The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy.

Aim: The primary factor causing chronic renal failure is diabetic nephropathy (DN) worldwide. However, the current biomarkers for DN have limited diagnostic utility. Thus, this work aimed to clarify the implications of microRNA-200a (miR-200a) and microRNA-132 (miR-132) and their correlation with NF-κB (nuclear factor- kappa beta), and, TNF-α (tumor necrosis factor -alpha) signaling to identify biomarkers able to distinguish late-stage from early- stage DN. Methods: Fifty healthy controls, and 271 type 2 diabetic (T2D) patients (166 male plus 105 female) were enrolled. Participants were stratified into seven groups according to along with the estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c%), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and four DN grades (G3a, G3b, G4, and G5). Results: Compared to healthy controls, the DN groups exhibited linear increases in serum miR-200a, TNF-α, NF-κB, matrix metalloproteinase (MMP-9) and interleukin-6 (IL-6) levels and reductions in miR-132 serum expression. Among the patients, NF-κB and TNF-α produced a negative correlation with miR-132, while, positive correlation has been discovered with miR-200-a. The operating characteristic of the receiver curve (ROC), proved that, miR-200a also miR-132 had good diagnostic performance in distinguishing early from advanced DN. Conclusion: MiR-200a as well as miR-132 expression levels, and their correlations with NF-κB/TNF-alpha signaling, were able to differentiate between DN patients with lower eGFR, suggesting their utility as diagnostic and prognostic biomarkers.

The amelioration effect of antidiabetic agents on cytokine expression in patients with type 2 diabetes mellitus.

Inflammation is a condition that is closely linked to diabetes mellitus type 2 (T2DM), short for T2DM several different antidiabetic medications have been produced to regulate hyperglycemia, with indications that these therapies may have anti-inflammatory effects along with their glucose-lowering efficacy. Thus, this research was planned to explore the impact of antidiabetic agents on the cytokine expression levels -interleukin (IL)-1ß, IL-6, IL-17, and IL-37 when patients have T2DM. In this study, 168 eligible subject matter was split into two groups: 50 healthy individuals and 118 cases with T2DM, who were classified into two subgroups: 30 untreated patients and 88 patients treated with metformin-based therapy. The outcome exhibited a significant increase within HbA1c% and proinflammatory cytokines (i.e., IL-1ß, IL- 6, and IL-17), whereas IL-37 decreased considerably in untreated cases with T2DM compared to those in subjects who are healthy. Furthermore, the results showed increased levels Regarding waist size, body mass index and assessment using that homeostasis model, cholesterol, triglycerides, low-density lipoprotein levels, and heart danger elements in untreated cases with T2DM in comparison with hygienic subjects. Notably, treated patients with T2DM revealed an ameliorative impact on HbA1c, IL-6, IL-17, IL-37, IL-1ß levels and lipid profile compared with untreated patients with T2DM. Antidiabetic agents may have a beneficial activity on the inflammatory status by reducing blood glucose levels, hyperlipidemia, and proinflammatory cytokines. The anti-inflammatory activity of IL-37 can apply a potentially effective therapeutic goal in treating T2DM and its complications.

Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers.

Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1ß mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.

Polydatin-loaded chitosan nanoparticles ameliorates early diabetic nephropathy by attenuating oxidative stress and inflammatory responses in streptozotocin-induced diabetic rat.

In various developed countries, diabetic nephropathy (DN) is the principal cause of end-stage kidney disease and a main reason of injury and mortality in individuals with renal morbidity worldwide. Polydatin (POL) has been evaluated as a potential antioxidant, anti-inflammatory and a nephroprotective agent. In spite of this, the possible benefits and protective effects of POL on early diabetic nephropathy are not quite clarified. For the effective clearance from the body besides safe drug delivery, biodegradable nanoparticles have interesting attraction. This work was designed to evaluate the positive effect and possible mechanisms of Polydatin-loaded Chitosan-Nanoparticles (POL-NPs) on early DN in streptozotocin-induced diabetic rats. Followed the induction of diabetes, rats classified into four groups, diabetic control and diabetic rats treated daily and orally with; POL, Polydatin-loaded chitosan-Nanoparticles (POL-NPs), plus normal control rats. Our findings showed that diabetic group presented a significant high level of the blood glucose, blood glycosylated hemoglobin (HbA1c), serum insulin, renal function related parameters, renal Advanced glycation-end products (AGEs) and lipid peroxidation level compared to normal control rats, while serum albumin level and the activities of renal antioxidant enzymes were significantly decreased. Moreover, in the kidney of diabetic rat mRNA expression of nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (Cox-2) were up-regulated. Besides, increase in serum levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-18) and decrease in anti-inflammatory cytokine (IL-10). POL and POL-NPs supplementation were significantly attenuate the above-mention results and returned the normal equilibrium between pro- and anti-inflammatory cytokines. In conclusion, POL and POL-NPs have antidiabetic effect, suppresses oxidative stress and mitigates renal inflammation through inhibition of NF-κB in diabetic kidney in early progressive DN.