Publications by authors named "Mahmoud Mahmoudi"

185 Publications

Prevalence and genetic characterization of Cryptosporidium in pre-weaned cattle in Urmia (Northwestern Iran).

J Infect Dev Ctries 2021 Mar 31;15(3):422-427. Epub 2021 Mar 31.

Department of Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Introduction: Cryptosporidiosis is a zoonotic disease causing digestive problems in pre-weaned calves. Considering the zoonosis of the parasite and its importance in veterinary medicine, we evaluated the prevalence and genotyping of Cryptosporidium spp. in diarrheic pre-weaned calves in the northwest of Iran.

Methodology: A total of 100 stool samples of the infant calves with diarrhea were collected from industrial and conventional livestock farms in Urmia City. All the samples were tested with acid-fast staining, ELISA, and PCR. Positive samples of the PCR method were sequenced to determine the Cryptosporidium species. The obtained results were compared for the mentioned methods based on statistical factors, sensitivity, specificity, positive and negative predictive values, as well as duration of the experiment and the costs of testing.

Results: The results of this study showed that the prevalence of Cryptosporidium spp. in diarrheic infant calves in Urmia city was 5%, and C. parvum species of Cryptosporidium was detected in all the sequenced samples. According to the findings of the current study, the most appropriate method for the detection of the parasite is the ELISA that has a higher sensitivity and predictive value than acid-fast staining method and should be used in veterinary laboratories.

Conclusions: In the current investigation, C. parvum was identified as the only infectious agent in the region and could be the main cause of human infection. More studies are needed to find the source of infection for establishing the control measures.
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http://dx.doi.org/10.3855/jidc.12122DOI Listing
March 2021

Flavonoids, the compounds with anti-inflammatory and immunomodulatory properties, as promising tools in multiple sclerosis (MS) therapy: A systematic review of preclinical evidence.

Int Immunopharmacol 2021 Mar 23;95:107562. Epub 2021 Mar 23.

Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, are diseases resulting in neurological disabilities that are regarded as chronic, inflammatory, and autoimmune diseases of central nervous system (CNS). In this respect, the use of anti-inflammatory compounds including flavonoids, polyphenolic compounds abundantly found in vegetables and fruits, has proposed to combat MS to dampen the inflammation and thereby ameliorating the disease severity. The objective of this study was to clarify the probable therapeutic effect of flavonoids for treatment of MS. Therefore, only English published articles that reported the therapeutic effect of flavonoids alone or in combination with other anti-MS therapeutic agents on MS, were selected by searching scientific electronic databases including PubMed, Scopus and Web of Science. Evaluation of the selected researches (686) showed that a total of 13 studies were suitable to be included in this systematic review. Interestingly, all of the studies (11 studies concerning EAE and 2 studies concerning MS) reported positive outcomes for the therapeutic effect of flavonoids on EAE and MS. All flavonoid compounds which are mentioned herein could successfully decrease the maximum clinical score of EAE, which is particularly connected to the anti-inflammatory property of these compounds. The literature review clearly discloses that flavonoids alone or in combination with other anti-MS therapeutic agents can pave the way for improving MS therapeutic strategies.
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http://dx.doi.org/10.1016/j.intimp.2021.107562DOI Listing
March 2021

Design of a Model for Management of Referral System in the Iranian Urban Family Physician Program.

Iran J Public Health 2020 Nov;49(11):2144-2151

Department of Health Services Management, School of Medical Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background: The purpose of this research was to identify the main dimensions of management of referral systems in family physician program and then introduce them to policymakers of the country primary health care.

Methods: This descriptive-correlation study was designed in Mazandaran Province, northern Iran (2017). The participants were employees of health centers of Mazandaran and Fars Provinces, Iran. The dimensions influencing on the referral system were identified systematically in the selected countries by using researcher-made questionnaire according to a statistical method called Factor Analysis. The data sufficiency was evaluated by the Bartlett's and Kaiser-Meyer-Olkin's tests. Reliability of test was calculated and confirmed according to Cronbach's Alpha and Combined Reliability tests. Validity of the test was calculated and confirmed based on the average variance extracted (AVE).

Results: In confirmatory factor analysis, coefficient of effect of Electronic Health Record on referral system (as the most important dimension), coefficient of Family Physician, coefficient of structure of insurance, coefficient of policymaking in health care system, coefficient of proper stewardship of health system, and basic health care services, were 0.887, 0.877, 0.860, 0.804, 0.568, and 0.522, respectively.

Conclusion: Six effective dimensions including Electronic Health Record (as the most important dimension), family physician, structure of insurance, policymaking in health care system, proper stewardship of health system, and basic health care services were identified. According to six effective dimensions on management model of the referral system in the Iranian urban family physician program, the health system authorities pay serious attention to the six identified dimensions of the current study to improve the health of the urban community.
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http://dx.doi.org/10.18502/ijph.v49i11.4732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917490PMC
November 2020

Efficacy and safety of convalescent plasma therapy in severe COVID-19 patients with acute respiratory distress syndrome.

Int Immunopharmacol 2021 Apr 2;93:107239. Epub 2020 Dec 2.

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Since SARS-CoV-2 infection is rapidly spreading all around the world, affecting many people and exhausting health care resources, therapeutic options must be quickly investigated in order to develop a safe and effective treatment. The present study was designed to evaluate the safety and efficacy of convalescent plasma (CP) for treating severe cases of COVID-19 who developed acute respiratory distress syndrome (ARDS). Among 64 confirmed cases of severe COVID-19 with ARDS in this study, 32 patients received CP besides first line treatment. Their clinical response and outcome in regard to disease severity and mortality rate were evaluated and compared with the other 32 patients in the control group who were historically matched while randomly chosen from previous patients with the same conditions except for receiving CP therapy. Analysis of the data was performed using SPSS software. Patients with plasma therapy showed improvements in their clinical outcomes including a reduction in disease severity in terms of SOFA and APACHE II scores, the length of ICU stay, need for noninvasive ventilation and intubation and also showed an increase in oxygenation. They also showed reduction in mortality which was statistically significant in less severe cases with mild or moderate ARDS. Early administration of the convalescent plasma could successfully contribute to the treatment of severe COVID-19 patients with mild or moderate ARDS at risk of progressing to critical state.
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http://dx.doi.org/10.1016/j.intimp.2020.107239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709614PMC
April 2021

Does the application of GaAlAs laser and platelet-rich plasma induce cell proliferation and increase alkaline phosphatase activity in human dental pulp stem cells?

Lasers Med Sci 2021 Jan 18. Epub 2021 Jan 18.

Dental Research Center, Mashhad University of Medical Sciences, P.O. Box: 91735-984, Vakilabad Blvd, Mashhad, Iran.

Blood extracts containing platelet products are gaining popularity in promoting healing and pulp regeneration. This study was designed to evaluate the effect of platelet-rich plasma (PRP) and gallium-aluminum-arsenide (GaAlAs) laser on proliferation and differentiation of human dental pulp stem cells (hDPSCs). In this ex vivo study, hDPSCs isolated from impacted mandibular third molars were cultured in Dulbecco's Modified Eagle's medium )DMEM(with 10% fetal bovine serum (FBS). After reaching the desired confluence, the cells were distributed into 4 groups, namely, control, PRP, laser, and PRP+laser for MTT assay and alkaline phosphatase (ALP) test. In the PRP and PRP+laser groups, 10% PRP was added to each well on the plate. In the laser and PRP+laser groups, as for the proliferation test, laser irradiation was carried out for 45 s, while 135 s was designated for ALP test. After 1, 3, and 5 days, cell proliferation and ALP activity were assessed using MTT and ALP colorimetric assay, respectively. Two-way ANOVA was utilized to analyze data. In PRP and PRP+laser groups, cell proliferation and viability increased until day 3 but began to decline afterwards until the 5th day. In the laser group, the increase in proliferation and viability was observed till day 5 which was less than the control group. Laser and control groups exhibited significantly higher cell viability and proliferation than both PRP and PRP+laser groups. ALP activity was more pronounced in PRP+laser, PRP, and laser in descending order; however, all were less than that of the control group. Only in the control group did the ALP activity augment during the 5-day period. Laser irradiation could induce pulp cell proliferation and demonstrated a better performance than PRP in this regard.
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http://dx.doi.org/10.1007/s10103-020-03239-0DOI Listing
January 2021

Cytokine analysis in patients with different stages of thromboangiitis obliterans.

Curr Mol Med 2020 Nov 19. Epub 2020 Nov 19.

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

Background: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases.

Objective: The changes in transforming growth factor β (TGFβ), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptomswereinvestigated in this research.

Methods: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital between 2012 and 2016. They were then categorized into three groups: mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFβ, IL6, TNFα, and IFNγwere determinedby the ELISA method and compared among the groups.

Results: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFβ and IL6 were dysregulatedas the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant(p > 0.05). In the multiple logistic regression model, increased TNFαlevelswere seen in the presence of the moderatesymptoms as compared to the severe ones (p < 0.05).

Conclusion: It could be concluded that TNFα, as part of the defining cytokine-production profile of Thelper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.
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http://dx.doi.org/10.2174/1566524020666201120112828DOI Listing
November 2020

The immunomodulatory effects of mesenchymal stromal cell-based therapy in human and animal models of systemic lupus erythematosus.

IUBMB Life 2020 11 2;72(11):2366-2381. Epub 2020 Oct 2.

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

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune inflammatory disease with no absolute cure. Although the exact etiopathogenesis of SLE is still enigmatic, it has been well demonstrated that a combination of genetic predisposition and environmental factors trigger a disturbance in immune responses and thereby participate in the development of this condition. Almost all available therapeutic strategies in SLE are primarily based on the administration of immunosuppressive drugs and are not curative. Mesenchymal stromal cells (MSCs) are a subset of non-hematopoietic adult stem cells that can be isolated from many adult tissues and are increasingly recognized as immune response modulating agents. MSC-mediated inhibition of immune responses is a complex mechanism that involves almost every aspect of the immune response. MSCs suppress the maturation of antigen-presenting cells (DC and MQ), proliferation of T cells (Th1, T17, and Th2), proliferation and immunoglobulin production of B cells, the cytotoxic activity of CTL and NK cells in addition to increasing regulatory cytokines (TGF-β and IL10), and decreasing inflammatory cytokines (IL17, INF-ϒ, TNF-α, and IL12) levels. MSCs have shown encouraging results in the treatment of several autoimmune diseases, in particular SLE. This report aims to review the beneficial and therapeutic properties of MSCs; it also focuses on the results of animal model studies, preclinical studies, and clinical trials of MSC therapy in SLE from the immunoregulatory aspect.
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http://dx.doi.org/10.1002/iub.2387DOI Listing
November 2020

Comparative assessment of immunomodulatory, proliferative, and antioxidant activities of crocin and crocetin on mesenchymal stem cells.

J Cell Biochem 2021 Jan 20;122(1):29-42. Epub 2020 Sep 20.

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

Saffron (Crocus sativus L) is a well-known spice with active pharmacologic components including crocin, crocetin, safranal, and picrocrocin. Similar to crocin/crocetin, mesenchymal stem cells (MSCs) have been shown to display immunomodulatory and antioxidant properties, which could be beneficial in treatment of various diseases. In the current study, we have evaluated the effects of crocin and crocetin on the functions of MSCs. We used the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate MSCs proliferation, and flow cytometry assay to measure the percentage of apoptotic MSCs and Tregs populations. Furthermore, we used the real-time polymerase chain reaction method to quantify messenger RNA (mRNA) expression of inflammatory and anti-inflammatory cytokines. Antioxidant assay was employed to quantify antioxidant parameters including nitric oxide and malondialdehyde levels besides superoxide dismutase activity. Our findings indicated that both crocin and crocetin at low concentrations (2.5 and 5 µM) exhibited significant effects on increasing MSCs viability and on protecting them against apoptosis-induced death. Furthermore, crocin and crocetin at low concentrations (2.5 and 5 µM) displayed a better antioxidant function. Moreover, increased Treg population was observed at lower doses. In addition, crocin/crocetin at low concentrations caused an elevation in mRNA expression of anti-inflammatory cytokines (transforming growth factor-β, interleukin-10 [IL-10], and IL-4), while at higher doses (25 and 50 µM) they led to lowering inflammatory cytokines (IL-1β, IL-6, IL-17, and interferon gamma). Altogether, both crocin and crocetin at lower concentrations exhibited more efficacies on MSCs with a better effect toward crocin. It seems that crocin and crocetin may be considered as complementary treatments for the patients who undergo MSCs transplantation.
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http://dx.doi.org/10.1002/jcb.29826DOI Listing
January 2021

Dicrocoelium ova can block the induction phase of experimental autoimmune encephalomyelitis.

Parasite Immunol 2020 12 25;42(12):e12792. Epub 2020 Oct 25.

Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Aims: This study aimed at investigating the impact of Dicrocoelium ova on experimental autoimmune encephalomyelitis (EAE) treatment in C57BL6 mice.

Methods And Results: Twenty-eight C57BL/6 mice were assigned into four groups as PBS, prophylaxis (P), treatment1 (T1) and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected intraperitoneally to each mouse. The clinical score, weight changes and incidence time of EAE were recorded. IFN-γ and IL-4 expression is quantified on spleen cells. Also, histopathological study by (H&E) and Toluidine-Blue (TB), and Luxol Fast Blue (LFB) were performed. The data were analysed using SPSS version 21. Mean disease scores were significantly lower in P and T1 groups than the PBS group (P = .01). IFN-γ was lower in P and T1 groups than the PBS group. The highest level of IL-4 was observed in T1 group. The total number of neuroglia cells of corpus callosum was similar in all groups, but the density increased in T1 group compared to the PBS group (P = .03).

Conclusions: Dicrocoelium eggs have a great potential to stimulate immunomodulation towards treatment of EAE during the initial phase.
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http://dx.doi.org/10.1111/pim.12792DOI Listing
December 2020

Berberine Inhibits the Gene Expression and Production of Proinflammatory Cytokines by Mononuclear Cells in Rheumatoid Arthritis and Healthy Individuals.

Curr Rheumatol Rev 2021 ;17(1):113-121

Immunology Research Centre, Bu Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris, and its anti-inflammatory effect has been identified.

Methods: Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 μg/ml), exposed to different concentrations of berberine (10 and 50μM) and dexamethasone (10-7 M) as a reference. The toxicity of compounds was evaluated by WST-1 assay. The expression of TNF-α and IL-1β was determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL-1β was measured by using ELISA.

Results: Berberine did not have any toxic effect on cells, whereas Lipopolysaccharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL-1β, and inhibited TNF-α and IL-1β secretion from LPS-stimulated PBMCs.

Discussion: This study provided a molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels.

Conclusion: Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cell viability. Future studies with a larger sample size are needed to prove the idea.
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http://dx.doi.org/10.2174/1573397116666200907111303DOI Listing
January 2021

Sesquiterpene fractions of plants as potent inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 expression.

Iran J Basic Med Sci 2019 Jul;22(7):774-780

Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Science, Mashhad, Iran.

Objectives: species are important medicinal plants throughout the world. Some species are traditionally used for their anti-inflammatory effect. The present study was designed to isolate sesquiterpene fractions from several species and evaluate their anti-inflammatory activities on key mediators and signaling molecules involved in regulation of inflammation.

Materials And Methods: Sesquiterpene fractions were prepared from several species using the Herz-Högenauer technique. Lipopolysaccharide (LPS)-stimulated J774A.1 macrophages were exposed to isolated fractions. Their possible cytotoxic effect was examined using MTT assay. In addition, nitric oxide (NO) release was measured using Griess method and prostaglandin E2 (PGE2) level was determined by enzyme-linked immunosorbent assay (ELISA). Moreover, protein expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were investigated using Western blot analysis.

Results: Nitric oxide level produced by LPS-primed macrophages was significantly decreased with all prepared fractions in a dose-dependent manner. Saturated sesquiterpene lactones-rich species () showed the highest suppressive activity on NO and PGE2 production via suppression of iNOS and COX-2 expression. Fractions bearing unusual ( and ) and unsaturated sesquiterpene lactones () possess less modulatory effect on PGE2 production and COX-2 expression.

Conclusion: It can be concluded that some of the medicinally beneficial effects attributed to plants may be associated with the inhibition of pro-inflammatory signaling pathways. However, these effects could be dependent on the type of their sesquiterpene content. These findings also introduce new species cultivated in Iran as a useful anti-inflammatory agents.
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http://dx.doi.org/10.22038/ijbms.2019.34792.8249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196345PMC
July 2019

Humoral and cellular immune response to Buerger's disease.

Vascular 2020 Aug 25;28(4):457-464. Epub 2020 Mar 25.

Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Science, Mashhad, Iran.

Objective: Thromboangiitis obliterans is a nonatherosclerotic occlusive disease, affecting small to moderate sized arteries of the upper and lower extremities, leading to progressive inflammation and clot formation. However, the role of humoral and cell-mediated immunity in the development of this disease has not been clearly identified. The present study was intended to investigate the humoral and cellular immune response in patients with Buerger's disease with different disease severity.

Methods: In an observational study, 80 male patients with Buerger's disease were included and categorized into three groups (mild, moderate, and severe) based on clinical manifestations. After blood sampling, cellular phenotypes were determined, and erythrocyte sedimentation rate, immunoglobulins (Ig) A, M, G, and E, as well as C3 and C4 components of the complement system and complement hemolytic activity (CH50) were measured.

Results: The mean age of the patient was 42.85 ± 8.39 years. Pulse abnormality, cold intolerance, and claudication were the most common symptoms. Eleven (13.75%), 46 (57.50%), and 23 (28.75%) patients had mild, moderate, and severe symptoms. Regression analyses showed that the presence of severe symptoms was significantly associated with elevated erythrocyte sedimentation rate and C4 levels ( < 0.05).

Conclusion: Buerger's disease in severe cases was associated with increased erythrocyte sedimentation rate and abnormal C4 levels. The alterations in these inflammatory biomarkers might be due to a secondary inflammatory response to the presence of ulcer or gangrene and the inflammatory process in patients with severe symptoms.
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http://dx.doi.org/10.1177/1708538120910055DOI Listing
August 2020

Higher frequency of circulating, but not tissue regulatory T cells in patients with endometriosis.

J Reprod Immunol 2020 06 18;139:103119. Epub 2020 Mar 18.

Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, PO Box: 19615-1177, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Endometriosis is one of the most common chronic gynecological disorders affecting women at reproductive age. Dysregulation of immune cells, including regulatory T (Treg) cells has contributed to the growth of ectopic lesion in patients with endometriosis.

Objective: The present study investigated the frequency of Tregs in peripheral blood and the expression of Foxp3 in eutopic and ectopic endometriotic tissues in women with and without endometriosis.

Materials And Methods: Peripheral blood mononuclear cells (PBMCs) and eutopic and ectopic endometriotic tissues were obtained from 23 endometriotic and 20 non-endometriotic control women. The frequency of Treg cells in PBMCs was measured using flowcytometry and the expression of Foxp3 in eutopic and ectopic endometriotic tissues was determined by real-time PCR, western blotting and immunohistochemistry.

Result: The frequency of circulating Tregs was significantly higher in endometriotic patients compared with non-endometriotic controls (P < 0.01). The mRNA and protein expression of Foxp3 in eutopic and ectopic endometriotic tissues had no significant differences between the two study groups.

Conclusion: Higher frequency of circulating Tregs in patients with endometriosis compared with controls may be considered as a compensatory mechanism to regulate the inflammatory condition in this disease.
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http://dx.doi.org/10.1016/j.jri.2020.103119DOI Listing
June 2020

Immunization against infection in BALB/c mice using a subunit-based DNA vaccine derived from TSA, LmSTI1, KMP11, and LACK predominant antigens.

Iran J Basic Med Sci 2019 Dec;22(12):1493-1501

Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: To design a multivalent DNA vaccine encoding the most immunogenic regions of the antigens including TSA (Thiol-specific antioxidant protein), LmSTI1 ( stress-inducible protein1), LACK ( homologue of receptors for activated C Kinase), and KMP11 (kinetoplastid membrane protein-11) on BALB/c mice.

Materials And Methods: The chimeric construct was generated including the most immunogenic epitopes containing a combination of domains and oligopeptides of the aforementioned genes. The construct was cloned into pcDNA 3.1 plasmid and named "pleish-dom." Following intramuscular injection of mice, the capability of the vector pleish-dom alone and with pIL-12 (expressing murine IL-12) to raise protective cytokines and parasite burden was evaluated in the BALB/c mice as a susceptible animal model against .

Results: The immunized mice with pleish-dom/pIL-12 showed the highest and the lowest levels of interferon-gamma (IFN-γ) and interleukin-10 (IL-10), as well as the lowest leishmanin skin test (LST) reactions, were found through 8 weeks post-infection.

Conclusion: Although the obtained DNA vaccine from the immunogenic chimeric protein of antigens was able to induce a high level of IFN-γ, it partially protected mice against L. major. However co-administration with pIL-12 led to shift immune response to Th1 phenotype, granuloma formation, and lowered parasite burden, and consequently distinct protection was found.
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http://dx.doi.org/10.22038/IJBMS.2019.14051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043880PMC
December 2019

Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls.

BMC Womens Health 2020 01 6;20(1). Epub 2020 Jan 6.

Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.

Background: Endometriosis is a chronic, painful, and inflammatory disease characterized by extra-uterine growth of endometrial tissues. Increased angiogenesis and resistance to apoptosis have been suggested to be involved in pathogenesis and development of endometriosis. The objective of this study was to examine apoptosis potential and angiogenesis contribution of eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells in patients with endometriosis compared to endometrial stromal cells from non-endometriotic controls (CESCs).

Methods: Stromal cells were isolated by enzymatic digestion of ectopic (n = 11) and eutopic (n = 17) endometrial tissues from laparoscopically-confirmed endometriotic patients. Endometrial stromal cells of 15 non-endometriotic patients served as control. Following cell characterization by immunofluorescent staining and flow cytometry using a panel of antibodies, the total RNA was isolated from the cultured cells, and analyzed for the expression of genes involved in apoptosis (Bcl-2, Bcl-xL, Bax, and caspase-3) and angiogenesis [vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)] by Real-time PCR.

Results: Significantly higher gene expression levels of Bcl-2 and Bcl-xL were found in EESCs compared with EuESCs and CESCs (p < 0.01). The gene expression of Bax in EESCs, EuESCs, and CESCs was not statistically significant. Furthermore, EuESCs exhibited a significantly lower caspase-3 gene expression compared with CESCs (p < 0.01) or EESCs (p < 0.05). Regarding angiogenesis, VEGF-A gene expression in EESCs (p < 0.001) and EuESCs (p < 0.05) were significantly higher compared with those of CESCs. EESCs exhibited a significantly higher HGF gene expression compared with EuESCs (p < 0.05).

Conclusions: These findings suggest reduced propensity to apoptosis and increased angiogenesis potential of EESCs, which may be involved in pathogenesis of endometriosis.
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http://dx.doi.org/10.1186/s12905-019-0865-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945780PMC
January 2020

The Association of HLA-A, B and DRB1 with Buerger's Disease.

Rep Biochem Mol Biol 2019 Jul;8(2):153-160

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

Background: Thromboangiitis obliterans (TAO), also known as Burger's disease, is a devastating disease affecting the arteries and veins of the upper and lower distal limbs most commonly afflicting young male smokers of low socioeconomic status. The expression of human leukocyte antigen (HLA)-A, B and -DRB1 genes have been implicated in the pathogenesis of TAO. Our study aimed to examine the association of different HLA-A, B and -DRB1 genes in TAO patients in the Iranian population.

Methods: A case-control study examining 55 Iranian patients with TAO and 500 healthy subjects was performed in Imam Reza hospital, Mashhad, Iran. The prevalence of major histocompatibility complex (MHC) class I (-A, -B) and class II (-DRB) alleles were determined for each participant.

Results: Our results revealed the -A*03 (odds ratio [OR]=5.394), -A*24 (OR=5.143), -A*31 (OR=4.251), -A*11 (OR=3.034), HLA-B*27 (OR=6.680), HLA-B*15 (OR=3.959), -B*07 (OR=3.698), -B*51 (OR=3.370), -B*44 (OR=3.326), -DRB1*16 (OR=20.583), HLADRB1* 04 (OR=8.960), -DRB1*14 (OR=3.746), -DRB1*03 (OR=2.303), and -DRB1*15 (OR=2.111) alleles to occur at a significantly higher frequency in TAO patients compared to controls (p<0.05). The -A*25, -A*66, -DRB1*08, -DRB1*10, and -DRB1*12 alleles resulted in infinite OR, and was associated with an increased risk of TAO. However, the alleles -A*30, -B*08, -B*45, -B*46, and -B*53 were associated with a protective role against TAO with an OR = 0.

Conclusion: This is the first study examining the pattern in patients with Burger's disease in the Iranian population. Our findings have revealed an association between class I and II alleles with TAO.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844607PMC
July 2019

Alteration in inflammatory mediators in seriously eye-injured war veterans, long-term after sulfur mustard exposure.

Int Immunopharmacol 2020 Mar 1;80:105897. Epub 2019 Nov 1.

Immunoregulation Research Center, Shahed University, Tehran 3319118651, Iran; Department of Immunology, Shahed University, Tehran 3319118651, Iran. Electronic address:

Background: Sulfur mustard (SM) exposure produces extensive systemic and ocular adverse effects on the victims. One of the most important effects is immunological insults that can lead to other organ damages, including the eyes.

Methods: In this descriptive study, 128 SM-exposed veterans with severe eye injury were compared with 31 healthy controls. Tear levels of tumor necrosis factor (TNF)-α and serum concentrations of interleukin (IL)-1α, IL-1β, IL1Ra, IL-6, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and Fas Ligand (FasL) were compared between the two groups.

Results: Meibomian gland dysfunction (MGD); tear breakup time (TBUT < 10″); and conjunctival, limbal, and corneal abnormalities were more frequent among the cases (MS-exposed veterans) than the controls. Ocular involvement was mild in 14.8%, moderate in 24.2%, and severe in 60.9% of the cases. Serum levels of IL-1α and FasL were significantly higher among the cases than among the controls (P < 0.001 and P = 0.037, respectively). Also, a significant decrease was observed in serum and tear levels of TNF-α in the cases as compared with controls (P < 0.001, P < 0.001, respectively). Serum levels of FasL were significantly higher in cases with severe ocular involvement than in the controls (P = 0.03). Nonetheless, serum levels of IL-1β, IL-1Ra, IL-1α/IL-1Ra, and IL-6 were not significantly different between the two groups.

Conclusion: Serum levels of IL-1α and FasL may cause different ocular surface abnormalities in SM-exposed patients. Lower tear TNF-α concentration may be due to lower serum levels of this cytokine in these patients.
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http://dx.doi.org/10.1016/j.intimp.2019.105897DOI Listing
March 2020

Tear and serum MMP-9 and serum TIMPs levels in the severe sulfur mustard eye injured exposed patients.

Int Immunopharmacol 2019 Dec 31;77:105812. Epub 2019 Oct 31.

Department of Immunology, Shahed University, Tehran, Iran; Immunoregulation Research Center, Shahed University, Tehran, Iran. Electronic address:

Introduction: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study, the relationship between tear and serum matrix metalloproteinase (MMP)-9 and serum tissue inhibitors of metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties.

Methods: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA).

Results: Serum level of MMP-9 was significantly higher in the SM-exposed group compared to the control group (P = 0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was significantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal calcification had significantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem (P = 0.045). The SM-exposed group with severe ocular injuries had significantly higher MMP-9/TIMP-1 than the controls (P = 0.046). The SM-exposed group had significantly lower levels of MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had significantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P = 0.009 and P = 0.020).

Conclusion: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages.
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http://dx.doi.org/10.1016/j.intimp.2019.105812DOI Listing
December 2019

Induction of Apoptosis and Growth-Inhibition by Thymoquinone in ACHN and GP-293 Cell Lines in Comparable with Cis-Platinum.

J Pharmacopuncture 2019 Sep 30;22(3):176-183. Epub 2019 Sep 30.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: In the current work, we investigated the cytotoxic and apoptotic effects of Thymoquinone (TQ), an active compound of Nigella sativa (N. sativa) and Cis-platinum, on normal renal epithelial (GP-293) and human renal adenocarcinoma cell lines (ACHN).

Methods: GP-293 and ACHN cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% Fetal bovine serum (FBS) and 1% penicillin plus streptomycin antibiotic. The MTT assay was used for cellular viability assessment. Viability of cells was observed using inverted light microscope 24, 48 and 72 h after exposure of the cells to various concentrations of TQ (1, 2.5, 5, 10, 50 and 100 μg/ml) and Cis-platinum (0.5, 1, 1.5, 2, 3, 6 and 12.5 μg/ml). Moreover, apoptosis was analyzed with a flow-cytometry method. The untreated cells were considered as control group.

Results: Morphological changes such as reduced cell number and increased intercellular distance and reduced cell viability in ACHN and GP-293cell lines were observed in both TQ and Cis-platinum groups; however, Cis-platinum had greater effect on ACHN cell line than GP-293 cell line. In addition, GP-293 cell line was more sensitive to TQ compared to ACHN cell line. Furthermore, TQ and Cis-platinum had apoptotic effects on both ACHN and GP-293 cell lines.

Conclusion: Our findings demonstrated that TQ and Cis-platinum had cytotoxic and apoptotic effects on both cell lines, However, GP-293 cell line was more sensitive to TQ. Additionally, Cis-platinum was more effective on ACHN cell line than on GP-293 cell line.
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http://dx.doi.org/10.3831/KPI.2019.22.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820476PMC
September 2019

Tear and serum interleukin-8 and serum CX3CL1, CCL2 and CCL5 in sulfur mustard eye-exposed patients.

Int Immunopharmacol 2019 Dec 24;77:105844. Epub 2019 Oct 24.

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, 14115111 Tehran, Iran. Electronic address:

Background: The serum and tear levels of four inflammatory chemokines were evaluated in sulfur mustard (SM)-exposed with serious ocular problems.

Materials And Methods: In this study, 128 SM-exposed patients and 31 healthy control participants participated. Tear and serum levels of chemokines were assessed by ELISA method.

Results: There was no significant difference in the serum level of IL-8/CXCL8, CX3CL1/fractalkine, CCL2/MCP-1, and CCL5/RANTES between all SM-exposed subjects and control groups. The tear level of IL-8 in the SM-exposed group was lower than the control group, but the difference was not significant. In the SM-exposed group with the abnormalities in tear breakup time (TBUT) test, fundus and pannus formation were significantly higher than SM-exposed patients without these problems. CX3CL1 levels have significantly increased in SM-exposed group with blepharitis, pterygium, and conjunctival pigmentation as compared with the control group. Besides, significantly higher levels of CX3CL1 were observed in SM-exposed group with or without bulbar conjunctival hyperemia and abnormal vessels a well as with fundus abnormality compared to the control group. Only, SM-exposed group with subconjunctival fibrosis had significantly lower levels of CCL5 than SM-exposed group without this problem.

Conclusion: The higher level of CX3CL1 and consistent levels of IL-8/CXCL8, MCP-1/CCL2, and RANTES/CCL5 in SM-exposed individuals may indicate an anti-inflammatory response against the destructive effects of SM gas. High tear level of IL-8/CXCL8 reflects the severity of ocular surface abnormalities, yet significantly low tear level found in mild SM-exposed subgroup compared with the control group. The lower levels of CX3CL1 and RANTES/CCL5 may represent the different pathophysiology which requires further studies.
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http://dx.doi.org/10.1016/j.intimp.2019.105844DOI Listing
December 2019

Analysis of different signal peptides for the secretory production of Ama r 2 in gram-positive systems (Lactococcus lactis).

Microb Pathog 2020 Jan 25;138:103819. Epub 2019 Oct 25.

Department of Food Science and Technology, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran.

Prokaryotic systems have been considered the most affordable and simplest hosts which are being employed to express recombinant proteins such as allergens; nevertheless, without appropriate signal peptide (SP), these systems cannot be used for secretory proteins. Recently, a lot of effort has been put into assessing the potential of gram-positive strains such as lactic acid bacteria for new applications in the production of heterologous proteins. Ama r 2 is a respiratory allergen from Amaranthus retroflexus, whose recombinant production in the probiotic host could be introduced as a specific and effective way to rapid diagnosis and immunotherapy of this allergy. Consequently, the production of this recombinant protein using the prokaryotic system, requires a suitable SP to protect disulfide bonds and to prevent misfolding. This study was designed to predict the best SPs for the expression of Ama r 2 protein in Lactococcus lactis as the host. In this study, 42 signal sequences were selected from SP databases and the most important features of them were evaluated. First, n, h and c regions of the SPs and their probabilities were investigated by signalP software version 4.1. Then, their physicochemical properties were evaluated by Portparam and SOLpro. Moreover, the secretion sorting and sub-cellular localization sites were evaluated by PRED-TAT and ProtcompB software programs. The results revealed that yjgB, entC2 (Entrotoxine type C-2), ent B (Entrotoxine type), blaZ (Beta lactamase), dex (number 21), blm (Beta lactamase 2), dex (Dextranase; number 20) and number 26 were introduced theatrically as the best SPs to express Ama r 2 in Lactococcus lactis.
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http://dx.doi.org/10.1016/j.micpath.2019.103819DOI Listing
January 2020

Improvement of fertility parameters with Tribulus Terrestris and Anacyclus Pyrethrum treatment in male rats.

Int Braz J Urol 2019 Sep-Oct;45(5):1043-1054

Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences.

Objective: Anacyclus Pyrethrum (AP) and Tribulus Terrestris (TT) have been reported as male infertility treatment in several studies; however, in Iranian traditional medicine these two plants are prescribed simultaneously. In this study, we aimed to determine the effects of AP and TT extracts both separately and simultaneously on the male Wistar rat fertility parameters.

Materials And Methods: 32 male Wistar rats were divided into 4 groups: Control, TT, AP, and AT treated groups. Treatment continued for 25 days and rats were weighed daily. Their testes were dissected for histological studies. Sperm analysis including sperm count, viability and motility were performed. Serum was obtained to evaluate testosterone, LH and FSH levels. Histological studies were conducted to study Leydig, and Sertoli cells, spermatogonia and spermatid cell numbers, and to measure seminiferous diameter and epithelium thickness.

Results: Sperm count increased in all the treatment groups. Sperm viability and motility in AT and AP groups were elevated. TT and AT groups showed signifi cantly increased testosterone level compared to control group (P=004, P=0.000, respectively) and TT, AP and AT treatment groups showed increased LH level (P=0.002, P=0.03 and P=0.000, respectively) compared to control, while only AT group showed increased FSH (p=0.006) compared to control. Histological studies showed signifi cant increase of spermatogonia, Leydig and Sertoli cell numbers and epithelial thickness in AT group compared to other groups. All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells.

Conclusion: TT and AP improved sexual parameters; however, their simultaneous administration had higher improving effects on studied parameters.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2018.0843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844349PMC
October 2019

Alteration in serum levels of ICAM-1 and P-, E- and L-selectins in seriously eye-injured long-term following sulfur-mustard exposure.

Int Immunopharmacol 2019 Nov 31;76:105820. Epub 2019 Aug 31.

Immunoregulation Research Center, Shahed University, Tehran, Iran; Department of Immunology, Shahed University, Tehran, Iran. Electronic address:

Introduction: In this study, the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1), P-, E-, and L-selectins were investigated in seriously eye-injured patients exposed to sulfur mustard (SM).

Material And Methods: A total of 128 individuals with SM-induced serious eye injuries and 31 healthy male controls were included in this study. The serum concentration of soluble forms of adhesion molecules was measured by enzyme-linked immunosorbent assay (ELISA) method.

Result: The serum level of soluble ICAM-1 was significantly higher in the SM-exposed individuals with an abnormality in tear meniscus height, corneal verticillata, and pannus compared with SM-exposed individuals without these abnormalities. There were no significant differences in the level of all three measured selectins between the SM-exposed group and the control groups. SM-exposed individuals with corneal defect had a significantly higher level of soluble E-selectin than SM-exposed individuals without this abnormality. The serum level of soluble P-selectin in the SM-exposed group with limbal abnormality was significantly lower than that in the SM-exposed without this abnormality; also it was significantly higher in SM-exposed group with fundus abnormality compared to that in the control group or SM-exposed group without this abnormality.

Conclusion: The changes in the levels of selectins and ICAM-1 in the SM-exposed group with various ocular abnormalities is a defense mechanism against the toxicity of SM. Further analysis is required to understand the molecular mechanisms of the relationship between adhesion molecules with ocular complications in SM-exposed individuals.
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http://dx.doi.org/10.1016/j.intimp.2019.105820DOI Listing
November 2019

Prevention and treatment of experimental autoimmune encephalomyelitis induced mice with 1, 25-dihydroxyvitamin D.

Neurol Res 2019 Oct 12;41(10):943-957. Epub 2019 Aug 12.

Immunology Research Center, Department of Immunology and Allergy, Mashhad University of Medical Sciences , Mashhad , Iran.

Multiple sclerosis (MS) is a complex inflammatory and demyelinating disease of the central nervous system (CNS) frequently starts in young adulthood. Demyelination, inflammatory and axonal damage in the CNS is the pathological hallmark of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 1, 25-dihydroxyvitamin D (Vitamin D) is involved in calcium regulation, phosphorus homeostasis, and bone mineralization. In addition, vitamin D has potential inhibitory effects on immune cells in various inflammatory and autoimmunity disease. C57BL/6 female mice were divided into prevention groups (low, middle and high doses) and treatment groups (middle and high doses). Prevention groups received vitamin D 2 weeks before EAE induction, and treatment groups were treated with vitamin D simultaneous with EAE induction. Vitamin D inhibits the development of EAE in a dose-dependent manner. Histological studies revealed reduced demyelination and limited infiltration into CNS, moreover vitamin D increased the production of IL-4, IL-10, and TGF-β, while a significant reduction in the production of IFN-γ, IL-6, TNF-α, and IL-17 was observed. Flow cytometry results for CD4 T cell subsets in compliance with ELISA cytokine assay results showed a significant decrease in the percentage of Th1 and Th17, but also a significant increase in the percentage of Th2 and Treg for middle and high dose vitamin D treated mice. Real-time PCR results indicated that middle and high dose vitamin D treatment reduced T-bet and ROR-γt expression, but enhanced GATA3 and Foxp3 expression. Real-Time PCR results in CNS for T cell subsets related cytokines and transcription factors supported the results of flow cytometry and ELISA. This study indicated that middle and high doses of vitamin D3 deviate the balance between Th1/Th2 and Th17/Treg to Th2 and Treg. Moreover, vitamin D3 could reduce the incidence and severity of EAE clinical disease.
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http://dx.doi.org/10.1080/01616412.2019.1650218DOI Listing
October 2019

Correlation between Allergic Rhinitis and Otitis Media with Effusion.

Iran J Otorhinolaryngol 2019 Jul;31(105):209-215

Cancer Molecular Pathology Research Center, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Otitis media with effusion (OME) is prevalent among children in such a way that it is the most common cause of hearing loss and surgery in childhood. Immunoglobulin E (IgE) mediated hypersensitivity has been proposed as a causative factor in the development of OME; however, there has been contrasting data in this regard. Therefore, the present study aimed to detect the possibilities of interconnection.

Materials And Methods: In this study, 37 OME children were selected as the case group and 52 children were randomly chosen as the control group. Allergic rhinitis prevalence, serum total IgE concentration, serum eosinophil count, and nasal scraping cytology were evaluated in all the children. Furthermore, the skin prick test was performed in the OME group and suspected allergic rhinitis patients in the control group.

Results: Allergic rhinitis prevalence was notably higher among OME patients than in the control group (P0.01). There were no remarkable differences in eosinophil counts and serum IgE concentrations in the two groups. Nasal smear eosinophils did not show any significant difference between the two groups; however, Appreciable difference was observed in the allergic rhinitis patients, compared to other OME patients (P0.004).

Conclusion: There may be a correlation between allergic rhinitis and development of OME. Therefore, it seems reasonable to examine allergic rhinitis patients for OME.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666939PMC
July 2019

P53 expression in various types of hydropic placentas (through ploidy analysis as a complementary tool in diagnosis of samples).

Caspian J Intern Med 2019 ;10(2):205-210

Department of Biomedical Engineering, School of Electrical Engineering, Iran University of Science & Technology (IUST), Tehran, Iran.

Background: Placentas characterized by hydropic swelling of chorionic villi occur in a spectrum of pathological conditions including hydropic abortion (HA), partial hydatidiform mole (PHM) and complete hydatidiform mole (CHM). The purpose of this study was to investigate whether the expression of p53 tumour suppressor protein could differentiate these various types of hydropic placentas.

Methods: p53 immunohistochemical staining was performed in 19 molar (8 PHM and 11 CHM) and 10 non-molar (HA) formalin-fixed, paraffin-embedded tissue samples. Ploidy analysis using flow cytometry was performed as a complementary tool in diagnosis of samples.

Results: DNA histograms obtained from all samples had confirmed diploidy in HAs and CHMs and triploidy in PHMs. p53 immunoreactivity was assessed in villous cytotrophoblasts, syncytiotrophoblasts and stromal cells. The p53 positive reaction was predominantly observed in the nuclei of cytotrophoblastic cells and rarely in stromal cells, no reaction was seen in syncytiotrophoblasts. The mean percentage of p53 positive cells were 6.10±3.75 for HA, 25.87±13.4 for PHM and 39.83±18.76 for CHM. There was a significant difference in P53 immunoreactivity of cytotrophoblastic cells between CHM and HA (<0.001), and between PHM and HA (=0.004). There was no significant difference in immunohistochemical reactivity between CHM and PHM (=0.068).

Conclusion: This study confirms that p53 immunostaining may be helpful in distinguishing complete and partial hydatidiform mole from hydropic abortion, but not complete hydatidiform mole from partial hydatidiform mole.
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http://dx.doi.org/10.22088/cjim.10.2.205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619464PMC
January 2019

Single Nucleotide Polymorphisms of FCRL3 in Iranian Patients with Behcet's Disease.

Iran J Public Health 2019 Jun;48(6):1133-1139

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

Background: Both genetic and environmental factors influence, susceptibility to autoimmune disorders including Behcet's disease (BD). FCRL3 (Fc receptor like 3 genes), a novel immunoregulatory gene, has recently been reported as a new promising candidate gene for general autoimmunity. This study was conducted to explore the potential association of FCRL3 polymorphisms with BD.

Methods: This study was conducted from 2010 to 2015 in Tehran University of Medical Sciences, Tehran, Iran. Four single-nucleotide polymorphisms of FCRL3 (rs7528684, rs11264799, rs945635, and rs3761959) were genotyped in 220 patients and 220 healthy controls. Typing of the polymorphisms in this case-control study was carried out using polymerase chain reaction-restriction fragment length polymorphism analysis.

Results: Analysis of the alleles revealed a significantly lower frequency of the A allele at the -169 site (rs7528684) in BD patients compared with that in controls (=0.000, 66.4% versus 82%, χ= 30.23). Moreover, a significant lower frequency of AA genotype and higher frequency of GG genotype was recorded for rs7528684. There was also relationship between posterior uveitis as a clinical sign of disease and polymorphism of allele A at the -169 site (=0.015).

Conclusion: This study revealed a significant difference in both allele and genotype frequency at position -169 of FCRL3 gene between Iranian patients with BD and normal subjects. These data suggest FCRL3 gene polymorphisms might be the autoimmunity risk factor for BD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635340PMC
June 2019

Immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells.

EXCLI J 2019 17;18:405-421. Epub 2019 Jun 17.

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

Curcuminoids are dietary complexes extracted from the seeds of . that contain curcumin, bisdemethoxycurcumin and desmethoxycurcumin. Curcuminoids are popular for their pleiotropic therapeutic functions, such as their anti-inflammatory and anti-oxidant effects. Nonetheless, their clinical use is associated with poor systemic bioavailability and insolubility. The nano-formulation of curcuminoids eliminates these shortcomings. In the present study, we explored immunoregulatory, proliferative and anti-oxidant effects of nanocurcuminoids on adipose-derived mesenchymal stem cells (AT-MSCs). Flow cytometry analysis and MTT assay were employed to explore the effects of nanocurcuminoids on the apoptosis and proliferation of adipose-derived MSCs (AT-MSCs). The anti-oxidant effect of nanocurcuminoids on AT-MSCs also was examined. The immune regulatory effect of nanocurcuminoids was evaluated by the flow cytometric measurement of the T regulatory (Treg) population. The expression of inflammatory and anti-inflammatory cytokines was quantified using real-time PCR. Our findings demonstrate that low concentrations of nanocurcuminoids are beneficial for MSC proliferation, protection of MSCs from apoptosis, reducing inflammatory cytokines and SOD activity. A high concentration of nanocurcuminoids increases the population of Tregs and elevates the expression of TGFβ and FOXP3 genes. The beneficial effects of nanocurcuminoids on AT-MSCs were mainly observed at low doses of nanocurcuminoids.
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http://dx.doi.org/10.17179/excli2019-1366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635727PMC
June 2019

Developmental regulation and lateralization of GABA receptors in the rat hippocampus.

Int J Dev Neurosci 2019 Aug 17;76:86-94. Epub 2019 Jul 17.

Department of Anatomy and cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

GABA is the chief inhibitory neurotransmitter in the adult brain. However, in the developing brain it acts as an excitatory transmitter causing depolarization. Thereby, activates calcium-dependent processes that are crucial for brain development. Accordingly, GABA receptors have the great role in the brain development, especially in the area with persisting neurogenesis such as hippocampus. The present study investigated the development and lateralization of two important subunits of GABA receptors, GABA and GABA, in the developing rat hippocampus during the neurogenesis-active period, at the first two postnatal weeks. Real-time PCR, western blot and immunohistochemistry were used. We found that the mRNA and protein of these GABA receptor subunits have already been expressed at birth and significantly increased at postnatal day (P) 7, and also at P14. Also, regarding the optical densities of GABA and GABA expressing hippocampal cells, we found a significant increase in the distribution pattern of these subunits in the all hippocampal subregions on day 14 after birth. The highest optical density of GABA was observed in the CA3, and GABA in the CA2. Nevertheless, our results did not show a significant laterality differences in the expression of these subunits. Regarding the crucial role of GABA receptors in the hippocampus development; they probably have the same effects on development of the rat hippocampus on both sides.
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http://dx.doi.org/10.1016/j.ijdevneu.2019.07.006DOI Listing
August 2019