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Correlation between leukocyte-platelet aggregates and thrombosis in myeloproliferative neoplasms
No full textIntroduction: The impact of activated blood and endothelial cells on the thrombosis in myeloproliferative neoplasms (MPN) has not yet been clarified. We prospectively analyzed correlation between circulating leukocyte-platelet aggregates and soluble selectins to thrombosis occurrence in MPN, in the context of standard and cardiovascular risk factors, and different clinical and biological characteristics. Methods: Flow cytometric analysis of neutrophil-platelet (Neu-Plt) and monocyte-platelet (Mo-Plt) aggregates in peripheral blood, as well as quantification of soluble E-/L-/P-selectins by enzyme immunoassay, was performed on 95 newly diagnosed MPN patients. Results: During the follow-up, thrombosis occurred in 12.6% MPN patients (arterial 9.4%, venous 3.2%), with a mean time of 39 months. The overall incidence rate of main thrombotic events was 4.36 per 100 patient-years. The incidence of arterial hypertension (HTA) was significantly higher in patients with thrombosis, compared to those without thrombosis (P <.05). The level of soluble P-selectin was significantly higher in patients with thrombosis compared to those without thrombosis (346.89 ng/mL vs 286.39 ng/mL, P =.034). The mean level of Neu-Plt (26.7% vs 22.4%) and Mo-Plt (17.8% vs 12.3%) aggregates did not differ significantly between the groups with and without thrombosis. A multivariate COX proportional hazard regression model confirmed an independent predictive significance of Mo-Plt aggregates (HR = 1.561, 95% CI: 1.007-2.420, P =.046), as well as the cumulative effect of Mo-Plt aggregates and HTA (HR = 1.975, 95%CI: 1.215-3.212, P =.006) for thrombosis occurrence. Conclusion: Monocyte-platelet aggregates represent an independent risk factor for thrombosis occurrence, further on supported by HTA
West Nile virus in the Republic of Serbia—Diagnostic performance of five serological tests in dog and horse sera
Get PDFWest Nile virus (WNV) is a zoonotic mosquito-borne virus classified as family Flaviviridae and genus Flavivirus. The first WNV outbreak in humans in the Republic of Serbia was recorded in 2012. Equids and dogs can show clinical symptoms after WNV infection and are often used as sentinels. This study aimed to (i) give insight into seropositivity for WNV in clinically healthy dog and horse sera in different regions of Serbia and (ii) compare diagnostic value of ‘in-house’ and commercially available indirect immunofluorescence (IFA) and enzyme-linked immunoassay (ELISA) tests to ‘gold standard’ virus neutralization test (VNT). Due to cross-reactivity, sera were tested for Usutu virus and tick-borne encephalitis virus in VNT based on the epidemiological data of field presence. Blood sera of dogs (n = 184) and horses (n = 232) were collected from 2011 to 2013. The seropositivity was confirmed by VNT in 36.9 % tested dog sera and 34.9% tested horse sera with highest positivity in regions near two big rivers, while in four dog and seven horse sera, positivity resulted from Usutu virus infection. Comparative results of diagnostic tests in dogs ranged from 18.7 % seropositivity by ‘in-house’ ELISA to 31.9% by commercially available ELISA. In horses, seropositivity ranged from 36.2% by ‘in-house’ IFA to 32.5% by commercially available IFA and from 26.3% by ‘in-house’ IgG ELISA to 20.9% by commercially available ELISA. There were no statistically significant differences according to the McNemar test between ‘in-house’ and commercially available IFA and ELISA test in horse sera, while the same was not true for two ELISAs used in dog sera (χ2 = 8.647, p = .003). Established seropositivity in dogs and horses was in accordance with the epidemiological situation and WNV spread in the Republic of Serbia and proven Usutu virus co-circulation. ‘In-house’ tests remain a valuable tool in early diagnostics of WNV
Vitamin D3 Stimulates Proliferation Capacity, Expression of Pluripotency Markers, and Osteogenesis of Human Bone Marrow Mesenchymal Stromal/Stem Cells, Partly through SIRT1 Signaling
Get PDFThe biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine—mainly in combination with various biomaterial matrices—has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs’ features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation
A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus
Get PDFType 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted. Methods: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2−), superoxide anion radical (O2−), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed. Results: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2−, O2−) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group. Conclusions: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients
Personalized Frequency Modulated Transcranial Electrical Stimulation for Associative Memory Enhancement
Get PDFAssociative memory (AM) is the ability to remember the relationship between previously unrelated items. AM is significantly affected by normal aging and neurodegenerative conditions, thus there is a growing interest in applying non-invasive brain stimulation (NIBS) techniques for AM enhancement. A growing body of studies identifies posterior parietal cortex (PPC) as the most promising cortical target for both transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) to modulate a cortico-hippocampal network that underlines AM. In that sense, theta frequency oscillatory tES protocols, targeted towards the hallmark oscillatory activity within the cortico-hippocampal network, are increasingly coming to prominence. To increase precision and effectiveness, the need for EEG guided individualization of the tES protocols is proposed. Here, we present the study protocol in which two types of personalized oscillatory tES–transcranial alternating current stimulation (tACS) and oscillatory transcranial direct current stimulation (otDCS), both frequency-modulated to the individual theta-band frequency (ITF), are compared to the non-oscillatory transcranial direct current stimulation (tDCS) and to the sham stimulation. The study has cross-over design with four tES conditions (tACS, otDCS, tDCS, sham), and the comprehensive set of neurophysiological (resting state EEG and AM-evoked EEG) and behavioral outcomes, including AM tasks (short-term associative memory, face–word, face–object, object-location), as well as measures of other cognitive functions (cognitive control, verbal fluency, and working memory)
Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart
Get PDFIncreased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health
A systematic review of meta-research studies finds substantial methodological heterogeneity in citation analyses to monitor evidence-based research
Get PDFObjectives: This systematic review aimed to identify the characteristics and application of citation analyses in evaluating the justification, design, and placement of the research results of clinical health studies in the context of earlier similar studies. Study Design and Setting: We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Methodology Register for meta-research studies. We included meta-research studies assessing whether researchers used earlier similar studies and/or systematic reviews of such studies to inform the justification or design of a new study, whether researchers used systematic reviews to inform the interpretation of new results, and meta-research studies assessing whether redundant studies were published within a specific area. The results are presented as a narrative synthesis. Results: A total of 27 studies were included. How authors of citation analyses define their outcomes appears rather arbitrary, as does how the reference of a landmark review or adherence to reporting guidelines was expected to contribute to the initiation, justification, design, or contextualization of relevant clinical trials. Conclusion: Continued and improved efforts to promote evidence-based research are needed, including clearly defined and justified outcomes in meta-research studies to monitor the implementation of an evidence-based approach
Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women
Get PDFGrapefruit is a rich source of flavanones, phytochemicals suggested excreting
vasculoprotective effects. We previously showed that flavanones in grapefruit juice
(GFJ) reduced postmenopausal women’s pulse-wave velocity (PWV), a measure of
arterial stiffness. However, mechanisms of flavanone action in humans are largely
unknown. This study aimed to decipher molecular mechanisms of flavanones by
multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free
control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified
using microarrays. Bioinformatics analyses assessed their functions, interactions and
correlations with previously observed changes in PWV. GFJ modified gene and
miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes
suggests regulation of inflammation, immune response, cell interaction and mobility.
Bioinformatics identified putative mediators of the observed nutrigenomic effect
(STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone
metabolites to transcription factors and cell-signaling proteins. We also observed 34
significant correlations between changes in gene expression and PWV. Moreover, global
gene expression was negatively correlated with gene expression profiles in arterial
stiffness and hypertension. This study revealed molecular mechanisms underlying
vasculoprotective effects of flavanones, including interactions with transcription factors
and gene and miRNA expression changes that inversely correlate with gene expression
profiles associated with cardiovascular risk factors
Effects of apocynin treatment and HBO preconditioning on immunohistochemical 4-HNE, HIF alpha, HIF2 alpha and NGAL tissue expression in postiscemic acute kidney injury in SHR rats
Get PDFObjective:
Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). 4-hydroxynonenal (4-HNE) is a product of lipid peroxidation and may serve as non-invasive biomarker of oxidative stress while neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of AKI. Hypoxia-inducible factors (HIFs) are the “master’’ transcription factors responsible for gene expression in hypoxia, which play an important role in kidney injury and repair by regulating HIF target genes, including microRNAs.
Design and method:
The study was conducted on male SHR rats, randomly divided into following groups: sham-operated group (SHAM) AKI control group, AKI group with apocynin treatment (AKI+APO), group with HBO preconditioning before AKI induction (AKI+HBO) and group with HBO preconditioning before and apocynin treatment after AKI induction (AKI+APO+HBO). HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24 h before AKI induction. Apocynin, NADPH oxidase inhibitor was injected 5 minutes before reperfusion.
Results:
AKI induction significantly decreased creatinine (CCr), urea (CU) and phosphate (CPhos) clearances when compared to SHAM group. Remarkable increase in CCr, CU, CPhos levels were observed in all treated groups (AKI+APO, AKI+HBO, AKI+APO+HBO) in comparison to AKI group. Sham – operated rats did not express 4-HNE and NGAL in any parenchymal structure. AKI induced abundant and strong glomerular expression of 4-HNE along with expression in interstitial compartment. All treatments (AKI+APO, AKI+HBO, AKI+APO+HBO) significantly decreased 4-HNE expression both in glomeruli and interstitium. Also, AKI stimulated widespread NGAL expression in renal epithelial tubular cells with fine granular appearance on the apical surface of the cells, affecting entire circumference of tubular cross-sectioning, which was decreased in all treated groups. In SHAM group, the expression of HIF1 alpha and HIF2 alpha was focal with weak intensity in glomeruli and interstitium. In AKI group, the expression was diffuse and strong, with remarkable improvement in all treated groups.
Conclusions:
Considering our results, we can conclude that apocynin treatment, as well as HBO preconditioning may have protective effects in postischemic acute kidney injury induced in spontaneously hypertensive rats
Efficacy of a Lipid-Lowering Diet on Key Fatty Acid Ratios and Omega-3 Index in Hyperlipidemic Subjects
Get PDFPolyunsaturated fatty acid (PUFA) dietary intake, status and serum key fatty acid
(FA) ratios may aid in cardiovascular disease-related risk assessment. The aim of this study was to investigate
the effects of lipid-lowering diet on key FA ratios in serum phospholipids and omega-3 index in
erythrocyte phospholipids in moderately hyperlipidemic subjects. The study included 41 subjects, mean
age 56±6 years. Nutritional habits were evaluated by food frequency questionnaire. Participants followed
lipid lowering diet for 12 weeks. Energy intake of omega-6 and omega-3 FA was changed from 7.6%
and 0.6% to 5.7% and 1.2%, respectively. Marked decrease in four FA ratios in serum phospholipids,
i.e., omega-6/omega-3, arachidonic acid (AA)/eicosapentaenoic acid (EPA), AA/docosahexaenoic acid
(DHA), AA/(EPA+DHA) and omega-3 index (EPA+DHA) was found in study subjects after lipid-
lowering diet. Total cholesterol/high-density lipoprotein (HDL), low-density lipoprotein (LDL)/
HDL and triacylglycerol/HDL-cholesterol ratios positively correlated with all FA ratios, and negatively
correlated with total omega-3 levels in serum phospholipids and omega-3 index in erythrocytes. Total
serum omega-3 levels showed strongest association with lipoprotein ratios and positive correlation with
homeostatic model assessment (HOMA) index. In conclusion, lipid-lowering diet resulted in decreased
serum key FA ratios, increased omega-3 levels, and improved insulin sensitivity that may lead to a lower
risk of cardiovascular disease in subjects with moderate hyperlipidemia