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The main causes of death among patients with hepatocellular carcinoma (HCC) are a recurrence, metastasis, and deterioration of primary tumors by the epithelial‐to‐mesenchymal transition (EMT) which is controlled by several molecules including E‐cadherin and N‐cadherin. Microribonucleic acids (miRNAs) have been identified to play a regulatory role in EMT. miR‐215 is important in repressing migration/invasion of cancer cells. In this study, we aimed to evaluate the crosstalk between miR‐215 and EMT specific markers (E‐cadherin and N‐cadherin) with a spotlight on its role in the EMT process in hepatitis C virus (HCV)‐infected patients. One hundred forty‐five patients were studied, 75 had HCV‐induced cirrhosis classified into child A, B, and C and 25 had HCC. In parallel, 45 healthy volunteers considered as controls. Serum levels of E‐ and N‐cadherin were measured using enzyme‐linked immunosorbent assay and miR‐215 expression measured by a quantitative reverse transcription‐polymerase chain reaction. Insignificant change in serum levels of E‐cadherin and N‐cadherin in HCV‐infected patients compared with normal controls was observed with a slight increase in E‐cadherin and N‐cadherin in the child B group. HCC patients had the lowest amount of E‐cadherin and N‐cadherin compared with cirrhotic and normal subjects. A maximum reduction in miR‐215 was observed in HCC patients compared with cirrhotic and control ones. A positive correlation (r = .202; P < .05) was observed between miR‐215 and E‐cadherin. Our data stressed on the potential role of miR‐215 as an important mediator in HCC progression. miRNAs participating in EMT needs further studies to provide insight into the metastasis of HCC.

A series of novel neocryptolePine–rhodanine hybrids (9a,b, 11a–d, 14, and 16a,b) have been synthesized by combining neocryptolePine core 5 modified at the C-11 position with rhodanine condensed with the appropriate aryl/hetero aryl aldehydes. Based on these findings, the structures of the hybrids were confirmed by spectral analyses. By employing the MTT assay, all hybrids were tested for their in vitro antiproliferative activity against two cancer cell lines, including MDA-MB-231 (human breast) and HepG-2 (hepatocellular carcinoma). Interestingly, the IC50 values of all hybrids except 9b and 11c showed activity comparable to the standard anticancer drug, 5-fluorouracil, against HepG-2 cancer cells. Furthermore, the cytotoxicity of all the synthesized hybrids was investigated on a normal skin human cell line (BJ-1), and the results showed that these compounds had no significant cytotoxicity toward these healthy cells at the highest concentration used in this study. This study also indicated that the active hybrids exert their cytotoxic activity via the induction of apoptosis. A molecular docking study was used to shed light on the molecular mechanism of their anticancer activity. The docking results revealed that the hybrids exert their mode of action through DNA intercalation. Furthermore, in silico assessment for pharmacokinetic properties was performed on the most potent compounds, which revealed candidates with good bioavailability, high tolerability with cell membranes, and positive drug-likeness values.

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Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa) treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years) with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32%) previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.