Cells

Hyperglycemia is linked to a higher risk of diabetes, epilepsy, and seizures, which contribute to increased mortality. Previous research has shown that hyperglycemia impairs the function of the polyamine-dependent Kir4.1 channels in cultured astrocytes, and a similar effect was observed in male astrocytes from diabetic (db/db) mice. However, whether there are sex differences in this effect remains unclear. This study aims to compare Kir4.1 channel function in 10–12 week old brains of female db/db mice with that in males and non-diabetic heterozygous (db/+). We performed mRNA analyses, Western blotting (WB), glucose level measurements, and patch-clamp recordings from hippocampal astrocytes in brain slices to assess Kir4.1 channel activity in db/db and db/+ mice of both sexes. Our results showed increased glucose levels in diabetic db/db mice, especially in males, along with (1) reduced synthesis of Kir4.1 channel protein, (2) reduced membrane potential, (3) decreased Kir currents, and (4) compromised potassium uptake. Female diabetic astrocytes exhibited significantly lower barium-blocked Kir4.1 currents compared to diabetic males. Additionally, barium-insensitive currents (leakage currents) were upregulated in db/db mice, likely as a compensatory response to hyperglycemia. In conclusion, diabetes impairs astrocyte function by downregulating Kir4.1 channels, with a more pronounced effect in male diabetic mice. This impairment may increase seizure risk by affecting the ability of astrocytes to maintain extracellular ion balance.

Sunite sheep are well-adapted to the cold Mongolian steppe, exhibiting robust metabolic flexibility in which adipose tissue contributes significantly to energy homeostasis. Proteomics analysis of scapular fat in Sunite sheep during winter and summer identified 432 upregulated and 493 downregulated differentially expressed proteins (DEPs). These DEPs were notably enriched in essential biological functions such as energy metabolism, lipogenesis, and thermogenesis. Furthermore, they exhibited significant enrichment of signaling pathways such as oxidative phosphorylation and fatty acid metabolism. Meanwhile, the precursor protein of asprosin (ASP),profibrillin-1 (pFBN1), showed a marked decrease during winter. Given that ASP had been demonstrated to exert metabolic regulatory effects promoting lipid synthesis and suppressing thermogenesis in model animals, it was hypothesized that the seasonal downregulation of pFBN1 might drive adaptive thermogenesis through ASP. Therefore, this study focused on functional validation of the ASP-encoding gene FBN1 (fibrillin-1). In Adipose-Derived Mesenchymal Stem Cells (ADMSCs), FBN1 was specifically downregulated through overexpressing of its regulatory factor miR-29b-1. The results indicated that downregulation of the FBN1 led to the inhibition of adipogenesis in ADMSCs. This was reflected by a reduction in the number of lipid droplets, a decrease in the expression of adipogenesis marker genes, and a significant drop in triglyceride levels. Furthermore, the reduction in FBN1 levels enhanced the thermogenic function of differentiated adipocytes derived from ADMSCs, as evidenced by enhanced expression of thermogenic marker genes, along with a notable rise in both uncoupling protein 1 (UCP1) and non-esterified fatty acid (NEFA) levels.

The long-lasting, varied, and complicated nature of immune system issues in autoimmune disorders continues to make treatment difficult. Although standard immunosuppressive and biologic therapies have enhanced disease management, they infrequently provide enduring remission and often result in cumulative damage. Due to this, stem cell treatment has emerged as a potential alternative that aims to restore immunological homeostasis rather than maintain long-term immune suppression. This editorial review provides a comprehensive overview of the current evidence, unmet requirements, and future directions in the field, summarizing the primary contributions of the Special Issue “Stem Cell Therapy for Autoimmune Diseases”. We examine the conceptual distinction between immune reset, as demonstrated by hematopoietic stem cell transplantation, and immune modulation, which is facilitated by mesenchymal stromal cells and their secretome. Systemic sclerosis, neuroimmunological disorders, inflammatory bowel disease, and type 1 diabetes exhibit disease-specific clinical experiences that underscore both context-dependent limitations and therapeutic potential. Meanwhile, an urgent need to address persistent issues such as incomplete immune reconstitution, autoreactive memory cell-driven relapse, a lack of predictive biomarkers, safety concerns, and complex ethical and regulatory problems is addressed. This review concludes by offering perspectives on the future development of this approach, highlighting standardization, biomarker-driven patient selection, and next-generation techniques, including extracellular vesicles and genetically modified cells. This overview marks stem cell therapy as a crucial area of research for the treatment of autoimmune disorders.