plasticity gut microbiota chinese medicine

Understanding the global cancer statistics 2022: growing cancer burden

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Science China Life Sciences 2024年第10期67卷 2274-2276页

作者： Yuxi Liu Zhibo Zheng School of basic medicine Shanghai Medical College Fudan University Department of Thoracic Surgery Department of International Medical ServicesPeking Union Medical College HospitalChinese Academy of Medical Sciences

The International Agency for Research on Cancer(IARC) established in 1965 as the cancer agency of the World Health Organization, focuses on cancer research and dedicates to developing strategies for cancer control glo...

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Seco-cyclic phorbol derivatives and their anti-HIV-1 activities

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chinese Journal of Natural medicines 2024年第4期22卷 365-374页

作者： HUANG Xiaolei HUANG Xusheng LI Qirun MA Mengdi CUI Yadong YANG Liumeng WANG Haibo LUO Ronghua CHEN Jinglei YANG Jingxuan LIN Jinrong LI Duxin ZHENG Yongtang ZHANG Jian college of Pharmaceutical Science Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of the chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming college of Life Science University of Chinese Academy of SciencesKunming 650204China college of Traditional chinese medicine Yunnan University of Chinese MedicineKunming 650500China

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C(PKC).The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20,C3/C4,and C9 of ***,the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand *** influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further *** research entailed the hydrolysis of phorbol,producing seco-cyclic phorbol *** anti-HIV-1 efficacy of these derivatives was assessed,and the affinity constant(Kd)for PKC-δprotein of selected seco-cyclic phorbol derivatives was determined through isothermal titration *** findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding ***,compound S11,with an EC_(50) of 0.27μmol·L^(−1) and a CC_(50) of 153.92μmol·L^(−1),demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription(ssDNA and 2LTR),likely acting at the viral entry stage,yet showed no affinity for the PKC-δ*** results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

关键词： seco-Cyclic phorbol derivatives Hydrolysis reaction Cyclopropane ring Esterification Anti-HIV-1 agent

Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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chinese Journal of Natural medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China State Key Laboratory of medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional chinese medicine(TCM)formula,is known for treating gynecological diseases and liver *** previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed ***,the mechanisms by which SWT influences H19 remain ***,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the *** results showed that SWT markedly improved ECM deposition and bile duct reactions in the ***,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular *** modulation collectively led to reduced ECM *** extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory ***,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver ***,these protective effects of SWT were diminished with the overexpression of H19 in *** conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs Cytoskeleton ECM deposition