Portal hypertension and esophageal varices complicating hepatitis C virus ({HCV})-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism ({SNP}), and serum apelin level in patients with chronic {HCV}, and their association with liver fibrosis and esophageal varices in 112 patients with {HCV}-related chronic liver disease (40 with liver cirrhosis [{LC}]/low-grade varices, 33 with {LC}/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 {SNP} analysis in peripheral blood samples. The serum apelin level was measured by {ELISA}. Apelin gene expression was undetectable in the studied samples. The {SNP} analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with {LC}/varices (median, 31.6 ng/L) compared with patients without {LC}/varices (median, 2.9 ng/L; P {\textless} 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P {\textless} 0.001) and portal hypertension (r = 0.438, P {\textless} 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of {HCV}-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer. Differential expression of microRNAs (miRNAs)-326, miRNA-424, and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations. However, limited information is available regarding their expression in Egyptian HCC patients.

AIM: To assess the role of circulating miRNAs-326, miRNA-424, and miRNA-511 in Egyptian HCC patients.

METHODS: This prospective observational study included 70 HCC patients and 25 healthy controls. The circulating levels of these three miRNAs were evaluated by real-time PCR. Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of microRNA expression levels.

RESULTS: All miRNAs were differentially expressed in HCC patients; miRNAs326 and miRNA-424 were upregulated, while miRNA-511 was downregulated. Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%, 71.4%, and 52%, 60%, respectively, to differentiate HCC from controls. Moreover, miRNA-326 was associated with survival and could differentiate between Child grades (A B); miRNA-424 significantly differentiated early intermediate stages of HCC; while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors (mRECIST).

CONCLUSION: We conclude that miRNA-326, miRNA-424, and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

This study evaluated the mechanistic sequel of aldehyde dehyrogenase (ALDH2) and Klotho protein in cyclophosphamide (CP)-induced cardiotoxicity in rats and the protective effect of astaxanthin (AST) against that sequel. A total of 40 male Wistar albino rats were divided into four groups of 10 animals each: Group 1 was injected intraperitoneally (i.p.) with normal saline for 10 successive days. Group 2 was injected with normal saline for 5 days before and after a single dose of CP (200 mg/kg, i.p.). Group 3 received AST (50 mg/kg/day, i.p.) for 10 days. Group 4 received CP as group 2 and AST as group 3. After the last dose of the treatment protocol, serum was separated to measure cardiotoxicity indices and the left ventricle was then dissected for mRNA and protein expression studies and histopathological examinations. Treatment with CP significantly increased serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and troponin, while significantly decreased soluble α Klotho protein and caused histopathological lesions in cardiac tissues. In cardiac tissues, CP significantly decreased gene expression of ALDH2, Klotho protein, mTOR, IGF, AKT, AMPK, BCL2, but significantly increased expression of BAX and caspase-8. Interestingly, administration of AST in combination with CP completely reversed all the biochemical, histopathological and gene expression changes induced by CP to the control values. The current study suggests that inhibition of ALDH2, Klotho protein, mTOR, and AMPK signals in cardiac tissues may contribute to CP-induced acute cardiomyopathy. AST supplementation attenuates CP-induced cardiotoxicity by modulating ALDH2 and Klotho protein expression in heart tissues, along with its downstream apoptosis effector markers.

The full-length BRCA1-associated RING domain 1 (BARD1) gene encodes a 777-aa protein. BARD1 displays a dual role in cancer development and progression as it acts as a tumor suppressor and an oncogene. Structurally, BARD1 has homologous domains to BRCA1 that aid their heterodimer interaction to inhibit the progression of different cancers such as breast and ovarian cancers following the BRCA1-dependant pathway. In addition, BARD1 was shown to be involved in other pathways that are involved in tumor suppression (BRCA1-independent pathway) such as the TP53-dependent apoptotic signaling pathway. However, there are abundant BARD1 isoforms exist that are different from the full-length BARD1 due to nonsense and frameshift mutations, or deletions were found to be associated with susceptibility to various cancers including neuroblastoma, lung, breast, and cervical cancers. This article reviews the spectrum of BARD1 full-length genes and its different isoforms and their anticipated associated risk. Additionally, the study also highlights the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and as a therapeutic target for cancer susceptibility testing and treatment.