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Abstract Background and aims Predictors of chronic HCV response to oral antiviral therapy (OAT) are related to host genetic variations. Single nucleotide polymorphisms (SNP) and alleles variations of host genes in association with hepatic fibro-cirrhotic changes have a distinct role in OAT outcomes. The current research evaluated the association of Cirrhosis-Risk-Scores (CRS) values, based on the correlation of seven genes signature-SNPs, with sonographic liver parenchymal changes in determining OAT outcomes. Methods All study subjects (n = 54) were recruited three months after completing OAT and classified into three groups. Group I (n = 21) had negative HCV PCR, group II (n = 17) showed positive solitary intra-PBMCs HCV infection, and group III(n = 16) was serum HCV RNA PCR-positive. All study-population were subjected to examination by hepatic-ultrasound (US), FIB-4-scoring, and screening for 7 gene-signature that addressed CRS values as low, intermediate, and high depending on gene SNPs identification. Results Group I showed a significant association with low CRS values compared to other groups (P

Background and objective: The allelic discrimination of IFNL3-(rs12979860 C > T) polymorphism reveals ambiguous associations with the effectiveness of oral HCV treatment. Solitary intra peripheral-blood-mononuclear-cells (PBMCs) HCV-RNA antisense-strands are independently detected in naïve and experienced cases regardless of viremia or hepatic-parenchymal alterations. We examined the frequencies of IFNL3-genetic variants with chronic-HCV-induced liver changes during the sustained virologic response (SVR) by evaluating the PBMCs- HCV-PCR after oral antiviral therapy. Methods: Twelve weeks after finishing oral antiviral therapy, the effects of IFNL3-genetic variants were evaluated in three groups of patients: Group-I (n = 25) showed HCV-RNA negativity in both serum and PBMCs-, group II (n = 52) showed positivity of HCV-RNA in PBMCs, and group-III (n = 25) had positive HCV-RNA in serum. The genetic variants of the IFNL3-gene were estimated for all the enrolled cases and correlated with their hepatic image changes. Results: IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: a) high frequency of CC-genotype and C-allele in group I compared to group II (P

Abstract Background Human breast cancer is the most prevalent malignancy in women all-over the world. The aim is to look further into the effectiveness of the nanoformulation of tamoxifen and even certain bioactive compounds (yeast, isoflavone, and silymarin) and their impacts on diminishing the breast cancer progression. A single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) was administered intragastrically by fifty-four female Sprague–Dawley rats. After fourteen days of DMBA admission, the procedure protocol actually started out. At long last, all of the experimental findings assessed, tabulated, and statistically analyzed. Results In contrast to the normal groups, a substantial elevation in apoptosis and lipid peroxide was observed in all nanogroups. Conclusion The best biochemical outcome and beneficial factors which elevate the occurrence and activation of the apoptosis process have been demonstrated by nanotamoxifen.

Background: The striking difference in severity of SARS CoV2 infection among global population is partly attributed to viral factors. With the spike (S) and nucleocapsid (N) are the most immunogenic subunits, genetic diversity and antigenicity of S and N are key players in virulence and in vaccine development. Aim: This paper aims at identifying immunogenic targets for better vaccine development and/or immunotherapy of COVID 19 pandemic. Methods: 18 complete genomes of SARS CoV2 (n = 14), SARS CoV (n = 2) and MERS CoV (n = 2) were examined. Bioinformatics of viral genetics and protein folding allowed functional tuning of NH2 Terminal Domain (NTD) of S protein and development of epitope maps for B and T cell responses. Conclusion: A deletion of amino acid residues Y144 and G107 were discovered in NTD of S protein derived from Indian and French isolates resulting in altered pocket structure exclusively located in NTD and reduced affinity of NTD binding to endogenous nAbs and disrupted NTD mediated cell entry. We therefore, proposed a set of B and T cell epitopes based on Immune Epitope Database, homologous epitopes for nAbs in convalescent plasma post SARS CoV infection and functional domains of S (NTD, Receptor Binding domain and the unique polybasic Furin cleavage site at S1/S2 junction). Nevertheless, laboratory data are required to develop vaccine and immunotherapeutics.

In Egypt, Sofosbuvir (SOF) in combination with Dataclasvir (DCV) is the broadly used DAAs with excellent therapeutic profile. This study is designed to explore the relation between IL28B/TLR4 genetic variants and each of the followings; HCC development post SOF/DCV treatment, progression to HCC in naïve patients and SOF/DCV therapy outcome. A total of 493 blood samples were collected (controls (n = 70); HCV patients treated with SOF/DCV (n = 252) of whom 65 patients developed HCC, 187 patients didn't develop HCC (125 responders, 62 relapsers); naïve HCV patients (n = 171) had early (n = 48), late liver fibrosis (n = 21) and HCC (n = 102)). Both SNPs were genotyped using a TaqMan 5′ allelic discrimination assay. At IL28B rs12979860 SNP, the C allele was significantly correlating with the response rate more than T allele (OR 1.9, 95% CI 1.29–2.9, p = 0.004), while at TLR4 rs4986791 SNP, no association was found (OR 6.5, 95% 0.57–75.28, p = 0.09). Both SNPs couldn't detect the probability for HCC emergence after treatment. In naïve patients, the protective alleles were detected in their lowest frequency in HCC patients (p = 0.1, for rs12979860 and, p = 0.001 for rs4986791). SOF/DCV combination improved SVR rates in HCV genotype 4a infected patients regardless of IL28B genotype, with the best rates in those lacking the T allele.

Abstract Background Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice. Methods Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 μg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ɣ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture. Results HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks. Conclusion We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.

The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects. Our data revealed downregulation in GCLM, SOD2, NCF2, PRNP , and PTGS2 transcripts (1.5, 3.8, 1.2, 1.7, and 2.2, respectively; P < .05 for all) in autistic group compared with controls. In addition, TXN and FTH1 exhibited 1.4- and 1.7-fold downregulation, respectively, in severe autistic patients when compared with mild/moderate group ( P = .005 and .0008, respectively). This study helps in a better understanding of the underlying biology and related genetic factors of autism, and most importantly, it presents suggested candidate biomarkers for diagnosis and prognosis purposes as well as targets for therapeutic intervention.

IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention.

Introduction The variable number of tandem repeats (VNTR) of the dopamine receptor D4 (DRD4) gene among humans may elucidate individual differences in susceptibility to neuropsychiatric diseases. Dopamine dysfunction may be involved with Attention Deficit Hyperactivity Disorder (ADHD) symptoms. In this study, we report the association between the phenotype of ADHD, a condition characterized by inattentiveness, hyperactivity, and impulsiveness, and a 48–base pair VNTR in exon 3 of the DRD4 polymorphism. Subjects and Methods We used a case control approach conducted on 29 ADHD and 31 ethnically matched control Egyptian children (ages 6–12 years). Cases were assessed by a psychiatric semi–structured interview and the Conners’ Parent Rating Scale. VNTR polymorphisms of the DRD4 gene were done by touchdown PCR program using exon 3–specific primers followed by agarose gel electrophoresis. Results We observed a significant association between the existence of D4.4 allele of DRD4 and ADHD (P < 0.002); 6.9% of cases showed a single D4.4 and 10.3% showed a double D4.4 as compared to controls in whom D4.4 has never been detected. Conclusion Children with smaller number of repeat alleles (two to four repeats) of the DRD4 gene have higher possibility to develop ADHD in Egyptian children.