miR-124 Levels Research Articles

Characteristics of Pulmonary Inflammation in Patients with Different Forms of Active Tuberculosis.

Targeted treatment of tuberculosis-associated lung damage requires an understanding of the precise mechanisms of immunopathology. A major obstacle to the longitudinal study of tuberculosis (TB) immunopathogenesis in humans is the lack of serial lung biopsies during disease progression and treatment, which could be used to characterize local immune pathways involved in tissue damage. Understanding of the immunobiology of lung tissue damage in tuberculosis has largely been based on animal models. Our study looked for signs of inflammation in TB patients' lung biopsies. Results were compared between a site of infection and relatively healthy tissue outside the site. The most significant differences in the expression of microRNAs (miRs) and cytokine/chemokines were observed between the non-decayed tuberculoma and the surrounding parenchyma. In addition, these parameters showed almost no differences between the cavitary wall and surrounding tissue. This is an indication that the inflammatory process is more prevalent in fibrotic cavitary tuberculosis (FCT). In FCT subjects, no difference was observed between the cavity wall and the parenchyma in the production of key inflammatory factors such as IL-6, IL-11, IL-17, and IFNγ. This is an indication that the limits of the inflammatory response are broader in FCT. The expression levels of miR-191, miR-193a, miR-222, miR-223, miR-18, miR-155, miR-376c, miR-26a, miR-150, and miR-124 were not significantly different between the cavernous wall and lung tissue in patients with FCT, further confirming the spread of inflammatory and destructive processes beyond the focus of infection.

Profiling mRNA and miRNA expression variations associated with cyclin-dependent kinase pathway in the low-grade luminal early breast cancer.

Luminal A and B subtypes of breast tumors have fluctuated in proliferation rates, which arise from cell cycle dysregulation in cancer. Besides, microRNAs can regulate various cell processes through integration with mRNA. miRNAs that target the cell cycle are significant because of their prediction capability of prognosis. The objective of this study is to discover the integration between miRNA-mRNA and miRNA-miRNA related to cyclin-dependent kinase. Thirty-four pairs of human primary breast cancer and tumor margin samples from luminal breast cancer patients were investigated to assess the expression levels of CCND1, E2F1, miR-124, miR-503, miR-449a, and miR-449b. Afterward, the expression levels of mRNAs and miRNAs were investigated by real-time PCR. Statistical analysis was conducted to compare the expression levels between breast cancer and corresponding normal tissues. The protein expressions of E2F1 and CCND1 were verified by western blotting. Further, the correlation between mRNAs and miRNAs was calculated. E2F1 was significantly increased in both luminal A and B patients, while CCND1 was upregulated only in luminal B. Significant differences in all miRNAs were detected in both luminal A and B biopsy specimens (p < 0.0001). The correlation analysis revealed a positive strong correlation between miR-124 and E2F1 in luminal A patient. Moreover, the correlation test confirmed the ability of miR-449a to increase the CCND1 gene in luminal B subtypes. Also, miRNA correlation exhibited the miRNA-miRNA interaction in luminal breast cancer. This study demonstrated the novel miRNA-mRNA and miRNA-miRNA interactions, providing new insights into the molecular integration in luminal A and B patients. The authors propose that this research could contribute to introducing valuable biomarkers for luminal cancerous cells.

Dysregulated miR-124 mediates impaired social memory behavior caused by paternal early social isolation.

Early social isolation (SI) leads to various abnormalities in emotion and behavior during adulthood. However, the negative impact of SI on offspring remains unclear. This study has discovered that paternal early SI causes social memory deficits and anxiety-like behavior in F1 young adult mice, with alterations of myelin and synapses in the medial prefrontal cortex (mPFC). The 2-week SI in the F1 progeny exacerbates social memory impairment and hypomyelination in the mPFC. Furthermore, the down-regulation of miR-124, a key inhibitor of myelinogenesis, or over-expression of its target gene Nr4a1 in the mPFC of the F1 mice improves social interaction ability and enhances oligodendrocyte maturation and myelin formation. Mechanistically, elevated levels of miR-124 in the sperm of paternal SI mice are transmitted epigenetically to offspring, altering the expression levels of miR-124/Nr4a1/glucocorticoid receptors in mPFC oligodendrocytes. This, in turn, impedes the establishment of myelinogenesis-dependent social behavior. This study unveils a novel mechanism through which miR-124 mediates the intergenerational effects of early isolation stress, ultimately impairing the establishment of social behavior and neurodevelopment.

Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression

BACKGROUND To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124, miR-132, and brain-derived neurotrophic factor (BDNF) levels in patients with mild to moderate depression following coronary artery intervention [percutaneous coronary intervention (PCI)] for coronary heart disease. AIM To evaluate the therapeutic efficacy of Shugan Jieyu capsules and their effects on the peripheral blood levels of miR-124, miR-132, and BDNF in patients with mild to moderate depression following PCI for coronary heart disease. METHODS Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305th Hospital of the People’s Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups: Experimental (treated with Shugan Jieyu capsules) and control (treated with escitalopram oxalate tablets). This study compared the antidepressant effects of these treatments using 17-item Hamilton Rating Scale for Depression (HAMD-17) scores, metabolic equivalents, low-density lipoprotein cholesterol, BDNF, high-sensitivity C-reactive protein levels, miR-124 and miR-132 levels, distribution of immune-related lymphocyte subsets, and traditional Chinese medicine syndrome scores before and after 6 weeks of treatment. RESULTS No significant difference was observed in any index between the two groups before treatment (P &gt; 0.05). After treatment, the total efficacy rates were 93.33% and 90.00% in the experimental and control groups, respectively. Experimental group had significantly lower scores for the main and secondary syndromes compared to the control group (P &lt; 0.05). No significant difference was observed in the metabolic equivalents between the two groups before and after treatment (P &gt; 0.05). The levels of low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and miR-132 were significantly lower, whereas those of miR-124, BDNF, CD3+T lymphocytes, CD3+CD4+T helper lymphocytes, and CD3+CD4+/CD3+CD8+ cells were significantly higher in the experimental group compared to the control group (P &lt; 0.05). The incidence of adverse reactions during experimental group was significantly lower than that in control group (P &lt; 0.05). CONCLUSION Shugan Jieyu capsules have good efficacy in patients with mild-to-moderate depression after PCI, and its mechanism may contribute to the regulation of miR-124, miR-132, BDNF levels, and lymphoid immune cells.

MiR-124 mediates the effects of gut microbial dysbiosis on brain function in chronic stressed mice

The gut microbiota plays a key role in the brain function impairment caused by chronic stress, yet its exact mechanism remains unclear. Many studies have revealed the important role of miR-124 in the central nervous system. Meanwhile, previous studies have indicated that miR-124 may be regulated by chronic stress and gut microbiota. Here, we aimed to explore whether miR-124 serves as a mediator for the impacts of gut microbial dysbiosis on brain function in mice subjected to chronic stress. Repeated daily restraint stress for 4 weeks was used to induce chronic stress in mice. Chronic stress resulted in gut microbial dysbiosis, abnormal behaviors, and a decrease in hippocampal miR-124 levels. Treatment with different probiotic mixtures significantly alleviated the effects of chronic stress on hippocampal miR-124 levels and mouse behaviors. Suppression of hippocampal miR-124 expression reversed the beneficial effects of probiotics on cognitive function, neurogenesis, and related molecular markers in chronically stressed mice. Bioinformatics analysis and qPCR suggested that Ptpn11 might be a target gene for miR-124 in mediating the effects of gut microbial dysbiosis on brain function in these mice. These findings suggest that miR-124 is a pivotal regulator that mediates the detrimental effects of gut microbial dysbiosis on brain function and the subsequent cognitive impairment during chronic stress.

Multicenter, prospective, observational study for urinary exosomal biomarkers of kidney allograft fibrosis

Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P < 0.001) and miR-29c (AUC = 0.795; P < 0.001) showed good predictive accuracy for IFTA. In the No IFTA group, the eGFR level at 1 week after transplantation was significantly higher compared to the IFTA group (41.34 mL/min/1.73m2 vs. 28.65 mL/min/1.73m2, P = 0.012). These findings signify the potential of urinary exosomal miRNAs as valuable biomarker candidates for evaluating the severity of IFTA in deceased donor kidneys before they undergo recovery.

Long non-coding RNA TMEM147 antisense RNA 1/microRNA-124/signal transducer and activator of transcription 3 axis in estrogen receptor-positive breast cancer.

This research aimed to probe the expression of long noncoding RNA TMEM147 antisense RNA 1 (TMEM147-AS1)/micro-RNA (miR)-124/signal transducer and activator of transcription 3 (STAT3) axis in estrogen receptor (ER)-positive breast cancer (BC). Sixty ER-positive BC patients undergoing surgical treatment were gathered. TMEM147-AS1, miR-124, and STAT3 expression levels in BC cells and tissues were measured. The binding sites of TMEM147-AS1 and miR-124, miR-124, and STAT3 were analyzed and validated. The miR-124, STAT3 overexpression (oe) sequences, TMEM147-AS1 oe, and interference sequences and their control sequences were planned and cells were transfected to assess their functions in BC cells biological functions. TMEM147-AS1, as well as STAT3 was extremely expressed and miR-124 was lowly expressed in BC cells and tissues. Interference with TMEM147-AS1 restrained ER-positive BC cell malignant activities. Mechanistically, TMEM147-AS1 could competitively bind miR-124 in refraining miR-124 expression, and STAT3 was a target gene of miR-124. Oe of miR-124 effectively reversed the enhancement of BC cell proliferation and invasion induced by TMEM147-AS1 upregulation. Oe of STAT3 could reverse the inhibitory effect of miR-124 on BC cell malignant behaviors. TMEM147-AS1 has oncogenic activity in ER-positive BC, which may be a result of the altered miR-124/STAT3 axis. Therefore, targeting the TMEM147-AS1/miR-124/STAT3 axis may be a target for ER-positive BC therapy.

MiR-122, miR-133a, and miR-206 as potential biomarkers for post-mortem interval estimation.

Accurate estimation of post-mortem interval (PMI) is crucial in forensic investigations. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable within the cell nucleus despite post-mortem changes. We assessed three target genes (miR-122, miR-133a, and miR-206) for PMI estimation using 72 healthy adult male BALB/c mice exposed to two different temperatures (4 and 21℃) at nine different time points over 10days. Initially, the stability of the two reference genes (RNU6B and 5 srRNA) was evaluated using gene stability analysis tools (Delta Ct, Best Keeper, and Genorm) to select the optimal reference gene. RNU6B was found to be the most stable endogenous control. Subsequently, the expression patterns of miR-122, miR-133a, and miR-206 were analyzed within a 10-day PMI period using the heart, skeletal muscle, liver, and brain tissues. At 4℃, miR-122 levels significantly decreased on days 8 and 10 in all tissues, with only the liver showing significant changes at 21℃. MiR-133a decreased over time in the heart, muscles, and brain, showing a dramatic decrease on days 8 and 10 in the heart and muscles at both temperatures. Although miR-206 levels decreased over time in muscles and liver at 4℃, these increased in the brain at 21℃, with no expression changes in other organs. In summary, miR-122, miR-133a, and miR-206 are potential PMI markers in heart and skeletal muscle tissues.

Danggui-Shaoyao-San (DSS) ameliorating cognitive impairment in ischemia–reperfusion vascular dementia mice through miR-124 regulating PI3K/Akt signaling pathway

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia–reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice.

MicroRNA-124-3p targets Sp1 transcription factor to regulate glioma progression in rats

Gliomas are the most prevalent malignancies of the central nervous system (CNS). Downregulation of microRNA‑124 (miR‑124) has been identified in glioma; however, its biological functions in glioma are not yet fully understood. Specificity protein 1 (SP1) is a type of transcription factor that is involved in cancer progression. In this study, we examined the targeting of Sp1 mRNA by miR-124-3p in a rat glioma model. After confirming and selecting the binding of Sp1 to miR-124 with the help of bioinformatics methods, adult male Wistar rats were used to induce glioma by microinjection of 1 × 106 C6 cells into the striatum area of brain. The rats were divided into 3 groups; intact, sham and glioma groups. The presence of glioma was confirmed 21 days after implantation through histological analysis. The expression levels of miR-124 and SP1 genes in the experimental groups were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Our data showed that the expression of miR-124 was significantly downregulated in glioma group compared to the sham and intact group, while the expression of SP1 was significantly upregulated. We found that the expression levels of miR-124 and Sp1 were decreased and increased in C6 cell line compared to the normal brain tissue cell line, respectively. The results indicated that Sp1 was identified as a direct target of miR‑124 through luciferase reporter assays. In summary, this study demonstrated for the first time that miR-124 expression is downregulated and Sp1 expression is upregulated in an animal model of glioma, which, in turn, may be involved in the development of glioma brain cancer.

Study of MicroRNA-124 in Patients with Lupus Nephritis.

Lupus nephritis is associated with a six-fold increase in mortality compared with the general population. MicroRNAs studies revealed that increased MicroRNA -21 and MicroRNA -155 levels represent risk factors for active LN patients. MicroRNAs can be used as biomarkers in the diagnosis of clinical stages of LN. The present study aimed to determine the level of miR-124 in patients with lupus nephritis by reverse transcriptase real-time polymerase chain reaction compared to healthy control and correlate its levels with biochemical findings in those patients. The study was a case-control study that included fifty patients with lupus nephritis in addition to fifty healthy controls. Blood samples from the participants were subjected to the determination of serological markers of SLE. Moreover, real-time PCR was used for the determination of miR-124. The comparison of Micro-RNA124 between patients and control subjects revealed a statistically significant decrease in Micro-RNA124 in patients (1.193 ± 0.56) compared to the control (3.36 ± 0.50, p <0.001); the comparison of the level of MicroRNA 124 in the patients with different clinical and serological findings of SLE revealed a significant decrease in the level of MicroRNA 124 in patients with muscular findings (1.02 ± 0.5) compared to the patients with negative manifestations (1.47 ± 0.5, p =0.005). In the present study, a comparison of MicroRNA-124 in LN patients with different stages compared to normal control showed a statistically significant decrease in Micro-RNA124 in patients with lupus nephritis p <0.001 with significant correlation to the patients' different clinical and serological findings of SLE. Therefore, it may be used as a new noninvasive therapeutic approach to monitor response to therapy, predict relapses, and identify the degree of the activity of the disease or the progression to the chronic stage.

Schisandrin B restores M1/M2 balance through miR-124 in lipopolysaccharide-induced BV2 cells.

In this study, Schisandrin B (SCHB), the main active component of Schisandra chinensis extract (SCE), was taken as the research object. From gene, microRNA (miR-124), and the level of protein expression system to study the influences of microglia phenotype to play the role of nerve inflammation. In this study, we investigated the role of miR-124 in regulating microglial polarization alteration and NF-κB/TLR4 signaling and MAPK signaling in the LPS-induced BV2 by PCR, western blot, ELISA, immunofluorescence, and cytometry. SCE and SCHB significantly reduced the NO-releasing, decreased the levels of TNF-α, iNOS, IBA-1, and ratio of CD86+/CD206+, and increased the levels of IL-10, Arg-1. In addition, SCE and SCHB inhibited the nucleus translocation of NF-κB, decreased the expressions of IKK-α, and increased the expressions of IκB-α. Besides, the expressions of TLR4 and MyD88, and the ratios of p-p38/p38, p-ERK/ERK, and p-JNK/JNK were reduced by SCE and SCHB treatments. Furthermore, SCHB upregulated the mRNA levels of miR-124. However, the effects of SCHB were reversed by the miR-124 inhibitor. These findings suggested SCHB downregulated NF-κB/TLR4/MyD88 signaling pathway and MAPK signaling pathway via miR-124 to restore M1/M2 balance and alleviate depressive symptoms.

Identification of reference microRNAs in skeletal muscle of a canine model of Duchenne muscular dystrophy

Background Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the dystrophin gene. DE50-MD dogs are a canine model of DMD used as final translational models for evaluation of promising treatments. MicroRNA (miR) expressions in the muscle of DE50-MD dogs represent potential biomarkers, but stable reference miRs must first be identified. The aim of this paper was to establish a panel of reference miRs for WT and DE50-MD dogs over a range of ages and muscle groups. Methods RNA was extracted from WT and DE50-MD dog (N=6 per genotype) vastus lateralis muscle samples collected longitudinally at 3, 6, 9, 12, 15 and 18 months of age, and from muscles collected post-mortem (N=3 per genotype; cranial tibial, semimembranosus, lateral triceps and diaphragm). 87 RNAs were quantified in a subset of 6-month-old WT and DE50-MD muscles (N=4 per genotype) using the QIAcuity miFinder panel. GeNorm, BestKeeper and Normfinder were used to identify a candidate panel of the 8 most stable small RNAs, which were then quantified in all RNA samples, alongside the commonly used reference RNA snRNA U6. Results The most stable miRs of this subset were used to normalise quantities of dystromiRs miR-1, miR-133a and miR-206, and fibromiR miR-214. MicroRNAs miR-191, let-7b, miR-125a and miR-15a were the most stable miRs tested, while snRNA U6 performed poorly. DystromiR expression, normalised to the geometric mean of the panel of reference miRs, was lower for miR-1 and miR-133a in DE50-MD compared to WT muscles, while miR-206 levels did not significantly differ between genotypes. FibromiR miR-214 was 2- to 4-fold higher in DE50-MD versus WT muscles. Conclusions A normalisation factor derived from miR-191, let-7b, miR-125a and miR-15a is suitable for normalising miR expression data from WT and DE50-MD muscle over a range of ages and muscle types.

Sensitive fluorescence detection of miRNA-124 in cardiomyocytes under oxidative stress using a nucleic acid probe

MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.

HK2 and LDHA upregulation mediate hexavalent chromium-induced carcinogenesis, cancer development and prognosis through miR-218 inhibition

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.

Effect of Oxygen-Glucose Deprivation of Microglia-Derived Exosomes on Hippocampal Neurons: A Study on miR-124 and Inflammatory Cytokines.

Stroke is a cerebrovascular disease that threatens human health. Developing safe and effective drugs and finding therapeutic targets has become an urgent scientific problem. The aim of this study was to investigate the effect of oxygen-glucose deprivation of the microglia-derived exosome on hippocampal neurons and its relationship to miR-124 in the exosome. We incubated hippocampal neurons with exosomes secreted by oxygen-glucose deprivation/ reoxygenation (OGD/R) microglia. The levels of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) in the culture supernatant were detected by ELISA. CCK-8 was used to measure neuronal survival rates. The mRNA levels of TNF-α and IL-6 were detected by RT-qPCR to evaluate the effect of exosomes on neurons. RT-qPCR was then used to detect miR-124 in microglia and their secreted exosomes. Finally, potential targets of miR-124 were analyzed through database retrieval, gene detection with dual luciferase reporters, and western blotting experiments. The results showed that the contents of GLU, TNF-α and IL-6 mRNA increased in the supernatant of cultured hippocampal neurons, the content of GABA decreased, and the survival rate of neurons decreased. Oxygen-glucose deprivation increases miR-124 levels in microglia and their released exosomes. miR-124 acts as a target gene on cytokine signaling suppressor molecule 1(SOCS1), while miR-124 inhibitors reduce the expression of TNF-α and IL-6 mRNA in neurons. These results suggest that oxygen- and glucose-deprived microglia regulate inflammatory cytokines leading to reduced neuronal survival, which may be achieved by miR-124 using SOCS1 as a potential target.

MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients

This study aimed to investigate the neurobiological mechanisms by which microRNA 124 (miR-124) is involved in major depressive disorder (MDD). We enrolled 53 untreated MDD patients and 38 healthy control (HC) subjects who completed behavior assessments and resting-state functional MRI (rs-fMRI) scans. MiR-124 expression levels were detected in the peripheral blood of all participants. We determined that miR-124 levels could influence depressive symptoms via disrupted large-scale intrinsic intra- and internetwork connectivity, including the default mode network (DMN)-DMN, dorsal attention network (DAN)-salience network (SN), and DAN-cingulo-opercular network (CON). This study deepens our understanding of how miR-124 dysregulation contributes to depression.

The Role of Epstein-Barr Virus (EBV) Infected Gastric Cancer in Increasing microRNA124 (miR-124) Promoter Methylation and Enhancer of Zeste Homolog 2 (EZH2) Gene Expression.

The tumor suppressor microRNAs, miR-21, miR-124, and miR-494, participate in the controlling several cellular processes. To assess target miRNAs promoter methylation levels, we investigated 304 pairs of gastric cancer (GC) tissues and non-tumor tissues. We used a commercial real-time polymerase chain reaction (RT-PCR) for Epstein-Barr virus (EBV) and Helicobacter pylori kit to detect EBV and H. pylori DNA in GC tissues. After finding hypermethylation in the promoter of the miR-124 gene, we evaluated its expression level using quantitative PCR (qPCR). Bioinformatics analysis confirmed miR-124 as a target of enhancer of Zeste homolog 2 (EZH2). Additionally, qPCR confirmed the association between EZH2 and miR-124. EBV and H. pylori DNA were detected in 9.5% and 15.1% of GC patients, respectively. Our findings also revealed significant differences in the miR-124 methylation levels among EBV-infected GC patients, H. pylori infected GC patients, GC patients without EBV and H. pylori infection, and non-tumor tissue. Bioinformatics and qPCR assays suggested an inverse relationship between the expression levels of EZH2 and miR-124 in EBV-infected GC patients. Our data revealed hypermethylation of the miR-124 promoter and significant reduction in its expression in EBV-infected GC tissues. It is possible that miR-124 may target EZH2 by binding to the 3'-UTR of the EZH2 gene, thus potentially contributing to the development of EBV-infected GC.

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.

Circulating miR-206, miR-181b, and miR-21 as promising biomarkers in hypothyroidism and their relationship to related hyperlipidemia and hepatic steatosis.

Background: Thyroid hormones (THs) signaling has profound effects on many physiological processes. The regulation of THs signaling in various tissues involves the action of microRNAs (miRNAs) on thyroid deiodinases and receptors. THs regulate the expression of certain miRNAs and their target messenger RNAs (mRNAs) in various tissues and cells. The modulation of miRNA levels by THs affects their functions in processes such as liver lipid metabolism, skin physiology, and muscle and heart performance. Aim: This research aimed to investigate miR-181b, miR-206, and miR-21 in the serum of patients with subclinical and overt hypothyroidism to determine their possible role in the diagnosis of the disease and their relationship to clinical disorders related to hypothyroidism. Methods: This study included ninety participants, divided evenly into three groups as follows: patients with overt hypothyroidism diagnosed clinically, radiologically, and by investigation, subclinical hypothyroid patients, and healthy volunteers. The patients had a thorough medical history and underwent a clinical examination. Laboratory tests included plasma cholesterol, LDL, HDL, TGs, liver and renal function tests, CBC, fasting insulin, HOMA-IR, HbA1c, TSH, and free T4. The serum levels of miR-21, miR-206, and miR-181b were measured using qRT-PCR. Results: miR-206 and miR-181b levels were higher in the subclinical group, followed by the hypothyroid and control groups. For miR-21, there was a significantly lower mean value in both the hypothyroid and subclinical groups than in the control group, with no difference between the two groups. Both miR-206 and miR-181b showed a significant negative association with albumin and free T4 levels and a significant direct association with GGT, ALT, AST, creatinine, uric acid, TGs, TC, LDL, TSH, thyroid volume, and CAP score. The same correlation pattern was observed for miR-181b, except that it was not significantly correlated with the TGs. For miR-21 levels, there was a significant positive correlation with albumin, free T4 level, and kPa score and a negative correlation with GGT, ALT, AST, creatinine, uric acid, HOMA-IR, HbA1c, TC, LDL, TSH, and CAP score. Cases with F1 kPa score and S2 CAP scores had significantly higher averages for miR-206 and miR-181b, with a p-value of 0.05. Moreover, miR-21 levels were significantly lower in the S2 CAP score group. Conclusion: These miRNAs (miR-206, miR-181b, and miR-21) may be used as diagnostic biomarkers for hypothyroidism. They may be used as therapeutic targets to control dyslipidemia and hepatic steatosis during hypothyroid disease.