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Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction

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Chinese Journal of Integrative medicine 2024年第10期30卷 886-895页

作者： CUI Xin-yu LIU Tian-hua BAI Ya-li ZHANG Meng-di LI Guo-dong ZHANG Yu-ting YUAN Yue-ying ZHANG Ya-wen YU Li-shuang HAN Li-na WU Yan School of Traditional Chinese medicine Beijing University of Chinese Medicine Key Laboratory of Traditional Chinese medicine Syndrome and Formula Ministry of Education Beijing University of Chinese Medicine Beijing Research Institute of Chinese medicine Beijing University of Chinese Medicine

Objective: To study the effect of Shexiang Tongxin Dropping Pill(STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction(CMD). Methods: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve(CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor(VEGF)/endothelial nitric oxide synthase(eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. Results: Compared with the model group, medium-and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening(P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level(all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS(P<0.05 or P<0.01). Co

关键词： Shexiang Tongxin Dropping Pill angiogenesis coronary microcirculation dysfunction diabetic cardiomyopathy type 1 diabetes

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Effect of Chinese medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study

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Chinese Journal of Integrative medicine 2024年第11期30卷 974-983页

作者： ZHAO Guo-zhen YAN Shi-yan LI Bo GUO Yu-hong SONG Shuang HU Ya-hui GUO Shi-qi HU Jing DU Yuan LU Hai-tian YE Hao-ran REN Zhi-ying ZHU Ling-fei XU Xiao-long SU Rui LIU Qing-quan Beijing Hospital of Traditional Chinese medicine Capital Medical University Beijing Institute of Traditional Chinese Medicine School of Clinical medicine Beijing University of Chinese Medicine School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine College of Integrated Chinese medicine Tianjin University of Traditional Chinese Medicine

Objective: To evaluate the effectiveness and safety of Chinese medicine(CM) in the treatment of coronavirus disease 2019(COVID-19) in China. Methods: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of 3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting(IPTW), and the Cox proportional hazards regression model was used for statistical analysis. Results:A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio(HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval(CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29(95% CI: 0.19 to 0.44, P<0.001).Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. Conclusion: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions.(Registration No. ChiCTR2200062917)

关键词： Chinese medicine all-cause mortality cohort study coronavirus disease 2019 deterioration rate

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Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第11期30卷 1001-1006页

作者： HE Dan TAN Xiao-ning LI Lin-pei GAO Wen-hui TIAN Xue-fei ZENG Pu-hua Hunan Academy of Chinese medicine School of Integrated Chinese and Western medicine Hunan University of Chinese Medicine Scientific Research Department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine Oncology Department The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine School of Traditional Chinese medicine Hunan University of Chinese Medicine

Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer ***:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentration(IC50),IC50,2×IC50,erastin（10 μg/mL） and capecitabine（10 μg/mL） *** effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was *** effect of brazilin on the mitochondrial morphology of 4T1 cells,and the mitochondrial damage was evaluated under electron *** levels of Fe2+,reactive oxygen species（ROS）,malondialdehyde（MDA）,glutathione（GSH） and glutathione peroxidase 4（GPX4） were estimated using various detection *** invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell *** expressions levels of tumor protein p53, solute carrier family 7 member 11（SLC7A11）,GPX4 and acyl-CoA synthetase long-chain family member 4（ACSL4） proteins were quantified by Western blot ***:Compared to the control group,the 10(1/2 IC50),20(IC50) and 40(2×IC50) μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A11 and GPX4 protein expression levels,and mitochondrial volume and ridge（P<0.05）,and a significant increase in the mitochondria membrane density,Fe2+,ROS and MDA levels,and p53 and ACSL4protein expression levels（P<0.05）.Conclusions:Brazilin actuated ferroptosis in breast cancer cells,and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

关键词： Chinese medicine brazilin breast cancer ferroptosis p53/SLC7A11/GPX4 axis

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Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice

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Chinese Journal of Integrative medicine 2024年第8期30卷 692-700页

作者： LU Chao GAO Zi-wei XING Shan WANG Hui-hui HUANG Yun-ke ZHOU Hang WU Lei Department of Chinese medicine Preparations Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjing210029China College of Chinese medicine Nanjing University of Chinese MedicineNanjing210046China Department of Chinese medicine Women’s HospitalSchool of MedicineZhejiang UniversityHangzhou310000China

Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female *** Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content of main components in CSS to determine its *** C57BL/6J mice were randomly divided into 4 groups,including control(saline),vehicle(saline),CSS(4 g/kg)and ketamine(30 mg/kg)*** were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress(CMS)model,then received a single administration of *** hours later,the behavioral tests were performed,including open field test,tail suspension test(TST),forced swimming test(FST),novelty suppression feeding test(NSF),and sucrose preference test(SPT).Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor(NMDA)subtypes[N-methyl-D-aspartate receptor 1(NR1),NR2A,NR2B],synaptic proteins[synapsin1 and post synaptic density protein 95(PSD95)],and brain-derived neurotrophic factor(BDNF).Moreover,the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors,*** Compared with the vehicle group,a single administration of CSS(4 g/kg)reversed all behavioral defects in TST,FST,SPT and NSF caused by CMS(P<0.05 or P<0.01).CSS also significantly decreased the expressions of NMDA subtypes(NR1,NR2A,NR2B)at 2 h in hippocampus of mice(all P<0.01).In addition,similar to ketamine,CSS increased levels of synaptic proteins and BDNF(P<0.05 or P<0.01).Furthermore,the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus(all P<0.01).Conclusion Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.

关键词： Chaihu Shugan San female rapid antidepressant potential N-methyl-D-aspartate receptor synapticprotein optogenetic Chinesemedicine

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Zinc-based metal-organic frameworks as efficient carriers for anticancer drug to reduce toxicity and increase efficacy

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Rare Metals 2024年第10期43卷 5152-5163页

作者： Dong-Wei Ma Jing-Sheng Lu Xiang-Xin Cao Yan-Wei Cheng Gang Wang Zi-Qian Zhang Bo-Cheng Chen Ning Lin Qing Chen College of Pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine Center of Engineering and Technology

The rational design of a specific co-drug delivery platform that can address the unavoidable resistance, toxic side effects and low targeting efficiency of traditional cancer treatments is of great ***, Zn-based MOF-zeolitic imidazole framework-90(ZIF-90) was selected as the drug delivery carrier, with the cancer therapeutic drug mercaptopurine(6-MP) and glucose oxidase(GOD) as the drug models, hyaluronic acid(HA) was used for protection and targeted delivery, which designed and fabricated an intelligent drug delivery platform(6-MP@ZIF-90@GOD@HA). This platform aims to reduce the toxic side effects of 6-MP and enhance its efficacy while improving the targeting ability of GOD,thereby further enhancing the treatment outcome. Notably,results from both in vitro and in vivo experiments demonstrate that the targeted synergistic chemo/reactive oxygen species(ROS)-mediated/starvation therapy inhibited the cancer cell growth while reducing the chemotherapy toxicity, which provides new possibilities for the development of more precise and effective treatment strategies.

关键词： Cancer treatment Combination therapy Drug delivery Metal-organic framework Reduced toxicity

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Application of nanoscale metal–organic frameworks in tumor immunotherapy

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Rare Metals 2024年第10期43卷 4867-4883页

作者： Xiao-Xuan Zeng Jing-Sheng Lu Dong-Wei Ma Yu-Ting Huang Ling Chen Gang Wang Qing Chen Ning Lin College of Pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao medicine Center of Engineering and Technology

Immunotherapy has attracted wide attention because it can not only kill tumor cells but also effectively prevent tumor recurrence. However, due to the poor efficacy of the monotherapy in tumor immunotherapy, combination therapies are needed to enhance their efficacy,such as chemodynamic therapy/immunotherapy, photodynamic therapy/immunotherapy, sonodynamic therapy/immunotherapy and so on. Nanoscale metal–organic frameworks(nMOFs) are widely used for drug delivery because of their rich and variable composition, high drug loading capacity and good biodegradability. Compared with other conventional drug delivery systems(DDSs),nMOFs play more advantageous role in inducing immune cell death of tumor cells and combination therapies. This article focuses on the application of n MOFs in tumor immunotherapy in terms of their use as gatekeepers, supplementary agents and drug carriers, respectively, with the aim of providing some ideas and references for the design of smart nanoscale DDS for tumor immunotherapy.

关键词： Drug delivery system Immunotherapy Metal–organic frameworks Tumor

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Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第3期30卷 230-242页

作者： WANG Yi CHEN Ming-qi DAI Lin-feng ZHANG Hai-dong WANG Xing Department of Critical Care medicine Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineChangzhouJiangsu Province213000China Department of Critical Care medicine Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210029China

Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo ***:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell *** pharmacology analysis identified the key molecular pathway associated with FFD in *** ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was ***:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during *** confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

关键词： sepsis Fangji Fuling Decoction mitogen-activated protein kinase 14/Forkhead Box O 3A signaling pathway inflammatory response apoptosis lung injury Chinese medicine

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Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

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Journal of Traditional Chinese medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru School of Chinese medicine Beijing University of Chinese MedicineBeijing 102488China National Institute of TCM Constitution and Preventive medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study *** clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome *** differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were ***:There were no statistical differences found in the baseline *** vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial *** are 66 differentially expressed serum proteins between the two *** A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with ***:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese ***,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index

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GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

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Journal of Pharmaceutical Analysis 2024年第5期14卷 653-665页

作者： Jiani Zhong Hang Chen Qiming Liu Shenghua Zhou Zhenguo Liu Yichao Xiao Department of Cardiovascular medicine Second Xiangya HospitalCentral South UniversityChangsha410011China Xiangya School of medicine Central South UniversityChangsha410008China Center for Precision medicine and Division of Cardiovascular medicine Department of MedicineSchool of MedicineUniversity of MissouriColumbiaMO65211USA

Atrial fibrillation(AF)is the most common cardiac *** medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for *** have unique metabolic characteristics to maintain adenosine triphosphate *** changes occur in myocardial metabolism in ***-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and ***-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial *** article reviews the changes in metabolic characteristics in cardiomyocytes in *** the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

关键词： Atrial fibrillation Glucagon-like peptide-1 receptor agonists Metabolism

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CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

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