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The role of adipose mesenchymal stem cells (Ad-MSCs) in metabolic syndrome remains unclear. We aimed to assess the expression of selected microRNAs in Ad-MSCs of non-diabetic adults in relation to Ad-MSC secretion of protein regulators and basic metabolic parameters. Ten obese, eight overweight, and five normal weight subjects were enrolled: 19 females and 4 males; aged 43.0 ± 8.9 years. Ad-MSCs were harvested from abdominal subcutaneous fat. Ad-MSC cellular expressions of four microRNAs (2−ΔCt values) and concentrations of IL-6, IL-10, VEGF, and IGF-1 in the Ad-MSC-conditioned medium were assessed. The expressions of miR-21, miR-122, or miR-192 did not correlate with clinical parameters (age, sex, BMI, visceral fat, HOMA-IR, fasting glycemia, HbA1c, serum lipids, CRP, and eGFR). Conversely, the expression of miR-155 was lowest in obese subjects (3.69 ± 2.67 × 10−3 vs. 7.07 ± 4.42 × 10−3 in overweight and 10.25 ± 7.05 × 10−3 in normal weight ones, p = 0.04). The expression of miR-155 correlated inversely with BMI (sex-adjusted r = −0.64; p < 0.01), visceral adiposity (r = −0.49; p = 0.03), and serum CRP (r = −0.63; p < 0.01), whereas it correlated positively with serum HDL cholesterol (r = 0.51; p = 0.02). Moreover, miR-155 synthesis was associated marginally negatively with Ad-MSC secretion of IGF-1 (r = −0.42; p = 0.05), and positively with that of IL-10 (r = 0.40; p = 0.06). Ad-MSC expression of miR-155 appears blunted in visceral obesity, which correlates with Ad-MSC IGF-1 hypersecretion and IL-10 hyposecretion, systemic microinflammation, and HDL dyslipidemia. Ad-MSC studies in metabolic syndrome should focus on miR-155. [ABSTRACT FROM AUTHOR]

PD-L1 is one of the two programmed cell death 1 (PD-1) ligands and a part of an immune checkpoint system (PD-1/PD-L1) with widespread clinical application. The aim of this study was to investigate PD-L1 expression and its association with clinicopathological and prognostic significance in non-clear cell renal cell carcinoma (non-ccRCC) patients. A total of 41 papillary (pRCC) and 20 chromophobe (chRCC) RCC tumors were examined for PD-L1 expression by immunohistochemistry in the cancer cells and tumor-infiltrating mononuclear cells (TIMCs). PD-L1 positivity was detected in 36.6% pRCC and 85.0% chRCC cancer cells, while PD-L1 positivity was observed in 73.2% pRCC and 50.0% chRCC TIMCs. PD-L1 positivity in both pRCC and chRCC tumor cells was not correlated with any of the examined clinicopathological features, while PD-L1 positivity in TIMCs was associated with the age of patients with pRCC. During follow-up, the death was documented among 6 patients with pRCC. Papillary RCC patients with PD-L1-positive tumor cells were significantly associated with an increased risk of death compared with patients with PD-L1-negative cancer cells. A similar trend was observed when comparing PD-L1 expression in TIMCs. However, no differences in overall survival for PD-L1-positive pRCC patients with compared to PD-L1-negative patients were observed in tumor cells or TIMCs. [ABSTRACT FROM AUTHOR]

Introduction: Fractalkine chemokine (CX3CL1) is a protein cytokine which is associated with the pathophysiology of lifestyle-related diseases such as obesity, diabetes and atherosclerosis. This study aimed to assess the influence of fractalkine gene variants (rs 614230, rs 170364) on body mass. Material and methods: Study group consisted of 295 patients (152 women and 133 men). The blood samples were collected and stored at -70°C. Afterwards the DNA material was isolated and prepared (quality and quantity were checked by spectrophotometry). Allelic discrimination of fractalkine gene (rs 614230, rs 170364) was performed using Roche Lightcycler96 thermocycler. Real-Time PCR was conducted using fluorescence-labeled TaqMan Pre-designed SNP Genotyping Assay probes. Results: The CC genotype of fractalkine (rs 614230) had a positive association with BMI compared to CT and TT genotypes. The GG genotype of fractalkine (rs 170364) had a negative association with body size, body mass index and body fat content compared to GT. The TT genotype of fractalkine (rs 170364) shows a negative association with BMI compared to GT. Conclusions: Fractalkine polymorphism rs 614230 may be associated with high body mass index (BMI), but not with waist size or body fat content. Single nucleotide polymorphisms (SNP) of fractalkine rs 170364 may be associated with high body mass. Further studies in a larger group of patients are necessary to completely assess this association. [ABSTRACT FROM AUTHOR]

Introduction: Visfatin and nesfatin are active proteins that are involved in the regulation of physiological functions such as glucose metabolism and inflammatory response. This study aimed to assess the influence of visfatins and nystatins gene variants on the occurrence of the full metabolic syndrome or its components. Material and methods: The research cohort comprised 285 diabetic patients, 132 men and 153 women. Specific DNA segments were amplified and labelled, and the rs 4730153 gene of visfatin and the rs 1330 gene of nesfatin were analysed. Real-Time PCR was conducted using fluorescence-labelled probes. Results: The AA genotype of visfatin (rs 4730153) shows a positive association with glucose concentration or pharmacological treatment in patients with type 2 diabetes, compared to AG and GG genotypes. The GG genotype of nesfatin (rs 1330) shows a positive association with incidents of metabolic syndrome, compared to the AA genotype. Conclusions: Visfatin polymorphism in rs 4730153 may be associated with inappropriate glucose concentration. Nesfatin polymorphism in rs 1330 may be associated with metabolic syndrome. Further studies in a larger group of patients are necessary to completely assess this association. [ABSTRACT FROM AUTHOR]

The most common subtype of renal cell carcinoma (RCC) is clear cell type (ccRCC), which accounts for approximately 75% of cases. von Hippel-Lindau (VHL) gene has been shown to be affected in more than half of ccRCC cases. Two single nucleotide polymorphisms (SNPs) located in VHL gene, rs779805 and rs1642742, are reported to be involved in the occurrence of ccRCC. The aim of this study was to assess their associations with clinicopathologic and immunohistochemical parameters, as well as risk and survival of ccRCC. The study population consisted of 129 patients. No significant differences in genotype or allele frequencies of VHL gene polymorphisms were observed between ccRCC cases and control population, and we have found that our results do not indicate a significant relationship of these SNPs with respect to ccRCC susceptibility. Additionally, we did not observe a significant association of these two SNPs with ccRCC survival. However, our results conclude that rs1642742 and rs779805 in the VHL gene are associated with increased tumor size, which is the most important prognostic indicator of renal cancer. Moreover, our analysis showed that patients with genotype AA of rs1642742 have a trend towards higher likelihood of developing ccRCC within their lifetime, while allele G of rs779805 can have a preventive effect against the development of renal cancer in stage 1. Therefore, these SNPs in VHL may be useful as genetic tumor markers for the molecular diagnostics for ccRCC patients. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is considered to be one of the most prevalent health problems which lead to diabetes and cardiovascular diseases thus increasing mortality rate and decreasing life expectancy, particularly in western countries. The variants within the FTO gene were identified to be associated with adiposity and diabetes in genome-wide association studies (GWAS). Aim of the study: To investigate the association between FTO rs17817449 polymorphism and risk of obesity, type 2 diabetes, lipid disorders, and cardiovascular diseases: arterial hypertension and coronary artery disease (CAD). Material and methods: Study group consisted of 295 patients (159 women and 136 men). Collected venous blood samples were stored at minus 70 C until the study group was completed. In the laboratory of the Department and Clinic of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia in Zabrze the DNA material was isolated, proper concentration of the DNA (15 ng/μL) were prepared and quality and quantity were checked by spectrophotometry. Allelic discrimination was performed in Roche Lightcycler96 thermocycler with the use of fluorescent-labeled TaqMan Pre-designed SNP Genotyping Assay probes. Results: BMI, body fat percentage, and waist circumference did not differ by rs17817449 genotype. There were no significant differences in genotypes distribution between patients with obesity and normal body weight. We found a significant association of GT but not GG genotype with lower risk of arterial hypertension (OR, 0.55; 95% CI, 0.325-0.940; p = 0.003) and coronary artery disease (OR, 0.3; 95% CI, 0.145-0.620); p = 0.001). The frequencies of the FTO genotypes did not differ significantly between individuals with and without diabetes. Parameters of lipid profile (total cholesterol, HDL, LDL, TAG) and carbohydrate metabolism (fasting glucose, fasting insulin, HOMA-IR, QUICKI) did not differ by s17817449 genotype. Conclusion: The association between the FTO polymorphism in rs17817449 and increased risk of obesity and type 2 diabetes mellitus in the Upper Silesian population was not confirmed in this study. The rs17817449 variant of FTO gene may be related to decreased risk of arterial hypertension and coronary artery disease. Further studies in a larger cohort are required to confirm the association between FTO polymorphism in rs17817449 or/and in other FTO gene polymorphisms and diabetes and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Leaky gut contributes to metabolic syndrome. Zonulin is an intestinal protein that is involved in gut permeability. We aimed to assess the relationships between circulating zonulin and lipopolysaccharide (LPS), body composition, liver characteristics, and cytokines involved in obesity or liver disease. Forty seven nondiabetic, euthyreotic adults were included: 12 with BMI <25 kg/m2, 11 with BMI 25-29.9 kg/m2 and 24 with BMI ≥30 kg/m2. They were divided into the "Lean" group of 15 F and 5 M with BMI <27.5 kg/m2 and "Obese" group of 21 F and 6 M with BMI >29 kg/m2. Basic clinical parameters, total and visceral fat (bioimpedance; Tanita), liver steatosis and fibrosis (transient elastography; Fibroscan), as well as serum Sirtuin-1, Fetuin-A, Fatty Acid-Binding Protein 1 (FABP-1), Angiopoietin-like 4 (ANGPTL4) (all Fine Biotech Co.), Zonulin (DRG International), and LPS (Qayee Biotechnology Co.) were analyzed. "Obese" subjects presented insulin resistance and liver injury. In the "Obese" serum zonulin was ~50% lower, whilst serum CRP and LPS significantly higher than in the "Lean." Serum zonulin was correlated inversely with BMI, total fat, liver fibrosis, serum CRP and LPS, but no studied cytokine (table 1). Our data point to decreased circulating zonulin in obese subjects, indicative of leaky gut as implied by its associations with endotoxemia, microinflammation, fat accumulation, and fibrotic liver damage. Disclosure: G. Wystrychowski: Other Relationship; Self; Roche Pharma. W. Grzeszczak: Other Relationship; Self; Berlin-Chemie AG, Roche Pharma. A. Witkowska: None. E. Wojtyna: None. A. Golda: Other Relationship; Self; Servier Laboratories. M. Wróbel: None. K. Bochenek: None. W. Trautsolt: None. S. Gorczynska-kosiorz: None. N. Szweda-gandor: None. Funding: Medical University of Silesia (KNW-1-178/N/7/K, KNW-1-008/K/8/K) [ABSTRACT FROM AUTHOR]