Hepatitis E Virus (HEV) is a major cause of acute and chronic hepatitis. The severity of HEV infection increases manyfold in pregnant women and immunocompromised patients. Despite the extensive research on HEV in the last few decades, there is no widely available vaccine yet. In the current study, immunoinformatic analyses were applied to predict a multi-epitope vaccine candidate against HEV. From the ORF2 region, 41 conserved and immunogenic epitopes were prioritized. These epitopes were further analyzed for their probable antigenic and non-allergenic combinations with several linkers. The stability of the vaccine construct was confirmed by molecular dynamic simulations. The vaccine construct is potentially antigenic and docking analysis revealed stable interactions with TLR3. These results suggest that the proposed vaccine can efficiently stimulate both cellular and humoral immune responses. However, further studies are needed to determine the immunogenicity of the vaccine construct.
Background: Combination of different chemotherapy drugs and nanoparticles as a carrier have shown promising delivery system in cancer treatment. Doxorubicin is considered as a potent anticancer drug. However, it’s off target activities and possible side effects, make its use limited. Recently, in the field of nanomedicine, different nanoconjugates have been developed as a unique platform for the delivery of therapeutic drugs. Objective: The aim of present study was to evaluate the best possible combination for efficient delivery of DOX with combination of gold, silver and zinc oxide nanoparticles to target site against carbon tetrachloride induced rat hepatotoxicity. Methodology: Effect of different conjugates administrated for 14 consecutive days was evaluated. Results: In comparison to DOX, Au:DOX, ZnoO:DOX and Ag:DOX showed less sign of liver fibrosis as evaluated by serum enzymes and histo-pathological analysis. However, among all the conjugates, Ag: DOX conjugate showed most significant results. The serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase values were (111.2 ± 38.21, 323.2 ± 46.88 and 303.6 ± 73.80 respectively) very close to control group (72.2 ± 19.41, 368 ± 59.78 and 259.4 ± 61.54 respectively). Conclusion: Our results demonstrated that Ag: DOX may exhibit hepato-protective activity against CCl4 induced liver damage.
Hepatocellular carcinoma (HCC) is a type of malignant tumor. miRNAs are noncoding RNAs and their differential expression patterns are observed in HCC-induced by alcoholism, HBV and HCV infections. By acting as a competing endogenous RNA (ceRNA), circRNA regulates the miRNA function, indirectly controlling the gene expression and leading to HCC progression. In the present study, data mining was performed to screen out all miRNAs and circRNA involved in alcohol, HBV or HCV-induced HCC with statistically significant (≤0.05%) expression levels reported in various studies. Further, the interaction of miRNAs and circRNA was also investigated to explore their role in HCC due to various causative agents. Together, these study data provide a deeper understanding of the circRNA–miRNA regulatory mechanisms in HCC. These screened circRNA, miRNA and their interactions can be used as prognostic biomarkers or therapeutic targets for the treatment of HCC.
Background: Gold nanoparticles have the potential to be used as a carrier in drug delivery system due to their small size, large surface area and short circulation time in blood. Objective: This study aims that doxorubicin conjugation with gold nanoparticles (AuNPs) may reduce its toxicity as well as improve therapeutic efficacy. Methods: Five groups of Albino rats were used; 1: healthy control, 2: Injured, 3: injured and treated with Dox, 4: Injured and treated with AuNPs, 5: Injured and treated with AuNPs: Dox. At the end of the experiment, blood and liver tissues were processed for biochemical and histopathological analysis. The expression of collagen, HO-1, IL-6 and TNF-α genes involved in liver fibrosis was observed through real-time PCR. Results: At the end of the experiment, it was observed that the body weights of DOX treated rats decreased by 0.72%, however, AuNPs and Au: DOX treated rats were 15.3% and 29.13% respectively. The percentage of liver protection determined through alanine aminotransferase and aspartate aminotransferase levels in DOX, AuNPs and AuNPs: DOX treated groups were 39.21%, 79.26%, 98.17% and 47.77%, 84.17%, 97.92% respectively. That represents better recovering liver in Dox-AuNPs treated rats compared to others. Histopathological and gene expression studies further support the findings. The mRNA expression levels of inflammatory and oxidative stress related genes HO-1, IL-6 and TNF-α were upregulated in the injured group but downregulated in the treated group. Conclusion: As depicted through biochemical, histopathological and gene expression studies, Au: DOX conjugate group seems to be protective against liver fibrosis.
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