lncRNA-XIST protects the hypoxia-induced cardiomyocyte injury through regulating the miR-125b-hexokianse 2 axis.

Ischemic injury in the heart is associated with low oxygen, leading to the damage of cardiomyocytes. The lncRNA-XIST is known to involve in post-ischemia myocardial remodeling. However, the roles and mechanism of XIST in the hypoxia-induced cardiomyocyte are still under investigation. Moreover, studies that elucidated the impaired glucose metabolism present new hallmark of ischemic cardiovascular injury. The objective of this study is to investigate the effects of lncRNA-XIST on cardiomyocyte injury under hypoxia. Here, we demonstrate that the XIST expressions of cardiomyocyte line, H9c2 were apparently suppressed by long-time hypoxia exposure under low glucose supply. On the contrary, miRNA-125b showed reverse expression pattern to XIST. We identified that XIST functioned as a ceRNA of miR-125b to downregulate its expression in both cell line and rat primary cardiomyocyte. Under low glucose supply, H9c2 cells exhibited increased susceptibility to hypoxia. We observed overexpression of XIST significantly elevated glycose metabolism rate under hypoxia, but overexpression of miR-125b inhibited glycose metabolism rate of cardiomyocyte under hypoxia. The glycolysis enzyme, hexokinase 2 (HK2) was validated as a direct target of miR-125b, which binds to the 3'-UTR region of HK2 mRNA in cardiomyocytes. Moreover, inhibition of miR-125b significantly protected the hypoxia-induced cardiomyocyte injury through restoration of glucose metabolism. Finally, we demonstrated that transfection of miR-125b in lncRNA-XIST overexpressed H9c2 cells effectively abolished the XIST-activated glucose metabolism and cardiomyocyte protection under hypoxia. The present study illustrates roles of the XIST-miR-125b-HK2 axis in the hypoxia-induced cardiomyocyte injury and proposes that maintaining glucose metabolism might be an effective approach for protection of cardiomyocyte injury.

Neural stem cell transplantation for the treatment of primary torsion dystonia: A case report.

Primary torsion dystonia (PTD) occurs due to a genetic mutation and often advances gradually. Currently, there is no therapy available that is able to inhibit progression. Neural stem cells (NSCs) are being investigated as potential therapies for neurodegenerative diseases, such as stroke and trauma. The present study evaluated the clinical effectiveness of NSC transplantation in an 18-year-old male patient with PTD, to assess the ability of this therapy to inhibit PTD progression. Genetic testing of the patient revealed a mutation in the torsion dystonia-1 (DYT1) gene (907-909 delGAG). NSCs were bilaterally implanted in the globus pallidus of the patient through stereotactic surgery. Prior to surgery, the patient's Burke-Fahn-Marsden dystonia movement score (BFMDMS) was 21, which progressively decreased after surgery to 18, 17, 15 and 13 at 1, 2, 3 and 4 postoperative years, respectively. BFMDMS was improved by 38.1% over the 4 postoperative years. Although computed tomography and magnetic resonance imaging examinations showed no significant changes prior to and following surgery, postoperative brain positron emission tomography scans revealed increased glucose metabolism in the transplanted region. The clinical efficacy of NSC transplantation in this patient suggests its potential for the treatment of DYT1-positive patients with PTD.

Extracellular α-synuclein--a possible initiator of inflammation in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons of the substantia nigra and the presence of Lewy bodies which contain high levels of α-synuclein. Although the causative factors of PD remain unclear, the progression of PD is accompanied by a highly localized inflammatory response mediated by reactive microglia. Recently, attention has focused on the relationship between α-synuclein and microglial activation. This review examines the role of α-synuclein on microglia in PD pathogenesis and progression, we also discuss the way of α-synuclein induced microglial activation.