Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.     

Determinants of survival following hepatocellular carcinoma in Egyptian patients with untreated chronic HCV infection in the pre-DAA era

Background and Study Aims

In this study we assessed rates and determinants of survival in people with untreated chronic HCV infection and hepatocellular carcinoma (HCC) in an Egyptian liver clinic setting.

Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes,Which Exert Differing Effects on Plazomicin and Other Agents

We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistant Klebsiella pneumoniae strains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10% of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6′)-Ib (98%), APH(3′)-Ia (56%), AAC(3)-IV (38%), and ANT(2″)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r = 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6′)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6′)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6′)-Ib alone (P = 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P = 0.0006, P < 0.0001, and P = 0.01, respectively). The combination of AAC(6′)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3′)-Ia were each associated with gentamicin resistance (P = 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K. pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant K. pneumoniae strains should be a research priority.     

Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment

Colon cancer is an adenocarcinoma, which subsequently develops into malignant tumors, if not treated properly. The current colon cancer therapy mainly revolves around chemotherapy, radiotherapy and surgery, but the search continues for more effective interventions. With the advancement of nanoparticles (NPs), it is now possible to diagnose and treat colon cancers with different types, shapes, and sizes of NPs. Nanoformulations such as quantum dots, iron oxide, polymeric NPs, dendrimers, polypeptides, gold NPs, silver NPs, platinum NPs, and cerium oxide have been either extensively used alone or in combination with other nanomaterials or drugs in colon cancer diagnosis, and treatments. These nanoformulations possess high biocompatibility and bioavailability, which makes them the most suitable candidates for cancer treatment. The size and shape of NPs are critical to achieving an effective drug delivery in cancer treatment and diagnosis. Most NPs currently are under different testing phases (in vitro, preclinical, and clinical), whereas some of them have been approved for therapeutic applications. We have comprehensively reviewed the recent advances in the applications of NPs-based formulations in colon cancer diagnosis and treatment.     

T Helper Cell Polarization in Healthy People: Implications for Cardiovascular Disease

Atherosclerosis is a chronic inflammatory disease characterized by T lymphocyte infiltration into the atherosclerotic plaque. Assessments of T cell subtypes have demonstrated a predominance of CD4⁺ T helper (Th) cells, implicated Th1 and Th17 immunity in both human and mouse atherogenesis, and provided some evidence suggesting protective roles of Th2 and T regulatory cells. Observations that certain inbred mouse strains have an inherent T helper bias suggest a genetic predisposition toward developing a particular T helper phenotype. This review summarizes our current understanding of mechanisms of antigen processing for major histocompatibility complex molecules, describes the different T helper cell subsets and their roles in atherosclerosis, and discusses mechanisms of genetic predisposition toward Th1/Th2 bias in mice. We also present data from our laboratory demonstrating inherent Th1/Th2 phenotypes in apparently healthy human volunteers that are stable over time and discuss the potential implications for cardiovascular disease.     

Role of transforming growth factor beta in peritoneal fibrosis

SUMMARY: Technique survival of peritoneal dialysis is seriously limited by the development of peritoneal fibrosis. the mesothelial cell layer lining the peritoneum is important in the pathogenesis of peritoneal fibrosis. Mesothelial cells are able to produce transforming growth factor beta (TGF-β), and respond to stimulation by this cytokine. In this review, we will detail the evidence available so far for the role of the complex interaction between TGF-β and mesothelial cells in the development of peritoneal fibrosis.     

Gamma interferon induction in human thymocytes activated by lectins and B cell lines.

Human thymocytes in culture synthesized small quantities of interferon (IFN) when stimulated by the lectins concanavalin A or phytohemagglutinin. IFN production by lectin-activated thymocytes was enhanced in the presence of live B lymphoblastoid cells, irradiated B lymphoblastoid cells, or the conditioned medium from B lymphoblastoid cell cultures. The IFN synthesized in mixed cultures had characteristics of IFN-gamma, whereas the IFN synthesized by B lymphoblastoid cells alone could be identified as IFN-alpha on the basis of its neutralization with specific antisera and stability at pH 2. These findings indicate that human thymocytes in culture synthesize IFN-gamma and that B lymphoblastoid cells and their products considerably stimulate IFN-gamma synthesis by lectin-activated human thymocytes in culture. This stimulation was not diminished in the presence of antibodies to IFN-alpha, indicating that IFN-alpha production by B lymphoblastoid cells was not responsible for the stimulatory effect. Removal of adherent cells from thymocyte suspensions did not abrogate IFN-gamma production.