Non-coding RNA genes modulate PI3K/AKT signaling pathway in polycystic ovary syndrome.

BACKGROUND: The PI3K protein kinase B (PI3K/AKT) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. The purpose of this study is to validate the association of PCOS with PI3K/AKT pathway target genes, miRNA486-5p, and miRNA483-5p as well as to evaluate the outcome of metformin on the pathogenesis of PCOS.  METHODS: This case-controlled study included 3 subject groups: twenty healthy females (control group), twenty PCOS females before treatment, and twenty PCOS females treated with metformin at a dose (500 mg 3 times per day for 3 months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miRNA486-5p, and miRNA483-5p in the whole blood. RESULTS: There was a significant decrease in miRNA486-5p and miRNA483-5p in the PCOS group with a significant negative correlation between miRNA486-5p and PI3K and a significant negative correlation between miRNA483-5p and ERK. Metformin treatment resulted in significant elevation of the studied miRNA, significant downregulation of PI3K/AKT target genes, and significant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression. CONCLUSIONS: miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, influence glucose metabolism, and result in IR in PCOS. Metformin's upregulation of those miRNAs affects glucose metabolism by controlling the expression of GLUT4, ameliorates PCOS-related insulin resistance, and improves PCOS-related hormonal imbalance by controlling the PI3K/AKT signaling pathway.

The association between vitamin D levels and oxidative stress markers in Egyptian Behcet's disease patients.

BACKGROUND: Oxidative stress is postulated to have a major role in the pathophysiology of Bechet's Disease (BD). Growing evidence suggests that vitamin D has important roles in enhancing the expression of anti-inflammatory cytokines as well as certain antioxidants. However, there is little evidence currently about the antioxidant properties of vitamin D in BD. OBJECTIVE: To study the relationship between vitamin D levels and the oxidative stress markers in patients with BD in addition to its association with disease activity and severity. METHODS: Sixty BD patients (45 males, 15 females; mean age: 34.2 ± 9.6 years) were enrolled in this study and compared to a sex and age matched control group. Plasma 25-Hydroxy vitamin D (25-OH-D) was measured using Human (25-OH-D) ELISA assay. Plasma malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD) activity, catalase (CAT) activity and total antioxidant capacity (TAC) were determined by spectrophotometric methods in both groups. Plasma calcium (Ca) was measured by ELISA assay. RESULTS: When compared to controls vitamin D, GSH, CAT activity, TAC and Ca were significantly lower in BD patients, while MDA and NO levels were significantly increased in BD patients. Our Results Found that vitamin D was inversely correlated to BD current Activity form (BDCAF), disease severity score, ESR, CRP, MDA and NO, while vitamin D was significantly positively correlated to GSH, SOD, TAC and Ca. CONCLUSION: Our study confirms that a lower level of vitamin D is associated with the oxidative stress state in BD patients as detected by MDA and NO elevation as well as decreased GSH, SOD activity, CAT activity and TAC. Hence, Vitamin D fortified foods and beverages or supplementation may improve disease severity and oxidative stress in BD patients.

Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy.

DN is recognized as not only a leading cause of end stage renal disease (ESRD) but also an independent risk factor for cardiovascular disease (CVD). Novel therapeutic approaches to diabetic nephropathy (DN) are needed, or else, healthcare resources will be overwhelmed by the expected worldwide increase in associated cases of ESRD and CVD. Reactive oxygen species (ROS) and advanced glycation end product (AGE) are implicated in the development of DN. Hydrogen sulfide (H2S) is known for its antioxidant and antiapoptotic characteristics. Simultaneously diabetics have lower H2S levels. Thus, it is worth investigating the use of H2S in treatment of DN. To investigate the potential therapeutic role of H2S in DN. Sixty male rats were divided into four groups: control, DN, DN+NaHS30 µmol/kg/day and DN+NaHS100 µmol/kg/day. Fasting blood sugar (FBS), kidney function tests, SIRT1 activity, superoxide dismutase activity (SOD), malondialdehyde (MDA) and expression of caspase3 and p53 in renal tissues were assessed. Kidney was examined histopathologically. DN rats had higher FBS, renal dysfunction, decreased SIRT1 and SOD activity levels, increased caspase3 and p53 relative expression and increased MDA in renal tissues. NaHS increased SIRT1 and reversed biochemical, apoptotic, oxidant and pathologic parameters characteristic of DN, with better results using a dose of 100 µmol/kg/day. H2S has a protective role against DN through decreasing FBS, ROS, apoptosis and upregulating SIRT1, thus preserving renal cells from further damage caused by DM.

The association between RANKL and Osteoprotegerin gene polymorphisms with breast cancer.

Breast cancer is the most common cause of cancer death among women (522,000 deaths in 2012). Imbalance between RANKL and OPG is observed in many cancers, including breast cancer. Consequently, SNPs in the genes of RANKL and OPG may be involved in breast cancer development. This study included 276 subjects. Group I (n = 100) healthy females as a control group, group II (n = 96) breast cancer patients without bone metastases, and group III (n = 80) breast cancer patients with bone metastases. RANKL rs9533156, OPG rs2073618, and OPG rs2073617 SNPs and their serum protein levels were studied for a possible association with breast cancer development. The allele frequency [(OR: 4.832 CI 2.18-10.71, P = 0.001) and genotype distribution (P = 0.001)] of OPG SNP rs2073618 showed a highly significant difference between breast cancer patients and healthy controls. The allele C is more common in breast cancer patients. The allele frequency [(OR: 0.451 CI 0.232-0.879, P = 0.018) and genotype distribution (P = 0.003)] of RANKL SNP rs9533156 differed significantly between breast cancer patients and healthy controls. The allele T is more common in breast cancer patients. The allele frequency [(OR: 0.36 CI 0.184-0.705, P = 0.002) and genotype distribution (P = 0.011)] of OPG SNP rs2073617 differed significantly between breast cancer patients and healthy controls. The allele T is more common in breast cancer patients. The C allele of OPG SNP rs2073618 may be associated with breast cancer development. No association was found between any of the SNPs and the serum protein levels of RANKL and OPG.