Interleukin-6 (IL-6) has emerged as an important cytokine involved in the regulation of metabolism. However, the role of IL-6 in the etiology of obesity and insulin resistance is not fully understood. Mitochondria are key organelles of energy metabolism, and there is growing evidence that mitochondrial dysfunction plays a crucial role in the pathogenesis of obesity-associated insulin resistance. In this study, we determined the direct effect of IL-6 on lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were investigated. We found that cells treated with IL-6 displayed fewer lipids and an elevated glycerol release rate. Further, IL-6 treatment led to decreased mitochondrial membrane potential, decreased cellular ATP production, and increased intracellular ROS levels. The mitochondria in IL-6-treated cells became swollen and hollow with reduced or missing cristae. However, insulin-stimulated glucose transport was unaltered. PGC-1α, NRF1, and mtTFA mRNA levels were markedly increased, and the mitochondrial contents were also increased. Our results demonstrate that IL-6 can exert a direct lipolytic effect and induce mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial biogenesis might play a compensatory role in glucose transport.
Different types of cancer exhibit distinct gene expression profiles. The present study aimed to identify a specific gene dysregulated in hepatocellular carcinoma (HCC) that was essential for cancer progression. The whole transcriptomes of primary HCC tissue samples were analyzed with microarrays. The most significantly differentially expressed gene was identified, specifically karyopherin subunit-α 2 (KPNA2), and an analysis using the Oncomine online tool was performed with data from The Cancer Genome Atlas to predict associated genes in HCC. Reverse transcription-quantitative polymerase chain reaction was performed to confirm the gene expression levels of KPNA2, and the RNA interference knockdown of KPNA2 was performed to identify the effect on putative downstream target genes. A proliferation assay and flow cytometry analysis was used to assess the function of KPNA2 in the regulation of the cell cycle. The results demonstrated that KPNA2 expression was significantly upregulated in HCC tumor tissues compared with liver tissues and was associated with cyclin B2 (CCNB2) and cyclin-dependent kinase 1 (CDK1) expression. KPNA2 expression was identified a novel marker to predict the outcome of patients. In addition, KPNA2 knockdown downregulated CCNB2 and CDK1, inhibited cell proliferation and induced cell cycle arrest in the G2/M phase. In conclusion, it was demonstrated that KPNA2 may promote tumor cell proliferation by increasing the expression of CCNB2/CDK1. KPNA2 could be a target for therapeutic intervention in HCC.
BackgroundAlthough the age-specific incidence and mortality of stroke is higher among men, stroke has a greater clinical effect on women. However, the sex differences in stroke among elderly patients are unknown. Therefore, we aimed to assess the sex differences in stroke among elderly stroke patients.MethodsBetween 2005 and 2013, we recruited 1484 consecutive acute ischemic stroke (AIS) patients (≥75 years old) from a specialized neurology hospital in Tianjin, China. Information regarding their stroke subtypes, severity, risk factors, and outcomes at 3 and 12 months after stroke were recorded.ResultsComparing with men, women had a significantly higher prevalence of severe stroke (17.20 vs. 12.54%), hypertension (76.42 vs. 66.39%), dyslipidemias (30.35 vs. 22.76%), and obesity (18.40 vs. 9.32%), P < 0.05. Comparing with women, men had a significantly higher prevalence of intracranial artery stenosis (23.11 vs. 17.45%), current smoking (29.60 vs. 13.05%), and alcohol consumption (12.15 vs. 0.47%), P < 0.05. Moreover, dependency was more common among women at 3 and 12 months after stroke, although the sex difference disappeared after adjusting for stroke subtypes, severity, and risk factors.ConclusionElderly women with AIS had more severe stroke status and worse outcomes at 3 and 12 months after stroke. Thus, elderly female post-AIS patients are a crucial population that should be assisted with controlling their risk factors for stroke and changing their lifestyle.
Background: Constraint-induced movement therapy (CIMT) promotes upper extremity recovery post stroke, however, it is difficult to implement clinically due to its high resource demand and safety of the restraint. Therefore, we propose that modified CIMT (mCIMT) be used to treat individuals with acute subcortical infarction.Objective: To evaluate the therapeutic effects of mCIMT in patients with acute subcortical infarction, and investigate the possible mechanisms underlying the effect.Methods: The role of mCIMT was investigated in 26 individuals experiencing subcortical infarction in the preceding 14 days. Patients were randomly assigned to either mCIMT or standard therapy. mCIMT group was treated daily for 3 h over 10 consecutive working days, using a mitt on the unaffected arm for up to 30% of waking hours. The control group was treated with an equal dose of occupational therapy and physical therapy. During the 3-month follow-up, the motor functions of the affected limb were assessed by the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL). Altered cortical excitability was assessed via transcranial magnetic stimulation (TMS).Results: Treatment significantly improved the movement in the mCIMT group compared with the control group. The mean WMF score was significantly higher in the mCIMT group compared with the control group. Further, the appearance of motor-evoked potentials (MEPs) were significantly higher in the mCIMT group compared with the baseline data. A significant change in ipsilesional silent period (SP) occurred in the mCIMT group compared with the control group. However, we found no difference between two groups in motor function or electrophysiological parameters after 3 months of follow-up.Conclusions: mCIMT resulted in significant functional changes in timed movement immediately following treatment in patients with acute subcortical infarction. Further, early mCIMT improved ipsilesional cortical excitability. However, no long-term effects were seen.
Resveratrol, a member of a class of polyphenolic compounds known as flavonols, has been extensively studied for its anticancer, antiviral, anti-inflammatory, and neuroprotective roles. Caenorhabidits elegans is a well-established animal for investigating responses to radiation. We found that resveratrol may provide protection against hazardous radiation. Pre-treatment with resveratrol extended both the maximum and mean life span of irradiated C. elegans. Resveratrol acted as a strong radical scavenger and regulated superoxide dismutase (SOD) expression. In addition, resveratrol was shown to be capable of alleviating gamma-ray radiation exposure-induced reduction in mitochondrial SOD expression. Ultimately, a correlation may exist between dietary intake of trace amounts of resveratrol and anti-aging effects. A specific response mechanism may be activated after the administration of resveratrol in irradiated animals. Our results suggest the protective effect of resveratrol is due to its strong ability to protect from oxidative stress and protective effects in mitochondria. Therefore, resveratrol is potentially an effective protecting agent against irradiative damage.
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