miR-124 Expression Research Articles

MiR-495 reverses in the mechanical unloading, random rotating and aging induced muscle atrophy via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 axis.

Mechanical unloading can lead to homeostasis imbalance and severe muscle disease, in which muscle atrophy was one of the disused diseases. However, there were limited therapeutic targets for such diseases. In this study, miR-495 was found dramatically reduced in atrophic skeletal muscle induced by mechanical unloading models both in vitro and in vivo, including the random positioning model (RPM), tail-suspension (TS) model, and aged mice model. Enforced miR-495 expression by its mimic could enormously facilitate the differentiation and regeneration of both mouse myoblast C2C12cells and muscle satellite cells. Furthermore, MyoD was proved as the directly interacted gene of miR-495, and their interaction was crucial for myotube formation. Enforced miR-495 expression could intensively strengthen the muscle mass, in situ muscular electrophysiological indexes, including peak tetanic tension (Po) and peak twitch tension (Pt), and the cross-sectional areas (CSA) of muscle fibers via targeting MyoD and inactivating the Myostatin/TGF-β/Smad3 signaling pathway, indicating that miR-495 can be proposed as an effective target for muscle atrophy treatment induced by in the mechanical unloading, random rotating and aging.

Differential Neurotoxicity Induced in Rats by Injection of PMs from 31 Major Cities in China.

The effects of particulate matter (PMs) from different cities on the nervous system remain unclear. In this study, aqueous solutions of 0.45 μm membrane-filtered PM from 31 major Chinese cities were intravenously administered to rats. Neurotoxicity and mechanisms were investigated by quantifying rat behavior, analyzing in vivo biomarkers, and examining the PM physicochemical properties. PMs from different cities had variable impacts on rat responses, as manifested by the movement speed of the right ear, particularly at 1 h and 4-6 days postexposure. Physiological mechanisms were linked to the regulation of glucocorticoids via the hypothalamic-pituitary-adrenal axis and miR-107/miR-124 expression in the blood. Additionally, PM toxicity was strongly influenced by particle morphology, size, and zeta potential, which varied greatly across cities. Using random forest and multiple linear regression, we revealed that PM particle sizes (458.67 and 531.17 nm) and PM zeta potentials (-3.78, -17.01, and -20.31 mV) had the most important impacts on rat responsiveness, which was in line with blood biomarkers levels in rats such as Glucocorticoid, IL-1β, and IFN-α. These findings indicate that PMs from 31 cities contribute to varying neurotoxicity, thus presenting a possible differential burden on Alzheimer's disease in the aging population across many different regions.

Divergent roles of circulating miR-133 and miR-155 in modulating angiotensin II levels among hypertensive patients in Melanesian and non-Melanesian populations

The therapeutic approach to hypertension often varies across racial and ethnic groups; however, antihypertensive treatments have not yet been tailored to account for these variations in Indonesia, a country with diverse racial and ethnic groups. In addition, microRNA-133 (miR-133) and microRNA-155 (miR-155) play critical roles in cardiac muscle homeostasis and inflammatory responses, but their specific functions in hypertension remain unclear. The aim of this study was to investigate the correlation between circulating miR-133 and miR-155 levels and angiotensin II (ANG-II) levels in hypertensive patients from Melanesian and non-Melanesian populations in Indonesia. A cross-sectional study was conducted in Jayapura, Indonesia among Melanesian and non-Melanesian hypertensive patients. The levels of ANG-II were quantified using sandwich ELISA, while the relative expression of miR-133 and miR-155 levels were measured by real-time PCR. Differences between the two groups were assessed using the Mann-Whitney test, and correlations between miR and ANG-II levels were determined using the Spearman correlation test. The relative expression levels of miR-133 and miR-155 in the Melanesian group were significantly higher than in the non-Melanesian group; 6.94-fold (3.85 vs 0.55) and 2.1-fold higher (0.19 vs 0.09), respectively. MiR-133 had a moderate negative correlation with ANG-II in both Melanesian (r=-0.538; p<0.001) and non-Melanesian (r=-0.649; p<0.001). However, miR-155 had no significant correlation with ANG-II levels in either the Melanesian group (p=0.551) or non-Melanesian group (p=0.159). This study highlights that miR-133 levels are significantly correlated with ANG-II concentrations in both Melanesian and non-Melanesian hypertensive patients, suggesting that miR-133 may play a regulatory role in the ANG-II pathway. These findings provide insights into the potential of miR-133 as a biomarker for hypertension management in diverse populations.

MicroRNA‑96 promotes the proliferation and migration of breast cancer cells by inhibiting Smad7 expression.

The present study aimed to investigate the effects of microRNA (miR)-96 on the proliferation and migration of breast cancer cells, and indicated that miR-96 may have a promoting role in breast cancer by inhibiting Smad7. Reverse transcription-quantitative (RT-q)PCR was used to detect the expression levels of miR-96 and Smad7 in breast cancer tissues and adjacent tissues. Western blotting and immunohistochemistry were conducted to determine the expression levels of SMAD7 in breast cancer and adjacent tissues. A dual luciferase assay was performed to verify the targeted binding between miR-96 and Smad7. Furthermore, the different expression patterns of miR-96 and Smad7 were compared in various breast cancer cell lines using RT-qPCR and western blotting. Among these cell lines, MDA-MB-231, which exhibited the highest expression of miR-96, was chosen for subsequent functional verification. The expression levels of miR-96 were significantly higher in breast cancer tissues compared with those in adjacent tissues. By contrast, the expression levels of Smad7 were significantly lower in breast cancer tissues compared with those in adjacent tissues. The dual luciferase assay revealed a targeted binding effect between miR-96 and Smad7. Notably, transfection with miR-96-5p mimics and short hairpin RNA-Smad7 markedly promoted the proliferation, adhesion, invasion and migration of breast cancer cells. Conversely, transfection with a miR-96-5p inhibitor and Smad7 overexpression plasmid exhibited the opposite trend. In conclusion, the expression levels of miR-96 were significantly elevated in breast cancer tissues compared with those in adjacent tissues. Overexpression of miR-96 was shown to promote the migration of breast cancer cells by downregulating the expression of Smad7. These findings indicated that miR-96 may serve as a prognostic marker for breast cancer.

Qingda Granules alleviate brain damage in spontaneously hypertensive rats by modulating the miR-124/STAT3 signaling axis.

To explore the mechanism of Qingda Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs). Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks. The control rats, along with 6 age-matched WKY rats, were treated with saline only. Blood pressure changes of the rats were monitored, and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining. Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR, and the protein expressions of NeuN, STAT3, Bcl-2, Bax, and cleaved caspase-3 were detected with immunohistochemistry and Western blotting. In a HT22 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis, expressions of miR-124 and STAT3 mRNA, and protein expressions of STAT3, Bcl-2, Bax, and cleaved caspase-3 were evaluated using CCK8 assay, Hoechst 33342 staining, RT-qPCR, and Western blotting. Compared with WKY rats, SHRs had significantly elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex, reduced expressions of NeuN, miR-124 and Bcl-2, and enhanced expressions of STAT3, Bax and cleaved caspase-3 (P<0.05). All these changes in the SHRs were significantly ameliorated by treatment with QDG (P<0.05). In the HT22 cell model, QDG treatment obviously reduced OGD/R-induced cell apoptosis, increased the expressions of miR-124 and Bcl-2, and suppressed the elevation of protein expressions of STAT3, Bax and cleaved caspase-3. QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.

Knockdown of miR-182 changes the sensitivity of triple-negative breast cancer cells to cisplatin

Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study’s objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231. To determine the expression of miR-182, PCR was performed with primers specific to miR-182, and agarose gel electrophoresis was performed. To reduce the expression of miR-182 in MDA-MB-231 cells, anti-miR-182 oligonucleotides were used. RT-qPCR was used to confirm knockdown. The knockdown and control groups were treated with cisplatin at the same time. Propidium iodide (PI) and Annexin V staining were performed for apoptosis assay. Flow cytometric analysis was used to investigate the effect of miR-182 knockdown on cell cycle arrest. In comparison to untreated control MDA-MB-231 cells with MDA-MB-231 cells treated with anti-miR-182, there was a significant increase in the cisplatin-induced early apoptosis phase (p = 0.023). Also, inhibition of miR-182 significantly increased the cell cycle arrest at the G2/M phase in MDA-MB-231 cells (p = 0.031). Our results revealed that miR-182 inhibition may play a role in the overcoming of cisplatin resistance by inducing apoptosis and, cell cycle arrest in TNBC.

Exercise promotes peripheral glycolysis in skeletal muscle through miR-204 induction via the HIF-1α pathway

The mechanisms underlying exercise-induced insulin sensitization are of great interest, as exercise is a clinically critical intervention for diabetic patients. Some microRNAs (miRs) are secreted from skeletal muscle after exercise where they regulate insulin sensitivity, and have potential as diagnostic markers in diabetic patients. miR-204 is well-known for its involvement in development, cancer, and metabolism; however, its role in exercise-induced glycemic control remains unclear. In the present study, endurance exercise in mice increased miR-204 expression levels in skeletal muscle. In a chronic exercise model, miR-204 expression levels were elevated along with glycolytic enzymes in skeletal muscle. When muscular hypoxia was induced after exercise, miR-204 expression also increased with the upregulation of hypoxia-inducible factor 1-alpha (HIF-1α). Furthermore, HIF-1α overexpression led to increased miR-204 expression. Treatment with a miR-204 mimic in C2C12 cells significantly enhanced the glycolysis rate and the mRNA expression of glycolytic enzymes. Notably, intravenous administration of miR-204 in mice increased the glucose clearance rate following refeeding. miR-204 initially elevated blood glucose levels at an early stage of refeeding but later promoted blood glucose reduction as refeeding continued. Additionally, glycolytic enzymes were upregulated in the skeletal muscles of miR-204-injected mice. These findings suggest a novel physiological role for miR-204 in promoting skeletal muscle glycolysis, particularly in situations where insulin action is limited.

An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer Cells In Vitro and In Vivo.

Gastric cancer has become one of the major diseases threatening human health. This study aimed to investigate the mechanism of an anticancer bioactive peptide (ACBP) combined with oxaliplatin (OXA) on MKN-45, SGC7901, and NCI-N87 differentiated human gastric cancer cells and GES-1 immortalized human gastric mucosal epithelial cells. The therapeutic effect and action mechanism of short-term intermittent ACBP combined with OXA on nude mice with human gastric cancer were also investigated. The half-maximal inhibitory concentrations of these agents in these cells were measured by an MTT assay, and cell morphological changes were observed by H&E staining. The expression of Lin28, miR-107, miR-609, and Let-7 in these four cell lines was determined by q-PCR after drug treatment. Lin28 protein expression in these four cell lines treated with these drugs was measured by western blotting. Furthermore, activity and quality of life were observed daily in all tumor-bearing nude mice, and the expression of Lin28 in tumor tissue was determined by immunohistochemistry and RT-PCR. The results showed that ACBP inhibited the proliferation of MKN-45, SGC7901, and NCI-N87 gastric cancer cells in a dose-dependent manner and weakly suppressed the proliferation of GES-1 cells. Moreover, its inhibitory effect on proliferation was stronger in poorly differentiated gastric cancer cells. ACBP, OXA, and the combination upregulated Lin28 gene expression in MKN-45 cells and downregulated it in SGC7901 and GES-1 cells. ACBP and the combination therapy downregulated Let-7 expression in MKN-45 cells and upregulated Let-7 expression in SGC7901 cells. The combination of ACBP with OXA demonstrated significant anticancer sensitization. Moreover, it also significantly improved the quality of life of tumor-bearing nude mice and reduced the toxic side effects of chemotherapeutic drugs on nude mice. ACBP alone and in combination with oxaliplatin influenced the expression of tumor stem cell marker gene Lin28 and regulated the expression of microRNAs specifically regulated by Lin28. In addition, the anticancer effects and attenuated sensitization effects of ACBP may be related to the Lin28/miRNA-107 signaling pathway, acting by inhibiting the proliferation of cancerous stem cells. The findings of this study provide a scientific basis for exploring the antitumor mechanism of ACBP alone and combined with chemotherapeutic drugs.

Exercise preconditioning increases circulating exosome miR-124 expression and alleviates apoptosis in rats with cerebral ischemia-reperfusion injury.

Exercise as a non-pharmacological intervention can exert beneficial effects directly through exosomes crossing the blood-brain barrier and reduce apoptosis after cerebral ischaemia/reperfusion injury (CI/RI). miRNA-124 (miR-124) is present in exosomes and plays an important role in regulating cerebral neurological activity; however, the mechanism of the relationship between exercise and the activity of exosomes and apoptosis after CI/RI remains unclear. Therefore, the present study investigated the effects of exercise preconditioning on cerebral ischemia/reperfusion injury from the perspective of exosomal miR-124 and apoptosis. The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by blocking the middle cerebral artery, and a motorized running wheel was chosen as the method of exercise preconditioning for rats, the morphology, particle concentration and particle size distribution of the exosome samples were identified at the 6 h, 12 h, and 24 h time points. RT-PCR, western blotting, immunohistochemistry, TUNEL staining, TTC staining and mNSS scores were used to investigate the effects of exercise preconditioning on apoptosis in MCAO/R rats. The results showed exercise reduced neurological dysfunction and infarct size, increased the content of plasma exocrine miR-124 at 24 h, which inhibited the expression of STAT3, increased the expression of the anti-apoptotic BCL-2, and decreased the expression of the pro-apoptotic BAX, thereby reducing cell apoptosis. Our findings indicated that exercise preconditioning can enhance the anti-apoptotic capacity of tissues in the rat ischemic penumbra and reduce apoptosis after CI/RI via the exosomal miR-124, STAT3, BCL-2/BAX pathway.

CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis

Renal fibrosis is a long-term and progressively worsening condition that impacts kidney function during aging and in the context of chronic kidney disease (CKD). CKD and renal fibrosis affect approximately 10% of the global population and are prevalent in about half of individuals over the age of 70. Despite ongoing research, the mechanisms underlying renal fibrosis are still not well understood, and there is currently a lack of effective treatments available. In the present study, we demonstrated a significant increase of circPWWP2A in renal tubular cells both in vivo and in vitro models of renal fibrosis. Suppressing circPWWP2A has the potential to reduce mitochondrial dysfunction and the production of mitochondrial reactive oxygen species (mtROS), ultimately leading to the inhibition of renal fibrosis. Whereas, supplementation of circPWWP2A led to more serve mitochondrial dysfunction, mtROS production and renal fibrosis. Mechanistically, we found the expression of circPWWP2A was negatively correlated with the expression of miR-182. And we further confirmed miR-182 was the direct target of circPWWP2A by dual-luciferase reporter assay and RIP assay. Then, we found miR-182 suppressed the expression of ROCK1 in both in vitro and in vivo models of renal fibrosis. Luciferase microRNA target reporter assay further indicated ROCK1 as a direct target of miR-182. Knockdown of ROCK1 inhibits renal fibrosis and mitochondrial dysfunction, suggesting ROCK1 not only served as an injurious role in mitochondrial homeostasis but also a pro-fibrotic factor in CKD. Taking together, our findings suggest that circPWWP2A may promote renal interstitial fibrosis by modulating miR-182/ROCK1-mediated mitochondrial dysfunction.

Differential Expression of miR-192, miR-221, miR-15 Among the Nodule Tissues of Sarcoidosis and Lung Cancer

Background: Patients with sarcoidosis were found to have a higher risk of lung cancer compared to the general population. Being aware of all possible associations between these two diseases and identification of biomarkers such as miRNA profiles can be helpful in differentiating the mechanisms of these two diseases, which can aid in clinical decision-making. Methods: The aim of the study was to investigate the expression of selected miRNAs (miR-192 miR-221, miR-15) in lymph nodes of patients with pulmonary sarcoidosis, non-small cell lung carcinomas (NSCLC) and control group (n = 30 per groups) by qRT-PCR. Results: Relative expression of miR-221 in sarcoidosis and NSCC patients was higher than in the control group. Furthermore, the relative expression of miR-15 in patients with sarcoidosis and NSCLC tissue was lower than in the control group. Interestingly, miR-192 is differentially expressed in sarcoidosis and NSCLC patients compared to the control group. Conclusions: The obtained results suggest that the studied miRNAs may have potential diagnostic and therapeutic implications, but further research is necessary to fully understand their roles in these diseases.

Circulating miR-29c, miR-195, and miR-486 Are Objective Indicators to Determine the Moderate Intensity of Resistance Exercise.

Background and objective Moderate exercise is important for health; however, there are variations among individuals in terms of characterizing moderate intensity and it is difficult to identify. In light of this, the purpose of this study was to identify new objective indicators to determine effective exercise intensity. Methods This study involved both human and animal experiments. After subjectingmice to exercise of effective intensity, microarray analysis of circulating microRNA expression was conducted to identifycandidates for objective indicators to determine effective exercise intensity. Then, we assessed if these microRNAs were altered after aerobic or resistance exercises in humans using quantitative real-time PCR. Twelve healthy males were randomly assigned to two groups: the low-intensity exercise group (LI group) and the high-intensity exercise group (HI group) and they underwent four weeks of exercise program. Results Based on microarray analysis, 188 microRNAs were altered after aerobic exercise, and 167 microRNAswere altered after resistance exercise. Combining these findings with the data from some published reports, we selected miR-29c, miR-23b, miR-222, miR-195, miR-126, miR-133a, and miR-486 as the candidates for biomarkers to determine the effective exercise intensity. In the human study, physical performance improved after resistance exercise only in the HI group. Of themicroRNAs, miR-29c, miR-195, and miR-486 increased immediately after resistance exercise only in the HI group. Fold change of miR-486 correlated with changes in knee extensor strength (r=0.744, p=0.005). Conclusions Resistance exercise ateffective intensity upregulated the expression of miR-29c, miR-195, and miR-486. Hence, these microRNAs may serve as objective indicators to determine the intensity of resistance exercise. Among them, miR-486 may aid in predicting the response to resistance exercise.

Considering SOD and miRNA analysis as potential prognostic markers in white lesion malignant transformation: A report of two cases.

Predictive biomarkers can be effective in the identification of the oral leukoplakia with an increased probability of malignant transformation. A 63-year-old patient presents with persistent burning sensations throughout the oral cavity, accompanied by a white lesion on the tongue. Additionally, a 57-year-old patient with multiple white lesions in the oral cavity. Histopathological analysis of the excised tissue. Changes in the expression miRNAs (miR17, miR206, and miR23), the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase), and concentration of reduced glutathione were detected, followed by meta-analysis of previous studies. In both patients (verrucous leukoplakia, oral squamous cell carcinoma) upregulated expression of miR-23a, miR-17, and downregulated expression of miR206 were detected when compared to healthy individuals. In the plasma of a patient diagnosed with carcinoma, higher activity of antioxidant enzymes connected to glutathione was measured in comparison to healthy individuals. The connection between miRNA expression changes, the increase in glutathione-S-transferase and especially the decrease in superoxide dismutase activities in patients with white lesion potential malignant transformation using the provided statistical analysis was confirmed.

Clinical value of serum miRNA-206 in pulmonary tuberculosis.

This study sought to investigate the diagnostic value and the effect of microRNA (miR)-206 on drug resistance in pulmonary tuberculosis (TB) patients. This study included 88 TB patients (TB group) as study subjects, 80 healthy subjects as control 1 (Control group), and 85 latent TB infection (LTBI) patients as control 2 (LTBI group). The drug resistance of TB patients after standard anti-TB treatment was recorded. TB patients were assigned into the pan-sensitive and drug-resistance groups, with miR-206 level in drug-resistant TB patients analyzed. The correlation coefficients between inflammatory indicators (TNF-α, IgG, IL-4, IFN-γ, IP-10) and drug resistance in TB patients were analyzed, and the independent correlation between miR-206 levels and drug resistance was analyzed. Compared to the Control and LTBI groups, serum miR-206 and IP-10 were highly-expressed in TB group. The miR-206 levels positively correlated with IP-10 levels. miR-206 had potential diagnostic value for TB. Levels of TNF-α, IgG, IFN-γ, and IL-4 were elevated in TB group and positively-correlated with miR-206 levels. Moreover, miR-206 levels were higher in the Drug-resistance group than the pan-sensitive group. The low-expression group had a lower incidence of drug resistance than the high-expression group (χ2 = 16.84, P < 0.0001). miR-206 was the most significant indicator affecting drug resistance in TB patients (β = 0.516, P = 0.013). miR-206 was an independent risk factor for drug resistance. High miR-206 expression helps TB diagnosis and may predict drug-resistance incidence. miR-206 may be an independent risk factor for drug resistance in TB patients.

Dysregulation of MiR-21, MiR-221 and MiR-451 During Neoadjuvant Treatment of Breast Cancer: A Prospective Study.

Breast cancer is highly heterogeneous disease in which different responses are observed to the same treatment for different subtypes and extents of similar diseases. Considering this scenario, the search for tumor biomarkers is indispensable, with current evidence suggesting that circulating microRNAs are viable biomarkers. This study evaluated the expression of miR-21, miR-221, miR-195, and miR-451 in patients with breast cancer undergoing neoadjuvant treatment at oncology outpatient facilities in Brazil. We conducted a prospective and observational study in which blood samples were collected for microRNA expression analysis, comparing control and breast cancer patients who were candidates for neoadjuvant treatment groups. The expression of microRNAs was investigated by qRT-PCR method. For parametric data analysis, one-way ANOVA with Tukey's post hoc test was used. Thirty-three participants (all female) were included in the control group and twenty-seven participants were included in the study group. The non-special subtype of breast cancer was found in 96% of the study group participants; 88.9% were locally advanced tumors (T3, T4), 40.7% were luminal tumors, 33.3% were HER-2-positive, and 26% were triple negative tumors. Expression analysis of microRNAs during neoadjuvant treatment, using miR-16 as a normalizer, showed higher expression levels of miR-21 and miR-221 at the end of treatment, and high expression levels for miR-451 were also observed at the beginning of treatment. This is the first study that evaluates the expression of microRNAs in the context of neoadjuvant treatment of breast cancer in the Brazilian population. Our results suggest that there is a deregulation of miR-21, miR-221, and miR-451 during neoadjuvant treatment in these patients.

Polystyrene Nanoparticles-coated Astragalus Polysaccharides Affects the Development of Prostate Cancer by Regulating Glycolysis of DAP12/SYK Axis Through miR-370

Background This study aims to explore the use of polystyrene nanoparticles as a carrier to encapsulate astragalus polysaccharides and regulate the glycolytic pathway of the DNAX-activating protein of 12 kDa/spleen tyrosine kinase (DAP12/SYK) axis through miR-370, thereby affecting the development mechanism of prostate cancer. Materials and Methods Polystyrene nanoparticles coated with astragalus polysaccharide nanoparticles (APS/PDA NPs) were prepared, and PC-3 cell experiments were used for culture and further detection of miRNA and other genes, detection of glycolysis-related proteins and genes, and observation of the biology of PC-3 cells behavioral changes, exploring the mechanism of action of APS/PDA NPs. Results We successfully prepared composite materials of APS/PDA NPs, and found that APS/PDA NPs could inhibit glycolysis and induce apoptosis in PC-3 cells. Further experiments showed that APS/PDA NPs could increase miR-370 expression, inhibit glycolysis, and induce apoptosis. APS/PDA NPs play a strong role in inhibiting the DAP12/SYK axis, inhibiting glycolysis, and causing apoptosis. Combined with biological information and multiple experiments, it was confirmed that miR-370 targeted DAP12, and the inhibition of PCa progression by APS/PDA NPs was achieved through targeting miR-370 and negatively regulating the DAP12/SYK axis. Conclusion As a drug carrier, polystyrene nanoparticles can effectively deliver astragalus polysaccharides to prostate cancer cells, thereby increasing the local concentration of drugs and enhancing the therapeutic effect. More encouragingly, this drug carrier not only performed well in inhibiting glycolysis but also significantly upregulated the level of miR-370, which further inhibits the expression of DAP12, providing a new therapeutic idea for inhibiting the development of prostate cancer.

MiR-137 regulates autophagy and apoptosis in duodenal ulcer by targeting BNIP3L.

Duodenal ulcer (DU) represents a clinical manifestation and disease state that occurs when the mucosal surface of the duodenum is damaged. The processes of autophagy and apoptosis have been linked to the development of DU, yet the precise roles they play remain unclear. This study aimed to investigate the expression and mechanism of action of microRNAs (miRNA)-137 (miR-137) in DU. Dysregulated miRNAs and targeted genes were identified from the Gene Expression Omnibus database, and the immune cell infiltration levels were analyzed using CIBERSORT. To confirm the targeting of the miRNAs, we conducted dual luciferase reporter assays in vitro. The detection of cell apoptosis was conducted using flow cytometry. Moreover, quantitative reverse transcription polymerase chain reaction, cell counting kit-8, and Western blot were employed to ascertain the levels of autophagy- and apoptosis-related proteins. Bioinformatics analysis identified 5 miRNAs, with miR-137 showing the most pronounced dysregulation. Its target gene, BNIP3L, was subsequently identified. In vitro experiments confirmed that miR-137 targeted BNIP3L. The upregulation of miR-137 expression in HIEC-6 cells resulted in the inhibition of BNIP3L expression, a reduction in autophagy, and an increase in apoptosis. A reduction in the expression of miR-137 would have the opposite effect. miR-137 is upregulated in DU patients and contributes to ulcer progression by inhibiting BNIP3L, reducing autophagy, and promoting apoptosis. Targeting miR-137 could provide a novel therapeutic strategy for DU management.

Evaluation of betanin-loaded liposomal nanocarriers in AlCl3-induced Alzheimer's disease in rats: Impact on cognitive function, neurodegeneration, and TREM2/ADAM10 pathways.

Betanin (BET) has been studied for its therapeutic benefits in various diseases, but its low bioavailability and uncertain brain penetration limit its efficacy. Accordingly, this study aimed to explore BET-loaded liposomal nanocarriers (LPN) as a novel treatment for Alzheimer's disease (AD), focusing on the triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways implicated in AD. In an AlCl3-induced AD rat model, 48 male Wistar rats were divided into four groups: control, AlCl3 (50 mg/kg, intraperitoneal), AlCl3+BET (100 mg/kg, per os), and AlCl3+BET LPN (25 mg/kg, intranasally), with treatments administered for 28 days. Morris water maze test and histopathological examination showed that BET LPN-treated rats had improved spatial and learning memory and less hippocampal and cortical degeneration compared with the AlCl3 and oral BET groups. Mechanistically, BET LPN treatment corrected AD biomarkers, increased miR-132 and ADAM10 expression, and reduced oxidative stress, inflammation, and apoptosis. Additionally, BET LPN treatment suppressed the expression of TREM2, DAP12, ERK1/2, and mitogen-activated protein kinase 1/2 (MEK1/2), showing greater improvement than oral BET. These findings suggest that BET LPN enhances cognitive function and neuroprotection in AD by modulating miR-132 and ADAM10 and inhibiting ERK1/2 and TREM2/DAP12 pathways, providing a more effective treatment compared with traditional oral BET administration.

Expression of miR-93 and Glucose Transporter Type 4 Mediated by Ginkgolide in Peripheral Blood with Polycystic Ovary Syndrome and Its Clinical Significance

Decreased Glucose transporter 4 (GLUT4) expression leads to abnormal glucose regulation. miR-93 regulates GLUT4 expression and studies have shown that, ginkgolide mediates miR-93 and GLUT4 in polycystic ovary syndrome (PCOS). 50 patients with PCOS and 50 healthy women were recruited. RT-qPCR detected miR-93 and GLUT4 expression. Luteinizing hormone (LH) (11.84 ± 4.08), T (76.87±30.24), FINs (20.06±11.37) and HOMA-IR (3.75±1.04) in the PCOS group was higher than control group (7.42±3.63, 43.58±13.9, 8.74±4.62, 1.55±0.39) (P &lt; 0.05). miR-93 expression in peripheral blood of PCOS group was significantly elevated, while GLUT4 mRNA expression was reduced (P &lt; 0.05). miR-93 negatively correlated with GLUT4. miR-93 in insulin resistance (IR) group was higher than non-IR group, while GLUT4 was lower (P&lt;0.05). miR-93 positively correlated with T (r=0.374, P =0.019), FINs (r=0.322, P =0.026) and HOMA-IR (r = 0.507, P = 0.005), while GLUT4 had a negative correlation. miR-93 and GLUT4 are abnormally expressed in PCOS, which is related to complications such as IR and endocrine metabolism.

Plasma expression and bioinformatic analysis of Mir-16, Mir-132, Mir-146 and Mir-223 in patients with rheumatoid arthritis

BackgroundMicroRNAs (miRNAs) are involved in the pathogenesis of rheumatoid arthritis (RA) through modulating gene expression. AimTo assess the plasma expression of miR-16, miR-132, miR-146 and miR-223 in patients with RA and their relation to activity and severity of the disease and their potential value as biomarkers. Through bioinformatics study we aim to determine the predictor target genes of the studied miRNAs to clarify their role in RA pathogenesis. MethodsThe study comprised 73 patients suffering from RA and 50 healthy individuals. We used the disease activity score-28 (DAS-28) to assess disease activity. Joint damage was assessed by Kaarela and Kautiainen modification of Larsen scale. Anti-anticyclic citrullinated peptide (anti-CCP) antibodies, serum high sensitive C reactive protein (hsCRP) and rheumatoid factor (RF) were assayed by ELISA. Plasma miR-223, miR-146a, miR-16 and miR-132 were quantified by qRT-PCR followed by a simple dry laboratory analysis of the involved target genes of the studied miRNAs in RA pathogenesis by KEGG pathways. ResultsIn comparison to controls, RA patients showed overexpressed miR-146a, miR-223and miR-16, while miR-132 was down-regulated. Additionally, miR-146a correlated positively with DAS28, anti-CCP antibodies and RF. Bioinformatics revealed that the predicted targeted genes of miR-146a, miR-16, miR-223 and miR-132 are potential contributing factors for RA pathogenesis and bone degradation. ConclusionmiR-146a, miR-223, miR-16 and miR-132 may be potential non-invasive molecular biomarkers for RA diagnosis. Plasma miR-146a might be considered as potential biomarker for disease activity. The predicted genes targeted by miR-146a, miR-223, miR-16 and miR-132 are implicated in RA pathogenesis and ultimately can be used in future target therapeutic approach.