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.

Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), glioblastoma (GB), and hepatocellular carcinoma (HCC) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. The tumor suppressor lncRNA GAS5 was significantly under-expressed in the three types of cancer [0.08 (0.006–0.38) in RCC, p <0.001; 0.10 (0.003–0.89) in GB, p < 0.001; and 0.12 (0.015–0.74) in HCC, p < 0.001]. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003–22.69), p <0.001] and a decreased expression in GB [0.35 (0.04–0.95), p <0.001]. Consistent to the computationally predicted miRNA-lncRNA interaction, negative correlations were observed between levels of GAS5 and miR-34a in RCC samples (r = -0.949, p < 0.001), GB (r = -0.518, p < 0.001) and HCC (r = -0.455, p = 0.013). Kaplan-Meier curve analysis revealed that RCC patients with down-regulated miR-34a levels had significantly poor overall survival than their corresponding (p < 0.05). Hierarchical clustering analysis showed RCC patients could be clustered by GAS5 and miR-34a co-expression profile. Our results suggest potential applicability of GAS5 and miR-34a with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.

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Monosodium glutamate (MSG) is a neurotoxin found in most processed and infant formulas. Amphora coffeaeformis (AC) has neuroprotective properties. We investigated, for the first time, the potential neuroprotective role of AC on MSG-induced neurotoxicity in brain using a unique procedural approach. The AC extract was characterized via high performance liquid chromatography (HPLC). Animals were assigned into six groups; a control group, low dose MSG (LD-MSG), high dose MSG (HD-MSG), combined groups (LD-MSG + AC) (HD-MSG + AC) and AC only group for eight weeks. Assessment of the cognitive and mood domains was done via Barnes maze and an open field. Gene expression of Bdnf, TrkB, NMDA-B2 and mGlur5 in the hippocampus was obtained via real-time PCR. The hippocampi of the animals were assessed for structural changes. Oxidative stress was assessed in the cerebrum. The results revealed that omega-6 and β-coumaric acid represented the highest percentage among the constituents in the AC extract. The NO level was decreased in the LD-MSG + AC compared to LD-MSG. SOD was diminished in both treated groups compared to the untreated group. HD-MSG + AC exhibited an increase in the number of wrongly visited quadrants compared to the HD-MSG group. HD-MSG + AC showed decreased anxiety-like behavior compared to HD-MSG. LD-MSG + AC and AC groups revealed enhanced anxiety-like behavior. HD-MSG + AC showed under expressed NMDA-B2 and over expressed Bdnf and TrkB genes, compared to HD-MSG. LD-MSG + AC revealed under expression of Bdnf gene compared to LD-MSG. The AC group revealed under expressed TrkB gene compared to the control group. Overall, the results refer to the potential neuroprotective properties of AC alga against MSG neurotoxicity.

Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (, , , and , resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies. Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (, , , and , resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies.

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by a wide spectrum of clinical manifestations with varying severity. The dysregulation of cytokines contributes strongly to disease pathogenesis. Recently, it has been shown that the imbalanced antagonist/agonist profile of interleukin (IL)-36 cytokines, might play a role in autoimmune disorders. Our aim is to investigate mRNA expression of Interleukin-36α (IL-36α) in the peripheral blood of Egyptian systemic lupus erythematosus (SLE) patients and its association with disease activity and organs involvement. We assessed the relative expression of IL-36α mRNA by real time polymerase chain reaction and the comparative CT method on the peripheral blood of 49 SLE patients, and 40 healthy controls. Patients were subjected to thorough history and clinical examination, in addition to routine hematological, biochemical, and serological studies. Disease activity was evaluated using the SLE Disease Activity Index (SLEDAI). The relative expression of IL-36α mRNA was significantly higher in SLE patients compared to healthy controls (4.3±2.9 vs 1, respectively, P5) than patients with mild disease activity (SLEDAI≤5) (4.3±1.2 vs 2.7±2.0, respectively, P=0.006) and positively correlated with SLEDAI (r=0.505, P=0.001). Regarding major organ involvement, the mean±SD expression of IL-36α in patients with arthritis and mucocutaneous involvement was significantly higher compared to those without organ involvement (4.2±1.5 vs 2.8±1.8, P=0.039 and 4.1±1.4 vs 2.8±2.1, P=0.041, respectively). In conclusion, the IL-36α is significantly more expressed in SLE patients compared to healthy controls and correlated with SLE disease activity and arthritis. IL-36α expression could be a useful biomarker for SLE disease activity in Egyptian patients with SLE.