Expression Of miRNA-146a Research Articles

Expression of miRNAs (146a and 155) in human peri-implant tissue affected by peri-implantitis: a case control study

BackgroundIn literature, the levels of miRNA-146a and miRNA-155 are increased in periodontitis. Limited data are available regarding the expression of miRNA-146a and miR-NA-155 in diseased human peri-implant tissue. Therefore, the objective of this study was to explore the expression of miRNA-146a and miRNA-155 in human gingival peri-implant tissue affected by peri-implantitis.MethodsAfter recording the clinical parameters, human peri-implant pocket tissues were harvested from sites diagnosed with peri-implantitis (n = 15 cases) in addition to healthy peri-implant sulcus tissues (n = 15 controls). The levels of miRNA-146a and miRNA-155 were assessed using real-time qPCR.ResultsCases exhibited a significantly higher mean expression of miRNA-155 (5.2-fold increase) and miRNA-146a (2.8-fold increase) than controls. MiRNA-155 and miRNA-146a demonstrated an appropriate sensitivity (87.5% and 87.5%, respectively) and specificity (73.3% and 66.7%, respectively) in discriminating cases from controls. A moderate correlation (r = 0.544, p = 0.029) was found between miRNA-155 and miRNA-146a levels in the case group.ConclusionsThe expressions of miRNA-146a and miR-NA-155 are different between healthy and peri-implantitis affected tissues. Both miRNAs might potentially able to discriminate healthy from peri-implantitis affected tissues.

Transplantation of bioengineered dermal derived matrix-scaffold in combination with hyperbaric oxygen therapy improves wound healing in diabetic rats

Successful treatment of diabetic wounds requires multifactorial approaches. Herein we investigated the effects of a bioengineered three-dimensional dermal derived matrix-scaffold (DMS) in combination with hyperbaric oxygen (HBO) in repairing of wound model in diabetic rats. Thirty days after induction of diabetes, a circular wound was created and treatments were performed for 21 days. Animals were randomly allocated into the untreated group, DMS group, HBO group, and DMS+HBO group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. Our results showed that the wound closure rate, volume of new dermis and epidermis, numerical density fibroblasts and blood vessels, collagen density, and biomechanical characterize were significantly higher in the treatment groups than in the untreated group, and these changes were more obvious in the DMS+HBO ones. Moreover, the expression of TGF-β, bFGF, miRNA-21, miRNA-146a, and VEGF genes were meaningfully upregulated in treatment groups compared to the untreated group and were greater in the DMS+HBO group. This is while expression of TNF-α and IL-1β, as well as the numerical density of neutrophil and macrophage decreased more considerably in the DMS+HBO group than in the other groups. Overall, using both DMS engraftment and HBO treatment has more effects on diabetic wound healing.

The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model

Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.

Theranostics of uterine leiomyoma: present and future

Research objectives: to develop an algorithm for predicting the growth of uterine fibrodis, taking into account the state of epigenetic regulation.Materials and methods. The study was conducted on the basis of clinical divisions of the Department of Obstetrics and Gynecology in 2018–2021. 28 patients with uterine fibroids were examined. Expression of miRNA-29b and miRNA-146a in tumor tissue was determined in all women using real-time PCR. Obtained data were analyzed using the statistical program Statistica 10.0 (StatSoft Inc., USA).Results. The average age of the patients was 39.3 ± 1.0 years. The average number of nodes was 2.7 ± 0.4. The expression levels of microRNA-29b were most frequently determined in the range of 2–7 units and microRNA-146a in the range of 30–67 units in most of the examined tissue samples. The expression of miRNA-29b has the greatest significance for the growth forecast (Wald statistic). According to the logistic regression equation the prognostic factors are patient’s age, estradiol and progesterone level in the I and II phases of the menstrual cycle, diameter of the largest node, expression of miRNA-29b and miRNA-146a.Conclusions. This study shows that the use of miRNA expression profile as an additional marker in the diagnosis and treatment of uterine fibroids is promising and requires more detailed research. Further study of the correlation of clinical and paraclinical parameters can make it possible to predict the course of uterine fibroids, and therefore to apply an effective personalized treatment plan. Theranostics is a new approach to the diagnosis and treatment of patients, based on the uniqueness of each person in order to choose the optimal treatment strategy against the background of the molecular genetic technologies, in particular to determine epigenetic changes in hyperproliferative diseases. The study of miRNA expression may find its place in the theranostics of uterine fibroids in the future.

Association of MicroRNA-146a expression level and it’s Gene Polymorphism rs2910164 C/G in patients with Rheumatoid Arthritis

MicroRNAs are small non-coding RNAs that can regulate a variety of immune functions. MicroRNA146a (miRNA-146a) is regarded as a crucial regulator of posttranscriptional gene expression, suggesting a role in autoimmune disorders. This study was performed to investigate association miRNAs-146a expression and its polymorphisms in patient with Rheumatoid arthritis. The current study includes 120 subjects classified into two main groups: 60 RA patients and 60 healthy controls. Quantitative expression of serum miRNA-146a, as well as its genotyping rs2910164 (C/G) were done to all subjects using real-time PCR and Tetra primer ARMS-PCR respectively. Serum miRNA-146a significantly over expressed in RA patients (fold change 2.59±1.18), compared to the controls (fold change 1.07±0.41), (P=< 0.0001).The receiver operating characteristics (ROC) curve was plotted to compare the expression efficiency of miR-146a showing high sensitivity 91.7 % and high specificity 91.1 %, AUC 0.95, (95% CI 0.91-0.99), the cut off value was (1.57). On the other hand MiRNA-146a (rs2910164) genotyping revealed that no significant variation between the RA patients in the comparison with the control group under all co-dominant model heterozygous genotype (C/G), co-dominant model homozygous genotype (G/G), dominant pattern (C/G+G/G) genotypes, recessive model (G/G) genotype. Analysis of the allele frequencies no statistically significant differences between patients and controls. Conclusion miRNAs-146a expression can be used as diagnostic markers for RA patients and miRNA-146a rs2910164 C/G not associated with RA susceptibility. The C allele of miRNA-146a (rs2910164) can be considered to be protective.

Wenhua Juanbi Recipe Attenuates Rheumatoid Arthritis via Inhibiting miRNA-146a-Mediated Autophagy.

Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA-146a-mediated cellular autophagy. A collagen-induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC-Q/TOF-MS. Histological changes; miRNA-146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA-146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR-containing serum to observe the effects of miRNA-146a-mediated autophagy via the PI3K/AKT/mTOR pathway on CIA-affected rats. Forty and thirty-one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA-146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA-146a-mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA-146a-mediated PI3K/AKT/mTOR pathway.

The Protective Effect of miRNA-146a Liposome Nanoparticles on Vascular Smooth Muscle Cells After Coronary Intervention

The abnormal expression of miRNA-146a is related to the progression of coronary arteries. This study intends to explore the protective effect of miRNA-146a on vascular smooth muscle cells (VSMCs) after coronary intervention and the related mechanism. 10 miniature pigs were randomly assigned into control group, model group, blank group, miRNA-146a group, cilostazol group, and STAT3 signaling agonist group followed by analysis of the morphology and viability of VSMCs, expression of miRNA-146a, STAT3, NF-kB, TNF-a, IL-6, and AT-1R as well as the relationship between miR-146a and STAT3. The BNP (192.39±12.32) pg/ml and cTnI (14.20±2.12)μg/L of model group were significantly higher than those of control group (P< 0.05). miRNA-146a level was highest in miRNA-146a group and cilostazol group, while lower in other two groups with the lowest level in agonist group (P<0.05). The cell viability and AngII level of miRNA-146a group and cilostazol group were lower, and higher in the other two groups with highest level in pathway agonist group (P< 0.05). miRNA-146a group and cilostazol group showed lower expressions of STAT3, NF-kB, TNF-a, IL-6, AT-1R than the other two groups. The pathway agonist group showed significantly higher level than blank group (P<0.05). liposome nanoparticles carrying miRNA-146a inhibited the activity of STAT3 signaling, down-regulated the levels of downstream factors including TNF-a, IL-6, and TNF-a and subsequently decreased AngII and AT-1R levels, therefore playing a protective effect on VSMCs after coronary intervention.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Serum vitamin D level and micro-ribonucleic acid-146a expression pattern in dry eye disease associated with rheumatoid arthritis in an Egyptian population

Aim The aim of this research was to study serum vitamin D and micro-ribonucleic acid-146a (miRNA-146a) expression in dry eye disease (DED) associated with rheumatoid arthritis (RA) and their clinical correlations to DED parameters. Setting and design This is an observational cross-sectional study that was conducted at Cairo University, Cairo, Egypt. Patients and methods The study participants were divided into three groups: group A, DED/RA (n=35); group B, non-DED/RA (n=36); and group C, non-DED/non-RA (n=35). All participants were assessed for ocular surface disease index, tear breakup time (TBUT), serum level of vitamin D, and miRNA-146a expression. In the DED group (with TBUT˂10 s), DED evaluation was performed, including Schirmer I test, corneal and conjunctival scoring, and impression cytology. Results The mean serum vitamin D level was 17.1±16.2 ng/ml in group A, 35.1±13.4 ng/ml in group B, and 38.1±8.7 ng/ml in group C, with a statistically significant difference (P˂0.001). The mean miRNA-146a expression was 4.7±1.5 in group A compared with 4.8±1.8 in group B (P=0.959) and 1.0±0.1 in group C (P˂0.001, compared with each of groups A and B). In group A, serum vitamin D level showed a significant moderate negative correlation to each of impression cytology grading (r=−0.456, P=0.019) and miRNA-146a expression (r=−0.387, P=0.041). Both serum vitamin D and miRNA-146a expression showed nonsignificant correlations to ocular surface disease index, TBUT, Schirmer I test, and corneal and conjunctival scoring. Conclusion DED associated with RA showed a statistically significantly lower serum level of vitamin D, which was negatively correlated to impression cytology grading and miRNA-146a expression. Expression of miRNA-146a did not differ between the dry eye and non-dry eye RA groups.

Molecular Analysis of rs2910164 Polymorphism and its Association with TNF-α Gene Expression in Colorectal Cancer

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world, which has been introduced as the third most common cancer and the third leading cause of death. This cancer is uncommon before the age of 50. Its prognosis is controversial, and many studies report a poor prognosis in older patients, and the others show no difference. In addition to the factors, such as diet, environmental factors, somatic, and hereditary mutations, genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor-α (TNF-α) gene, may be involved in CRC. Objectives: This study aimed to investigate the rs2910164 polymorphism from the miRNA146a gene and its association with the expression of TNF-α gene in CRC before and after the age of 50 for early diagnosis and treatment. Methods: In this study, 65 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with cancerous lesions of colorectal tissue (37 cases over 50 years were considered as the case group and 28 cases under 50 years were considered as the control group). DNA was extracted from the samples, and rs2910164 polymorphism of the miRNA146a gene was investigated by PCR. Moreover, RNA was extracted from the samples, and the expression of the miRNA146a and TNF-α genes were evaluated. Finally, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used for data analysis. Results: The frequency of GG, GC, and CC genotypes from rs2910164 polymorphism of miRNA146a gene in the control group was 0.29, 0.46, and 0.25, respectively, but in the case group, it was 0.54, 0.38, and 0.08, respectively. The results also showed that the expression of miRNA146a (P = 0.00006) and TNF-α (P = 0.009) genes was higher in the case group than in the control group. Conclusions: Based on the results of this study, a significant correlation was found between GG genotype and rs2910164 polymorphism of miRNA146a gene and TNF-α gene expression in the CRC samples. Therefore, investigation of these factors may be helpful in patients with CRC over 50 years.

Allergoid–mannan conjugates reprogram monocytes into tolerogenic dendritic cells via epigenetic and metabolic rewiring

Allergoid-mannan conjugates are novel vaccines for allergen-specific immunotherapy being currently assayed in phase 2 clinical trials. Allergoid-mannan conjugates target dendritic cells (DCs) and generate functional forkhead box P3 (FOXP3)-positive Treg cells, but their capacity to reprogram monocyte differentiation remains unknown. We studied whether allergoid-mannan conjugates could reprogram monocyte differentiation into tolerogenic DCs and the underlying molecular mechanisms. Monocytes from nonatopic and allergic subjects were differentiated into DCs under conventional protocols in the absence or presence of allergoid-mannan conjugates. ELISA, real-time quantitative PCR, coculture, flow cytometry, and suppression assay were performed. Metabolic and epigenetic techniques were also used. Monocyte differentiation from nonatopic and allergic subjects into DCs in the presence of allergoid-mannan conjugates yields stable tolerogenic DCs. Lipopolysaccharide-stimulated mannan-tolDCs show a significantly lower cytokine production, lower TNF-α/IL-10 ratio, and higher expression of the tolerogenic molecules PDL1, IDO, SOCS1, SOCS3, and IL10; and they induce higher numbers of functional FOXP3+ Treg cells than conventional DC counterparts. Mannan-tolDCs shift glucose metabolism from Warburg effect and lactate production to mitochondrial oxidative phosphorylation. They also display epigenetic reprogramming involving specific histone marks within tolerogenic loci and lower expression levels of histone deacetylase genes. Mannan-tolDCs significantly increase the expression of the anti-inflammatory miRNA-146a/b and decrease proinflammatory miRNA-155. Allergoid-mannan conjugates reprogram monocyte differentiation into stable tolerogenic DCs via epigenetic and metabolic reprogramming. Our findings shed light on the novel mechanisms by which allergoid-mannan conjugates might contribute to allergen tolerance induction during allergen-specific immunotherapy.

Circulating miRNA expression in asthmatics is age-related and associated with clinical asthma parameters, respiratory function and systemic inflammation

BackgroundThe course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA.MethodsControl and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry.ResultsNo difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs.ConclusionSerum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

Evaluation of inflammatory miRNA155 and 146a expression in heart tissue of ovalbumin-sensitized male rats

Introduction: Asthma is a chronic pulmonary inflammation occurred in response to different allergens, leading to respiratory system insufficiency. The production of different inflammatory factors and enhanced immune system response may affect the function of other organs. The aim of this study was to investigate the expression of inflammatory microRNAs in cardiac tissue in asthmatic rat model. Methods: In this study, the animals were allocated into Control and Asthmatic rats (n=8). To induce asthma, rats were challenged with ovalbumin. 14 days after induction of asthma, rats were euthanized and Hematoxylin-Eosin staining was performed to assess pathological changes in pulmonary tissue. Serum levels of cardiac enzymes were measured using ELISA kits. Finally, transcription level of inflammatory miRNAs, miRNA-146a and -155, were measured using real-time PCR analysis. Results: Based on our findings, histological examination indicated the existence of pathological changes in pulmonary tissue after asthma induction. Bright-field analysis revealed an existence of inflammatory response and cytotoxicity in cardiac tissue. Also, the serum levels of CpK-MB, ALT, and AST were significantly higher in the serum of asthmatic group compared to control group (p&lt;0.05). Finally, asthmatic condition induced the expression of (2-fold) miRNA-146a and (1.5-fold)-155 in cardiac tissue, respectively. Conclusion: As a conclusion, it could be concluded that asthmatic condition induces systemic inflammation in cardiac tissue. On a more general note, we propose that therapeutical approaches directed to inflammatory pathway may be required to preserve cardiac injuries caused of asthma.

Expression of miR-146a and miR-155 in Egyptian patients with Beh\xe7et\u2019s disease: clinical significance and relationship with disease activity

BackgroundBehçet’s disease (BD) is a systemic vasculitis disorder with multifactorial immunopathogenesis and associated with significant morbidity and mortality. MicroRNAs (miRNAs) are involved in the pathogenesis of inflammatory diseases. MiR-146 and miR-155 are known key regulators of immune response. This study was conducted to determine the expression of miRNA-146a and miRNA-155 in patients with BD and to link their possible association with the clinical manifestations and activity of this disease to evaluate their role as diagnostic or prognostic markers. A total of 60 patients with BD and 25 age- and gender-matched healthy controls were examined in a case-control study from October 2017 to September 2018 for the expression levels of miR-146a and miR-155 using singleplexTaqMan two-step stem loop quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR).ResultsPatients with BD had significantly lower miR-146a levels than control subjects (P < 0.001). Regarding the miR-155 expression level, no statistically significant differences were detected between patients and healthy controls (P = 0.736). The expression level of miR-146a showed no significant association with the different clinical manifestations of patients with BD.ConclusionThis study suggests the possibility that miR-146a expression in patients with BD is involved in the pathogenesis of disease. Furthermore, it can be used as a diagnostic biomarker and a therapeutic target for BD in the future.

Relationship of miRNA-146a to systemic lupus erythematosus: A PRISMA-compliant meta-analysis.

miRNA-146a is a microRNA that plays an important role in systemic lupus erythematosus (SLE). Several studies have examined the role of miRNA-146a in SLE, but have demonstrated equivocal or even contradictory conclusions. Therefore, this meta-analysis aimed to assess the role of miRNA-146a in SLE by examining data from previous studies. A meta-analysis of relevant papers published before August 31, 2019, in the WanFang, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), PubMed, EMBASE, and Web of Science databases was performed to verify the relationship of miRNA-146a expression level to SLE. Two investigators independently extracted the data and conducted a quality assessment of the studies. All statistical analyses were performed using Stata 14.0. Trial sequence analysis (TSA) was conducted to assess the quality and strength of the studies using the TSA software. Six publications, involving 151 SEL patients and 132 healthy individuals as controls were included in this meta-analysis. The results showed that the expression of miRNA-146a was associated with SLE risk [standard mean difference (SMD) = -1.21, 95% confidence interval (95% CI) (-2.18, -0.23), P = .015]. The stratified analysis revealed that the expression of miRNA-146a was highly related to higher SLE risk among Asian (SMD = -1.30, 95% CI (-2.52, -0.07), P = .038) and Caucasian (SMD = -0.72, 95% CI (-1.20, -0.24), P = .003) populations. Besides, the serum levels of miRNA146a were significantly different (SMD = -1.73, 95% CI (-3.11, -0.36), P = .014). The TSA revealed that the cumulative Z-curve crossed the typical boundary value, and reached the TSA monitoring boundary, but did not reach the required information size. This indicates that even if the cumulative sample size did not meet required information size, no more trials were needed and a reliable conclusion was reached in advance. Sensitivity analyses indicated the instability of the meta-analysis. Overall, the expression of miRNA-146a is associated with SLE risk. Therefore, miRNA-146a is a promising candidate for the effective diagnosis of SLE. But, due to the limitations of this study, it is necessary to cautiously explain the results of this study. PROSPERO CRD42019151381.

Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival

BackgroundEndometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain subtypes of EC that lose nuclear hormone receptor (NHR) expression are associated with poor survival rates. For example, estrogen receptor (ER)-negative EC typically harbors a worse prognosis compared to ER-positive EC. The molecular basis for the loss of NHR expression in endometrial tumors and its contribution to poor survival is largely unknown. Furthermore, there are no tools to systematically identify tumors that lose NHR mRNA expression relative to normal tissue. The development of such an approach could identify sets of NHR-based biomarkers for classifying patients into subgroups with poor survival outcomes.MethodsHere, a new computational method, termed receptLoss, was developed for identifying NHR expression loss in endometrial cancer relative to adjacent normal tissue. When applied to gene expression data from The Cancer Genome Atlas (TCGA), receptLoss identified 6 NHRs that were highly expressed in normal tissue and exhibited expression loss in a subset of endometrial tumors.ResultsThree of the six identified NHRs – estrogen, progesterone, and androgen receptors – that are known to lose expression in ECs were correctly identified by receptLoss. Additionally, a novel association was found between thyroid hormone receptor beta (THRB) expression loss, increased expression of miRNA-146a, and increased rates of 5-year survival in the EC TCGA patient cohort. THRB expression loss occurs independently of estrogen and progesterone expression loss, suggesting the discovery of a distinct, clinically-relevant molecular subgroup.ConclusionReceptLoss is a novel, open-source software tool to systematically identify NHR expression loss in cancer. The application of receptLoss to endometrial cancer gene expression data identified THRB, a previously undescribed biomarker of survival in endometrial cancer. Applying receptLoss to expression data from additional cancer types could lead to the development of biomarkers of disease progression for patients with any other tumor type. ReceptLoss can be applied to expression data from additional cancer types with the goal of identifying biomarkers of differential survival.

Diagnostic value of microRNA-150 and microRNA-146a in critically ill patients with suspected sepsis

Background: Sepsis is a major cause of death; therefore, early diagnosis is crucial. A promising method for diagnosis is the use of specific miRNA as biomarkers for sepsis. Objective: This study aimed to validate the diagnostic value of miRNA-150 and 146-a as biomarkers for sepsis patients in different intensive care units in Alexandria, Egypt. Methodology: Blood samples from fifty sepsis patients from different intensive care units and twenty healthy volunteers were collected, inoculated onto aerobic culture bottle for culture and sensitivity, and sera was separated for quantification of miRNA 146-a and 150 using real-time PCR. Results: 56% and 52% showed overexpression of miRNA 146-a and 150 respectively in sepsis patients. Their co-expression showed a moderate positive correlation in the studied group which was found to be statistically significant. Conclusion: Up to our Knowledge, this is the first study to associate between type of organism and expression of miRNA 146-a and 150.

The Expression of miRNA-146a in Peripheral Blood Mononuclear Cells of Patients with Myasthenia Gravis and Its Bioinformatics Analysis

The study is to investigate the expression of miRNA-146a in PBMC of myasthenia Gravis (MG), and to explore the molecular regulatory network of miRNA-146a in the pathogenesis of MG by bioinformatics. 108 patients with MG were selected as the experimental group (MG group), and 50 healthy subjects were selected as the control group. The relative expression of miRNA-146a in PBMC was detected by RT-PCR. The cross-target gene of miRNA-146a was predicted by TargetScan and CoMeTa database. miRNA-146a target gene GO enrichment and KEGG Pathway enrichment analysis was performed using the DAVID database. Our results shows that the expression level of miRNA-146a in peripheral blood of MG patients was significantly higher than that of the control group, the difference was statistically significant (P &lt; 0 05), and the nucleotide sequence was highly conserved. The potential target genes of miRNA-146a include 88 kinds; GO analysis showed that miRNA-146a target gene function is mainly enriched in cell proliferation regulation, neuronal differentiation, etc. KEGG Pathway analysis shows that miRNA-146a is mainly enriched in Toll-like receptor signaling pathway, neurotransmitter regulatory signaling pathways, EB signaling pathways and other signaling pathways. In conclusion, the expression of miRNA-146a in PBMC of MG patients is up-regulated and participates in the pathogenesis of MG by acting on multiple signaling pathways.

Plasma oxidized low-density lipoprotein level and miRNA-146a gene expression, as a strong predictor for atherosclerotic coronary artery disease and its associated response to atorvastatin in a sample of the Iraqi population

BackgroundAtherosclerosis is considered to be a chronic inflammatory disease of the artery wall. Complications of atherosclerosis, such as myocardial infarction (MI) or ischemic stroke, are the major causes of disability and death in the modern world. Atorvastatin is broadly used as statin therapy to lower the serum lipid level with better safety and tolerance and is a class of statin medication that used in Iraqi healthcare services. The aim of the present study is to explore the expression level of miRNA146a and OX-LDL as a potential diagnostic biomarker of atherosclerotic coronary artery disease which depends upon vessel affected and its associated with the lipid lowering medication (atorvastatin).Subjects and methodsA total of 200 blood specimens were collected from adults with atherosclerosis comprise 100 patients subdivided to patients with 20 mg atorvastatin (n = 52) and patients with 40 mg atorvastatin (n = 48), and healthy control subjects which comprise 100. The age range between 30‐ and 60 years old. The disease activity of patients᾿ groups to determine by vessel disease affected. OxLDL determined by competitive ELISA, relative quantification (RQ) of miRNA146a expression, in whole blood was estimated using reverse transcriptase quantitative real time polymerase chain reaction. ResultThe statistical analysis showed significant statistical differences between patients and healthy controls in multiple studied parameters. Regarding lipid profile and oxLDL levels in patients taking 20 mg atorvastatin were significantly higher than controls (P < .05). A significant difference in total cholesterol (TC) and low density lipoprotein (LDL-C) between two classes of patients with double disease affected and a significant decrease in the rate of oxidizing LDL (oxLDL) in patients with 40 mg compared to 20 mg. Highly significant upregulated gene expression of miRNA-146a in patients with 20 mg versus 40 mg and the highest folds in a single vessel was observed. OxLDL and miRNA146a demonstrated better performance in atherosclerotic coronary artery disease (ACAD) diagnosis, showing sensitivity (95.3; 75%) (AUC: 0.81; 0.83 at cutoff value 57.94; 1.17) P 0.05. The level of miRNA-146a is positively correlated with oxLDL (p < .05). ConclusionThe applicability of miRNA146a and ox-LDL as potential diagnostic biomarkers of ACAD, by using different protocols. Its diagnostic performance was better than lipid variable and other traditional risk factor. Therefore, our data strongly suggest measuring both parameters for more specific prediction of ACAD.

The expression of microRNA 146a in patients with ischemic stroke: an observational study.

AimWe conducted the present prospective study to assess the level of microRNA (miRNA) 146a in patients with ischemic stroke and its correlation with patients’ characteristics.MethodsWe conducted an observational study that included adult patients (≥18 years old) who presented within 24 hrs after the onset of the symptoms of acute ischemic stroke. In addition, age- and sex-matched healthy volunteers were included as control group. The primary outcome in the present study was the difference in miRNA 146a expression between patients with ischemic stroke and control group participants. The expression of miRNA 146a was measured using quantitative real-time PCR. Quantitative real-time PCR amplification and analysis were performed using Rotor-Gene Q thermal cycler.ResultsThe present study included 44 patients with ischemic stroke and 22 matched controls. Regarding the primary outcome of the present study, the median expression of miRNA 146a in patients with ischemic stroke was −1.98 fold (IQR −27.1–3.9) compared to 1.75 fold (IQR −2.25–5.27) in control group (P<0.001). However, the subgroup analysis showed that the expression of miRNA 146a was significantly downregulated in comatosed patients only (P<0.001). The expression of miRNA 146a correlated negatively with Glasgow Coma Scale score in comatose patients (r=−0.352, P=0.022).ConclusionIn conclusion, the expression of miRNA 146a is significantly downregulated in ischemic stroke patients. Further studies are needed to assess its diagnostic utility and therapeutic potentials.