Implication of miR-122, miR-483, and miR-335 Expression Levels as Potential Signatures in HCV-Related Hepatocellular Carcinoma (HCC) in Egyptian Patients.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with chronic hepatitis C virus (HCV) infection as a major risk factor of HCC. Circulating microRNAs are deregulated in HCC and are candidate biomarkers. The aim of this study was to explore the expression profile of miRNA-122, miR-483, and miR-335 in the serum of HCV-related hepatocellular carcinoma (HCC). 90 HCV-related hepatocellular carcinoma (HCC) patients, 90 non-malignant HCV patients, and 60 healthy controls were included. Serum microRNAs were measured by a qRT-PCR custom array. The expression levels of miR-122 and miR-483 were upregulated in HCC patients, while the miR-335 expression level was downregulated versus controls and HCV groups. Receiver-operating characteristic (ROC) curve analysis was created to examine miRNAs. miR-483 presented the best diagnostic potential because it showed the highest diagnostic accuracy for distinguishing HCV-related HCC patients from controls (AUC = 0.98) with 100% sensitivity. Moreover, there was obvious prognostic power in distinguishing HCV from HCC (AUC = 0.95) with 88% sensitivity. In conclusion, studied microRNAs (miR-122, miR-483, and miR-335) could serve as potential non-invasive early diagnostic biomarkers for HCC, and we identified a panel of three serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.

Effect of leukotriene receptor antagonists on lung fibrosis in rats.

To compare the effects of montelukast, prednisone and the combination of both drugs in a rat model of bleomycin-induced lung fibrosis. Rats, injected intravenously with bleomycin daily for five consecutive days, were treated with either montelukast, prednisone or a combination of both drugs orally daily for 35 days starting 14 days after the commencement of the first dose of bleomycin. Montelukast-treated rats showed reduction in collagen deposition by 29% and significant reduction in lung hydroxyproline content by 32%. Prednisone produced nonsignificant difference in collagen deposition and in lung hydroxyproline content compared with the bleomycin group. There was also a significant reduction in collagen deposition and hydroxyproline content in montelukast and prednisone treated rats by 15 and 17%, respectively, compared with bleomycin group. A significant reduction occurred in the mean area percentage of myofibroblast α smooth muscle actin in montelukast and montelukast and prednisone-treated groups by 41 and 37%, respectively, with nonsignificant difference in prednisone-treated rats as compared with the bleomycin group. Montelukast may be therapeutically effective for inhibiting further progression of lung fibrosis through inhibition of α-SMA positive myofibroblasts.

How to protect doxorubicin-induced cardiomyopathy in male albino rats?

The present study was designed to compare the cardioprotective effects of the combination of lisinopril with growth hormone over lisinopril alone in doxorubicin (Dox)-induced cardiomyopathy in rats. Forty male Wister albino rats were divided into 4 groups: group 1, control group; group 2, received Dox; group 3, received lisinopril + Dox; and group 4, received lisinopril + Dox + growth hormone. Dox (cumulative dose) was administered to rats in 6 equal intraperitoneal injections over a period of 2 weeks. Histopathological changes and plasma aspartate aminotransferase, lactate dehydrogenase, and creatine kinase and plasma levels of matrix metalloproteinase (MMP)-2, tissue inhibitor matrix metalloproteinase (TIMP)-1, and cardiac inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression were determined 9 weeks after the first dose of Dox. Dox produced cardiac structural injury and significant elevation in plasma levels of cardiac enzymes, MMP-2, and cardiac iNOS mRNA expression together with significant reduction in plasma TIMP-1 level. Lisinopril significantly decreases plasma MMP-2 level and cardiac iNOS mRNA expression by 13% and 15%, respectively, in group 3 compared with 36% and 47%, respectively, in group 4 as compared with group 2. In addition, compared with Dox group, lisinopril significantly increases plasma TIMP-1 level by 23% compared with 49% in group 4. We can conclude that the combination of lisinopril and growth hormone produced better cardioprotective effect against Dox-induced cardiomyopathy. This effect may be attributed on their antiremodeling actions by regulating plasma MMP-2/TIMP-1 levels and to the reduction of cardiac iNOS mRNA expression.