Expression Levels Of miR-34a Research Articles

Unraveling the Exosome-miR-133a Axis: Targeting TGF-β Signaling via WJ-MSC-Derived Exosomes for Anti-Fibrotic Therapy in Liver Fibrosis.

One of the primary drivers of liver fibrosis is the excessive accumulation of ECM, primarily caused by the over-proliferation of HSCs. The activation of HSCs by TGF-β has a critical role in initiating fibrosis. Recent studies have suggested that miRNA-133a significantly regulates the fibrogenesis process, which its downregulation is associated with the fibrosis progression. Understanding the role of miRNA-133a provides potential therapeutic insights for targeting TGF-β signaling and mitigating liver fibrosis. We investigated whether exosomes could attenuate liver fibrosis by enhancing the antifibrotic effects of miR-133a. The LX-2 cell line was treated with TGF-β for 24 hours, followed by an additional 24 hours of treatment with exosomes. After this treatment period, we assessed the mRNA expression levels of α-SMA, collagen 1, and miR-133a, as well as the protein levels of p-Smad3. TGF-β exposure significantly increased the expression level of α-SMA and collagen 1 genes and elevated the levels of p-Smad3 protein. Additionally, it resulted in a significant downregulation of miR-133a compared to the control group. Exosome administration effectively reduced the TGF-β-induced upregulation of p-Smad3, α-SMA, and collagen 1 genes, but increased miR-133a expression levels. Our findings indicate that by partially mitigating the downregulation of miR-133a, exosomes can effectively inhibit the persistent activation of HSCs. Furthermore, in the context of in vitro liver fibrosis, exosomes can suppress the TGF-β/Smad3 pathway, reducing the accumulation of ECM.

MicroRNA-34a and promoter methylation contribute to peroxisome proliferator-activated receptor gamma gene expression in patients with type 2 diabetes

AimsThis study aimed to investigate the roles of DNA methylation and miR-34a in the regulation of peroxisome proliferator-activated receptor gamma (PPARγ) in patients with type 2 diabetes (T2D). MethodsWe investigated the methylation status of four regions of the PPARγ promoter and PPARγ expression in a panel of 84 T2D patients using methylation-specific PCR (MSP) and RT-qPCR, respectively. Moreover, we quantified DNA methyltransferases (DNMTs) expression and global DNA methylation levels by RT-qPCR and ELISA, respectively. We measured the expression levels of miR-34a and protein expression of PPARγ by stem-loop RT-qPCR and ELISA, respectively. ResultsWe found significant DNA hypermethylation in the R2 and R3 regions of the PPARγ promoter in people with diabetes. Functionally, this was associated with a significant reduction in PPARγ expression. In addition, we observed a significant increase in 5-methylcytosine levels in people with diabetes. A marked increase in circulating miR-34a in the early stages of T2D (up to 10 years) and a significant decrease in circulating miR-34a with increasing diabetes duration from 10 years after the onset of diabetes. Interestingly, upregulation of DNA methyltransferases 1 (DNMT1), DNMT3A, and DNMT3B was observed in people with diabetes, and the average expression of DNMTs was negatively correlated with circulating miR-34a levels. In contrast, the serum protein level of PPARγ, a direct target of miR-34a, increased considerably with diabetes duration and showed a negative correlation with circulating miR-34a, cholesterol, triglyceride, and low-density lipoprotein. ConclusionPPARγ promoter hypermethylation and miR-34a upregulation are associated with T2D pathogenesis through PPARγ dysregulation.

Major considerations on the relationship of triple negative breast cancer with microRNAs and nutrological triggers: a systematic review

Introduction: Triple-negative breast cancer (TNBC) accounts for 15% of all cases. Its incidence is usually higher in young women (under 40 years of age). The classification as triple-negative occurs because, in this case, there are no estrogen, progesterone, and HER2 receptors, which are responsible for controlling tumor growth. Higher levels of physical activity and better diet quality are associated with lower mortality from breast cancer in observational studies. Furthermore, physical activity and optimal nutrition can improve the relative dose intensity of chemotherapy, as they can activate miRNAs that regulate several biological processes. Objective: This was to conduct a systematic review to establish the main considerations of the relationship between triple-negative breast cancer and microRNAs as biomarkers and regulators of gene expression in cancer cells, as well as to show some nutritional triggers of microRNA activation desirable for breast cancer control. Methods: The PRISMA Platform systematic review rules were followed. The search was conducted from April to June 2024 in the Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE and AMSTAR-2 instrument and the risk of bias was analyzed appropriately. According to the Cochrane instrument. Results and Conclusion: 112 articles were found, and 40 were evaluated in full and included in this article, 22 of which were included in the systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 15 studies with a high risk of bias and 25 studies that did not reach GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=81.5%>50%. It was concluded that an increasing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), play a significant role in tumorigenesis. Although a diet and exercise intervention did not affect relative dose intensity, the intervention was associated with a higher pCR in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy. High expression levels of miR-27a/b, miR-210, and miR-454 were associated with shorter overall survival, whereas high expression levels of miR-454 and miR-374a/b were associated with disease-free survival. The miRNAs associated with triple-negative breast cancer may provide new avenues for early diagnosis and treatment of breast cancer. Furthermore, specific miRNAs may serve as potential prognostic biomarkers in triple-negative breast cancer.

Evaluating the Serum Level of ACTH and Investigating the Expression of miR-26a, miR-34a, miR-155-5p, and miR-146a in the Peripheral Blood Cells of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder affecting white and gray matter. This study aimed to investigate the association between clinical outcomes in MS patients and the levels of certain molecules in their serum, including ACTH, IL-17, and specific miRNAs: miR-26a, miR-34a, miR-155-5p, and miR-146a. Fifty healthy people and 75 blood samples from MS patients were selected. MS patients had higher expression levels of IL-17, miR-26a, miR-34a, and miR-146a compared to healthy individuals (p < 0.0001). There was no significant difference in miR-155-5p expression between the two groups (p = 0.203). MS patients also had higher serum levels of ACTH compared to the normal population (p < 0.0001). In MS patients, there was a negative correlation between IL-17 and miR-155-5p expression levels (p = 0.048, r = - 0.229). Similarly, a significant negative correlation was observed between ACTH and miR-155-5p in the control group (p = 0.044, r = - 0.286). The study's analysis revealed no significant difference in the expression of miR-155-5p between MS patients and normal individuals; the study's examination revealed that the expression level of IL-17, miR-26a, miR-34a, and miR-146a was higher in MS patients than in normal individuals.

Oxaliplatin activates P53/miR-34a/survivin axis in inhibiting the progression of gastric cancer cells.

The purpose of this research was to determine how the P53/microRNA-34a (miR-34a)/survivin pathway contributes to oxaliplatin-induced (L-OHP) cell inhibition in gastric cancer. The BGC-823 gastric cancer cells were selected, and we examined their viability following treatment with L-OHP at different concentrations and time periods. The expression levels of miR-34a, P53, and survivin in the cells were determined. In the 12- and 24-h groups, drug concentration of 15 μg/cm² (p < .005 in both) significantly lowered cell viability. In comparison to the control group, miR-34a mRNA expression, P53 mRNA expression, and protein expression were all significantly greater in the 24-h group (p = .0324, p = .0069, p = .0260, respectively), but survivin mRNA and protein expressions were significantly lower than those in the control group (p = .0338, p = .0032, respectively). There was a significant decrease in gastric cancer cells in the miR-34a overexpression group (p = .0020), a significant increase in P53 mRNA and protein expression compared to the control group (p = .0080, p = .0121, respectively), and a significant decrease in survivin mRNA and protein expression compared to the control group. (p = .0213, p = .0069, respectively). Oxaliplatin inhibits tumor growth, invasion, and metastasis by upregulating miR-34a, activating the expression of the upstream P53 gene, and driving the downregulation of survivin (P53/miR-34a/survivin axis) in BGC-823 gastric cancer cells.

Inflamma-miRs Profile in Myelodysplastic Syndrome Patients.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.

The involvement of circulating miR-146a and miR-27a in patients with atherosclerotic cardiovascular disease after SARS-CoV-2 infection.

Atherosclerotic cardiovascular disease (ASCVD) is a group of clinical diseases based on pathology of atherosclerosis that is the leading cause of mortality worldwide. There is a bidirectional interaction between ASCVD and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alterations in circulating miRNAs levels are involved in the development of ASCVD in patients infected with SARS-CoV-2, however, the correlation between ASCVD co-infection with SARS-CoV-2 and alterations of cardiac-specific miRNAs is not well understood. The circulating miR-146a and miR-27a are involved in bidirectional interactions between ASCVD and SARS-CoV-2 infections. Circulating miR-146a and miR-27a levels were measured in serum and PBMCs deriving from ASCVD patients and controls after SARS-CoV-2 infection by qRT-PCR analysis. The levels of neutralizing antibodies-resistant SARS-CoV-2 in human serum was determined by competitive magnetic particle chemiluminescence method. Interleukin (IL)-6 levels were detected by automatic biochemical analyzer using electrochemiluminescence. Significant downregulation of circulating miR-146a and upregulation of miR-27a in ASCVD patients after infection with SARS-CoV-2 compared with controls were observed, among which the alterations were more evident in ASCVD patients comorbid with hyperlipidemia and diabetes mellitus. Consistently, correlation analysis revealed that serum miR-146a and miR-27a levels were associated with the levels of lipids and glucose, inflammatory response, and immune function in ASCVD patients. Remarkably, SARS-CoV-2 S protein RBD stimulation of PBMCs derived from both ASCVD and controls significantly downregulated miR-146a, upregulated miR-27a expression levels, and promoted IL-6 release in vitro. The circulating miR-146a and miR-27a are involved in metabolism, inflammation, and immune levels in patients with ASCVD after SARS-CoV-2 infection, laying the foundation for the development of strategies to prevent the risk of SARS-CoV-2 infection in ASCVD patients.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.

This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Effects of Multi-species Synbiotic Supplementation on Circulating miR-27a, miR-33a Levels, and Lipid Parameters in Adult Men with Dyslipidemia; A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

MicroRNAs (miRNAs) have emerged as important regulators of lipid metabolism. Recent studies have suggested synbiotics may modulate miRNA expression and lipid metabolism. This study aimed to investigate the effects of synbiotic supplementation on circulating miR-27a, miR-33a, and lipid parameters in patients with dyslipidemia. Fifty-six eligible participants were randomly allocated to receive either synbiotic or placebo sachets twice a day for 12 weeks. Each synbiotic sachet contained 3×1010 CFU six species of probiotic microorganisms and 5 grams of inulin and fructooligosaccharide (FOS) as prebiotics. Serum miR-27a and miR-33a expression levels, serum lipids, and apolipoproteins, the fecal concentration of short-chain fatty acids (SCFAs), and Firmicutes and Bacteroidetes phyla were assessed before and after the study. Real-time PCR was used to determine the relative expression levels of miRNAs. The results showed synbiotic supplementation significantly downregulated the expression levels of miR-27a and miR-33a compared to the placebo group (p = 0.008 and p = 0.001, respectively). Furthermore, the intervention group exhibited significant improvements in serum high-density lipoprotein (HDL-C), small dense low-density lipoprotein (sdLDL-C), apoA-I, and apoB-100 (p = 0.008, p = 0.006, p = 0.003, p = 0.001, respectively). The results showed a significant negative correlation between miR-33a expression levels with HDL-C, butyrate, propionate, and a significant positive correlation with total cholesterol (TC), low-density lipoprotein (LDL-C), and sdLDL-C in the intervention group. Fecal bacteria and SCFAs were significantly increased in the intervention group. This study provides evidence that synbiotic supplementation can modulate miR-27a and miR-33a expression and improve lipid metabolism in patients with dyslipidemia.

Serum miR-124a and miR-34a as Potential Biomarkers for Rheumatoid Arthritis

Abstract Background: MicroRNAs (miRs) are defined as noncoding small RNAs that are involved in the regulation of various immune functions, indicating they could be possible biomarkers for immune-mediated disorders. We aimed to evaluate miR-124a and miR-34a levels in serum as diagnostic biomarkers for rheumatoid arthritis (RA) and to investigate their correlation with the disease activity in RA patients. Methods: Our study consisted of 40 patients with RA and 40 controls. The disease activity for the RA patients was evaluated using the Disease Activity Score in 28 joints (DAS28). Relative quantification of miR-124a and miR-34a expressions in serum was conducted by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Expression levels of miR-124a and miR-34a in serum were significantly lower in RA patients (median: 0.64 and 0.30, respectively) compared to controls (median: 3.12 and 1.88, respectively), P &lt; 0.001. Their serum levels were negatively associated with disease activity and inversely correlated with DAS28, C-reactive protein, and erythrocyte sedimentation rate (P &lt; 0.001). Conclusion: Serum miR-124a and miR-34a could serve as potential noninvasive biomarkers for RA diagnosis and reflect the disease activity in RA patients.

The interrelation between the high expression level of MIR34a and the trisomic abortion materials.

The underlying mechanism and constitution of spontaneous abortions are complicated and heterogeneous. Many factors, including epigenetic scenarios like micro-ribonucleic acids (miRNAs, MIRs), can additively affect the progression of pregnancy losses. This study aimed to evaluate whether the expression levels of placental inhibitor and/or activator miRNAs had a difference between the numerically abnormal and normal karyotyped spontaneous abortions. The case-control study included 100 spontaneous abortion materials consisting of trophoblastic tissues with 42 disomies (controls), 43 aneuploidies (including trisomy 16, 21, 22, and monosomy X), and 15 triploidies. Disomic abortion materials with XX normal karyotypes were omitted from the study to exclude possible maternal decidual cell contamination. Total RNA isolation was performed with TRIzol™ reagent directly from frozen trophoblastic tissues, and the mature miRNAs were obtained by reverse transcription via quantitative real-time polymerase chain reaction (qRT-PCR). Then, the expression levels of placental activators MIR378a-5p, MIR376c, MIR195, and inhibitors MIR34a and MIR210 were relatively evaluated using MIR130 as a reference. The expression level of placental inhibitor MIR34a was detected to be high in trisomic abortion materials (trisomy 16 and 21) when compared to the disomic ones (p = 0.0324). MIR195 (p = 0.0484) and MIR34a (p = 0.0346) expression levels were increased in numerically abnormal cases with advanced maternal age compared to the disomic ones within all maternal ages. It seems likely that the high expression level of MIR34a and the coexistence of trisomic abortion materials are quite interrelated with the additive effect of advanced maternal age.

Acacetin inhibited non-small-cell lung cancer (NSCLC) cell growth via upregulating miR-34a in vitro and in vivo

Acacetin, one of the flavonoid compounds, is a natural product found in various plants, including Silver birch, and Damiana. Previous studies showed that acacetin has anti-cancer effects on many kinds of cancer cells, however, the role of and the mechanisms of actions of acacetin on non-small cell lung cancer (NSCLC) cells is still not fully understood. Herein, we found that, in vitro, acacetin inhibited the proliferation, invasion, and migration of NSCLC cells, A549 and H460, in a dose-dependent manner. Meanwhile, flow cytometry assay results showed that acacetin induced G2/M phase cell cycle arrest, and apoptosis of NSCLC cells. In vivo, acacetin suppressed tumor formation of A549-xenografted nude mice model with no obvious toxicities. Western blotting results showed that the protein levels of cell cycle-related proteins cyclin B1, cyclin D, and anti-apoptotic protein Bcl-2 had decreased, while the apoptosis-related protein Bak had increased both in NSCLC cells and in A549-xenografted tumor tissues. For investigating the molecular mechanism behind the biological effects of acacetin on NSCLC, we found that acacetin induced the expression levels of tumor suppressor p53 both in vitro and in vivo. MicroRNA, miR-34a, the direct target of p53, has been shown anti-NSCLC proliferation effects by suppressing the expression of its target gene programmed death ligand 1 (PD-L1). We found that acacetin upregulated the expression levels of miR-34a, and downregulated the expression levels of PD-L1 of NSCLC cells in vitro and of tumors in vivo. In vitro, knockdown p53 expression by siRNAs reversed the induction effects of acacetin on miR34a expression and abolished the inhibitory activity of acacetin on NSCLC cell proliferation. Furthermore, using agomir and antagomir to overexpress and suppress the expression miR-34a in NSCLC cells was also examined. We found that miR-34a agomir showed similar effects as acacetin on A549 cells, while miR-34a antagomir could partially or completely reverse acacetin’s effects on A549 cells. In vivo, intratumor injection of miR-34a antagomir could drastically suppress the anti-tumor formation effects of acacetin in A549-xenografted nude mice. Overall, our results showed that acacetin inhibits cell proliferation and induces cell apoptosis of NSCLC cells by regulating miR-34a.

The miR-19a/Cylindromatosis Axis Regulates Pituitary Adenoma Bone Invasion by Promoting Osteoclast Differentiation.

The presence of bone invasion in aggressive pituitary adenoma (PA) was found in our previous study, suggesting that PA cells may be involved in the process of osteoclastogenesis. miR-19a (as a key member of the miR-17-92 cluster) has been reported to activate the nuclear factor-кB (NF-кB) pathway and promote inflammation, which could be involved in the process of the bone invasion of pituitary adenoma. In this work, FISH was applied to detect miR-19a distribution in tissues from patients with PA. A model of bone invasion in PA was established, GH3 cells were transfected with miR-19a mimic, and the grade of osteoclastosis was detected by HE staining. qPCR was performed to determine the expression of miR-19a throughout the course of RANKL-induced osteoclastogenesis. After transfected with a miR-19a mimic, BMMs were treated with RANKL for the indicated time, and the osteoclast marker genes were detected by qPCR and Western Blot. Pit formation and F-actin ring assay were used to evaluate the function of osteoclast. The TargetScan database and GSEA were used to find the potential downstream of miR-19a, which was verified by Co-IP, Western Blot, and EMSA. Here, we found that miR-19a expression levels were significantly correlated with the bone invasion of PA, both in clinical samples and animal models. The osteoclast formation prior to bone resorption was dramatically enhanced by miR-19, which was mediated by decreased cylindromatosis (CYLD) expression, increasing the K63 ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Consequently, miR-19a promotes osteoclastogenesis by the activation of the downstream NF-кB and mitogen-activated protein kinase (MAPK) pathways. To summarize, the results of this study indicate that PA-derived miR-19a promotes osteoclastogenesis by inhibiting CYLD expression and enhancing the activation of the NF-кB and MAPK pathways.

The antitumour efficacy of hesperidin vs. cisplatin against non-small lung cancer cells A549 and H460 via targeting the miR-34a/PD-L1/NF-κB signalling pathway.

Lung cancer is the most common type of cancer, causing worldwide mortality. Therefore, this study is necessary for continuing research into new effective and safe treatments. Recently, herbal medicines have been used for the treatment of various diseases such as cancer. This study aimed to investigate the potential anti-proliferative activity and investigate the mechanisms of hesperidin extract on the non-small lung cancer cells A549 and H460 vs. cisplatin via targeting the miR 34a/PD-L1/NF-κB signalling pathway. To determine the cytotoxic effects of the hesperidin extract on non-small lung cancer cells, sulphorhdamine B assay was performed. To show the inhibition of migration by hesperidin extract, wound healing assay was conducted. A quantitative polymerase chain reaction test was used to quantify the expressions of miR-34a, programmed cell death ligand-1 (PDL-1), epidermal growth factor receptor (EGFR), and P53 genes, which are involved in apoptosis pathway. Also, cell cycle assay was performed by using a flow cytometer. The hesperidin extract could significantly inhibit proliferation of non-small lung cancer cells A549 and H460. Western blot assay demonstrated that hesperidin induced suppression of nuclear factor κB signalling pathway. The messenger RNA expression levels of MiR-34a and P53 were up-regulated significantly by hesperidin treatment, while the EGFR and P53 genes were down-regulated. The flow cytometer confirmed that cell cycle arrest occurred at the sub-G1 and G2 phases in A549 and H460, respectively. Our study demonstrated that hesperidin extract could significantly inhibit non-small lung cancer cell growth by induction of the apoptosis signalling pathway. Therefore, hesperidin might open novel strategies for effective and safe cancer treatment and reduce the adverse side effects of several chemotherapeutic treatments such as cisplatin.

Citronellal can alleviate vascular endothelial dysfunction by reducing ectopic miR-133a expression

Endothelial dysfunction (ED) is the initial cause of atherosclerosis (AS) and an early marker of many cardiovascular diseases (CVD). Citronellal (CT), a monoterpenoid natural product extracted from grass plant Citronella, has been shown to have anti-thrombotic, anti-hypertensive and anti-diabetic cardiomyopathy activities. The aim of this study is to investigate the effects of citronellal on vascular endothelial dysfunction and the underlying mechanisms. The left common carotid artery was subjected to one-time balloon injury to cause vascular endothelial injury, and the AS model was established by feeding with high-fat diet. Use of HUVECs H2O2 treatment induced HUVECs oxidative stress damage model. The blood lipid level, histopathology, Western blot, immunohistochemistry, RT-PCR, ELISA and in situ fluorescence hybridization of common carotid artery tissues and HUVECs were studied. CT significantly reduced vascular plate area and endothelial lipid and cholesterol deposition in the common carotid artery of mice in a dose-dependent manner. CT increased the expression of activated protein 2α (AP-2α/TFAP2A) and circRNA_102979, and inhibited the ectopic expression level of miR-133a. However, the constructed lentivirus with AP-2α silencing and circRNA_102979 silencing reversed this phenomenon. The current study verifies CT can increase the expression levels of AP-2α and circRNA_102979 in vascular endothelium, increase the adsorption effect of circRNA_102979 on miR-133a and relieve the inhibitory effect of miR-133a on target genes, thereby alleviating AS-induced ED.

The role of miR1 and miR133a in new-onset atrial fibrillation after acute myocardial infarction

BackgroundThe development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is a clinical complication that requires a better understanding of the causative risk factors. This study aimed to explore the risk factors and the expression and function of miR-1 and miR-133a in new atrial fibrillation after AMI.MethodsWe collected clinical data from 172 patients with AMI treated with emergency percutaneous coronary intervention (PCI) between October 2021 and October 2022. Independent predictors of NOAF were determined using binary logistic univariate and multivariate regression analyses. The predictive value of NOAF was assessed using the area under the receiver operating characteristic (ROC) curve for related risk factors. In total, 172 venous blood samples were collected preoperatively and on the first day postoperatively; the expression levels of miR-1 and miR-133a were determined using the polymerase chain reaction. The clinical significance of miR-1 and miR-133a expression levels was determined by Spearman correlation analysis.ResultsThe Glasgow prognostic score, left atrial diameter, and infarct area were significant independent risk factors for NOAF after AMI. We observed that the expression levels of miR-1 and miR-133a were significantly higher in the NOAF group than in the non-NOAF group. On postoperative day 1, strong associations were found between miR-133a expression levels and the neutrophil ratio and between miR-1 expression levels and an increased left atrial diameter.ConclusionsOur findings indicate that the mechanism of NOAF after AMI may include an inflammatory response associated with an increased miR-1-related mechanism. Conversely, miR-133a could play a protective role in this clinical condition.

Conjugated linoleic acid and L-carnitine combination effects on obesity-related miRNAs in diet-induced obese rats

ObjectivesObesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels. Subjects /methodsForty male Wistar rats weighing 150–200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg−1), CLA (500 mg kg−1), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software. ResultsAt the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression. ConclusionCLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment.

MiR-34a targets SIRT1 to reduce p53 deacetylation and promote sevoflurane inhalation anesthesia-induced neuronal autophagy and apoptosis in neonatal mice

This study is to investigate the function of miR-34a and interactions between miR-34a, SIRT1, and p53 in sevoflurane-induced neuronal apoptosis and autophagy in neonatal mice. A mouse model was established by inhalation anesthesia with sevoflurane and injected with genetic reagents, followed by tests of learning and memory abilities and histological staining of the hippocampus. CCK-8 and AnnexinV/PI staining respectively measured the survival and apoptosis rates of primary hippocampal neurons cultured with sevoflurane. The expression levels of miR-34a, SIRT1, p53, Ac-p53, and autophagy- or apoptosis-related proteins were measured. Sevoflurane impaired the learning and memory abilities of mice, increased TUNEL-positive cells in their hippocampus, and hindered the survival of hippocampal neurons. Sevoflurane increased miR-34a, Bax, cleaved caspase-3, and the ratio of LC3-II/LC3-I and reduced SIRT1 and p62. MiR-34a overexpression promoted sevoflurane-induced neural damage, whereas SIRT1 inhibition or p53 upregulation counteracted the neuroprotection of miR-34a knockdown. SIRT1 was a target of miR-34a and promoted p53 deacetylation. MiR-34a promotes sevoflurane-stimulated neuronal apoptosis and autophagy in neonatal mice by inhibiting SIRT1 expression and subsequent p53 deacetylation.

The protective effect of p-Coumaric acid on hepatic injury caused by particulate matter in the rat and determining the role of long noncoding RNAs MEG3 and HOTAIR.

Increasing air pollution is associated with serious human health problems. P-coumaric acid (PC) is a herbal phenolic compound that exhibits beneficial pharmacological potentials. Here, the protective effect of PC on liver injury induced by air pollution was examined. Thirty-two adult male Wistar rats (200-250 g) were divided randomly into four groups (n = 8). The groups were; Control (rats received DMSO and then exposed to clean air), PC (rats received PC and then exposed to clean air), DMSO + Dust (rats received DMSO and then exposed to dust), and PC + Dust (the animals received PC and then exposed to dust). The clean air, DMSO, PC, and dust were administrated 3 days a week for 6 consecutive weeks. The rats were anesthetized and their blood samples and liver sections were taken to conduct molecular, biomedical, and histopathological tests. Dust exposure increased the liver enzymes, bilirubin, triglyceride, cholesterol, and the production of liver malondialdehyde, and decreased in liver total anti-oxidant capacity and serum high-density lipoprotein. It also increased the mRNA expression of inflammatory-related cytokines, decreased the mRNA expression of SIRT-1, decreased the expression levels of miR-20b5p, and MEG3 while increased the expression levels of miR-34a, and HOTAIR. Dust exposure also increased the liver content of three cytokines TNF-α, NF-κB, HMGB-1, and ATG-7 proteins. PC enhanced liver function against adverse effects of dust through recovering almost all the studied variables. Exposure to dust damaged the liver through induction of oxidative stress, inflammation, and autophagy. PC protected the liver against dust-induced cytotoxicity.

Analysis of hsa-miR-19a-3p and hsa-miR-19b-3p modulation and phosphodiesterase type 5 expression in the vaginal epithelium of premenopausal women with genital arousal disorder.

Few studies have investigated the role of the phosphodiesterase type 5A (PDE5A) isoenzyme in female genital tissue disorders, exclusively taken from cadavers, as well as the epigenetic mechanisms responsible for the regulation of PDE5A levels. The aim was to study the in vivo association between microRNA (miRNA) expression and the expression levels of PDE5A in women with female genital arousal disorder (FGAD) compared with healthy women. Premenopausal women affected by FGAD (cases) and sexually healthy women (control group) underwent microbiopsy of the periclitoral anterior vaginal wall for the collection of tissue samples. Computational analyses were preliminarily performed in order to identify miRNAs involved in the modulation of PDE5A by using miRNA-messenger RNA interaction prediction tools. Differences in the expression levels of miRNAs and PDE5A were finally investigated in cases and control subjects by using the droplet digital polymerase chain reaction amplification system and stratifying women considering their age, number of pregnancies, and body mass index. Expression levels of miRNAs were able to target PDE5A and the tissue expression in women with FGAD compared with healthy women. The experimental analyses were performed on 22 (43.1%) cases and 29 (56.9%) control subjects. Two miRNAs with the highest interaction levels with PDE5A, hsa-miR-19a-3p (miR-19a) and hsa-miR-19b-3p (miR-19b), were identified and selected for validation analyses. A reduction of the expression levels of both miRNAs was observed in women with FGAD compared with the control subjects (P < .05). Moreover, PDE5A expression levels were higher in women with FGAD and lower in women without sexual dysfunctions (P < .05). Finally, a correlation between body mass index and the expression levels of miR-19a was found (P < .01). Women with FGAD had higher levels of PDE5 compared with control subjects; therefore, the administration of PDE5 inhibitors (PDE5 inhibitors) could be useful in women with FGAD. The strength of the current study was to analyze genital tissue obtained in vivo from premenopausal women. A limitation was to not investigate other factors, including endothelial nitric oxide synthetases, nitric oxide, and cyclic guanosine monophosphate. The results of the present study indicate that the modulation of selected miRNAs could influence PDE5A expression in genital tissues in healthy women or in those with FGAD. Such findings further suggest that treatment with PDE5 inhibitors, as a modulator of PDE5A expression, could be indicated for women with FGAD.