Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders

Aim. To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). Methods. The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. Results. IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. Conclusions. Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients

Cornus mas L. Increases Glucose Uptake and the Expression of PPARG in Insulin-Resistant Adipocytes

Cornus mas L., also known as cornelian cherry (CM), is a species that has long been cultivated in many different countries. In numerous scientific reports, cornelian cherry is used to treat numerous diseases and conditions. The presented study evaluated the effect of red and yellow Cornus mas L. extract on insulin sensitivity in adipocytes. 3T3-L1 fibroblasts as well as human SAT-derived and VAT-derived adipocytes were differentiated in vitro, and insulin resistance was induced using palmitic acid (16:0). The effect of CM fruit extract was analyzed in terms of glucose uptake and insulin signaling gene expression. In the glucose uptake test after insulin stimulation, a significant increase in glucose uptake was demonstrated in cells treated with CM fruit extracts. Furthermore, CM fruit extracts increased the expression of insulin signaling genes in adipocytes stimulated with insulin in control cells and adipocytes treated with CM extract. Additionally, a significant increase in peroxisome proliferator activated receptor gamma (PPARG) expression was observed in cells supplemented with CM extract. In conclusion, studies have shown that CM fruits can overcome insulin resistance and thus they have a positive effect on cell metabolism

The Preliminary Evaluation of Epigenetic Modifications Regulating the Expression of IL10 in Insulin-Resistant Adipocytes

A higher level of IL10 expression in obesity and insulin resistance was observed in both human and mouse WAT. In our research, we analyzed the influence of insulin resistance on epigenetic modification within the promoter region IL10 gene and the potential influence of these modifications on its expression. Studies were performed using two cell models for the analysis: human, preadipocytes derived from adipose (visceral and subcutaneous) tissues and murine 3T3-L1 fibroblasts. We demonstrated a significant increase in the IL10 expression level, IL10 promoter region methylation, and histone 3 epigenetic modifications: H3K4me and H3K9/14ac, in insulin resistance cells (IR) from SAT cell culture. In IR cells from VAT cell culture, we observed decreased IL10 expression with a simultaneous increase of IL10 promoter region methylation. In IR cells from 3T3L1 cell culture, we observed the increased expression of IL10 as well as the decreased levels of methylation in the IL10 promoter region and histone methylation (H3K4me) and acetylation (H3K9/14ac). The presented analyses suggest a potential impact of epigenetic modifications on gene expression and a potential mutual influence of epigenetic modifications on each other or the activation of specific epigenetic regulation at a different stage of the development of insulin resistance in cells

Metabolic Differences between Subcutaneous and Visceral Adipocytes Differentiated with an Excess of Saturated and Monounsaturated Fatty Acids

Obesity is a major health problem in highly industrialized countries. High-fat diet (HFD) is one of the most common causes of obesity and obesity-related disorders. There are considerable differences between fat depots and the corresponding risks of metabolic disorders. We investigated the various effects of an excess of fatty acids (palmitic 16:0, stearic 18:0, and oleic acids 18:1n−9) on adipogenesis of subcutaneous- and visceral-derived mesenchymal stem cells (MSCs) and phenotypes of mature adipocytes. MSCs of white adipose tissue were acquired from adipose tissue biopsies obtained from subcutaneous and visceral fat depots from patients undergoing abdominal surgery. The MSCs were extracted and differentiated in vitro with the addition of fatty acids. Oleic acid stimulated adipogenesis, resulting in higher lipid content and larger adipocytes. Furthermore, oleic acid stimulated adipogenesis by increasing the expression of CCAAT enhancer binding protein β (CEBPB) and peroxisome proliferator activated receptor γ (PPARG). All of the examined fatty acids attenuated the insulin-signaling pathway and radically reduced glucose uptake following insulin stimulation. Visceral adipose tissue was shown to be more prone to generate inflammatory stages. The subcutaneous adipose tissue secreted a greater quantity of adipokines. To summarize, oleic acid showed the strongest effect on adipogenesis. Furthermore, all of the examined fatty acids attenuated insulin signaling and secretion of cytokines and adipokines

<i>Cornus mas</i> L. Increases Glucose Uptake and the Expression of <i>PPARG</i> in Insulin-Resistant Adipocytes

Cornus mas L., also known as cornelian cherry (CM), is a species that has long been cultivated in many different countries. In numerous scientific reports, cornelian cherry is used to treat numerous diseases and conditions. The presented study evaluated the effect of red and yellow Cornus mas L. extract on insulin sensitivity in adipocytes. 3T3-L1 fibroblasts as well as human SAT-derived and VAT-derived adipocytes were differentiated in vitro, and insulin resistance was induced using palmitic acid (16:0). The effect of CM fruit extract was analyzed in terms of glucose uptake and insulin signaling gene expression. In the glucose uptake test after insulin stimulation, a significant increase in glucose uptake was demonstrated in cells treated with CM fruit extracts. Furthermore, CM fruit extracts increased the expression of insulin signaling genes in adipocytes stimulated with insulin in control cells and adipocytes treated with CM extract. Additionally, a significant increase in peroxisome proliferator activated receptor gamma (PPARG) expression was observed in cells supplemented with CM extract. In conclusion, studies have shown that CM fruits can overcome insulin resistance and thus they have a positive effect on cell metabolism

VDR gene single nucleotide polymorphisms and their association with risk of oral cavity carcinoma

Vitamin D3 (1,25(OH)2D3 (1,25-dihydroxyvitamin D3)) is a hormone playing a crucial role in numerous biological processes in the human body, including induction and control of cell proliferation and differentiation. Numerous data relate the vitamin D3 level with various types of cancer. It has been suggested that SNPs in the vitamin D3 receptor (VDR) gene might influence both the risk of cancer occurrence and cancer progression. The aim of this study was to search for genetic correlations between individual SNPs in the VDR gene and the risk of oral cavity carcinoma. Two SNPs were selected based on the literature and our previous results. Seventy-three patients with squamous cell carcinoma of the head and neck and one hundred control subjects were investigated. Two SNPs in the VDR gene were genotyped in minisequencing reactions followed by capillary electrophoresis. Hardy-Weinberg equilibrium (HWE), the χ2 test and logistic regression were used for statistical analysis. The SNP rs2238135 in the VDR gene displayed statistical differences in frequency between the tested groups (p=0,0007). Furthermore, the G/C genotype of the rs2238135 in the VDR gene was characterized by a 3.16 fold increased risk of oral cavity carcinoma. The obtained results provide evidence for a genetic association between rs2238135 in the VDR gene and the occurrence and risk of oral cavity cancer

Complementary Gene Therapy after Revascularization with the Saphenous Vein in Diabetic Foot Syndrome

Diabetic foot syndrome (DFS) is one of the most serious macroangiopathic complications of diabetes. The primary treatment option is revascularization, but complementary therapies are still being sought. The study group consisted of 18 patients diagnosed with ischemic ulcerative and necrotic lesions in DFS. Patients underwent revascularization procedures and, due to unsatisfactory healing of the lesions, were randomly allocated to two groups: a group in which bicistronic VEGF165/HGF plasmid was administered and a control group in which saline placebo was administered. Before gene therapy administration and after 7, 30, 90, and 180 days, color duplex ultrasonography (CDU) was performed, the ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) were measured, and DFS changes were described and documented photographically. In the gene therapy group, four out of eight patients (50%) healed their DFS lesions before 12 weeks. During this time, the ABI increased by an average of 0.25 and TcPO2 by 30.4 mmHg. In the control group, healing of the lesions by week 12 occurred in six out of nine patients (66.67%), and the ABI increased by an average of 0.14 and TcPO2 by 27.1 mmHg. One major amputation occurred in each group. Gene therapy may be an attractive option for complementary treatment in DFS