The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.

Background: Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD. Subjects and methods: We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs. Results: Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction. Conclusion: The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.

Vitiligo is considered a disabling disease that affects physical, social, psychological, and occupational aspects of an individual's quality of life. The search for non-invasive and reliable biomarkers for vitiligo's early diagnosis, prognosis, and treatment prediction is under intensive investigation. There is currently an emerging interest in employing miRNAs as biomarkers to predict vitiligo diagnosis and prognosis, inspired by the well-preserved nature of miRNAs in serum or plasma. In the current study, we assessed a panel of 20 melanogenesis pathway-related microRNAs (miRNAs) using quantitative real-time PCR technique in 85 non-segmental vitiligo (NSV) patients compared to 85 normal controls followed by function and pathway enrichment analysis for the miRNAs with significant results. Twelve out of the 20 circulating miRNAs showed significantly higher expression levels in vitiligo patients relative to controls where miR-423 show the highest expression level followed by miR-182, miR-106a, miR-23b, miR-9, miR-124, miR-130a, miR-203a, miR-181, miR-152, and miR-320a. While six miRNAs (miR-224, miR-148a, miR-137, and miR-7, miR-148b, miR-145, miR-374b, and miR-196b) didn’t show significant expression level. The analysis of the receiver operating curve indicated that miR-423, miR-106a, and miR-182 were outstanding biomarkers with the highest areas under the curve in vitiligo. This study is the first Egyptian study to investigate a panel of miRNAs expression profile in the plasma of patients with NSV. Our results suggest that specific circulating miRNAs signature might be implicated in vitiligo pathogenesis and could potentially be used as biomarkers in vitiligo.

Background Psoriasis and vitiligo are both chronic, skin-specific diseases classified as autoimmune diseases due to the involvement of several biochemical pathways in their pathogenesis, similar to those altered in other autoimmune diseases. The role of miRNAs in regulating skin autoimmune function has yet to be fully characterized. Aim The aim of this study was to assess the expression profile of a panel of 11 circulating immune-related miRNAs in patients with autoimmune skin diseases, specifically psoriasis and vitiligo, and correlate their expression signature with the clinicopathological features of the diseases. Subjects and Methods Relative gene expression quantification for 11 immune-related circulating miRNAs in plasma was done for 300 subjects—100 patients with psoriasis, 100 patients with vitiligo and 100 normal healthy volunteers—followed by different modalities of bioinformatics analysis for the results. Results The expression levels of all the studied immune-related miRNAs were elevated in both autoimmune skin disorders, with much higher levels of expression in psoriasis than in vitiligo patients. There was a significant correlation between most of the studied miRNAs, suggesting shared target genes and/or pathways. Moreover, all the studied miRNAs showed significant results as biomarkers for autoimmune skin disease, with miRNA-145 being the best candidate. Regarding the clinicopathological data, miRNA-7, miRNA-9, miRNA-145, miRNA-148a, and miRNA-148b were positively correlated with age. All the miRNAs were inversely correlated with obesity and disease duration. Conclusion This study highlights the critical role of miRNAs in skin-specific autoimmune diseases that proved to be potential biomarkers for autoimmune skin disorders, warranting their exploration as therapeutic targets.

Background The interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management. Methods We investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients’ clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study. Results The lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002). Conclusions Based on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.

(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus.