Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) α1 in mice fed high-fat diet

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Scope: Enhancing the formation and function of brown adipose tissue (BAT) increases thermogenesis and hence reduces obesity. Thus, we investigate the effects of resveratrol (Resv) on brown adipocyte formation and function in mouse interscapular BAT (iBAT). Methods and results: CD1 mice and stromal vascular cells (SVCs) isolated from iBAT were treated with Resv. Expression of brown adipogenic and thermogenic markers, and involvement of AMP-activated protein kinase (AMPK)α1 were assessed. In vivo, Resv-enhanced expression of brown adipogenic markers, PR domain-containing 16 (PRDM16) and thermogenic genes, uncoupling protein 1 (UCP1) and cytochrome C in iBAT, along with smaller lipid droplets, elevated AMPKα activity and increased oxygen consumption. Meanwhile, Resv promoted expression of PRDM16, UCP1, PGC1α, cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iBAT SVCs, suggesting that Resv enhanced brown adipocyte formation and function in vitro. In addition, Resv stimulated AMPKα and oxygen consumption in differentiated iBAT SVCs. However, the promotional effects of Resv were diminished by AMPK inhibition or AMPKα1 knockout, implying the involvement of AMPKα1 in this process. Conclusion: Resv enhanced brown adipocyte formation and thermogenic function in mouse iBAT by promoting the expression of brown adipogenic markers via activating AMPKα1, which contributed to the anti-obesity effects of Resv

Polymorphisms of Glutathione S-transferases Omega-1 among ethnic populations in China

<p>Abstract</p> <p>Background</p> <p>Glutathione S-transferases (GSTs) is a genetic factor for many diseases and exhibits great diversities among various populations. We assessed association of the genotypes of Glutathione S-transferases Omega-1 (GSTO1) A140D with ethnicity in China.</p> <p>Results</p> <p>Peripheral blood samples were obtained from 1314 individuals from 14 ethnic groups. Polymorphisms of GSTO1 A140D were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was employed to adjustment for regional factor. The frequency of GSTO1 140A allele was 15.49% in the total 14 ethnic populations. Compared to Han ethnic group, two ethnic populations were more likely to have AA or CA genotype [odds ratio (OR): 1.77, 95% confidence interval (95% CI): 1.05–2.98 for Uygur and OR: 1.78, 95% CI: 1.18–2.69 for Hui]. However, there were no statistically significant differences across 14 ethnic groups when region factor was adjusted. In Han ethnicity, region was significantly associated with AA or CA genotype. Han individuals who resided in North-west of China were more likely to have these genotypes than those in South of China (OR: 1.63, 95% CI: 1.21–2.20).</p> <p>Conclusion</p> <p>The prevalence of the GSTO1 140A varied significantly among different regional populations in China, which showed that geography played a more important role in the population differentiation for this allele than the ethnicity/race.</p

Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study

BackgroundThe relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial.ObjectiveThis study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy.MethodsFirst, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses.ResultsIn the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors.ConclusionOur results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy

Role of Pyroptosis in Intervertebral Disc Degeneration and Its Therapeutic Implications

Intervertebral disc degeneration (IDD), a progressive and multifactorial pathological process, is predominantly associated with low back pain and permanent disability. Pyroptosis is a type of lytic programmed cell death triggered by the activation of inflammasomes and caspases. Unlike apoptosis, pyroptosis is characterized by the rupture of the plasma membrane and the release of inflammatory mediators, accelerating the destruction of the extracellular matrix (ECM). Recent studies have shown that pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis in nucleus pulposus (NP) cells is activated in the progression of IDD. Furthermore, targeting pyroptosis in IDD demonstrates the excellent capacity of ECM remodeling and its anti-inflammatory properties, suggesting that pyroptosis is involved in the IDD process. In this review, we briefly summarize the molecular mechanism of pyroptosis and the pathogenesis of IDD. We also focus on the role of pyroptosis in the pathological progress of IDD and its targeted therapeutic application

LncRNA (HOTAIR) /miR-206/TAGLN2 signal axis regulates the invasion of papillarythyroid carcinoma cells

Objective To investigate the molecular mechanism of lncRNA (HOTAIR)/miR-206/TAGLN2 signaling axis in regulating the invasion of papillary thyroid carcinoma cells line TPC-1. Methods The papillary thyroid carcinoma(PTC) and paracancerous tissues were collected from the First Hospital of Lanzhou University, and the expression of lncRNA (HOTAIR), miR-206 and TAGLN2 in PTC tissues as well as paracancerous tissues was detected by RT-qPCR and Western blot; The thyroid papillary cancer cells with miR-206 over-expression and HOTAIR under-expression were constructed to detect the expression of target gene and its effect on the invasion of TPC-1 cells by Transwell assay. Results Compared with the adjacent tissue, the expression of HOTAIR in papilla-rythyroid cancer tissue was increased by 2.48 times. miR-206-5p was decreased down to 0.6,and the expression of TAGLN2 was increased (P＜0.05). After over-expression of miR-206, the protein expression of TAGLN2 was decreased in TPC-1 cell, and the invasion of TPC-1 cells was inhibited (P＜0.05). Knockdown of HOTAIR increased expression of miR-206 in TPC-1 cells and decreased the expression of TAGLN2. The Transwell assay showed that the invasion of TPC-1 cells was significantly reduced (P＜0.05). Conclusions In PTC, reducing the expression of HOTAIR results in over-expression of miR-206 then further inhibits the expression of TAGLN2. The biological outcome is inhibition of invasion of thyroid cancer

An enhanced thermo-actuated shape memory polymer composite coupled with elastomer

A new enhanced thermo-actuated shape memory polymer (SMP) composite PE-NBR was developed and its properties were compared with traditional SMPs. The numerical simulation and experiment study on packer element were performed by the way of newly developed constitutive model. The functional composite system with shape memory effect is mainly composed of polyolefin acting as shape memory component and particle-filled elastomer acting as modified enhancement component. The PE-NBR system has advantages over traditional SMP with tensile strength of 14.3 MPa, hardness of 71 and shape recovery ratio of 95%. The ratio of polyolefin in the system can be adjusted from 20% to 90% and that of elastomer can be adjusted from 10% to 70%. The constitutive model with rubber plastic blending for PE-NBR system based upon mesomechanics and macroscopic properties of materials is used to meet the numerical study requirements of large-deformation, temperature-dependence and nonlinear composites. The rating pressure of packer element using PE-NBR system is more than 10 MPa and the maximum of contact pressure is obtained in the location which is 60 mm away from the end surface of the element. Key words: shape memory polymer, composite material, mesomechanics, constitutive model, polyolefin, elastomer, packe