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.

Background: Immune-regulatory genes such as CTLA-4, FOXO-3, and PTPN-22 influence immune tolerance and metabolic adaptation, but their interaction with environmental factors in type 1 diabetes (T1DM) remains unclear. Methods: In this observational associated study, we analyzed CTLA-4 (rs3087243, rs231775), FOXO-3 (rs2802292, rs9400239), and PTPN-22 (rs12730735) polymorphisms in 277 adults with T1DM, assessing associations with probiotic and vitamin D use, self-reported dietary patterns, metabolic control, autoimmune thyroid disease (AITD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Results: Across the cohort, CTLA-4 rs3087243 G and FOXO-3 rs2802292 T alleles were associated with higher AITD risk (p = 0.016–0.03), significant in both dominant and additive models. The effect persisted by sex: CTLA-4 in women and FOXO-3 in men. Stratified analyses revealed metabolic advantages for CTLA-4 G and FOXO-3 T carriers (vegetarian diet, lower HbA1c, stress adaptation). FOXO-3 rs9400239 T was linked to MASLD (p ≈ 0.037–0.041), with similar trends for CTLA-4 rs231775, stronger in men. Vitamin D supplementation showed protective trends, particularly in FOXO-3 rs2802292 GG and CTLA-4 GG/AG carriers. Conversely, probiotic use was associated with higher AITD in FOXO-3 rs2802292 GT and CTLA-4 rs3087243 GG genotypes. Conclusions: CTLA-4, FOXO-3, and PTPN-22 variants may modulate the metabolic and autoimmune response to environmental factors including nutrients in T1DM.

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, i.e. elevated blood sugar levels, which stems from a defect in production or action of insulin secreted by pancreatic beta cells. Type 2 diabetes, which involves reduced sensitivity of tissues to insulin, is the most common form of diabetes. Over the years knowledge concerning the etiology of both type 1 and type 2 diabetes was extended, which enabled implementation of new methods of treatment and prevention. Unfortunately, a monogenic factor conditioning the emergence of this disease still has not been isolated, hence scientists more often focus on regulators of expression of various metabolic proteins, e.g. miRNA, which are one of the more important factors regulating expression. First reports concerning the role of miRNA in metabolism in animal organisms come from observations of miR-14 mutants in fruit flies (Drosophila melanogaster). miRNA are single-stranded RNA molecules with a length of approx. 19–150 nucleotides. A single miRNA molecule can excite expression of several genes, inhibit it, or excite some and inhibit others. MicroRNA regulates the process of insulin secretion, cellular differentiation of beta cells in pancreatic islets and additionally influence glucose and lipid metabolism. All these issues are potential subjects of further research. Expansion of knowledge concerning microRNA and its role in disease processes is a target for devising new therapeutic strategy, and therefore utilization in production of drugs. Most research is currently in its initial phase, but even preliminary results are highly promising. Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, i.e. elevated blood sugar levels, which stems from a defect in production or action of insulin secreted by pancreatic beta cells. Type 2 diabetes, which involves reduced sensitivity of tissues to insulin, is the most common form of diabetes. Over the years knowledge concerning the etiology of both type 1 and type 2 diabetes was extended, which enabled implementation of new methods of treatment and prevention. Unfortunately, a monogenic factor conditioning the emergence of this disease still has not been isolated, hence scientists more often focus on regulators of expression of various metabolic proteins, e.g. miRNA, which are one of the more important factors regulating expression. First reports concerning the role of miRNA in metabolism in animal organisms come from observations of miR-14 mutants in fruit flies (Drosophila melanogaster). miRNA are single-stranded RNA molecules with a length of approx. 19–150 nucleotides. A single miRNA molecule can excite expression of several genes, inhibit it, or excite some and inhibit others. MicroRNA regulates the process of insulin secretion, cellular differentiation of beta cells in pancreatic islets and additionally influence glucose and lipid metabolism. All these issues are potential subjects of further research. Expansion of knowledge concerning microRNA and its role in disease processes is a target for devising new therapeutic strategy, and therefore utilization in production of drugs. Most research is currently in its initial phase, but even preliminary results are highly promising.

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.

Background: Many factors influence the development of insulin resistance, among other genetic factors. Cortisol is one of the factors that has a significant impact on the development of insulin resistance. The proteins that have a substantial effect on blood cortisol levels include 11β-hydroxysteroid dehydrogenase type 1. HSD11B1 is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. Gene encoding HSD11B1 is located on 1q32.2. This study was designed to assess the association between four polymorphic sides in HSD11B1 (rs12086634, rs846910, rs4844880, rs3753519) between subjects with and without insulin resistance in the Polish population of people living in Upper Silesia. Methods: The study included a total of 507 consecutive patients, 374 (73.77%) with and 133 (26.23%) without insulin resistance. Results: The results show that there were no statistically significant differences in the distribution of genotypes and alleles of the examined polymorphisms of the 11β-hydroxysteroid dehydrogenase type 1 gene between subjects with and without insulin resistance (determined using the HOMA-IR, insulin resistance index) and that rs846910 and rs1208663 polymorphisms of the 11β-hydroxysteroid dehydrogenase type 1 gene in the examined subjects have a significant effect on the magnitude of the HOMA-IR insulin resistance index. Conclusions: The study results suggested that genetic variation of rs846910 and rs1208663 polymorphism of the HSD11B1 gene is related to the susceptibility to insulin resistance. Our results provide a basis to begin basic research on the role of the HSD11B1 gene in the pathogenesis of insulin resistance.

Visfatin (nicotinamide phosphoribosyltransferase) is adipokine which performed many function in organism. It can be expressed in different tissues such as brain, kidneys and visceral adipose tissue. Visfatin takes part in many molecular processes including apoptosis, inflammation, cell proliferation. It affects the glucose metabolism and is involved in pathogenesis of diabetes, insulin resistance, arterosclerosis and obesity. Moreover studies suggest that visfatin also may be associated with development of diabetic nephropathy and retinopathy. The goal of the study is the assessment of influence of different visfatin’s gene variants on occurrence of late diabetic complications. Study group consisted 272 patients with diabetes- 139 men and 133 women from Southern Poland. Selected DNA fragments were amplificated and marked. Visfatin’s gene in rs4730153 was examined. The Real Time PCR was conducted with fluorescence-labelled probes. The most common genotypes were heterozygote AG- 138 patients (51%) and homozygote GG- 89 patients (33%). In the study group there are 92 diabetics with retinopathy, 26 with nephropathy, 88 with neuropathy and 103 with macroangiopathy. It has been assessed using χ2 test that there are no differences between variability of different variants of visfatin’s gene in distribution of genotypes. According to Hardy-Weinberg's test the variety of population is maintained. Visfatin (nicotinamide phosphoribosyltransferase) is adipokine which performed many function in organism. It can be expressed in different tissues such as brain, kidneys and visceral adipose tissue. Visfatin takes part in many molecular processes including apoptosis, inflammation, cell proliferation. It affects the glucose metabolism and is involved in pathogenesis of diabetes, insulin resistance, arterosclerosis and obesity. Moreover studies suggest that visfatin also may be associated with development of diabetic nephropathy and retinopathy. The goal of the study is the assessment of influence of different visfatin’s gene variants on occurrence of late diabetic complications. Study group consisted 272 patients with diabetes- 139 men and 133 women from Southern Poland. Selected DNA fragments were amplificated and marked. Visfatin’s gene in rs4730153 was examined. The Real Time PCR was conducted with fluorescence-labelled probes. The most common genotypes were heterozygote AG- 138 patients (51%) and homozygote GG- 89 patients (33%). In the study group there are 92 diabetics with retinopathy, 26 with nephropathy, 88 with neuropathy and 103 with macroangiopathy. It has been assessed using χ2 test that there are no differences between variability of different variants of visfatin’s gene in distribution of genotypes. According to Hardy-Weinberg's test the variety of population is maintained.