The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene.

Astrocytes perform multiple essential functions in the developing and mature brain, including regulation of synapse formation, control of neurotransmitter release and uptake, and maintenance of extracellular ion balance. As a result, astrocytes have been implicated in the progression of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. Despite these critical functions, the study of human astrocytes can be difficult because standard differentiation protocols are time-consuming and technically challenging, but a differentiation protocol recently developed in our laboratory enables the efficient derivation of astrocytes from human embryonic stem cells. We used this protocol along with microarrays, luciferase assays, electrophoretic mobility shift assays, and ChIP assays to explore the genes involved in astrocyte differentiation. We demonstrate that paired-like homeodomain transcription factor 1 (PITX1) is critical for astrocyte differentiation. PITX1 overexpression induced early differentiation of astrocytes, and its knockdown blocked astrocyte differentiation. PITX1 overexpression also increased and PITX1 knockdown decreased expression of sex-determining region Y box 9 (SOX9), known initiator of gliogenesis, during early astrocyte differentiation. Moreover, we determined that PITX1 activates the SOX9 promoter through a unique binding motif. Taken together, these findings indicate that PITX1 drives astrocyte differentiation by sustaining activation of the SOX9 promoter.

Mitochondrial transplantation: an overview of a promising therapeutic approach.

Mitochondrial transplantation is a promising therapeutic approach for the treatment of mitochondrial diseases caused by mutations in mitochondrial DNA, as well as several metabolic and neurological disorders. Animal studies have shown that mitochondrial transplantation can improve cellular energy metabolism, restore mitochondrial function, and prevent cell death. However, challenges need to be addressed, such as the delivery of functional mitochondria to the correct cells in the body, and the long-term stability and function of the transplanted mitochondria. Researchers are exploring new methods for mitochondrial transplantation, including the use of nanoparticles or CRISPR gene editing. Mechanisms underlying the integration and function of transplanted mitochondria are complex and not fully understood, but research has revealed some key factors that play a role. While the safety and efficacy of mitochondrial transplantation have been investigated in animal models and human trials, more research is needed to optimize delivery methods and evaluate long-term safety and efficacy. Clinical trials using mitochondrial transplantation have shown mixed results, highlighting the need for further research in this area. In conclusion, although mitochondrial transplantation holds significant potential for the treatment of various diseases, more work is needed to overcome challenges and evaluate its safety and efficacy in human trials. [BMB Reports 2023; 56(9): 488-495].

Depletion of Janus kinase-2 promotes neuronal differentiation of mouse embryonic stem cells.

Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3ꞵ, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTPbound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3ß/Fyn/CDK5 signaling pathway responsible for morphological maturation. [BMB Reports 2021; 54(12): 626-631].

Succinonitrile as a corrosion inhibitor of copper current collectors for overdischarge protection of lithium ion batteries.

Succinonitrile (SN) is investigated as an electrolyte additive for copper corrosion inhibition to provide overdischarge (OD) protection to lithium ion batteries (LIBs). The anodic Cu corrosion, occurring above 3.5 V (vs Li/Li(+)) in conventional LIB electrolytes, is suppressed until a voltage of 4.5 V is reached in the presence of SN. The corrosion inhibition by SN is ascribed to the formation of an SN-induced passive layer, which spontaneously develops on the copper surface during the first anodic scan. The passive layer is composed mainly of Cu(SN)2PF6 units, which is evidenced by Raman spectroscopy and electrochemical quartz crystal microbalance measurements. The effects of the SN additive on OD protection are confirmed by using 750 mAh pouch-type full cells of LiCoO2 and graphite with lithium metal as a reference electrode. Addition of SN completely prevents corrosion of the copper current collector in the full cell configuration, thereby tuning the LIB chemistry to be inherently immune to the OD abuses.

Fermented garlic protects diabetic, obese mice when fed a high-fat diet by antioxidant effects.

This study examined the bioactivity of yeast (Saccharomyces cerevisiae)-fermented aged black garlic (FBG) on obese mice supplied a high-fat diet (HFD) and its in vitro antioxidant activity. Aged black garlic (BG) exhibits potent antioxidative effects and has been subjected to extensive research. In addition, the bioactivity of some natural products is increased by fermentation. In a preliminary test, this study found that the antioxidant activity of FBG is stronger than that of BG. Therefore, it was hypothesized that the bioactivity of BG would be increased by yeast fermentation and would be a good candidate as a nutraceutical product for improving the oxidative defense systems in older patients or patients affected by various oxidative stresses, for example, diabetes and diabetic complications. To test this hypothesis, the bioactivities of FBG in diabetic and obese mice as well as the antioxidant activity in vitro were examined. After 91 days of continuous HFD supply, the mice showed marked obesity, hyperglycemia, hyperlipemia, and liver and kidney damages. Black garlic and all 3 different doses of FBG showed favorable hepatoprotective, nephroprotective, hypolipidemic, and antiobesity effects compared with the HFD control, but no hypoglycemic effects. In particular, more favorable bioactivity against all 4 HFD-induced diabetic complications was detected in the FBG-treated groups compared with the group given equivalent doses of BG. These findings suggest that the bioactivities of BG can be improved by yeast fermentation.