1.Regulatory Pathways of Cell Apoptosis in Diabetic Kidney Disease and Intervention by Traditional Chinese Medicine: A Review
Yunjie YANG ; Mingqian JIANG ; Chen QIU ; Yaqing RUAN ; Senlin CHEN ; Wenxin HUANG ; Hangbin ZHENG ; Yi WEI ; Pengfei LI ; Xueqin LIN ; Jing WU ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):294-306
Diabetic kidney disease(DKD) is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise, DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease(ESRD), posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD, with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)/B-cell lymphoma-2(Bcl-2)/cysteinyl aspartate-specific proteinase(Caspase)-3, protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/activating transcript factor 4(ATF4)/CCAAT enhancer-binding protein homologous protein(CHOP), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β), Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) and silent information regulator 1(SIRT1)/tumor suppressor protein 53(p53), thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine(TCM), leveraging its unique therapeutic advantages of multi-target, multi-component and multi-pathway approaches, has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile, traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation, detoxifying and dredging collaterals, tonifying kidney essence, and removing stasis and purging turbidity, thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this, this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms, while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components, compound formulations, and proprietary Chinese medicines on DKD through modulation of these pathways, with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.
2.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
3.Clinical Efficacy of Yishen Jiangtang Decoction Combined with Conventional Western Medicine Treatment for Diabetic Kidney Disease with Pattern of Qi-Yin Deficiency Combined with Dampness-heat and Blood Stasis
Yunjie YANG ; Yasheng DENG ; Kaiying HE ; Qi ZHANG ; Yongxin YU ; Yaqing RUAN ; Zhuang HAN ; Qiwei CHEN ; Yi WEI ; Qiu CHEN ; Jing WU ; Mingqian JIANG ; Shiwei RUAN ; Jianting WANG ; Yuliang QIU ; Lixiang ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):157-167
ObjectiveTo observe the clinical efficacy and safety of Yishen Jiangtang decoction combined with conventional Western medicine treatment in managing stage G3A3 diabetic kidney disease (DKD) in the patients with the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis, and to explore its mechanism of inhibiting the endoplasmic reticulum stress (ERS)-apoptosis axis and delaying renal fibrosis (RF). MethodsA single-center, randomized, parallel-controlled clinical trial was conducted. A total of 78 patients diagnosed with stage G3A3 DKD and traditional Chinese medicine (TCM) pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis and treated in the Department of Nephrology and the Department of Endocrinology of the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine from March 2025 to February 2026 were enrolled. They were randomly assigned at a 1∶1 ratio into a control group (conventional Western medicine treatment) and an experimental group (Yishen Jiangtang decoction combined with conventional Western medicine treatment), with 39 patients in each group. The treatment lasted for 12 weeks. Basic demographic data and medical history were collected before and after treatment. The two groups before and after treatment were compared in terms of the following parameters: Blood urea nitrogen (BUN), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Enzyme-linked immunosorbent assay (ELISA) kits were used to measure serum glucose-regulated protein 78 (GRP78), serum cysteinyl aspartate-specific protease-3 (Caspase-3), and serum and urinary transforming growth factor-β1 (TGF-β1) levels before and after treatment. TCM symptom scores, TCM syndrome efficacy, and overall clinical efficacy were evaluated before and after treatment. Spearman correlation analysis was performed to explore the correlations of serum levels of GRP78 and Caspase-3, as well as serum and urinary levels of TGF-β1, with renal function, proteinuria, and glucose and lipid metabolism indicators in patients with DKD. In addition, safety indicators were also monitored. ResultsA total of 75 patients completed the study (38 in the control group and 37 in the experimental group). ① Baseline data: The two groups were comparable in terms of sex and age, with no statistically significant difference. ② Efficacy outcomes: Compared with baseline levels, both groups showed reductions in BUN, SCr, UACR, FBG, TG, TC, LDL-C, and TCM symptom scores (P<0.01) and increases in eGFR level (P<0.01). Moreover, the experimental group outperformed the control group in altering the indicators above (P<0.05). Regarding TCM syndrome efficacy, the total response rate in the experimental group was 83.78%, which was higher than that (57.89%) in the control group (P<0.05). Regarding overall clinical efficacy, the total response rate in the experimental group was 78.38%, which was higher than that (50.00%) in the control group (P<0.05). ③ Mechanism outcomes: Compared with baseline levels, both groups showed declined serum levels of GRP78, Caspase-3, and TGF-β1 and urinary level of TGF-β1 after treatment (P<0.01). Moreover, the experimental group showed greater declines than the control group (P<0.05). The serum levels of GRP78, Caspase-3,and TGF-β1 and the urinary level of TGF-β1 in DKD patients showed positive correlations with BUN, SCr, UACR, and FBG and negative correlations with eGFR (P<0.05). ④ Safety outcomes: Neither group showed drug-related adverse reactions, and laboratory safety parameters remained within normal ranges. ConclusionYishen Jiangtang decoction combined with conventional Western medicine treatment may safely and effectively alleviate clinical symptoms, correct glucose and lipid metabolism disorders, and protect the renal function in patients with stage G3A3 DKD and the pattern of Qi-Yin deficiency combined with dampness-heat and blood stasis. The mechanism may be associated with inhibition of the ERS-apoptosis axis and delay of the RF process.
4.Real world clinical data analysis of fuzuloparib for the treatment of ovarian epithelial cancer patients
Danhui WENG ; Jie JIANG ; Yingjie YANG ; Mingqian LU ; Jiaying BAI ; Ming LIU ; Xiaoling LI ; Jun TIAN ; Yutao GUAN ; Quan LI ; Liang CHEN ; Qiubo LYU ; Lixia MA ; Yali WANG ; Huicheng XU ; Hailong GUO ; Li SUN ; Ding MA ; Qinglei GAO
Chinese Journal of Obstetrics and Gynecology 2025;60(8):590-599
Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.
5.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress mediated Bcl-2/Caspase-3 to improve diabetic kidney disease
Mingqian JIANG ; Binhua YE ; Yunjie YANG ; Kailin ZHENG ; Fang GUO ; Zhigang YANG ; Chen QIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1257-1269
Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10%YSJTD drug-containing serum(30 mmol/L high glucose+10%drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P<0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P<0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P<0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P<0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P<0.05).Compared to the model group,the 10%YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P<0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.
6.Analysis of Major Syndromes and Their Typical Related Symptoms and Signs in 135 Patients with Metabolic Syndrome:A Clinical Study Based on Syndrome Element Differentiation and Latent Class Analysis
Tong WANG ; Mingqian JIANG ; Lifen MI ; Shanyi SHEN ; Shujie XIA ; Candong LI
Journal of Traditional Chinese Medicine 2025;66(4):376-381
ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome (MS). MethodsTraditional Chinese medicine (TCM) diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis (LCA) were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes, and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included, involving 163 symptoms and signs with a total frequency of 1749; twenty-three syndrome elements were extracted, 367 times frequency in total, among which 8 syndrome elements occurred ≥10 times with 323 frequencies (88.01% of the total). These included location-related elements such as kidney (48 times), spleen (14 times), and stomach (14 times), and nature-related elements such as phlegm (71 times), yin deficiency (64 times), dampness (57 times), heat (42 times), and qi deficiency (13 times). Based on LCA, the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm, forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified,i.e. obesity (39 times), greasy coating (38 times), slippery pulse (33 times), white coating (31 times), preference for fatty and heavy foods (30 times), excessive urination (30 times), fatigue and lack of strength (29 times), wiry pulse (25 times), and dark red tongue (25 times). A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results, ultimately identifying obesity, greasy coating, fatigue and lack of strength, and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients (P<0.05). ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome, and obesity, greasy coating, fatigue and lack of strength, and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.
7.Real world clinical data analysis of fuzuloparib for the treatment of ovarian epithelial cancer patients
Danhui WENG ; Jie JIANG ; Yingjie YANG ; Mingqian LU ; Jiaying BAI ; Ming LIU ; Xiaoling LI ; Jun TIAN ; Yutao GUAN ; Quan LI ; Liang CHEN ; Qiubo LYU ; Lixia MA ; Yali WANG ; Huicheng XU ; Hailong GUO ; Li SUN ; Ding MA ; Qinglei GAO
Chinese Journal of Obstetrics and Gynecology 2025;60(8):590-599
Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.
8.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress mediated Bcl-2/Caspase-3 to improve diabetic kidney disease
Mingqian JIANG ; Binhua YE ; Yunjie YANG ; Kailin ZHENG ; Fang GUO ; Zhigang YANG ; Chen QIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(9):1257-1269
Objective To explore the mechanism of Yishen Jiangtang Decoction(YSJTD)in improving diabetic kidney disease(DKD)based on the apoptotic Bcl-2/Caspase-3 pathway mediated by endoplasmic reticulum stress(ERS).Methods Thirty 8-week-old SPF male db/db mice were used to establish the DKD model and were randomly divided into model,YSJTD,ERS inhibitor(4-phenylbutyric acid[4-PBA]),and control groups(db/m mice),with 10 mice per group.Mice in the YSJTD and 4-PBA groups were gavaged daily with 5.6 mg/(g·d)YSJTD or 0.5 mg/(g·d)4-PBA,respectively,whereas the model and control groups received sodium carboxymethyl cellulose.Each mouse was orally administered 0.01 mL/(g·d)for 8 weeks.The mice were administered 0.01 mL/(g·d)YSJTD or 0.5mg/(g·d)4-PBA via gavage for 8 weeks.The general condition of the mice was observed,and blood glucose and plasma lipid levels were measured.Oral glucose tolerance tests(OGTT)and insulin tolerance tests(ITT)were performed,and the area under the curve(AUC)was calculated.Renal pathological changes(assessed using hematoxylin and eosin,periodic acid-Schiff,and Masson staining)and cell apoptosis,evaluated via TUNEL staining,were examined.Protein expression levels of Caspase-3 and Bcl-2 in kidney tissues were analyzed using Western blotting.A DKD model was established using high-glucose-induced mouse glomerular mesangial cells,SV40 MES 13.The Cell Counting Kit-8 assay was used to screen for high glucose concentrations and to determine the concentration of the YSJTD drug-containing serum.Cells were divided into four groups:control,model(30 mmol/L high glucose),10%YSJTD drug-containing serum(30 mmol/L high glucose+10%drug-containing serum),and 1 mol/L 4-PBA(30 mmol/L high glucose+1 mmol/L 4-PBA).Western blotting was used to detect the protein levels of GRP78,Caspase-3,and Bcl-2 in the cells.Results Compared to the control group,the model,YSJTD,and 4-PBA groups exhibited significantly increased OGTT-AUC,ITT-AUC,triglyceride(TG),and cholesterol(CHOL)levels(P<0.05).These groups also showed severe renal pathological damage,increased glycogen deposition,and exacerbated fibrosis in kidney tissues.Compared to the model group,both the YSJTD and 4-PBA groups showed significantly reduced OGTT-AUC,TG,and CHOL levels,alleviated renal pathological damage,and decreased glycogen deposition and fibrosis.The YSJTD group also exhibited significantly reduced ITT-AUC(P<0.05).Compared to the control group,the model group exhibited an increased number of apoptotic cells in renal tissue,reduced Bcl-2 expression,and elevated Caspase-3 expression(P<0.05).Compared to the model group,both the YSJTD and 4-PBA groups demonstrated a reduced number of apoptotic cells,decreased Caspase-3 expression,and increased Bcl-2 expression,with the YSJTD group showing a more pronounced decrease in apoptotic cells(P<0.05).In vitro experiments revealed that,compared to the control group,the model group exhibited increased GRP78 and Caspase-3 expression,as well as decreased Bcl-2 expression(P<0.05).Compared to the model group,the 10%YSJTD drug-containing serum and 1 mol/L 4-PBA groups showed reduced GRP78 and Caspase-3 expression,as well as upregulated Bcl-2 expression(P<0.05).Conclusion YSJTD improves glucose and lipid metabolism disorders in DKD by inhibiting the ERS-induced apoptotic pathway mediated by Bcl-2/Caspase-3,thereby exerting protective effects on renal function.
9.Research progress on dyadic coping in patients with gestational diabetes mellitus and their spouses
Ran YANG ; Cuixia LIN ; Yanhui YANG ; Mingqian JIANG ; Rui YAO
Chinese Journal of Modern Nursing 2024;30(22):3076-3080
This article reviews the overview of dyadic coping, assessment tools, and the current application status of dyadic coping interventions in patients with gestational diabetes mellitus (GDM) and their spouses, aiming to provide a reference for related research.
10.Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins.
Jiang XU ; Shuai GUO ; Xianmei YIN ; Mingqian LI ; He SU ; Xuejiao LIAO ; Qiushi LI ; Liang LE ; Shiyu CHEN ; Baosheng LIAO ; Haoyu HU ; Juan LEI ; Yingjie ZHU ; Xiaohui QIU ; Lu LUO ; Jun CHEN ; Ruiyang CHENG ; Zhenzhan CHANG ; Han ZHANG ; Nicholas Chieh WU ; Yiming GUO ; Dianyun HOU ; Jin PEI ; Jihai GAO ; Yan HUA ; Zhihai HUANG ; Shilin CHEN
Acta Pharmaceutica Sinica B 2023;13(5):2234-2249
The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

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