1.The Role of Platelet-Derived Zyxin in Promoting Tumor Migration
Meng-Nan YANG ; Shuang CHEN ; Li-Li ZHAO ; Kang-Xi ZHOU ; Rong YAN ; Ke-Sheng DAI ; Xin-Xin GE
Journal of Experimental Hematology 2025;33(6):1708-1713
Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.
2.Mechanism of hedysarum polybotrys polysaccharide in improving diabetic gastroparesis based on network pharmacology and molecular docking
Qian GUO ; Rong-ke LI ; Lei ZHANG ; Zhao-hui WEI ; Sheng-fang WAN ; Jing SHAO
Chinese Pharmacological Bulletin 2025;41(6):1158-1166
Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by in-tegrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experi-mentation to validate its potential as a treatment for di-abetic gastroparesis.Methods The chemical constit-uents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key tar-gets.Subsequently,a compound-target-pathway net-work diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular doc-king was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Addi-tionally,Western blot was conducted to detect the ex-pression of AGEs,RAGE,and NF-κB in eggs.The re-sults revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carci-nogenesis,hepatitis B,and alcoholism signaling path-way among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histo-pathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improve-ment of DGP.
3.Mechanism of hedysarum polybotrys polysaccharide in improving diabetic gastroparesis based on network pharmacology and molecular docking
Qian GUO ; Rong-ke LI ; Lei ZHANG ; Zhao-hui WEI ; Sheng-fang WAN ; Jing SHAO
Chinese Pharmacological Bulletin 2025;41(6):1158-1166
Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by in-tegrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experi-mentation to validate its potential as a treatment for di-abetic gastroparesis.Methods The chemical constit-uents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key tar-gets.Subsequently,a compound-target-pathway net-work diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular doc-king was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Addi-tionally,Western blot was conducted to detect the ex-pression of AGEs,RAGE,and NF-κB in eggs.The re-sults revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carci-nogenesis,hepatitis B,and alcoholism signaling path-way among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histo-pathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improve-ment of DGP.
4.Establishment of animal model of blood stasis syndrome in diabetic kidney disease and metabonomic analysis
Qian GUO ; Sheng-fang WAN ; Rong-ke LI ; Lei ZHANG ; Zhao-hui WEI ; Zi-hui ZHONG ; Jing SHAO
Chinese Pharmacological Bulletin 2025;41(3):592-599
Aim To establish an animal model of diabetic kidney disease(DKD)integrating blood stasis syndrome and syndrome evaluation indicators.Methods Twenty-five SD rats were ran-domly divided according to body weight into a control group(8 rats)and a modeling group(17 rats).The modeling group was fed a high-sugar and high-fat diet for four weeks and induced to form diabetic rats by intraperitoneal injection of 30 mg·kg-1 streptozocin.The modeling rats were randomly divided into the DKD group and blood stasis syndrome combination group accord-ing to 24-hour urinary protein(24-hUP).The blood stasis syn-drome combination group was induced to replicate the DKD blood stasis syndrome model by injecting 10%high molecular weight D-glucoside three times at a dose of 0.05 mg·kg-1 via tail vein.The model was evaluated based on random blood glu-cose level,24-hUP level,syndrome assessment,pathological staining etc,and differential metabolites were selected using metabolomics.Results The comprehensive evaluation of syn-drome manifestations and pathological staining in the combined model of blood stasis syndrome in rats demonstrated successful replication.Utilizing the technique of liquid chromatography-mass spectrometry,22 differential metabolites were identified,with associated pathways showing a certain relevance to blood stasis syndrome in DKD.Conclusions The successful replica-tion of an animal model combining the syndrome of blood stasis in DKD has been achieved in this study.Evaluation of indicators and results from metabolomics studies consistently demonstrate a correlation with the syndrome of blood stasis in DKD.
5.Analysis of the effectiveness and acceptability of antidepressants in the treatment of postpartum depression
Wen-feng LI ; Ke XU ; Xin WEN ; Meng LI ; Hai YUAN ; De-rong KONG ; Wei-feng MI
The Chinese Journal of Clinical Pharmacology 2025;41(2):245-249
Objective To systematically evaluate the effectiveness and acceptability of antidepressant drugs in the treatment of postpartum depression(PPD).Methods The PubMed,Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Journals of Chinese Scienc were searched,and Chinese Biomedical Literature Service System(SinoMed)database until November 2023.Screen randomized controlled trials(RCTs)of antidepressant drugs for the treatment of PPD.The treatment group was given antidepressant drugs,and the control group was given placebo or another antidepressant drug.Meta-analysis of effectiveness and acceptability is performed using Stata 17.0 software.Results A total of 27 RCTs with a total of 2 202 patients were included.The results of meta-analysis showed:The top three efficacy relative to placebo were mirtazapine[odds ratio(OR)=2.25,95%confidence interval(CI)=(1.20-3.30),P<0.05],nortriptyline[OR=1.50,95%CI=(0.55-2.44),P>0.05],venlafaxine[OR=1.35,95%CI=(0.13-2.56),P>0.05].Acceptability is compared with placebo in the top three Chinese herbal medicine[OR=0.47,95%CI=(-0.72-1.66),P>0.05],nortriptyline[OR=-0.08,95%CI=(-1.16-1.33),P>0.05],venlafaxine[OR=-0.12,95%CI=(-1.47-1.24),P>0.05].Conclusion Nortriptyline,venlafaxine,trazodone,and duloxetine are effective in treating PPD without obvious adverse drug reactions.
6.Research progress of renin-angiotensin system in hypertensive depression
Lu-fan SHEN ; Xiao-ke WANG ; Hong WANG ; Ling-na ZHANG ; Jia-wei LI ; Yu-yuan LU ; Jiao TIAN ; Wan-rong KANG ; A-ni YANG ; Lin YI
Chinese Pharmacological Bulletin 2025;41(9):1629-1635
With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.
7.Research progress of renin-angiotensin system in hypertensive depression
Lu-fan SHEN ; Xiao-ke WANG ; Hong WANG ; Ling-na ZHANG ; Jia-wei LI ; Yu-yuan LU ; Jiao TIAN ; Wan-rong KANG ; A-ni YANG ; Lin YI
Chinese Pharmacological Bulletin 2025;41(9):1629-1635
With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.
8.The Role of Platelet-Derived Zyxin in Promoting Tumor Migration
Meng-Nan YANG ; Shuang CHEN ; Li-Li ZHAO ; Kang-Xi ZHOU ; Rong YAN ; Ke-Sheng DAI ; Xin-Xin GE
Journal of Experimental Hematology 2025;33(6):1708-1713
Objective:To investigate the role of platelet-derived zyxin in promoting tumor migration by platelets.Methods:The gene expression profile of platelets was analyzed from cancer patients by using the GEO database.Isolated platelets from wild-type(WT)and Zyx-/-mice were co-cultured with B16F10 cells labeled with green fluorescence to investigate the influence of zyxin deficiency on tumor cell migration,invasion,and wound healing.Optical microscopy was employed to evaluate the impact of zyxin deficiency on epithelial-mesenchymal transition(EMT)in B16F10 cells induced by platelets.Employing specific markers to label platelets,fluorescence confocal microscopy was utilized to investigate the impact of platelet-derived zyxin on the binding between tumor cells and platelets.And an aggregometer was employed to observe the influence of zyxin deficiency on tumor cell-induced platelet aggregation.Results:Compared to platelets from healthy volunteers,zyxin was upregulated in platelets from cancer patients.Zyx-/-mouse platelets exhibited a significant reduction in tumor cell invasion and migration,impaired wound healing,and delayed tumor cell EMT compared to WT mouse platelets.Additionally,zyxin deficiency attenuated the interaction between platelets and tumor cells,and diminished the capacity for tumor cell-induced platelet aggregation.Conclusion:Platelet-derived zyxin deficiency diminishes platelet-tumor cell interactions and weakens the ability of tumor cell-induced platelet aggregation,ultimately suppressing tumor cell migration.
9.Modulation of cardiac inflammation by Qifu Yixin Granules in rats with heart failure via TLR4/MyD88/NF-κB signaling pathway
Qian-rong LI ; Xiao-dong ZHI ; Bing JIANG ; Chun-ling WANG ; Chun-zhen REN ; Xin-ke ZHAO ; Kai LIU ; Ying-dong LI
Chinese Traditional Patent Medicine 2025;47(8):2535-2541
AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P<0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P<0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P<0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P<0.05,P<0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P<0.05,P<0.01);mitigated inflammation and collagen deposition(P<0.05,P<0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P<0.05,P<0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.
10.Analysis of the effectiveness and acceptability of antidepressants in the treatment of postpartum depression
Wen-feng LI ; Ke XU ; Xin WEN ; Meng LI ; Hai YUAN ; De-rong KONG ; Wei-feng MI
The Chinese Journal of Clinical Pharmacology 2025;41(2):245-249
Objective To systematically evaluate the effectiveness and acceptability of antidepressant drugs in the treatment of postpartum depression(PPD).Methods The PubMed,Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Journals of Chinese Scienc were searched,and Chinese Biomedical Literature Service System(SinoMed)database until November 2023.Screen randomized controlled trials(RCTs)of antidepressant drugs for the treatment of PPD.The treatment group was given antidepressant drugs,and the control group was given placebo or another antidepressant drug.Meta-analysis of effectiveness and acceptability is performed using Stata 17.0 software.Results A total of 27 RCTs with a total of 2 202 patients were included.The results of meta-analysis showed:The top three efficacy relative to placebo were mirtazapine[odds ratio(OR)=2.25,95%confidence interval(CI)=(1.20-3.30),P<0.05],nortriptyline[OR=1.50,95%CI=(0.55-2.44),P>0.05],venlafaxine[OR=1.35,95%CI=(0.13-2.56),P>0.05].Acceptability is compared with placebo in the top three Chinese herbal medicine[OR=0.47,95%CI=(-0.72-1.66),P>0.05],nortriptyline[OR=-0.08,95%CI=(-1.16-1.33),P>0.05],venlafaxine[OR=-0.12,95%CI=(-1.47-1.24),P>0.05].Conclusion Nortriptyline,venlafaxine,trazodone,and duloxetine are effective in treating PPD without obvious adverse drug reactions.

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