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Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects' PBMCs, and the serum level of TGFß2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFß1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-ß2 transcript and elevated levels of the TGF-ß2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFß1, TGIF1 transcripts, and TGFß2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-ß1, and TGF-ß2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-ß and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.

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HCV recurrence after liver transplantation is one of the causal agents for graft rejection. This study aims to profile non-invasive biomarkers in patients with HCC who had liver transplants. One hundred participants were categorized into three groups (20 control, 32 recurrent HCV (RHCV), and 48 non-RHCV). The expression of six miRNAs (hsa-miR-124-3p, hsa-miR-155-5p, hsa-miR-205-5p, hsa-miR-499a-5p, hsa-miR-574-3p, and hsa-miR-103a-3p) and two mRNAs IL-1ß, STAT1 were quantified. RHCV group has higher levels of hsa-miR-574-3p and hsa-miR-155-5p and lesser levels of hsa-miR-499a-5p than control groups (p = 0.024, 0.0001, 0.002; respectively). RHCV and non-RHCV groups revealed a significant reduction in levels of IL-1ß and STAT1 mRNA compared to the control (p = 0.011, 0.014; respectively). According to ROC analysis, miR-155-5p can differentiate among the patients' groups, while miR-574-3p, IL-1ß, and STAT1 mRNA can discriminate between RHCV and control groups. In conclusion, RHCV patients have dysregulated expression of five transcripts compared to non-RHCV and control groups.

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BACKGROUND: Hepatitis C Virus (HCV) infection is one of the causal agents of liver disease burden. Six multiple antigenic peptides were synthesized including (P315, P412, and P517) plus (P1771, P2121, and P2941) to induce humoral and cellular responses, respectively against HCV infection. AIM: This paper aimed to employ computational tools to evaluate the efficacy of each peptide individually and to determine the most effective one for better vaccine development and/or immunotherapy. METHODS: VaxiJen web and AllerTOP servers were used for antigenicity and allergenicity prediction, respectively. The ToxinPred web server was used to investigate the peptide toxicity. Each peptide was docked with its corresponding receptors. RESULTS: No peptides were expected to be toxic. P315 and P2941 are predicted to have robust antigenic properties, lowest allergenicity, and minimal sOPEP energies. In turn, P315 (derived from gpE1) formed the highest hydrophobic bonds with the BCR and CD81 receptors that will elicit B cell function. P2941 (derived from NS5B) was shown to strongly bind to both CD4 and CD8 receptors that will elicit T cell function. CONCLUSION: P315 successfully bound to B cell (BCR and CD81) receptors. Also, P2941 is strongly bound to T cell (CD4 and CD8) receptors.

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INTRODUCTION: Globally, Breast cancer (BC) is considered the second most common type of cancer and the principal cause of death among affected women. AIM: In this study, we targeted to demonstrate the association of MTHFR single gene polymorphisms (SNPs) with the susceptibility of breast cancer, in addition to its correlation with the clinical patient features. PATIENTS AND METHODS: This work was conducted on 100 Egyptian females with breast cancer and 60 healthy matched controls. Clinical examinations and pathological investigations were recorded. Genotyping of MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) by using Restriction Fragment length Polymorphisms (RFLP) and Sequencing assays were performed. Univariate, Multivariate and Haplotype analysis for the allelic frequencies and the association with clinicopathological features of BC were assessed. RESULTS: The present data showed a strong significant association between the CT and TT of MTHFR (C677T), and AC and CC of (A1289C) with the susceptibility of BC showing highly statistical P- value (0.001). It was also demonstrated that the most frequent haplotype of the two loci of MTHFR (rs1801133-rs1801131) was TC. The latter was strongly associated with the aggressive clinical features of each of tumor size, advanced stage, involvement of cancer in lymph nodes, overexpression of HER2neu and dual negativity of both ER and PR hormones. CONCLUSIONS: SNPs within the MTHFR gene (C677T) and (A1289C) have strong correlation with BC among Egyptian females; These SNPs should be considered as important prognostic markers for identifying the individuals at high risk of developing BC and its progression.

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AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease BsmI and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of this single nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibrosis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001). CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.