1.Protective Effect of Shengxiantang on Myocardial Microvascular Injury in Rats with Chronic Heart Failure
Hui GAO ; Zeqi YANG ; Fan GAO ; Hongjing LI ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):35-42
ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure (CHF). MethodsThe CHF rat model was prepared by aortic arch constriction (TAC). Of the 72 SD rats, 8 were randomly selected as the sham operation group, where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group, the Shengxiantang low-, medium-, and high-dose groups (5.1, 10.2, 20.4 g·kg-1), and the trimetazidine group (6.3 mg·kg-1), with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage, while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of nitric oxide (NO), endothelin (ET-1), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF). Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit (ATP5D) and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin, claudin, vascular endothelial cadherin (VE-Cadherin), and zonula occludens-1 (ZO-1). Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group, the ejection fraction (EF) and left ventricular shortening fraction (FS) in the model group were significantly decreased (P<0.01), while the left ventricular diastolic diameter (LVIDd), left ventricular systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs) were significantly increased (P<0.01). The levels of NO and VEGF were significantly decreased (P<0.01), while the levels of ET-1 and vWF were significantly increased (P<0.01). Under electron microscopy, the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin were significantly decreased (P<0.05, P<0.01), and the relative density of microvessels was significantly reduced (P<0.05, P<0.01). After intervention with Shengxiantang, the EF and FS of CHF rats significantly increased (P<0.01), while the LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs significantly decreased (P<0.01). The levels of NO and VEGF significantly increased (P<0.01), while the levels of ET-1 and vWF significantly decreased (P<0.01). Under electron microscopy, the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin significantly increased (P<0.05, P<0.01), and the relative density of microvessels significantly increased (P<0.01). ConclusionShengxiantang can effectively improve the cardiac function of CHF rats, reduce microvascular endothelial injury, strengthen the connection between endothelial cells, and increase microvessel density, thereby protecting myocardial microvascular injury.
2.Protective Effect of Shengxiantang on Myocardial Microvascular Injury in Rats with Chronic Heart Failure
Hui GAO ; Zeqi YANG ; Fan GAO ; Hongjing LI ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):35-42
ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure (CHF). MethodsThe CHF rat model was prepared by aortic arch constriction (TAC). Of the 72 SD rats, 8 were randomly selected as the sham operation group, where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group, the Shengxiantang low-, medium-, and high-dose groups (5.1, 10.2, 20.4 g·kg-1), and the trimetazidine group (6.3 mg·kg-1), with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage, while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of nitric oxide (NO), endothelin (ET-1), vascular endothelial growth factor (VEGF), and von Willebrand factor (vWF). Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit (ATP5D) and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin, claudin, vascular endothelial cadherin (VE-Cadherin), and zonula occludens-1 (ZO-1). Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group, the ejection fraction (EF) and left ventricular shortening fraction (FS) in the model group were significantly decreased (P<0.01), while the left ventricular diastolic diameter (LVIDd), left ventricular systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs) were significantly increased (P<0.01). The levels of NO and VEGF were significantly decreased (P<0.01), while the levels of ET-1 and vWF were significantly increased (P<0.01). Under electron microscopy, the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin were significantly decreased (P<0.05, P<0.01), and the relative density of microvessels was significantly reduced (P<0.05, P<0.01). After intervention with Shengxiantang, the EF and FS of CHF rats significantly increased (P<0.01), while the LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs significantly decreased (P<0.01). The levels of NO and VEGF significantly increased (P<0.01), while the levels of ET-1 and vWF significantly decreased (P<0.01). Under electron microscopy, the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D, F-actin, occludin, claudin, ZO-1, and VE-Cadherin significantly increased (P<0.05, P<0.01), and the relative density of microvessels significantly increased (P<0.01). ConclusionShengxiantang can effectively improve the cardiac function of CHF rats, reduce microvascular endothelial injury, strengthen the connection between endothelial cells, and increase microvessel density, thereby protecting myocardial microvascular injury.
3.Effect of Yiqi Wenyang Huoxue Lishui Components on Cardiac Function and Mitochondrial Energy Metabolism in CHF Rats
Hui GAO ; Zeqi YANG ; Xin LIU ; Fan GAO ; Yangyang HAN ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):27-36
ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure (CHF) and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction (TAC). Eight of the 50 SD rats were randomly selected as the sham group, and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model, trimetazidine (6.3 mg·kg-1), and Yiqi Wenyang Huoxue Lishui components (60 mg·kg-1 total saponins of Astragali Radix, 10 mg·kg-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma, 190 mg·kg-1 aqueous extract of Lepidii Semen, and 100 mg·kg-1 cinnamaldehyde) groups. The rats were administrated with corresponding agents by gavage, and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide (NT-ProBNP), hypersensitive troponin(cTnI), creatine kinase (CK), lactate dehydrogenase (LD), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA). The colorimetric assay was employed to measure the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta (ATP5D), glucose transporter 4 (GLUT4), and carnitine palmitoyltransferase-1 (CPT-1). The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ, Ⅱ, Ⅲ, and Ⅳ. ResultsCompared with the sham group, the model group showed a loosening arrangement of cardiac fibers, fracture and necrosis of partial cardiac fibers, inflammatory cells in necrotic areas, massive blue fibrotic tissue in the myocardial interstitium, increased collagen fiber area and myocardial fibrosis, destroyed mitochondria, myofibril disarrangement, sparse myofilaments, and fractured and reduced cristae. In addition, the rats in the model group showed declined ejection fraction (EF) and fractional shortening (FS), risen left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs), elevated levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, lowered level of SOD, down-regulated protein levels of GLUT4 and CPT-1, decreased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and declined levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). Compared with the model group, the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue, risen EF and FS, declined LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs, lowered levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, elevated level of SOD, up-regulated protein levels of GLUT4 and CPT-1, increased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and elevated levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function, reduce myocardial injury, regulate glucose and lipid metabolism, optimize the utilization of substrates, and alleviate the damage of mitochondrial structure and function, thus improving the energy metabolism of the myocardium in the rat model of CHF.
4.Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the m6A modification of calsequestrin 2 in diabetic cardiomyopathy.
Xiaohan LI ; Ling LIU ; Han LOU ; Xinxin DONG ; Shengxin HAO ; Zeqi SUN ; Zijia DOU ; Huimin LI ; Wenjie ZHAO ; Xiuxiu SUN ; Xin LIU ; Yong ZHANG ; Baofeng YANG
Frontiers of Medicine 2025;19(2):329-346
Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca2+ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca2+ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m6A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca2+ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals
;
Diabetic Cardiomyopathies/pathology*
;
RNA, Long Noncoding/genetics*
;
Myocytes, Cardiac/metabolism*
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Mice
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Calsequestrin/genetics*
;
Calcium/metabolism*
;
Male
;
Sarcoplasmic Reticulum/metabolism*
;
Methyltransferases/metabolism*
;
Mice, Inbred C57BL
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Mitochondria, Heart/metabolism*
;
Disease Models, Animal
;
Mitochondria/metabolism*
5.Visualization Analysis of Studies on Prediction Models in Field of Traditional Chinese Medicine
Chengyang JING ; Zeqi DAI ; Xue WU ; Le ZHANG ; Lirong LIANG ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):209-217
ObjectiveBased on knowledge mapping, the studies on prediction models in the field of traditional Chinese medicine (TCM) were visually analyzed, which provided a reference basis for the excavation and evolution of the future research direction by combing the development process and summarizing the research hotspots and dynamic trends. MethodChina National Knowledge Infrastructure and Web of Science Core Collection databases were searched to obtain studies on prediction models in the field of TCM from inception to February 28, 2023. Endnote X20 software was used for document management. Knowledge mapping generated by CiteSpace software and VOSviewer software was used to visually analyze the characteristics of publication, institutional cooperation relationship, author cooperation network, co-citation, and keywords. ResultA total of 264 pieces of Chinese literature and 266 pieces of English literature were included, and the overall number of research publications showed an increasing trend year by year. The cooperation relationship between the issuing institutions showed obvious regional characteristics, with the closest cooperation relationship between the universities of TCM and their affiliated hospitals, as well as secondary units subordinate to scientific research institutions. The number of research teams and team members publishing papers in English was higher, and cooperation between different teams was more frequent. Groundbreaking and/or referential studies were widely cited and referred to. The highly cited literature was mainly published in complementary and alternative medicine journals and pharmaceutical journals. Research hotspots mainly focused on clinical prediction models of TCM, quantitative models of TCM, and specific modeling methods. The application of artificial intelligence technologies such as machine learning and deep learning in the field of TCM will be the most cutting-edge research direction in the future. ConclusionThe field of TCM is paying more and more attention to the studies on prediction models, while the research cooperation mode involving multiple organizations and teams has increasingly become the mainstream. With the continuous development of multi-disciplinary integration, studies on prediction models are closely related to the development and rise of innovative techniques and methods, and any breakthrough in theory or application will induce and guide a new round of research upsurge. Systematic reviews of topic-specific prediction models should be carried out in the future to provide evidence-based evidence.
6.Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma: A Review
Han YANG ; Yonghuang YAN ; Wenting ZHANG ; Peixuan ZHU ; Fang YAN ; Yujie WU ; Shiqing QIAO ; Tieshan WANG ; Zeqi SU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):206-212
Cough variant asthma (CVA) is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation, and its pathogenesis involves environmental, genetic, immune, and other factors. In recent years, the advantages of traditional Chinese medicine (TCM) in the treatment of CVA have attracted the attention of experts and scholars in China and abroad, especially its prominent role in regulating immune balance, relieving cough symptoms in CVA patients, and reducing recurrence. T Helper cells 1 (Th1), T helper cells 2 (Th2), T helper cells 17 (Th17), and regulatory T cells (Treg) are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions, maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells (Th0) can be differentiated into Th1, Th2, Th17, Treg, and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function, and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper, the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile, the latest research on the regulation of immune imbalance by TCM compound, single TCM, and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA, as well as the development of clinical treatment and basic research of CVA.
7.Establishment and evaluation of non-obese polycystic ovary syndrome rat model
Shiqing QIAO ; Ting WANG ; Yonghuang YAN ; Jiusi YANG ; Yuling YU ; Yanmin WANG ; Yateng SUN ; Yujie WU ; Peixuan ZHU ; Min LI ; Cong CHEN ; Zeqi SU ; Cai ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):965-975
Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P<0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P<0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P<0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.
8.Clinical Study of Tongfengke Granules Combined with External Treatment of TCM in the Treatment of Patients with Acute Gouty Arthritis
Lin YANG ; Guifang PI ; Zeqi MU ; Peng XIANG ; Qin WU ; Rui FANG ; Dan LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):152-158
Objective To observe the clinical efficacy of Tongfengke Granules combined with external treatment of TCM in acute gouty arthritis(AGA)with damp-heat accumulation type.Methods A total of 96 patients with AGA were divided into the experimental group and the control group according to random number table method,with 48 patients in each group.The control group received meloxicam treatment.On this basis,the experimental group was treated with Tongfengke Granules(1 bag at a time,three times a day,orally)combined with external therapy of TCM(once a day),and mobile continuing care.The treatment for both groups lasted for 2 weeks.The clinical efficacy of both groups was observed.Before and after the treatment,pain visual analogue scale(VAS),TCM syndrome scores,major symptom scores,and levels of serum uric acid(UA),interleukin-6(IL-6),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),platelet/lymphocyte ratio(PLR),as well as engagement in self-care ability scale(ESCA),general self-efficacy scale(GSES),negative psychological condition[self-rating depression scale(SDS),self-rating anxiety scale(SAS)]were measured.The adverse reactions in both groups were monitored.Results Totally 45 and 47 patients in the experimental group and control group were finally included respectively in the analysis.The total effective rate of the experimental group was 75.6%(34/45),while that of the control group was 63.8%(30/47),with statistical significance(P<0.05).Compared with before treatment,the VAS score and TCM syndrome score in the experimental group decreased significantly(P<0.05);after treatment,the VAS score and TCM syndrome score of the experimental group were lower than those of the control group(P<0.05).Compared with before treatment,the joint pain,joint tenderness,joint swelling,and joint mobility limitation scores in both groups were significantly decreased after treatment(P<0.05,P<0.01);after treatment,the scores of joint pain,joint tenderness,and joint swelling in the experimental group were lower than those in the control group(P<0.01).Compared with before treatment,the levels of UA,ESR,CRP and PLR in both groups decreased significantly after treatment(P<0.01);after treatment,the levels of UA,ESR,CRP and PLR in the experimental group were lower than those in the control group(P<0.05,P<0.01).Compared with before treatment,the experimental group showed significant improvement in ESCA,GSES and SAS after treatment(P<0.05,P<0.01),while the control group showed significant improvement in ESCA(P<0.01);after treatment,the ESCA and GSES of the experimental group were better than those of the control group(P<0.05,P<0.01).There was no statistical significance in safety indicators and incidence of adverse reactions between the two groups(P>0.05).Conclusion Tongfengke Granules combined with external treatment of TCM can significantly improve the clinical efficacy of AGA,reduces UA levels,significantly improves inflammatory response,and has anti-inflammatory,anti-inflammatory,and analgesic effects.
9.Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial-mesenchymal transition via directly targeting TGFβR1.
Jingnan ZHANG ; Ze ZHANG ; Zhenlin HUANG ; Manlin LI ; Fan YANG ; Zeqi WU ; Qian GUO ; Xiyu MEI ; Bin LU ; Changhong WANG ; Zhengtao WANG ; Lili JI
Acta Pharmaceutica Sinica B 2023;13(7):2990-3007
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.
10.Research on Syndrome and Treatment Rules of Famous Doctors in Treating Ulcerative Colitis Based on Data Mining
Yujie WU ; Ting WANG ; Peixuan ZHU ; Yonghuang YAN ; Han YANG ; Wenting ZHANG ; Fang YAN ; Shiqing QIAO ; Cai ZHANG ; Zeqi SU
Journal of Traditional Chinese Medicine 2023;64(21):2241-2247
ObjectiveTo systematically review the clinical experience of four sessions of Masters of Traditional Chinese Medicine and two sessions of National Famous Chinese Medicine Practitioners in treating ulcerative colitis (UC). Data mining and analysis were conducted to clarify the diagnosis and treatment ideas and characteristics of prescription used by these famous doctors in treating UC. MethodsRelevant literature on the treatment of UC by renowned doctors was retrieved from the establishment of the database until March 31, 2023. The literature was collected from databases such as China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, Chinese Science and Technology Periodicals Database, and China Biomedical Literature Database. The data mining techniques including frequency analysis, association rules, and cluster analysis were conducted using the Ancient and Modern Medical Case Cloud Platform V2.3.5. ResultsA total of 157 literatures were included in this study, including 115 clinical case data. The study found that UC can be categorized into 14 types of syndrome patterns for treatment, including large intestine dampness-heat syndrome (75,65.22%), syndrome of dampness stagnancy due to spleen deficiency (23, 20.00%), spleen-kidney yang deficiency syndrome (21, 18.26%). The main affected organs were the spleen (85, 73.91%) and large intestine (75, 65.22%), and they were closely related to liver (24, 20.87%) and the kidney (21, 18.26%). The predominant pathogenic factors were dampness (83, 72.17%) , heat (80, 69.57%) and qi deficiency (65, 56.52%). The treatment involved 30 kinds of treatment methods, including heat-clearing and dampness-draining method (75, 65.22%), pleen-tonifying and qi-boosting method (25,21.74%) and spleen-invigorating and dampness-transforming method (23, 20.00%). The medication involved 187 ingredients, with the most commonly used being heat-clearing herbs (37, 19.79%) and tonifying herbs (27, 14.44%). The tastes of the herbs were mostly sweet (85, 45.45%) , bitter (80, 42.78%) , and pungent (71, 37.97%). The association rules revealed 16 high-frequency combinations mainly composed of Huanglian (黄连), Baishao (白芍) and Gancao (甘草) along with Baizhu (白术), Fuling (茯苓), Muxiang (木香) and Danggui (当归). ConclusionFamous doctors are skilled in diagnosing and treating UC based on the differentiation of the zang-fu organs and qi-blood. The key pathological mechanism is “spleen deficiency as the root, and large intestine damp-heat as the manifestation”. The core treatment approach is “heat-clearing, spleen-tonifying, and dampness-draining”, with the inclusion of “regulating qi and blood, and balancing cold and heat”.

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