Publications by authors named "Solmaz Sadeghi"

15 Publications

  • Page 1 of 1

Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches.

J Biomol Struct Dyn 2020 Sep 24:1-16. Epub 2020 Sep 24.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Most recently, the new coronavirus (SARS-CoV-2) has been recognized as a pandemic by the World Health Organization (WHO) while this virus shares substantial similarity with SARS-CoV. So far, no definitive vaccine or drug has been developed to cure Covid-19 disease, since many important aspects about Covid-19 such as pathogenesis and proliferation pathways are still unclear. It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. Based on this observation, it is expected that the virus infection can be inhibited if protein-protein interaction is prevented. In this study, using structure-based virtual screening of FDA databases, several lead drugs were discovered based on the ACE2-binding pocket of SARS-CoV-2 S protein. Then, binding affinity, binding modes, critical interactions, and pharmaceutical properties of the lead drugs were evaluated. Among the previously approved drugs, Diammonium Glycyrrhizinate, Digitoxin, Ivermectin, Rapamycin, Rifaximin, and Amphotericin B represented the most desirable features, and can be possible candidates for Covid-19 therapies. Furthermore, molecular dynamics (MD) simulation was accomplished for three S protein/drug complexes with the highest binding affinity and best conformation and binding free energies were also computed with the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Results demonstrated the stable binding of these compounds to the S protein; however, in order to confirm the curative effect of these drugs, clinical trials must be done.
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http://dx.doi.org/10.1080/07391102.2020.1824816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576931PMC
September 2020

Genetically modified immune cells targeting tumor antigens.

Pharmacol Ther 2020 10 15;214:107603. Epub 2020 Jun 15.

Targeted Tumor Vaccines Group, Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address:

Immunotherapy approaches consisting of genetically modified immune cells have become a promising platform for cancer treatment. Such 'living' therapies targeting tumor antigens have shown success in many cancer patients in the form of durable responses in a growing number of clinical studies. Besides, a large number of ongoing studies have been designed to introduce reliable methods for identification of tumor antigens. In addition, technical and biotechnological developments are being applied to the generation and expansion of genetically modified immune cells. In this review, we summarize and discuss the latest progress and current challenges in the tumor antigen landscape and in the generation of genetically modified immune cells in view of their clinical efficacy, either as monotherapy or combinational therapy.
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http://dx.doi.org/10.1016/j.pharmthera.2020.107603DOI Listing
October 2020

In silico mutagenesis in recombinant human keratinocyte growth factor: Improvement of stability and activity in addition to decrement immunogenicity.

J Mol Graph Model 2020 06 28;97:107551. Epub 2020 Jan 28.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

The recombinant human keratinocyte growth factor (rhKGF) is clinically applied to decrease the incidence and duration of cancer therapeutic agents. Particularly, it is extensively used for oral mucositis after chemotherapy-induced damage of different human cancers. However, the usage of rhKGF in treatment is limited owing to its short half-life, poor stability, immunogenicity, tendency to aggregate, and side effects. Therefore, there is a need to enhance the stability and to reduce immunogenicity of rhKGF for therapeutic applications. In this study, the stability, activity, and immunogenicity of rhKGF were improved using computational methods. The several mutations were generated based on sequence alignment, amino acids physic-chemical properties, and the structure simulation. The 3D structure of rhKGF and proposed mutants were predicted by Modeller v9.15 program, and then were evaluated using PROSESS, PROCHECK, and ProSA web tools. Afterwards, the effect of these mutants on rhKGF structure, stability, activity, and its interaction with fibroblast growth factor receptor2-IIb (FGFR2-IIb) was analyzed through utilizing GROMACS molecular dynamics simulations and docking tools, respectively. Also, binding free energies were calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. We found that F63Y, R121K, and combine1 (K38R, F63Y, K72E, N105S) mutants lead to reduction of the number of T-cell epitopes. However, all of the selected mutants, except for R121K, could considerably increase stability and affinity of the rhKGF to FGFR2-IIb, in silico. In conclusion, this study, for the first time, offered that the combine1 and F63Y mutants could highly improve the stability and activity of rhKGF and even reduce immunogenicity without having any significant effect on the biological functions of rhKGF.
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http://dx.doi.org/10.1016/j.jmgm.2020.107551DOI Listing
June 2020

Evaluation the potential of recombinant anti-CD3 nanobody on immunomodulatory function.

Mol Immunol 2020 02 26;118:174-181. Epub 2019 Dec 26.

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. Electronic address:

T cells are the most predominant effector cells in immune-mediated elimination of cancer and circumventing tumor progression. Among various approaches, T cells activation by specific antibodies independently of their TCR specificity, is considered as an effective approach to circumvent tumor progression. The most common surface marker for all T cells which is crucial for T cell activation is regarded as CD3. Therefore, the goal of our study was to evaluate the preclinical efficacy of recombinant anti-CD3 nanobody. To this end, anti-CD3 sequence, was PCR amplified, following cloning and expression in E.coli and purification, the purified nanobody with a molecular weight of ∼17 kDa was confirmed by western blot. Furthermore, flow cytometry analysis demonstrated that purified nanobody could bind to CD3 on Jurkat cell line. Subsequently, results from inoculation of 3 μg/g of nanobody to tumor bearing balb/c mice indicate inhibition of tumor growth. Furthermore, circulating levels of tumoricidal cytokines such as IL-2 and IFNγ were raised whereas tolerogenic cytokines such as IL-4, 6 and 10 were decreased at the end of the treatment. Moreover, IHC analysis confirmed the presence and also the percentage of TILs in tumor sites in response to anti-CD3 therapy. Hence, our results suggest that the purified anti-CD3 nanobody may become a promising candidate for targeting and activating CTLs to induce anti-tumor responses and may provide groundwork for future studies involving other kind of cancers.
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http://dx.doi.org/10.1016/j.molimm.2019.12.017DOI Listing
February 2020

Evaluation of eight formulas for LDL-C estimation in Iranian subjects with different metabolic health statuses.

Lipids Health Dis 2019 Dec 28;18(1):231. Epub 2019 Dec 28.

Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Background: Considering the crucial role of low-density lipoprotein-cholesterol (LDL-C) concentration in determining cardiovascular risk, the accuracy of LDL-C estimation is essential. To date, various types of formulae have been introduced, albeit their accuracy has not been assessed in varied populations. In this study, the accuracy of eight formulae for LDL-C estimation was evaluated in an Iranian population.

Methods: A data set of 2752 individuals was included in the study and all samples were analyzed in term of lipid profiles using direct homogeneous assay. The population was divided into various subgroups based on the triglyceride (TG), high-density lipoprotein- cholesterol (HDL-C), total cholesterol (TC), fasting blood sugar (FBS) and age values and estimated LDL-C values by Friedewald, Chen, de Cordova, Vujovic, Anandaraja, Hattori, Ahmadi, and Puavillai equations were compared to the directly measured LDL-C in each subgroup.

Results: Estimated LDL-C values by Puavillai formulae showed an insignificant difference compared to the directly measured LDL-C in subjects with high level of TG. However, for TG range < 3.38 mmol/L and high levels of HDL-C, the difference between the means of estimated LDL-C by Hattori and de Cordova formulas, and directly measured LDL-C was relatively lower than other equations. In addition, estimated LDL-C by Hattori and de Cordova formulae had insignificant differences as compared to the direct LDL-C at some levels of cholesterol, the normal level of FBS and some age ranges.

Conclusions: Therefore, it seems that Hattori and de Cordova formulas can be considered as the best alternatives for LDL-C direct measurement in the Iranian population, especially for healthy subjects.
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http://dx.doi.org/10.1186/s12944-019-1178-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935216PMC
December 2019

Identification of candidate genes and miRNAs for sensitizing resistant colorectal cancer cells to oxaliplatin and irinotecan.

Cancer Chemother Pharmacol 2020 01 28;85(1):153-171. Epub 2019 Nov 28.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Drug resistance to irinotecan and oxaliplatin, two widely used chemotherapeutic, has become a common problem in cancerous patients. Despite numerous valuable studies, distinct molecular mechanisms involved in the acquisition of resistance to these anti-cancer drugs have remained a challenge. In this study, we studied the possible resistance mechanisms to irinotecan and oxaliplatin in three CRC cell lines (HCT116, HT29, and LoVo) via integration of microarray data with gene regulatory networks. After determination of hub genes, corresponding miRNAs were predicted using several databases and used in construction and subsequent analysis of miRNA-gene networks. Following to preparation of chemo-resistance CRC cells, a standard real-time PCR was conducted for validation of in silico findings. Topological and functional enrichment analyses of the resulted networks introduced several previously reported drug-resistance genes as well as novel biomarkers as hub genes which seem to be crucial in resistance of colon cancer cells to irinotecan and oxaliplatin. Furthermore, results of the functional annotation revealed the essential role of different signaling pathways like metabolic pathways in drug resistance of CRC cell lines to these drugs. A part of in silico findings was also validated in vitro using oxaliplatin-resistant cell lines. While FOXC1 and NFIC were upregulated in cell lines which were resistant to oxaliplatin, silencing FOXC1 decreased the resistance of SW480 cell line to oxaliplatin. In conclusion, our comparative in silico and in vitro study introduces several novel genes and miRNAs as the resistance-mediators which can be used for sensitizing resistant CRC cells to oxaliplatin and irinotecan.
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http://dx.doi.org/10.1007/s00280-019-03975-3DOI Listing
January 2020

Production of CAR T-cells by GMP-grade lentiviral vectors: latest advances and future prospects.

Crit Rev Clin Lab Sci 2019 09 17;56(6):393-419. Epub 2019 Jul 17.

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR , Tehran , Iran.

Chimeric antigen receptor (CAR) T-cells represent a paradigm shift in cancer immunotherapy and a new milestone in the history of oncology. In 2017, the Food and Drug Administration approved two CD19-targeted CAR T-cell therapies (Kymriah™, Novartis, and Yescarta™, Kite Pharma/Gilead Sciences) that have remarkable efficacy in some B-cell malignancies. The CAR approach is currently being evaluated in multiple pivotal trials designed for the immunotherapy of hematological malignancies as well as solid tumors. To generate CAR T-cells , lentiviral vectors (LVs) are particularly appealing due to their ability to stably integrate relatively large DNA inserts, and to efficiently transduce both dividing and nondividing cells. This review discusses the latest advances and challenges in the design and production of CAR T-cells, and the good manufacturing practices (GMP)-grade production process of LVs used as a gene transfer vehicle. New developments in the application of CAR T-cell therapy are also outlined with particular emphasis on next-generation allogeneic CAR T-cells.
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http://dx.doi.org/10.1080/10408363.2019.1633512DOI Listing
September 2019

Improved osteogenic differentiation of human induced pluripotent stem cells cultured on polyvinylidene fluoride/collagen/platelet-rich plasma composite nanofibers.

J Cell Physiol 2020 02 27;235(2):1155-1164. Epub 2019 Jun 27.

Department of Biology, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran.

Blood transfusion or blood products, such as plasma, have a long history in improving health, but today, platelet-rich plasma (PRP) is used in various medical areas such as surgery, orthopedics, and rheumatology in many ways. Considering the high efficiency of tissue engineering in repairing bone defects, in this study, we investigated the combined effect of nanofibrous scaffolds in combination with PRP on the osteogenic differentiation potential of human induced pluripotent stem cells (iPSCs). Electrospinning was used for fabricating nanofibrous scaffolds by polyvinylidene fluoride/collagen (PVDF/col) with and without PRP. After scaffold characterization, the osteoinductivity of the fabricated scaffolds was studied by culturing human iPSCs under osteogenic medium. The results showed that PRP has a considerable positive effect on the biocompatibility of the PVDF/col nanofibrous scaffold when examined by protein adsorption, cell attachment, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. In addition, the results obtained from alkaline phosphatase activity and calcium content assays demonstrated that nanofibers have higher osteoinductivity while grown on PRP-incorporated PVDF/col nanofibers. These results were also confirmed while the osteogenic differentiation of the iPSCs was more investigated by evaluating the most important bone-related genes expression level. According to the results, it can be concluded that PVDF/col/PRP has much more osteoinductivity while compared with the PVDF/col, and it can be introduced as a promising bone bio-implant for use in bone tissue engineering applications.
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http://dx.doi.org/10.1002/jcp.29029DOI Listing
February 2020

Identification of new DNA gyrase inhibitors based on bioactive compounds from streptomyces: structure-based virtual screening and molecular dynamics simulations approaches.

J Biomol Struct Dyn 2020 02 27;38(3):791-806. Epub 2019 Mar 27.

Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

DNA gyrase enzyme has vital role in bacterial survival and can be considered as a potential drug target. Owing to the appearance of resistance to gyrase-targeted drugs, especially fluoroquinolone, screening new compounds which bind more efficiently to the mutant binding pocket is essential. Hence, in this work, using Smina Autodock and through structure-based virtual screening of StreptomeDB, several natural products were discovered based on the SimocyclinoneD8 (SD8) binding pocket of GyrA subunit of DNA gyrase. After evaluation of binding affinity, binding modes, critical interactions and physicochemical and pharmaceutical properties, three lead compounds were selected for further analysis. Afterward 60 ns molecular dynamics simulations were performed and binding free energies were calculated by the molecular mechanics/Poisson-Boltzmann surface area method. Also, interaction of the selected lead compounds with the mutated GyrA protein was evaluated. Results indicated that all of the selected compounds could bind to the both wild-type and mutated GyrA with the binding affinities remarkably higher than SimocyclinoneD8. Interestingly, we noticed that the selected compounds comprised angucycline moiety in their structure which could sufficiently interact with GyrA and block the DNA binding pocket of DNA gyrase, . In conclusion, three DNA gyrase inhibitors were identified successfully which were highly capable of impeding DNA gyrase and can be considered as potential drug candidates for treatment of fluoroquinolone-resistant strains.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1588784DOI Listing
February 2020

In silico studying of the whole protein structure and dynamics of Dickkopf family members showed that N-terminal domain of Dickkopf 2 in contrary to other Dickkopfs facilitates its interaction with low density lipoprotein receptor related protein 5/6.

J Biomol Struct Dyn 2019 Jul 17;37(10):2564-2580. Epub 2018 Nov 17.

a Department of Medical Biotechnology, School of Advanced Technologies in Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Wnt (Wingless Int) signaling pathway has been known to be dysregulated in several human cancers, especially colorectal cancer (CRC). The Dickkopf (DKK) family which consists of four secreted proteins in vertebrates (DKK 1, 2, 3, 4) is one of the most critical antagonist families for Wnt signaling pathway. They typically antagonize Wnt/β-catenin signaling by binding and inhibiting Wnt co-receptors, LRP5/6 (low density lipoprotein receptor related protein 5/6). However, except for DKK1 (Dickkopf 1), details about structure and function of the members of this family are poorly defined. In this study, main Dickkopf family members were analyzed structurally, using protein structure prediction tools, molecular dynamics (MD), molecular docking and energy analyses. Three dimensional structure of whole DKKs was predicted and their interaction with LRP6 was investigated in detail. The results indicated that in DKK family members, a considerable diversity, in the case of structure, activity and physicochemical properties was seen. This diversity was more profound in DKK3 (Dickkopf3). Interestingly, the interaction mode of DKK2 (Dickkopf2) with its receptor, LRP6, was shown to be substantially different from other Dickkopf family members while N-terminal region of this ligand was also involved in the binding to the LRP6-P3P4. Moreover, the cysteine-rich domain 2 (CRD2) of DKK1 and DKK3 had a higher binding affinity to LRP6 in comparison with the whole protein structures. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2018.1491891DOI Listing
July 2019

Immunomodulatory effects of a rationally designed peptide mimetic of human IFNβ in EAE model of multiple sclerosis.

Prog Neuropsychopharmacol Biol Psychiatry 2018 03 1;82:49-61. Epub 2017 Dec 1.

Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran. Electronic address:

The efficiency of interferon beta (IFNβ)-based drugs is considerably limited due to their undesirable properties, especially high immunogenicity. In this study, for the first time we investigated the impact of a computationally designed peptide mimetic of IFNβ, called MSPEP27, in the animal model of MS. A peptide library was constructed using the Rosetta program based on the predominant IFNAR1-binding site of IFNβ. Molecular docking studies were carried out using ClusPro and HADDOCK tools. The GROMACS package was subsequently used for molecular dynamics (MD) simulations. Validation of peptide-receptor interaction was carried out using intrinsic fluorescence measurements. To explore in silico findings further, experimental autoimmune encephalomyelitis (EAE) was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein (MOG35-55). Mice were then separated into distinct groups and intravenously received 10 or 20mgkg of MSPEP27 or IFNβ. The inflammatory mediators were monitored by immunohistochemistry (IL17, CD11b, CD45), quantitative real-time PCR (MMP2, MMP9, TIMP-1) and enzyme-linked immunosorbent assay (IL1β, TNFα) methods. Among the library of tolerated peptides, MSPEP27, a peptide with favorable physicochemical properties, was chosen for further experiments. This peptide was shown to significantly interact with IFNAR1 in a dose-dependent manner. Like IFNβ, MSPEP27 could efficiently bind to IFNAR1 and form a stable peptide-receptor complex during 30ns MD simulations. In vivo analyses revealed that MSPEP27 could lessen inflammation by modulating the levels of inflammatory mediators. According to our results, MSPEP27 peptide could efficiently bind to IFNAR1 and suppress neuroinflammation in vivo. We conclude that MSPEP27 has protective effects against MOG-induced EAE via reduction of immune dysfunction and inflammation.
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http://dx.doi.org/10.1016/j.pnpbp.2017.11.028DOI Listing
March 2018

Rational design of DKK3 structure-based small peptides as antagonists of Wnt signaling pathway and in silico evaluation of their efficiency.

PLoS One 2017 24;12(2):e0172217. Epub 2017 Feb 24.

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Dysregulated Wnt signaling pathway is highly associated with the pathogenesis of several human cancers. Dickkopf proteins (DKKs) are thought to inhibit Wnt signaling pathway through binding to lipoprotein receptor-related protein (LRP) 5/6. In this study, based on the 3-dimensional (3D) structure of DKK3 Cys-rich domain 2 (CRD2), we have designed and developed several peptide inhibitors of Wnt signaling pathway. Modeller 9.15 package was used to predict 3D structure of CRD2 based on the Homology modeling (HM) protocol. After refinement and minimization with GalaxyRefine and NOMAD-REF servers, the quality of selected models was evaluated utilizing VADAR, SAVES and ProSA servers. Molecular docking studies as well as literature-based information revealed two distinct boxes located at CRD2 which are actively involved in the DKK3-LRP5/6 interaction. A peptide library was constructed conducting the backrub sequence tolerance scanning protocol in Rosetta3.5 according to the DKK3-LRP5/6 binding sites. Seven tolerated peptides were chosen and their binding affinity and stability were improved by some logical amino acid substitutions. Molecular dynamics (MD) simulations of peptide-LRP5/6 complexes were carried out using GROMACS package. After evaluation of binding free energies, stability, electrostatic potential and some physicochemical properties utilizing computational approaches, three peptides (PEP-I1, PEP-I3 and PEP-II2) demonstrated desirable features. However, all seven improved peptides could sufficiently block the Wnt-binding site of LRP6 in silico. In conclusion, we have designed and improved several small peptides based on the LRP6-binding site of CRD2 of DKK3. These peptides are highly capable of binding to LRP6 in silico, and may prevent the formation of active Wnt-LRP6-Fz complex.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172217PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325476PMC
September 2017

In silico enhancement of the stability and activity of keratinocyte growth factor.

J Theor Biol 2017 04 16;418:111-121. Epub 2017 Jan 16.

Molecular Medicine Department, Biotechnology Research Center., Pasteur Institute of Iran, Iran. Electronic address:

Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family, has been implicated in some biological processes such as cell proliferation, development and differentiation. High mitogenic activity of this protein has made it very suitable for repairing radiation-and chemotherapy-induced damages. Palifermin, which has been developed from human KGF, is clinically applied to reduce the incidence and duration of cancer therapeutic agents. However, the activity of Palifermin is limited during treatment due to its poor stability. In this study, we have improved the stability and activity of recombinant human KGF (Palifermin) using a computational mutagenesis approach. According to the KGF multiple sequence alignment among different species as well as literature-based information, we have generated several mutations using PyMOL program and evaluated their effects on the stability and activity of KGF in silico. In order to preserve the KGF activity, we did not change the predicted functional residues. Prior to mutagenesis, the 3D structure of rhKGF was predicted by Modeller v9.15 program and quantitative evaluation of predicted models were carried out using VADAR and PROSESS servers. The stability and activity of rhKGF mutants were analyzed using GROMACS molecular dynamics (MD) simulations and docking tools, respectively. The results showed that N159S (N105S in rhKGF sequence) and I172V (I118V in rhKGF) substitutions caused an increased stability and affinity of the rhKGF to Fibroblast growth factor receptor 2 (FGFR2). We will evaluate the effects of favorable mutations on the rhKGF stability and activity in vitro.
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http://dx.doi.org/10.1016/j.jtbi.2017.01.009DOI Listing
April 2017

Impacts of the G145R Mutation on the Structure and Immunogenic Activity of the Hepatitis B Surface Antigen: A Computational Analysis.

Hepat Mon 2016 Jul 28;16(7):e39097. Epub 2016 Jun 28.

Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Vaccine-escaped hepatitis B virus (HBV) mutations occur within the "a" determinant area, which is located in the major hydrophilic region (MHR) of the hepatitis B surface antigen (HBsAg) protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated.

Objectives: The present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg.

Materials And Methods: Three-dimensional (3D) structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package.

Results: The G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the "a" determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the "a" determinant.

Conclusions: These data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.
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http://dx.doi.org/10.5812/hepatmon.39097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018363PMC
July 2016

The role of mother's oral and vaginal yeasts in transmission of Helicobacter pylori to neonates.

Arch Iran Med 2013 May;16(5):288-94

Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran.

Background: Oral cavity has been proposed as an important reservoir of H.pylori, being implicated in bacterial transmission through oral-oral route. However, some investigators believe that the newborn acquires H.pylori from mother through vaginal delivery. In this study, oral and vaginal yeasts were examined for the intracellular occurrence of H.pylori and their possible role in bacterial transmission. 

Methods: Sixty nine oral and vaginal yeasts from expecting mothers (39 oral and 30 vaginal) and seven oral yeasts from neonates(6/46 vaginal delivery, 1/43 cesarean) were identified and studied by light and fluorescent microscopy for observing the intracellular bacterium-like bodies(BLBs). Whole DNAs of yeasts were recruited for detection of H.pylori-specific genes. Urea breath test (UBT) was performed for detection of H.pylori infection in mothers. Stool antigen test (SAT) was used for detection of H.pylori antigens in infants' stool at birth and six months of age. 

Results: Oral yeasts were isolated more frequently from normally-delivered neonates. The frequency of H.pylori genes in mothers' vaginal yeasts was significantly higher than in mothers' oral yeasts. A significant correlation was found between the occurrence of H.pylori genes in vaginal yeasts and that in neonates' oral yeasts, occurrence of H.pylori genes in mothers' vaginal yeasts or neonates' oral yeasts, and UBT+ results in mothers.

Conclusion: C.albicans which colonizes the oral cavity of neonates through vaginal delivery or contact with environment or healthcare workers could be an important reservoir of H.pylori. Vaginal yeasts are more potent in accommodating H.pylori than oral yeasts. Accordingly, vaginal yeast is proposed as the primary reservoir of H.pylori which facilitates H.pylori transmission to neonates.
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http://dx.doi.org/013165/AIM.009DOI Listing
May 2013