Publications by authors named "Sayed Mahdi Marashi"

60 Publications

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Arch Virol 2021 Feb 3. Epub 2021 Feb 3.

Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.
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http://dx.doi.org/10.1007/s00705-021-04964-9DOI Listing
February 2021

Vitamin D and Covid-19: From potential therapeutic effects to unanswered questions.

Rev Med Virol 2020 Aug 28:e2159. Epub 2020 Aug 28.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Evidence suggests that vitamin D supplementation could potentially be effective either in treatment or prevention of coronavirus disease 2019 (Covid-19). Indeed, several studies and trials have begun to investigate the impact of vitamin D supplementation on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we focus on the potential mechanisms of vitamin D in the pathogenesis of Covid-19. We consider whether deficiency of vitamin D may be one of the underlying biological factors that could explain the excess mortality seen among non-Caucasians. We also raise several important questions which need to be addressed to provide a clear picture of the extent to which vitamin D supplementation may benefit patients with Covid-19, particularly those with underlying risk factors.
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http://dx.doi.org/10.1002/rmv.2159DOI Listing
August 2020

Effect of Cytomegalovirus Recombinant Phosphoprotein 150 (pp150) on Maturation and Function of Murine Dendritic Cells: an In-Vitro Study.

Iran J Immunol 2020 Mar;17(1):26-40

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated.

Objective: To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs).

Methods: Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized. Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs.

Results: A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α.

Conclusion: Despite improvements in maturity status, pp150-stimulated DCs did not seem to be able to induce Th1 or Th2 immunity. In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's mechanism of action. However, it is necessary to conduct further investigations to corroborate these observations.
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http://dx.doi.org/10.22034/iji.2020.80292DOI Listing
March 2020

Ventilator settings and outcome of respiratory failure in paraquat-induced pulmonary injury.

Sci Rep 2019 11 12;9(1):16541. Epub 2019 Nov 12.

Emergency Room, Division of Medical Toxicology, Hazrat Ali-Asghar (p) Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Paraquat is a nonselective contact herbicide that has significant importance in clinical toxicology due to its high mortality rate. The cause of mortality in the acute phase of poisoning is a multi-organ failure while in the sub-acute phase is alveolar injury and lung fibrosis. The aim of this study was to evaluate the advantages and drawbacks of mechanical ventilation (MV) in paraquat-induced pulmonary injury and its consequential respiratory failure (PIPI-CRF). This retrospective descriptive analytical study was done to investigate the outcome of patients who had developed PIPI-CRF and underwent conventional treatments with invasive MV in three teaching hospitals in Shiraz, Iran, from March 2010 to February 2015. In total, 44 patients (mean age of 27.9 ± 9.98 years) had undergone MV due to PIPI-CRF. None of the patients had a successful wean off from the ventilator. Although all the patients' were on aggressive life support and full efforts to resuscitate were carried out in case of cardiac arrest, all of them expired. We suggest that in the case of conventional treatment of paraquat poisoning, only noninvasive ventilation should be applied. However, considering the chance of patient's survival performing novel treatments, such as extracorporeal membrane oxygenation (ECMO), lung protective ventilation with optimal positive end-expiratory pressure (PEEP) could be applied only in such circumstances.
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http://dx.doi.org/10.1038/s41598-019-52939-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851175PMC
November 2019

Ventilator settings and outcome of respiratory failure in paraquat-induced pulmonary injury.

Sci Rep 2019 11 12;9(1):16541. Epub 2019 Nov 12.

Emergency Room, Division of Medical Toxicology, Hazrat Ali-Asghar (p) Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Paraquat is a nonselective contact herbicide that has significant importance in clinical toxicology due to its high mortality rate. The cause of mortality in the acute phase of poisoning is a multi-organ failure while in the sub-acute phase is alveolar injury and lung fibrosis. The aim of this study was to evaluate the advantages and drawbacks of mechanical ventilation (MV) in paraquat-induced pulmonary injury and its consequential respiratory failure (PIPI-CRF). This retrospective descriptive analytical study was done to investigate the outcome of patients who had developed PIPI-CRF and underwent conventional treatments with invasive MV in three teaching hospitals in Shiraz, Iran, from March 2010 to February 2015. In total, 44 patients (mean age of 27.9 ± 9.98 years) had undergone MV due to PIPI-CRF. None of the patients had a successful wean off from the ventilator. Although all the patients' were on aggressive life support and full efforts to resuscitate were carried out in case of cardiac arrest, all of them expired. We suggest that in the case of conventional treatment of paraquat poisoning, only noninvasive ventilation should be applied. However, considering the chance of patient's survival performing novel treatments, such as extracorporeal membrane oxygenation (ECMO), lung protective ventilation with optimal positive end-expiratory pressure (PEEP) could be applied only in such circumstances.
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http://dx.doi.org/10.1038/s41598-019-52939-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851175PMC
November 2019

Will Nanotechnology Bring New Hope for Stem Cell Therapy?

Cells Tissues Organs 2018 9;206(4-5):229-241. Epub 2019 Jul 9.

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

The potential of stem cell therapy has been shown in preclinical trials for the treatment of damage and replacement of organs and degenerative diseases. After many years of research, its clinical application is limited. Currently there is not a single stem cell therapy product or procedure. Nanotechnology is an emerging field in medicine and has huge potential due to its unique characteristics such as its size, surface effects, tunnel effects, and quantum size effect. The importance of application of nanotechnology in stem cell technology and cell-based therapies has been recognized. In particular, the effects of nanotopography on stem cell differentiation, proliferation, and adhesion have become an area of intense research in tissue engineering and regenerative medicine. Despite the many opportunities that nanotechnology can create to change the fate of stem cell technology and cell therapies, it poses several risks since some nanomaterials are cytotoxic and can affect the differentiation program of stem cells and their viability. Here we review some of the advances and the prospects of nanotechnology in stem cell research and cell-based therapies and discuss the issues, obstacles, applications, and approaches with the aim of opening new avenues for further research.
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http://dx.doi.org/10.1159/000500517DOI Listing
July 2019

Improved Function and Maturation of Dendritic Cells Stimulated by Recombinant pp65 Protein: An in-vitro Design.

Iran J Immunol 2019 Mar;16(1):11-25

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Stimulated dendritic cells (DCs) have been shown to be effective in the induction of specific immune cells. Also, the CMV pp65 plays an important role in CMV life cycle and immune recognition.

Objective: To assess the effect of CMV pp65 on the maturity and function of dendritic cells.

Methods: Splenic DCs were treated with non-cytotoxic concentrations of the pp65 and analyzed for MHC II, CD86, and CD40 expression by flow cytometry. Then, ROR-γ, GATA3, T-bet, and FOXP3 gene expression levels were evaluated in T cells co-cultured with DCs using Real time-PCR. Finally, the effects of pp65 on allogenic T-cell responses in mixed lymphocyte culture (MLR), and the release of cytokines were investigated by ELISA and flow cytometry.

Results: The phagocytosis rate was significantly lower in the pp65-treated DCs than the non-stimulated DCs. There were significant differences in the raised level of CD40, CD86, and CCR7 in DCs as maturation markers. Furthermore, ROR-γ, and T-bet overexpression in T cells of the pp65-treated group compared with the non-stimulated group was observed. Significant differences were observed in the levels of IL-2, IL-6, IL-17, IL-22, TNF-α, and IFN-γ in pp65-stimulated groups compared with the non-stimulated DCs.

Conclusions: The pp65-treated DCs can induce differentiation and functional activity of the cellular immune system, including Th17, and Th1, but not other major T-cell subsets such as Tregs, and Th2 population.
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http://dx.doi.org/10.22034/IJI.2019.39403DOI Listing
March 2019

Rotavirus VP6 as a potential vaccine candidate.

Rev Med Virol 2019 03 6;29(2):e2027. Epub 2019 Jan 6.

Virology Department, Pasteur Institute of Iran, Tehran, Iran.

By the age of 5 years, virtually all children have been infected by group A rotavirus (RVA), which is responsible for around half million mortality annually prior to vaccination. Relatively high rate of the morbidity and mortality highlights the necessity of applying preventive procedures particularly in developing countries. Two live attenuated RVA vaccines (Rotarix and RotaTeq) are licensed and now being used in many countries worldwide. Although these vaccines are shown to reduce the mortality up to 50%, several key questions yet remained to answer. Indeed, the licensed RV vaccines were found to be less effective in countries of sub-Saharan Africa and Southeast Asia. Therefore, developing next generation RVA vaccines is warranted. VP6 is highly abundant and conserved protein that forms the middle layer of RV particles and was shown to be both antigenic and immunogenic. Although it does not induce neutralizing antibodies, different VP6 preparations were found to induce homologous and cross-reactive immune responses with partial protection from RVA replication. Although the molecular mechanisms are not fully elucidated, VP6-based RVA vaccine candidates are worthy of further consideration. This review aims to focus on different aspects of VP6 protein and its potentiality for an alternative RV vaccine against RV disease.
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http://dx.doi.org/10.1002/rmv.2027DOI Listing
March 2019

The interplay between vitamin D and viral infections.

Rev Med Virol 2019 03 6;29(2):e2032. Epub 2019 Jan 6.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti-viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti-viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.
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http://dx.doi.org/10.1002/rmv.2032DOI Listing
March 2019

Integrational analysis of miRNAs data sets as a plausible missing linker between Epstein-Barr virus and vitamin D in relapsing remitting MS patients.

Gene 2019 Mar 12;689:1-10. Epub 2018 Dec 12.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Given the multifactorial state of autoimmune complex diseases such as multiple sclerosis (MS), it is not clear if different risk factors act jointly or independently. Despite intensive studies investigating multi aspects of MS risk factors, findings with regards to potential biomarkers that may link these risk factors remained largely inconclusive. System biology or data integration utilizes different validated datasets to extract meaningful information and map the plausible biological pathways and networks. As such, we integrated eight transcriptome datasets to find the differentially expressed miRNAs in peripheral blood (PB) between relapsing remitting MS patients (RRMS) and normal group. After identification the targeted genes of miRNAs, the hub genes were used to construct the underlying protein-protein interaction network and signaling pathways. As results, 9 miRNAs were best exemplified by significant dysregulation including hsa-mir-15a, hsa-mir-484, hsa-mir-30d, hsa-mir-145, hsa-mir-363, has-let-7e, hsa-mir-30a, hsa-let-7b, and hsa-mir-146a. System biology analysis of miRNAs in PB of RRMS patients clearly indicates the involvement of miRNAs in many vital pathways and highlighted the possibility of an association between miRNAs with EBV and vitamin D in MS pathogenesis. Described novel pathways and genes related to miRNAs such as Transient receptor potential channels and Acid sphingomyelinase may provide a potential target for therapeutic approaches although further functional studies are warranted to test these candidates.
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http://dx.doi.org/10.1016/j.gene.2018.12.004DOI Listing
March 2019

Human herpesvirus 8 DNA detection and variant analysis in patients with multiple sclerosis.

Virusdisease 2018 Dec 10;29(4):540-543. Epub 2018 Aug 10.

1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155 Iran.

Several studies reported a complex interplay between viral infections and neural cells leading to multiple sclerosis. A role for some viral infections has been proposed in MS. In this study, DNA sequences of human herpesvirus 8 (HHV-8) were searched in the peripheral blood of 54 patients with multiple sclerosis and 130 healthy subjects using nested-PCR assay to amplify ORF26 locus. Furthermore, HHV-8 positive samples were subjected to a nested-PCR to amplify K1 gene of HHV-8 followed by direct nucleotide sequencing. HHV-8 genome was detected in 18.5% (10/54) and 3% (4/130) of MS patients and controls, respectively, and the difference reached statistically significant level ( = 0.0017). Genotyping analysis revealed that genotype C was common (88.9%) in all study subjects, followed by genotype A. Our results showed higher detection of HHV-8 DNA in MS patients than control group.
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http://dx.doi.org/10.1007/s13337-018-0481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261899PMC
December 2018

The potential roles of herpesvirus and cytomegalovirus in the exacerbation of pemphigus vulgaris.

Dermatol Pract Concept 2018 Oct 31;8(4):262-271. Epub 2018 Oct 31.

Autoimmune Bullous Disease Research Center, Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Among exogenous etiologies, the critical role of microbial agents such as herpesviruses (HSV1/2) and cytomegalovirus (CMV) in triggering and flaring autoimmune conditions such as pemphigus vulgaris (PV) has been recently discovered.

Objectives: The present study aimed to investigate the plausible role of these viruses in the exacerbation of PV using serological and molecular methods.

Patients/methods: Sixty patients with PV (30 with relapse type and 30 with remission type) were recruited for the purpose of this case-control study. Skin, mucosal, and throat specimens were obtained and examined for viruses by reverse transcriptase polymerase chain reaction. To determine the immunoglobulin G (IgG) titer, enzyme-linked immunosorbent assay was used.

Results: Desmoglein1-specific IgG was positive in 56.7% of patients with the relapse form and in 20.0% of those with the remission form indicating a significant difference across the 2 groups (P = 0.003), but the rate of positivity for desmoglein3-specific IgG in the relapse and remission types was 76.7% and 63.3%, respectively, with no significant difference (P = 0.260). There was no difference in the mean levels of HSV-IgG and CMV-IgG in the relapse and remission groups. HSV and CMV positivity in PV patients was independent of the site of the samples. Using the multivariable linear regression model, the level of CMV-IgG in PV patients was directly affected by female sex and advanced ages.

Conclusions: Our study could not demonstrate the role of HSV1/2 and CMV as triggering factors for PV exacerbation. Further studies are needed to evaluate the potential role of these viruses in PV exacerbation especially considering demographic variables.
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http://dx.doi.org/10.5826/dpc.0804a03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246069PMC
October 2018

Prevalence and genetic diversity of norovirus genogroup II in children less than 5 years of age with acute gastroenteritis in Tehran, Iran.

Med Microbiol Immunol 2018 Aug 4;207(3-4):201-210. Epub 2018 Apr 4.

Virology Department, Pasteur Institute of Iran, Tehran, Iran.

Viral gastroenteritis is a major public health problem worldwide. In Iran, very limited studies have been performed with regard to the epidemiology of noroviruses. This study aimed to evaluate the prevalence and molecular epidemiology of GII noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE). A total of 210 stool specimens were collected from Ali Asghar Children's Hospital and Bahrami Children's Hospital in Tehran, from June 2015 to June 2016. The samples were screened by real-time RT-PCR for genogroup II (GII). Positive samples were genotyped by semi-nested PCR followed by Sanger sequencing and phylogenetic analysis. Norovirus was identified in 36 (17.1%) of 210 specimens. Based on genetic analysis of RdRp and capsid sequences, the strains were clustered into eight RdRp-capsid genotypes: GII.P4-GII.4 Sydney_2012 (41.7%), GII.Pe-GII.4 Sydney_2012 (30.6%), GII.P21-GII.3 (13.9%), GII.P16-GII.4 Sydney_2012 (2.8%), GII.P16-GII.12 (2.8%), GII.P2-GII.4 Sydney_2012 (2.8%), GII.P7-GII.7 (2.8%) and GII.P2-GII.2 (2.8%). We determined several different co-circulating norovirus genotypes in children < 5 years of age with AGE in our hospital in Tehran, Iran. Continued molecular surveillance of noroviruses, including typing of both RdRp and capsid genes, is important for monitoring emerging strains in our continued efforts to reduce the overall burden of norovirus disease.
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http://dx.doi.org/10.1007/s00430-018-0541-6DOI Listing
August 2018

The Role of Cannabinoid Receptor 1 in the Immunopathology of Respiratory Syncytial Virus.

Viral Immunol 2018 05 20;31(4):292-298. Epub 2018 Feb 20.

1 Department of Virology, School of Public Health, Tehran University of Medical Sciences , Tehran, Iran .

Endocannabinoid system plays an important role in pathophysiologic processes such as immune functions and impacts on disease severity. Our previous study showed that cannabinoid receptor 2 (CB2) affects clinical course of respiratory syncytial virus (RSV) infection. In this study, we investigated the role of cannabinoid receptor 1 (CB1) in RSV immunopathology and its therapeutic potential in mice model. To study the role of CB1 receptors in the immunopathology of RSV, CB1 was blocked daily with AM281 as a selective antagonist in Balb/c mice and were infected by intranasal inoculation of RSV-A2 24 h following the first dose of antagonist administration. The potential pharmacological therapeutic effects of cannabinoid receptor activation during RSV infection were studied using JZL184 as a selective indirect agonist, 24 h after infection. Mice were sacrificed on day 5 after infection and experimental analyses were performed to study the CB1 receptor expression, airway immune cell influx, cytokine/chemokine secretion, lung histopathology, and viral load. RSV infection of airways significantly induced the expression of CB1 receptors in lung cells of mice. Blockade of CB1 receptors using AM281 enhanced immune cell influx and cytokine/chemokine production, and aggravated lung pathology. Activation of cannabinoid receptors using JZL184 decreased immune cell influx and cytokine/chemokine production, and alleviated lung pathology. This study and our previous finding indicated that endocannabinoid signaling regulates the inflammatory response to RSV infection, and is a potential therapeutic candidate for alleviation of RSV-associated immunopathology.
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http://dx.doi.org/10.1089/vim.2017.0098DOI Listing
May 2018

Epidemiological and clinical characteristics of scorpionism in Shiraz (2012-2016); development of a clinical severity grading for Iranian scorpion envenomation.

Med J Islam Repub Iran 2017;31:27. Epub 2017 May 17.

Social Determinants of Health Research Center and, Department of Environmental Health, College of Health, Kashan University of Medical Sciences, Kashan, Iran.

Scorpionism is a public health problem in some provinces in Iran. The present study aimed to assess the clinical manifestations of scorpion envenomation in Shiraz and determine a clinical severity grading for Iranian scorpion envenomation in order to suggest a treatment guideline for emergency physicians. In this analytic retrospective study, all medical charts of patients with scorpion sting admitted in the adult medical toxicology center in Shiraz during July 2012 to July 2016 were assessed. Data regarding the patient's age, gender, sting site, month of envenomation, time of sting, clinical manifestations, vital signs, presence of blood or hemoglobin in urine analysis, duration of admission, color of scorpion, received treatments, and administration of scorpion antivenin were recorded. The scorpions in Shiraz and its suburban area were classified into two groups: yellow scorpions ( , and ) and scorpions ( and ). A total of 126 cases of scorpion stings were assessed. About 59% (n=74) were males. The patients aged 8-63 years (mean age, 33.8±11.5 years). About 38.4% (n=48) of the stings occurred during summer. More than 40% of patients (n=51) referred to the emergency department (ED) at night. Localized pain was the most frequent presenting complaint (76.2%). The most frequent general symptom was nausea (6.3%). The most prevalent envenomation site was the lower extremities followed by upper extremities (43.5% and 41.9%, respectively). Based on the clinical severity grading for Iranian scorpion envenomation, 65, 43, and 18 patients (51.6%, 34.1%, and 14.3%) were classified in the grades I, II, and III, respectively. Eighty-one (73%) patients stayed in the ED from 1 to 6 hours, and 30 (27%) patients stayed for >6 hours for observation. Severe localized pain was more prevalent in stings with scorpions than yellow scorpions (P=0.01). The season of envenomation with scorpions was summer in all cases, but envenomation with yellow scorpions was seen throughout the year. All patients received symptomatic treatment, and five were given scorpion antivenin. No death was reported. is recommended to be listed among the medically important scorpions in Iran. Moreover, scorpion-stung patients in geographical regions where and are not prevalent may be treated in outpatient departments. The presented grading system can be used for treating patients with scorpion envenomation.
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http://dx.doi.org/10.18869/mjiri.31.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804458PMC
May 2017

Immunization of Mice by Rotavirus NSP4-VP6 Fusion Protein Elicited Stronger Responses Compared to VP6 Alone.

Viral Immunol 2018 04 29;31(3):233-241. Epub 2017 Nov 29.

2 Virology Department, Pasteur Institute of Iran , Tehran, Iran .

Due to the limitations and safety issues of the two currently approved live attenuated rotavirus (RV) vaccines "RotaTeq and Rotarix," studies on nonreplicating sources of RV vaccines and search for proper RV antigens are actively carried out. The adjuvant activity of NSP4 and highly immunogenic properties of RV VP6 protein prompted us to consider the construction of a NSP4-VP6 fusion protein and to assess the anti-VP6 IgG, IgA, and IgG subclass responses induced by Escherichia coli-derived NSP4-VP6 fusion protein compared to that of VP6 protein with/without formulation in Montanide ISA 50V2 (M50) in BALB/c mice. Results indicated to the proper expression of the fused NSP4-VP6 and VP6 proteins in E. coli. Intraperitoneal immunization by M50 formulated NSP4-VP6 fusion protein (M5+NSP4-VP6) induced the highest titration of VP6-specific IgG and IgA responses compared to the other groups. Indeed, the presence of NSP4 resulted to the induction of stronger humoral immune responses against the fused protein compared to that elicited by administration of VP6 protein alone (with/without M50 formulation), implying the adjuvant properties of NSP4 for the fused protein. Moreover, the "M50+NSP4-VP6" formulation induced higher serum IgG2a titers than IgG1 and increased Interferon-γ levels, despite unchanged interleukin-4 amounts compared to other groups, indicating Th1-oriented responses with a possible role of NSP4. In conclusion, this study further highlights the potentiality of NSP4-VP6 fusion protein as an efficient and cost-effective immunogen in the field of RV vaccine development.
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http://dx.doi.org/10.1089/vim.2017.0075DOI Listing
April 2018

Human papillomavirus type 16 lineage analysis based on E6 region in cervical samples of Iranian women.

Infect Genet Evol 2017 11 25;55:26-30. Epub 2017 Aug 25.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

It is suggested that distinct HPV 16 variants differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 16 would be of great importance for evolutionary, epidemiological and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 16 in normal cells, premalignant and malignant lesions of the cervix. In total, 106 isolates of HPV 16 were analyzed by PCR and sequencing. Overall, two different lineages (A and D) were identified. Lineage D comprised 70.7% of samples and the remaining 29.3% belonged to lineage A. Regarding to cytology/histology, lineage D was dominant in both normal+CIN I-II and CIN III+ICC groups as it was detected in 80% and 66.2% of cases, respectively. The comparison of the lineages between different groups (35 normal+CIN I-II samples and 71 CIN III+ICC samples) revealed that lineage A is more prevalent in cervical cancer cases (7 (20%) vs. 24 (33.8%)) although the difference observed did not reach statistical significance (p=0.07). In conclusion, our findings confirm that HPV lineages A and D are more prevalent in Iran, with the lineage D as the most dominant in all studied groups.
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http://dx.doi.org/10.1016/j.meegid.2017.08.025DOI Listing
November 2017

Sophism in the Management of Acute Aluminum Phosphide Poisoning may Cause Patient Harm.

Indian J Crit Care Med 2017 Mar;21(3):182

Department of Forensic Medicine and Clinical Toxicology, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://dx.doi.org/10.4103/ijccm.IJCCM_39_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363112PMC
March 2017

Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran.

World J Exp Med 2017 Feb 20;7(1):31-39. Epub 2017 Feb 20.

Saeed Kavousi-Gharbi, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134845794, Fars Province, Iran.

Aim: To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning.

Methods: In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period (September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and test for categorical. The significance level was considered to be < 0.05.

Results: A total of 104 patients (66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients' was 27.21 ± 11.06 years. Ninety seven (93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than 22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality.

Conclusion: Treatment should start immediately for these patients. Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.
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http://dx.doi.org/10.5493/wjem.v7.i1.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316902PMC
February 2017

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

J Med Virol 2017 07 8;89(7):1309-1313. Epub 2017 Mar 8.

Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody.
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http://dx.doi.org/10.1002/jmv.24774DOI Listing
July 2017

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

J Med Virol 2017 07 8;89(7):1309-1313. Epub 2017 Mar 8.

Virology Department, School of Public Health (SPH), Tehran University of Medical Sciences (TUMS), Tehran, Iran.

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody.
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http://dx.doi.org/10.1002/jmv.24774DOI Listing
July 2017

MDM2 gene polymorphisms and risk of classic Kaposi's sarcoma among Iranian patients.

Med Microbiol Immunol 2017 Apr 12;206(2):157-163. Epub 2017 Jan 12.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 14155, Iran.

A single-nucleotide polymorphism (SNP) in the promoter region of MDM2 (SNP309T>G, rs2279744) has been shown to increase the expression of the MDM2 protein in various cancer types. However, only one study has analyzed the role of the MDM2 polymorphism in the development of Kaposi's sarcoma (KS). The association of MDM2 SNP309 with classic KS risk was evaluated in 79 Iranian patients with classic KS and 123 healthy controls. The MDM2 SNP309 was genotyped using PCR and restriction fragment length polymorphism methods. No significant correlation was found between the SNP309 polymorphism in MDM2 promoter and classic KS risk. There was no significant correlation between gender and disease stage. However, a significant association was found between SNP309 GG genotype and younger age (≤50 years) (odds ratio 9.5, 95% confidence intervals 1.5-60, p = 0.03). Our findings support no major role for the MDM2 SNP309 in KS development although it might influence the clinical outcome of KS in younger patients.
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http://dx.doi.org/10.1007/s00430-016-0491-9DOI Listing
April 2017

Gastric decontamination in aluminium phosphide poisoning: a case against the use of water-based solutions.

Arh Hig Rada Toksikol 2016 Dec;67(4):364-365

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http://dx.doi.org/10.1515/aiht-2016-67-2900DOI Listing
December 2016

Management of indoxacarb poisoning in a regional setting.

Indian J Crit Care Med 2016 Oct;20(10):627-628

Department of Forensic Medicine and Clinical Toxicology, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://dx.doi.org/10.4103/0972-5229.192067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073783PMC
October 2016

How much Tramadol should be considered lethal in overdose?

Arh Hig Rada Toksikol 2016 Sep;67(3):259

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http://dx.doi.org/10.1515/aiht-2016-67-2863DOI Listing
September 2016

Molecular typing of human herpesvirus 8 among HIV positive in comparison to HIV-negative individuals in Iran.

J Med Virol 2017 04 26;89(4):703-709. Epub 2016 Dec 26.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

It is still unclear whether different HHV-8 genotypes may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression. In some areas where genotype C was found to be prominent among classic KS patients, genotype A was shown to be more frequent among AIDS-associated KS patients. Genotype C was previously reported to be widespread in Iran, with genotype A being less frequent among patients with classic KS although no data are available with regards to the HHV-8 genotyping among Iranian HIV-infected patients. In order to analyze HHV-8 genotypes (ORF K1), six HIV-infected patients (with or without KS), and 22 HIV-negative subjects (classic/iatrogenic KS patients and IVDUs) were investigated using nested PCR. Genotype A was detected more frequently among HIV-infected patients with or without KS (three out of six) whereas genotype C was found more common among HIV-negative subjects including classic/iatrogenic KS patients and IVDSs (21 out of 22), and this difference was statistically significant (P = 0.044). In conclusion, our data further support the dominancy of HHV-8 genotype C in Iranian general population. Moreover, genotype A was more common among HIV-infected patients with or without KS. J. Med. Virol. 89:703-709, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24644DOI Listing
April 2017

Molecular typing of human herpesvirus 8 among HIV positive in comparison to HIV-negative individuals in Iran.

J Med Virol 2017 04 26;89(4):703-709. Epub 2016 Dec 26.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

It is still unclear whether different HHV-8 genotypes may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression. In some areas where genotype C was found to be prominent among classic KS patients, genotype A was shown to be more frequent among AIDS-associated KS patients. Genotype C was previously reported to be widespread in Iran, with genotype A being less frequent among patients with classic KS although no data are available with regards to the HHV-8 genotyping among Iranian HIV-infected patients. In order to analyze HHV-8 genotypes (ORF K1), six HIV-infected patients (with or without KS), and 22 HIV-negative subjects (classic/iatrogenic KS patients and IVDUs) were investigated using nested PCR. Genotype A was detected more frequently among HIV-infected patients with or without KS (three out of six) whereas genotype C was found more common among HIV-negative subjects including classic/iatrogenic KS patients and IVDSs (21 out of 22), and this difference was statistically significant (P = 0.044). In conclusion, our data further support the dominancy of HHV-8 genotype C in Iranian general population. Moreover, genotype A was more common among HIV-infected patients with or without KS. J. Med. Virol. 89:703-709, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24644DOI Listing
April 2017

Molecular typing of human herpesvirus 8 among HIV positive in comparison to HIV-negative individuals in Iran.

J Med Virol 2017 04 26;89(4):703-709. Epub 2016 Dec 26.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

It is still unclear whether different HHV-8 genotypes may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression. In some areas where genotype C was found to be prominent among classic KS patients, genotype A was shown to be more frequent among AIDS-associated KS patients. Genotype C was previously reported to be widespread in Iran, with genotype A being less frequent among patients with classic KS although no data are available with regards to the HHV-8 genotyping among Iranian HIV-infected patients. In order to analyze HHV-8 genotypes (ORF K1), six HIV-infected patients (with or without KS), and 22 HIV-negative subjects (classic/iatrogenic KS patients and IVDUs) were investigated using nested PCR. Genotype A was detected more frequently among HIV-infected patients with or without KS (three out of six) whereas genotype C was found more common among HIV-negative subjects including classic/iatrogenic KS patients and IVDSs (21 out of 22), and this difference was statistically significant (P = 0.044). In conclusion, our data further support the dominancy of HHV-8 genotype C in Iranian general population. Moreover, genotype A was more common among HIV-infected patients with or without KS. J. Med. Virol. 89:703-709, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24644DOI Listing
April 2017

Is there a role for sildenafil in the management of paraquat-induced lung fibrosis?

Arh Hig Rada Toksikol 2016 Jun;67(2):167-8

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http://dx.doi.org/10.1515/aiht-2016-67-2804DOI Listing
June 2016

Comparison of Ciprofloxacin-Based Triple Therapy with Conventional Triple Regimen for Helicobacter pylori Eradication in Children.

Acta Med Iran 2016 Jun;54(6):395-400

Department of Pediatrics, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.

Helicobacter pylori infection is a prevalent disease among Iranian children. The purpose of this study was to compare the effect of ciprofloxacin and furazolidone on eradicating helicobacter pylori in Iranian children in combination with amoxicillin and omeprazole. In this cohort study, helicobacter pylori infection was confirmed by gastroscopy, rapid urease test or pathologic assessments. A total of 66 children were randomly enrolled; based on the random number table, and were divided into two groups; first, a combination regimen consisting of ciprofloxacin, amoxicillin, and omeprazole; second, a three-medication regimen consisting of amoxicillin, furazolidone, and omeprazole. The effect of both medical regimens on the successful eradication of helicobacter pylori infection was assessed and compared. Chi-square test was used for evaluating the association between quantitative variables. All comparisons were made at the significance of P<0.05. Endoscopic tests prior to initiating treatments showed that 66.7% of the patients had a degree of nodularity while peptic ulcer was only observed in one patient. One month after the end of the treatments, eradication of the helicobacter pylori infection was reported 87.9% (29/33) in the first group (CAO) and 60.6% (20.33) in the second group (FAO) (P=0.011). It appears that a major advantage of our proposed regimen over others is a lack of wide use of fluoroquinolones for treating children's diseases. Given FDA's recommendation about the possibility of prescribing ciprofloxacin for infected patients with multidrug resistance, we can use the regimen proposed in this study in patients with resistance to standard treatments.
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June 2016