Publications by authors named "Mohammad Derakhshan"

88 Publications

State-of-the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2.

ACS Appl Mater Interfaces 2021 Apr 29;13(13):14816-14843. Epub 2021 Mar 29.

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

The pandemic outbreak of SARS-CoV-2, with millions of infected patients worldwide, has severely challenged all aspects of public health. In this regard, early and rapid detection of infected cases and providing effective therapeutics against the virus are in urgent demand. Along with conventional clinical protocols, nanomaterial-based diagnostics and therapeutics hold a great potential against coronavirus disease 2019 (COVID-19). Indeed, nanoparticles with their outstanding characteristics would render additional advantages to the current approaches for rapid and accurate diagnosis and also developing prophylactic vaccines or antiviral therapeutics. In this review, besides presenting an overview of the coronaviruses and SARS-CoV-2, we discuss the introduced nanomaterial-based detection assays and devices and also antiviral formulations and vaccines for coronaviruses.
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http://dx.doi.org/10.1021/acsami.0c22381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028022PMC
April 2021

Preparation and characterization of polyurethane/chitosan/CNT nanofibrous scaffold for cardiac tissue engineering.

Int J Biol Macromol 2021 Jun 9;180:590-598. Epub 2021 Mar 9.

Regenerative Nanomedicine Research Group, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Myocardial infarction of cardiomyocytes is a leading cause of heart failure (HF) worldwide. Since heart has very limited regeneration capacity, cardiac tissue engineering (TE) to produce a bioactive scaffold is considered. In this study, a series of polyurethane solutions (5-7%wt) in aqueous acetic acid were prepared using electrospinning. A variety of Polyurethane (PU)/Chitosan (Cs)/carbon nanotubes (CNT) composite nanofibrous scaffolds with random and aligned orientation were fabricated to structurally mimic the extracellular matrix (ECM). Electrospun nanofibers were then characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), water contact angle, degradation studies, tensile tests, electrical resistance measurement and cell viability assay. The biocompatibility of electrospun random and aligned nanofibrous scaffolds with H9C2 Cells was confirmed. The results revealed that fabricated PU/Cs/CNT composite nanofibrous scaffolds were electro-conductive and aligned nanofibers could be considered as promising scaffolds with nano-scale features for regeneration of infarcted myocardium.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.001DOI Listing
June 2021

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

Gut 2021 May 2;70(5):876-883. Epub 2020 Nov 2.

Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.

Results: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.

Conclusion: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.
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http://dx.doi.org/10.1136/gutjnl-2020-320913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040155PMC
May 2021

Depression and anxiety in an early rheumatoid arthritis inception cohort. associations with demographic, socioeconomic and disease features.

RMD Open 2020 10;6(3)

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.

Objective: Depression and anxiety are not uncommon in Rheumatoid arthritis (RA). It is increasingly recognised that they are associated with high disease activity and worse disease outcomes. We aimed to examine the frequency of depression and anxiety in an early RA inception cohort and to explore associations with disease-related measures.

Methods: The Scottish Early Rheumatoid Arthritis inception cohort recruited newly diagnosed RA patients followed-up 6-monthly. Anxiety and depression were assessed using the hospital anxiety and depression scale. Associations with demographic characteristics and disease-related measures were examined at baseline, 6 months and 12 months.

Results: 848 RA patients were included. The prevalence of anxiety and depression at baseline was 19.0% and 12.2%, respectively. Depression and anxiety scores correlated with DAS28 at all time-points (all p<0.0001). In multivariable linear regression, anxiety score at baseline was associated with younger age and Health Assessment Questionnaire (HAQ) score. Anxiety scores at 6 months and 12 months were associated with low body mass index (BMI), baseline anxiety score and current patient global score and HAQ. Depression score at baseline was associated with younger age, being single and HAQ, while depression scores at 6 months and 12 months were associated with male gender (only at 6 months), baseline anxiety and depression scores and current patient global score, HAQ and C-reactive protein (CRP) levels.

Conclusion: Depression and anxiety are associated with disease activity, worse functional status and other variables in early RA. There is a close relationship between CRP and depression but not anxiety.
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http://dx.doi.org/10.1136/rmdopen-2020-001376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722367PMC
October 2020

Nanotechnology-driven advances in the treatment of diabetic wounds.

Biotechnol Appl Biochem 2020 Oct 12. Epub 2020 Oct 12.

Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetic foot ulcers (DFUs) are chronic severe complications of diabetes disease and remain a worldwide clinical challenge with social and economic consequences. Diabetic wounds can cause infection, amputation of lower extremities, and even death. Several factors including impaired angiogenesis, vascular insufficiency, and bacterial infections result in a delayed process of wound healing in diabetic patients. Treatment of wound infections using traditional antibiotics has become a critical status. Thus, finding new therapeutic strategies to manage diabetic wounds is urgently needed. Nanotechnology has emerged as an efficient approach for this purpose. This review aimed to summarize recent advances using nanotechnology for the treatment of diabetic wounds.
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http://dx.doi.org/10.1002/bab.2051DOI Listing
October 2020

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis.

RMD Open 2020 07;6(2)

Rheumatology Department, Norfolk and Norwich University Hospital, Norwich, UK

Objectives: Extra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a 'real-world' cohort of patients with axSpA.

Methods: Clinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.

Results: AAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.

Conclusion: The higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.
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http://dx.doi.org/10.1136/rmdopen-2020-001206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425116PMC
July 2020

Abnormal vitamin D and lipid profile in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

Mol Biol Rep 2020 Jan 11;47(1):631-637. Epub 2019 Nov 11.

Inflammation and Inflammatory Diseases Division, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

The HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of host-HTLV-1 interactions. In many virus-associated diseases and multiple sclerosis, the importance of vitamin-D and lipid profile has been demonstrated, thus similarly, their impacts were evaluated in HAM/TSP patients, in this study. Vitamin D and lipid profile were assessed in 120 healthy subjects (HSs), along with a proviral load (PVL) in 91 HAM/TSPs and 169 HTLV-1 carriers (ACs). The mean level of triglyceride and LDL in the HAM/TSPs were higher than HSs (P = 0.008 and 0.008, respectively), but no significant difference has been found between ACs and HSs. However, the level of HDL and vitamin-D in the HAM/TSP subjects were lower than HSs (P = 0.01 and P = 0.006, respectively). In HTLV-1 infected subjects, PVL was statistically associated with cholesterol (R = 0.24, P = 0.038), triglycerides (R = 0.26, P = 0.01) and HDL (R = 0.28, P = 0.001), and in HAM/TSPs there was a strong association between the severity of the disease, as determined by the OMDS and cholesterol (P = 0.01). Furthermore, in the HAM/TSPs, positive correlations between vitamin-D and age (R = 0.23, P = 0.028) and triglycerides (R = 0.38, P = 0.001) were found, also a significant correlation between PVL and LDL (R = 0.21, P = 0.001) and a weak correlation between PVL and OMDS (R = 0.4, P = 0.07) were noted. However, there was no correlation between PVL and urinary disturbance. Furthermore, PVL range of more than 600 copies/10 lymphocytes had a strong correlation with OMDS (P = 0.05), but not with urinary disturbance. It's more likely that HAM/TSP patients have an imbalanced lipid profile and low levels of vitamin D and may represent a potentially useful target for intervention in HTLV-1 associated diseases.
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http://dx.doi.org/10.1007/s11033-019-05171-1DOI Listing
January 2020

Enhancing immunogenicity of novel multistage subunit vaccine of using PLGA:DDA hybrid nanoparticles and MPLA: Subcutaneous administration.

Iran J Basic Med Sci 2019 Aug;22(8):893-900

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against ().

Materials And Methods: PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA.

Results: Both particles had spherical shape and smooth surface with 316.7±12.7 nm in size, surface charge of -33±1.7 mV, and encapsulation efficiency of 92.2±2% for PLGA NPs and 249.7±16.7 nm in size, surface charge of 39±1.8 mV, and encapsulation efficiency of 35.7±1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster.

Conclusion: With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost.
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http://dx.doi.org/10.22038/ijbms.2019.33962.8079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760476PMC
August 2019

Formulation and Optimization of a New Cationic Lipid-Modified PLGA Nanoparticle as Delivery System for HspX/EsxS Fusion Protein: An Experimental Design.

Iran J Pharm Res 2019 ;18(1):446-458

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Polymeric particles and liposomes are efficient tools to overcome the low immunogenicity of subunit vaccines. The aim of the present study was formulation and optimization of a new cationic lipid-modified PLGA nanoparticles (NPs) as a delivery system for HspX/EsxS fusion protein. The cationic lipid-modified PLGA NPs containing HspX/EsxS fusion protein were prepared using a modified double emulsion solvent evaporation method. Scanning electron microscopy and dynamic light scattering (DLS) tools were used to determine physical properties of hybrid NPs. A multi-level full factorial design was used to evaluate the influence of two factors of PLGA:DDA weight ratio (w/w) and PVA concentration (%) on size, surface charge, polydispersity index, encapsulation efficiency and yield. Finally, the optimal formulation was achieved based on desired responses. Mathematical models were obtained to indicate the relation between the studied factors and responses. The DDA concentration showed an increasing effect on surface charge and also a decreasing effect on particle size, encapsulation efficiency and yield. Higher amounts of DDA increased surface charge of NPs; however, the size, encapsulation efficiency and yield were decreased. The influence of various concentrations of PVA on different physical characteristics of PLGA:DDA hybrid NPs was variable. The optimal formulation consisted of 0.91 (55:5, w/w) weight ratio of PLGA:DDA and 0.5% PVA. The hybrid NPs showed acceptable particle size distribution, strong positive surface charge, prolonged antigen release and good encapsulation efficiency in comparison to PLGA alone. However, further preclinical and clinical studies are needed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487422PMC
January 2019

Sex differences in the prevalence of Helicobacter pylori infection: an individual participant data pooled analysis (StoP Project).

Eur J Gastroenterol Hepatol 2019 05;31(5):593-598

EPIUnit - Instituto de Saúde Pública.

Background: Helicobacter pylori (H. pylori) infection is more frequent among men, though the magnitude of the association might be inaccurate due to potential misclassification of lifetime infection and publication bias. Moreover, infection is common, and most studies are cross-sectional. Thus, prevalence ratios (PRs) may be easier to interpret than odds ratios (ORs).

Aim: The aim of this study was to quantify the association between sex and H. pylori infection using controls from 14 studies from the Stomach Cancer Pooling (StoP) Project.

Participants And Methods: H. pylori infection was defined based on IgG serum antibody titers or multiplex serology. Participants were also classified as infected if gastric atrophy was present, based on histological examination or serum pepsinogen (PG) levels (PG I≤70 and PG I/II ratio≤3). Summary ORs and PRs, adjusted for age, social class and smoking, and corresponding 95% confidence intervals (CIs), were estimated through random-effects meta-analysis.

Results: Men had significantly higher OR (OR: 1.33, 95% CI: 1.04-1.70) and PR (PR: 1.05, 95% CI: 1.00-1.10) of infection, with stronger associations among hospital-based or older controls. Results were similar when considering the presence of gastric atrophy to define infection status, particularly among participants older than 65 years.

Conclusion: This collaborative pooled-analysis supports an independent effect of sex on the prevalence of H. pylori infection, while minimizing misclassification of lifetime infection status and publication bias.
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http://dx.doi.org/10.1097/MEG.0000000000001389DOI Listing
May 2019

Association of Diverticulitis with Prolonged Spondyloarthritis: An Analysis of the ASAS-COMOSPA International Cohort.

J Clin Med 2019 Feb 26;8(3). Epub 2019 Feb 26.

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G61 1QH, UK.

This study examined the relationship between spondyloarthritis (SpA) duration and gastrointestinal comorbidities other than inflammatory bowel disease (IBD). We evaluated the association between SpA duration and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis using data from a large international cross-sectional study. Binary regression models were created, adjusted for age, sex, body mass index (BMI), smoking, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, IBD history and country. Subgroup analysis was performed by disease phenotype. The data of 3923 participants were analysed. The prevalence of gastrointestinal conditions were 10.7% upper gastrointestinal ulcers; 4.7% viral hepatitis and 1.5% diverticulitis. While SpA duration was not associated with upper gastrointestinal ulcers, HBV or HCV, longer SpA duration was significantly associated with diverticulitis (odds ratios (OR) = 1.18, 95% confidence interval (CI): 1.03⁻1.34), reflecting an 18% increase for every five years of SpA duration. Other significant associations with diverticulitis were age and high alcohol intake but not medication history. In subgroup analyses, the association was strongest with those with axial SpA. The reasons for this association of increased diverticulitis with disease duration in SpA, especially those with axial disease, are unclear but may reflect shared underlying gut inflammation. Diverticulitis should be considered, in addition to IBD, when SpA patients present with lower gastrointestinal symptoms.
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http://dx.doi.org/10.3390/jcm8030281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462988PMC
February 2019

Designing and Construction of a Cloning Vector Encoding Fragments of as a DNA Vaccine Candidate.

Iran J Pathol 2018 25;13(4):403-407. Epub 2018 Sep 25.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: Tuberculosis (TB) remains a major cause of death around the world. Bacillus Calmette Guérin (BCG) is the only vaccine used in TB prevention that has a protective effect in children, but its effectiveness declines in adults. Design and development of new vaccines is the most effective way against TB.The aim of this study was to design and construct a DNA vaccine encoding and fusion genes of .

Methods: First, fragment was amplified by PCR method. The pcDNA3.1+/ plasmid was transformed into JM109 and then extracted. The gene and pcDNA3.1+/ plasmid were both digested with RI and HI restriction enzymes followed by ligation of 51 fragment into the digested vector. The recombinant plasmid containing and was subsequently transformed into competent TOP10 strain. The clones were confirmed by colony-PCR, restriction enzyme digestion and sequencing.

Results: Using agarose gel electrophoresis, a 926 bp fragment corresponded to was observed. Digestion of the vector pcDNa3.1+/ and gene was confirmed by electrophoresis. Then, the pcDNA3.1+/ plasmid was extracted. Sequencing results confirmed the accuracy of the desired plasmid.

Conclusion: In this study, we constructed a cloning vector encoding gene of . The eukaryotic expression of this vector can be confirmed in future studies. It can be considered as a DNA vaccine in animal models later. Successful cloning provides a basis for the development of new DNA vaccines against TB.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358561PMC
September 2018

Serum Proteomic Study of Women With Obsessive-Compulsive Disorder, Washing Subtype.

Basic Clin Neurosci 2018 Sep-Oct;9(5):337-346. Epub 2018 Sep 1.

Department of Psychosomatic, Taleghani Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Many genetic studies are conducted on Obsessive-Compulsive Disorder (OCD). however, a high-throughput examination of proteome profile of this severe disease has not been performed yet.

Methods: Here, the proteomic study of OCD patients' serum samples was conducted by the application of Two-Dimensional Electrophoresis (2DE) followed by Mass Spectrometry (MALDI-TOF-TOF).

Results: A total of 240 protein spots were detected and among them, five significant differentially expressed protein spots with the fold change of ≥1.5 were considered for further evaluations. These proteins include IGKC, GC, HPX, and two isoforms of HP. While IGKC and HP show down-regulation, GC and HPX indicate up-regulation. Moreover, a validation study of overall HP levels in patients' serum via nephelometric quantification confirmed the lower levels of this protein in the serum of OCD patients. Additionally, enrichment analysis and validation test revealed that inflammation is one of most dominant processes in OCD.

Conclusion: It is suggested that these candidate proteins and their underlying processes (especially, inflammation) may be linked to OCD pathophysiology and can promise a clinical use after extensive validation studies.
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http://dx.doi.org/10.32598/bcn.9.5.337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360490PMC
September 2018

Increased Risk of Hypertension Associated with Spondyloarthritis Disease Duration: Results from the ASAS-COMOSPA Study.

J Rheumatol 2019 07 15;46(7):701-709. Epub 2019 Jan 15.

From the Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow; Academic Rheumatology, Musculoskeletal Biology, Institute of Chronic Disease and Ageing, University of Liverpool, Liverpool; Haywood Rheumatology Centre, Stoke on Trent; Keele University, Keele; Royal National Hospital for Rheumatic Diseases, Bath, UK; Paris Descartes University, Hôpital Cochin, Paris, France; UK National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, UK.

Objective: Spondyloarthritis (SpA) is associated with a number of cardiovascular (CV) comorbidities. We examined the association of SpA disease duration and delay in diagnosis with CV-related conditions.

Methods: Using data from the COMOSPA study, the associations between SpA disease duration and CV-related conditions were evaluated in univariable and multivariable logistic regression models. Each model examined 1 CV-related factor as dependent and "SpA disease duration" as a predictor, adjusted for relevant confounders.

Results: Data from 3923 subjects (median SpA disease duration 5.1 yrs, interquartile range 1.3-11.8 yrs) were available for analysis. The main CV-related conditions were hypertension (HTN; 22.4%), ischemic heart disease (2.6%), stroke (1.3%), and diabetes mellitus (5.5%). HTN was associated with SpA disease duration in both univariable and multivariable analysis, with an OR of 1.129 (95% CI 1.072-1.189; p < 0.001) for each 5-year increase in SpA disease duration. Other factors associated with HTN were age, male sex, current body mass index, ever steroid therapy, and ever synthetic disease-modifying antirheumatic drug therapy, but not nonsteroidal antiinflammatory drugs (NSAID). In subgroup analysis, the strongest association of HTN and disease duration was seen in subjects with the axial-only SpA phenotype (OR 1.202, 95% CI 1.053-1.372) but not in those with peripheral-only SpA (OR 0.902, 95% CI 0.760-1.070). The other CV conditions were not associated with SpA disease duration.

Conclusion: Duration of SpA disease in the ASAS-COMOSPA cohort is associated with higher odds of HTN, particularly in those with axial disease, but not with other CV-related conditions. The association with HTN does not appear to be related to NSAID exposure.
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http://dx.doi.org/10.3899/jrheum.180538DOI Listing
July 2019

PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury.

J Cell Physiol 2019 07 24;234(7):11060-11069. Epub 2018 Dec 24.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The significant consequences of spinal cord injury (SCI) include sensory and motor disability resulting from the death of neuronal cells and axon degeneration. In this respect, overcoming the consequences of SCI including the recovery of sensory and motor functions is considered to be a difficult tasks that requires attention to multiple aspects of treatment. The breakthrough in tissue engineering through the integration of biomaterial scaffolds and stem cells has brought a new hope for the treatment of SCI. In the present study, human endometrial stem cells (hEnSCs) were cultured with human Schwann cells (hSC) in transwells, their differentiation into nerve-like cells was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunocytochemistry techniques. The differentiated cells (co-hEnSC) were then seeded on the poly ε-caprolactone (PCL)/gelatin scaffolds. The SEM images displayed the favorable seeding and survival of the cells on the scaffolds. The seeded scaffolds were then transplanted into hemisected SCI rats. The growth of neuronal cells was confirmed with immunohistochemical study using NF-H as a neuronal marker. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions. The results suggested that combination therapy using the differentiated hEnSC seeded on PCL/gelatin scaffolds has the potential to heal the injured spinal cord and to limit the secondary damage.
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http://dx.doi.org/10.1002/jcp.27936DOI Listing
July 2019

The efficacy of first-line regimens for Helicobacter pylori eradication in different continents: A systematic review and network meta-analysis protocol.

Medicine (Baltimore) 2018 Dec;97(50):e13682

Department of Internal Medicine, Rohani Hospital, Babol University of Medical Sciences, Babol, Iran.

Background: Striking prevalence of Helicobacter pylori infection has been convoluted with considerable resistance to various antibiotics worldwide. Although many eradication regimens have been introduced as the first-line therapies against H pylori, lack of appropriate multiple comparison studies makes hard to implement such results to the clinical practice. This project attempts to utilize a comprehensive network meta-analysis to pool the results of clinical trial comparing various first-line eradication therapies simultaneously in different continents.

Methods: We will include all randomized controlled trials assessing the first-line regimens for treatment of H pylori published in last 10 years. We will search the databases of PubMed, EMBASE, Scopus, Web of Science and Cochrane Central Register of Controlled Trials, International Standard Randomised Controlled Trial Number registry, World Health Organisation International Clinical Trials Registry Platform, and ClinicalTrials.gov for randomized controlled trials published since January 2009 without language limitation. The primary and secondary outcomes will be H pylori eradication rate and adverse events, respectively. Subgroup analyses will be conducted for different continents. Two reviewers will independently contribute in study selection and data extraction. For evaluating quality of studies, Cochrane Collaboration tool score will be used. We will conduct network meta-analysis for treatment comparisons using STATA software version 13.

Results: These findings will be submitted to a peer-reviewed journal for publication.

Conclusion: Our results will provide the guidance for clinicians in deferent regions to select the best possible therapeutic regimen for treatment of H pylori infected patients.

Registration Number: This systematic review and network meta-analysis has been registered in the PROSPERO International Prospective Register of Systematic Reviews, with registration number CRD42017077061.
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http://dx.doi.org/10.1097/MD.0000000000013682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320060PMC
December 2018

Neutropaenia in early rheumatoid arthritis: frequency, predicting factors, natural history and outcome.

RMD Open 2018 8;4(2):e000739. Epub 2018 Oct 8.

Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.

Objectives: To determine the frequency, severity and natural history of neutropaenia in early rheumatoid arthritis (RA), explore its associations with clinical features and assess its impact on clinical management.

Methods: The Scottish Early Rheumatoid Arthritis inception cohort prospectively recruited patients with newly diagnosed RA and followed them up every 6 months. Patients with RA who developed at least one episode of neutropaenia (grade 1: <2.0×10^9/L; grade 2: <1.5×10^9/L; grade 3: <1.0×10^9/L; grade 4: <0.5×10^9/L) were compared with those who did not. Comparisons were also made between patients who experienced one or more episodes of neutropaenia and between patients with different neutropaenia grades.

Results: 77 neutropaenia episodes were recorded in 58 of 771 (7.5%) patients with RA, who were followed up for a median (range) of 18 (6-48) months. Neutropaenia occurred at a median (range) of 12 (0-120) months after RA diagnosis. The majority had mild neutropaenia (grade 1: n=42; grade 2: n=14; grade 3: n=1; grade 4: n=1). Neutropaenia was transient (single episode) in the majority (44; 75.8%) of cases but led to treatment discontinuation in 14 (24.1%) patients. Patients who developed neutropaenia were more likely to be female (p=0.01) and non-smokers (p=0.007) and had lower baseline neutrophil levels (p<0.0001). Binomial regression analysis confirmed the latter (p<0.0001, B: -0.491) as neutropaenia predictor. The rate of infections did not differ between patients who developed neutropaenia and those who did not (p=0.878).

Conclusion: Neutropaenia was a common finding in this cohort. It was usually mild, transient and not associated with increased infection rates. Neutropaenia occurrence was associated with non-smoking, female gender and lower baseline neutrophil levels.
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http://dx.doi.org/10.1136/rmdopen-2018-000739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203094PMC
October 2018

Novel electro-conductive nanocomposites based on electrospun PLGA/CNT for biomedical applications.

J Mater Sci Mater Med 2018 Nov 3;29(11):168. Epub 2018 Nov 3.

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

Electro-conductive nanocomposites have several applications in biomedical field. Development of a biocompatible electro-conductive polymeric materials is therefore of prime importance. In this study, electro-conductive nanofibrous mats of PLGA/CNT were fabricated through different methods including blend electrospinning, simultaneous PLGA electrospinning and CNT electrospraying and ultrasound-induced adsorption of CNTs on the electrospun PLGA nanofibers. The morphology and diameter of fibers were characterized by SEM and TEM, showing the lowest average diameters of 477 ± 136 nm for PLGA/MWCNT blend nanocomposites. MWCNT-sprayed PLGA specimens showed significant lower water contact angle (83°), electrical resistance (3.0 × 10 Ω) and higher mechanical properties (UTS: 5.50 ± 0.46 MPa) compared to the untreated PLGA scaffolds. Also, results of PC12 cell study demonstrated highest viability percentage on the MWCNT-sprayed PLGA nanofibers. We propose that the conductive nanocomposites have capability to use as tool for the neural regeneration and biosensors.
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http://dx.doi.org/10.1007/s10856-018-6176-8DOI Listing
November 2018

A novel antigen of Mycobacterium tuberculosis and MPLA adjuvant co-entrapped into PLGA:DDA hybrid nanoparticles stimulates mucosal and systemic immunity.

Microb Pathog 2018 Dec 21;125:507-513. Epub 2018 Oct 21.

Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles.

Methods: In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA. Three weeks after the last nasal immunization of BALB/c mice, IgA antibody levels in nasal lavage and IFN-γ, IL-4, IL-17 and TGF-β cytokines in supernatant of cultured splenocytes and also serum IgG1 and IgG2a titers were evaluated using ELISA method.

Results: Our results indicated that nasal vaccination with PLGA:DDA nanoparticles loaded with HspX/EsxS protein±MPLA, both with and without a prime dose of BCG could provide efficient Th1, Th17, IgA, IgG1 and IgG2a immune responses.

Conclusion: These findings demonstrate that both PLGA:DDA hybrid nanoparticles as carrier/adjuvant and MPLA as adjuvant, could efficiently induce mucosal and systemic immune responses against HspX/EsxS antigen, alone or as a booster for BCG.
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http://dx.doi.org/10.1016/j.micpath.2018.10.023DOI Listing
December 2018

Smoking and Helicobacter pylori infection: an individual participant pooled analysis (Stomach Cancer Pooling- StoP Project).

Eur J Cancer Prev 2019 09;28(5):390-396

EPIUnit - Instituto de Saúde Pública.

Smoking has been associated with acquisition and increased persistence of Helicobacter pylori infection, as well as with lower effectiveness of its eradication. A greater prevalence of infection among smokers could contribute to the increased risk for gastric cancer. We aimed to estimate the association between smoking and seropositivity to H. pylori through an individual participant data pooled analysis using controls from 14 case-control studies participating in the Stomach Cancer Pooling Project. Summary odds ratios and prevalence ratios (PRs), adjusted for age, sex and social class, and the corresponding 95% confidence intervals (CIs) were estimated through random-effects meta-analysis. Heterogeneity was quantified using the I statistic and publication bias with Egger's test. There was no significant association between smoking (ever vs. never) and H. pylori seropositivity (adjusted odds ratio = 1.08; 95% CI: 0.89-1.32; adjusted PR = 1.01; 95% CI: 0.98-1.05). The strength of the association did not increase with the intensity or duration of smoking; stratified analyses according to sex, age, region or type of sample did not yield a consistent pattern of variation or statistically significant results, except for participants younger than 55 years and who had been smoking for more than 30 years (adjusted PR = 1.08; 95% CI: 1.02-1.15). This is the first collaborative analysis providing pooled estimates for the association between smoking and H. pylori seropositivity, based on detailed and uniform information and adjusting for major covariates. The results do not support an association between smoking and H. pylori infection.
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http://dx.doi.org/10.1097/CEJ.0000000000000471DOI Listing
September 2019

High prevalence of sequence type 131 isolates producing CTX-M-15 among extended-spectrum β-lactamase-producing Escherichia coli strains in northeast Iran.

J Glob Antimicrob Resist 2018 12 25;15:74-78. Epub 2018 May 25.

Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Azadi Square, Medical Campus, Mashhad 9177948564, Iran. Electronic address:

Objectives: The recent expansion of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a worldwide problem. The purpose of this study was to investigate the molecular characteristics of ESBL-producing E. coli strains in Mashhad, located in the northeast of Iran.

Methods: A total of 455 clinical E. coli isolates were collected at three hospitals in Mashhad between April-September 2015. Antimicrobial susceptibility was determined by the Kirby-Bauer disk diffusion test. The combination disk test was performed for phenotypic detection of ESBLs. PCR was used to screen isolates for ESBL typing. Phylogenetic groups and sequence type 131 (ST131) were determined by multiplex PCR.

Results: The prevalence of ESBL-producing E. coli among the collected strains was 51.6% (235/455). Among the 235 ESBL-producing strains, 222 (94.5%) tested positive for CTX-M type, whilst 115 (48.9%), 92 (39.1%) and 21 (8.9%) were positive for TEM, OXA and SHV, respectively. Moreover, CTX-M-15 (94.1%; 209/222) was the most common ESBL among E. coli. Based on multiplex PCR, phylogenetic group B2 was predominant (169/235; 71.9%), followed by D (32/235; 13.6%), A (21/235; 8.9%) and B1 (13/235; 5.5%). ST131 was the predominant clonal group among the phylogenetic group B2 isolates (151/169; 89.3%).

Conclusion: The results revealed that an urgent investigation of the source and transmission pathways of the CTX-M-15-B2-ST131 E. coli clone is needed to mitigate this emergent public-health problem.
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http://dx.doi.org/10.1016/j.jgar.2018.05.016DOI Listing
December 2018

Alcohol intake and gastric cancer: Meta-analyses of published data versus individual participant data pooled analyses (StoP Project).

Cancer Epidemiol 2018 06 16;54:125-132. Epub 2018 May 16.

Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Individual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer.

Methods: We compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies.

Results: A total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07-1.36) vs. 1.10 (0.99-1.23)] and more heterogeneous (I: 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias.

Conclusion: Meta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes.
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http://dx.doi.org/10.1016/j.canep.2018.04.009DOI Listing
June 2018

Tobacco smoking and gastric cancer: meta-analyses of published data versus pooled analyses of individual participant data (StoP Project).

Eur J Cancer Prev 2018 05;27(3):197-204

Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Tobacco smoking is one of the main risk factors for gastric cancer, but the magnitude of the association estimated by conventional systematic reviews and meta-analyses might be inaccurate, due to heterogeneous reporting of data and publication bias. We aimed to quantify the combined impact of publication-related biases, and heterogeneity in data analysis or presentation, in the summary estimates obtained from conventional meta-analyses. We compared results from individual participant data pooled-analyses, including the studies in the Stomach Cancer Pooling (StoP) Project, with conventional meta-analyses carried out using only data available in previously published reports from the same studies. From the 23 studies in the StoP Project, 20 had published reports with information on smoking and gastric cancer, but only six had specific data for gastric cardia cancer and seven had data on the daily number of cigarettes smoked. Compared to the results obtained with the StoP database, conventional meta-analyses overvalued the relation between ever smoking (summary odds ratios ranging from 7% higher for all studies to 22% higher for the risk of gastric cardia cancer) and yielded less precise summary estimates (SE ≤2.4 times higher). Additionally, funnel plot asymmetry and corresponding hypotheses tests were suggestive of publication bias. Conventional meta-analyses and individual participant data pooled-analyses reached similar conclusions on the direction of the association between smoking and gastric cancer. However, published data tended to overestimate the magnitude of the effects, possibly due to publication biases and limited the analyses by different levels of exposure or cancer subtypes.
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http://dx.doi.org/10.1097/CEJ.0000000000000401DOI Listing
May 2018

Services for spondyloarthritis: a survey of patients and rheumatologists.

Rheumatology (Oxford) 2018 06;57(6):987-996

Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.

Objectives: There have been significant advances in axial spondyloarthritis (axSpA), with implications for service delivery. We evaluated the state of axSpA rheumatology services and how people with axSpA perceive their care.

Methods: An online patient survey was emailed to all members of the National Ankylosing Spondylitis Society and advertised widely via social media. Separately, a Web-based questionnaire about axSpA services was sent to rheumatologists at all 172 acute hospital trusts in the UK.

Results: From the National Ankylosing Spondylitis Society survey, data for 1979 surveys (56% males) were available for analysis. The majority of respondents had longstanding disease and identified their diagnosis as AS, with only 44% aware of the term axSpA. Eighty-two per cent of respondents were currently attending a rheumatologist, with 43% on biologic agents. Satisfaction scores for rheumatology care were high. Respondents' concerns included access during disease flares and adverse effects of analgesics. From the rheumatology survey, the concept and terminology of axSpA was widely accepted by respondents (88%). The majority of centres had at least one rheumatologist with a specialist interest in axSpA (62%), dedicated axSpA clinics (58%) or a multidisciplinary team for axSpA (64%). BASDAI (99%), BASFI (74%) and BASMI (65%) were routinely performed. All centres had access to MRI scans, but scanning protocols varied and were often sub-optimal.

Conclusion: Although overall satisfaction with rheumatology care was high, the results indicate significant unmet patient needs and discrepancies in service provision. This information will inform the development of quality standards for axSpA in order to improve quality and deliver equitable care for all patients.
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http://dx.doi.org/10.1093/rheumatology/kex518DOI Listing
June 2018

Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review.

Iran J Basic Med Sci 2018 Feb;21(2):116-123

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB.

Materials And Methods: PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria.

Results: It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants.

Conclusion: It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.
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http://dx.doi.org/10.22038/IJBMS.2017.22059.5648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811749PMC
February 2018

Fluoxetine Regulates Ig Kappa Chain C Region Expression Levels in the Serum of Obsessive-Compulsive Disorder Patients: A proteomic Approach.

Iran J Pharm Res 2017 ;16(3):1264-1271

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Obsessive-Compulsive Disorder (OCD) is one of the most common mental conditions. Proteome profiling may help identifying important proteins and finally shed lights to complexity of OCD underlying mechanisms. Here, by the application gel-based proteomic approach the proteome profile of patients with washing subtype of OCD before and after treatment with Fluoxetine (positive responders) are compared to healthy matched controls. However, only one of the differentially expressed proteins is examined and introduced in this paper. Proteomic analysis was done by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS)-based. Furthermore, network analysis and biological annotation were handled by Cytoscape Plug-in and CluePedia. The proteome comparison between groups identified protein with the significant expression changes (p<0.05 and fold change ≥ 1.5). While the expression level of Ig Kappa Chain C Region is significantly decreased in OCD patients before any treatments, the trend is almost normalized after treatment with Fluoxetine in positive responders. In addition, interaction profile of IGKC shows that the interacting proteins may be affected as the expression pattern of IGKC changes in OCD patients. In conclusion, IGKC may be introduced as potential biomarker in our study; yet, investigation in bigger sample size and application of validation methods is a requirement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610783PMC
January 2017

Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost?

Expert Rev Vaccines 2018 01 22;17(1):31-44. Epub 2017 Nov 22.

b Antimicrobial Resistance Research Center, Bu-Ali Research Institute , Mashhad University of Medical Sciences , Mashhad , Iran.

Introduction: More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections.

Areas Covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG.

Expert Commentary: Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.
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http://dx.doi.org/10.1080/14760584.2018.1406309DOI Listing
January 2018

Mycobacterium tuberculosis HspX/EsxS Fusion Protein: Gene Cloning, Protein Expression, and Purification in Escherichia coli.

Rep Biochem Mol Biol 2017 Oct;6(1):15-21

Immunobiochemistry Lab, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The purpose of this study was to clone, express, and purify a novel multidomain fusion protein of in a prokaryotic system.

Methods: An gene construct was synthesized and ligated into a pGH plasmid, TOP10 cells were transformed, and the vector was purified. The vector containing the construct and pET-21b (+) plasmid were digested with the same enzymes and the construct was ligated into pET-21b (+). The accuracy of cloning was confirmed by colony PCR and sequencing. BL21 cells were transformed with the pET-21b (+)/hspX/esxS expression vector and protein expression was evaluated. Finally, the expressed fusion protein was purified on a Ni-IDA column and verified by SDS-PAGE and western blotting.

Results: The gene construct was inserted into pET-21b (+) and recombinant protein expression was induced with IPTG in BL21 cells. Various concentrations of IPTG were tested to determine the optimum concentration for expression induction. The recombinant protein was expressed in insoluble inclusion bodies. Three molar guanidine HCl was used to solubilize the insoluble protein.

Conclusion: An HspX/EsxS fusion protein was expressed in and the recombinant protein was purified. After immunological analysis, the HspX/EsxS fusion protein might be an anti-tuberculosis vaccine candidate in future clinical trial studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643456PMC
October 2017

A single nucleotide polymorphism in codon F31I and V57I of the AURKA gene in invasive ductal breast carcinoma in Middle East.

Medicine (Baltimore) 2017 Sep;96(37):e7933

Department of Anatomy, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran Department of Microbiology and Immunology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran Academic Unit of Medical Genetics and Pathology, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

Although few studies have suggested a carcinogenic role for polymorphism of F31I and V57I codons of AURKA gene in invasive ductal carcinoma, contradictory results from different populations mandates regional investigations. We aimed to determine polymorphisms of F31I and V57I codons of AURKA gene and their association with cancer prognosis in patients compared with controls in an eastern population of Iran.A case-control study was conducted on specimens from 100 patients and 100 age- and gender-matched controls. DNA was extracted and the codons F31I and V57I were amplified. The different genotypes were analyzed by PCR-RFLP and electrophoresis.In codon F31I, the frequency of Phe/Ile was 70% and 82% in patients and healthy controls respectively, whereas (Ile/Ile) was 30% in patients and 18% in healthy (P = .047). Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048). No association was observed between SNPs of either F31I or V57I genotypes and histological grades. However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran. Determination of allelic polymorphism of those codons will help to understand background genetic predisposition and could have prognostic value in management of breast cancer in the target population.
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http://dx.doi.org/10.1097/MD.0000000000007933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604643PMC
September 2017