Percutaneous Closure vs. Surgical Repair for Postinfarction Ventricular Septal Rupture: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ventricular septal rupture is an important high-mortality complication in the scope of myocardial infarctions. The effectiveness of different treatment modalities is still controversial. This meta-analysis compares the efficacy of percutaneous closure vs. surgical repair for the treatment of postinfarction ventricular septal rupture (PI-VSR). METHODS: A meta-analysis was performed on relevant studies found through PubMed®, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (or CNKI), Wanfang Data, and VIP databases searching. The primary outcome was a comparison of in-hospital mortality between the two treatments, and the secondary outcome was documentation of one-year mortality, postoperative residual shunts, and postoperative cardiac function. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. RESULTS: Qualified studies (742 patients from 12 trials) were found and investigated for this meta-analysis (459 patients in the surgical repair group, 283 patients in the percutaneous closure group). When comparing surgical repair to percutaneous closure, it was found that the former significantly reduced in-hospital mortality (OR: 0.67, 95% CI 0.48-0.96, P=0.03) and postoperative residual shunts (OR: 0.03, 95% CI 0.01-0.10, P<0.00001). Surgical repair also improved postoperative cardiac function overall (OR: 3.89, 95% CI 1.10-13.74, P=0.04). However, there was no statistically significant difference in one-year mortality between the two surgical strategies (OR: 0.58, 95% CI 0.24-1.39, P=0.23). CONCLUSION: We found that surgical repair appears to be a more effective therapeutic option than percutaneous closure for PI-VSR.

TRIM6 silencing for inhibiting growth and angiogenesis of gliomas by regulating VEGFA.

Gliomas are the highest prevalent primary central nervous system (CNS) cancers with poor overall survival rate. There is an urgent need to conduct more research into molecular therapies targeting critical elements of gliomas. This study herein targeted to assess the impact of tripartite motif protein 6 (TRIM6) on gliomas. Using public databases, we found the increased TRIM6 expression in tissues of glioma which was linked with worst overall survival. Silencing TRIM6 promoted glioma cell proliferation, migration and angiogenesis, suggesting the promoting effects of TRIM6 on gliomas. Knockdown of TRIM6 expression downregulated the expression levels of Forkhead box M1 (FOXM1) and vascular endothelial growth factor A (VEGFA) in glioma cells. Afterwards, impact of TRIM6 on VEGFA expression was regulated by FOXM1. VEGFA overexpression reversed the decreased abilities of glioma cell proliferation, migration and angiogenesis caused by silencing TRIM6. Furthermore, we also found that TRIM6 promoted the growth of gliomas in the xenograft mouse model. In summary, the expression of TRIM6 was increased which was related to poor prognosis of glioma patients. TRIM6 promoted glioma cell proliferation, migration and angiogenesis through the FOXM1-VEGFA pathway. Therefore, TRIM6 carries capacity to be explored as a novel therapeutic target in clinical.

Percutaneous Closure vs. Surgical Repair for Postinfarction Ventricular Septal Rupture: A Systematic Review and Meta-Analysis

ABSTRACT Introduction: Ventricular septal rupture is an important high-mortality complication in the scope of myocardial infarctions. The effectiveness of different treatment modalities is still controversial. This meta-analysis compares the efficacy of percutaneous closure vs. surgical repair for the treatment of postinfarction ventricular septal rupture (PI-VSR). Methods: A meta-analysis was performed on relevant studies found through PubMed®, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (or CNKI), Wanfang Data, and VIP databases searching. The primary outcome was a comparison of in-hospital mortality between the two treatments, and the secondary outcome was documentation of one-year mortality, postoperative residual shunts, and postoperative cardiac function. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. Results: Qualified studies (742 patients from 12 trials) were found and investigated for this meta-analysis (459 patients in the surgical repair group, 283 patients in the percutaneous closure group). When comparing surgical repair to percutaneous closure, it was found that the former significantly reduced in-hospital mortality (OR: 0.67, 95% CI 0.48-0.96, P=0.03) and postoperative residual shunts (OR: 0.03, 95% CI 0.01-0.10, P<0.00001). Surgical repair also improved postoperative cardiac function overall (OR: 3.89, 95% CI 1.10-13.74, P=0.04). However, there was no statistically significant difference in one-year mortality between the two surgical strategies (OR: 0.58, 95% CI 0.24-1.39, P=0.23). Conclusion: We found that surgical repair appears to be a more effective therapeutic option than percutaneous closure for PI-VSR.

Components of Salvia miltiorrhiza and Panax notoginseng Protect Pericytes Against OGD/R-Induced Injury via Regulating the PI3K/AKT/mTOR and JNK/ERK/P38 Signaling Pathways.

Salvia miltiorrhiza (SAL) and Panax notoginseng (PNS) are widely used in treating of ischemic stroke. However, it is unknown which components of SAL and PNS protect brain microvascular pericytes after an ischemic stroke. We evaluated the protective effects and mechanisms of SAL and PNS components in pericytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Pericytes were subjected to OGD/R. Cell Counting Kit-8 (CCK-8) was used to evaluate cell viability. ROS and SOD kits were used to detect oxidative stress. Flow cytometry was performed to analyze cell apoptosis. To evaluate cell migration, a scratch assay was performed. Expression of cleaved caspase-3, Bcl-2, Bax, VEGF, Ang-1, PDGFR-ß, PI3K/AKT/mTOR, and JNK/ERK/P38 signaling pathways were identified using western blot. The results revealed that salvianolic acid B (Sal B), salvianolic acid D (Sal D), notoginsenoside R1 (R1), ginsenoside Rb1 (Rb1), and ginsenoside Rg1 (Rg1) increased the cell viability of pericytes subjected to OGD/R, reduced the level of ROS, and increased the expression of SOD. The components reduced cell apoptosis, increased the protein level of Bcl-2/Bax, reduced the level of cleaved caspase-3/caspase-3, increased cell migration, and enhanced the levels of Ang-1, PDGFR-ß, and VEGF. The components could activate PI3K/AKT/mTOR pathway while inhibiting the JNK/ERK/P38 pathway. Studies found that Sal B, Sal D, R1, Rb1, and Rg1 inhibited oxidative stress and apoptosis while increasing the release of pro-angiogenic regulators of pericytes related to the PI3K/AKT/mTOR and JNK/ERK/P38 signaling pathways. This provides a potential foundation for developing monomeric drugs for treating ischemic stroke.

Preclinical evidence and possible mechanisms of ß-asarone for rats and mice with Alzheimer's disease: A systematic review and meta-analysis.

Background: Currently, there are many different drugs to improve Alzheimer's disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients. Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of ß-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models. Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of ß-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP. Results: For the primary endpoint, compared with the modeling group, ß-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31-2.70). For the secondary endpoint, ß-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = -2.25, 95% CI: -2.49 to -2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = -2.40, 95% CI: -3.51 to -1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38-0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = -0.70, 95% CI: -0.93 to -0.47) over the control group. Conclusion: ß-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways.

SETD3 Methyltransferase Regulates PLK1 Expression to Promote In Situ Hepatic Carcinogenesis.

Background: The development of a new strategy to overcome chemoresistance to hepatocellular carcinoma (HCC) treatment is a long-standing issue. We have previously found that upregulated SETD3 levels are closely correlated with HCC. This study aims to explore the mechanism underlying how upregulation of SETD3 promotes liver carcinogenesis. Methods: RNA-Sequencing analysis was used to explore the correlation of SETD3 with regulatory targets. In vitro assays including cell proliferation and migration were performed to study the oncogenic roles of SETD3 and PLK1. Western blotting, immunohistochemical staining, and blood biochemical assays were performed to examine protein expression or pathological index in tumor tissues and mice liver tissues. Luciferase reporter system and chromatin immunoprecipitation assays were used to explore the mechanism. Results: We revealed that SETD3 regulates gene expression in subgroups, including cell division, cell proliferation, and cell cycle, in hepatocellular tumor cells. We found that SETD3 upregulation is associated with elevated PLK1 level in both hepatic tumor cells and clinical liver tissues. We further showed that overexpression of SETD3 promoted tumor cell proliferation and migration, whereas inhibition of PLK1 activity attenuated these phenotypes caused by SETD3. By taking advantage of the Sleep Beauty transposase system, we confirmed that upregulated mouse Setd3 promoted hepatic carcinogenesis in situ, but knockdown of mouse Plk1 mitigated Setd3-promoted tumorigenesis in mice. Mechanistically, we showed that SETD3 could be recruited to the promoter of PLK1 gene to facilitate PLK1 transcription. Conclusions: Our data demonstrate that elevated SETD3 may promote HCC by enhancing PLK1 expression, which suggests that SETD3 may act as a potential drug target combined with PLK1 inhibition to treat HCC.

Xueshuantong injection combined with Salvianolate lyophilized injection improves the synaptic plasticity against focal cerebral ischemia/reperfusion injury in rats through PI3K/AKT/mTOR and RhoA/ROCK pathways.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.