Reno-protective effects of GLP-1 receptor agonist and anti-platelets in experimentally induced diabetic kidney disease in male albino rats.

Objectives: The prevalence of chronic kidney disease in diabetics is progressively increasing with an increased risk of fatal complications. Materials and Methods: Sixty male albino rats were used in the study, and type 2 diabetes mellitus were induced. Diabetic rats were divided randomly into 5 groups, the control diabetic group and 4 treated groups were treated with metformin (group3), dulaglutide (group 4), metformin & cilostazol (group 5), and the last group was treated with dulaglutide & cilostazol (group 6). At the end of the experiment, the weight of rats and systolic blood pressure were estimated. After overnight fasting, the serum levels of blood glucose, lipid profile, and kidney function were measured. After scarification, gene expression of eNOS and NFKB in kidney tissue were estimated and kidney tissues were examined for histopathology. Results: Diabetic rats showed a significant increase in body weight, blood pressure, serum blood glucose, lipid profile, and impaired kidney function. Metformin and dulaglutide are associated with a significant decrease in blood pressure, blood glucose level, serum lipid profile, and improved kidney function. These changes are associated with a significant increase in anti-oxidative markers, and decreased inflammatory and fibrotic markers, especially with the addition of cilostazol. Conclusion: Metformin and dulaglutide have been shown to ameliorate kidney damage in diabetics by stimulating the anti-oxidant defense system, normalizing kidney functional parameters, and improving histopathological changes. The addition of cilostazol to metformin or dulaglutide increased some of their anti-oxidants and anti-inflammatory properties.

The Ifng antisense RNA 1 (IFNG-AS1) and growth arrest-specific transcript 5 (GAS5) are novel diagnostic and prognostic markers involved in childhood ITP.

Background/aim: IFNG-AS1 is a long noncoding RNA that works as an enhancer for the Interferon-gamma (IFN-γ) transcript. GAS5 (growth arrest-specific 5) is a lncRNA that is associated with glucocorticoid resistance. Aberrant expressions of IFNG-AS1 and GAS5 are directly linked to numerous autoimmune disorders but their levels in childhood ITP are still obscure. This study aims to elucidate expressions of target lncRNAs in childhood ITP and their association with pathophysiology and clinical features of the disease as well as their association with types and treatment responses. Method: The fold changes of target lncRNAs in blood samples from children with ITP and healthy controls were analyzed using quantitative real-time PCR (qRT-PCR). Results: There were overexpressed lncRNAs IFNG-AS1 and GAS5 in serum of childhood ITP patients [(median (IQR) = 3.08 (0.2-22.39) and 4.19 (0.9-16.91) respectively, Also, significant higher IFNG-AS1 and GAS5 (p < 0.05) were present in persistent ITP (3-12 months) [ median (IQR) = 4.58 (0.31-22.39) and 3.77 (0.87-12.36) respectively] or chronic ITP (>12 months) [ median (IQR) = 5.6 (0.25-12.59) and 5.61 (1.15-16.91) respectively] when compared to newly diagnosed <3 months patients [IFNG-AS1 median (IQR) = 1.21 (0.2-8.95), and GAS5 median (IQR) = 1.07 (0.09-3.55)]. Also, significant higher lncRNAs IFNG-AS1 and GAS5 were present in patients with partial response to treatment [IFNG-AS1 median (IQR) = 4.15 (0.94-19.25), and GAS5 (median (IQR) = 4.25 (0.81-16.91)] or non-response [IFNG-AS1 median (IQR) = 4.19 (1.25-22.39) and GAS5 median (IQR) = 5.11 (2.34-15.27)] when compared to patients who completely responded to treatment (IFNG-AS1 median (IQR) = 2.09 (0.2-14.58) and GAS5 (median (IQR) = 2.51 (0.09-10.33). In addition, following therapy, the expressions of IFNG-AS1 and GAS5 are significantly negatively correlated with platelet count. Conclusion: Findings suggest that lncRNAs IFNG-AS1 and GAS5 are novel diagnostic and prognostic genetic markers for childhood ITP that can aid in a precise prediction of the disease's progress at the time of diagnosis and could be a useful tool for treatment planning.

The Potential Therapeutic Effect of Orexin-Treated versus Orexin-Untreated Adipose Tissue-Derived Mesenchymal Stem Cell Therapy on Insulin Resistance in Type 2 Diabetic Rats.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by resistance to peripheral insulin actions. Mesenchymal stem cells have been studied for years in T2DM therapy, including adipose tissue-derived mesenchymal stem cells (AD-MSCs). Orexin neuropeptides (A and B) are well-known regulators of appetite and physical activity. The aim of this work was to elucidate the possible therapeutic effect of AD-MSC preconditioning with orexin A (OXA) on insulin resistance in rats. Twenty-eight adult male albino rats were divided into 4 equal groups: a normal control group and 3 diabetic groups (a control T2DM group, diabetic rats treated by an AD-MSCs group, and diabetic rats treated by AD-MSCs preconditioned with OXA). We noticed that the treated groups showed a significant alleviation of insulin resistance parameters as shown in lowering the serum levels of glucose, insulin, total cholesterol, inflammatory markers, and HOMA-IR as compared to the control diabetic group with more significant reduction observed in the OXA-pretreated AD-MSCs-administrated group. More improvement was also noted in the glucose uptake and GLUT-4 gene expression in the skeletal muscle and adipose tissue in the OXA-pretreated AD-MSCs-administrated group compared to the untreated diabetic group. Conclusion. Preconditioning of AD-MSCs with OXA can significantly increase their potential to reduce the insulin resistance in the rat model of T2DM.

Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study.

The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.

Effect of Short-term Erythropoietin Therapy on Insulin Resistance and Serum Levels of Leptin and Neuropeptide Y in Hemodialysis Patients.

INTRODUCTION: Insulin resistance (IR) is a known complication of end-stage kidney disease (ESKD). It may be an important therapeutic target in stages of chronic kidney disease. AIM: The study was conducted to evaluate the effect of short-term treatment with recombinant human erythropoietin (rHuEpo) therapy on IR, serum leptin, and neuropeptide Y in ESKD patients on hemodialysis. MATERIALS AND METHODS: Thirty ESKD patients were enrolled in the study and were randomly assigned into two groups. Erythropoietin (rHuEpo) group consisted of 15 patients (7 females, 8 males, mean age 47.8 ± 9.3 years) treated with rHuEpo therapy after each session of dialysis. No-rHuEpo group consisted of 15 patients (7 females, 8 males, mean age 45.5 ± 8.6 years) not treated with rHuEpo. In addition to, control group consisted of 15 healthy controls (6 females, 9 males, mean age 48.8 ± 11 years). RESULTS: The mean fasting insulin (11 ± 4.2 mU/L) and homeostatic model assessment of IR (HOMA-IR) test (2.6 ± 1.1) were significantly higher in ESKD patients than control group (6.6 ± 1.4 mU/L and 1.5 ± 0.3, respectively). There were significant decreases in glycated hemoglobin (HbA1c) (5.6 ± 1%), fasting insulin level (9.3 ± 3.1 µU/mL), HOMA-IR (2.2 ± 0.7), and serum leptin levels (17.4 ± 8.7 ng/mL) also significant increase in neuropeptide Y levels (113 ± 9.9 pg/mL) after 3 months of rHuEpo therapy, in addition to further significantly decrease fasting insulin levels (7.1 ± 2.1 µU/mL) and HOMA-IR (1.7 ± 6) after 6 months in rHuEpo group. In contrast, there were significantly increases in HbA1c% (5.9 ± 0.5%) and leptin levels (42.3 ± 25.3 ng/mL) in No-rHuEpo group throughout the study. CONCLUSION: IR and hyperleptinemia are improved by recombinant human erythropoietin therapy.