Diet-derived circulating antioxidants and risk of epilepsy: A study combining metabolomics and mendelian randomization.

Background: Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy. Objective: This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy. Methods: Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode). Results: Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335-0.905, P = 0.018) with genetically determined higher absolute circulating ß-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness. Conclusion: This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for ß-carotene.

Causal relationship between addictive behaviors and epilepsy risk: A mendelian randomization study.

BACKGROUND: Previous studies have reported inconsistent results regarding the potential relationships between addictive behaviors and the risk of epilepsy. OBJECTIVE: To assess whether genetically predicted addictive behaviors are causally associated with the risk of epilepsy outcomes. METHODS: The causation between five addictive behaviors (including cigarettes per day, alcoholic drinks per week, tea intake, coffee intake, and lifetime cannabis use) and epilepsy was evaluated by using a two-sample Mendelian Randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR Egger, weighted median, simulation extrapolation corrected MR-Egger, and Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO)) were performed to complement IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis. RESULTS: The IVW analysis method indicated an approximately 20% increased risk of epilepsy per standard deviation increase in lifetime cannabis use (odds ratio [OR], 1.20; 95% confidence interval [CI]), 1.02-1.42, P = 0.028). However, there is no causal association between the other four addictive behaviors and the risk of epilepsy (cigarettes per day: OR, 1.04; 95% CI, 0.92-1.18, P = 0.53; alcoholic drinks per week: OR, 1.31; 95% CI, 0.93-1.84, P = 0.13; tea intake: OR, 1.15; 95% CI, 0.84-1.56, P = 0.39; coffee intake: OR, 0.86; 95% CI, 0.59-1.23, P = 0.41). The other MR analysis methods and further leave-one-out sensitivity analysis suggested the results were robust. CONCLUSION: This MR study indicated a potential genetically predicted causal association between lifetime cannabis use and higher risk of epilepsy. As for the other four addictive behaviors, no evidence of a causal relationship with the risk of epilepsy was found in this study.

The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke.

Ischemic stroke is the predominant cause of severe morbidity and mortality worldwide. Post-stroke neuroinflammation has recently received increasing attention with the aim of providing a new effective treatment strategy for ischemic stroke. Microglia and astrocytes are major components of the innate immune system of the central nervous system. They can be involved in all phases of ischemic stroke, from the early stage, contributing to the first wave of neuronal cell death, to the late stage involving phagocytosis and repair. In the early stage of ischemic stroke, a vicious cycle exists between the activation of microglia and astrocytes (through astrocytic connexin 43 hemichannels), aggravating neuroinflammatory injury post-stroke. However, in the late stage of ischemic stroke, repeatedly activated microglia can induce the formation of glial scars by triggering reactive astrogliosis in the peri-infarct regions, which may limit the movement of activated microglia in reverse and restrict the diffusion of inflammation to healthy brain tissues, alleviating the neuroinflammatory injury poststroke. In this review, we elucidated the various roles of astrocytes and microglia and summarized their relationship with neuroinflammation. We also examined how astrocytes and microglia influence each other at different stages of ischemic stroke. Several potential therapeutic approaches targeting astrocytes and microglia in ischemic stroke have been reviewed. Understanding the details of astrocytemicroglia interaction processes will contribute to a better understanding of the mechanisms underlying ischemic stroke, contributing to the identification of new therapeutic interventions.

Causal relationship between human blood omega-3 fatty acids and the risk of epilepsy: A two-sample Mendelian randomization study.

Background: Though omega-3 fatty acids reduce seizures in several animal models, considerable controversy exists regarding the association between omega-3 fatty acids and epilepsy in human. Objective: To assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes. Methods: We conducted a two-sample Mendelian randomization (MR) analysis by applying summary statistics of genome-wide association study datasets of both exposure and outcomes. Single nucleotide polymorphisms significantly associated with blood omega-3 fatty acids levels were selected as instrumental variables to estimate the causal effects on epilepsy. Five 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 (MR-Egger, weighted median, simple mode, and weighted mode) were conducted as the complement to IVW. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. Results: Genetically predicted the increase of human blood omega-3 fatty acids levels was associated with a higher risk of epilepsy (OR = 1.160, 95%CI = 1.051-1.279, P = 0.003). Conclusions: This study revealed a causal relationship between blood omega-3 fatty acids and the risk of epilepsy, thus providing novel insights into the development mechanism of epilepsy.

Cross-linking methods of type I collagen-based scaffolds for cartilage tissue engineering.

Cartilage defects are one of the hardest injures to cure, given the limited regenerative ability of cartilage tissues. Moreover, cartilage defects affect an increasing number of people worldwide. Therefore, scientists have attempted to develop effective strategies to repair cartilage defects in recent years. Recent advances in tissue engineering have led to the strategies for inducing cartilage regeneration. Among the emerging strategies, scaffolds are commonly used in cartilage tissue engineering (CTE) as they provide favorable environment for the growth and proliferation of chondrocytes. An ideal scaffolding material should be highly biocompatible. Type I collagen is one such material, which is widely used in CTE. However, type I collagen has poor mechanical properties and stability, which limit its use. Cross-linking is a simple method known to improve degradability, biological and mechanical properties of biomaterials by enhancing chemical and physical interactions between polymers. Cross-linking can be induced through chemical, physical or biological processes. In this review, we present cross-linking methods that can enhance the mechanical strength of type I collagen for CTE and highlight future directions in this field.

Role of RhoC in cancer cell migration.

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.

L-polylactic acid porous microspheres enhance the mechanical properties and in vivo stability of degummed silk/silk fibroin/gelatin scaffold.

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.

Small molecule compounds promote the proliferation of chondrocytes and chondrogenic differentiation of stem cells in cartilage tissue engineering.

The application of tissue engineering to generate cartilage is limited because of low proliferative ability and unstable phenotype of chondrocytes. The sources of cartilage seed cells are mainly chondrocytes and stem cells. A variety of methods have been used to obtain large numbers of chondrocytes, including increasing chondrocyte proliferation and stem cell chondrogenic differentiation via cytokines, genes, and proteins. Natural or synthetic small molecule compounds can provide a simple and effective method to promote chondrocyte proliferation, maintain a stable chondrocyte phenotype, and promote stem cell chondrogenic differentiation. Therefore, the study of small molecule compounds is of great importance for cartilage tissue engineering. Herein, we review a series of small molecule compounds and their mechanisms that can promote chondrocyte proliferation, maintain chondrocyte phenotype, or induce stem cell chondrogenesis. The studies in this field represent significant contributions to the research in cartilage tissue engineering and regenerative medicine.

The Multifaceted Role of Astrocyte Connexin 43 in Ischemic Stroke Through Forming Hemichannels and Gap Junctions.

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.