Detection of rtN236T mutation associated with adefovir dipivoxil resistance in Hepatitis B infected patients with YMDD mutations in Tehran

Background Objectives: The risk of adefovir dipivoxil resistance emergence has increased in lamivudine-resistant hepatitis B infected patients. The mutations known as causing adefovir resistance, rtN236T and rtA181V/T, are detected within the D and B functional domain of the HBV polymerase, respectively. In this study, we intended to determine the pre-existing adefovir-resistance mutations in patients infected with LAM resistant mutants prior to starting adefovir therapy. Material and Methods: The study included 30 patients with chronic hepatitis B with lamivudine resistance mutations in the YMDD motif that experienced viral breakthrough. Results: After alignment of protein coding sequences, the rtN236T mutation was observed in two (6.6 %) patients, while twenty-eight others had neither rtN236T, nor rtA181V/T mutation. All 30 patients were infected with genotype D of hepatitis B virus. Conclusions: The early detection of LAM-resistance mutations may allow a timely chance of therapy to avoid hepatitis flare-up. This data suggests that monitoring of ADV-resistance mutations in ADV naïve patients can be considered in selecting the appropriate anti-viral regimen

Design, Synthesis and Docking studies of New Quinazolinone Derivatives as Anti-HIV-1 Agents: Quinazolinone Derivatives as Anti-HIV-1 Agents

The Human Immunodeficiency Virus (HIV) infection is a global health challenge that creates an urgent need to develop new therapeutic agents. In this work, a new group of quinazolinone derivatives were designed and synthesized and evaluated their anti-HIV activity. The antiviral assay revealed that some analogues inhibited HIV replication in the cell culture. A docking study using the later crystallographic data available for PFV integrase including its complexes with Mg2+ and dolutegravir, showed that the designed compounds bind into the active site of integrase enzyme such that both carbonyl groups chelate Mg2+ ions. Interestingly, all of the synthesized compounds were found to present no significant cytotoxicity at a concentration of 100 μM. According to the anti-HIV evaluation results, the compound 10f was found as the most active with the inhibition rate of 38%. Therefore, these compounds can provide a very good basis for the development of new anti-HIV agents

Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

Background: Fusion of Hepatitis B virus surface antigen (HBsAg) to a DNA construct might be considered as a strategy to enhance cellular and cytotoxic T-lymphocytes (CTL) responses of a Hepatitis C Virus core protein (HCVcp)-based DNA vaccine comparable to that of adjuvanted protein (subunit) immunization. Materials and Methods: pCHCORE vector harboring coding sequence of HBsAg and HCVcp (amino acids 2-120) in tandem within the pCDNA3.1 backbone was constructed. The corresponding recombinant HCVcp was also expressed and purified in Escherichia coli. Mice were immunized either by adjuvanted HCVcp (pluronic acid + protein) or by pCHCORE vector primed/protein boosted immunization regimen. The cellular immune responses (proliferation, In vivo CTL assay and IFN-g/IL-4 ELISpot) against a strong and dominant H2-d restricted, CD8 + -epitopic peptide (C39) (core 39-48; RRGPRLGVRA) of HCVcp were compared in immunized animals. Result: Proper expression of the fused protein by pCHCORE in transiently transfected HEK 293T cells and in the expected size (around 50 kDa) was confirmed by western blotting. The immunization results indicated that the pCHCORE shifted the immune responses pathway to Th1 by enhancing the IFN-g cytokine level much higher than protein immunization while the proliferative and CTL responses were comparable (or slightly in favor of DNA immunization). Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine) immunization

Demographics and laboratory data of study samples.

<p>SD, standard deviation</p><p>Demographics and laboratory data of study samples.</p

Summarized phylogenetic tree of 40 Sanandaj (SDJ) samples based on protease and reverse-transcriptase (PR-RT, 1017 bp) sequences.

<p>Tree was constructed using neighbor-joining method with 1000 replicates. As a summarized representation, only reference sequences from HIV-1 subtypes/CRFs previously reported in Iran including B (●; closed circles), D (□; open squares), A1 (■; closed squares), A2 (○; open circles), CRF01_AE (◆; closed diamonds) and CRF35_AD (▲; closed triangle) are included. GenBank accession numbers for the reference sequences, as well as, bootstrap values over 70% are shown. The scale bar represents nucleotidesubstitutions per site.</p

Frequency of HIV-1 drug resistance-associated mutations among 40 sequenced samples.

<p>SDRMs, surveillance drug-resistant mutations; NRTIs, nucleoside reverse transcriptase inhibitors; NNRTIs, non-nucleoside reverse transcriptase inhibitors; PIs, protease inhibitors; DRAMs, drug resistance-associated mutations.</p><p>Frequency of HIV-1 drug resistance-associated mutations among 40 sequenced samples.</p

ZnO Q-dots as a potent therapeutic nanomedicine for <i>in vitro</i> cytotoxicity evaluation of mouth KB44, breast MCF7, colon HT29 and HeLa cancer cell lines, mouse ear swelling tests <i>in vivo</i> and its side effects using the animal model

<p>Nanoformulations derived from fine porous ZnO quantum dot nanoparticles (QD NPs) can offer strong potential medical applications; especially in cancer therapy. ZnO QD NPs was synthesized by sol–gel hydrothermal process, fast cold quenching and further smart surface functionalization methods to obtain ultrasmall size (1–4 nm) NPs. ZnO nanopolymer, a wetting agent, PEG co-solvent and water<b>/</b>oil emulsion stabilizer were considered in our nanofluid formulation. The resulting nanofluid was characterized by SEM, FTIR, photoluminescence, band gap energy, zeta potential and UV–Vis spectroscopy. The cytotoxic effects on the growth of four cancer cell lines were evaluated by MTT assay. The IC₅₀ (µg/ml) values of 30, 41, 40 and 35 for KB44, MCF-7, HT29 and HeLa cells, respectively, after 48 h of nanoformulation treatment suggested the cytotoxic effect of this nanoformulation on these cell lines in a concentration-dependent manner (<i>p</i> < .05). ZnO nanofluid destroyed cancer cell lines more efficiently than the normal HFF-2 (IC₅₀= 105 µg/ml). The reduction in cell viability in response to ZnO nanofluid treatment induced apoptosis in the cultured cells. Skin sensitization test plus antibacterial activity were also measured. Side effect tests on 70 white mice <i>in vivo</i> resulted in only 3–4 abnormal situations in hepatic tissue section possibly due to the idiosyncratic drug reactions.</p