Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

Cigarette smoking and hyperglycemia increase renal response to low levels of cadmium in welders: cystatin C as a sensitive marker.

The present study was undertaken to investigate the utility of cystatin C (CysC) as an early biomarker of cadmium (Cd)-induced renal injury. The study was carried out on 50 adult male individuals divided into five groups of 10 individuals as follows: control, welders, smoker welders, diabetic welders, and smoker diabetic welders. The results indicated that plasma levels of CysC, creatinine, urea, and uric acid were significantly higher in welders compared to control individuals. In addition, the levels of whole blood Cd, lipid peroxidation, and protein oxidation products as well as erythrocyte osmotic fragility were significantly higher in welders compared to control individuals. In contrast, the levels of plasma albumin and whole blood glutathione were significantly decreased in welders compared to control individuals. The alterations of the measured parameters were enhanced in the presence of smoking and hyperglycemia besides exposure to welding fumes. These results suggest that CysC can be used as a sensitive biomarker of the early stages of Cd-induced renal injury.

Protective effect of pravastatin against mercury induced vascular cells damage: erythrocytes as surrogate markers.

In the present study we investigated the protective effect of pravastatin (PRV) against mercury-induced cellular damage. Human erythrocytes were incubated with PRV, HgCl(2) and HgCl(2) pretreated with PRV. Our results revealed that incubation of erythrocytes with HgCl(2) induces a significant increase the ratios of superoxide dismutase/glutathione peroxidase (SOD/GPx), superoxide dismutase/catalase (SOD/CAT), oxidized/reduced glutathione (GSSG/GSH), malondialdehyde(MDA) and protein carbonyl(PCO) by 60%, 50%, 333%, 400% and 208% respectively. Whereas, prior incubation of erythrocytes with PRV maintains these parameters at values similar to control cells. Furthermore, the level of nitrite in erythrocytes decreases significantly on treatment with HgCl(2), whereas it remains similar to the control when pretreated with PRV. Also, there was an increase in erythrocytes hemolysis when treated with HgCl(2), whereas it remained the like to the control when pretreated with PRV. In conclusion, PRV pretreatment maintained the erythrocytes oxidant/antioxidant balance and nitrite level during mercury exposure. Consequently, PRV pretreatment is worthy of further investigation in the reduction of the cardiovascular risk of mercury.

Effect of lead toxicity on coenzyme Q levels in rat tissues.

Lead is a persistent and common environmental contaminant, which chiefly plays a significant role in modern industry. Coenzyme Q acts as electron and proton carrier in mitochondria and functions as an antioxidant in its reduced form (ubiquinol). To investigate the hazardous effects of lead on the coenzyme Q level, rats were injected i.p. with lead acetate (5 mg/kg b.wt. daily for 6 weeks). Our results showed that the levels of both oxidized (ubiquinone) and reduced (ubiquinol) forms of coenzyme Q(9) and Q(10) in serum, brain, liver and kidney of lead-treated rats are quite different depending on the organ tissue type.