Cthrc1 deficiency aggravates wound healing and promotes cardiac rupture after myocardial infarction via non-canonical WNT5A signaling pathway.

Cardiac fibroblasts are crucial for scar formation and cardiac repair after myocardial infarction (MI). Collagen triple helix repeat containing 1 (CTHRC1), an extracellular matrix protein, is involved in the pathogenesis of vascular remodeling, bone formation, and tumor progression. However, the role and underlying mechanism of CTHRC1 in post-MI wound repair are not fully clear. Bioinformatics analysis demonstrated CTHRC1 up-regulation in cardiac fibroblasts after ischemic cardiac injury. Serum levels of CTHRC1 were increased in MI mice and CTHRC1 expression was up-regulated in cardiac fibroblasts after MI. In vitro results showed that the induction of CTHRC1 expression in cardiac fibroblasts was mediated by canonical TGFß1-Smad2/3 signaling axis. Moreover, CTHRC1 improved wound healing and boosted cardiac fibroblast activation in vitro. Cthrc1 deficiency aggravated cardiac function and reduced collagen deposition as well as increased mortality attributable to cardiac rupture after MI. Consistent with above phenotypes, reduced the levels of myocardial CD31, α-smooth muscle actin, collagen I, and collagen III was observed, whereas myocardial expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 were increased in Cthrc1 knockout mice post-MI. Above effects could be partly reversed by rCTHRC1 protein or rWNT5A protein. Our study indicates that cardiac fibroblast-derived, canonical TGFß1-Smad2/3-dependent CTHRC1 could improve wound repair and prevent cardiac rupture after MI via selectively activating non-canonical WNT5A-PCP signaling pathway.

The Clinical Efficacy of Ginkgo biloba Leaf Preparation on Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Ginkgo biloba leaf preparations (GLPs) are widely used in ischemic stroke, and uncertainty remains regarding their clinical efficacy. To evaluate systematically the clinical efficacy and safety of GLPs in the treatment of ischemic stroke, we examine evidence from randomized controlled trials (RCTs). METHODS: We examine studies published prior to November 2021 that were found from searching the following sources: PubMed, China National Knowledge Infrastructure (CNKI), WANFANG DATA, Chongqing VIP (CQVIP) databases, and Chinese Biomedical Literature (CBM). We evaluated the quality of the included references according to the Cochrane Manual of Systematic Evaluation and Meta-analysis (MA) performed using RevMan 5.2 software. RESULTS: We included a total of 13 RCTs with clinical therapeutic effects, the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), hemorheology index, and adverse reaction index as evaluation criteria. There were 631 cases in the observation group and 629 cases in the control group. MA results showed the following: NIHSS WMD = -3.89, 95% CI: [-4.22, -3.56], I 2 = 19%, P < 0.00001. This index is often used with nerve injury and can also be used to judge the recovery of nerve function. A lower score means less nerve damage and a better chance of recovery. The BI results were WMD = 11.30, 95% CI: [9.83, 12.77], I 2 = 7%, P < 0.00001. This index was used to assess patients' ability to take care of themselves, with a higher score indicating a stronger ability to live independently. Clinical effective rate results were WMD = 3.79, 95% CI: [2.49, 5.78], I 2 = 0%, P < 0.00001, and this measure can be used to evaluate the effect of treatment clearly and objectively. Hemorheological index results show that plasma viscosity has WMD = -0.16, 95% CI: [-0.20, -0.12], I 2 = 40%, P < 0.00001 and fibrinogen (FIB) has WMD = -1.13, 95% CI: [-1.23, -1.04], I 2 = 0%, P < 0.00001. Plasma viscosity is mainly related to the amount of fibrinogen, and fibrinogen degradation is an important function of the fibrinolytic system. The imbalance of the fibrinolytic system plays an important role in the pathogenesis of cerebral infarction. Fibrinogen is a risk factor of ischemic cerebrovascular disease. Studies have shown that the infarct size of patients with secondary cerebral infarction after CEREBRAL infarction is correlated with their FIB level. In addition, FIB elevation is also one of the risk factors for early infarction after thrombolysis. Therefore, FIB can be used as a detection index for the prevention of cerebral infarction recurrence adverse reactions. Our MA results for FIB show WMD = 0.81, 95% CI: [0.38, 1.73], I 2 = 0%, P = 0.58, and RR < 1. CONCLUSION: The existing clinical evidence shows that GLP has a good therapeutic effect on patients with ischemic stroke and can improve their hemorheology indices. In addition, GLP is shown to be relatively safe.