Alleviation of experimental allergic encephalomyelitis in C57BL/6 mice by Soy Daidzein

Experimental allergic encephalomyelitis (EAE) is considered as the murine model of multiple sclerosis. Daidzein a phytostrogenic compound of soy is known to impose immunomodulatory and antioxidative effects. We conducted this study to assess the potential protective and therapeutic effects of daidzein on allergic encephalomyelitis. C57BL/6 mice were induced with allergic encephalomyelitis using myelin oligodendrocyte glycoprotein (35-55) and received daidzein or dimethyl sulfoxide as the vehicle control. To assess the protective effect of daidzein, the mice were administered with 20 mg/kg of daidzein from 21 days prior to 21 days post EAE induction on a daily basis. To evaluate the therapeutic effect of daidzein, mice were fed with 300 mg/kg daidzein after the appearance of the first clinical signs for 10 days. One day after the last gavage, the mice were sacrificed. Spleen and brain were removed for further histological and immunological analysis. Feeding mice with low dose of daidzein prior to disease induction did not affect disease severity. However, treating with high dose of daidzein after the onset of the disease reduced interferon-3 and interleukin-12 secretion, enhanced interleukin-10 production, suppressed lymphocyte proliferation, and decreased cytotoxicity as judged by lactate dehydrogenase release. In conclusion, daidzein reduced the extent of demyelination and disease severity. Chronic oral therapy with low dose of daidzein did not prevent experimental autoimmune encephalomyelitis. However, high doses of daidzein could prohibit disease exacerbation. © Summer 2014, Iran J Allergy Asthma Immunol. All rights reserved

The Frequency of MRSA carriers in health care workers in Gorgan, North of Iran

Methicillin resistant Staphylococcus aureus (MRSA) is one of the most important pathogen in hospitals. Healthcare personnel are the main source of nosocomial infections and identification and control of MRSA carriers can reduce incidence of infections. The aim of this study was to determine the frequency of methicillin resistant Staphylococcus aureus (MRSA) and their antibiotic susceptibility profile among healthcare workers in Gorgan located in northern Iran. Three hundred and thirty three of healthcare workers were participated in this cross-sectional study in 2010. Samples were taken with sterile cotton swabs from both anterior nares. Swabs were plated onto Mannitol salt agar. S. aureus were identified by Gram stain, Catalase, Coagulase and DNase tests. MIC (micro dilution broth) method was used to determine resistance of strains to methicillin. Antimicrobial susceptibility pattern to other antibiotics was performed by diffusion method. Frequency of S. aureus and MRSA carriers among healthcare workers was 24% (80.33) and 3% (10.33) respectively. MIC of isolates was varied between 0.5 and 65.31 (39%) of cases were showed MIC of intermediate that ranged between 4 and 8. Penicillin and Imipenem resistance were seen in 97.5% and 1.4% of isolated S. aureus strains, respectively. Frequency of S. aureus carriers in healthcare workers in our area was median in compare with other region in Iran but the MRSA carriage in healthy staff was lower than most part of Iran. It would be considering to monitor healthy carrier staff because of high rate intermediate MIC in this group to prevent conversion to MRSA

Effects of intermittent fasting on experimental autoimune encephalomyelitis in C57BL/6 mice

Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease. © Summer 2016, Iran J Allergy Asthma Immunol. All rights reserved

Effect of oral genistein administration in early and late phases of allergic encephalomyelitis

Objective(s): Experimental allergic encephalomyelitis (EAE) is an autoimmune disease validated as animal model of multiple sclerosis (MS). Administration of genistein, a phytoestrogenic component of soy, to mice at the onset of EAE is known to attenuate the clinical signs of the disease. The potential effects of genistein on established EAE is less studied. In the current study, we aimed to compare the effects of genistein administration on EAE severity in early and late phases of the disease. Materials and Methods: The C57BL/6 mice were induced with EAE, using MOG 35-55 and gavaged with genistein (300 mg/kg) either after the appearance of the first clinical sign or 30 days post disease induction for ten days. 24 hr after the last gavage, mice were sacrificed. Brains and spleens were removed for assessing lymphocyte proliferation, cell cytotoxicity, and cytokine profile. Spinal cords were dissected to assess the amount of demyelination using Luxol fast blue/cresyl violet staining. Results: Administering mice with genistein, after the establishment of EAE, did not reverse the clinical signs of disease. However, treating with genistein at the onset of disease alleviated the clinical signs by reducing neuronal demyelination. Genistein suppressed the production of IFN-γ and enhanced IL-10 secretion in splenocyte and brain. Genistein also reduced IL-12 and TNF-α secretion in splenocytes, suppressed the proliferation of T-cells, and reduced the cell cytotoxicity. Conclusion: Genistein oral therapy might only reduce EAE severity if started in early phases of the disease

Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

Background: Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). Results: Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment. © 2020 The Author(s)

Rapamycin Augments Immunomodulatory Properties of Bone Marrow-Derived Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis

The immunomodulatory and anti-inflammatory properties of bone marrow-derived mesenchymal stem cells (BM-MSCs) have been considered as an appropriate candidate for treatment of autoimmune diseases. Previous studies have revealed that treatment with BM-MSCs may modulate immune responses and alleviate the symptoms in experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis. Therefore, the present study was designed to examine immunomodulatory effects of BM-MSCs in the treatment of myelin oligodendrocyte glycoprotein (MOG) 35-55-induced EAE in C57BL/6 mice. MSCs were obtained from the bone marrow of C57BL mice, cultured with DMEM/F12, and characterized with flow cytometry for the presence of cell surface markers for BM-MSCs. Following three passages, BM-MSCs were injected intraperitoneally into EAE mice alone or in combination with rapamycin. Immunological and histopathological effects of BM-MSCs and addition of rapamycin to BM-MSCs were evaluated. The results demonstrated that adding rapamycin to BM-MSCs transplantation in EAE mice significantly reduced inflammation infiltration and demyelination, enhanced the immunomodulatory functions, and inhibited progress of neurological impairments compared to BM-MSC transplantation and control groups. The immunological effects of rapamycin and BM-MSC treatments were associated with the inhibition of the Ag-specific lymphocyte proliferation, CD8+ cytolytic activity, and the Th1-type cytokine (gamma-interferon (IFN-γ)) and the increase of Th-2 cytokine (interleukin-4 (IL-4) and IL-10) production. Addition of rapamycin to BM-MSCs was able to ameliorate neurological deficits and provide neuroprotective effects in EAE. This suggests the potential of rapamycin and BM-MSC combined therapy to play neuroprotective roles in the treatment of neuroinflammatory disorders. © 2016, Springer Science+Business Media New York

The Prevalence of plcD Gene and Evaluation of IS6110 Insertion Status in This Gene in Some Clinical Mycobacterium tuberculosis Isolates

Abstract: Objectives: Tuberculosis (TB) is a dangerous and fatal infection. Phospholipid genes can be involved in the pathogenesis of this disease. The aims of this study were evaluation of the plcD gene prevalence and polymorphisms in some clinical Mycobacterium tuberculosis and the position of IS6110 element in this gene. Methods: This study was conducted on 250 clinical M. tuberculosis isolates. The frequency and polymorphism of the plcD gene were detected by PCR-Restriction Fragment Length Polymorphism (RFLP). As well as, the ability and place of the IS6110 element to insert into the plcD gene were evaluated. Results: The plcD gene was present in 88 (35.2) isolates. Among them, 73 cases (82.95) had a normal PCR product without the IS6110 element, and the size of PCR products of plcD was 2837 bp in other positive cases, which indicated the presence of the IS6110 element. Surprisingly, the plcD gene was absent in all Beijing isolates. Conclusions: Based on the data, the plcD gene is one of the normal sites for the insertion of the IS6110 element. In addition, these findings indicated that the role of plcD in the pathogenesis of TB may be covered by other plc genes, as this gene was deleted in all Beijing isolates studied in this research. © 2021, Allerton Press, Inc