Modulation of miR-155-5p signalling via 5-ASA for the prevention of high microsatellite instability: an in vitro study using human epithelial cell lines.

5-aminosalicylic acid (5-ASA) is a first-line treatment for maintaining colitis remission. It is a highly effective, safe, and well-tolerated drug with anti-inflammatory and chemo-preventive properties. While patients with primary sclerosing cholangitis (PSC) with concomitant ulcerative colitis are treated with 5-ASA, the molecular mechanisms underlying the drug's chemo-preventive effects are not entirely understood.

Previous hepatitis E virus infection is associated with increased liver stiffness in patients with autoimmune hepatitis.

Introduction: Autoimmune hepatitis (AIH) is a chronic, progressive liver disease that, in most cases, may require lifelong immunosuppression. Hepatitis E virus (HEV) is a leading cause of acute, typically self‑limited hepatitis worldwide, although immunocompromised patients may develop chronic hepatitis.

Objectives: We aimed to evaluate the impact of HEV seropositivity on the clinical course of AIH.

Effect of Low Testosterone Levels on the Expression of Proliferator-Activated Receptor Alpha in Female Patients with Primary Biliary Cholangitis.

Sex-dependent patterns in chronic immune-mediated cholangiopathies, like primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), remain poorly understood. Peroxisome proliferator-activated receptor alpha (PPAR-α), expressed in immune cells, plays a key role in innate defence. In this study, the relationship between PPAR-α expression in peripheral blood mononuclear cells (PBMCs), serum androgen levels, IFNγ production, and sex-dependent tendencies during the development of PBC and PSC was investigated.

Fluoride as a Potential Repressor of Glycogen Metabolism in Skeletal Muscle Cell Line CCL136.

The exposure of humans to fluorine is connected with its presence in the air, food and water. It is well known that fluorides even at a low concentration but with long time exposure accumulate in the body and lead to numerous metabolic disorders. Fluoride is recognised as a factor modulating the energy metabolism of cells.

The Role of hsa-miR-125b-5p Interaction with S1P/Ceramide Axis in the Potential Development of Inflammation-Associated Colon Cancer in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is characterised by the co-occurrence of inflammatory bowel diseases, particularly ulcerative colitis (UC). We investigated how the interaction of miR-125b with the sphingosine-1-phosphate (S1P)/ceramide axis may predispose patients with PSC, PSC/UC, and UC to carcinogenesis in the ascending and sigmoid colons. The overexpression of miR-125b was accompanied by the upregulation of S1P, ceramide synthases, ceramide kinases, and the downregulation of AT-rich interaction domain 2 in the ascending colon of PSC/UC, which contributed to the progression of high microsatellite instability (MSI-H) colorectal carcinoma.

Effectiveness of Autogenic Drainage in Improving Pulmonary Function in Patients with Cystic Fibrosis.

The use of autogenic drainage (AD) in patients with cystic fibrosis (CF) has been officially approved; therefore, the purpose of this study was to compare the efficiency of the leading therapeutic techniques based on AD in patients with CF; Among patients with CF assessments were made of spirometric parameters, percent blood oxygen saturation, and the general feeling of the patients (Borg, VAS, and mMRC dyspnea scale) before and after therapy using AD, using AD in connection with a belt or a Simeox device and AD in combination with both a belt and Simeox device simultaneously. The best therapeutic effects were generated by the combination of AD with the belt and with the Simeox device. The greatest improvements were observed for FEV1, FVC, PEF, FET, saturation, and patient comfort.

Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155.

Background: PPARα is a ligand-activated transcription factor that shows protective effects against metabolic disorders, inflammation and apoptosis. Primary biliary cholangitis and primary sclerosing cholangitis result in the intrahepatic accumulation of bile acids that leads to liver dysfunction and damage. Small, non-coding RNAs such as miR-155 and miR-21 are associated with silencing PPARα.

Modulation of Mismatch Repair and the SOCS1/p53 Axis by microRNA-155 in the Colon of Patients with Primary Sclerosing Cholangitis.

Deficient mismatch repair (MMR) proteins may lead to DNA damage and microsatellite instability. Primary sclerosing cholangitis (PSC) is a risk factor for colitis-associated colon cancer. MiR-155 is suggested to act as a key regulating node, linking inflammation and tumorigenesis.

5-aminosalicylic acid inhibits the expression of oncomiRs and pro-inflammatory microRNAs: an in vitro study.

5-aminosalicylic acid (5-ASA) is commonly used as the first-line treatment for ulcerative colitis (UC). In this study, we show that the mechanism responsible for the protective effect of 5-ASA is associated with the modulation of non-coding microRNA molecule (miRNA) expression. Stimulation of human intestinal epithelial cells (Caco-2) with 1000 μM of 5-ASA suppressed the levels of miR-125b, miR-150, miR-155, miR-346 and miR-506, which are known to be involved in the regulation of colitis and/or colorectal cancer in patients with inflammatory bowel disease.

Role of miR-506 in ulcerative colitis associated with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is commonly accompanied by ulcerative colitis (UC). MicroRNA-506 modulates expression of genes which are essential for sphingosine-mediated signaling pathway and intestinal mucosa protection. We investigated whether miR-506 and its target genes are involved in phenotypic presentations of colonic inflammation and/or neoplasia.

Relation of the C/T-13910 LCT Polymorphism with Body Composition Measures and Their Modulation by Dairy Products in a Caucasian Men.

The C/T-13910 LCT is closely associated with lactase persistence and LCT has emerged as a new candidate gene for obesity, in particular in northern Europeans. The aim of this research is to investigate to what degree sex determines the association between the LCT variant and anthropometric traits in a cohort of healthy individuals. We recruited 1000 (500 males and 500 females aged 18-65 years) healthy blood donors.

Melatonin Protects Cholangiocytes from Oxidative Stress-Induced Proapoptotic and Proinflammatory Stimuli via miR-132 and miR-34.

Biosynthesis of melatonin by cholangiocytes is essential for maintaining the function of biliary epithelium. However, this cytoprotective mechanism appears to be impaired in primary biliary cholangitis (PBC). MiR-132 has emerged as a mediator of inflammation in chronic liver diseases.

Vitamin-D Receptor-Gene Polymorphisms Affect Quality of Life in Patients with Autoimmune Liver Diseases.

Vitamin D deficiency has been associated with depressive symptoms and reduced physical functioning. The aim of the study was to characterize the relationship between polymorphisms of the vitamin D receptor (VDR) gene and the quality of life in patients with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). Three polymorphisms of the gene (, , and ) were analyzed in patients with AIH ( = 142) and PBC ( = 230) and in healthy individuals ( = 376).

Oncomir MicroRNA-346 Is Upregulated in Colons of Patients With Primary Sclerosing Cholangitis.

Introduction: Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder that is frequently associated with ulcerative colitis (UC). Patients with PSC and UC (PSC-UC) have a higher risk of colorectal neoplasia compared with patients with UC. The oncogenic properties of microRNA-346 (miR-346) have been recently reported.

Enhanced expression of miR-21 and miR-150 is a feature of anti-mitochondrial antibody-negative primary biliary cholangitis.

Background & Aims: Anti-mitochondrial-autoantibodies (AMA) remain a hallmark of Primary Biliary Cholangitis (PBC) however approximately 10% of patients test negative for these antibodies. They do not differ in terms of biochemistry or clinical presentation from AMA positive ones. Epigenetics play a key role in immune signalling.

The Association between SOCS1-1656G>A Polymorphism, Insulin Resistance and Obesity in Nonalcoholic Fatty Liver Disease (NAFLD) Patients.

Suppressor of cytokine signaling (SOCS) proteins prevent uncontrolled cytokine signaling and appear to play a role in the pathological processes behind obesity and insulin resistance. The polymorphism of the gene (rs243330, -1656G>A) is associated with obesity and glucose sensitivity. To estimate the effect of this gene polymorphism on nonalcoholic fatty liver disease (NAFLD) susceptibility, we performed a study on 138 patients with ultrasound-confirmed NAFLD and 1000 healthy blood donors.

ApaI polymorphism of vitamin D receptor affects health-related quality of life in patients with primary sclerosing cholangitis.

Background: Polymorphisms of vitamin D receptor (VDR) contribute to the pathogenesis of multiple autoimmune conditions.

Methods: We investigated the incidence of VDR polymorphisms (rs1544410-BsmI; rs7975232-ApaI; rs731236-TaqI) in a group of patients with primary sclerosing cholangitis (PSC, n = 275) and in healthy controls (n = 376). Additionally, correlations of the VDR polymorphisms with clinical and biochemical factors of the disease were analysed.

Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis.

In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner.

Decreased Expression of Vitamin D Receptor Affects an Immune Response in Primary Biliary Cholangitis via the VDR-miRNA155-SOCS1 Pathway.

Primary biliary cholangitis (PBC) is an immune-mediated cholestatic disease. Vitamin D receptor (VDR)-dependent signaling constrains an inflammatory response by targeting the miRNA155-SOCS1 (suppressor of cytokine signaling 1) axis. The VDR-miRNA155-SOCS1 pathway was investigated in the context of the autoimmune response associated with PBC.

Impaired Hepatic Adaptation to Chronic Cholestasis induced by Primary Sclerosing Cholangitis.

Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression.

Leisure time physical activity and health-related behaviours after liver transplantation: a prospective, single-centre study.

Introduction: Leisure time physical activity is of proven significance in surveys of fitness levels in various patient groups. Low physical functioning may affect recovery after liver transplantation (LTx).

Aim: To assess patients' leisure time activity and health-related habits after transplantation.

Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.

Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21).

Female Sex But Not Original Indication Affects Physical Activity After Liver Transplant: A Prospective, Single Center Study.

Objectives: Physical activity has an effect on long-term recovery after major surgical operations including liver transplant. Seven-Day Physical Activity Recall Questionnaire is a semistructured survey that assesses an individual's time spent in physical activity, strength, and flexibility activities during the 7 days prior to the interview. In this study we applied the Seven-Day Physical Activity Recall Questionnaire in patients who underwent liver transplant in our center.

Relationship between pretransplantation liver status and health-related quality of life after grafting: a single-center prospective study.

Background: Severity of liver disease evaluated with Model for End-Stage Liver Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36) is a widely used generic questionnaire of health-related quality of life (HRQoL). This study was a prospective analysis of the effect of pretransplantation liver status on HRQoL after the procedure.

Body surface temperature distribution in relation to body composition in obese women.

Adipose tissue levels and human obesity are known to be associated with increased heat production. At the same time, subcutaneous adipose tissue provides an insulating layer that impedes heat loss. The energy implications of obesity and body thermoregulatory mechanisms remain relatively poorly understood.