Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.     

Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (?196 to ?174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16–0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versuss C/T [p = 0.033; OR: 2.03(1.00–4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00–3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58–13.06)], [p = 0.001; OR: 3.49(1.44–8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87–16.29)], [p = 0.007; OR: 5.21(1.65–16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22–7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.     

Association between Medicare high-risk criteria and outcomes after carotid revascularization procedures

Background

The U.S. Centers for Medicare and Medicaid Services (CMS) has defined a set of high-risk criteria to help define patients who are appropriate for carotid artery stenting (CAS), but these criteria have never been validated. We aimed to validate the CMS high-risk criteria in a nationally representative cohort of patients undergoing CAS and carotid endarterectomy (CEA).

Anesthetic type and hospital outcomes after carotid endarterectomy from the Vascular Quality Initiative database

Objective

Studies on the safety of carotid endarterectomy (CEA) under different anesthetic techniques are sometimes contradictory. The aim of this study was to compare real-world outcomes of CEA under general anesthesia (GA) vs regional or local anesthesia (RA/LA).

HLA class II polymorphism: Protective or risk factors to breast cancer in Tunisia?

HLA system plays a key role in the tumor cells’ escape from immune surveillance. Herein is the first report on the correlation of the susceptibility to breast cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and -DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele and haplotype distribution between patients and 70 female control subjects reveals a negative association between HLA-DRB1*07-DQB1*02 and the incidence of breast cancer in the Tunisian population. (Pathology Oncology Research Vol 12, No 2, 79–81)     

A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction

Loss of FAS (CD95) expression is a common feature of malignant transformation, which has been related to loss of epithelial cell differentiation and loss of sensitivity to apoptosis. We investigated the potential association between FAS promoter polymorphism and the genetic susceptibility to the Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. The in vivo functional significance of the FAS polymorphism was investigated by assessing the correlation between FAS genotypes and the presence of autoantibodies to cytoskeleton and nuclear antigens frequently detected in nasopharyngeal carcinoma. We determined the FAS polymorphism distributions by RFLP-PCR in 170 patients with nasopharyngeal carcinoma and in 224 sex and age-matched controls. We used ELISA and the immunofluorescence analysis to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in patients' sera. A significantly increased risk of nasopharyngeal carcinoma was associated with heterozygote FAS-A/G (OR=2.00, P=0.001) and homozygote FAS-G/G (OR=3.19, P=0.0001) variants. The increased frequency of FAS-G/G genotype is correlated with the presence of anti-nuclear autoantibodies in patients with nasopharyngeal carcinoma (P=0.0298). Our results demonstrated that FAS promoter polymorphism was significantly associated with the nasopharyngeal carcinoma in Tunisians. The anti-nuclear autoantibodies induction was also found to be related to FAS polymorphism. The FAS promoter polymorphism associated not only with the increased risk of nasopharyngeal carcinoma in Tunisians but also with immune response deregulation observed in this cancer.     

Epidemiologic features of myocardial infarction in young patients

Acute myocardial infarction (AMI) in persons under the age of 45 years is uncommon. To determine the clinical features in young patients presenting with AMI, we include 38 patients with mean age 35 years who survive from myocardial infarction. This disease is almost associated with cardiovascular risk factors, the most common of which are tobacco abuse (90%) and diabetes (20%).The coronary arteries are most often normal (40%) or single vessel (33%). In hospital complications are the same as in the older adult but the prognosis seems to be better.