Publications by authors named "Ali Namvar"

17 Publications

  • Page 1 of 1

In silico design and in vitro expression of novel multiepitope DNA constructs based on HIV-1 proteins and Hsp70 T-cell epitopes.

Biotechnol Lett 2021 May 13. Epub 2021 May 13.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Objectives: Epitope-driven vaccines carrying highly conserved and immunodominant epitopes have emerged as promising approaches to overcome human immunodeficiency virus-1 (HIV-1) infection.

Methods: Two multiepitope DNA constructs encoding T cell epitopes from HIV-1 Gag, Pol, Env, Nef and Rev proteins alone and/or linked to the immunogenic epitopes derived from heat shock protein 70 (Hsp70) as an immunostimulatory agent were designed. In silico analyses were applied including MHC-I and MHC-II binding, MHC-I immunogenicity and antigen processing, population coverage, conservancy, allergenicity, toxicity and hemotoxicity. The peptide-MHC-I/MHC-II molecular docking and cytokine production analyses were carried out for predicted epitopes. The selected highly immunogenic T-cell epitopes were then used to design two multiepitope fusion constructs. Next, prediction of the physicochemical and structural properties, B cell epitopes, and constructs-toll-like receptors (TLRs) molecular docking were performed for each construct. Finally, the eukaryotic expression plasmids harboring totally 12 cytotoxic T Lymphocyte (CTL) and 10 helper T lymphocytes (HTL) epitopes from HIV-1 proteins (i.e., pEGFP-N1-gag-pol-env-nef-rev), and linked to 2 CTL and 2 HTL epitopes from Hsp70 (i.e., pEGFP-N1-hsp70-gag-pol-env-nef-rev) were generated and transfected into HEK-293 T cells for evaluating the percentage of multiepitope peptides expression using flow cytometry and western blotting.

Results: The designed DNA constructs could be successfully expressed in mammalian cells. The expression rates of Gag-Pol-Env-Nef-Rev-GFP and Hsp70-Gag-Pol-Env-Nef-Rev-GFP were about 56-60% as the bands of ~ 63 and ~ 72 kDa confirmed in western blotting, respectively.

Conclusion: The combined in silico/in vitro methods indicated two multiepitope constructs can be produced and used as probable effective immunogens for HIV-1 vaccine development.
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http://dx.doi.org/10.1007/s10529-021-03143-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118377PMC
May 2021

Combination of human papillomaviruses L1 and L2 multiepitope constructs protects mice against tumor cells.

Fundam Clin Pharmacol 2021 Apr 30. Epub 2021 Apr 30.

Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Different types of cancer including cervical (> 90%), anal (~ 88%), vaginal (~ 40%), and penile (~ 40%) cancers are associated with HPV infections. Three prophylactic vaccines (Cervarix, Gardasil, and Gardasil-9) were approved to provide immuno-protection against certain types of HPVs. Currently, next-generation HPV vaccines such as L1/L2-based vaccines are being developed to provide broad-type HPV protection. In this study, we introduced a comprehensive framework for design of L1/L2 polyepitope-based HPV vaccine candidate. This framework started with protein sequence retrieval and followed by conservancy analysis between high-risk HPVs, MHC-I and MHC-II epitope mapping, and B-cell and T-cell epitope mapping. Subsequently, we performed Tap transport and proteasomal cleavage, population coverage, antigenicity, allergenicity and cross-reactivity. After that, peptide-MHCI/II flexible docking and comprehensive conservancy analysis against all HPV-types were carried out. The next steps were prediction of interferon-gamma and interleukin-10 inducing epitopes, epitope selection and construct design, tertiary structure prediction, refinement and validation, discontinuous B cell epitope prediction, vaccine-TLR4 molecular docking, and codon optimization. Our data showed that two designed vaccine constructs harboring 8 L1 peptides or 7 L2 peptides, individually were highly conserved between all well-known HPV types. In addition, the combination of in silico/in vivo approaches indicated the potential ability of L1 and L2 polyepitope constructs for development of next generation prophylactic/therapeutic HPV vaccine.
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http://dx.doi.org/10.1111/fcp.12690DOI Listing
April 2021

Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis.

PLoS One 2020 15;15(10):e0240577. Epub 2020 Oct 15.

Department of Hepatitis, AIDS and Blood-borne diseases, Pasteur Institute of Iran, Tehran, Iran.

The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2). A computational approach was adopted to identify multiepitope vaccine candidates against SARS-CoV-2 based on S, N and M proteins being able to elicit both humoral and cellular immune responses. In this study, the sequence of the virus was obtained from NCBI database and analyzed with in silico tools such as NetMHCpan, IEDB, BepiPred, NetCTL, Tap transport/proteasomal cleavage, Pa3P, GalexyPepDock, I-TASSER, Ellipro and ClusPro. To identify the most immunodominant regions, after analysis of population coverage and epitope conservancy, we proposed three different constructs based on linear B-cell, CTL and HTL epitopes. The 3D structure of constructs was assessed to find discontinuous B-cell epitopes. Among CTL predicted epitopes, S257-265, S603-611 and S360-368, and among HTL predicted epitopes, N167-181, S313-330 and S1110-1126 had better MHC binding rank. We found one putative CTL epitope, S360-368 related to receptor-binding domain (RBD) region for S protein. The predicted epitopes were non-allergen and showed a high quality of proteasomal cleavage and Tap transport efficiency and 100% conservancy within four different clades of SARS-CoV-2. For CTL and HTL epitopes, the highest population coverage of the world's population was calculated for S27-37 with 86.27% and for S196-231, S303-323, S313-330, S1009-1030 and N328-349 with 90.33%, respectively. We identified overall 10 discontinuous B-cell epitopes for three multiepitope constructs. All three constructs showed strong interactions with TLRs 2, 3 and 4 supporting the hypothesis of SARS-CoV-2 susceptibility to TLRs 2, 3 and 4 like other Coronaviridae families. These data demonstrated that the novel designed multiepitope constructs can contribute to develop SARS-CoV-2 peptide vaccine candidates. The in vivo studies are underway using several vaccination strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240577PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561160PMC
October 2020

An overview of vaccine design against different pathogens and cancer.

Expert Rev Vaccines 2020 08 10;19(8):699-726. Epub 2020 Aug 10.

Iranian Comprehensive Hemophilia Care Center , Tehran, Iran.

Introduction: Due to overcome the hardness of the vaccine design, computational vaccinology is emerging widely. Prediction of T cell and B cell epitopes, antigen processing analysis, antigenicity analysis, population coverage, conservancy analysis, allergenicity assessment, toxicity prediction, and protein-peptide docking are important steps in the process of designing and developing potent vaccines against various viruses and cancers. In order to perform all of the analyses, several bioinformatics tools and online web servers have been developed. Scientists must take the decision to apply more suitable and precise servers for each part based on their accuracy.

Areas Covered: In this review, a wide-range list of different bioinformatics tools and online web servers has been provided. Moreover, some studies were proposed to show the importance of various bioinformatics tools for predicting and developing efficient vaccines against different pathogens including viruses, bacteria, parasites, and fungi as well as cancer.

Expert Opinion: Immunoinformatics is the best way to find potential vaccine candidates against different pathogens. Thus, the selection of the most accurate tools is necessary to predict and develop potent preventive and therapeutic vaccines. To further evaluation of the computational and vaccine design, analyses are required to develop vaccine candidates.
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http://dx.doi.org/10.1080/14760584.2020.1794832DOI Listing
August 2020

Impact of Blood Transfusion on the Prevalence of HHpgV-1, HPgV-1, and B19V Among Iranian HCV-infected Patients With Hemophilia.

J Pediatr Hematol Oncol 2020 05;42(4):e213-e218

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Objective: Blood-derived products from patient with hemophilia treated by factor VIII concentrates are potential sources of transfusion-transmitted infections, including human immunodeficiency virus, hepatitis, human pegivirus-1 (HPgV-1), B19 virus, and also human hepegivirus-1 (HHpgV-1). In the current study, we investigated the impact of blood transfusion on the prevalence of HHpgV-1, HPgV-1, and B19 virus in plasma of Iranian patient with hemophilia after direct-acting antiviral treatment of hepatitis C virus (HCV) infections for the first time.

Materials And Methods: A total of 170 patients with hemophilia who received direct-acting antivirals were enrolled in this study. Among them, 92 patients had a history of blood transfusion. The presence of HHpgV-1, HPgV-1, and B19 virus was detected by nested polymerase chain reaction analysis using the conserved primers. The plasmids harboring 5'-UTR and NS3 were used as positive controls for HPgV-1 and HHpgV-1, respectively.

Results: Our data identified 3 individuals with HHpgV-1 viremia (1.76%), 11 individuals with HPgV-1 viremia (6.47%), and 33 individuals with B19 viremia (19.4%). All patients were negative for hepatitis B virus, human immunodeficiency virus, and HCV infections. These findings indicated lower transmissibility or higher rates of virus clearance for HHpgV-1, HPgV-1, and B19 virus as compared with other bloodborne human flaviviruses such as HCV. However, the prevalence of B19 virus was significantly higher than the other 2 viruses.

Conclusion: In general, these findings showed that the history of blood transfusion could increase the risk of viral transmission of bloodborne viruses among patient with hemophilia.
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http://dx.doi.org/10.1097/MPH.0000000000001717DOI Listing
May 2020

Development of HPV E5 and E7 peptides-based vaccines predicted by immunoinformatics tools.

Biotechnol Lett 2020 Mar 8;42(3):403-418. Epub 2020 Jan 8.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Objectives: Viral oncoproteins are ideal targets in therapeutic vaccines for functional inhibition of human papillomaviruses (HPVs). Herein, we designed the peptide constructs derived from E5 and E7 oncoproteins of high-risk HPV types 16, 18, 31 and 45 using the bioinformatics tools and investigated their potency in mice.

Results: The framework of the combined in silico/in vivo analysis included (1) to determine physicochemical properties of the designed constructs, (2) to identify potential IFN-γ-inducing epitopes, (3) to assess allergenicity, (4) to recognize linear and discontinuous B cell epitopes using modeling and validation of 3D structure of the designed constructs, and (5) to evaluate immune responses and tumor growth in vivo. Our in silico data determined high potency of the HPV E5 and HPV E7 peptides for trigger B- and T-cell responses, and IFN-γ secretion. In vivo study indicated that the mixture of E5 and E7 immunodominant peptides from four types of high-risk HPV could induce Th1 immune response, and protect completely mice against TC-1 tumor cells.

Conclusion: Generally, the combined in silico/in vivo approaches showed the ability of the designed E5 and E7 peptide constructs from four major high-risk HPV types for development of therapeutic vaccines.
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http://dx.doi.org/10.1007/s10529-020-02792-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087594PMC
March 2020

In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine.

Sci Rep 2019 10 23;9(1):15225. Epub 2019 Oct 23.

Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4 and CD8 T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.
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http://dx.doi.org/10.1038/s41598-019-51679-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811573PMC
October 2019

First Report of Prevalence of Blood-Borne Viruses (HBV, HCV, HIV, HTLV-1 and Parvovirus B19) Among Hemophilia Patients in Afghanistan.

Sci Rep 2019 05 13;9(1):7259. Epub 2019 May 13.

Molecular Diagnostic Divisions, Iranian Comprehensive Hemophilia Care Center, Tehran, Iran.

Blood-borne viruses including Hepatitis B and C, HIV, HTLV-1 and parvovirus B19 are still a factor of concern, especially for hemophilia patients. Although the safety of the blood supply continues to improve worldwide, the blood supply system in Afghanistan was damaged by many years of conflict and political instability. To date, there are few studies focused on the prevalence of blood-borne viruses in hemophilia patients. This study is first to investigate the prevalence of five blood-borne viruses in Afghanistan hemophilia patients in four cities including Kabul, Herat, Mazar-i-Sharif and Jalal Abad. A total of 80 hemophilia male patients were screening for the presence of five transfusion-transmitted viruses using ELISA and PCR. Data obtained showed 2.5% seropositivity for HBV, 8.75% seropositivity for HCV, and 91.25% seropositivity for parvovirus B19. None of the patients were positive for HIV and HTLV-1 and the prevalence of HCV was higher in older patients rather than younger patients. This finding, the first to report in Afghanistan, shows a high prevalence of parvovirus B19 in Afghanistan hemophilia patients and implementation of highly sensitive screening is necessary.
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http://dx.doi.org/10.1038/s41598-019-43541-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513844PMC
May 2019

Inflammatory and immune response genes: A genetic analysis of inhibitor development in Iranian hemophilia A patients.

Pediatr Hematol Oncol 2019 Feb 19;36(1):28-39. Epub 2019 Mar 19.

c Department of Hepatitis and AIDS , Pasteur Institute of Iran , Tehran , Iran.

A major problem of hemophilia A (HA) treatment is the development of factor VIII (FVIII) inhibitor, which usually occurs shortly after initiating replacement therapy. Several studies showed the correlation between inhibitor development and polymorphisms in inflammatory and immune response genes of HA patients; however, literature data are not available to prove this association in Iranian population. The aim of this study was to investigate a possible association between FVIII inhibitor formation and the polymorphisms of 16 inflammatory and immune response genes in Iranian severe HA patients (FVIII activity < 1%). This case-control study was performed on 55 patients with severe HA inhibitors and 45 samples without inhibitors from Iranian Comprehensive Hemophilia Care center. After extraction of whole genomic DNA from blood samples and design of primers for 16 genes, the genotyping was performed by Tetra primer ARMS PCR, and the validation of single nucleotide polymorphisms was determined by DNA sequencing. The data indicated that there was a significant association between inhibitor development, and F13A1 (TT), DOCK2 (CC& CT), and MAPK9 (TT) genotypes. Moreover, a considerably increased inhibitor risk carrying T, C, and T allele for F13A1, DOCK2, and MAPK9 genes was observed in patients with inhibitors, respectively. In contrast, there was no statistically significant difference between the genotypic and allelic frequencies for other genes in patients with inhibitors compared to patients without inhibitors. These results demonstrate that only polymorphisms in F13A1, DOCK2, and MAPK9 genes are associated with the risk of developing FVIII inhibitors in Iranian HA patients.
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http://dx.doi.org/10.1080/08880018.2019.1585503DOI Listing
February 2019

Analysis of long non-coding RNA expression in hemophilia A patients.

Hematology 2019 Dec;24(1):255-262

c Department of Hepatitis and AIDS , Pasteur Institute of Iran , Tehran , Iran.

Objectives: Hemophilia A (HA) is an inherited and rare X-linked bleeding disorder which is caused by mutations of the factor VIII gene (FVIII). Long non-coding RNAs (lncRNAs) are non-protein coding sequence transcripts containing more than 200 nucleotides and have potential in diagnosis, prevention and treatment of cancers and inherited bleeding disorders like thalassemia. The goal of this study was to determine the relationship between the expression of lncRNAs and the incidence of hemophilia A in Iranian population.

Methods: In this study, after bioinformatics analysis and lncRNA identification, the expression of two lncRNAs including NONHSAT139215 and NONHSAT139219 was investigated among the blood samples of severe hemophilia A and healthy (non-hemophilia) subjects using the relative qRT-PCR technique.

Results: The melting curve analysis confirmed the specificity of primers. Also, the standard curve showed that the efficiency of reactions for β2-microglobulin (B2M), NONHSAT139215 and NONHSAT139219 was 1.91, 1.96 and 2.01, respectively. On the other hand, the statistical analysis using REST software indicated that the expression of NONHSAT139219 and NONHSAT139215 in severe HA patients was significantly down-regulated as compared to control group (p < .05).

Discussion: Our results demonstrated that a decrease in the expression of two lncRNAs located in FVIII gene may play an important role for the development of severe hemophilia A for the first time.

Conclusions: Briefly, the abnormal expression levels of lncRNAs in hemophilia A cases may be correlated with disease intensity. However, further studies of these lncRNAs are required to provide a useful insight into hemophilia biology.
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http://dx.doi.org/10.1080/16078454.2018.1560934DOI Listing
December 2019

Human platelet antigens polymorphisms; association to the development of liver fibrosis in patients with chronic hepatitis C.

J Med Virol 2020 01 9;92(1):45-52. Epub 2019 Oct 9.

Department of Clinical Consult, Blood Transfusion Research Center, High Institute for Research & Education in Transfusion Medicine, Tehran, Iran.

Recently, human platelet antigens (HPAs) polymorphisms are found to play a role in susceptibility to hepatitis C virus (HCV) infection and fibrosis progression. The aim of the current study was to evaluate the possible association between the HPAs polymorphisms with liver fibrosis progression in HCV patients. HPAs polymorphisms genotyping was performed in HCV patients (n = 71) by Sequence-specific primers-polymerase chain reaction. Fibrosis progression was evaluated using the Metavir scoring system and liver biopsy, and the patients were assigned to two groups, namely, G1 (n = 35) that included patients with F1 (portal fibrosis without septa) or F2 (few septa) and G2 (n = 36) that comprised patients with F3 (numerous septa) or F4 (cirrhosis). The data analyses were performed using Pearson's χ test. The genotype frequency of HPA-3ab was significantly higher in G1 patients than in G2 patients (P = 0.015). No statistically significant differences were found between the patient groups (G1 and G2) regarding the distributions of the allelic and genotypic frequencies of the HPA-1, -2, -4, -5, and -15 systems. Multivariate logistic regression showed an independent association between the genotype HPA-3aa/BB and severe fibrosis (F3-F4), when compared with genotype HPA-3ab, independent of the viral genotype, high alanine transaminase, sex, age, time of infection, diabetes, and high cholesterol as risk factors. The present study suggested that the HPA-3ab genotype could be noticed as a potential protecting factor against hepatic fibrosis. Therefore, the antigenic variation of integrins might be considered as a part of the coordinated inflammatory process involved in the progression of liver fibrosis.
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http://dx.doi.org/10.1002/jmv.25423DOI Listing
January 2020

Prediction of cross-clade HIV-1 T-cell epitopes using immunoinformatics analysis.

Proteins 2018 12 1;86(12):1284-1293. Epub 2018 Nov 1.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Epitope mapping has emerged as a powerful tool to develop peptide vaccines against hypervariable viruses such as HIV. This method has led to stimulate a specific immune response and achieve advanced vaccine formulations. In this study, we identified peptides that were potentially immunostimulatory and highly conserved in HIV-1 main group. The analyses included were CTL assay, Tap transport, and the potential allergenicity. The highest population coverage rate was also found for all potential T-cell epitopes in 16 specified geographic regions of the world. The current study is the first attempt to explore peptide-protein flexible docking across all the major epitopes of HIV-1. Our data indicated that REV and VPU with the highest epitope identification scores, GP160 and VPR with the highest conservation (98.89%), and NEF and GP160 epitopes with a higher quality of peptide-protein interaction models in docking procedure were chosen as putative epitopes among all HLA class I epitopes. TAT , VPR , and VPU with the highest score of binding affinity, VPR with the highest conservation (97.55%), and GP160 epitope with a higher quality of peptide-protein interaction models in docking procedure were determined as putative epitopes among all HLA-DR epitopes. Furthermore, two epitopes of GP160 and VIF were predicted to bind 22 and 21 HLA-II alleles, respectively. Accumulative population coverage of potential helper T-cell epitopes and CTL epitopes varied between 90.82% and 100%. Generally, these predicted highly immunogenic T-cell epitopes can contribute to design HIV-1 peptide vaccine candidates. Combination of bioinformatics tools with in vivo methods will be necessary for HIV-1 vaccine development.
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http://dx.doi.org/10.1002/prot.25609DOI Listing
December 2018

Acute changes in cardiac function by direct acting antiviral therapy for hepatitis C-infected patients with thalassemia.

J Med Virol 2019 03 9;91(3):419-427. Epub 2018 Oct 9.

Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: Patients with thalassemia may also have cardiac abnormalities due to congenital problems, anemia, and increased burden of iron in their myocardium. This study was designed to evaluate the effects of direct acting antiviral (DAA) therapy on the cardiac function of hepatitis C virus (HCV)-infected patients with thalassemia.

Method: HCV-infected thalassemia patients were enrolled to this prospective evaluation. Daily tablets of 90 mg Ledipasvir (or 60 mg Daclatasvir) plus 400 mg Sofosbuvir (±ribavirin) were prescribed for the patients according to the Iran Hepatitis Network's guidelines. An echocardiography fellow collected the echocardiography findings before and after the treatment of all the patients. The patients were followed up for any cardiac events within 12 weeks after finishing the treatment.

Results: Thirty-two patients with the mean age of 24.2 ± 6.4 years were evaluated. All patients showed a sustained virological response at the 12th week after finishing the treatment. The patients' left ventricular end systolic diameter (3.0 vs 3.24; P = 0.003) and volume (33.8 vs 43.6; P = 0.001), global longitudinal strain of the left ventricle (-22.0 vs -20.6, P = 0.046), and average (-21.4 vs -20.3; P = 0.048), and the right ventricle size (3.12 vs 3.31; P = 0.012) were significantly increased after finishing the treatment. Changes in the abovementioned parameters were not correlated with the patients' myocardium iron load. There were no significant differences in other echocardiographic parameters ( P > 0.05) before and after the treatment.

Conclusion: Sofosbuvir-based regimens for HCV treatment were safe for our HCV-infected patients with thalassemia. Our patients' ejection fraction remained unchanged. Hence, more specialized echocardiographic evaluations were recommended for those with a history of cardiac abnormalities, cardiac iron overload, and in case of any cardiac adverse event during DAA therapy in patients with thalassemia.
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http://dx.doi.org/10.1002/jmv.25314DOI Listing
March 2019

Polymorphisms in the TGF-β1 (rs1982037) and IL-2 (rs2069762, rs4833248) genes are not associated with inhibitor development in Iranian patients with hemophilia A.

Hematology 2018 Dec 11;23(10):839-843. Epub 2018 Jul 11.

c Department of Hepatitis and AIDS , Pasteur Institute of Iran , Tehran , Iran.

Objectives Development of neutralizing antibodies against factor VIII is the major complication in hemophilia care which makes replacement therapies ineffective. The reports showed that inflammatory cytokines play an important role in inhibitor production. In the present study, the relationship between inhibitor development and the polymorphisms of two cytokine genes was studied in severe hemophiliac patients from Iran. Methods In this case-control study, three polymorphisms of immune regulatory genes [TGF-β (rs1982037) and IL-2 (rs2069762, rs4833248)] were analyzed in 100 Iranian hemophilia A patients divided into 55 inhibitor positive and 45 inhibitor negative patients using Tetra primer ARMS PCR, and DNA sequencing. Results The analysis of polymorphisms in the TGF-β and IL-2 genes showed no association between the genotypes and the production of inhibitors (p > 0.05). Also, comparison of allele frequencies for TGF-β and IL-2 genes between two groups indicated no significant differences associated with the development of FVIII inhibitors (p > 0.05). Discussion In contrast with some reports involving the correlation between polymorphisms of the TGF-β1 and IL-2 genes and inhibitor development in the world, no statistically significant differences in analysis of the alleles and genotypes for TGF-β and IL-2 genes were found between the inhibitor and non-inhibitor Iranian patients. Thus, other genetic markers influencing the immune response to replacement therapy in patients with hemophilia should be identified. Conclusions Regarding our results in molecular predisposition for inhibitor development, further studies of effective genetic markers are required as a prerequisite for the development of novel immunogenic therapeutic approaches in the future.
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http://dx.doi.org/10.1080/10245332.2018.1498168DOI Listing
December 2018

Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline.

Hepat Mon 2016 Aug 13;16(8):e40959. Epub 2016 Aug 13.

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran.

Context: Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran.

Evidence Acquisition: The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3 national consensus on management of Hepatitis C in Iran, held on 22 of July 2016.

Results: Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered.

Conclusions: Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.
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http://dx.doi.org/10.5812/hepatmon.guidelineDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075356PMC
August 2016

Physicochemical properties of polymers: An important system to overcome the cell barriers in gene transfection.

Biopolymers 2015 Jul;103(7):363-75

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

Delivery of the macromolecules including DNA, miRNA, and antisense oligonucleotides is typically mediated by carriers due to the large size and negative charge. Different physical (e.g., gene gun or electroporation), and chemical (e.g., cationic polymer or lipid) vectors have been already used to improve the efficiency of gene transfer. Polymer-based DNA delivery systems have attracted special interest, in particular via intravenous injection with many intra- and extracellular barriers. The recent progress has shown that stimuli-responsive polymers entitled as multifunctional nucleic acid vehicles can act to target specific cells. These nonviral carriers are classified by the type of stimulus including reduction potential, pH, and temperature. Generally, the physicochemical characterization of DNA-polymer complexes is critical to enhance the transfection potency via protection of DNA from nuclease digestion, endosomal escape, and nuclear localization. The successful clinical applications will depend on an exact insight of barriers in gene delivery and development of carriers overcoming these barriers. Consequently, improvement of novel cationic polymers with low toxicity and effective for biomedical use has attracted a great attention in gene therapy. This article summarizes the main physicochemical and biological properties of polyplexes describing their gene transfection behavior, in vitro and in vivo. In this line, the relative efficiencies of various cationic polymers are compared.
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http://dx.doi.org/10.1002/bip.22638DOI Listing
July 2015