Antioxidant effect of lactic acid bacteria in human bronchial epithelial cells exposed to cigarette smoke.

AIMS: Chronic lung diseases are a major and increasing global health problem, commonly caused by cigarette smoke. We aimed to explore the antioxidant effects of lactic acid bacteria (LAB) against cigarette smoke in bronchial epithelial cells. METHODS AND RESULTS: The antioxidant effects of 21 heat-killed (HK) LAB strains were tested in cigarette smoke-stimulated BEAS-2B cells and 3-D bronchospheres organoids. We showed that HK Lactiplantibacillus plantarum BGPKM22 possesses antioxidant activity against cigarette smoke, resistance to hydrogen peroxide, and free radical neutralizing activity. We demonstrated that HK BGPKM22 inhibited cigarette smoke-induced expression of the Aryl hydrocarbon receptor (AhR) and Nuclear factor erythroid 2 related factor 2 (Nrf2) genes. The cell-free supernatant (SN) of BGPKM22 fully confirmed the effects of HK BGPKM22. CONCLUSIONS: For the first time, we revealed that HK and SN of Lactip. plantarum BGPKM22 possess antioxidant activity and modulate AhR and Nrf2 gene expression in bronchial epithelial cells exposed to cigarette smoke.

Effects of Transcranial Electrical Stimulation on Gambling and Gaming: A Systematic Review of Studies on Healthy Controls, Participants with Gambling/Gaming Disorder, and Substance Use Disorder.

Gambling disorder (GD) and internet gaming disorder (IGD) are formally recognized behavioral addictions with a rapidly growing prevalence and limited treatment options. Recently, transcranial electrical stimulation (tES) techniques have emerged as potentially promising interventions for improving treatment outcomes by ameliorating cognitive functions implicated in addictive behaviors. To systematize the current state of evidence and better understand whether and how tES can influence gambling and gaming-related cognitive processes, we conducted a PRISMA-guided systematic review of the literature, focusing on tES effects on gaming and gambling in a diverse range of population samples, including healthy participants, participants with GD and IGD, as well as participants with substance abuse addictions. Following the literature search in three bibliographic databases (PubMed, Web of Science, and Scopus), 40 publications were included in this review, with 26 conducted on healthy participants, 6 focusing on GD and IGD patients, and 8 including participants with other addictions. Most of the studies targeted the dorsolateral prefrontal cortex, using transcranial direct current stimulation (tDCS), and assessed the effects on cognition, using gaming and gambling computerized cognitive tasks measuring risk taking and decision making, e.g., balloon analogue risk task, Iowa gambling task, Cambridge gambling task, etc. The results indicated that tES could change gambling and gaming task performances and positively influence GD and IGD symptoms, with 70% of studies showing neuromodulatory effects. However, the results varied considerably depending on the stimulation parameters, sample characteristics, as well as outcome measures used. We discuss the sources of this variability and provide further directions for the use of tES in the context of GD and IGD treatment.

Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a complex disorder with unexplained heritability. Interactions of genetic and environmental factors are thought to be crucial in COPD. So, we aim to examine interactions of the endothelial nitric oxide synthase (eNOS) and angiotensin converting enzyme (ACE) genes and cigarette smoking in COPD. Methods: The eNOS G 894T and ACE ID variants were analyzed in 122 COPD patients and 200 controls from Serbia. The effect of the variants on COPD was assessed by logistic regression. Interactions between eNOS, ACE and cigarette smoking in COPD were evaluated using a case-control model. Interaction between the genes was analyzed in silico. Results: No effect of the eNOS G 894T and ACE ID variants on COPD was found in our study. Gene-gene interaction between the eN OS T T and A CE D was identified (p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environment interactions between the eNOS T and cigarette smoking (p=0.013), and the ACE II and cigarette smoking (p=0.009) were detected in COPD in our study. Conclusions: This is the first research to reveal interactions of the eNOS and ACE genes and cigarette smoking in COPD progressing our understanding of COPD heritability and contributing to the development of appropriate treatments.

Determining the Individual Theta Frequency for Associative Memory Targeted Personalized Transcranial Brain Stimulation.

Non-invasive brain stimulation (NIBS) methods have gained increased interest in research and therapy of associative memory (AM) and its impairments. However, the one-size-fits-all approach yields inconsistent findings, thus putting forward the need for electroencephalography (EEG)-guided personalized frequency-modulated NIBS protocols to increase the focality and the effectiveness of the interventions. Still, extraction of individual frequency, especially in the theta band, turned out to be a challenging task. Here we present an approach to extracting the individual theta-band frequency (ITF) from EEG signals recorded during the AM task. The method showed a 93% success rate, good reliability, and the full range of variability of the extracted ITFs. This paper provides a rationale behind the adopted approach and critically evaluates it in comparison to the alternative methods that have been reported in the literature. Finally, we discuss how it could be used as an input parameter for personalized frequency-modulated NIBS approaches-transcranial alternating current stimulation (tACS) and transcranial oscillatory current stimulation (otDCS) directed at AM neuromodulation.

ST2 and the alteration of cobalt, sodium, potassium and calcium concentration in acute inflammation.

INTRODUCTION: ST2 is the receptor for interleukin (IL)-33, the last discovered member of the IL-1 cytokine family. Acute inflammation is an early response of vascularized tissue to injury, in which alteration of micro- and macro-elements occurs. This study aimed to examine the alteration of cobalt, sodium, potassium, and calcium concentration at the site of acute inflammation and the role of ST2 in these alterations. MATERIAL AND METHODS: Wild-type (WT) and ST2 knockout (ST2-/-) mice were divided into groups: WT control group (WT-C), ST2 knockout control group (KO-C), WT inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). We induced acute inflammation by intramuscular injection of turpentine oil or saline in the case of the control group. After 12 h, we anesthetized mice and collected treated tissues for histopathological analysis and determination of cobalt, sodium, potassium, and calcium concentration by atomic absorption spectrometer. RESULTS: Histopathological analysis showed the inflammatory infiltrate and cell necrosis in the treated tissue in WT-I and KO-I. The concentration of sodium was significantly lower in WT-I than in WT-C. The concentration of potassium and cobalt was significantly lower in WT-I and KO-I when compared to WT-C and KO-C, respectively. However, the concentration of potassium and cobalt in the tissue was significantly lower in WT-I than in KO-I. The concentration of calcium in the tissue did not significantly differ between groups. CONCLUSION: We reported, to our knowledge for the first time, that ST2 is involved in decreasing sodium, potassium, and cobalt concentration at the site of acute inflammation.

Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-κB and MAPK Signaling in Human Bronchial Epithelial Cells.

Bronchial epithelial cells are exposed to environmental influences, microbiota, and pathogens and also serve as a powerful effector that initiate and propagate inflammation by the release of pro-inflammatory mediators. Recent studies suggested that lung microbiota differ between inflammatory lung diseases and healthy lungs implicating their contribution in the modulation of lung immunity. Lactic acid bacteria (LAB) are natural inhabitants of healthy human lungs and also possess immunomodulatory effects, but so far, there are no studies investigating their anti-inflammatory potential in respiratory cells. In this study, we investigated immunomodulatory features of 21 natural LAB strains in lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Our results show that several LAB strains reduced the expression of pro-inflammatory cytokine and chemokine genes. We also demonstrated that two LAB strains, Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22, effectively attenuated LPS-induced nuclear factor-κB (NF-κB) nuclear translocation. Moreover, BGZLS10-17 and BGPKM22 reduced the activation of p38, extracellular signal-related kinase (ERK), and c-Jun amino-terminal kinase (JNK) signaling cascade resulting in a reduction of pro-inflammatory mediator expressions in BEAS-2B cells. Collectively, the LAB strains BGZLS10-17 and BGPKM22 exhibited anti-inflammatory effects in BEAS-2B cells and could be employed to balance immune response in lungs and replenish diminished lung microbiota in chronic lung diseases.

Fatty acid in colorectal cancer in adult and aged patients of both sexes.

PURPOSE: Colorectal cancer represents the second most common type of cancer in Serbia. Alteration of lipid metabolism begins early, and can represent a central hallmark in cancer evolution. Fatty acids have various important functions as building components of cell membranes, as signaling molecules in immune responses and also manage the general cancer signaling network. The purpose of this study was to investigate the difference of various fatty acids content between colorectal cancer and adjacent healthy intestinal tissue in adult and aged patients of both sexes. METHODS: 52 subjects participated in this study. Healthy colon mucosa and tumor tissue samples were obtained from patients previously diagnosed with colorectal carcinoma. Simplified method of Berstad et al was used for direct transesterification of total lipids in tumor and healthy mucosa tissue samples and separations of the methyl esters was carried out using a gas chromatograph equipped with a split/splitless injector and a flame ionization detector. RESULTS: 18 0, 18 1 n7, 20 3, 20 4, 20 5, 22 4, 22 5 22 6, SFA, PUFA, n6, n3 and AA/EPA were significantly higher in tumor tissue. On the other hand, 18 1 n9, 18 2, 18 3 n3, MUFA, n6/n3 were significantly higher in healthy tissue. CONCLUSIONS: Saturation index (SI) could be a valuable tool to delineate robust immune response and worse prognosis in patients with colorectal cancer. Our study demonstrated significant differences in fatty acid profiles between tumor tissue and healthy mucosa. Parameters, such as gender, age, stage and mucinous component didn't influence altered fatty acid content.

Static magnetic field on behavior, hematological parameters and organ damage in spontaneously hypertensive rats.

Previous studies showed contradictory results of static magnetic field (SMF) influence on behavior, hematological parameters and organ damage. The aim of this study was to investigate influence of subchronic continuous exposure to upward and downward oriented SMF of moderate intensity on behavior, hematological characteristics, heart and kidney tissue of spontaneously hypertensive rats. SH rats exposed to downward oriented SMF demonstrated lack of anxious-like behavior. SMF of either orientation caused decrease in the number of platelets in peripheral blood, granulocytes in the spleen and bone marrow and increase in the number of erythrocytes in the spleen, in both exposed groups. We also demonstrated that spontaneously hypertensive rats exposed to upward oriented SMF exhibited decreased lymphocytes count in blood, decreased bone marrow erythrocytes count and rats exposed to downward oriented SMF had increased lymphocytes count in bone marrow. The results showed adverse effect of differently oriented SMF on hematological parameters of spontaneously hypertensive rats. Also, exposure to different oriented SMF didn't affect their heart and kidney morphological characteristics.

Blinding in tDCS Studies: Correct End-of-Study Guess Does Not Moderate the Effects on Associative and Working Memory.

Transcranial direct current stimulation (tDCS) has become a valuable tool in cognitive neuroscience research as it enables causal inferences about neural underpinnings of cognition. However, studies using tDCS to modulate cognitive functions often yield inconsistent findings. Hence, there is an increasing interest in factors that may moderate the effects, one of which is the participants' beliefs of the tDCS condition (i.e., real or sham) they received. Namely, whether participants' correct guessing of sham condition may lead to false-positive tDCS effects. In this study, we aimed to explore if participants' beliefs about received stimulation type (i.e., the success of blinding) impacted their task performance in tDCS experiments on associative (AM) and working memory (WM). We analyzed data from four within-subject, sham-controlled tDCS memory experiments (N = 83) to check if the correct end-of-study guess of sham condition moderated tDCS effects. We found no evidence that sham guessing moderated post-tDCS memory performance in experiments in which tDCS effects were observed as well as in experiments that showed null effects of tDCS. The results suggest that the correct sham guessing (i.e., placebo-like effect) is unlikely to influence the results in tDCS memory experiments. We discuss the results in light of the growing debate about the relevance and effectiveness of blinding in brain stimulation research.

Cloning and expression profiling of muscle regulator ANKRD2 in domestic chicken Gallus gallus.

Striated muscle signaling protein and transcriptional regulator ANKRD2 participates in myogenesis, myogenic differentiation, muscle adaptation and stress response. It is preferentially expressed in slow, oxidative fibers of mammalian skeletal muscle. In this study, we report on characterization of chicken ANKRD2. The chicken ANKRD2 coding region contains 1002 bp and encodes a 334-amino acid protein which shares approximately 58% identity with human and mouse orthologs, mostly in the conserved region of ankyrin repeats. Comprehensive analysis of the ANKRD2 gene and protein expression in adult chicken demonstrated its predominant expression in red muscles of thigh and drumstick, compared to white muscle. It was not detected in heart and white pectoral muscle. Uneven expression of ANKRD2 in chicken skeletal muscles, observed by immunohistochemistry, was attributed to its selective expression in slow, oxidative, type I and fast, oxidative-glycolytic, type IIA myofibers. Association of chicken ANKRD2 with phenotypic differences between red and white muscles points to its potential role in the process of myofiber-type specification. In addition to expression in slow oxidative myofibers, as demonstrated for mammalian protein, chicken ANKRD2 was also detected in fast fibers with mixed oxidative and glycolytic metabolism. This finding suggests that ANKRD2 is responsive to metabolic differences between types of avian myofibers and orientates future studies towards investigation of its role in molecular mechanisms of myofiber-type-specific gene expression.

Gene-Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians.

Chronic obstructive pulmonary disease (COPD) is a complex disorder influenced by multiple genetic and environmental factors, as well as their interactions. Since elevated oxidative stress and protease activity characterize the pathogenesis of COPD, variants of genes that can affect these processes have been commonly studied in COPD. However, interactions among genes that can influence oxidative stress and protease activity remain poorly investigated in COPD. The aim of this study was to look into the role of functional variants in matrix metalloproteinases (MMPs) 1, 9, and 12 in the occurrence and/or modulation of COPD, and to analyze their interactions with glutathione S-transferases (GSTs) M1, T1, and P1 in the pathogenesis of COPD in Serbians. The MMP1 rs1799750 G > GG, MMP9 rs3918242 C > T, and MMP12 rs2276109 A > G variants were analyzed by direct detection methods. Gene-gene interactions between variants in MMPs and GSTs were assessed using a case-control model. Our results showed association of the MMP1 GG/GG genotype with COPD (p = 0.036, OR = 2.50). Gene-gene interactions between the GSTM1 null and MMP1 GG (p = 0.028, OR = 2.99) and the GSTM1 null and MMP12 AA variants (p = 0.015, OR = 3.82) were found to significantly increase the risk of COPD occurrence. Furthermore, the MMP12 G variant was found to modify the age of COPD onset (p = 0.025, OR = 3.30), while interaction between the GSTM1 null and MMP9 T variants was found to modify the severity of disease (p = 0.019, OR = 4.83). To our best knowledge, this is the first study revealing several gene-gene interactions affecting oxidative stress and protease activity in the pathogenesis of COPD.

Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults.

The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.

Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease.

The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. © 2016 Wiley Periodicals, Inc.

Effects of IL-33/ST2 pathway in acute inflammation on tissue damage, antioxidative parameters, magnesium concentration and cytokines profile.

AIM: The aim of this study was to examine the role of IL-33/ST2 pathway in a pathogenesis of acute inflammation and its effects on tissue damage, antioxidative capacity, magnesium concentration and cytokine profile in acutely inflamed tissue. MATERIAL AND METHODS: Male mice were randomly divided in four groups: wild-type control group (WT-C), ST2 knockout control group (KO-C), wild-type inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). Acute inflammation was induced in WT-I and KO-I by intramuscular injection of turpentine oil, while mice in WT-C and KO-C were treated with saline. After 12h, animals were euthanized, and blood was collected for determination of creatine kinase (CK) and aspartate transaminase (AST) activity. The treated tissue was used for histopathological analysis, determination of volume density of inflammatory infiltrate (Vdii) and necrotic fiber (Vdnf), gene expression of interleukin (IL)-33, ST2, tumor necrosis factor alpha (TNF-alpha), IL-6, IL-12p35, and transforming growth factor beta (TGF-beta), concentration of magnesium (Mg), copper (Cu), selenium (Se), manganese (Mn) and reduced glutathione (GSH), and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. RESULTS: Presence of inflammatory infiltration and necrosis in the treated tissue was histopathologically confirmed in WT-I and KO-I. Vdii was significantly higher in WT-I when compared to KO-I, whereas Vdnf did not significantly differ between WT-I and KO-I. CK and AST significantly increased in both inflammatory groups when compared to corresponding control groups. However, the values of CK and AST were significantly higher in WT-I than in KO-I. Mg in the treated tissue was significantly lower in WT-I in comparison to WT-C and KO-I, while there was no significant difference between KO-C and KO-I. There was no significant difference in Cu, Se, and Mn in the treated tissue between WT-C, KO-C, WT-I and KO-I. Gene expression of IL-33 in the treated tissue increased in both inflammatory groups when compared to the corresponding control groups, but it was significantly higher in KO-I than in WT-I. Gene expression of ST2 in the treated tissue was significantly higher in WT-I than in WT-C. Gene expression of TNF-alpha, IL-6, and IL-12p35 in the treated tissue was significantly higher in WT-I and KO-I than in the corresponding control groups, and IL-6 was significantly higher in KO-C than in WT-C. TGF-beta gene expression in the treated tissue was significantly higher in KO-I when compared to WT-I, while there was no difference between WT-C and KO-C. SOD activity decreased at the site of acute inflammation in both inflammatory groups, while the GPx activity increased. GSH in the treated tissue was significantly higher in KO-I than in KO-C or WT-I. CONCLUSION: The results of our study have indicated, to our knowledge for the first time, that IL-33/ST2 pathway plays a role in enhancing inflammation and tissue damage at the site of acute inflammation by affecting the concentration of magnesium and GSH, important for antioxidative capacity, as well as gene expression of anti-inflammatory cytokine TGF-beta.

Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults.

Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI <25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.

Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation.

The aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue. Acute inflammation was induced by injection of turpentine oil into the right and left hind limb muscles of mice, whereas control animals received intramuscular saline injection. After 12 h, animals were anesthetised and treated muscles collected. The tissue was stained by hematoxylin and eosin, digital micrographs produced, enabling determination of fractal dimension of the cells, angular second moment and correlation of studied tissue. Histopathological analysis showed presence of inflammatory infiltrate and tissue damage in inflammatory group, whereas tissue structure in control group was preserved, devoid of inflammatory infiltrate. Fractal dimension of the cells, angular second moment and correlation of treated tissue in inflammatory group decreased in comparison to the control group. In this study, we were first to observe and report that fractal dimension of the cells, angular second moment, and correlation were reduced in acutely inflamed tissue, indicating loss of overall complexity of the cells in the tissue, the tissue uniformity and structure regularity. Fractal dimension, angular second moment and correlation could be useful methods for quantification of structural changes in acute inflammation.

Effects of Il-33/St2 pathway on alteration of iron and hematological parameters in acute inflammation.

AIM: The aim of this study was to examine the role of the IL-33/ST2 pathway in pathogenesis of acute inflammation by investigating its possible role in alteration of iron and hematological parameters in experimental model of acute inflammation. MATERIAL AND METHODS: Wild-type and ST2 knockout BALB/c mice were divided into four groups: wild-type control group, ST2-/- control group, wild-type inflammatory group, and ST2-/- inflammatory group. Acute inflammation was induced by intramuscular injection of turpentine oil, while control groups were injected with saline. After 12h animals were anesthetized, and the treated tissue, blood and spleen were collected. Iron concentration in the treated tissue, hemoglobin blood concentration, mean corpuscular hemoglobin (MCH), hematocrit, erythrocyte, neutrophil and lymphocyte blood count, and erythrocytes percentage in spleen were determined. RESULTS: Iron concentration in the treated tissue was significantly higher in wild-type inflammatory group (WT-I) when compared to both, the wild-type control group (WT-C) and ST2-/- inflammatory group (KO-I). There was no significant difference in iron concentration between ST2-/- control group (KO-C) and the KO-I. MCH had significantly decreased in WT-I when compared to WT-C, while there was no significant difference between KO-C and KO-I. Hemoglobin blood concentration significantly increased in KO-I in comparison to KO-C, while it did not significantly differ between WT-I and KO-I. Erythrocyte count and hematocrit had significantly increased, while the percentage of erythrocytes in spleen decreased in both inflammatory groups when compared to their controls. Neutrophil count significantly decreased in WT-I, when compared to WT-C. Lymphocyte count decreased in both inflammatory groups when compared to their controls. CONCLUSION: Results of this study indicate that the IL-33/ST2 axis could have a role in the alteration of iron in acute inflammation, namely in an increase of iron concentration at the site of acute inflammation and a decrease of blood mean corpuscular hemoglobin.

Association of Functional Variants of Phase I and II Genes with Chronic Obstructive Pulmonary Disease in a Serbian Population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by increased oxidative stress. Functional genetic variants of phase I and II genes are implicated in oxidants-antioxidants imbalance and may be involved in COPD development. In this study, we aimed to investigate the role of cytochrome P450 (CYP), glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) functional variants in the pathogenesis of COPD in a Serbian population. METHODS: The genotypes of 122 COPD patients and 100 controls with normal lung function were determined for CYP1A1 *1A/*2A, CYP2E1 *1A/*5B, GSTM1 null, GSTT1 null GSTP1 Ile105Val, mEH Tyr113His and mEH His139Arg gene variants. RESULTS: Results obtained showed that GSTM1 null variant was significantly more represented in COPD patients than in controls (61.5% vs. 47.0%; OR=1.80; p=0.042). Also, a significant difference was observed for combinations of GSTM1 null and GSTP1 105Val/(Val) (38.5% vs. 24.0%; OR=1.98; p=0.029), as well as for CYP1A1 *1A/*2A, GSTM1 null and mEH 113His/(His) genotypes (7.4% vs. 1.0%; OR=7.88; p=0.025). CONCLUSIONS: These are the first data concerning the analysis of the variants of phase I and II genes in the pathogenesis of COPD in a Serbian population. Results obtained in this study open up the possibility for thorough analyses of the role of genetic factors in COPD on larger cohorts. Also, they implicate the importance of previously described genetic associations with COPD in our population, as well as reveal a new one, not reported so far.

Polymorphisms of beta2-adrenergic receptor gene in serbian asthmatic adults: effects on response to Beta-agonists.

BACKGROUND AND OBJECTIVES: Polymorphisms of beta2-adrenergic receptor gene (ADRB2) are clinically relevant for several reasons, including as a risk factor for asthma development/severity and predicting the effectiveness of treatment with beta2-agonists in reducing asthma symptoms. The aim of this study was to examine the association between ADRB2 gene polymorphisms and asthma in the Serbian population, and to evaluate the therapeutic response in relation to the ADRB2 genotype. METHODS: The study included 171 patients with asthma and 101 healthy subjects as the control group. Genotyping of Arg16Gly and Gln27Glu polymorphisms was performed by direct sequencing of polymerase chain reaction (PCR) products. RESULTS: In Serbian adults, carriers of the 27Gln allele and 27Gln/Gln genotype were at higher risk of asthma [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.6-3.8, and OR 3.00, 95% CI 1.7-5.3, respectively], while the presence of the 27Glu allele and 27Gln/Glu genotype were found to be protective of asthma (OR 0.4, 95% CI 0.3-0.6, and OR 0.3, 95% CI 0.1-0.7, respectively). Furthermore, we found that the presence of the 27Gln allele in asthmatics younger than 50 years leads to a better response to therapy with long-acting beta2-agonists (LABA) in combination with prevailing low and moderate doses of inhaled corticosteroids (ICS), while carriers of the 27Glu allele over 50 years old are more likely to respond to LABA + ICS therapy. CONCLUSION: We identified that in Serbian adults the 27Gln allele and 27Gln homozygosity are risk factors for asthma, which may be of clinical interest in disease prevention. The finding that younger carriers of the 27Gln allele respond better to LABA + ICS therapy may be utilized in personalized asthma treatment.

The effects of caloric restriction against ethanol-induced oxidative and nitrosative cardiotoxicity and plasma lipids in rats.

Caloric restriction (CR) prevents or delays a wide range of aging-related diseases possibly through alleviation of oxidative stress. The aim of our study was to examine the effect of CR on oxidative and nitrosative cardiac damage in rats, induced by acute ethanol intoxication. Male Wistar rats were divided into following groups: control; calorie-restricted groups with intake of 60-70% (CR60-70) and 40-50% of daily energy needs (CR40-50); ethanol-treated group (E); calorie-restricted, ethanol-treated groups (CR60-70 + E, CR40-50 + E). Ethanol was administered in five doses of 2 g/kg every 12 h, while the duration of CR was five weeks before ethanol treatment. Malondialdehyde level was significantly lower in CR60-70 + E and significantly higher in CR40-50 + E vs. control. Nitrite and nitrate level was significantly higher in CR40-50 + E compared to control group. Activity of total superoxide dismutase (SOD) and its isoenzyme, copper/zinc-SOD (Cu/ZnSOD), was significantly higher in CR60-70 + E and lower in CR40-50 + E vs. control. Activity of manganese-SOD (MnSOD), that is also SOD isoenzyme, was significantly lower in CR40-50 + E compared to control group. Plasma content of sulfhydryl (SH) groups was significantly higher in CR60-70 group vs. control. Plasma concentration of total cholesterol, triacylglycerol, low-density lipoproteins and high-density lipoproteins was significantly lower in CR60-70 group compared to control values. Food restriction to 60-70% of daily energy needs has a protective effect on acute ethanol-induced oxidative and nitrosative cardiac damage, at least partly due to alleviation of ethanol-induced decrease in SOD activity, while restriction to 40-50% of energy needs aggravates lipid peroxidation and nitrosative stress.