The Wnt signaling is involved in angiogenesis and tumor development. β-catenin is the core component of the Wnt pathway, which mediates oncogenic transcription and regulated by a series of proteins. Sex-determining region Y-box 7 (SOX7) is a member of high-mobility-group transcription factor family, which inhibits oncogenic Wnt signaling in lots of tumor cells with unknown mechanism. By coimmunoprecipitation (co-IP) and super Topflash reporter assay, SOX7 can bind β-catenin and inhibit β-catenin/T cell factor (TCF)-mediated transcription. Meanwhile, B cell lymphoma 9 (BCL9) drives Wnt signaling path through direct binding-mediated β-catenin. Finally, we found that SOX7 inhibits oncogenic β-catenin-mediated transcription by disrupting the β-catenin/BCL9 interaction. Mechanistically, SOX7 compete with BCL9 to bind β-catenin. Our results show SOX7 inhibited Wnt signaling as suppressor and could be an important target for anticancer therapy.
Context Salvianolic acid B (SalB) can attenuate myocardial ischemia/reperfusion (I/R) injury, but the mechanisms are not entirely known. Objective Our study investigates if SalB protects cardiomyocytes against I/R injury by regulating Tripartite motif (TRIM) protein. Materials and methods AC16 cardiomyocytes were treated with I/R, and then with SalB (10, 25 and 50 μM) for 24 h, while control cells were cultured under normal conditions. Female Sprague-Dawley rats were subjected to I/R injury, and then intravenously injected with 20, 40, or 60 mg/kg SalB or saline, as a control, rats received sham operation and saline injection. Results Upon treatment, apoptotic rate, reactive oxygen species (ROS), and malondialdehyde (MDA) were increased 10-, 3.8-, and 1.3-fold, respectively, while superoxide dismutase (SOD) activity was reduced by 62.1% compared to control cells. I/R treatment elevated the mRNA and protein expression of TRIM8. SalB treatment remarkably abolished the above-mentioned effects of I/R treatment. TRIM8 knock-down could partially alleviate I/R-induced myocardial injury. TRIM8 overexpression promoted cardiomyocyte injury, which was alleviated by SalB. Moreover, TRIM8 negatively regulated protein expression of antioxidant enzyme glutathione peroxidase 1 (GPX1). TRIM8 protein interacted with GPX1 and TRIM8 overexpression promoted GPX1 ubiquitnation. GPX1 knock-down abolished the protective effects of SalB on I/R-injured cardiomyocytes. Our in vivo experiments confirmed the effects of SalB on I/R-induced myocardial injury. Discussion and conclusions SalB protected cardiomyocytes from I/R-induced apoptosis and oxidative stress in vitro and in vivo , which was partly mediated by the TRIM8/GPX1 axis. This suggests that down-regulation of TRIM8 expression may ameliorate I/R-induced myocardial injury.
Objective: To evaluate the efficacy of ginseng-containing traditional Chinese medicine (TCM) for acute decompensated heart failure (ADHF).Methods: Seven databases were included from establishment until 10 July 2022. Pooled data were analyzed with random-effects model. The risk of bias was measured by the risk of bias tool for randomized trials (RoB 2). Modified Jadad scale score was used to assess the quality of including studies. The meta-analysis was performed with RevMan 5.3. Trial sequential analysis was assessed to avoid type I errors. We have registered our protocol in PROSPERO (CRD42021267742).Results: Twenty-eight articles were included. The results demonstrated that compared with conventional western therapy (WT), ginseng-containing TCM combined with WT further improved clinical efficacy (RR: 1.25, 95% CI: 1.20–1.29, p < 0.00001, I2 = 8%), left ventricular ejection fraction (LVEF) (MD: 5.80, 95% CI: 4.86–6.74, p < 0.00001, I2 = 89%), stroke volume (MD: 13.80, 95% CI: 12.66–14.95, p < 0.00001, I2 = 93%), 6-min walk test (MD: 53.03, 95% CI: 20.76–85.29, p = 0.001, I2 = 97%), decreased 6-month rehospitalization (RR: 0.44, 95% CI: 0.18–1.11, p = 0.08, I2 = 0%), brain natriuretic peptide (MD: 188.12, 95% CI: 248.13 to -128.11, p < 0.00001, I2 = 94%), N-terminal pro-B-type natriuretic peptide (MD = -503.29; 95% CI: 753.18 to -253.40, p < 0.0001, I2 = 89%) and Minnesota living heart failure questionnaire scores (MD: 9.68, 95% CI: 13.67 to -5.70, p < 0.00001, I2 = 83%). The ROB2 assessment and modified Jaded scores showed most studies included were with some concerns.Conclusion: Compared with WT alone, ginseng-containing TCM is a possible way to benefit ADHF patients. However, limited by the quality of including trials, more high-quality studies are needed to provide reliable evidence.
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