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Aim: The purpose of the study was to observe the ultrastructural changes of neuronal mitochondria in perihematomal brain tissue and assess the therapeutic potential of Huperzine A (HA, a mitochondrial protector) following intracerebral hemorrhage (ICH). Methods: Brain hemorrhage was induced in adult Sprague Dawley rats by injecting autologous blood into the striatum and then removing the brains 3, 6, 12, 24, or 48 hours later to analyze mitochondrial ultrastructure in a blinded manner. Parallel groups of ICH rats were treated with HA or saline immediately after ICH. Perihematomal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase-3 activation and cytochrome C translocation were tracked by immunoblots, and neurobehavioral test results were compared between the groups. Results: Mitochondria in perihematomal neurons demonstrated dramatic changes including mitochondrial swelling, intracristal dilation, and decreased matrix density. HA treatment decreased mitochondrial injury and apoptosis, inhibited caspase-3 activation and cytochrome C translocation, and improved behavioral recovery. Conclusion: These data show that ICH induces dramatic mitochondrial damage, and HA exhibits protective effects possibly through ameliorating mitochondrial injury and apoptosis. Collectively, these findings suggest a new direction for novel therapeutics. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epidemiological studies have indicated that noise exposure is associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the nature of the connection between noise exposure and T2DM remains to be explored. OBJECTIVES: We explored whether and how noise exposure affects glucose homeostasis in mice as the initial step toward T2DM development. METHODS: Male ICR mice were randomly assigned to one of four groups: the control group and three noise groups (N20D, N10D, and N1D), in which the animals were exposed to white noise at 95 decibel sound pressure level (dB SPL) for 4 hr per day for 20 successive days, 10 successive days, or 1 day, respectively. Glucose tolerance and insulin sensitivity were evaluated 1 day, 1 week, and 1 month after the final noise exposure (1DPN, 1WPN, and 1MPN). Standard immunoblots, immunohistochemical methods, and enzyme -linked immunosorbent assays (ELISA) were performed to assess insulin signaling in skeletal muscle, the morphology of β cells, and plasma corticosterone levels. RESULTS: Noise exposure for 1 day caused transient glucose intolerance and insulin resistance, whereas noise exposure for 10 and 20 days had no effect on glucose tolerance but did cause prolonged insulin resistance and an increased insulin response to glucose challenge. Akt phosphorylation and GLUT4 translocation in response to exogenous insulin were decreased in the skeletal muscle of noise -exposed animals. CONCLUSIONS: Noise exposure at 95 dB SPL caused insulin resistance in male ICR mice, which was prolonged with longer noise exposure and was likely related to the observed blunted insulin signaling in skeletal muscle. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect and mechanism of valproic acid (VPA) on the neurosphere formation in rat embryonic cortical cells. We used free-floating neurosphere formation as a model system to evaluate the VPA on the proliferation of neural stem cells (NSCs). We found a time- and dose-dependent increase in neurosphere formation and NSC proliferation after VPA treatment. Further RNA-seq analysis demonstrated that the upregulated TGFβ1 signaling might attribute to the effect of VPA on the neurosphere formation and NSC proliferation. Consistently, the neurosphere formation and NSC proliferation were blocked by the treatment with SB431542, an inhibitor of TGFβ1 receptor. Moreover, in a coculture system, NSCs treated with VPA significantly reduced the oxygen-glucose deprivation-induced neuronal apoptosis. Taken together, our results showed that VPA could enhance neurosphere formation and NSC proliferation by activating TGFβ1, which might be a novel therapeutic strategy for neurological disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of thyroid dysfunction (TD) and IgG subclasses of thyroid autoantibodies (TAs) and to determine the predictive factors of TD in chronic hepatitis C (CHC) patients. Design: Three hundred and twelve untreated hepatitis C virus-infected patients without a history of TD or treatment with thyroid hormones were enrolled in a cross-sectional study. Clinical and biological factors were statistically analyzed to determine the correlation between TD and this patient population. Results: The incidence of TD was 12.5% in CHC patients. Clinical hypothyroidism (5.8%) and subclinical hypothyroidism (3.8%) were more frequent than clinical hyperthyroidism (1.6%) and subclinical hyperthyroidism (1.3%). The percentage of TA-positive patients was significantly higher in people >60 years than in those ⩽60 years (31.9 vs 18.6%; P=0.042). Positive thyroid peroxidase antibody (TPOAb) was more frequent, and alanine aminotransferase (ALT) levels were lower in patients who displayed TD (TPOAb: 62.1 vs 10.8%, P=0.000; ALT: 43.5 vs 51 IU/l, PZ0.046). The positive percentage of TPOAb IgG2 subclass in the TD group was significantly higher than that of patients without TD (66.7 vs 16.7%, P=0.005). Multiple logistic regression analysis indicated that only TPOAb IgG2 subclass positivity was an independent risk factor for TD in CHC patients (odds ratioZ8; 95% CI: 1.225-52.246; P=0.030). Conclusions: TPOAb IgG2 subclass positivity is a risk factor for TD in CHC patients before antiviral treatment. IgG2 subclass of TPOAb might play an important role in the presence of TD in CHC patients. [ABSTRACT FROM AUTHOR]