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.

Expression profile of serum LncRNA THRIL and MiR-125b in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. We aimed to investigate, for the first time, the expression profile of serum level of LncRNA THRIL and MiR-125b in IBD patients and their relations with patient's clinical and biochemical investigations. METHODS: Our study included 210 subjects divided into 70 healthy subjects considered as control group (male and female), 70 patients with ulcerative colitis (UC), and 70 patients with Crohn's disease (CD). Blood samples were obtained from all subjects. Expression of LncRNA THRIL and MiR-125b in serum was detected by Quantitative real time PCR (qRT-PCR). RESULTS: Our results showed a significant increase in the fold change of LncRNA THRIL in UC patients (Median = 11.11, IQR; 10.21-12.45, P<0.001) and CD patients (Median = 5.87, IQR; 4.57-7.88, P<0.001) compared to controls. Meanwhile there was a significant decrease in the fold change of MiR-125b in UC patients (Median = 0.36, IQR; 0.19-0.61, P<0.001) and CD patients (Median = 0.69, IQR; 0.3-0.83, P<0.001) compared to controls. Furthermore, there was a negative significant correlation between LncRNA THRIL and MiR-125b in UC patients (r = -0.28, P = 0.016) and in CD patients (r = -0.772, P<0.001). ROC curve analysis was done showing the diagnostic value of these markers as predictors in differentiating between cases of UC, CD, and control. CONCLUSION: Serum LncRNA THRIL and MiR-125b could be used as potential biomarkers for diagnosis and prognosis of ulcerative colitis and Crohn's disease.

Serum miR-34a-5p and miR-199a-3p as new biomarkers of neonatal sepsis.

BACKGROUND: Neonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition. PATIENTS AND METHODS: A total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p. RESULTS: miR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis. CONCLUSION: miR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.

Association Between rs1859168/HOTTIP Expression Level and Colorectal Cancer and Adenomatous Polyposis Risk in Egyptians.

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 A>C and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 A>C single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868, P = 0.003] when compared with controls and (adjusted OR = 9.521, 95% CI = 3.330-27.217, P < 0.0001) when compared with adenomatous polyposis. Serum HOTTIP was upregulated in the colorectal cancer group when compared with adenomatous polyposis or controls [median (interquartile range) = 3.64 (2.46-5.02) (P < 0.0001)]. A significant difference in serum HOTTIP was found to be associated with different rs1859168 genotypes. rs1859168 A>C and higher serum HOTTIP were significantly associated with distant metastasis, lymph nodes metastasis, and grade III of colorectal cancer. Both rs8159168 and high HOTTIP confer increased risk for colorectal cancer development. [Figure: see text].

Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent form of cancer. Various long non coding RNA (lncRNAs) and micro RNA have been confirmed to have a role in the progression of HCC. Our aim was to investigate for the first time the expression profile of serum level of LNC NEAT (nuclear enrich abundant transcript) and MiR-129-5p in HCC patients and their relations with patient's clinical and biochemical investigations rather than previous studies on tissue cell lines. Our study includes 72 subjects divided into 36 as control subjects and 36 patients with HCC. Complete physical and laboratory investigations were done on all subjects. RNAs were extracted from sera of all subjects. RNAs were reversed transcribed into cDNAs using Qiagen, Valenica, CA. Quantitative PCR (qPCR) was performed using Rotor gene Q System (Qiagen). Relative NEAT1 expression level was significantly increased in serum of HCC patients 4.7 (1.31-6.82) (p < .0001). Meanwhile MiR-129-5p relative expression level was significantly decreased in serum of HCC patients 0.17 (0.14-20) (p < .0001). Also there was negative significant correlation between the expression level of LNC NEAT and MiR-129-5p in HCC group (p < .0001). ROC curve analysis revealed that LNC NEAT; AUC = 0.981, p < .0001, cutoff value (1.02), sensitivity 100%, specificity 88.9%. MiR-129-5p; AUC = 0.997, p < .0001, cutoff value (0.43), sensitivity 100%, specificity 97.2%. Serum LNC NEAT and MiR-129-5p could be used as potential biomarkers for HCC cancer diagnosis and prognosis.

Association of MicroRNA-155rs767649 Polymorphism with Susceptibility to Preeclampsia.

Preeclampsia (PE) is a multifactorial disorder. Several studies showed that micro RNAs may play a critical role in PE pathogenesis. We aimed to investigate for the first time the association of mir-155rs767649 polymorphism with PE. Eighty patients with preeclampsia and 80 normal subjects were enrolled in the study. Serum expression levels of mature mir-155were evaluated using real-time PCR, and mir-155 rs767649 (T/A) polymorphism was genotyped using TaqMan SNP genotyping. There was a significant difference between the expression level of mir-155 in cases (5.86 ± 3.11) in comparison with controls (0.58 ± 0.30) (P<0.0001). Also,the minor allele of rs767649 was significantly associated with increased risk of PE [Recessive model: adjusted Odds ratio (OR) = 5.240, 95% confidence interval (CI) = (1.999-13.733),P= 0.001]. There was a significant difference between different genotypes according to expression levels of mir-155 in PE (P<0.0001) with high expression levels in TA genotype (7.10 ± 3.11 ). Mir-155 may play a critical role in PE pathogenesis. The obtained data suggest that a minor allele of rs767649 might be a predisposing factor for PE.

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.