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Effects of Dietary α-Linolenic Acid Treatment and the Efficiency of Its Conversion to Eicosapentaenoic and Docosahexaenoic Acids in Obesity and Related Diseases
Get PDFThe essential fatty acid alpha-linolenic acid (ALA) is present in high amounts in oils such as flaxseed, soy, hemp, rapeseed, chia, and perilla, while stearidonic acid is abundant in echium oil. ALA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by desaturases and elongases in humans. The conversion of ALA to EPA and DHA is limited, and these long-chain n−3 polyunsaturated fatty acids (PUFAs) are mainly provided from dietary sources (fish and seafood). This review provides an overview of studies that explored the effects of dietary supplementation with ALA in obesity and related diseases. The obesity-associated changes of desaturase and elongase activities are summarized, as they could influence the metabolic conversion of ALA. Generally, supplementation with ALA or ALA-rich oils leads to an increase in EPA levels and has no effect on DHA or omega-3 index. According to the literature data, stearidonic acid could enhance conversion of ALA to long-chain n−3 PUFA in obesity. Recent studies confirm that EPA and DHA intake should be considered as a primary dietary treatment strategy for improving the omega-3 index in obesity and related diseases
Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans – Evidence from untargeted mRNA and miRNA studies
No full textCardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives
Predictors of Vancomycin-Resistant Enterococcus spp. Intestinal Carriage among High-Risk Patients in University Hospitals in Serbia
Get PDFThe predictors of intestinal carriage of vancomycin-resistant Enterococcus spp. (VRE) among high-risk patients in the counties of the Southeast Europe Region are insufficiently investigated, yet they could be of key importance in infection control. The aim of the study was to identify risk factors associated with fecal VRE colonization among high-risk inpatients in university hospitals in Serbia. The study comprised 268 inpatients from three university hospitals. Data on patient demographics and clinical characteristics, length of hospital stay, therapy, and procedures were obtained from medical records. Chi-squared tests and univariate and multivariate logistic regressions were performed. Compared to the hemodialysis departments, stay in the geriatric departments, ICUs, and haemato-oncology departments increased the risk for VRE colonization 7.6, 5.4, and 5.5 times, respectively. Compared to inpatients who were hospitalized 48 h before stool sampling for VRE isolation, inpatients hospitalized 3–7, 8–15, and longer than 16 days before sampling had 5.0-, 4.7-, and 6.6-fold higher risk for VRE colonization, respectively. The use of cephalosporins and fluoroquinolones increased the risk for VRE colonization by 2.2 and 1.9 times, respectively. The age ≥ 65 years increased the risk for VRE colonization 2.3 times. In comparison to the University Clinical Centre of Serbia, the hospital stays at Zemun and Zvezdara University Medical Centres were identified as a protector factors. The obtained results could be valuable in predicting the fecal VRE colonization status at patient admission and consequent implementation of infection control measures targeting at-risk inpatients where VRE screening is not routinely performed
On the importance of hippocampal segmentation for the neural mapping of memory: Evidence from a large-scale study of neural architecture in healthy adults
Get PDFThe hippocampus (HC) is traditionally considered the key neuroanatomical hub responsible for memory. However, previous MRI studies that aimed to relate volumetric hippocampal measures to associative memory (AM) performance have yielded mixed results. In the current study, we aimed to reevaluate these findings in a large sample of young healthy participants (N = 246; age M = 24.95, SD = 4.58; 56% female). Participants were scanned with 3T MAGNETOM Prisma using a 64-channel head coil, followed by the AM assessment in the lab setting. To maximize the scope of AM assessment, we employed four paired-associate tasks of various stimuli modalities (faces, words, scenes) and outcome measure types (recognition, recall). Synthetic T1-weighted images were produced out of relaxometry parameter maps, after which volumetric measures were
calculated using FreeSurfer. The whole HC volume showed no correlation with any of the memory measures. However, further segmentation of HC into its functional and anatomical subfields (Parasubiculum, Presubiculum, Subiculum, CA1, CA2/3, CA4, GC-DG, HATA, Fimbria, Molecular layer, Hippocampal fissure, Hippocampal tail) showed scattered yet consistent patterns of significant correlations between different subfield volumes and memory outcomes. The results suggest that distinctive contributions of HC subfields may lead to a null effect when the whole HC volume is considered, thus demonstrating that drawing conclusions based on the volumetric measures of neural macrostructures can be misleading. The results highlight the importance of in-depth segmentation for neural mapping
P1474: Molecural mechanism of chemotherapeutic hydroxyurea is mediated by NOS2
Get PDFBackground:: Hydroxyurea (HU) is a chemotherapeutic agent that reduces ribonucleotide reductase, stops DNA synthesis and repar, and therefore causes cell proliferation inhibition and apoptosis. Due to its cytostatic properties, HU is frequently used for treatment of myeloproliferative neoplasms, ovarian cancer, and sickle cell anemia. Nitric oxide (NO), produced by nitric oxide synthase (NOS) enzymes is a potent signaling molecule involved in blood flow regulation, neutrotransmission, and immunity. Although HU treatment increases NO levels, up to date it is not clear whether it originates from activation of NOS enzymes or HU degradation.
Aims: The aim of this study was to determine the involvement of NOS2 enzyme in the cytostatic effect of HU.
Methods: To examine the involvement of the NOS2 enzyme in the molecular mechanism of HU, we treated erythroleukemic HEL92.7.1 cells with pan-selective NOS inhibitor L-NAME (200µM, 1mM, and 5mM), NOS2 specific inhibitor 1400W (1, 10, and 100µM), or NOS2/NOS3 inhibitor DPI (1, 5, and 10µM), in combination with hydroxyurea (200µM), and monitored their effect on proliferation and cell cycle. Immunocytochemistry for the proliferation marker Ki67 was performed to assess proliferation, while cell distribution in cell cycle phases was determined by flow cytometry after propidium iodide staining. Colony forming assay have been performed with the bone marrow cells of Nos2 null mice after oral HU treatment to corroborate the data obtained by enzymatic inhibition.
Results: In this study, we demonstrated that treatment of HEL92.7.1 cells with HU induces a dose-dependent increase in NOS2 protein levels and two products of the enzyme NOS - NO and citrulline. HU-induced citrulline levels can be reduced by treatment with the NOS inhibitor L-NAME, indicating that NO is produced de novo by the NOS enzyme rather than HU degradation. Inhibition of the NOS2 enzyme by L-NAME, 1400W, or DPI was sufficient to abolish HU-mediated inhibition of proliferation. While HU increased the number of cells in S-phase of the cycle at the expanse of the G0/G1 due to blocked DNA synthesis, combined treatment with HU and L-NAME or DPI inhibitor resulted in decreased G0/G1 phase and increased S and G2/M phases pointing to increased proliferation. These data indicate that the cytostatic properties of HU are mediated by the NOS2 enzyme. A colony formation assay showed that Nos2 deficient bone marrow cells isolated from mice treated orally with HU (200mg/kg) formed significantly more erythroid colonies (BFU-E and CFU-E) and granulocyte/macrophage progenitors (CFU-GM) compared to HU treated wild-type and untreated Nos2 null mice showing the involvement of Nos2 in the molecular mechanism of HU in vivo.
Summary/Conclusion: Our results show that HU induces the enzymatic activity of the NOS2 protein which in turn is involved in the HU regulation of proliferation and cell cycle. Comprehensive knowledge of the molecular mechanism of HU might help to improve its beneficial properties and decrease adverse effects
Effects of NADPH oxidase blockade and hyperbaric oxygen preconditioning on 4-HNE, NGAL, and HO-1 tissue expression in postischemic acute kidney injury induced in spontaneously hypertensive rat
Get PDFKidney disease represents a serious global health problem. Free radicals and prooxidants produced during ischemic acute kidney injury (AKI) may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. The aims of our study were to examine the importance of NADPH oxidase blockade and to determine the effect of hyperbaric oxygen preconditioning on the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. NADPH oxidase blockade was performed by Apocynin (40 mg/kg body weigh)t, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning,with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, NADPH oxidase blockade and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition
Three Episodes of COVID-19 in a Nursing Home in Belgrade, Serbia
Get PDFBackground: Over the two years of the COVID-19 pandemic, the elderly in nursing
homes (NH) have been hit particularly hard.
Methods: We conducted a retrospective study of 3 episodes of COVID-19 in one NH in
suburban Belgrade, Serbia, at the time of pre-alpha (Nov 2020), delta (Nov 2021) and
omicron (Jan 2022) variants of SARS-CoV-2. All staff and 95% of residents were vaccinated
in the early spring of 2021, with BBIBP-CorV, Gam-COVID-Vac and BNT162b2
vaccines. COVID-19 was diagnosed by positive PCR and/or antigen test. Specific IgG
antibodies against SARS-CoV-2 S glycoprotein RBD were assessed by ELISA.
Results: The 3 episodes involved a total of 188 infections. The first involved 65/126
(51.9%) residents and 44/64 (68.7%) staff, the second 22/75 (29.3%) residents and 3/40
(7.5%) staff, and the third 36/110 (32.7%) residents and 18/56 (32.1%) staff. Clinical presentation
ranged from asymptomatic to severe, with severe cases being referred to
hospital ICUs. Mortality per episode was 19.8%, 2.7% and 0%, respectively, and involved
residents only. After the first episode, all 36 examined residents and 43 of the
44 staff had specific antibodies. Interestingly, higher levels (20.45±13.27) were detected
in the residents than in the staff (9.74±9.52) (p<0.001) despite a double difference
in age (79.6±7.48 vs. 40.8±11.43) (p<0.001). Episodes 2 and 3 involved 4 (1 resident, 3
staff) and 22 (13 residents, 9 staff) breakthrough infections.
Conclusions: Elderly individuals mounted a good immunological response to the
vaccines, which prevented significant mortality in the next episodes, despite a significant
number of omicron-induced breakthrough infections
Differences in mouse strains determine the outcome of Der p 2 allergy induction protocols
No full textIn vivo animal models can provide worthy information on various aspects of asthma mechanism and pathogenesis. The genetic predisposition and phenotype of mice may affect the immune response itself. Here we compare the early immune response to Der p 2 or HDM allergen extract upon injection and inhalation in BALB/c and C57BL/6 mice. Female C57BL/6 and BALB/c mice were immunized with Der p 2 allergen subcutaneously followed by inhalation of Der p 2 or HDM extract. After challenge, the mice were euthanized; blood, bronchoalveolar lavage (BAL), spleens and lungs were collected. Cells from BAL were identified by May-Grünwald Giemsa staining and lung leukocyte populations were analyzed by flow cytometry. Serum antibody levels of Der p 2 specific IgE, IgG, IgG1 and IgG2a were assessed by ELISA, and cytokine secretion (IL-4, IFN-γ and IL-10) was evaluated upon stimulation with Der p 2 or HDM extract. The Th2 immune response was confirmed by elevated allergen-specific immunoglobulin E (IgE) and the allergic reaction was evidenced by infiltration of eosinophils and/or neutrophils into BAL. We found that BALB/c mice were inefficient in integrating local with systemic immune response, evidenced by almost no IgG or IgE production upon one subcutaneous injection and subsequent inhalation of Der p 2 allergen; also, the bronchoalveolar lavage infiltrate in these mice consisted of neutrophil infiltration, unlike C57BL/6 mice in which eosinophilic infiltrate predominated. The differences between BALB/c and C57BL/6 mice strains could be exploited for generating different types of responses to the Der p 2 allergen
Blinding in tDCS Studies: Correct End-of-Study Guess Does Not Moderate the Effects on Associative and Working Memory
Get PDFTranscranial 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
Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia
Get PDFChronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the pro-liferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dis-mutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML. In addition, nitrogen species (nitrotyrosine, iNOS, eNOS) and inflammation markers (IL-6, NFkB, and S100 protein) were increased in granulocytes of CML while anti-inflammatory levels of IL-10 were decreased in plasma. CML granulocytes exhibited greater resistance to cytotoxic H2O2 activity compared to healthy subjects. Moreover, phosphorylation of the apoptotic p53 protein was reduced while the activity of the AKT/mTOR signaling pathway was increased, which was further enhanced by oxidative stress (H2O2) in granulocytes and erythroleukemic K562 cells. IL-6 caused oxidative stress and DNA damage that was mitigated using antioxidant or inhibition of inflammatory NFkB transcription factor in K562 cells. We demonstrated the presence of oxidative and ni-trosative stress in CML, with the former mediated by AKT/mTOR signaling and stimulated by in-flammation