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.

Serum lncRNAs, NBAT-1, and FOXCUT signature in hepatocellular carcinoma developed on top of chronic hepatitis C.

BACKGROUND: Hepatocellular Carcinoma (HCC) is a universal health problem responsible for 8.2% of all cancer deaths. Numerous risk factors were documented to be contributed to HCC development with viral hepatitis C ranking as the major predisposing factor in Egypt. The presence of a detectable amount of long noncoding RNAs (lncRNAs) in the circulation is linked to the development and spread of tumors. LncRNAs NBAT-1 and FOXCUT expression levels were used as genetic markers for the detection of gastrointestinal tract cancers. We hypothesized that serum expression levels of NBAT-1 and FOXCUT are new biomarkers for HCC that are related to laboratory and pathological markers. PATIENTS AND METHODS: This study included 165 hepatitis C virus (HCV)-related HCC Egyptian patients, 180 HCV-infected noncancer patients, and 180 healthy controls, the serum expression levels of NBAT-1 and FOXCUT were measured by using quantitative real-time polymerase chain reaction. RESULTS: This study's results include that medians (inter-quartile range [IQRs]) of NBAT-1 in HCC and HCV patients were (1.9 [0.87-4.94], 10.01 [7.34-13.29] respectively) which exhibited significantly higher expression than controls, while the medians (IQRs) of FOXCUT in HCC and HCV patients were (0.15 [0.04-0.52], 6.42 [2.49-10.10], respectively) that exhibited significantly lower expression than controls regarding HCC patients but significantly higher expression than controls regarding HCV patients. In comparing serum fold changes of NBAT-1 and FOXCUT between HCC patients and HCV patients; we obtained significantly higher levels of target genes in HCV patients (p < 0.001) than in HCC patients. Also, a positive correlation was detected between NBAT-1 and FOXCUT in HCC group (r = 0.262, p = 0.001) and in HCV group (r = 0.937, p < 0.001). Higher serum NBAT-1 and FOXCUT were significantly associated with better clinical and laboratory data of the disease. Multivariate regression analysis showed that FOXCUT was an independent predictor for HCC among HCV patients (p < 0.001). CONCLUSION: Our study cited that NBAT-1 and FOXCUT could be considered new diagnostic serum biomarkers for HCC on top of HCV.

Humanin Ameliorates Late-onset Hypogonadism in Aged Male Rats.

BACKGROUND: The potential to reproduce declines with age. Late-onset hypogonadism is characterized by reduced serum testosterone. Humanin is a mitochondrial-derived signaling peptide encoded by short open reading frames within the mitochondrial genome. It may protect against some age-related diseases such as atherosclerosis by its cytoprotective effects. OBJECTIVE: The study aimed to investigate the potential anti-aging effects of humanin on the testicular architecture, oxidative stress, some apoptotic and inflammatory markers in the hypogonadal aged male rats. METHODS: Forty male albino rats were divided into 4 groups: normal adult controls, aged vehicle- treated group, aged testosterone-treated group, and aged humanin-treated group. Twenty-month- old male rats with declined serum testosterone were selected to be the animal models of lateonset hypogonadism. Testicular weights, serum testosterone, and some sperm parameters were measured. Testicular tissue IL-6 and TNF-α, superoxide dismutase activity, glutathione peroxidase, and malondialdehyde were assessed. The activity of caspase-3, BCL2, PCNA, and the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway were evaluated. Testes were subjected to histopathological and immunohistochemical examination. Statistical analysis was executed using. One Way Analysis of variance (ANOVA) followed by Post hoc (LSD) test to compare means among all studied groups. RESULTS: Humanin treatment significantly improved serum testosterone, sperm characteristics, and antioxidant defenses. It decreased active caspase-3, pro-apoptotic BAX expression, and increased antiapoptotic BCL2 and proliferating cell nuclear antigen (PCNA) possibly via activating the (Nrf2- ARE) pathway. CONCLUSION: Humanin might be a promising therapeutic modality in late-onset hypogonadism as it ameliorated some age-related testicular and hormonal adverse effects.