Ischemic stroke is a multi-factorial cerebrovascular disease with high worldwide morbidity and mortality. In the past few years, multiple studies have revealed the underlying mechanism of ischemia/reperfusion injury, including calcium overload, amino acid toxicity, oxidative stress, and inflammation. Connexin 43 (Cx43), the predominant connexin protein in astrocytes, has been recently proven to display non-substitutable roles in the pathology of ischemic stroke development and progression through forming gap junctions and hemichannels. Under normal conditions, astrocytic Cx43 could be found in hemichannels or in the coupling with other hemichannels on astrocytes, neurons, or oligodendrocytes to form the neuro-glial syncytium, which is involved in metabolites exchange between communicated cells, thus maintaining the homeostasis of the CNS environment. In ischemic stroke, the phosphorylation of Cx43 might cause the degradation of gap junctions and the opening of hemichannels, contributing to the release of inflammatory mediators. However, the remaining gap junctions could facilitate the exchange of protective and harmful metabolites between healthy and injured cells, protecting the injured cells to some extent or damaging the healthy cells depending on the balance of the exchange of protective and harmful metabolites. In this study, we review the changes in astrocytic Cx43 expression and distribution as well as the influence of these changes on the function of astrocytes and other cells in the CNS, providing new insight into the pathology of ischemic stroke injury; we also discuss the potential of astrocytic Cx43 as a target for the treatment of ischemic stroke.

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Migration is one of the five major behaviors of cells. Although RhoC—a classic member of the Rho gene family—was first identified in 1985, functional RhoC data have only been widely reported in recent years. Cell migration involves highly complex signaling mechanisms, in which RhoC plays an essential role. Cell migration regulated by RhoC—of which the most well-known function is its role in cancer metastasis—has been widely reported in breast, gastric, colon, bladder, prostate, lung, pancreatic, liver, and other cancers. Our review describes the role of RhoC in various types of cell migration. The classic two-dimensional cell migration cycle constitutes cell polarization, adhesion regulation, cell contraction and tail retraction, most of which are modulated by RhoC. In the three-dimensional cell migration model, amoeboid migration is the most classic and well-studied model. Here, RhoC modulates the formation of membrane vesicles by regulating myosin II, thereby affecting the rate and persistence of amoeba-like migration. To the best of our knowledge, this review is the first to describe the role of RhoC in all cell migration processes. We believe that understanding the detail of RhoC-regulated migration processes will help us better comprehend the mechanism of cancer metastasis. This will contribute to the study of anti-metastatic treatment approaches, aiding in the identification of new intervention targets for therapeutic or genetic transformational purposes.

Cartilage defects are among the most difficult diseases to cure in clinic. Due to the limited regeneration capacity of chondrocytes, cartilage regeneration is very difficult. Tissue engineering is a potential strategy for cartilage regeneration. The choice of scaffold is a key factor for the successful construction of tissue engineering cartilage. In this research, we successfully constructed the silk/silk fibroin/gelatin/polylactic acid porous microspheres (S/SF/G/PLLA-PMs) scaffold, then further evaluated the physical and chemical properties and biocompatibility of the composite cartilage tissue in vitro and in vivo, also the long-term survival of the composite cartilage in large animals was carried out. The research results showed that S/SF/G/PLLA-PMs composite scaffold had good biocompatibility. The addition of L-polylactic acid porous microspheres (PLLA-PMs) could significantly enhance the mechanical strength of the scaffold and achieve a multi-level pore structure. After 4 weeks of culture in vitro, composite cartilage could be constructed. Further immunohistochemical results showed that S/SF/G/PLLA-PMs scaffold could increase the long-term stability of the composite cartilage transplantation in vivo.

Background Previous studies have reported inconsistent results on the association between circulating lipids and lipid-lowering drugs with the risk of epilepsy. Objective To assess whether genetically predicted circulating lipids and lipid-lowering drugs are causally associated with the risk of epilepsy outcome. Methods We performed a two-sample Mendelian Randomization (MR) analysis model to genetically predict the causal effects of circulating lipids (Apolipoprotein A [APOA] Apolipoprotein B [APOB], Cholesterol, High density lipoprotein cholesterol [HDL-C], Low density lipoprotein cholesterol [LDL-C], Lipoprotein A, Triglycerides) and lipid-lowering drugs (HMG-CoA reductase [HMGCR] and Proprotein Convertase Subtilisin/Kexin Type 9 [PCSK9] inhibitors) on epilepsy. Nine MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (simple mode, weighted mode, simple median, weighted median, penalized weighted median, MR Egger, and MR-Egger [bootstrap)) were conducted as the complement to IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis. Results The IVW analysis method demonstrated that there is no causal association between circulating lipids (APOA: odds ratio [OR], 0.958, 95% confidence interval (CI), 0.728-1.261, P=0.760; APOB: OR, 1.092; 95% CI, 0.979-1.219, P=0.115; Cholesterol: OR, 1.210; 95% CI, 0.981-1.494, P=0.077; HDL-C: OR, 0.964; 95% CI, 0.767-1.212, P=0.753; LDL-C: OR, 1.100; 95% CI, 0.970-1.248, P=0.137; Lipoprotein A: OR, 1.082; 95% CI, 0.849-1.379, P=0.528; Triglycerides: OR, 1.126; 95% CI, 0.932-1.360, P=0.221) and lipid-lowering drugs (HMGCR inhibitors: OR, 0.221; 95% CI, 0.006-8.408, P=0.878; PCSK9 inhibitors: OR, 1.112; 95% CI, 0.215-5.761, P=0.902) with risk of epilepsy. The other MR analysis methods and further leave-one-out sensitivity analysis confirmed the robustness of final results. Conclusion This MR study demonstrated that there was no genetically predicted causal relationships between circulating lipids and lipid-lowering drugs with the risk of epilepsy.