1,720,971 research outputs found
Expression pattern of miR-193a, miR122, miR155, miR-15a, and miR146a in peripheral blood mononuclear cells of children with obesity and their relation to some metabolic and inflammatory biomarkers
No full textBackgroundThe widespread presence of childhood obesity has increased considerably over three decades. The present study was designed to investigate expression patterns of miR-146a, miR-155, miR-15a, miR-193a, and miR-122 in peripheral blood mononuclear cells (PBMCs) in children who are obese along with their association with metabolic and inflammatory biomarkers.MethodsNinety test subjects were admitted. The profile of blood pressure, resting energy expenditure (REE), anthropometric measures, body composition, dietary intakes, physical activity levels, insulin, and lipid profile, fasting blood glucose (FBG), high-sensitivity C-reactive protein (hs-CRP), and pubertal stage have been measured. Total RNA (including small RNAs) was extracted from PBMCs. The expression levels of miRNAs were measured by stem-loop RT-qPCR.ResultsThe miR-155a expression level was significantly lower in obese children, children with high hs-CRP, and children with high-fat mass. Obese girls had significantly higher PBMC levels of miR-122. MiR-155a had a significant negative association with fasting insulin, HOMA-IR, and hs-CRP. There were significant positive associations between miR-193a and miR-122 expression levels and fasting insulin, HOMA-IR, and TG. MiR-15a was positively correlated with fasting insulin and HOMA-IR. Children with metabolic syndrome, insulin resistance, and high-fat mass had higher PBMC levels of miR-122 and miR-193a. Higher miR-193a and miR-122 levels were also detected in PBMCs of children with fast REE, compared to those with slow REE, and the subjects with high hs-CRP, respectively.Conclusionlower level of miR-155 expression in obese subjects and significant associations unfolds the need for more studies to detect the possible underlying mechanisms
Interplay between fatty acid desaturase2 (FADS2) rs174583 genetic variant and dietary antioxidant capacity: cardio-metabolic risk factors in obese individuals
No full textOBJECTIVE: Polymorphisms of the fatty acid desaturase (FADS) gene cluster have been associated with obesity and its-related consequences. This cross-sectional study aimed to investigate whether the adherence to dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, modifies the association of FADS2 rs174583 polymorphism with cardio-metabolic risk factors in obese adults. METHODS: The present study included 347 healthy obese adults (aged 20–50 years). Dietary NEAC was assessed by a validated food frequency questionnaire with 147 items and estimated through total radical-trapping antioxidant parameters (TRAP), oxygen radical absorbance capacity (ORAC), and ferric reducing ability of plasma (FRAP) with the use of published databases. FADS2 rs174583 polymorphism was characterized using PCR–RFLP. ANCOVA multivariate interaction model was used to analyze gene-diet interactions. RESULTS: after adjustment for the confounding variables (age, physical activity, SES and WC), this study showed significant interactions between rs174583 polymorphism and adherence to dietary ORAC on the serum cholesterol (P (Interaction) = 0.029), LDL-C (P (Interaction) = 0.025) and HDL-C levels (P (Interaction) = 0.049) among the male group; minor allele carriers who had the highest adherence to the NEAC (ORAC) showed a better metabolic profile (lower TG and LDL-C and higher HDL-C) (P < 0.05). Among women, the dietary ORAC-rs174583 interactions were statistically significant for the serum insulin concentration (P (Interaction) = 0.020), QUICKI (P (Interaction) = 0.023) and HOMA-IR (P (Interaction) = 0.017); the highest QUICKI and the lowest HOMA-IR and serum insulin levels were observed in the CC homozygote carriers with the moderate compliance with the dietary ORAC (P < 0.05). In addition, the dietary TRAP modified the association between FADS2 variant and change in LDL-C levels (P (Interaction) = 0.037); the homozygous wild-type (CC) women who placed in the top tertile of TRAP had significantly the lowest LDL-C levels than those in the second tertile (P < 0.05). CONCLUSION: These data indicate that the FADS2 rs174583 polymorphism interacts with the dietary NEAC to influence cardio-metabolic risk factors in obese subjects. Replication in prospective cohort studies among other populations is required to confirm the results of our study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-022-01075-7
Immunomodulation of the Breast Cancer Microenvironment by Tumor-Derived Exosomes: Implications for Immunotherapy
No full textExosomes are 30-150 nm extracellular vesicles released by nearly all cells, including tumor cells. Cancer cell-derived exosomes carry various molecular contents - proteins, mRNAs, microRNAs- that are transferred to recipient cells, contributing to cancer development, angiogenesis, metastasis, and immune evasion. Breast cancer-derived exosomes (BEXs) express multiple immunomodulatory molecules, particularly the ectoenzymes CD39 and CD73, which catalyze the conversion of adenosine triphosphate (ATP) into adenosine. Adenosine then binds its receptors (ADORs) to transmit immunosuppressive signals. BEXs also express immune checkpoint molecules such as programmed death ligand 1 (PD-L1), CD200, and CD47 that suppress immune surveillance through interaction with programmed cell death protein 1 (PD-1), CD200R, and signal-regulatory protein alpha (SIRP alpha), respectively. Notably, PD-L1 appears to be more enriched on exosomes than on tumor cell surfaces, underscoring the pivotal role of BEXs in immune regulation. Given their influence on several hallmarks of cancer, BEXs are promising candidates for future diagnostic and therapeutic strategies, particularly in immunotherapy.Funding
This work was supported by the Immunology Research Center, and Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran.
S. M., C. A., and F. S. contributed to the literature search; S. M. contributed to data collection, designed and drew the figures and manuscript writing; T. K. designed this manuscript; H. K., N. Sh., M. J., E. S., and T. K. edited this manuscript
Small extracellular vesicles: connecting early life exposure outcomes to air pollution during pregnancy to early childhood health
No full textExposure to air pollution poses a serious threat to maternal and child health, particularly during critical developmental periods. Extracellular vesicles (EVs), as key mediators of intercellular communication, have emerged as a novel mechanism through which environmental exposures, including air pollutants, exert systemic effects. This review synthesizes current evidence on the role of small EVs (sEVs) in mediating the biological impacts of prenatal air pollution exposure, with a focus on their molecular profile, including the presence of signaling molecules like miRNAs and proteins, and their implications for childhood health outcomes. In this review, we explore mechanisms involving sEVs in transplacental exposure, signaling and epigenetic modifications, linking exposure to adverse developmental and health effects in early life. Furthermore, we highlight the potential of sEVs as biomarkers for exposure assessment and predictors of adverse health outcomes. Relevant studies were identified through a comprehensive literature search and systematic review of experimental and epidemiological evidence. By integrating insights from toxicology, epidemiology, and molecular biology, we identify specific needs for further research into sEVs, both as mechanistic mediators and diagnostic tools for air pollution-related health risks.The authors express their gratitude to Hasselt University and Maastricht University for providing access to the required databases to extract articles and data necessary for this research
Fabrication and characterization smart gold-polymer nanostructure as promising theranostic agent for dual-imaging and chemo-photothermal therapy of cancer: An in vitro study
No full textIn order to enhance the effectiveness of cancer therapy, it is essential to have highly sensitive imaging techniques that provide accurate results and the selection of appropriate therapeutic strategies. Despite recent advances in technologies associated with tumor imaging, the application of conventional single -mode imaging is the subject of debate. Herein, we strategically engineered a nanostructure (GNSs-MTX@CD-Pol) designed from a pHresponsive polymer (Pol), gold nanostar (GNSs), carbon dot (CD), and methotrexate (MTX) as a theranostic agent for simultaneously fluorescent (FI) and X-ray computed tomography (CT) imaging and combination Chemo-Photothermal Therapy in response to near -infrared (NIR) laser irradiation. GNSs-MTX@CD-Pol NPs possess excellent photothermal conversion efficiency and dual FI/CT imaging properties, which are attributed to the strong NIR absorption and high atomic number of gold elements. Moreover, it is demonstrated that GNSsMTX@CD-Pol NPs are effectively responding to tumor acidity. With the PTT, the growth of cancer cells can be remarkably ablated in vitro. The results of the cell cycle, apoptosis, real -time PCR, and western blotting test on MDA-MB-231 cells revealed antitumor effect of GNSs-MTX@CD-Pol NPs caused by combination ChemoPhotothermal Therapy. Based on their high stability and excellent biocompatibility, GNSs-MTX@CD-Pol NPs have great potential for the treatment of various types of tumors.Funding
This study was financially supported by grant no. 59950 from Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
Evaluation of diagnostic methods for the detection of Bovine Coronavirus and Rotavirus in faeces of diarrhoeic calves
No full textThe purpose of the present study was to evaluate the efficacy of Enzyme-Linked Immunosorbent Assay (ELISA), immunochromatographic (ICG), and reverse transcription-polymerase chain reaction (RT-PCR) methods for the detection of rotavirus (RV) and bovine coronavirus (BCV). Faeces samples were collected from 90 diarrhoeic calves (male and female) up to one month of age and the immune response against RV and BCV infection was as-sessed by using AgELISA, ICG, and RT-PCR. To determine the performance and accuracy of each diagnostic method in comparison to the diagnostic gold standard (RT-PCR) method, different statistical tests including receiver operating characteristic curve (ROC) and concordance correlation were used. Results revealed the prevalence of RV and BCV and RV+BCV according to RT-PCR were equal to 8.89 (95% CI: 6.64-10.07), 14.44 (95% CI: 11.23-6.90), and 2.22 (95% CI: 0.89-3.72), respectively. The best agreement and the highest sensitivity and specificity were obtained be-tween the RT-PCR and AgELISA (100% and 94.3%), and also the ICG test (95% and 94.3%) was less accurate method in comparison to ELISA method for identifying RV and BCV, but a good correlation and concordance between ICG diagnostic techniques and RT-PCR were observed. To put it in a nutshell, our results demonstrate that the AgELISA is the most accurate technique in comparison to RT-PCR, however the ICG assay can help improve the speed of diagnosis RV and BCV infections in dairy field. New scientific strategies for promoting accuracy and transparency of ICG-based technique in early diagnosis of the cause of calf diarrhoea should be used. Altogether, we suggest that positive ICG samples should be tested by AgELISA or RT-PCR techniques to avoid false results in farm animals
Docosahexaenoic acid (DHA) impairs hypoxia-induced cellular and exosomal overexpression of immune-checkpoints and immunomodulatory molecules in different subtypes of breast cancer cells
No full textBackground: Tumor cells express immune-checkpoint molecules to suppress anti-tumor immune responses. In part, immune evasion takes place by secreting exosomes bearing immune-checkpoint and immunomodulatory molecules and their inducing and/or regulating agents e.g., microRNAs (miRs). This study aimed to evaluate the effects of omega-3 fatty acid, docosahexaenoic acid (DHA), on the expression of some selected immune-checkpoint and immunomodulatory molecules and their regulating miRs under both normoxic and hypoxic conditions in triple negative (TNBC) invasive and triple positive non-invasive breast cancer cell lines. Methods: MDA-MB-231 and BT-474 cells were treated with 100 µM DHA under hypoxic and normoxic conditions for 24 h. Exosomes were isolated by ultracentrifuge and confirmed by electron microscope and anti-CD9, -CD63, -CD81 immunoblotting. Total RNA from cells and exosomes were extracted and expression of CD39, CD73, CD47, CD80, PD-L1, B7-H3, B7-H4 genes and their related miRs were evaluated by quantitative Real-time PCR. Results: This study showed significant over-expression of immune-checkpoint and immunomodulatory molecules under hypoxic condition. Treatment with DHA resulted in a significant decrease in immune-checkpoint and immunomodulatory molecule expression as well as an upregulation of their regulatory miRNA expression. Conclusion: DHA supplementation may be utilized in breast cancer therapy for down-regulation of cellular and exosomal immune escape-related molecules
Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from relapsing-remitting multiple sclerosis patients
No full textEpstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-?), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-a) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-ß: TNF-a and TGF-ß: IFN-? attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS
DNA damage repair response in mesenchymal stromal cells: From cellular senescence and aging to apoptosis and differentiation ability
No full textMesenchymal stromal cells (MSCs) are heterogeneous and contain several populations, including stem cells. MSCs' secretome has the ability to induce proliferation, differentiation, chemo-attraction, anti-apoptosis, and immunomodulation activities in stem cells. Moreover, these cells recognize tissue damage caused by drugs, radiation (e.g., Ultraviolet, infra-red) and oxidative stress, and respond in two ways: either MSCs differentiate into particular cell lineages to preserve tissue homeostasis, or they release a regenerative secretome to activate tissue repairing mechanisms. The maintenance of MSCs in quiescence can increase the incidence and accumulation of various forms of genomic modifications, particularly upon environmental insults. Thus, dysregulated DNA repair pathways can predispose MSCs to senescence or apoptosis, reducing their stemness and self-renewal properties. For instance, DNA damage can impair telomere replication, activating DNA damage checkpoints to maintain MSC function. In this review, we aim to summarize the role of DNA damage and associated repair responses in MSC senescence, differentiation and programmed cell death.There were no funding resources for the current study.Kahroba, H; Sadeghi, MR (corresponding author), Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Mol Med, Tabriz, Iran.
[email protected]; [email protected]
The integrative panel of fatty acid desaturase-2 (FADS2) rs174583 gene polymorphism and dietary indices (DQI-I and HEI) affects cardiovascular risk factors among obese individuals
No full textBackgroundRecent studies have shown that dietary intakes and gene variants have a critical role in the obesity related comorbidities. This study aimed to evaluate the effects of the interactions between Fatty acid desaturase 2 (FADS2) gene rs174583 polymorphism and two dietary indices on cardiometabolic risk factors.MethodsThis cross-sectional study was carried out on 347 obese adults aged 20-50 years old in Tabriz, Iran. Healthy eating index (HEI) and Diet quality index-international (DQI-I) were evaluated by a validated semi-quantitative 147-item Food frequency questionnaire (FFQ). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine FADS2 gene variants. Multivariate analysis of covariance (MANCOVA) was used to identify gene-diet interactions on metabolic parameters.ResultsWaist circumference (WC) and serum triglyceride (TG) levels were significantly higher among carriers of TT genotype of FADS2 gene (P < 0.05). In addition, the interactions between FADS2 gene rs174583 polymorphism and DQI-I had significant effects on weight (P (interaction) = 0.01), fat mass (P (interaction) = 0.04), fat free mass (P (interaction) = 0.03), and Body mass index (BMI) (P (interaction) = 0.02); the highest level of these parameters belonged to TT carriers. Similarly, the interactions between FADS2 gene variants and HEI had significant effects on insulin (P (interaction) < 0.001), Homeostasis model assessment of insulin resistance (HOMA-IR) (P (interaction) < 0.001), Quantitative insulin check index (QUICKI) (P (interaction) = 0.001), and alpha Melanocyte stimulating hormone (alpha-MSH) (P (interaction) = 0.03).ConclusionIn this study, for the first time, we reported the effects of gene-diet interactions on metabolic traits. Compliance with dietary indices (DQI-I and HEI) ameliorated the adverse effects of gene variants on metabolic risk factors, especially in heterogeneous genotypes. Further prospective cohort studies are needed to confirm these results
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