Hanan Ghozlan

Hepatitis C virus core protein triggers hepatic angiogenesis by a mechanism including multiple pathways.

Chronic hepatitis C virus (HCV) infection is associated with the production of serum cytokines, including transforming growth factor (TGF)‐β2. Despite the occurrence of hepatic angiogenesis in liver conditions, the role of HCV proteins in this context is currently unknown. We demonstrated that the development of hepatic neoangiogenesis in patients infected with HCV is associated with the expression of TGF‐β2 and vascular endothelial growth factor (VEGF) and with activation of endothelial cells, as evidenced by CD34 expression. The analysis of liver biopsies of HCV‐positive and HCV‐negative patients using immunostaining showed significant elevation of TGF‐β2, VEGF, and CD34 expression in patients who were HCV‐positive. Using an HCV established culture system, we confirmed further the production of both TGF‐β2 and VEGF proteins, in the hepatoma cell lines HepG2 and Huh7 by transfection with full‐length HCV RNA (JFH1) or by the regulated expression of core. In addition, regulated expression of core protein in HepG2 or Huh7 cells was found to induce expression and activation of the transcription factor E2F1 and apoptosis signal‐regulating kinase 1 (ASK1), activation of c‐jun‐N‐terminal kinase (JNK) and p38, and extracellular‐regulated kinase (ERK), and transcription factors activator protein 1 (AP‐1), activating transcription factor 2 (ATF‐2), cyclic adenosine monophosphate response element binding (CREB), E2F1, hypoxia inducing factor 1 alpha (HIF‐1α), and specificity protein 1. Furthermore, data obtained from inhibitor experiments revealed the importance of E2F1 and ASK1 in the modulation of core‐induced activation of JNK and p38 pathways and suggested an essential role for JNK, p38, and ERK pathways in the regulation of core‐induced production of TGF‐β2 and VEGF proteins. Thus, our data provide insight into the molecular mechanisms whereby core protein mediates the development of hepatic angiogenesis in patients with chronic HCV infection. (HEPATOLOGY 2009.)

Hepatitis C virus-related hepatocellular carcinoma: An insight into molecular mechanisms and therapeutic strategies

Hepatitis C virus (HCV) infects more than 170 million people worldwide, and thereby becomes a series global health challenge. Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma. Although the multiple functions of the HCV proteins and their impacts on the modulation of the intracellular signaling transduction processes, the drive of carcinogenesis during the infection with HCV, is thought to result from the interactions of viral proteins with host cell proteins. Thus, the induction of mutator phenotype, in liver, by the expression of HCV proteins provides a key mechanism for the development of HCV-associated hepatocellular carcinoma (HCC). HCC is considered one of the most common malignancies worldwide with increasing incidence during the past decades. In many countries, the trend of HCC is attributed to several liver diseases including HCV infection. However, the development of HCC is very complicated and results mainly from the imbalance between tumor suppressor genes and oncogenes, as well as from the alteration of cellular factors leading to a genomic instability. Besides the poor prognosis of HCC patients, this type of tumor is quite resistance to the available therapies. Thus, understanding the molecular mechanisms, which are implicated in the development of HCC during the course of HCV infection, may help to design a general therapeutic protocol for the treatment and/or the prevention of this malignancy. This review summarizes the current knowledge of the molecular mechanisms, which are involved in the development of HCV-associated HCC and the possible therapeutic strategies.

Phylogenetic diversity and antimicrobial activity of marine bacteria associated with the soft coral Sarcophyton glaucum

Coral reefs are the most biodiverse and biologically productive of all marine ecosystems. Corals harbor diverse and abundant prokaryotic groups. However, little is known about the diversity of coral‐associated microorganisms. We used molecular techniques to identify and compare the culturable bacterial assemblages associated with the soft coral Sarcophyton glaucum from the Red sea. Different media were utilized for microbial isolation, and the phylogeny of the culturable bacteria associated with the coral was analyzed based on 16S rDNA sequencing. The coral associated bacteria were found to be representatives within the Gammaproteobacteria, Actinobacteria, and Firmicutes. Antimicrobial activities of twenty bacterial isolates were tested against four pathogenic bacteria (Staphylococcus aureus, Klebsiella pneumonia, Pseudomonas aeruginosa, Vibrio fluvialis) and three fungi (Penicillium sp., Aspergillus niger, Candida albicans). A relatively high proportion of bacterial strains displayed distinct antibacterial and antifungal activities, suggesting that soft coral‐associated microorganisms may aid their host in protection against marine pathogens. Members of genera Bacillus and Pseudomonas had the highest proportion of antimicrobial activity which supported the hypothesis that they might play a protective role in the coral hosts.

Hepatitis C virus-mediated angiogenesis: Molecular mechanisms and therapeutic strategies

Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus (HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.

Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies

Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies.

Microbial-Physical Synthesis of Fe and Fe3O4 Magnetic Nanoparticles Using Aspergillus niger YESM1 and Supercritical Condition of Ethanol

Magnetic Fe and Fe3O4 magnetite nanoparticles are successfully synthesized using Aspergillus niger YESM 1 and supercritical condition of liquids. Aspergillus niger is used for decomposition of FeSO4 and FeCl3 to FeS and Fe2O3, respectively. The produced particles are exposed to supercritical condition of ethanol for 1 hour at 300°C and pressure of 850 psi. The phase structure and the morphology measurements yield pure iron and major Fe3O4 spherical nanoparticles with average size of 18 and 50 nm, respectively. The crystal size amounts to 9 nm for Fe and 8 nm for Fe3O4. The magnetic properties are measured to exhibit superparamagnetic- and ferromagnetic-like behaviors for Fe and Fe3O4 nanoparticles, respectively. The saturation magnetization amounts to 112 and 68 emu/g for Fe and Fe3O4, respectively. The obtained results open new route for using the biophysical method for large-scale production of highly magnetic nanoparticles to be used for biomedical applications.