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Network pharmacology-Based Dissection of the bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 75-82页

作者： Yu-Xi Huang Jing-Jing Fan Lu-Lu Xu Rong Yu Yi Kuang Yue Chai Rui Zheng Xiao-Yu Zhang Hong-Cai Shang Xue Qiao Min Ye State Key laboratory of Natural and biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina Key laboratory of Chinese Internal Medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Yunnan Baiyao International Medical Research Center Peking UniversityBeijingChina Key laboratory of Molecular Cardiovascular Sciences of Ministry of Education Peking UniversityBeijingChina

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly *** and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index ***,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent ***:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 ***,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating *** was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and *** pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF *** Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in ***:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of *** Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

关键词： Contribution index heart failure network pharmacology traditional Chinese medicine yiqi fumai lyophilized injection

Molecular regulation of the key specialized metabolism pathways in medicinal plants

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Journal of Integrative Plant biology 2024年第3期66卷 510-531页

作者： Min Shi Siwei Zhang Zizhen Zheng Itay Maoz Lei Zhang Guoyin Kai Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of medicinal and Edible Plants and Health Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and TransformationSchool of Pharmaceutical SciencesJinhua AcademyZhejiang Chinese Medical UniversityHangzhou 310053China Department of Postharvest Science Agricultural Research OrganizationVolcani CenterRishonLeZion 7505101Israel Department of Pharmaceutical Botany School of PharmacyNaval Medical UniversityShanghai 200433China

The basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants,for example,terpenoids,alkaloids,and phenolic ***,in most cases,the availability of these valuable compounds is limited by cellular or organelle barriers or spatio-temporal accumulation patterns within different plant *** factors(TFs)regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic ***-edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of *** this review,we focus on recent progress in the transcription regulation mechanism of representative high-value products and describe the transcriptional regulatory network,and future perspectives are discussed,which will help develop high-yield plant resources.

关键词： biosynthesis medicinal plants omics secondary metabolism transcription factors

BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

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Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang Hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang Gao Baicheng He Yuxi Su Department of pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key laboratory of biochemistry and Molecular pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China Department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics Department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International Science and Technology Cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National Clinical Research Center for Child Health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often *** tissue engineering offers a promising approach to treating these conditions *** morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue ***-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone *** study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying *** marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal ***,LGR4 expression was increased by BMP9 in C3H10T1/2 ***4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these ***,the BMP9-induced li-pogenic markers were increased by LGR4 *** protein levels of Raptor and p-Stat3 were elevated by *** knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by ***4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic *** interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter *** conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

From the dust:extracellular vesicles as regulators of development and neuroregeneration

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Neural Regeneration Research 2024年第5期19卷 933-934页

作者： Leon G.Coleman Jr The University of North Carolina at Chapel Hill School of MedicineDepartment of PharmacologyBowles Center for Alcohol StudiesChapel HillNCUSA

First impressions can have a lasting *** science,this can be especially problematic,because our lack of understanding often causes us to mislabel and thus ignore important biological *** this vein,extracellular vesicles(EVs)were once considered to be“cellular dust”.Similar to the previous concept of“junk DNA”to describe protein non-coding regions,EVs are far more than just cellular *** fact,EVs are emerging as key mediators of intracellular communication across nearly all biological *** includes peripheral immune responses(e.g.,arthropathies and sepsis),intra-organ communication(Seim et al.,2023),and a host of other physiological and pathological states(Figure 1A and B).

关键词： Figure extracellular

bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

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Science China(Life Sciences) 2024年第5期67卷 1010-1026页

作者： Ziyue Qin Yanxing Han Yifei Du Yixuan Zhang Yifeng Bian Ruyu Wang Haoran Wang Fanyi Guo Hua Yuan Yongchu Pan Jianliang Jin Qigang Zhou Yuli Wang Feng Han Yan Xu Jiandong Jiang Department of Oral and Maxillofacial Surgery The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Province Key laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing 210029China State Key laboratoryof bioactiveSubstances andFunction of Natural Medicine Instituteof Materia MedicaChinese Academyof MedicalSciencesandPeking Union MedicalCollegeBeijing100050China Gusu school Nanjing medical universitySuzhou 215002China Key laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical UniversityNanjing 211166 China Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Human Anatomy Research Centre for Bone and Stem CellsKey Laboratory for Aging&DiseaseThe State Key Laboratory of Reproductive MedicineNanjing Medical UniversityNanjing 211166China Department of Clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing Jiangsu211166China Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjing 210029China Department of Virology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this ***(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic *** this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone *** from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in *** clarify the underlying mechanism,the bioactive materials were applied to different animal *** discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the *** of pure M-CSF attenuated experimental periodontal alveolar bone loss in ***-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated ***,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or *** results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT *** studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction ***,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

关键词： berberine human bone marrow mesenchymal stem cells alveolar bone regeneration macrophage colony-stimulating factor AKT phosphorylation

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Prognostic implications of overt congestion in heart failure with preserved ejection fraction and the interaction with spironolactone:Insights from TOPCAT

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Chinese Medical Journal 2024年第10期137卷 1249-1251页

作者： Yingwen Lin Hengli Zhao Dongtu Hu Jia Huang You Peng Juncong Li Dingli Xu Qingchun Zeng State Key laboratory of Organ Failure Research Department of CardiologyNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key laboratory of Clinical pharmacology Medical Research InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510515China Department of Radiology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510150China Department of Obstetrics and Gynecology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

To the Editor:Heart failure with preserved ejection fraction(HFpEF)is a clinical entity characterized by impaired diastolic *** recently,there have been few studies directly evaluating how volume status impacts future cardiac events for patients with *** supporting the application of spironolactone in HFpEF is mainly derived from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist(TOPCAT)*** though primary analysis of the trial reached a neutral result,subgroup and subsequent post hoc analyses have confirmed its efficacy in selected groups of patients,suggesting that identifying the potential subgroups of patients who would benefit from spironolactone treatment is important.[1]Data regarding the impact of congestion status on the efficacy of spironolactone in HFpEF are lacking.

关键词： function. fraction impaired

Dysbiosis of oral and gut microbiota and its association with metabolites in patients with different degrees of coronary artery stenosis

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Chinese Medical Journal 2024年第9期137卷 1121-1123页

作者： Zekun Wang Long Li Chenyang Wang Qian Wang Fengzhi Wang Xin Xu Xuedong Zhou State Key laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041China Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduSichuan 610041China Department of Cardiology Shanxi Provincial Key Laboratory of Cardiovascular Disease DiagnosisTreatment and Clinical PharmacologyThe Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China

To the Editor:Coronary atherosclerotic heart disease(CAD)arises from coronary atherosclerosis(CAS)plaque buildup,resulting in coronary stenosis(CS)and occlusion,ultimately causing myocardial ischemia,hypoxia,or *** showed that the high-grade CS may be an important predictor of ST segment elevation myocardial infarction in subsequent months.

关键词： coronary stenosis occlusion

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

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Asian Pacific Journal of Tropical biomedicine 2024年第6期14卷 236-244页

作者： Hital Shah Tejal Gandhi Gujarat Technological University AhmedabadGujarat 382424India Department of pharmacology Anand Pharmacy CollegeAnandGujarat 388001India

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in ***:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 ***(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial *** day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were *** levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were ***,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also ***:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic *** also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid ***,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory ***:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

关键词： NF-κB Isoproterenol Betulin Myocardial injury Oxidative stress Inflammation Apoptosis

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key laboratory of Cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic