Clock genes regulate the browning of white fat in obese rats undergoing hypoxia exercise / 中国组织工程研究

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Mitochondrial dysfunction in Parkinson's disease and the potential ameliorative effects of exercise / 中国组织工程研究

BACKGROUND:Parkinson's disease is a neurodegenerative disease,and its pathogenesis involves mitochondrial dysfunction.Exercise has a potential ameliorative effect on mitochondrial dysfunction related to Parkinson's disease,but there is no comprehensive review and in-depth analysis in this field. OBJECTIVE:To comprehensively review and analyze mitochondrial dysfunction related to Parkinson's disease and the potential ameliorative effect of exercise,thereby providing new ideas and methods for the treatment and prevention of Parkinson's disease. METHODS:We searched the Web of Science,PubMed,CNKI,WanFang,and VIP databases with the keywords of"mitochondria,mitochondrial function,mitochondrial disease,mitochondrial dysfunction,Parkinson's disease,Parkinson,exercise,physical activity,exercise training,exercise therapy,mitochondrial impairment,mitochondrial damage,mitochondrial defects"in Chinese and"mitochondria,Parkinson's disease,Parkinson disease,physical exercise,exercise,physical activity,mitochondrial dysfunction,mitochondrial damage,mitochondrial impairment,athletic training,exercise training,rehabilitation"in English.A total of 89 articles were included for review and analysis. RESLUTS AND CONCLUSION:Parkinson's disease is closely related to mitochondrial dysfunction,including mitochondrial biogenesis inhibition,reduced autophagy,increased apoptosis,abnormal elevation of Ca2+ concentration,and increased oxidative stress in Parkinson's disease patients.Exercise has a positive effect on mitochondrial dysfunction related to Parkinson's disease,by promoting mitochondrial biogenesisand autophagy,regulating mitochondrial morphology,altering the plasticity of the mitochondrial respiratory chain,and reducing oxidative stress,thus helping to improve the development and progression of Parkinson's disease.However,the detailed mechanism between mitochondrial dysfunction and the ameliorative effect of exercise is still not fully understood,and future clinical studies can be conducted to validate the results of animal models and gain insights into the benefits and mechanisms of exercise in patients with Parkinson's disease.

Quantitative Measurement of Serum MicroRNA-21 Expression in Relation to Breast Cancer Metastasis in Chinese Females

BACKGROUND: Breast cancer is the most common type of cancer in females. Aberrant expression of microRNA-21 (miR-21) has previously been reported in breast cancer tissue. The aim of this study was to investigate expression levels of serum miR-21 in breast cancer patients and evaluate its prognostic value in Chinese females. METHODS: Real-time quantitative (RQ)-PCR was used to analyze miR-21 expression in archived serum, tumor tissue, and adjacent normal tissue from 549 participants (326 with breast cancer, 223 without breast cancer). We also analyzed associations between serum miR-21 expression and breast cancer subtypes and patient prognosis. Recurrence and survival were analyzed by using the multivariate Cox proportional hazards model. RESULTS: Expression of miR-21 was significantly higher in breast cancer tissues compared with normal adjacent breast tissues (P<0.001). The 2(-DeltaDeltaCt) values for serum miR-21 in breast cancer patients versus healthy controls were 9.12+/-3.43 and 2.96+/-0.73, respectively. Multivariate Cox proportional hazards model suggested that serum miR-21 expression was an independent poor prognostic factor for both recurrence (hazard ratio [HR]= 2.942; 95% confidence interval [CI]=1.420-8.325; P=0.008) and disease-free survival (HR=2.732; 95% CI=1.038-7.273, P=0.003) in breast cancer. CONCLUSIONS: Increased serum miR-21 expression level was correlated with poor prognosis of breast cancer patients, indicating that serum miR-21 may be a novel prognostic marker for recurrence and survival of breast cancer patients before resection.

Meta-Analysis of the SLCO1B1 c.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins

BACKGROUND: Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS: We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I 2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS: No significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS: No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.

Metallothionein lower under-expression in benign tumors than that in malignant tumors: systematic review article and meta-analysis

Metallothionein [MT] manifests varying expression levels in carcinomas, and they may be considered as valuable cell cancerization biomarkers for diagnosis of patients with cancers. A meta-analysis was conducted to evaluate comprehensively the MT expression difference in various benign tumors and malignant tumors, which compared the high with low MT expression levels in patients of the available studies. Finally, a total of 13 studies dealing with various tumors were involved for this meta-analysis. The results indicated that lower expression of MT in various benign tumors tissue than that in corresponding malignant tumors with the pooled OR of 0.52 [95 % CI 0.18-1.47, P <0.001]. In conclusion, MT expression difference is associated with tumor various stages in tumor patients and could be a useful clinical criteria of distinguishing benign tumors and malignant tumors for those patients