A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury.

A prevalent clinical problem including sepsis, shock, necrotizing enterocolitis, and mesenteric thrombosis is intestinal ischemia/reperfusion (I/R) injury. Humanin (HN), a recently identified mitochondrial polypeptide, exhibits antioxidative and antiapoptotic properties. This work aimed to study the role of HN in a model of experimental intestinal I/R injury and its effect on associated dysmotility. A total of 36 male adult albino rats were allocated into 3 equal groups. Sham group: merely a laparotomy was done. I/R group: for 1 h, clamping of the superior mesenteric artery was done, and then reperfusion was allowed for 2 h later. HN-I/R group: rats underwent ischemia and reperfusion, and 30 min before the reperfusion, they received an intraperitoneal injection of 252 µg/kg of HN. Small intestinal motility was evaluated, and jejunal samples were got for biochemical and histological analysis. I/R group showed elevation of intestinal NO, MDA, TNF- α, and IL-6 and decline of GPx and SOD levels. Furthermore, histologically, there were destructed jejunal villi especially their tips and increased tissue expression of caspase-3 and i-NOS, in addition to reduced small intestinal motility. Compared to I/R group, HN-I/R group exhibited decrease intestinal levels of NO, MDA, TNF- α, and IL-6 and increase GPx and SOD. Moreover, there was noticeable improvement of the histopathologic features and decreased caspase-3 and iNOS immunoreactivity, beside enhanced small intestinal motility. HN alleviates inflammation, apoptosis, and intestinal dysmotility encouraged by I/R. Additionally, I/R-induced apoptosis and motility alterations depend partly on the production of nitric oxide.

Expression profile of serum LncRNAs MALAT-1 and CCAT-1 and their correlation with Mayo severity score in ulcerative colitis patients can diagnose and predict the prognosis of the disease.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16-9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57-16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p < 0.05). Linear regression analysis with Mayo Score as a dependent variable revealed that only the predictive power of CCAT-1 and ESR are significant. Moreover, ROC curve analysis when compared to that of the Mayo score revealed that CCAT-1 reached 99 % accuracy. In summary, both genes are prognostic factors for UC patients. Conclusion: MALAT-1 and CCAT-1 are diagnostic and prognostic serum biomarkers of ulcerative colitis.

1,25-Dihydroxycholecalciferol down-regulates 3-mercaptopyruvate sulfur transferase and caspase-3 in rat model of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of liver morbidity and mortality and has multiple unclear pathogenic mechanisms. Vitamin D deficiency was associated with increased incidence and severity of NAFLD. Increased hepatic expression of 3-mercaptopyruvate sulfur transferase (MPST) and dysregulated hepatocyte apoptosis were involved in NAFLD pathogenesis. We aimed to explore the protective effect of 1,25-Dihydroxycholecalciferol (1,25-(OH)2 D3) against development of NAFLD and the possible underlying mechanisms, regarding hepatic MPST and caspase-3 expression. 60 male adult rats were divided into 4 and 12 week fed groups; each was subdivided into control, high-fat diet (HFD), and HFD + VD. Serum levels of lipid profile parameters, liver enzymes, insulin, glucose, C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and hepatic levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and reactive oxygen species (ROS) were measured. BMI and HOMA-IR were calculated, and liver tissues were processed for histopathological and immunohistochemical studies. The present study found that 1,25-(OH)2 D3 significantly decreased BMI, HOMA-IR, serum levels of glucose, insulin, liver enzymes, lipid profile parameters, CRP, TNF-α, hepatic levels of MDA, ROS, hepatic expression of MPST, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3; and significantly increased hepatic TAC in both HFD-fed groups. In conclusion: Administration of 1,25-(OH)2 D3 with HFD abolished the NAFLD changes associated with HFD in 4-week group, and markedly attenuated the changes in 12-week group. The anti-apoptotic effect via decrement of caspase-3 and MPST expression are novel mechanisms suggested to be implicated in the protective effect of 1,25-(OH)2 D3.

Diagnostic and prognostic values of miR181b-5p and miR21-5p for neonatal sepsis risk and their link to SNAP II score and disease mortality.

Background: Neonatal sepsis is a lethal syndrome that necessitates prompt treatment to avoid disease complications. As a result, biomarkers that may either differentiate sepsis early or predict the outcome of sepsis are essential. Aim: The goal of this research was to find out the clinical weight of using miR181b-5p and miR21-5p expression levels as diagnostic and prognostic new genetic markers for neonatal sepsis. Method: A total of 60 neonates with sepsis and 60 healthy neonates were involved in this study. Laboratory tests include complete blood count (CBC), random blood sugar (RBS), arterial blood gases (ABG), and serum C-reactive protein (CRP). Neonates with sepsis were assessed by the Score for Neonatal Acute Physiology II (SNAP II). The serum fold changes of the target miRNAs were determined using qRT-PCR and the 2-ΔΔCt equation. Results: The relative serum level of miR181b-5p was [ median (IQR) = 0.2509 (0.0009-4.11)] and for miR21-5p was [median (IQR) = 0.07 (0.007-7.16)] which were significantly downregulated in patients with neonatal sepsis compared to controls (p < 0.001 each). There was a strong significant positive correlation between miR181b-5p and miR21-5p with r = 0.718 and p < 0.001. MiR181b-5p and miR21-5p were significantly negatively correlated with total leucocytic count (TLC), lymphocytic count, and CRP. While they were both positively correlated to the SNAP II score. Obvious association between higher expressions of target genes and higher SNAP II score groups. After a following-up period, twenty-two (36.7%) neonates died, while 38 (63.3%) of the babies became better and were released from the hospital. We reported that miR-181-5p, miR21-5p, SNAP II score and CRP were significantly higher in non-survivors than survivors. Only miR181b-5p, miR21-5p, and SNAP II were predictive factors of septic mortality. Conclusion: MiR181b-5p and miR21-5p are diagnostic and prognostic biomarkers of neonatal sepsis.

Liraglutide ameliorates diabetic-induced testicular dysfunction in male rats: role of GLP-1/Kiss1/GnRH and TGF-ß/Smad signaling pathways.

Introduction: Glucagon-like peptide -1 (GLP-1) is released by intestinal cells to stimulate glucose-dependent insulin release from the pancreas. GLP-1 has been linked to ameliorating obesity and/or diabetic complications as well as controlling reproductive function. Liraglutide is a GLP-1 receptor agonist (GLP-1RA) with 97% homology with GLP-1. The main objective of this study was to investigate the ameliorative role of liraglutide in diabetic-induced reproductive dysfunction in male rats. Methods: Rats were randomly allocated into 3 groups; a control group, a diabetic group, and a liraglutide-treated diabetic group. Results: In the diabetic group, a significant increase in BMI, FBG, HbA1c, HOMA-IR, TC, TAG, LDL, IL6, TNFα, and MDA, as well as decreased serum insulin, HDL, GSH, total testosterone, LH, and FSH, were shown compared to the control group. Furthermore, A significant downregulation in relative hypothalamic gene expression of GLP-1R, PPAR-α, PGC-1α, kiss, kiss1R, leptin, leptin R, GnRH GLP-1R, testicular PGC-1α, PPARα, kiss1, kiss1R, STAR, CYP17A1, HSD17B3, CYP19A, CYP11A1, and Smad7, as well as upregulation in hypothalamic GnIH and testicular TGF- ß and Smad2 expression, were noticed compared to the control group. Liraglutide treatment significantly improved such functional and structural reproductive disturbance in diabetic rats. Conclusion: GLP-1RAs ameliorated the deleterious effects of diabetes on reproductive function by targeting GLP-1/leptin/kiss1/GnRH, steroidogenesis, and TGF- ß/Smad pathways.