Genetic polymorphism of glutathion S-transferase P1 (GSTP1) Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus

One of the characteristics of type 2 diabetes mellitus (T2DM) is the state of persistent oxidative stress (OS) that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS) and increases OS. Glutathione S-transferase P1 (GSTP1) is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls) were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05) but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotypes and disease approached significance (P=0.08). Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients. [Projekat Ministarstva nauke Republike Srbije, br. 175075

Genetički polimorfizam glutation S-transferaze P1 (GSTP1) Ile105Val i osetljivost na aterogenezu kod pacijenata sa dijabetesom tipa 2

One of the characteristics of type 2 diabetes mellitus (T2DM) is the state of persistent oxidative stress (OS) that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS) and increases OS. Glutathione S-transferase P1 (GSTP1) is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls) were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05) but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotypes and disease approached significance (P=0.08). Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients.Jedna od osobina tipa 2 dijabetes mellitus (T2DM) je stanje perzistentnog oksidativnog stresa (OS) koji je sastavni deo patogeneze bolesti kao što je ateroskleroza i to najčešće putem hronične hiperglikemije koja stimuliše nastanak reaktivnih vrsta kiseonika (tzv ROS) i povećava nivo OS. Glutation S-transferaza P1 (GSTP1) pripada superfamiliji citosolnih GST. Kao enzim, ima važnu ulogu u neutralizaciji OS. Takođe, učestvuje u regulaciji signalnog puta stresa ali i štiti ćelije od apoptoze putem nekatalitičke ligand-vezujuće aktivnosti. Funkcionalni polimorfizam Ile105Val GSTP1 gena utiče na katalitičku aktivnost proteina i na njegovu stabilnost i cilj ove studije je bio da se utvrdi da li ova genska varijanta utiče na osetljivost na aterogenezu kod pacijenata sa T2DM. Ukupno 240 osobe (140 pacijenata sa T2DM i nekom od kliničkih manifestacija ateroskleroze i 100 zdravih kontrola) je bilo uključeno u ovu studiju. Genomska DNK je izolovana iz ćelija periferne krvi a genotipizacija je urađena primenom reakcije lančane polimeraze posle koje je urađena analiza dužine restrikcionih fragmenata (PCR-RFLP analiza). Nismo dobili statistički značajne razlike u raspodeli alela i genotipova između obolelih i kontrola (P>0.05) ali asocijacija između Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08) i Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08) genotipova i bolesti se približila značajnosti (P=0.08). Naši rezultaati pokazuju da je potrebna veća grupa ispitanika da bi se utvrdila prava veza između potencijalno protektivnog alela Val i bolesti kao i da bi se utvrdio uticaj drugih polimorfizama gena GSTP1 na aterogenezu kod T2DM pacijenata

Multiple Roles of LOXL2 in the Progression of Hepatocellular Carcinoma and Its Potential for Therapeutic Targeting

LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial–mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment

Antioxidant Response in Gills of Eurasian Perch ( Perca fluviatilis ) to Cyanobacterial Bloom Exposure in the Gruža Reservoir

The aim of this study was to assess the impact of an Aphanizomenon flos-aquae bloom in the Gruža Reservoir on the antioxidant parameters measured in the gill cells of Eurasian perch (Perca fluviatilis). Effects of the bloom were evaluated through copper, zinc and manganese containing superoxide dismutase (CuZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and biotransformation phase II enzyme glutathione-S-transferase (GST) activities and glutathione (GSH) and sulfydryl (–SH) groups concentrations. The activities of CuZn SOD and Mn SOD decreased during the cyanobacterial bloom compared to the period before the bloom. The opposite trend was observed for CAT and GSH-Px activities that increased. During the bloom GR and GST activities and GSH concentration decreased significantly. CuZn SOD, GR and GST activities are detected as the most important parameters for individual variations. Our results indicated that an A. flos-aquae bloom promotes oxidative stress in the gills of P. fluviatilis. The investigated parameters could be used in environmental risk assessment procedures to monitor the effects of A. flos-aquae blooms on fish. Observed changes in the antioxidant parameters in P. fluviatilis gills make them potential biomarkers in the research of ecological risk situations in freshwater ecosystems with frequent cyanobacterial blooms.Water Research and Management (2016), 6(2): 19-2

Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro

Chokeberry (Aronia melanocarpa) is known for its anti-oxidant, anti-inflammatory and anti-diabetic properties. Since the effects of chokeberry extract on the immune response have been only sporadically assessed, our aim was to investigate chokeberry fruit water extract on the immune response in vivo and in vitro. When administered orally to healthy mice, the extract exerted immunomodulatory effects in the gut evidenced by the altered proportion of macrophages, dendritic cells and T cells. Importantly, oral consumption of the chokeberry extract resulted in blood glucose level increase in C57BL/6 mice with chemically-induced diabetes. These in vivo results were corroborated by observed up-regulation of nitric oxide and interelukin-1β production in macrophages and dendritic cells, up-regulated phagocytic activity of macrophages, increased T and B lymphocytes proportions and differentiation of interferon-γ-producing T cells in vitro. The obtained results imply that our chokeberry extract stimulates pro-inflammatory properties in immune cells of innate and adaptive immunity

The influence of specific aspects of occupational stress on security guards' health and work ability: detailed extension of a previous study

In our earlier study of security guards, we showed that higher occupational stress was associated with health impairments (metabolic syndrome, diabetes, hypertension, cardiovascular diseases) and work disability. The aim of this study was to further explore the association of specific occupational stressors with health impairments and work disability parameters in 399 Serbian male security guards (aged 25-65 years). Ridge linear regression analysis revealed that, after controlling for age, body mass index, and smoking status, professional stressors including high demands, strictness, conflict/uncertainty, threat avoidance and underload were significant positive predictors of fasting glucose, triglycerides, total and LDL cholesterol, blood pressure, heart rate, Framingham cardiovascular risk score, and temporary work disability. The security profession is in expansion worldwide, and more studies are needed to establish precise health risk predictors, since such data are generally lacking

GLYCOSIDE HYDROLASES FROM FRESHWATER FISH GILL MICROBIOTA AS BIOFILM INHIBITORS FOR ENHANCED FOOD SAFETY

The formation of biofilms by foodborne pathogens is a constant challenge in the food industry, leading to an increased risk of contamination and compromising food safety. Many of the chemicals commonly used for sanitation in the food industry are unable to remove biofilms, are harmful to surfaces and can be toxic. The effectiveness of disinfectants can be improved using enzymes that specifically target biofilm components such as exopolysaccharides, extracellular DNA, or proteins. In this study we investigated the potential of glycoside hydrolases originating from the gill microbiota of freshwater fish to control biofilm formation in the most common foodborne pathogens. We demonstrated that β-glucosidase from Microbacterium sp. BG28 (BglB-BG28) effectively inhibits cellulose-rich biofilms formed by Salmonella enteritidis, S. typhimurium, S. infantis, and Escherichia coli. When these bacteria were cultivated overnight with 200 μL/mL enzyme, up to 80% less biofilm was formed. By fluorescence microscopy, we visualised the inhibition of biofilms on plastic, glass and aluminium, materials commonly used in the food industry. When used as a pre-treatment, BglB-BG28 increased the bactericidal efficacy of Oxicid®S, a commercially available surface disinfectant. Its effectiveness at temperatures up to 50 °C and in a pH range from 4 to 8 together with compatibility with non-ionic detergents and high tolerance to sodium chloride and glucose give BglB-BG28 advantages in harsh and diverse industrial environments. Importantly, no toxicity to Caenorhabditis elegans was observed at enzyme concentrations of up to 1 mg/ml. Overall, these results demonstrate the suitability of the β-glucosidase BglB-BG28 for the formulation of a novel enzyme-based disinfectant to be used in food processing facilities.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi

The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier.

Macrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-γ in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the "leakage" of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function

Health-related quality of life in elderly patients hospitalized with chronic heart failure

Background: Chronic heart failure is a very common condition in the elderly, characterized not only by high mortality rates, but also by a strong impact on health-related quality of life (HRQOL). Previous studies of HRQOL in elderly heart failure subjects have included mostly outpatients, and little is known about determinants of HRQOL in hospitalized elderly population, especially in Serbia. In this study, we tried to identify factors that influence HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Methods: The study population consisted of 136 patients aged 65 years or older hospitalized for chronic heart failure. HRQOL was assessed using the Minnesota Living with Heart Failure questionnaire. Predictors of HRQOL were identified by multiple linear regression analysis. Results: Univariate analysis showed that patients with lower income, a longer history of chronic heart failure, and longer length of hospital stay, as well as those receiving aldosterone antagonists and digoxin, taking multiple medications, in a higher NYHA class, and showing signs of depression and cognitive impairment had significantly worse HRQOL. Presence of depressive symptoms (P lt 0.001), higher NYHA class (P=0.021), lower income (P=0.029), and longer duration of heart failure (P=0.049) were independent predictors of poor HRQOL. Conclusion: Depressive symptoms, higher NYHA class, lower income, and longer duration of chronic heart failure are independent predictors of poor HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Further, there is an association between multiple medication usage and poor HRQOL, as well as a negative impact of cognitive impairment on HRQOL. Hence, measures should be implemented to identify such patients, especially those with depressive symptoms, and appropriate interventions undertaken in order to improve their HRQOL

Ultimate pH, colour characteristics and proximate and mineral composition of edible organs, glands and kidney fat from Saanen goat male kids

Ultimate pH value and instrumental colour (CIEL*a*b* values) characteristics, proximate (moisture, protein, total fat and total ash) and mineral composition (K, P, Na, Mg, Ca, Zn, Fe, Cu, Ni and Mn) were determined in 10 (heart, tongue, lungs, spleen, liver, kidney, brain, testicle, thymus and kidney fat) edible by-products of Saanen goat male kids. Many significant or numerical differences were found in the mean values of quality characteristics among the edible by-products. Among edible organs and glands, liver had the lowest surface CIEL* value (darkest colour), and the highest levels of protein, Zn, Cu and Mn. Furthermore, the highest pH(24h), total ash, K, P and Mg levels were determined in the thymus. The testicle had the highest moisture, Ca and Ni levels. The spleen had the lowest fresh cut cross-section CIEL* value (darkest colour), and the highest Fe level. The highest total fat content and Na level were determined in the brain and kidney, respectively. Among all the edible by-products, kidney fat had the highest pH(24h), surface CIEL* value (lightest colour) and total fat content, and the lowest moisture, protein, total ash, K, P, Na, Mg, Ca, Zn, Fe, Cu, Ni and Mn levels