Serum miR-122 Levels Research Articles

Association between circulating microRNAs and changes in kidney function: A five-year prospective study among Japanese adults without CKD

BackgroundAlthough a number of microRNAs (miRNA) reflecting kidney function has been identified, prospective studies are now urgently needed to determine a clinical utility of these miRNAs among general populations. The purpose of this study was to examine the associations between serum miRNAs and kidney function in a population-based study. MethodsWe conducted a five-year prospective study (2012–2017) of 169 individuals without chronic kidney disease (CKD) at the baseline survey (mean age, 62.5; 96 women). The real-time qPCR was used to measure serum levels of five previously reported miRNAs. Participants with eGFR < 60 mL/min/1.73 m2 were defined as having CKD. Changes in eGFR were defined as eGFR2017 − eGFR2012. ResultsAfter adjusting for covariates including baseline eGFR, lower serum levels (1st tertile) of miR-126 were associated with a greater decline of eGFR (β [SE] = −3.18 [1.50]) and a higher odds ratio (OR) of CKD onset over five years (OR [95% CI] = 3.85 [1.01–16.8]), compared with the 3rd tertile. ConclusionsWe found baseline serum miR-126 levels were associated with changes in eGFR and new CKD cases in a five-year prospective study. This result suggests that miR-126 may be a potential biomarker of CKD even among general populations.

Clinical significance of serum miR-21, CA153 and CEA in breast cancer

Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study. Methods: The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electro chemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three. Results: the serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P

High HBV Load Weakens Predictive Effect of Serum miR-122 on Response to Sorafenib in Hepatocellular Carcinoma Patients.

Background MiR-122 is a liver-specific microRNA. The aim of the study was to explore the association of serum miR-122 with response to sorafenib in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) patients and to further reveal the effect of the virus load on such potential relationship. Methods A total of 588 patients with HCC were retrospectively included. All of them were diagnosed with HBV-related locally advanced HCC and were treated with sorafenib. Therapeutic and prognostic information and other information were collected from medical records. Stored blood specimens that were obtained before sorafenib treatment were adopted to detect miR-122. Results The patients were divided into high-level group and low-level group according to the median of serum miR-122 level, and each group contained 294 patients. During the first 24 weeks after sorafenib treatment, the patients in the high-level group had more opportunities to experience progression-free survival (PFS) and overall survival (OS) than those in the low-level group (HR: 2.47, 95%CI: 1.24∼4.88; HR: 1.20, 95%CI: 1.09∼1.32). In the subgroup analysis, the relationship between serum miR-122 level and overall survival still existed in the patients with relatively lower HBV load (HR: 1.22, 95%CI: 1.09∼1.36), but not in the patients with higher HBV load (HR: 1.12, 95%CI: 0.93∼1.35). Conclusion Higher serum level of miR-122 at baseline was associated with a better response to sorafenib in HBV-related locally advanced HCC patients, and relatively high HBV load weakened such predictive effect mentioned above.

Analysis of Serum MicroRNA-122 Expression at Different Stages of Chronic Hepatitis B Virus Infection.

Objective To investigate the expression of microRNA-122 (miR-122) in the progression of chronic hepatitis B virus- (HBV-) infected liver diseases, thus determining the role of serum miR-122 as a marker of HBV-caused liver injury. Methods Sera were collected from patients with different stages of HBV infection (n = 63) and healthy volunteers (n = 11). And the serum miR-122 levels were detected using RT-qPCR. Moreover, an analysis was applied for identifying the specific correlation of the miR-122 level with HBV DNA, HBeAg, and ALT levels. After liver biopsy, Ishak scoring was utilized for evaluation of the fibrosis stage and the histological activity index (HAI). Results We confirmed, in the serum, increased miR-122 expression in HBV-infected patients and its highest expression in chronic HBV carriers, based on such comparison between the healthy controls and patients. The correlation analysis results were taken as confirmation of the positive relationship of miR-122 with HBV DNA (r = 0.354, P = 0.005) and ALT (r = 0.331, P = 0.009). But no correlation of this molecule with HBeAg levels was found (P = 0.187). In comparison with the HBeAg-negative patients, serum miR-122 expression showed an increase in the HBeAg-positive patients (P = 0.001). miR-122 expression, in addition, was of a significant correlation with HAI, but not with the liver fibrosis score. Conclusion The peak of the serum miR-122 expression normally occurs in the early stage of the progression from the HBV carrier phase to chronic hepatitis to cirrhosis. This molecule can be considered as a marker for evaluation of HBV-caused liver injury.

Hematocrit-Related Alterations of Circulating microRNA-21 Levels in Heart Failure Patients with Reduced Ejection Fraction: A Preliminary Study.

Aim: Circulating microRNA-21 (miR-21) has been utilized as a diagnostic tool in the assessment of heart failure (HF). Blood constitution may be altered when HF occurs and miR-21 may affect hematopoiesis. Sample hemolysis may influence the determination of circulating miRNAs, challenging the diagnostic use of miRNAs. Methods: We examined the relationship between blood measurements and miR-21 levels in ambulant chronic HF patients with reduced ejection fraction (HFrEF; n = 19). Healthy volunteers (n = 11) served as controls. Serum miR-21 levels were measured through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and we calculated the hemolysis score (H-score). Study was approved by an Institutional Review Board (EK FaF UK 02/2018). Results: MiR-21 serum levels were reduced in HFrEF patients compared with the controls (p < 0.05), without relationship to New York Heart Association class, left ventricular ejection fraction or N-terminal prohormone of brain natriuretic peptide levels. MiR-21 levels decreased markedly in anemic patients, compared with those with normal hematocrits (p < 0.05). We found a significant relationship between miR-21 to hematocrit (p < 0.05) and hemoglobin concentration (p < 0.05). Importantly, we found a correlation between hematocrit and sample H-score (p < 0.05) in the cohort of HFrEF patients; however, there was no correlation between hemolysis and miR-21. Conclusion: Circulating miR-21 levels were decreased in HFrEF patients and hematocrit was identified as a factor associated with this abnormality. This suggests that miR-21 mirrors other characteristics of HFrEF patients rather than the standard identifiers of HF severity and progression.

Clinical significance of serum mir-21,ca153 and cea in breast cancer

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: The serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P&lt;0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Assessing Determinants of the Current Account Deficit: A case study of India

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: the serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P&lt;0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Evaluation of miR-122 Serum Level and IFN-λ3 Genotypes in Patients with Chronic HCV and HCV-Infected Liver Transplant Candidate.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease. We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease. MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured. ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage. miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Preintervention MCP-1 serum levels as an early predictive marker of tumor response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BackgroundTransarterial chemoembolization (TACE) is a widely accepted treatment for unresectable or intermediate-stage hepatocellular carcinoma (HCC). However, response rates to TACE are heterogeneous and it is not fully understood which patients benefit most from TACE therapy in terms of tumor response. To identify the possible predictive roles of the perioperative monocyte chemoattractant protein-1 (MCP-1) levels in patients of HCC treated with TACE.MethodsForty patients of HCC receiving TACE were enrolled in a single center prospective observational study. MCP-1 and miR-210 levels were measured in 40 HCC patients at baseline before TACE and compared with 17 healthy controls by immunoassay and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Tumor response assessments were taken after TACE treatment 4–6 weeks. Univariate and multivariate analysis were conducted to analyze factors correlated with tumor response in a Logistic regression model. The predictive roles of the involved variables on tumor response in patients with HCC suffering TACE were examined by receiver operating characteristic (ROC) curve analysis.ResultsThe serum MCP-1 and miR-210 levels were significantly elevated in HCC patients compared to healthy subjects. Patients with the low preintervention MCP-1 and miR-210 levels attained a higher probability of achieving an objective response (OR) (88.5% vs.42.9%, P=0.007; 76.9% vs. 35.7%, P=0.010, respectively). Pre-TACE MCP-1 level (<816.63 pg/mL) was an independent risk factor associated with OR after TACE by univariate and multivariate analysis while Pre-TACE miR-210 level (<4.43 relative expression) was just positive by univariate analysis. ROC curve analysis showed that a combined index based on those two factors exhibited optimal predictive power of tumor response among all the involved variables (area under the curve =0.823, 95% CI: 0.681–0.965). Additionally, high pre-TACE serum MCP-1 level was correlated with cirrhosis, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage. Elevated pre-TACE serum miR-210 level was associated with and BCLC stage.ConclusionsThe study demonstrates that the pre-TACE serum MCP-1 level serves as an effective predictor for tumor response. These findings probably help discriminate HCC patients pre-TACE who specially benefit from TACE regarding OR.

Podocyte Injury Through Interaction Between Tlr8 and Its Endogenous Ligand miR-21 in Obstructed and Its Collateral Kidney.

While chronic kidney disease is prevalent in adults, obstructive nephropathy (ON) has been reported in both young and old patients. In ON, tubulointerstitial lesions (TILs) have been widely investigated, but glomerular lesions (GLs) have been largely neglected. Here, we show a novel mechanism underlying GL development in ON in young and old mice. TILs develop earlier than GLs owing to infiltration of inflammatory cells in the tubulointerstitium, but GLs develop following the activation of Toll-like receptor 8 (Tlr8) even though the absence of inflammatory cells infiltrating the glomerulus. TLR8 and interleukin 1 beta (IL1β) proteins colocalize with reducing podocyte function markers (PFMs), indicating the activation of TLR8 signaling in injured podocytes. Furthermore, glomerular and serum levels of miR-21, an endogenous ligand for Tlr8, were higher in the ON mouse model than in the sham control. The glomerular expression of Tlr8 positively correlates with miR-21 and the downstream cytokines Il1b and Il6 and negatively correlated with PFMs (Nphs1 and Synpo). We also show the colocalization of TLR8 and IL1β proteins with reducing PFMs in both obstructed and collateral kidney of young and old mice. Furthermore, in vitro study results revealed higher expression of Tlr8 and its downstream cytokines in glomeruli from obstructed kidneys following treatment with miR-21 mimic than in the control. In conclusion, the overexpression of Tlr8 may serve as a plausible mechanism underlying GL development in ON through podocyte injury.

Serum levels of miR-223 but not miR-21 are decreased in patients with neuroendocrine tumors.

Background and aimsMicroRNAs (miRNAs) are profoundly involved into the pathophysiology of manifold cancers. Recent data suggested a pivotal role of miRNAs as biomarkers in different biological processes including carcinogenesis. However, their role in neuroendocrine tumors (NETs) is only poorly understood.MethodsWe determined circulating levels of miR-21 and miR-223 in 45 samples from patients with NET treated between 2010 and 2019 at our department and compared them to healthy controls. Results were correlated with clinical records.ResultsIn the total cohort of Patients with NET, miR-223 presented significantly lower levels compared to healthy control samples. In contrast, levels of miR-21 indicated no significant changes between the two groups. Interestingly, despite being significantly downregulated in all NET patients, concentrations of miR-223 were independent of clinical or histopathological factors such as proliferation activity according to Ki-67 index, tumor grading, TNM stage, somatostatin receptor expression, presence of functional/ non-functional disease or tumor relapse. Moreover, in contrast to data from recent publications analyzing other tumor entities, levels of miR-223 serum levels did not reflect prognosis of patients with NET.ConclusionLower concentrations of circulating miR-223 rather reflect the presence of NET itself than certain tumor characteristics. The value of miR-223 as a biomarker in NET might be limited to diagnostic, but not prognostic purposes.

Serum micro-RNA Identifies Early Stage Colorectal Cancer in a Multi-Ethnic Population.

Objective:Certain microRNAs (miR) have been previously described to be dysregulated in cancers and can be detected in blood samples. Studies examining the utility of miRs for colon cancer screening have primarily been performed in ethnically homogeneous groups of patients, thus the performance of miRs in multiethnic populations is unknown. Methods:Four miRs were selected that were shown to be aberrantly expressed in the blood or stool of patients with colorectal cancer (CRC) of various ethnicities. In this study, the ability of these miRs to discern early stage CRC was determined in a previously untested multiethnic population of 73 CRC cases and 18 controls. Results:The ratios of non-vesicular to extracellular vesicular levels of miR’s -21, -29a, and -92a were statistically and quantitatively related to CRC stage compared to controls. Conclusion:Serum levels of miR-21, miR-29a and miR-92a were able to significantly detect early stage CRC in a multiethnic and previously untested population.

Circulating miR-155, let-7c, miR-21, and PTEN levels in differential diagnosis and prognosis of idiopathic granulomatous mastitis and breast cancer.

This study investigates whether the circulating miR-155, let-7c, miR-21, and PTEN levels to be used in the differential diagnosis of patients with idiopathic granulomatous mastitis (IGM) and breast cancer (BC). Forty-five patients with BC, 50 patients with IGM, and 48 healthy volunteers were included in the study. Serum miR-21 expression was significantly higher in BC (fold change = 2.42) and IGM group (fold change = 1.33) compared to control (p < .001). Serum miR-155 and let-7c expression levels were significantly lower in both groups compared to the control group (p < .001). miR-21 expression in BC was significantly higher than IGM (fold change = 1.976; p < .001). PTEN levels in BC were significantly higher than IGM (p < .001) and significantly lower than the control group (p < .001); the IGM group was significantly lower than the control group (p < .001). In addition to radiological data, serum miR-21 and PTEN levels may be noninvasive biomarkers that can help differentiate IGM from BC. The results of the study will lead to future studies in the differential diagnosis of IGM and BC.

Effect of Whole-Brain and Intensity-Modulated Radiotherapy on Serum Levels of miR-21 and Prognosis for Lung Cancer Metastatic to the Brain.

BackgroundThe goal of the present study was to explore the influence of whole-brain radiotherapy (WBRT) and intensity-modulated radiotherapy (IMRT) on serum levels of miR-21 and prognosis for lung cancer that has metastasized to the brain.Material/MethodsTwo hundred patients with lung cancer metastatic to the brain were randomized, half to the control group and half to the observation group. The observation group received WBRT and reduced-field IMRT (WBRT+RF-IMRT) and the control group received conventional-field IMRT (CF-IMRT). The total effective rate after treatment was determined. Serum levels of miR-21 were measured before and after radiotherapy with reverse transcriptase-polymerase chain reaction. In addition, tumor marker levels were measured with enzyme-linked immunosorbent assay. The relationship between miR-21 levels and tumor marker levels was assessed with a Pearson correlation coefficient test. Five-year survival was estimated with Kaplan-Meier curves.ResultsThe total effective rate was higher in the observation group (86%) than in the control group (69%). Lower levels of miR-21 and tumor markers were seen in the observation group. Moreover, miR-21 levels were positively correlated with levels of tumor necrosis factor-α, neuron-specific enolase, SCC-Ag, and carcinoembryonic antigen. Low levels of miR-21 were associated with longer overall survival in patients with lung cancer metastatic to the brain.ConclusionsWBRT+RF-IMRT is superior to CF-IMRT for lung cancer metastatic to the brain. MiR-21 may be a marker for prediction of the efficacy of radiotherapy in this disease setting.

MicroRNA-155 is upregulated in the placentas of patients with preeclampsia and affects trophoblast apoptosis by targeting SHH/GLi1/BCL2.

The pathogenesis of preeclampsia (PE) is complicated and multiple risk factors have been associated with its occurrence. Still, the underlying molecular mechanisms involved in PE remain elusive. Aberrant apoptosis and insufficient invasion of trophoblasts have been observed and are considered vital pathological features in PE. Herein, we found that miR-155 can specifically degrade the mRNA of the Hedgehog ligand sonic hedgehog (SHH), using dual luciferase reporter assays. Quantitative real-time PCR found that administering miR-155 mimics or inhibitors could significantly decrease or increase the expression of SHH in the trophoblasts, respectively. The transcription levels of miR-155 in the placenta were higher in patients with PE compared to the levels in healthy pregnant women, as shown by quantitative real-time PCR. Serum levels of miR-155 could predict the diagnosis of PE by receiver operating characteristic curve analysis and diagnosis evaluation tests. A significant increase in apoptosis was observed after administering miR-155 in HTR8/SVneo cells cultured ex vivo, accompanied by reduced proliferation. Mechanistically, transcriptional activity and expression of GLi1 were also inhibited under treatment of miR-155, and could be recovered after supplying additional recombinant human SHH to primary trophoblasts from patients, as determined by luciferase activity assays and western blotting. We further found that inhibiting miR-155 increased the production of SHH and improved the phenotype in primary trophoblasts from patients with PE. Our data show that miR-155 regulates apoptosis of trophoblasts in PE, which has potential value for predicting PE risk and might be deemed as a therapeutic target for treating PE.

Association between circulating vascular-related microRNAs and an increase in blood pressure: a 5-year longitudinal population-based study.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and play essential roles in the pathogenesis of cardiovascular disease. Previous cross-sectional studies showed that the levels of several circulating miRNA are associated with hypertension, but there are no prospective longitudinal studies using a general population. The aim of this study is to evaluate the impact of circulating vascular-related miRNA (miR-126, miR-221, and miR-222) on changes in blood pressure and new-onset hypertension in a Japanese population. We conducted a 5-year longitudinal study using 192 health examination participants (87 men and 105 women). Serum miRNAs were measured using quantitative reverse transcription-PCR. Information regarding lifestyle and health condition was obtained using a self-administered questionnaire. Logistic regression analyses were performed to calculate odds ratios and 95% confidence intervals for new-onset hypertension in the 5-year period between the low and high group of serum miRNAs. Serum levels of miR-126, miR-221, and miR-222 were significantly and negatively associated with changes in SBP and the rate of change of SBP. Serum miR-126, miR-221, and miR-222 levels were significantly lower in new-onset hypertensive patients compared with normotensive individuals. The confounding factors adjusted odds ratios of each 1 increment in serum miR-126, miR-221, and miR-222 levels were 0.82 (95% confidence interval: 0.69-0.98), 0.79 (0.68-0.91), and 0.61 (0.46-0.81) for new-onset hypertension, respectively. Low serum levels of miR-126, miR-221, and miR-222 were associated with increased blood pressure and new-onset of hypertension. These circulating miRNAs are potential candidate biomarkers for the prediction of hypertension.

Evaluation of the Diagnostic Properties of Serum hsa-miR-223-5p in the Detection of Gastric Cancer: A Case-Control Study.

MicroRNAs (miRs) are a group of small non-coding and single-stranded RNAs of 18 to 25 nucleotides. The study of microRNAs is one of the new ways to detect cancer. In this study, the serum expression of miR-223 in patients with GC was measured and compared with the control group. This case-control study was conducted on 39 patients with GC and 39 control subjects who visited the Reza Radiotherapy and Oncology Center, Mashhad, Iran, due to gastrointestinal complaints. The demographic information was collected, and the serum levels of miR-223 were measured using the real-time PCR technique in all study subjects. The association between the GC of miR-223 and tumor staging and cancer progression was assessed. The miR-223 expression in GC patients was 3.10-fold higher than that of the control group (p<0.0001). The miR-223 expression was significantly higher in the GC stages and grades compared to the control group (p<0.0001 each). However, there was no significant effect for age, smoking, and gender on miR- 223 expression in GC and controls. At the optimal cutoff value of 0.7436, the maximal sensitivity of 89.74% and specificity of 84.62% were achieved for miR-223 (p<0.001). The sensitivity and specificity for miR-223 for differentiating low grades from high grade were 92.31% and 73.08% (p=0.0003), and for differentiating low stages from the high stage was 81.82% and 39.29% respectively (p=0.696). This study revealed that miR-223 could be considered as a non-invasive diagnostic marker in the early diagnosis of GC.

Serum Exosomal MicroRNA-21, MicroRNA-126, and PTEN Are Novel Biomarkers for Diagnosis of Acute Coronary Syndrome.

Acute coronary syndrome (ACS) is a serious threat to public health. Based on clinical manifestations, ACS can be classified into unstable angina (UA) pectoris and acute myocardial infarction (AMI). The purpose of this study was to explore the possibility of using serum exosomal microRNA (miR)-126, miR-21, and phosphatase and tensin homolog (PTEN) expression levels as biomarkers of UA and AMI and to investigate whether these levels were positively correlated with the severity of coronary stenosis based on the Gensini score. Exosomes were isolated by ultracentrifugation from the serum of 34 patients with AMI, 31 patients with UA, and 22 healthy controls. The isolated exosomes were characterized by electron microscopy and particle size analysis; exosomal identity was further confirmed by western blotting using exosome-specific antibodies. Real-time quantitative polymerase chain reaction indicated that the serum exosomal levels of miR-126 and miR-21 were significantly higher in the patients with UA and AMI than in the healthy controls. Enzyme-linked immunosorbent assay showed that the serum exosomal PTEN levels were significantly higher in the UA and AMI groups than in the control group. Receiving operating characteristic curve analysis demonstrated the diagnostic efficiency of serum exosomal miR-126, miR-21, and PTEN levels for predicting AMI and UA. In addition, the circulating exosomal miR-126 level was positively correlated with the severity of coronary artery stenosis in patients with UA and AMI based on the Gensini score.

MiR-21 and Pellino-1 Expression Profiling in Autoimmune Premature Ovarian Insufficiency.

Background Premature ovarian insufficiency (POI) represents the hypergonadotropic hypoestrogenic symptoms that result in the loss of ovarian follicles. 5-30% POI cases are suggested to be involved in autoimmune etiology. MicroRNA-21 (miR-21) plays a vital role in ovarian folliculogenesis via regulating and interacting with multiple target genes. Here, we conduct the target prediction of miR-21, identify the expression and correlation of miR-21 and its putative target Pellino-1 (Peli1), and confirm their relationship with clinical characteristics in autoimmune POI. Methods Bioinformatic analysis was conducted to screen the miR-21 putative target gene. Autoimmune POI mouse models were established by ZP3 immunization. Serum miR-21, Peli1 mRNA of peripheral blood mononuclear cells (PBMCs) and regulatory T cells (Tregs), general status, spleen Tregs ratio, inflammatory factors, ovarian endocrine function, and ovarian structure were evaluated. For autoimmune POI patients, serum miR-21, PBMCs Peli1 mRNA levels, general data, immune parameters, hormone levels, and ultrasound examinations were obtained. The correlations of miR-21 with Peli1 and clinical characteristics in patients were analyzed. Results Peli1 was selected based on four microRNA prediction databases and literature retrieval. In mouse models, serum miR-21 level, PBMCs and Tregs Peli1 mRNA, and spleen Tregs ratio were 0.61 ± 0.09, 0.12 ± 0.12, 0.27±0.23 and 4.82 ± 0.58, respectively, lower than those in the control group. In patients, miR-21 level (0.60 ± 0.14) and Peli1 mRNA (0.30 ± 0.14) were lower than those in the control group (1.01 ± 0.07 and 1.63 ± 0.54); miR-21 was positively related with Peli1, AMH, E2, the size of the uterus, and ovarian volume and negatively related with FSH, LH, and the number of positive immune parameters (AOAb, EMAb, ACL, ANA, ds-DNA, ACA, IgG, IgA, IgM, IgE, C3, and C4). Conclusions Low expressions of miR-21 and Peli1 were detected in autoimmune POI mice and patients. Positive correlation between miR-21 and Peli1 was observed in autoimmune POI patients, suggesting that miR-21 and Peli1 might be associated with the pathogenesis of autoimmune POI.

Arum conophalloides Aqueous Extract Induced Hepatotoxicity in Rat; Histopathological, Biochemical, and mir-122 Assessments.

Background Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine.ObjectiveThis study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat.MethodsFifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically.ResultsLiver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009).ConclusionThe serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.