Expression Levels Of miR-155 Research Articles

Transcriptomic profiles-based approach to decode the role of miR-122 in triple negative breast cancer.

miR-122 has been considered both as tumor suppressor miRNA and oncomiR in breast tumor phenotypes. However, the role of miR-122 in triple-negative breast cancer (TNBC) is still unknown. In this study, the clinical value of miR-122 was used to describe the transcriptomic landscape of TNBC tumors obtained from The Cancer Genome Atlas database. Low expression levels of miR-122 were associated with poor overall survival (OS) of TNBC patients than those with higher expression levels of miR-122. We identified gene expression profiles in TNBC tumors expressed lower or higher miR-122. Gene coexpression networks analysis revealed gene modules and hub genes specific to TNBC tumors with low or high miR-122 levels. Gene ontology and KEGG pathways analysis revealed that gene modules in TNBC with gain of miR-122 were related to cell cycle and DNA repair, while in TNBC with loss of miR-122 were enriched in cell cycle, proliferation, apoptosis and activation of cell migration and invasion. The expression of hub genes distinguished TNBC tumors with gain or loss of miR-122 from normal breast tissues. Furthermore, high levels of hub genes were associated with better OS in TNBC patients. Interestingly, the gene coexpression network related to loss of miR-122 were enriched with target genes of miR-122, but this did not observed in those with gain of miR-122. Target genes of miR-122 are oncogenes mainly associated with cell differentiation-related processes. Finally, 75 genes were identified exclusively associated to loss of miR-122, which are also implicated in cell differentiation. In conclusion, miR-122 could act as tumor suppressor by controlling oncogenes in TNBC.

Cardiac angiogenesis enhances by activating Mir-126 and related target proteins in type 2 diabetic rats: Rescue combination effect of Sodium butyrate and voluntary exercise therapy.

type 2 diabetes, metabolic disorder, is one of the main risk factors for cardiovascular disease, leading to angiogenesis injury. The present study wanted to discover the effect of sodium butyrate (NaB) and voluntary exercise, alone or together, on miR-126 and related proteins in rats with type 2 diabetes. thirty-five male Wistar rats (200-250g) were randomly divided into five groups: control, diabetes, diabetes-NaB, diabetes-exercise, and diabetes-NaB-exercise. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (35mg/kg) and high-fat diet. The rats were then administrated NaB (200mg/kg. ip) or were subjected to voluntary exercise, or combined NaB and voluntary exercise for 8weeks. MiR-126 expression in the cardiac tissue was determined by real-time PCR, and the SPRED-1 and RAF proteins expression levels were measured by western blot. NaB and voluntary exercise up-regulated cardiac miR-126 and RAF expression levels and down-regulated SPRED-1 in cardiac tissue of type 2 diabetic rats. Moreover, the combination of NaB and voluntary exercise amplified their effects on those parameters. Both NaB and voluntary exercise or together markedly modulated serum glucose and HbA1c. The present findings demonstrated that NaB combined with exercise could improve cardiac angiogenesis by increasing miR-126 and affecting related proteins. Thus, NaB together with voluntary exercise might be a promising intervention for the treatment and prevention of type 2 diabetes.

MiR‑221 and miR‑222 regulate cell cycle progression and affect chemosensitivity in breast cancer by targeting ANXA3.

Breast malignancy remains one of the most common causes of cancer-associated mortalities among women. MicroRNA (miR)-221 and miR-222 are homologous miRs and have a substantial impact on cancer progression. In the present study, the regulatory mechanisms of miR-221/222 and its target annexin A3 (ANXA3) in breast cancer cells were investigated. Breast tissue samples were collected to evaluate the expression patterns of miR-221/222 levels in breast cancer cell lines and cancer tissues according to clinical characteristics. The levels of miR-221/222 were increased or decreased in cancer cell lines compared with normal breast cell lines according to cell line subtype. Subsequently, the changes in the progression and invasion of breast cancer cells were investigated using cell proliferation, invasion assay, gap closure and colony formation assays. Western blotting of cell cycle proteins and flow cytometry were performed to evaluate the possible pathway of miR-221/222 and ANXA3 axis. Chemosensitivity tests were performed to explore the suitability of the miR-221/222 and ANXA3 axis as a therapeutic target in breast cancer. The expression levels of miR-221/222 were associated with aggressive characteristics of breast cancer subtypes. Cell transfection assay demonstrated the regulation of breast cancer proliferation and invasiveness by miR-221/222. MiR-221/222 directly targeted the 3'-untranslated region of ANXA3 and suppressed the expression of ANXA3 at the mRNA and protein levels. In addition, miR-221/222 negatively regulated cell proliferation and the cell cycle pathway in breast cancer cells by targeting ANXA3. In combination with adriamycin, downregulation of ANXA3 may sensitize adriamycin-induced cell death to induction of persistent G2/M and G0/G1 arrest. Decreased expression of ANXA3 through increased expression of miR-221/222 reduced breast cancer progression and increased the effectiveness of the chemotherapy drug. The present results indicated the miR-221/222 and ANXA3 axis to be a possible novel therapeutic target for the treatment of breast cancer.

MicroRNA Expression Profiling of Diffuse Large B-Cell Lymphoma

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers that differ in pathogenesis and prognosis. The main methods of treating NHL include chemotherapy, immunochemotherapy, and radiation therapy. However, a significant proportion of these tumors are chemoresistant or rapidly recur after a short chemotherapy-induced remission. In this regard, the search for alternative cytoreductive therapeutic methods is relevant. Aberrant expression of microRNA (miRNA) is one of the mechanisms responsible for the emergence and progression of malignant lymphoid neoplasms. We analyzed the profile of miRNA expression in the biopsy material from lymph nodes affected by diffuse large B-cell lymphoma (DLBCL). The key material of the study was histological preparations of lymph nodes obtained by excisional diagnostic biopsy and treated using conventional histomorphological formalin fixation methods. The study group consisted of patients with DLBCL (n = 52); the control group consisted of patients with reactive lymphadenopathy (RL) (n = 40). It was shown that the miR-150 expression level in DLBCL was reduced by more than 12 times (</>p = 3.6 x 10^(-15)) compared with RL. Bioinformatics analysis revealed the involvement of miR-150 in the regulation of hematopoiesis and lymphopoiesis. The data we obtained allow us to consider miR-150 as a promising therapeutic target with great potential in clinical practice.

P101 Circulating MicroRNA-16 in Inflammatory Bowel Disease Patients - Potential Biomarker to Assess Inflammation

Abstract Background miR-16 is important for the inflammatory processes and the signal pathways that participate in the immune system regulation. As there is an immune mucosal inflammation in IBD, miR-16 could also serve as a potential biomarker to assess inflammation. Methods The study aims to assess the expression of serum miR-16 in IBD patients and to correlate its expression with clinical parameters such as disease extent, activity and severity. 35 patients with UC and 35 patients with CD were included in the study. Serum miR-16 expression was assessed with reverse transcriptase quantitative real time PCR (RT-qPCR), and was then correlated with the miR-16 levels in a group of 30 healthy subjects. Results miR-16 expression is increased in patients with CD, localized in the small intestine (3.54±2.33) and in pancolitis Е3 of UC (2.01±1.54). There is a significant difference in miR-16 expression in inflammatory (B1), stenotic (B2) and penetrating (B3) form of CD (р=0.010) with higher expression levels in the more severe B2 and B3 forms. There is no significant difference in miR-16 expression according to the forms of evolution in patients with UC. In patients with CD, there is a moderate direct correlation between the expression of miR-16 and the Crohn’s disease activity index CDAI (r=0.424; p=0.015). miR-16 expression levels increase progressively in correlation with the activity of CD. Patients with moderate activity of their CD have significantly higher miR-16 expression (4.27±3.00) as compared to patients with mild activity (2.38±1.06) or in remission (2.41±1.23) of the disease (р=0.048). The increased expression levels of miR-16 are a risk factor for CDAI &amp;gt; 150 levels (OR=4.80 (0.506-45.495); p=0.015). In patients with UC, there is no correlation between the miR-16 expression levels and the severity (S) index, measured as per the Montreal classification or the endoscopic activity, measured as per the Partial Mayo score. In patients with severe disease, measured by both S index (1.38±0.89) and Partial Mayo score (1.80±1.12), there is a decrease in miR-16, close to normal controls. MiR-16 expression levels do not correlate with any treatment that was given in patients with either CD or UC. Conclusion The increased miR-16 serum expression corelates with the localization of CD in the small intestine and the stenotic and penetrating form of the disease. Increased miR-16 levels are also found in extensive UC. In patients with CD there is a positive correlation between the expression of miR-16 and the activity of the disease as measured by the CDAI.

Hypoxia-induced paclitaxel resistance in cervical cancer modulated by miR-100 targeting of USP15

ObjectiveHypoxia, which occurs during the development of cervical cancer, confers chemotherapy resistance. MicroRNA expression is regulated by hypoxia and is associated with the onset and progression of certain types of cancer. MicroRNA-100 (miR-100) is a microRNA, associated with nasopharyngeal and oral squamous cell carcinomas, whose expression is decreased in cervical cancer. This study aims to ascertain the effect of hypoxia on expression levels of both miR-100 and its target genes, as well as exploring the sensitivity to paclitaxel under hypoxic conditions. MethodsWe investigated the effect of hypoxia on miR-100 expression. We also explored the regulators of paclitaxel response under hypoxic conditions of cervical cancer. ResultsUsing RT-qPCR, we found that expression of miR-100 in cervical cancer cell lines SiHa and HeLa is significantly higher under hypoxic conditions (1% O2). We also confirmed that human ubiquitin-specific protease 15 (USP15) is the one of the target proteins of miR-100. Hypoxia and overexpression of miR-100 both reduced the activity of the luciferase reporter containing the 3′-untranslated region of USP15, which contains the miR-100 binding site. Furthermore, a western blot analysis showed that hypoxia suppresses the expression of the USP15 protein, while RT-qPCR showed hypoxia-induced downregulation of USP15 mRNA levels. We also discovered that overexpression of miR-100 induces paclitaxel resistance, thereby reducing the drug’s therapeutic effect on cell death. ConclusionsOur results are consistent with the hypothesis that cervical cancer cells overexpress miR-100 in response to hypoxia and that miR-100 is a facilitator of USP15 downregulation and inactivation.

Impact of breast milk miR-155 on the health of preterm neonates

Background. Breast milk (BM) is an important source of microRNAs (miRs). MicroRNAs are highly resistant to gastrointestinal enzymes and are well absorbed in the intestine. MiR-155 is one of the most expressed miR of BM. Currently, the effect of miR-155 of BM on the health of preterm neonates has not been almost studied. The objective was to determine the effect of miR-155 of BM on the health of preterm neonates. Materials and methods. We examined 74 newborns, who were treated in neonatal departments. We determined the level of miR-155 in the BM of 44 mothers of exclusively breastfed children. In parallel, we evaluated gene expression of the transcription factor FOXP3 in buccal smears of all neonates. Three comparison groups were selected: group 1 consisted of 32 newborns of up to 37 weeks of gestation; group 2 — of 30 preterm newborns on artificial feeding; control group — of 12 full-term breastfed newborns. Results. The gestational age median in group 1 was 33 (31; 34) weeks; in group 2 — 32.5 (32; 35) weeks; it was higher in the control group (p &lt; 0.001) — 40 (39; 41) weeks. Neonatal encephalopathy as the main diagnosis occurred more often among full-term newborns (p &lt; 0.001). Children of groups 1 and 2 did not differ significantly in the frequency of respiratory distress syndrome and the duration of the necessary respiratory support (p &gt; 0.05). In group 2 compared to group 1, manifestations of necrotizing enterocolitis were detected significantly more often (p &lt; 0.05): 30.0 ± 8.4 % vs 9.4 ± 5.2 %. The results of evaluating the miR-155 expression level in the BM of mothers of group 1 children prove that the corresponding indicator in the control group was exceeded by an average of 6.2 (4.1; 9.2) times (p &lt; 0.001). Analysis of FOXP3 levels in buccal smears showed that all preterm newborns had significantly lower FOXP3 levels than that of full-term neonates (&lt; 0.001). However, the expression of this factor was the lowest in group 2 (&lt; 0.001): 0.08 (0.04; 0.16) c.u. in group 2 vs 0.21 (0.14; 0.38) c.u. in group 1. We found a direct moderate correlation between the expression levels of miR-155 of the BM and the FOXP3 in the mucosal cells of breastfed preterm neonates: r = 0.442 (p = 0.014). A significant decrease was noted in the expression of FOXP3 in children with necrotizing enterocolitis (0.11 (0.04; 0.25) c.u.) compared to newborns without such pathology (0.22 (0.09; 0.91) c.u.) (p &lt; 0.05). Conclusions. The results of the study confirm a lower number of necrotizing enterocolitis cases among preterm breastfed babies. BM of mothers, whose children were born prematurely, has a higher level of miR-155 expression, which promotes FOXP3 expression of mucous membranes. Thus, it is likely that miR-155 of BM stimulates maturation and maintains the level of T-reg cells of the mucous membranes that prevents the development of necrotizing enterocolitis in premature infants.

Discordant immune response among treatment experienced patients infected with HIV-1: Crosstalk between MiRNAs expression and CD4+ T cells count.

One of the problems with treating HIV-infected patients with ARVs is that the treatment can reduce viral load and does not increase the number of CD4 cells (immunological discordance). There are still challenges to treating HIV-positive patients. This study aimed to investigate the expression level of 18 miRNAs involved in the proliferation and differentiation of CD4+ T cells in a target (discordant immune response) and a control (immune response) group. In this case-control study, 18 miRNAs were selected and synthesized according to the in-silico analysis and published literatures. RNA extraction was performed from PBMC cells of 30 HIV-1 positive patients in the sample bank. The expression level of microRNAs was calculated by the relative q PCR method (2-ΔΔCt method), and data were analyzed using GraphPad Prism software version 8.0.2. The results of fold change calculation and statistical analysis showed that the expression levels of miR-30b (p value: 0.01, fold change: 0.23), miR-155 (p value: 0.04, fold change: 0.44), miR-181a (p value: 0.01, fold change: 0.37), and miR-190b (p value: 0.01, fold change: 0.39) had a significant decrease in the target group compared to the control group. In summary, various studies have shown that miRNAs, including miR-30b, miR-155, miR-181a, and miR-190b, are involved in the proliferation, differentiation, and development of CD4+ T cells. One reason for the lack of increase in CD4+ T cells may be the reduced expression of these miRNAs.

Changes in the components of salivary exosomes due to initial periodontal therapy.

Exosomes are membrane vesicles that are present in body fluids and contain proteins, lipids, and microRNA (miRNA). Periodontal tissue examinations assess the degree of periodontal tissue destruction according to the probing depth (PD), clinical attachment loss (CAL), bleeding on probing, and X-ray examinations. However, the accurate evaluation of the prognosis of periodontitis is limited. In this study, we collected saliva from patients before and after initial periodontal therapy (IPT) and compared changes in the clinical parameters of periodontitis with changes in the components of salivary exosomes. Saliva was collected from patients with stage III and IV periodontitis at the first visit and post-IPT. Exosomes were purified from the saliva, and total protein and RNA were extracted. Changes in expression levels of C6, CD81, TSG101, HSP70, and 6 kinds of miRNA were analyzed by western blots and real-time polymerase chain reaction. Patients with increased C6 expression after IPT had significantly higher levels of periodontal inflamed surface area (PISA), miR-142, and miR-144 before and after IPT than patients with decreased C6 expression after IPT. Patients with decreased and unchanged CD81 expression after IPT showed significantly higher PD, CAL, and PISA before IPT than after IPT. Patients with decreased and unchanged TSG101 expression after IPT had significantly higher PD before IPT than after IPT. Patients with increased HSP70 expression after IPT had significantly higher PD and PISA before and after IPT than patients with unchanged HSP70 after IPT. The expression levels of miR-142, miR-144, miR-200b, and miR-223 changed with changes in the levels of C6, CD81, TSG101, and HSP70 in the salivary exosomes of periodontitis patients before and after IPT. The expression levels of proteins and miRNAs in salivary exosomes significantly changed after IPT in periodontitis patients, suggesting that the components of exosomes could serve as biomarkers for periodontitis.

Association of the circulating micro-RNAs with susceptible and newly diagnosed type 2 diabetes mellitus cases

BackgroundDiabetes mellitus (DM) is an array of metabolic diseases, which results from deregulation in insulin secretion or its action leading to abnormally high levels of blood sugar associated with long-term damage, organs failure, especially the eyes, heart, kidneys, blood vessels and nerves whose frequency has increased progressively worldwide. ObjectivesThe aims of this study were to evaluate the plasma levels of miRNA-126, miRNA-486, miRNA-223 and miRNA-375 in newly diagnosed T2DM susceptible and healthy control individuals. MethodsIn this study, we evaluated the T2DM-related miRNAs miRNA-126, miRNA-486, miRNA-223 and miRNA-375 in plasma of three study groups comprising healthy control (N = 36), newly diagnosed T2DM (N = 29) and T2DM susceptible individuals (N = 30) using Real Time polymerase chain reaction (RT-PCR) (Taqman®). All the statistical analysis were done using SPSS version 21software. ResultsSignificant associations were found between these parameters. The expression levels of miR-126, miR-486, miR-223, and miR-375 were downregulated in T2DM patients and further reduced in T2DM-susceptible individuals compared to healthy controls. Additionally, miR-223 and miR-375 showed an inverse correlation with HbA1c levels, while all four miRs displayed an inverse correlation with FBS levels in the combined group analysis. ConclusionThese observed associations further suggest that miR-126, miR-223, and miR-375 may be involved in the regulation of glucose metabolism and glycemic control. Their down regulation could potentially contribute to impaired insulin signaling, beta-cell dysfunction, inflammation, and disrupted glucose homeostasis, all of which are characteristics of diabetes.

Evaluation of circulating miR-16-5p and miR-223-5p in association with musculoskeletal ultrasonography seven-joint score in the assessment of rheumatoid arthritis activity

Rheumatoid arthritis (RA) is characterized by ongoing joint destruction. MicroRNAs (miRs) are blood-based biomarkers linked to RA pathogenesis. The musculoskeletal ultrasonography seven-joint score (US7) is an objective tool to assess RA activity. We aimed to evaluate miR-223 and miR-16 roles in monitoring RA activity and to investigate if there is a link between their plasma levels and US7 score. This study enrolled 76 RA patients classified according to Disease Activity Score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 38) and active cases (n = 38). Each patient's joint was scored for synovial proliferation (gray-scale ultrasound 'GSUS7') and vascularization (power Doppler ultrasound 'PDUS7'). Real-time quantitative PCR was used to measure the expression levels of miR-16 and miR-223 in plasma. When compared to inactive group, the active group revealed significant upregulation of miR-16 and miR-223, (P = 0.001 and P = 0.02, respectively). miR-16 and miR-223 levels were correlated with synovitis PDUS7 (r = 0.34, p < 0.01 and r= 0.25, P = 0.03, respectively). miR-16 was also positively correlated with synovitis GSUS7 (r= 0.42, p < 0.001). miR-223 upregulation discriminated active from inactive RA patients at AUC = 0.64, with 76% sensitivity and 50% specificity at cutoff > 2.8-fold change), whereas miR-16 distinguished the two groups at AUC = 0.78 with 87% sensitivity and 53% specificity at cutoff >38.27-fold change. In conclusion, upregulated miR-16 may have more potential to serve as activity biomarkers than miR-223 in RA. The miR-16 level was linked to synovitis GSUS7 and synovitis PDUS7 changes but miR-223 only linked to synovitis PDUS.

Plasma microRNAs as non-invasive biomarkers in bovine endometritis caused by Gram-negative and Gram-positive bacteria.

The purpose was to identify differentially expressed plasma microRNAs (miRNAs) in cows with clinical and subclinical endometritis. In this study clinical endometritis (CE; n = 23) based on vaginal discharge score (VDS), subclinical endometritis (SCE; n = 17) based on VDS (0), and endometrial cytology (the presence of 8.00% polymorphonuclear neutrophils (PMN) on days 21-31 and 5.00% on days 41-51 days in milk(DIM) and healthy cows (n = 21) based on vaginal discharge score (0), and endometrial cytology (< 5.00% PMN on days 21 - 31 and < 5.00% on days 41 - 51 DIM) were selected. The results showed that the expression level of miR-146a was significantly higher in the CE (19.17-fold), and SCE (6.22-fold) groups than those of healthy cows. The relative transcript abundance of miR-223 was considerably down-regulated in the CE (0.26-fold) and SCE (0.06-fold) compared to the healthy cows. The expression levels of miR-146a and miR-223 were significantly higher in the CE group which could be caused by Gram-negative bacterial infection. Our results showed that the expression level of plasma miRNAs postpartum could be used as a reliable marker to distinguish between SCE, CE and healthy cows.

MiR-21, miR-93, miR-191, miR-let-7b, and miR-499 Expression Level in Plasma and Cerebrospinal Fluid in Patients with Prolonged Disorders of Consciousness

In recent decades, significant progress has been achieved in understanding the mechanisms of disturbance and restoration of consciousness in patients after severe brain damage resulting in prolonged disorders of consciousness (pDOC). MicroRNAs (miRs) may be potential candidates as possible biomarkers for the classification of disease subtypes, and prognosis in patients with pDOC. The aim of the study was to analyze miRs expression levels (hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-191-5p, mmu-miR-499-5p, hsa-let-7b-5p) by a real-time polymerase chain reaction in plasma and cerebrospinal fluid (CSF) from patients with pDOC and to identify a potential biomarker for dividing patients into groups according to disease severity. We analyzed the levels of investigated miRs in pDOC patients, divided by etiology, CRSI, and the total group compared with controls. Our results showed that dividing patients with pDOC into groups according to the etiology of the disease resulted in the most significant differences in the levels of miR-93, -21, and -191 in CSF and plasma samples between groups of patients. Among the analyzed miRs, we did not find a marker that would help to distinguish VS/UWS patient groups from MCS. Examining of miRs as possible prognostic markers in patients with pDOC, the starting point seems to be the cause that led to the development of the disease.

Differential Expression of AhR in Peripheral Mononuclear Cells in Response to Exposure to Polycyclic Aromatic Hydrocarbons in Mexican Women.

The exposure to air pollutants causes significant damage to health, and inefficient cooking and heating practices produce high levels of household air pollution, including a wide range of health-damaging pollutants such as fine particles, carbon monoxide and PAHs. The exposure to PAHs has been associated with the development of neoplastic processes, asthma, genotoxicity, altered neurodevelopment and inflammation. The effects on the induction of proinflammatory cytokines are attributed to the activation of AhR. However, the molecular mechanisms by which the PAHs produce proinflammatory effects are unknown. This study was performed on a group of 41 Mexican women from two rural communities who had stoves inside their houses, used wood as biomass fuel, and, thus, were vulnerable. According to the urinary 1-OHP concentration, the samples were stratified into two groups for determination of the levels of TNF-α, AhR, CYP1B1, miR-125b and miR-155 expression. Our results showed that the CYP1B1, TNF-α, miR-125b and miR-155 expression levels were not statistically different between women with the lowest and highest levels of 1-OHP. Interestingly, high levels of PAHs promoted augmented expression of AhR, which is a protein involved in the modulation of inflammatory pathways in vivo, suggesting that cell signaling of AhR may be implicated in several pathogenesis processes.

Evaluation of Cellular miR-122 Expression in Association with the Presence of Varicella-Zoster Virus among Central Nervous System Tumors

Background: Brain tumors are all primary central nervous system (CNS) tumors with unclear etiologies and viral infections, especially human herpesviruses, which have emerged as a hot topic for comprehensive research. Objectives: The present study aimed at assessing the molecular epidemiology of varicella-zoster virus (VZV) and its association with microRNA 122 (miR-122) expression in CNS tumor samples. Methods: Fresh frozen tissue samples were collected from 60 CNS tumor patients and 45 healthy controls. A nested PCR assay was performed to detect the VZV-DNA. Subsequently, the expression level of miR-122 was evaluated in the CNS tumor tissue samples of patients and the brain tissue samples were obtained from healthy controls, using a real-time PCR assay. Results: Of 60 patients with CNS tumors, 29 were men and 31 were women. VZV-DNA was detected in 13.3% of the CNS tumor tissue specimens. There was no statistically significant association between the presence of VZV-DNA and different types of CNS tumors (P &gt; 0.05). Furthermore, the expression level of miR-122 was significantly downregulated in the CNS tumor tissue samples obtained from the patients compared with those of the healthy controls (P &lt; 0.05). Additionally, the expression level of miR-122 was significantly lower in the VZV-positive tumor samples as compared with those of the VZV-negative tumor samples and the healthy controls. Conclusions: Although VZV plays no direct role in the development of CNS tumors, the virus may affect the biology of CNS tumors by decreasing the expression levels of miR-122, which consequently leads to an increased risk of malignancy. However, the experimental data are not conclusive enough; so, further investigations are needed.

Assessing the expression of two post-transcriptional BDNF regulators, TTP and miR-16 in the peripheral blood of patients with Schizophrenia

Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjusted P-value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls (r = 0.701, P < 0.001 and r = 0.777, P < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ.

Expression levels and network analysis of inflammamiRs in peripheral blood mononuclear cells exposed to DDE “in vitro”

Recent studies have demonstrated that dichlorodiphenyldichloroethylene (DDE) induced a pro-inflammatory condition in peripheral blood mononuclear cells (PBMC). However, the molecular mechanisms implicated in this condition are poorly understood. Therefore, this study aimed to evaluate miR-155, miR-126, and miR-21 expression levels in PBMC exposed “in vitro” to DDE. PBMC were dosed with increasing concentrations of DDE (10–80 µg mL-1) at different treatment times (0–24 h). The results showed an up-regulation in the expression levels of assessed miRNAs (miR-155, miR-146, and miR-21) after PBMCs were exposed to DDE. Besides, bioinformatic analysis was performed to understand the biological roles of assessed miRNAs. The bioinformatic analysis shows that assessed miRNAs are associated with regulating signaling pathways involved in cancer, apoptosis, cell cycle, inflammation, metabolism, etc. These findings offer new insights into the molecular mechanisms related to the inflammatory processes and their regulation induced by DDE in PBMC exposed “in vitro”.

Исследование профилей экспрессии экзосомальных микроРНК-126 и микроРНК-218 у пациентов с геморрагической лихорадкой с почечным синдромом (ГЛПС) И.

Background: Hemorrhagic fever with renal syndrome (HFRS), caused by orthohantaviruses, occupies one of the leading places among natural focal human diseases, for which there are no modern accurate and highly sensitive diagnostic methods. To improve this situation, a better understanding of the hantavirus pathogenesis of HFRS is required. The expression levels of circulating microRNAs in the serum or plasma of patients during infection make them potential therapeutic biomarkers for the diagnosis of HFRS. The aim of the study: To analyze the expression levels of miR-126 and miR-218 patients with HFRS at different stages of the disease. Materials and methods: The moderate disease severity group of HFRS patients included 105 RNA samples, severe – 99 and severe with complications – 84 RNA samples. Blood samples of HFRS patients for molecular genetic analysis were collected three times – during the initial febrile period (1-4 days of illness), the polyuric period (15-22 days of illness) and during the convalescence period. Total RNA isolation was performed using the miRNeasy Serum/Plasma Advanced Kit (Qiagen, Germany). Quantitative realtime PCR was performed using the miRCURY LNA SYBR Green PCR Kit (Qiagen, Germany) and the real time PCR product detection system LightCycler96 (Roch). Results: A pairwise comparison of miR-126 and miR-218 expression levels in patients with HFRS at the fever stage and at the polyuric stage of HFRS did not reveal statistically significant results (P&gt;0.05). Conclusion: Further studies of the network of genes that are targets of various microRNAs are needed to clarify the molecular mechanisms that can influence the occurrence and development of HFRS.

An Investigation of Exosome Concentration and Exosomal microRNA (miR-155 and miR-222) Expression in Pregnant Women with Gestational Hypertension and Preeclampsia.

Hypertensive disorders of pregnancy are characterized by widespread maternal endothelial dysfunction. Elevated secretion of exosomes has been associated with endothelial dysfunction. Exosomes play a role in cell-cell communication by transferring microRNAs. These microRNAs are associated with the pathogenesis of hypertensive disorders of pregnancy through the regulation of endothelial function. This study characterizes exosomes and determines exosomal miR-155 and miR-222 expression levels in women with gestational hypertension (GH) and preeclampsia (PE). Exosomes were isolated and thereafter characterised using NTA, microscopy and ELISA. Results: Exosomes were elevated in the serum of pregnant women with GH and PE (P<0.05). The circulating exosomes and placental exosomes were increased in both GH and PE (P<0.0001). The exosomal miR-155 increased in PE but not in GH (P < 0.05). MiR-222 decreased in PE (P < 0.05). Elevated exosomes in pregnant women with GH and PE may be indicative of exosomes being potential biomarkers for both GH and PE. The difference in the exosomal miR-155 and miR-222 expression in PE and GH suggested that these two disorders have different pathological pathways.

Prophylactic Resveratrol Ameliorates Thioacetamide Hepatotoxicity in A Dose-Dependent Fashion Through the Regulation of Gene Expression Levels of MiR-155 and MiR-21

Prophylactic Resveratrol Ameliorates Thioacetamide Hepatotoxicity in A Dose-Dependent Fashion Through the Regulation of Gene Expression Levels of MiR-155 and MiR-21