Bacillus coagulans T4 and Lactobacillus paracasei TD3 Ameliorate Skeletal Muscle Oxidative Stress and Inflammation in High-Fat Diet-Fed C57BL/6J Mice.

Background: This study aims to investigate the effects of Bacillus coagulans T4 and Lactobacillus paracasei TD3 probiotics on skeletal muscle inflammation and oxidative stress in C57BL/6J mice fed a high-fat diet (HFD). Methods: Probiotics B. coagulans T4, and L. paracasei TD3 were administered to male C57BL/6J mice fed with HFD. The gene expression of macrophage infiltration markers, inflammatory cytokines, and oxidative stress indicators in the muscle tissue was investigated. Results: Treatment with B. coagulans T4 and L. paracasei TD3 reduced macrophage infiltration, accompanied by a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1) and an increase in the expression of interleukin (IL)-10. On the other hand, L. paracasei TD3 decreased malondialdehyde (MDA) while B. coagulans T4 decreased carbonyl and increased catalase activity. Conclusions: Treatment with probiotics B. coagulans T4 and L. paracasei TD3 partially ameliorated obesity-induced skeletal muscle inflammation in HFD-fed mice.

The high-intensity interval training (HIIT) and curcumin supplementation can positively regulate the autophagy pathway in myocardial cells of STZ-induced diabetic rats.

OBJECTIVE: Targeting autophagy is a new therapeutic strategy for the complications of diabetes,such as diabetic cardiomyopathy (DCM). During diabetes, increased or insufficient autophagic activity causes aberrations in cellular homeostasis. Regarding the conflicting and unclear results regarding the effect of HIIT and curcumin supplementation on the expression of genes associated to autophagy, this study aimed to assess whether 4-week high-intensity interval training (HIIT) and curcumin supplementation are able to influence the expression of autophagy-related genes in myocardial cells of diabetic rats. METHODS: In an experimental design, 24 male Wistar rats were randomly divided into 4 groups: non-diabetic control (NC), diabetic control (DC), diabetes + HIIT (D + HIIT), and diabetes + curcumin (D + CU). After HIIT program and curcumin treatment, the genes expression of autophagy pathway were assessed in the myocardium by real-time PCR Tanique. RESULTS: The results indicated that the expression levels of ATG1, Beclin1, ATG5, and LAMP-2 genes were significantly reduced in the DC group compared to the NC group (p < 0.001). Following 4-week HIIT, the expression of Beclin1, ATG-5, and LAMP-2 improved considerably compared to the DC group (p < 0.001, p < 0.001, and p < 0.05, respectively). In addition, after 4 weeks of curcumin supplementation, the expression levels of ATG-5 and Beclin-1 were significantly improved compared to the DC group (p < 0.001, p < 0.05, respectively). It seems HIIT and curcumin supplementation can be an effective approach for inducing autophagy and improving cardiac function in DCM rats.However, HIIT seems more effective than curcumin in this regard.

Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women.

BACKGROUND: Animal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity. METHODS: This study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m 2] and women with normal-weight (n = 22) (BMI < 25 kg/m 2). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight. RESULTS: It was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non-obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (ß = - 0.448, P-value = 0.003) and SOCS3 (ß = 0.465, P-value = 0.002) in SAT of all participants. CONCLUSIONS: Our findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.

Association of rs2954029 and rs6982502 Variants with Coronary Artery Disease by HRM Technique: A GWAS Replication Study in an Iranian Population.

Background: Genome-wide association studies (GWAS) have been the primary tool for an unbiased study of the genetic background of coronary artery disease (CAD). They have identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). In this study, we aimed to replicate the association of rs2954029 and rs6982502, a GWAS identified SNP, to CAD in an Iranian population. Methods: A sample of 285 subjects undergoing coronary angiography, including 134 CAD patients and 151 healthy. The genotype determination of rs2954029 and rs6982502 SNPs performed using the high-resolution melting analysis (HRM) technique. Results: Our results revealed that the TT genotype of rs2954029 (p= 0.009) and rs6982502 (p< 0.001) were significantly higher in CAD patients compared with controls. Binary logistic regression showed that rs6982502 and rs2954029 increase the risk of CAD incidence (2.470 times, p= 0.011, 95% CI= [1.219-4.751], and 2.174 times, p= 0.033, 95% CI= [1.066-4.433] respectively). After adjusting for confounders, we found that rs6982502 and rs2954029 are significantly associated with CAD risk. Conclusion: These data showed that the TT genotype of rs2954029 and rs6982502 is associated with the risk of CAD in a hospital-based sample of the Iranian population, which has replicated the result of recent GWAS studies.

Low level of adiponectin predicts the development of Nonalcoholic fatty liver disease: is it irrespective to visceral adiposity index, visceral adipose tissue thickness and other obesity indices?

We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 µg/mL) and ones with NAFLD + T2D (3.21 µg/mL) is significantly lower rather than in controls (4.39 µg/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.

Association between HDACs and pro-inflammatory cytokine gene expressions in obesity.

Histone deacetylases (HDACs) are important players in a variety of physiological and pathological conditions. Few studies have addressed HDAC expressions in human adipose tissue in obese individuals, and their association with pro-inflammatory cytokines. Here, we compared 20 non-obese and 20 obese women to investigate possible changes in gene expressions of HDAC2, 4, 5, and 6 in the subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) of these individuals. Our findings showed decreased HDAC5 expression in SAT and elevated HDAC4 expression in VAT from the obese group compared with the non-obese group. Our analyses showed negative correlations between HDAC2, 5, and 6 and the obesity indices and positive correlations between HDAC4 and obesity indices. HDAC2 showed a positive correlation with pro-inflammatory cytokines whereas HDAC4, 5, and 6 were negatively correlated with pro-inflammatory cytokines. Our findings provide new evidence that implicates the important roles of HDACs in obesity and obesity-associated inflammation.

The gene expression of long non-coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices.

BACKGROUND: There is evidence regarding the role of two lncRNAs: MEG3 and H19 the pathomechanism of obesity and related disorders. Here, we aimed to evaluate the expression of MEG3 and H19 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women (n = 18), as compared to normal-weight women (n = 17). Moreover, we sought to identify the association of expression of MEG3 and H19 in SAT and VAT with obesity parameters, insulin resistance, and the mRNA expression of possible target genes involved in adipogenesis and lipogenesis including peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). METHODS: Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of H19 in SAT of obese women, compared to normal-weight women, while MEG3 expression was significantly higher in the SAT of the obese group rather than controls. Correlation analysis indicated that the transcript level of H19 had an inverse correlation with obesity indices and HOMA-IR values. However, MEG3 expression displayed a positive correlation with all the indicated parameters in all participants. Interestingly, a positive correlation was found between transcript level of MEG3 in SAT with FAS and PPARγ. However, there was an inverse correlation between SAT expression of H19 and FAS. CONCLUSIONS: It appears that lncRNAs, MEG3 and H19, are involved in obesity-related conditions. However, more clinical studies are still required to clarify the relationships between lncRNAs with obesity and related abnormalities.

The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: a preliminary study.

BACKGROUND: There is growing evidence that the C1qTNF-related protein (CTRP) family has a crucial role in the pathophysiology of metabolic disorders such as type 2 diabetes (T2D) and obesity. We sought to identify the association of CTRP1 and CTRP5 circulating levels with various obesity parameters such as visceral adipose tissue (VAT) thickness, visceral adiposity index (VAI), and with carotid intima-media thickness (cIMT) in patients with T2D and controls. METHODS: This preliminary study consisted of men with T2D (n = 42) and men without T2D (n = 42). The measurement of cIMT and VAT thickness was performed using an Accuvix XQ ultrasound. Circulating levels of CTRP1, CTRP5, and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: CTRP-1 and CTRP1/CTRP5 ratio were markedly higher in patients with T2D compared to controls (p < 0001 and p = 0004 respectively). Interestingly, binominal logistic regression revealed that a higher circulating level of CTRP1 was associated with the presence of T2D (odds ratio [OR]: 1.009 [95% CI: 1.004-1.015]; P = .001). CTRP1 circulating levels were correlated with WHR, VAT, and HOMA-IR in the whole population study. Also, we observed that the ratio of CTRP1 to CTRP5 in plasma (ß = 0.648, P = 0.005) and CTRP5 circulating levels (ß = 0.444, P = 0.049) are independently associated with cIMT value. CONCLUSIONS: Our results indicated that CTRP1 and CTRP5 concentrations were correlated with atherosclerosis in men with T2D and these adipokines might have a causal role for cardiometabolic risk in T2D.However, more studies in large sample sizes are required to clarify the role of CTRPs in T2D pathogenesis.

Increased mRNA Expression of CTRP3 and CTRP9 in Adipose Tissue from Obese Women: Is it Linked to Obesity-Related Parameters and mRNA Expression of Inflammatory Cytokines?

BACKGROUND: Obesity, a medical condition with impaired adipokine secretion and function, has a detrimental effect on insulin and glucose metabolism. CTRP3 and CTRP9 are adipokines with possible roles in energy homeostasis regulation. We sought to compare CTRP3, CTRP9, and inflammatory gene expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery and non-obese women as controls. METHODS: For this study, the investigators recruited 20 morbidly obese women (BMI> 35) who qualified for bariatric surgery and 20 normal-weight women (BMI< 25) who underwent elective surgeries. Real-time PCR was performed to investigate mRNA expression of CTRP3, CTRP9, and the inflammatory genes IL1-ß, IL-6, MCP-1, and TNF-α in SAT and VAT from both obese patients and controls. RESULTS: We observed that CTRP3 mRNA levels were significantly greater in VAT from obese patients than from controls (P< 0.0003). Also, patient group had higher levels of CTRP9 that control group (P< 0.0026). Inflammatory cytokines were markedly increased in SAT of obese patients compared to controls (P< 0.05). In addition, our results revealed a positive correlation of CTRP9 with HOMA-IR and waist circumference in VAT and CTRP3 with IL-1ß, MCP-1, and TNF-α in SAT. CONCLUSION: Both CTRP3 and CTRP9 expression were significantly higher in VAT from obese patients than from controls, and CTRP3 expression positively correlated with inflammatory parameters. Our findings indicate that CTRP3 and CTRP9 might be important in regulating glucose metabolism and obesity-related conditions such as inflammation.

The C1q/TNF-related proteins (CTRPs) in pathogenesis of obesity-related metabolic disorders: Focus on type 2 diabetes and cardiovascular diseases.

The growing evidence has been tried to explain and characterize C1q/TNF- related proteins (CTRPs) family as the potential diagnostic or therapeutic targets of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes (T2D), and cardiovascular disorders. However, the underlying mechanism is still obscure. Unraveling the signaling pathways downstream of CTRP family members is of great interest and could certainly be beneficial for finding new insights into therapeutic strategies for improving metabolic abnormalities. This review focused on the role of CTRP members in the initiation and development of obesity-related metabolic disorders with a focus on T2D and cardiovascular diseases. Here we summarize and discuss the role of CTRPs in the regulation of insulin signaling, inflammatory pathways, and energy metabolism, and other signaling pathways pertinent to the pathogenesis of T2D and cardiovascular diseases. We also review available clinical studies to better elucidate the roles of these potential molecules in the initiation and development of the afore-mentioned disorders.

High-Intensity Interval Training Reversed High-Fat Diet-Induced M1-Macrophage Polarization in Rat Adipose Tissue via Inhibition of NOTCH Signaling.

INTRODUCTION: There is accumulating evidence on the beneficial effect of exercise intervention in the management of metabolic disorders; however, the molecular mechanism is still unclear. Here, the current study aimed to compare the effect of high-intensity interval training (HIIT) and continuous endurance training (CET) on serum and adipose-tissue markers of M1/M2 macrophage polarization. METHODS: A total of 45 healthy male Wistar rats were divided into groups of normal chow (n=10) and high-fat diet (HFD) (n=35). Then, rats receiving the HFD were randomly divided into four groups. Training programs were performed for 5 days/week over 10 weeks. The CET protocol included 30 minutes running at 50%-60% of VO2max. The HIIT protocol consisted of five repeated intervals of 2-minute sprints on the treadmill at 80%-90% VO2max workload with 1 minute's 30%-35% VO2max interval for each rat. Then, biochemical parameters were assessed. Macrophage-polarization markers were assessed at mRNA and protein levels by real-time PCR and Western blotting, respectively. RESULTS: Both exercise-training programs, especially HIIT, reversed increased serum biochemical parameters (glucose, triglycerides, cholesterol, Homeostatic Model Assessment of Insulin Resistance, and hsCRP), M1-polarization markers (circulating IL6, TNFα, and adipose-tissue mRNA expression of IL6, TNFα and iNOS), M2 markers (CD206, CD163, and IL10 expression), as well as pIκKB, pNFκB, and NICD expression in HFD-induced diabetes. CONCLUSION: Our findings suggest that despite devoting less time, the HIIT workout is a more effective intervention for diabetes management. Moreover, HIIT reverses HFD-induced macrophage polarization by targeting the NFκB and NOTCH signaling pathways.

Emerging Role of miR-372 and miR-101a in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: microRNAs (miRNAs) have an important role in cancer development and progression. It has been shown that miR-372 and miR-101 are involved in cancer progression. In the present study we evaluated expressions of these miRNAs and their serum levels in patients with head and neck squamous cell carcinoma (HNSCC) and controls. METHODS: We conducted this case-control study on 60 patients with HNSCC and 30 controls. Patients were diagnosed by histological assessments of their tissues. Expressions of EGFR, PTEN, PI3K/CA, miR-372, and miR-101a were evaluated in the tissues, along with serum levels of the miRNAs. RESULTS: Tissue expression of PTEN decreased in HNSCC, and expressions of EGFR and PI3K increased in HNSCC tissues compared to the controls. Tissue expressions of miR-372 increased and miR-101a decreased in HNSCC tissues compared to the controls. We observed significantly lower serum levels of miR-101a in patients; however, these findings for miR-372 were not significant. A strong correlation existed between serum levels and tissue expression of miR-101a. Notably, miR-101a serum levels showed good sensitivity and specificity for diagnosis of HNSCC. CONCLUSIONS: The results showed that HNSCC patients had higher tissue expression of miR-372 and lower expression of miR-101a. Also, serum levels of miR-101a were lower in HNSCC patients. We observed that miR-101a had good sensitivity and specificity for diagnosis of HNSCC. The present study suggested that miR-101a could be a potential biomarker for HNSCC.

Inhibition of Cyclin-dependent Kinase (CDK) Decreased Survival of NB4 Leukemic Cells: Proposing a p53-Independent Sensitivity of Leukemic Cells to Multi-CDKs Inhibitor AT7519.

An unbounded number of events exist beneath the intricacy of each particular hematologic malignancy, prompting the tumor cells into an unrestrained proliferation and invasion. Aberrant expression of cyclin-dependent kinases (CDKs) is one of these events which disrupts the regulation of cell cycle and subsequently, results in cancer progression. In this study, we surveyed the repressive impact of multi-CDK inhibitor AT7519 on a panel of leukemia-derived cell lines. Our data underlined that AT7519 abated the survival of all tested cells; however, in an overview, the response rate of leukemic cells to the inhibitor was varied irrespective of p53 status. Notably, the less sensitivity of leukemia cells to AT7519 was found to be mediated partly by the compensatory activation of c-Myc oncogene which was confirmed by the induction of a superior cytotoxicity upon its suppression in less sensitive cell. The blockage of cell cycle, as announced by induction of sub-G1 arrest as well as reduced S phase, resulted in a significant decrease in survival of acute promyelocytic leukemia (APL)-derived NB4 cells, as the most sensitive cell line, either as monotherapy or in combination with arsenic trioxide. Anti-leukemic effects of the inhibitor were further verified by apoptosis analysis, where we discovered that AT7519 induced apoptosis via alteration of pro- and anti-apoptotic genes in NB4. All in all, this study proposed that AT7519 is a rewarding agent opposed to APL; however, additional examinations should be performed to determine the advantages of this inhibitor in clinical setting.

High-intensity interval training (HIIT) alleviated NAFLD feature via miR-122 induction in liver of high-fat high-fructose diet induced diabetic rats.

Background: Exercise intervention is strongly recommended to manage metabolic diseases. In this study, we investigate, whether HIIT and CET can induce hepatic miR-122 expression, NAFLD rats with diabetes.Methods: 40 Wistar rats divided into 2 groups, non-diabetic (NDC) and diabetic .Type 2 diabetes was induced by high-fat high-fructose diet (HFHFD). Then diabetic rats were subdivided into three groups: diabetic control (HFHFD + DC), CET (HFHFD + CET), and HIIT (HFHFD + HIIT). After eight weeks of exercise on a rodent treadmill, we measured miR-122 and its target genes expression in the liver of rats.Results: HIIT decreased the expression of FAS, ACC, SREBP-1c compared with HFHFD + DC (p = .004, p = .032, p = .043, respectively), and could partially increase miR-122 expression as compared with HFHFD + DC (26.8%, p = .68).Conclusions: Exercise training could be a non-pharmacological intervention for improvement of NAFLD of diabetic rats by induction of miR-122. HIIT had a greater effect on NAFLD amelioration than CET.

High-intensity interval training (HIIT) effectively enhances heart function via miR-195 dependent cardiomyopathy reduction in high-fat high-fructose diet-induced diabetic rats.

Aims: Regarding the fact that up-regulation of miR-195 in diabetic hearts has a potential role in diabetic cardiomyopathy, the present study investigated whether continuous endurance training (CET) and high-intensity interval training (HIIT) reduces miR-195 expression and which exercise is effective in this regard.Methods: Diabetes was induced by high-fat high-fructose diet (HFHFD). Then, the rats were sub-divided into three categories; sedentary (HFHFD + SED), continuous endurance training (HFHFD + CET), and high-intensity interval training group (HFHFD + HIIT). After eight weeks of running, expression of miR-195 and myocardial function were evaluated.Results: HIIT effectively decreases the expression of miR-195 and increases the expression of Sirt1 and BCL-2 in diabetic rats compared with CET. Our results showed that HIIT compared with CET increases left ventricular ejection fraction (LVEF%) and fractional shortening (FS%).Conclusions: Our results indicated that exercise, especially HIIT is an appropriate strategy for reducing miR-195 and improving myocardial function in diabetic rats compared with CET.

Deregulation of long noncoding RNA SNHG17 and TTC28-AS1 is associated with type 2 diabetes mellitus.

Long noncoding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases including type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the expression levels of SNHG17 and TTC28-AS1 in T2DM patients. Quantitative real-time RT-PCR analysis was performed using peripheral blood mononuclear cells (PBMCs) samples from patients diagnosed with T2DM and healthy controls. Binary logistic regression analysis was carried out to determine the odds of development of T2DM based on expression levels of lncRNAs and clinical characteristic of the subjects. Spearman's correlation analysis was used to clarify the correlation between SNHG17 and TTC28-AS1 expressions to metabolic features. We found that SNHG17 and TTC28-AS1were down-regulated in the T2DM group compared to the healthy control group. The logistic regression revealed that body mass index (BMI), systolic blood pressure (SBP), fasting blood glucose (FBG) and TTC28-AS1 expression substantially affect T2DM susceptibility. Furthermore, expression of SNHG17 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) and expression of TTC28-AS1 was positively correlated with low-density lipoprotein cholesterol (LDL-C). Decreased expressions of lncRNAs TTC28-AS1 and SNHG17 in T2DM are possibly associated with the development of T2DM.

The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects.

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35-40 kg/m2] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m2) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1ß (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.

Circulating miR-625 as an Emerging Biomarker for Liver Cirrhosis.

BACKGROUND: Sensitive and specific diagnostic indicators are essential for liver cirrhosis. This study aims to analyze two plasma microRNAs (miR-625 and miR-920) as possible biomarkers for liver cirrhosis. METHODS: miR-625 and miR-920 expressions were analyzed in the plasma of 40 patients with liver cirrhosis and 41 healthy controls. Plasma levels of miR-625 and miR-920 were assessed by qRT-PCR. Analysis of the results was performed by the Mann-Whitney U-test. Spearman's test was used to show correlations between the miR-625 and clinical parameters. Receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity. RESULTS: miR-625 is downregulated in patients with liver cirrhosis. Expression of miR-625 correlated with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. ROC curve analysis revealed that miR-625 had a sensitivity of 82.4% and specificity of 88.9% (area under the curve (AUC): 0.902) which indicated a high diagnostic power for cirrhosis. CONCLUSIONS: This study demonstrates for the first time that, miR-625 may be considered as a potential noninvasive biomarker for diagnosis of liver cirrhosis in patients, irrespective of etiology.

Clinical significance of long noncoding RNA VIM-AS1 and CTBP1-AS2 expression in type 2 diabetes.

BACKGROUND/AIMS: The risk of type 2 diabetes (T2D) is determined by a combination of genetic and environmental factors. Multiple studies have proposed that long noncoding RNAs (lncRNAs) are crucial molecules in regulating several biological processes and complex diseases. The study was aimed at investigating the association between the expression levels of lncRNA VIM-AS1, lncRNA CTBP1-AS2, and T2D susceptibility. METHODS: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 in the peripheral blood mononuclear cell (PBMC) of 100 healthy individuals and 100 T2D patients were collected for Quantitative Real-Time RT-PCR analysis. A logistic regression was performed to understand whether the likelihood of T2D can be predicted based on the expression levels of lncRNA VIM-AS1 and lncRNA CTBP1-AS2. Receiver operating characteristic (ROC) analysis was also performed to determine the statistical analysis of VIM-AS1 and CTBP1-AS2 levels in 200 samples. RESULTS: Our results display that decreased levels of VIM-AS1 and CTBP1-AS2 in PBMC were associated with diabetes in Iranian population. The logistic regression revealed that Systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), Fasting blood glucose (FBG) and CTBP1-AS2 are substantial predictors of T2D. The ROC analysis of CTBP1-AS2 revealed the area under the ROC curve (AUC) of 0.68 with a sensitivity of 58.7% and specificity of 75.3% in distinguishing nondiabetic from diabetic subjects. The ROC analysis of VIM-AS1 determined AUC of 0.63 with a sensitivity of 56.1% and specificity of 68.37% in distinguishing the two diagnostic groups. CONCLUSION: lncRNA VIM-AS1 and lncRNA CTBP1-AS2 expression levels are associated with T2D susceptibility.

Association between Vascular Endothelial Growth Factor Plasma Levels and rs699947 Polymorphism and Coronary Collateral Vessel Formation.

Background: The vascular endothelial growth factor (VEGF), as an angiogenic cytokine, binds endothelial cell receptors and stimulates angiogenesis and collateral formation. We evaluated the association between VEGF plasma levels and the gene polymorphism rs699947 and the formation of coronary collaterals in patients with coronary artery disease. Methods: A total of 195 patients with ≥70% narrowing in at least 1 coronary vessel (according to coronary angiography) were included in the study. The presence of the rs699947 polymorphism within the promoter of the VEGF gene was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma VEGF concentration was quantified via the ELISA method. The Rentrop method was used to grade the extent of collateral development. Results: There was no significant difference in VEGF levels between the groups with good and poor collaterals. The frequency of the A allele of rs699947 was found to be higher in the patients with good collaterals than in those with poor collaterals (P=0.014). The odds ratio of good collaterals for AA was 2.67 (P=0.025) when compared with the CC genotype. Further, our additive model revealed an association between the rs699947 polymorphism and collateral formation (OR: 1.96, 95% CI: 1.05-3.65, P=0.033). Conclusion: The rs699947 polymorphism might be a novel genetic factor affecting collateral development in Iranian patients with coronary artery disease.