miR-146a Expression Research Articles

Expression pattern of miR-193a, miR122, miR155, miR-15a, and miR146a in peripheral blood mononuclear cells of children with obesity and their relation to some metabolic and inflammatory biomarkers

BackgroundThe widespread presence of childhood obesity has increased considerably over three decades. The present study was designed to investigate expression patterns of miR-146a, miR-155, miR-15a, miR-193a, and miR-122 in peripheral blood mononuclear cells (PBMCs) in children who are obese along with their association with metabolic and inflammatory biomarkers.MethodsNinety test subjects were admitted. The profile of blood pressure, resting energy expenditure (REE), anthropometric measures, body composition, dietary intakes, physical activity levels, insulin, and lipid profile, fasting blood glucose (FBG), high-sensitivity C-reactive protein (hs-CRP), and pubertal stage have been measured. Total RNA (including small RNAs) was extracted from PBMCs. The expression levels of miRNAs were measured by stem-loop RT-qPCR.ResultsThe miR-155a expression level was significantly lower in obese children, children with high hs-CRP, and children with high-fat mass. Obese girls had significantly higher PBMC levels of miR-122. MiR-155a had a significant negative association with fasting insulin, HOMA-IR, and hs-CRP. There were significant positive associations between miR-193a and miR-122 expression levels and fasting insulin, HOMA-IR, and TG. MiR-15a was positively correlated with fasting insulin and HOMA-IR. Children with metabolic syndrome, insulin resistance, and high-fat mass had higher PBMC levels of miR-122 and miR-193a. Higher miR-193a and miR-122 levels were also detected in PBMCs of children with fast REE, compared to those with slow REE, and the subjects with high hs-CRP, respectively.Conclusionlower level of miR-155 expression in obese subjects and significant associations unfolds the need for more studies to detect the possible underlying mechanisms.

MicroRNAs as Biomarkers of Active Pulmonary TB Course

The spread of drug-resistant forms of TB dictates the need for surgical treatment in the complex of anti-tuberculosis measures in Russia. Most often, surgical intervention is performed in the case of pulmonary tuberculoma or fibrotic cavitary tuberculosis (FCT). This study is devoted to the search for biomarkers that characterize the course of disease in surgical TB patients. It is assumed that such biomarkers will help the surgeon decide on the timing of the planned operation. A number of serum microRNAs, potential regulators of inflammation and fibrosis in TB, selected on the basis of PCR-Array analysis, were considered as biomarkers. Quantitative real time polymerase chain reaction and receiver operating curves (ROC) were used to verify Array data and to estimate the ability of microRNAs (miRNAs) to discriminate between healthy controls, tuberculoma patients, and FCT patients. The study showed that miR-155, miR-191 and miR-223 were differentially expressed in serum of tuberculoma with "decay" and tuberculoma without "decay" patients. Another combination (miR-26a, miR-191, miR-222 and miR-320) forms a set to differentiate between tuberculoma with "decay" and FCT. Patients with tuberculoma without "decay" diagnosis differ from those with FCT in serum expression of miR-26a, miR-155, miR-191, miR-222 and miR-223. Further investigations are required to evaluate these sets on a larger population so as to set cut-off values that could be applied in laboratory diagnosis.

MiR-146a in ALS: Contribution to Early Peripheral Nerve Degeneration and Relevance as Disease Biomarker.

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive, irreversible loss of upper and lower motor neurons (UMNs, LMNs). MN axonal dysfunctions are emerging as relevant pathogenic events since the early ALS stages. However, the exact molecular mechanisms leading to MN axon degeneration in ALS still need to be clarified. MicroRNA (miRNA) dysregulation plays a critical role in the pathogenesis of neuromuscular diseases. These molecules represent promising biomarkers for these conditions since their expression in body fluids consistently reflects distinct pathophysiological states. Mir-146a has been reported to modulate the expression of the NFL gene, encoding the light chain of the neurofilament (NFL) protein, a recognized biomarker for ALS. Here, we analyzed miR-146a and Nfl expression in the sciatic nerve of G93A-SOD1 ALS mice during disease progression. The miRNA was also analyzed in the serum of affected mice and human patients, the last stratified relying on the predominant UMN or LMN clinical signs. We revealed a significant miR-146a increase and Nfl expression decrease in G93A-SOD1 peripheral nerve. In the serum of both ALS mice and human patients, the miRNA levels were reduced, discriminating UMN-predominant patients from the LMN ones. Our findings suggest a miR-146a contribution to peripheral axon impairment and its potential role as a diagnostic and prognostic biomarker for ALS.

Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.

MiR-92a and integrin expression in fibrovascular membranes in proliferative diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of vision impairment. The proliferative form of DR (PDR) involves fibrovascular membrane (FVM) formation at the vitreoretinal interface. MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play an important role in gene regulation; a single miRNA could regulate multiple genes. We previously reported that miR-92a, a suppressor of integrins α5 and αv, was downregulated in DR. Considering the integrin's role in FVM pathology and the potential involvement of miR-92a in DR, we asked a question whether miR-92a could play a critical role in FVM pathology. We collected the FVM and epiretinal membranes of individuals with PDR and macular pucker (control) undergoing pars plana vitrectomy. The frozen sections of membranes were stained for α5 and αvβ3 integrins. The miR-92a levels were assessed using real-time quantitative PCR. The FVMs of individuals with PDR stained brighter for integrin subunits α5 and αvβ3 compared to the epiretinal membranes of subjects with macular pucker. miR-92a levels were decreased in FVM subjects. In conclusion, our studies demonstrate that miR-92a decrease is associated with an increase in integrins α5 and αvβ3, thus contributing to the inflammatory milieu in PDR.

Investigating the Relationship between the Levels of IL18, RANKL Gene Expression, MicroRNA-146a and Inflammatory Factors with the Severity of COVID-19.

COVID-19 can induce lung inflammation, and inflammatory factors play an essential role in its pathogenesis. This inflammation can be controlled to a great extent by microRNAs(miRs). This study evaluated miR-146a-5p expression levels in the serum of patients with COVID-19 and their association with the expression of interleukin (IL)-18 and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes, and lung damage. patients with COVID-19 were divided into two groups: mild and severe phases. The severe phase is defined as having a positive polymerase chain reaction (PCR) for SARS-CoV2, and acute pulmonary symptoms. The subjects' demographic, clinical, and paraclinical characteristics were collected according to a pre-prepared checklist. Total RNA was isolated from all samples using the Trizol kit to assess gene expression. The extracted product was then evaluated for the expression of miR-146a and the target genes (i.e., IL-18 and RANKL) using real-time PCR. The miR-146a gene's mean expression in mild and severe patients was 0.73 and 1.89, respectively, and this difference was statistically significant between the two groups. Also, the mean Expression of the IL-18 gene, 1.37±0.38 in the mild and 2.83±0.58 in the severe groups of the disease, demonstrated a significant difference between the two groups. In contrast, the expression levels of the RANKL gene did not show a significant difference between the two groups. Therefore, it may be hypothesized that altered levels of miR-146a may contribute to the severe COVID-19 that is more commonly observed in smokers, but further research is required.

HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer

MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues, and this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence showed that knockdown of HNRNPA2B1 could significantly decrease miR-92a expression and secretion in RKO cells. HNRNPA2B1 mediated miR-92a via m6A RNA modification. These findings indicate that HNRNPA2B1-m6A RNA modification-derived MicroRNA-92a upregulation and section from the local CRC acts a candidate noninvasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis.

The miR-20a/miR-92b Profile Is Associated with Circulating γδ T-Cell Perturbations in Mild Psoriasis.

Psoriasis vulgaris (PV) is an autoinflammatory dermatosis of unknown etiology. Current evidence suggests a pathogenic role of γδT cells, but the growing complexity of this population has made the offending subset difficult to pinpoint. The work on γδTCRint and γδTCRhi subsets, which express intermediate and high levels of γδTCR at their surface, respectively, is particularly scarce, leaving their inner workings in PV essentially unresolved. We have shown here that the γδTCRint/γδTCRhi cell composition and their transcriptom are related to the differential miRNA expression by performing a targeted miRNA and mRNA quantification (RT-qPCR) in multiplexed, flow-sorted γδ blood T cells from healthy controls (n = 14) and patients with PV (n = 13). A significant loss of miR-20a in bulk γδT cells (~fourfold decrease, PV vs. controls) largely mirrored increasing Vδ1-Vδ2- and γδintVδ1-Vδ2- cell densities in the bloodstream, culminating in a relative excess of γδintVδ1-Vδ2- cells for PV. Transcripts encoding DNA-binding factors (ZBTB16), cytokine receptors (IL18R1), and cell adhesion molecules (SELPLG) were depleted in the process, closely tracking miR-20a availability in bulk γδ T-cell RNA. Compared to controls, PV was also associated with enhanced miR-92b expression (~13-fold) in bulk γδT cells that lacked association with the γδT cell composition. The miR-29a and let-7c expressions remained unaltered in case-control comparisons. Overall, our data expand the current landscape of the peripheral γδT cell composition, underlining changes in its mRNA/miRNA transcriptional circuits that may inform PV pathogenesis.

CircRNA-ZCCHC14 affects the chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells by regulating GREM1 through miR-181a

circRNAs play an important role in the progression of osteoarthritis (OA). Therefore, we aimed to reveal the mechanism of action of circRNA-ZCCHC14 in OA. OA animal and cell models were constructed, and clinical samples were collected. The expression of circRNA-ZCCHC14 and miR-181a was detected by RT‒qPCR. The chondrogenic differentiation ability of peripheral blood-derived mesenchymal stem cells (PBMSCs) was detected by Alcian blue staining. The expression of chondrogenic differentiation-related proteins was detected by Western blotting. Double fluorescein experiments verified the targeting relationship of miR-181a with circRNA-ZCCHC14 and GREM1. Upregulation of circRNA-ZCCHC14 was observed in blood, in BMP-2- and TGF-β3-treated PBMSCs from OA patients and in animal models. Knockdown of circRNA-ZCCHC14 promoted the chondrogenic differentiation ability of PBMSCs. circRNA-ZCCHC14 was found to bind to miR-181a and negatively regulate miR-181a expression. Inhibition of miR-181a reversed the promoting effect of circRNA-ZCCHC14 knockdown on the chondrogenic differentiation ability of PBMSCs. GREM1 was identified as a target of miR-181a. Overexpression and knockdown of GREM1 regulated the expression of BMP2, which in turn affected the chondrogenic differentiation ability of PBMSCs, indicating that GREM1 and BMP2 have antagonistic effects and that they jointly regulate the chondrogenic differentiation of PBMSCs. circRNA-ZCCHC14 may promote the chondrogenic differentiation ability of PBMSCs by regulating miR-181a and inhibiting the expression of GREM1.

Circulating miR-451a Expression May Predict Recurrence in Atrial Fibrillation Patients after Catheter Pulmonary Vein Ablation.

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

MiR-146a-5p Contributes to Microglial Polarization Transitions Associated With AGEs.

M1/M2 polarization transitions of microglial phenotypes determine the states of neuroinflammation, which is critical in the pathophysiology of diabetic encephalopathy. This study aims to investigate the effects of advanced glycation end products (AGEs) on the microglial polarization state, the role of miR-146a-5p in the regulation of microglial polarization, and the underlying signaling pathways. BV-2 cells were incubated with N-ε-carboxymethyl lysine (CML), one kind of Advanced Glycation End Products (AGEs), to induce polarization. CD11b and iNOS and CD206 and Arg-1 were used to evaluate M1 and M2 microglia, respectively. The mRNA and protein expression levels of miR-146a-5p, transcription factor NF-κB, and inflammasome NLRP3 were measured. High and low expression of miR-146a-5p in the BV-2 cell line was generated by lentivirus transfection technology. RAGE, TLR-4, and NF-κB antagonists were applied to evaluate the underlying signaling pathways. Compared with the control group, CML upregulated the M1 phenotype and downregulated the M2 phenotype. These effects were reversed by overexpression of miR-146a. Furthermore, the expression of inflammasome NLRP3 and NF-κB was upregulated in the CML group and was reduced after miR-146a overexpression. And then overexpression of miR-146a effects was reversed by inhibition miR-146a expression. An NF-κB antagonist (PDTC), a RAGE antagonist (FPS-ZMI), and a TLR-4 antagonist (TLI-095) all reversed the polarization state induced by CML. In summary, CML induced polarization transitions to M1 phenotype and promoted inflammasome NLRP3 expression in BV-2 cells. The RAGE or TLR-4/miR-146a/NLRP3/NF-кB pathway might participate in the regulation of CML-induced BV-2 polarization.

MiR-92a regulates PTEN/Akt signaling axis to promote paclitaxel resistance in ovarian cancer cells.

To investigate the function and possible mechanism of miR-92a in malignant behaviors such as paclitaxel resistance in ovarian cancer (OC) cells. The miR-92a and PTEN expression were detected by real-time PCR (RT-PCR). The cell viability and apoptosis were detected by MTT, colony formation and flow cytometry assay, respectively. Dual-luciferase reporter assay was adopted to verify the targeting relationship between miR-92a and PTEN. Besides, we measured the relative protein levels of PTEN and p-AKT/AKT by Western blot. MiR-92a was significantly highly expressed in OC cells, and its high expression could notably enhance paclitaxel resistance, cell proliferation and colony formation, as well as inhibit apoptosis in SKOV3-Tax cells. Further luciferase reporter assay and expression detection showed that miR-92a could target and regulate PTEN and that there was a targeted relationship between them. In addition, further exploration of the mechanism revealed that miR-92a regulated PTEN/Akt signaling pathway. MiR-92a not only promotes the proliferation, colony formation and paclitaxel resistance of SKOV3-Tax cells in OC, but also inhibits apoptosis, and it may be related to the regulation of the PTEN/Akt signaling pathway. MiR-92a serves as a potential biomarker for the malignant biological behavior of OC cells.

MicroRNA Expression in Subretinal Fluid in Eyes Affected by Rhegmatogenous Retinal Detachment.

Proliferative vitreoretinopathy (PVR) is an abnormal intraocular scarring process that can complicate cases of rhegmatogenous retinal detachment (RRD). Although previous studies have examined the relevance of microRNAs (miRNAs) in ophthalmic diseases, only a few studies have evaluated the expression profiles of microRNAs in subretinal fluid. We hypothesized that the expression profiles of specific miRNAs may change in response to RRD, in the subretinal fluid that is directly in contact with photoreceptors and the retinal pigment epithelium (RPE). We looked for a potential correlation between the expression of specific miRNAs in eyes with RRD and known clinical risk factors of PVR. A total of 24 patients (59 ± 11 years) who underwent scleral buckling procedure were enrolled in this prospective study. Twenty-four undiluted subretinal fluid samples were collected, RNA was isolated and qRT-PCR was performed to analyze the expression of 12 miRNAs. We found the existence of a positive association between the expression of miR-21 (p = 0.017, r = 0.515) and miR-34 (p = 0.030, r = 0.624) and the duration of symptoms related to retinal detachment. Moreover, the expression of miR-146a tended to decrease in patients who developed PVR. Subretinal fluid constitutes an intriguing biological matrix to evaluate the role of miRNAs leading to the development of PVR.

Oxymatrine-induced Apoptosis in Fibroblasts like Synoviocytes via Regulation of miR-146a/ TRAF6/JNK1 Axis in Rheumatoid Arthritis

Objective: Rheumatoid Arthritis (RA) is made when the synovial tissues and joints are destroyed by the inflammation refection, especially the chronic inflammation. The RA-FLS was treated with Oxymatrine, and the influence of miR-146a and TRAF6 /JNK pathway was explored. Method: Oxymatrine -treated RA-FLS were harvested to detect cell viability by CCK-8. The expression of miR-146a was detected by qRT-PCR. The expression of IRAK1, TRAF6, JNK1, and p-JNK1 was obtained by Western blot. Results: The optimum oxymatrine concentration inhibiting RA-FLS was 4mg/ml at 48h. The expression of miR-146a at 48h and 72h was higher than 0 and 24h in RA-FLS treated with 4mg/ml oxymatrine. IRAK1, TRAF6, and p-JNK at 48h and 72h were lower than 0 and 24h in RA-FLS treated with 4mg/ml oxymatrine. When the miR-146a was inhibited, the expression of miR-146a was very low in the miR- 146a inhibitor group. No matter whether oxymatrine existed, the expression of IRAK1, TRAF6, and p- JNK in the miR-146a inhibitor group with or without oxymatrine was higher than the mock group, blank group, and only oxymatrine added group. The cell viability in the miR-146a inhibitor group and oxymatrine + miR-146a inhibitor group was higher than in the other groups. When IRAK1 was over expressed, the expression of miR-146a in the oxymatrine + IRAK1 overexpression group was higher than in the IRAK1 overexpression group. However, The expression of IRAK1, TRAF6, and p-JNK1 in the IRAK1 overexpression group with or without oxymatrine was higher than the pcDNA3.1 group, blank group, and only oxymatrine added group. The cell viability in the IRAK1 overexpression group and oxymatrine + IRAK1 overexpression group was higher than in the other groups. Conclusion: Oxymatrine can inhibit RA-FLS proliferation via miR146a and IRAK1/TRAF6/JNK1 axis. Hence, oxymatrine may be a drug or adjuvant drug to treat RA in the future.

Discovery of miRNA and target signal molecules involved in inhibition of chlorogenic acid on N-acetyl-p-aminophenol-induced hepatotoxicity based on microRNA array

This study aims to observe the effect of chlorogenic acid(CGA) on microRNA(miRNA) in the process of protecting against N-acetyl-p-aminophenol(APAP)-induced liver injury. Eighteen C57BL/6 mice were randomly assigned into a normal group, a model group(APAP, 300 mg·kg~(-1)), and a CGA(40 mg·kg~(-1)) group. Hepatotoxicity of mice was induced by intragastric administration of APAP(300 mg·kg~(-1)). The mice in the CGA group were administrated with CGA(40 mg·kg~(-1)) by gavage 1 h after APAP administration. The mice were sacrificed 6 h after APAP administration, and plasma and liver tissue samples were collected for the determination of serum alanine/aspartate aminotransferase(ALT/AST) level and observation of liver histopathology, respectively. MiRNA array combined with real-time PCR was employed to discover important miRNAs. The target genes of miRNAs were predicted via miRWalk and TargetScan 7.2, verified by real-time PCR, and then subjected to functional annotation and signaling pathway enrichment. The results showed that CGA administration lowered the serum ALT/AST level elevated by APAP and alleviate the liver injury. Nine potential miRNAs were screened out from the microarray. The expression of miR-2137 and miR-451a in the liver tissue was verified by real-time PCR. The expression of miR-2137 and miR-451a was significantly up-regulated after APAP administration, and such up-regulated expression was significantly down-regulated after CGA administration, consistent with the array results. The target genes of miR-2137 and miR-451a were predicted and verified. Eleven target genes were involved in the process of CGA protecting against APAP-induced liver injury. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment with DAVID and R language showed that the 11 target genes were enriched in Rho protein-related signal transduction, vascular patterning-related biological processes, binding to transcription factors, and Rho guanyl-nucleotide exchange factor activity. The results indicated that miR-2137 and miR-451a played an important role in the inhibition of CGA on APAP-induced hepatotoxicity.

Therapeutic treatment with fluoxetine using the chronic unpredictable stress model induces changes in neurotransmitters and circulating miRNAs in extracellular vesicles

The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.

MiR-10a Ameliorates Renal and Myocardial Injury in Sepsis Through Regulation of PI3K/AKT Signaling

miR-10a participates in the prognosis of patients with sepsis, which also influence multiple organs and cause damages to the kidney and myocardial tissues. This study intends to assess miR-10a’s role in sepsis-induced renal and myocardial injury. 50 Wistar rats were randomized into sham-operation group, model group, MiR-10a group, positive control group and PI3K/AKT-agonist group (n = 10) followed by analysis of the histopathological changes of myocardial and renal tissues, kidney injury, expression of renal GR-α and CK-MB/CK, levels of inflammatory factors (IL-10, IL-6, IL-1β and TNF-α) and the level of miR-10a, PI3K and AKT. Rats in model group and PI3K/AKT-agonist group exhibited highest pathological score of kidney injury, expression of CK-MB, CK and renal GR-α, followed by rats in positive control group and miR-10a group. Furthermore, model group and PI3K/AKT-agonist group showed the highest level of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-10), followed by positive control group and miR-10a group. Lowest miR-10a expression and highest mRNA levels of PI3K and AKT was detected in model group, PI3K/AKT-agonist group and positive control group, followed by miR-10a group. PI3K is a target of miR-10a. In conclusion, miR-10a alleviates the sepsis-induced renal and myocardial injury mainly by mediating the PI3K/AKT transduction pathway, indicating that miR-10a can be utilized as a target gene for sepsis treatment.

The immunomodulatory effect of intradermal allogeneic PBMC therapy in patients with recurrent spontaneous abortion

BackgroundThere has been limited study on the impact of PBMC therapy in RSA patients with immunological disorders such as Th17 and Treg cell dysregulation, as well as their associated factors. This study aimed to assess the efficacy of PBMC therapy in modulating immune cell frequency, cytokine production, transcription factors, and miRNAs implicated in the regulation of their function, as well as their potential superiority to routine treatments. MethodsFifty RSA women who had received PBMCs and 50 matched-paired control RSA women who had received the routine treatments were recruited and followed for three months. The frequencies of Th17, Treg, NK, and B cells were assessed using flow cytometry. Thereafter, the gene expression level of the transcription factors and related miRNAs of Treg cell and Th17 cell was quantified using RT-PCR. Then ELISA was employed to assess the cytokine production of Th17 and Treg cells. Finally, the live birth rate and miscarriage rate were evaluated as clinical outcomes in this study. ResultsFlow cytometry analysis revealed that PBMC therapy significantly reduces the frequencies of Th17 and NK cells while enhancing the frequency of Treg cells. RT-PCR analysis confirmed that PBMC therapy significantly downregulates RORγt and upregulates FoxP3. Likewise, RT-PCR analysis showed that PBMC therapy reduces the expression of miR-25, miR-155, and miR-326 while increasing the expression of miR-10a. ELISA results demonstrated that PBMC therapy considerably decreases the concentration of inflammatory cytokines IL-1β, IL-17, and TNF-α and enhances the concentration of anti-inflammatory cytokines IL-10 and TGF-β. Following PBMC therapy live birth rate raised while miscarriage rate reduced. ConclusionOur findings suggested that, in contrast to routine treatments, PBMC therapy can significantly modulate the maternal immune system by enhancing the Treg/Th17 paradigm and regulating the expression of Treg and Th17 cell-associated cytokines, transcription factors, and miRNAs. This treatment also can increase the live birth rate in RSA patients.

Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis.

The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

A Group of Tumor-Suppressive micro-RNAs Changes Expression Coordinately in Colon Cancer.

MicroRNAs (miRNAs) are molecules with a role in the post-transcriptional regulation of messenger RNA, being involved in a wide range of biological and pathological processes. In the present study, we aim to characterize the behavior of a few miRNAs with roles in the cell cycle and differentiation of colon cancer (CC) cells. The present work considers miRNAs as reflections of the complex cellular processes in which they are generated, their observed variations being used to characterize the molecular networks in which they are part and through which cell proliferation is achieved. Tumoral and adjacent normal tissue samples were obtained from 40 CC patients, and the expression of miR-29a, miR-146a, miR-215 and miR-449 were determined by qRT-PCR analysis. Subsequent bioinformatic analysis was performed to highlight the transcription factors (TFs) network that regulate the miRNAs and functionally characterizes this network. There was a significant decrease in the expression of all miRNAs in tumor tissue. All miRNAs were positively correlated with each other. The analysis of the TF network showed tightly connected functional modules related to the cell cycle and associated processes. The four miRNAs are downregulated in CC; they are strongly correlated, showing coherence within the cellular network that regulates them and highlighting possible approach strategies.