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The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ''smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.

Introduction: Angiotensin-converting enzyme 2 (ACE2) is the central receptor of coronavirus disease 2019 (COVID-19) in host cells. Genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in a patient affected by COVID-19. Thus, the genetic background may account for the substantial inter-individual diversity in illness susceptibility or severity. Our study was conducted to find a significant relationship between ACE2 rs4646142 and rs2285666 polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In this study, we randomly selected 230 samples, including 76 patients with severe clinical symptoms and 154 patients with mild clinical symptoms (the positive case of COVID-19 was confirmed by real-time reverse transcriptase polymerase chain reaction [RT-PCR] assay). Then, we performed DNA extraction and investigated the polymorphisms of rs2285666 and rs4646142 by RFLP-PCR method with TaqI and Alu1 restriction enzymes. Results: The study population included 107 men and 123 women, and the mean (±SD) age of the participants was 42.66±10.2. First, the levels of IgM and IgG were examined, and a significant association was observed in the level of IgM between the two groups of COVID-19 patients with mild and severe symptoms, as opposed to IgG. Meanwhile, no significant difference was observed between ACE2 rs4646142 and rs2285666 polymorphisms and the severity of COVID-19. Conclusion: To better understand the genetic variations in people’s susceptibility to COVID-19, this study was designed to evaluate the association between various ACE2 polymorphisms and the infection risk of SARS-CoV-2. However, no statistical difference was discovered.

Gastric cancer (GC) is a malignancy cause associated with a high death rate in the world. Cancer stem cells (CSCs) are a rare immortal subpopulation of cells within tumors with characteristics of the ability to self-renew, initiate tumor, and differentiate into defined progenies as well as and high resistance to conventional therapies.Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Therefore, rapid isolation of CSCs in order to therapeutic targets, especially immunotherapy is very important.Cancerous cell suspension isolated from patients with GC was cultured in the serum-free medium containing EGF, bFGF, LIF, and heparin under non-adherent culture conditions to generate spheres. Expression of mRNA level stemness transcription factors (OCT4, SOX2, SALL4, and Cripto-1), CD44 variable isoforms (CD44s, CD44v3, CD44v6, CD44V8-10) of spheroid-forming single cells compared with gastric normal tissue cells using real time PCR and molecules of CD44, CD54, and EpCAM as gastric CSC markers, and stemness factor Oct4 using flow cytometry, as well as tumorgenicity using subcutaneous injection of sphere-forming cells to nude mice were investigated.Few cancerous cells isolated from patients with GC were able to generate three-dimensional spheroid colonies in the serum-free medium containing EGF, bFGF, LIF, and heparin under non-adherent culture conditions, and form xenograft tumors in immunodeficient nude mice after subcutaneous injection. Spheroid-forming single cells upregulated stemness transcription factors OCT4, SOX2, SALL4, and Cripto-1 that are associated with pluripotency and self-renewal and CD44 isoforms (CD44s, CD44v3, CD44v6, CD44V8-10) compared with gastric normal tissue cells. Finally, molecules of CD44, CD54, and EpCAM as gastric CSC markers and stemness factor Oct4 were expressed in sphere-forming cells.We suggested that the sphere formation and tumorigenicity assays are two procedures, leading to the rapid isolation of cancer cells with certain stem-like properties in order to target CSCs using autologous dendritic cell therapy, especially in patients with advanced disease.

Systematic lupus erythematosus (SLE) is an autoimmune disease reflecting an imbalance between effector and regulatory immune responses. Dendritic cells (DC) are a link between innate and adaptive immunity. Inflammatory DCs (inflDC) can initiate and trigger lymphocyte responses in SLE with over-expression of surface molecules and pro-inflammatory cytokine, including Interferon (IFN) α, Interleukin (IL) 1α, IL-1β, and IL-6, resulting in the overreaction of T helper cells (Th), and B cells immune responses. On the opposite side, tolerogenic DCs (tolDC) express inhibitory interacting surface molecules and repressive mediators, such as IL-10, Transforming growth factor beta (TGF-β), and Indoleamine 2, 3-dioxygenase (IDO), which can maintain self-tolerance in SLE by induction of regulatory T cells (Treg), T cells deletion and anergy. Hence, tolDCs can be a therapeutic candidate for patients with SLE to suppress their systematic inflammation. Recent pre-clinical and clinical studies showed the efficacy of tolDCs therapy in autoimmune diseases. In this review, we provide a wide perspective on the effect of inflDCs in promoting inflammation and the role of tolDC in the suppression of immune cells' overreaction in SLE. Furthermore, we reviewed the finding of clinical trials and experimental studies related to autoimmune diseases, particularly SLE.

Cancer stem cells (CSCs) are a subgroup of cells in malignant cancers, which possess self-renewal capacity, tumor-initiating capability, and pluripotency, as well as being responsible for tumor maintenance, metastasis, relapse, and chemoresistance. The treatment modalities previously established for cancer included surgery, chemotherapy, and radiotherapy. The majority of tumor cells of non-CSCs could be eradicated using conventional chemotherapy and radiotherapy. Therefore, novel and promising therapeutic strategies that selectively target CSCs are of great importance. In this review, we described different therapeutic strategies such as immunotherapy, metabolism-based therapeutic strategies, and additional potential therapeutic approaches (targeting microRNAs [miRNAs], histone deacetylase, and DNA methyl transferase) against CSCs. Taken together, due to the inefficiency of anticancer single therapies, targeting CSCs through their metabolism and using immunotherapy and miRNAs besides classical chemo- and radiotherapy may exert better therapeutic effects.

Type 2 diabetes mellitus (T2DM) is a global human disease that affects millions of people. Long non-coding RNAs (LncRNAs) are transcripts with more than two-hundred nucleotides that play essential roles in the management of mRNAs. In the present study, we examined whether the rs619586 (A/G) polymorphism in the gene encoding lncRNA-MALAT1 is associated with the susceptibility to T2DM among the Isfahan population, Iran. To this end, a case-control study was conducted on 200 healthy persons and 200 patients with T2DM. The genomic DNA was extracted from blood samples to strengthen the intended fragments containing rs619586 SNP. Using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), the wild allele (A) and the mutant allele (G) were examined. Results indicated that the mutant allele (G) and mutant genotypes (AG/GG) were absent in T2DM patients. This absence suggests that the rs619586 (A/G) polymorphism in the gene encoding lncRNA-MALAT1 might not be associated with the susceptibility to T2DM among the Isfahan population.

HIV-1 is a human immunodeficiency virus, which has three enzymes, Integrase (IN), Protease (PR) and Reverse-transcriptase (RT). Inhibitor pattern of two herbal ligands include Curcumin (CRC) and Delta-9-tetrahydrocannabinol (THC) with HIV-1 enzymes were investigated by using molecular docking. These ligands are chosen base on the Lipinski’s rules as an herbal inhibitor of HIV-1 virus. We found that CRC and THC ligands have similar orientation in active sites of IN, PR, and RT enzymes. The highest binding energy between PR, IN and RT with CRC and THC ligands are –8.8 and –8.7 Kcal/mol, respectively that reported for PR enzyme. Residues Asp25, Asp29, Asp30 placed in very important catalytic region in both chains of protease enzyme including the central domain which have H-bond with curcumin and THC. Moreover, residue Ile50 is the most flexible region of protease enzyme which plays a significant role in catalytic activity that has interaction with CRC and THC.

Background and Aims: Psoriasis is a chronic inflammation of the skin caused by the proliferation of inappropriately differentiated horn cells, resulting in plaque psoriasis formation. It is not often fatal, and it may lead to physical disabilities and severe mental stress in which professional and social activities could be highly affected. It is generally accepted that the human leukocyte antigen (HLA)-CW06 allele has a significant role in the onset of this disease. Materials and Methods: This study determines the association between the HLA-CW06 allele and psoriasis. The present case-control study was conducted to evaluate the relation between HLA-CW06 and psoriasis in a population in Iran. This study was performed on 30 samples of patients with psoriasis. Results: The results of polymerase chain reaction- sequence-specific primers for the detection of HLA-CW06 showed positive amplification in 7 out of 30 psoriasis patients as compared to 4 among 30 controls. Conclusion: This study showed that due to different allele frequencies associated with psoriasis in different parts of the world, it seems that other genetic and epigenetic factors may be involved in this disease.

Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NM...

Rheumatoid arthritis (RA) is known to be related to an elevated risk of infections because of its pathobiology and the use of immunosuppressive therapies. Reactivation of latent tuberculosis (TB) infection is a serious issue in patients with RA, especially after receiving anti-TNFs therapy. TNF blocking reinforces the TB granuloma formation and maintenance and the growth of Mycobacterium tuberculosis (Mtb). After intercurrent of TB infection, the standard recommendation is that the treatment with TNF inhibitors to be withheld despite its impressive effect on suppression of inflammation until the infection has resolved. Knowing pathways and mechanisms that are common between two diseases might help to find the mechanistic basis of this comorbidity, as well as provide us a new approach to apply them as therapeutic targets or diagnostic biomarkers. Also, screening for latent TB before initiation of an anti-TNF therapy can minimize complications. This review summarizes the shared gene signature between TB and RA and discusses the biomarkers for early detection of this infection, and screening procedures as well.

Adult T-cell leukemia (ATL) is a life-threatening malignant neoplasm of CD4+ T cells resulted from human T-cell leukemia virus type I (HTLV-I). Tax1 protein of HTLV-I can induce malignant proliferation of T-cells through modulating the expression of growth factors such as platelet-derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV-I in ATL, and also to evaluate mRNA expression of B chain of PDGF and PDGF-β receptor in ATL patients and HTLV-I-infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll-Histophaque density centrifugation. The mean of HTLV-I PVL in ATL patients (42759 ± 15737 copies/104 cells [95% CI, 9557-75962] was significantly (p = 0.01) higher than that in healthy carries (650 ± 107 copies/104 cells [95% CI, 422-879], respectively. The HTLV-I PVL in ATL patients exhibited a significant correlation with PBMC count (R= 0.495, p= 0.001). The mRNA expression of Tax, B chain of PDGF, and PDGF-β receptor genes was significantly higher in healthy patients than patients with ATL. In conclusion, the expression of the canonical PDGFβ and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV-I carriers. This article is protected by copyright. All rights reserved.

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.

Gynecologic cancer is one of the main causes of death in women. In this type of cancer, several molecules (oncogenes or tumor suppressor genes) contribute to the tumorigenic process, invasion, metastasis, and resistance to treatment. Based on recent evidence, the detection of molecular changes in these genes could have clinical importance for the early detection and evaluation of tumor grade, as well as the selection of targeted treatment. Researchers have recently focused on cancer stem cells (CSCs) in the treatment of gynecologic cancer because of their ability to induce progression and recurrence of malignancy. This has highlighted the importance of a better understanding of the molecular basis of CSCs. The purpose of this review is to focus on the molecular mechanism of gynecologic cancer and the role of CSCs to discover more specific therapeutic approaches to gynecologic cancer treatment.

Autoimmunity, hyperstimulation of the immune system, can be caused by a variety of reasons. Viruses are thought to be important environmental elements that contribute to the development of autoimmune antibodies. It seems that viruses cause autoimmunity with mechanisms such as molecular mimicry, bystander activation of T cells, transient immunosuppression, and inflammation, which has also been seen in post-Covid-19 autoimmunity. Infection of respiratory epithelium by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dysregulates the immune response, triggers both innate and acquired immunity that led to the immune system's hyperactivation, excessive cytokine secretion known as "cytokine storm," and finally acute respiratory distress syndrome (ARDS) associated with high mortality. Any factor in the body that triggers chronic inflammation can contribute to autoimmune disease, which has been documented during the Covid-19 pandemic. It has been observed that some patients produce autoantibody and autoreactive CD4

CD4+ T helper (Th) cells play a significant role in modulating host defense. In the presence of lineage specific cytokine cocktail, Naive CD4+ T cells can differentiate into several categories with distinct cytokines profile and effector functions. Th22 cells are a recently identified subset of CD4+ T cell, which differentiate from Naive CD4+ T in the presence of IL-6 and TNF-α. Th22 characterized by the production of interleukin-22 (IL-22) and expression of aryl hydrocarbon receptor (AHR). The main function of Th22 cells is to participate in mucosal defense, tissue repair, and wound healing. However, controversial data have shown that overexpression of IL-22 can lead to pathological changes under inflammatory conditions and tumor progression. This review summarizes our knowledge about the role of Th22 and IL-22 cells in tumor progression through induction of inflammation.

Background Ovarian cancer has the highest ratio of mortality among gynecologic malignancies. Chemotherapy is one of the most common treatment options for ovarian cancer. However, tumor relapse in patients with advanced tumor stage is still a therapeutic challenge for its clinical management. Main body Therefore, it is required to clarify the molecular biology and mechanisms which are involved in chemo resistance to improve the survival rate of ovarian cancer patients. Cancer stem cells (CSCs) are a sub population of tumor cells which are related to drug resistance and tumor relapse. Conclusion In the present review, we summarized the recent findings about the role of CSCs in tumor relapse and drug resistance among ovarian cancer patients. Moreover, we focused on the targeted and combinational therapeutic methods against the ovarian CSCs.

The stem cell-based therapy has emerged as a promising therapeutic strategy for treating cardiovascular ischemic diseases (CVIDs), such as myocardial infarction (MI). However, some important functional shortcomings of stem cell transplantation, such as immune rejection, tumorigenicity and infusional toxicity, have overshadowed stem cell therapy in the setting of cardiovascular diseases (CVDs). Accumulating evidence suggests that the therapeutic effects of transplanted stem cells are predominately mediated by secreting paracrine factors, importantly, microRNAs (miRs) present in the secreted exosomes. Therefore, novel cell-free therapy based on the stem cell-secreted exosomal miRs can be considered as a safe and effective alternative tool to stem cell therapy for the treatment of CVDs. Stem cell-derived miRs have recently been found to transfer, via exosomes, from a transplanted stem cell into a recipient cardiac cell, where they regulate various cellular process, such as proliferation, apoptosis, stress responses, as well as differentiation and angiogenesis. The present review aimed to summarize cardioprotective exosomal miRs secreted by transplanted stem cells from various sources, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and cardiac stem/progenitor cells, which showed beneficial modulatory effects on the myocardial infracted heart. In summary, stem cell-exosomal miRs, including miR-19a, mirR-21, miR-21-5p, miR-21-a5p, miR-22 miR-24, miR-26a, miR-29, miR-125b-5p, miR-126, miR-201, miR-210, and miR-294, have been shown to have cardioprotective effects by enhancing cardiomyocyte survival and function and attenuating cardiac fibrosis. Additionally, MCS-exosomal miRs, including miR-126, miR-210, miR-21, miR-23a-3p and miR-130a-3p, are found to exert cardioprotective effects through induction of angiogenesis in ischemic heart after MI.

Background Legionella pneumophila is the main cause for community-acquired pneumonia especially in hospital environments. In this systematic review and meta-analysis, we evaluated the prevalence of L. pneumophila in clinical samples obtained from Iranian patients. Methods The studies reporting L. pneumophila prevalence in Iranian clinical samples that were published between January 2000 and July 2016 were recruited. Comprehensive Meta-Analysis Software (version 3.3.070) was used for quantitative data analysis. Because of high heterogeneity between the studies according to the Cochrane Q and I2 statistics, a random-effects model was used for meta-analysis. Results Sixteen studies encompassing 1956 subjects were included in the meta-analysis. The overall prevalence of L. pneumophila was 9.6% in clinical samples obtained from the Iranian patients. The age spectrum ranged from 6 months to 80 years old. Dyspnea and cough comprised the most common clinical manifestations. In the subgroup analysis, the prevalence of L. pneumophila was higher in studies with sample size ≤100 (12.9%) in comparison with studies with sample size >100 (8.4%). In addition, the prevalence of L. pneumophila was higher in the years 2009–2016 (9.2%) compared with 2000–2008 (0.7%). Conclusion L. pneumophila is a major cause of community- and hospital-acquired pneumonia. It is of pivotal importance to implement sensitive and reliable molecular and culture-based techniques to detect and control this infection in healthcare environments.

Interleukin-33 (IL-33) is a member of the IL-1 family and plays an ambivalent role in autoimmune diseases. IL-33 signals via the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, NK cells, and T lymphocyte cells. The vital role of IL-33 as an active component gives rise to aberrant local and systemic damage which has been demonstrated in numerous inflammatory disorders and immune-mediated pathological conditions including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, Sjogren's syndrome, inflammatory bowel disease (IBD), etc. IL-33/ST2 axis can up-regulate pro-inflammatory cytokine release in autoimmune disease, however, in some metabolic diseases like diabetes mellitus type 1 IL-33 can be considered an anti-inflammatory cytokine. The purpose of this review is to discuss selected studies on IL-33/ST2 axis in autoimmune diseases and its potential role as a pathogenic or protective cytokine.

The amino acid tryptophan (TRP) is critical for the expansion and survival of cells. During the past few years, the manipulation of tryptophan metabolism via indoleamine 2,3 dioxygenase (IDO) has been presented as a significant regulatory mechanism for tolerance stimulation and the regulation of immune responses. Currently, a considerable number of studies suggest that the role of IDO in T helper 2 (Th2) cell regulation may be different from that of T helper 1 (Th1) immune responses. IDO acts as an immunosuppressive tolerogenic enzyme to decrease allergic responses through the stimulation of the Kynurenine-IDO pathway, the subsequent reduction of TRP, and the promotion of Kynurenine products. Kynurenine products motivate T-cell apoptosis and anergy, the propagation of Treg and Th17 cells, and the aberration of the Th1/Th2 response. We suggest that the IDO-kynurenine pathway can function as a negative reaction round for Th1 cells; however, it may play a different role in upregulating principal Th2 immune responses. In this review, we intend to integrate novel results on this pathway in correlation with allergic diseases.

Multiple sclerosis (MS) is a specific type of chronic immune-mediated disease in which the immune responses are almost run against the central nervous system (CNS). Despite intensive research, a known treatment for MS disease yet to be introduced. Thus, the development of novel and safe medications needs to be considered for the disease management. Application of mesenchymal stem cells (MSCs) as an emerging approach was recruited forthe treatment of MS. MSCs have several sources and they can be derived from the umbilical cord, adipose tissue, and bone marrow. Chemokines are low molecular weight proteins that their functional activities are achieved by binding to the cell surface G protein-coupled receptors (GPCRs). Chemokine and chemokine receptors are of the most important and effective molecules in MSC trafficking within the different tissues in hemostatic and non-hemostatic circumstances. Chemokine/chemokine receptor axes play a pivotal role in the recruitment and oriented trafficking of immune cells both towards and within the CNS and it appears that chemokine/chemokine receptor signaling may be the most important leading mechanisms in the pathogenesis of MS. In this article, we hypothesized that the chemokine/chemokine receptor axes network have crucial and efficacious impacts on behavior of the MSCs, nonetheless, the exact responsibility of these axes on the targeted tropism of MSCs to the CNS of MS patients yet remained to be fully elucidated. Therefore, we reviewed the ability of MSCs to migrate and home into the CNS of MS patients via expression of various chemokine receptors in response to chemokines expressed by cells of CNS tissue, to provide a great source of knowledge.

Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.

Background and Aims: Asthma is a complicated chronic inflammatory disease associated with pulmonary inflammation, severe immune responses of the respiratory tract, and change or destruction in the respiratory tract structure. Several factors, especially genetic and environmental factors, contribute to the pathogenesis of asthma. Interlukin (IL)-13 is considered the most important inflammatory mediator of asthma that play an effective role in the different stages of B cell maturation and differentiation. It also increases the expression of major histocompatibility complex II and CD23 and is effective in IgE isotypes switching. Single nucleotide polymorphisms (SNPs) cause the wide genetic diversity in the genome, and SNP analysis helps evaluate and diagnose disease-related genes. The present study was conducted to investigate the association of -1112C / T and + 2044 G /A polymorphisms in the IL-13 gene with asthma. Material and Methods: Blood samples (5 ml) from asthma patients (167) and controls (172) after spirometry test were collected into tubes, and then DNA was extracted to determine the genotype of asthma patients. Real-time polymerase chain reaction was performed by the Taq Man method, and the results were analyzed using SPSS software version 22. Results: There was a significant difference between the genotype of IL-13 -1112C / T polymorphism in the patient group and the control group (p = 0.028). The IL13 + 2044G / A polymorphism results showed no significant difference between the two groups (p = 0.319). Conclusions: The present study showed that IL-13 -1112C / T polymorphism positively correlates with the induction of asthma, but there was no significant association between the polymorphism + 2044G / A IL-13 and the risk of asthma.

Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.

Novel [Pd(

Background and Aims: Warfarin is an anticoagulant agent used for many years in treating various clinical conditions such as thromboembolisms in cardiovascular disease. Some patients require different doses of warfarin to reach the therapeutic international normalized ratio ratio. These patients have specific demographic characteristics. Genetic polymorphisms in specific genes have been reported to be an essential factor in response to warfarin. The present study investigated the effect of these polymorphisms of genes on warfarin dose necessities in pediatric of VCORC1 gene in patients. Material and Methods: Ninety-five patients with cardiovascular disease, who were receiving warfarin for at least three months, enrolled in the present cross-sectional study. Their genomic DNA was extracted from their peripheral blood, and the VKORC1 (rs9923231) polymorphism was evaluated by polymerase chain reaction and sequencing. Results: Among the study population, 48 patients (50.5%) had TC genotype and, 21 (22.1%) and 9 (9.5%) patients have TT and CC genotype, respectively. There was no significant relation between Warfarin dose and VCORC1 genotype in our population (p

Since half of the genes are inherited from the paternal side, the maternal immune system has to tolerate the presence of foreign paternal antigens. Regulatory T cells facilitate the development and maintenance of peripheral tissue tolerance of the fetus during pregnancy. Reduction in regulatory T cells is associated with complications of pregnancy, including spontaneous abortion. Recent studies in mouse models have shown that the adoptive transfer of Tregs can prevent spontaneous abortion in mouse models through improving maternal tolerance. Thus, adoptive cell therapy using autologous Tregs could potentially be a novel therapeutic approach for cell-based immunotherapy in women with unexplained spontaneous abortion. Besides, strategies for activating and expanding antigen-specific Tregs ex vivo and in vivo based on pharmacological agents can pave the foundation for an approach incorporating immunotherapy and pharmacotherapy. This review aims to elaborate on the current understanding of the therapeutic potential of the adoptive transfer of Tregs in the treatment of spontaneous abortion disease.

Therapeutic angiogenesis presents a potential approach for treating ischemic heart diseases especially in patients who are not appropriate candidates for traditional approaches of revascularization. This approach acts through inducing the neovascularization or maturation of pre-existing collateral vessels into functional arteries to bypass the blocked arteries and restore perfusion to ischemic myocardium. Successful stimulation of local angiogenesis can be established by the cross talk between stem cells, endothelial cells, and cardiomyocytes, which is mainly mediated by paracrine communication accompanied by secreted exosomes. Exosomes are extracellular vesicles carrying a complex of signaling molecules, such as microRNAs (miRs) that can modulate the function of recipient cells. Such particles have been indicated to exert cardioprotective role through providing signaling cues for angiogenesis, an effect ascribed mainly to their miRs content. Exosomal miRs-mediated therapeutic angiogenesis has been under drastic preclinical and clinical studies. In the current review, it was aimed to summarize pro-angiogenic exosomal miRs released by various cell types mediating angiogenesis, including stem cells, endothelial cells, and cardiomyocytes, which appear to exert a therapeutic effect on the myocardial ischemia. In brief, secreted exosomal miRs including miR-210, miR-23a-3p, miR-424, let-7f, miR-30b, miR-30c, miR-126, miR-21, miR-132, miR-130a-3p, miR-214, miR-378, miR-126, miR-133, and let-7b-5p could protect against myocardial ischemia through inducing cardiac angiogenesis and vascular regeneration resulting in the increase blood flow to ischemic myocardium.

Methicillin-resistant Staphylococcus aureus is the cause of nosocomial and community-acquired infections. This study aimed to evaluate the effect of zinc oxide and silver nanoparticles (ZnO-Ag NPs) on biofilms formation and icaA gene expression in methicillin-resistant S. aureus (MRSA). In this study, three standard strains (ATCC 43300, 25923, and 29913) and a clinical isolate are included. The minimum inhibitory concentration (MIC) of nanoparticles was determined by microdilution broth method. The antibacterial effects of ZnO-Ag NPs either alone or in combination with each other were compared with vancomycin (as the control group). The effect of MIC and sub-MIC concentrations of ZnO-Ag NPs on biofilm formation was determined by the microtiter plate method. The expression level of the icaA gene was assessed by real-time PCR LightCycler® 96 software (Version 1.1.0.1320, Roche, Germany). technique. All experiments were repeated three times. Data were analyzed using SPSS software through ANOVA and t-test. The P-value of less than .05 was considered as statistically significant. The average MICs of ZnO, Ag, and ZnO-Ag NPs compounds were 393.2, 179.8, and 60.8 μg/ml, respectively. The compound of ZnO-Ag NPs had a synergistic effect against all isolates. ZnO-Ag NPs decreased the biofilm formation rate at MIC and sub-MIC concentrations (P < .001). Sub-MIC ZnO-Ag NPs concentration significantly reduced the icaA gene expression in S. aureus strains (P < .03). The sub-MIC concentration of ZnO-Ag NPs reduced biofilm formation rate and icaA gene expression in Staphylococcus aureus strains compared with vancomycin. It can be used to cover medical devices after examining more clinical isolates to prevent bacterial colonization.

Esmaeili, Seyed-Alireza/0000-0002-9371-4170; Momtazi-Borojeni, Amir Abaas/0000-0002-4376-1083 WOS: 000450377600049 {[Ag(FBPY)(2)](+)(FBPYH)(+)}(OTF)(2), FBPY=FPhC(O)C(H)PPh3, FBPYH =FC6H4COCH2PPh3, OTF=CF3SO3, a ylidic complex, was prepared through the reaction of silver trifluoromethanesulfonate (AgOTf) and ylide [FBPY] in 1:2 M ratio and characterized using various techniques. X-ray crystallography was used to determine the crystal structure. CT-DNA binding interaction of the synthesis compound was tested by fluorescence spectroscopy, UV-Vis absorption spectroscopy, and viscometric titration method. The data by the analysis revealed that the Ag complex could bind to DNA through the groove binding mode. The emission titration of bovine serum albumin (BSA) with the complex showed a static process for the fluorescence quenching mechanism of BSA. In addition, the donor (BSA) - acceptor (Ag complex) distance was calculated by using fluorescence resonance energy transfer (FRET). The results of competitive binding by means of Warfarin, Ibuprofen and Digoxin site markers revealed that the complex was bound to the site I of BSA. Notably, molecular docking studies were used for the determination of DNA and BSA-Ag (I) complex binding. Finally, it was shown that the complex had remarkable in vitro cytotoxicity against melanoma (B16F0) and colon carcinoma (C26) cancer cell lines, as shown by the use of MIT([3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] colorimetric assay. (c) 2018 Elsevier B.V. All rights reserved. Isfahan University of Technology (IUT); Faculty of Arts and Sciences, Department of Physics, Ondokuz Mayrs University This research was funded by Isfahan University of Technology (IUT). Crystallography was provided by Faculty of Arts and Sciences, Department of Physics, Ondokuz Mayrs University.

Background: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is present at the intercellular junctions of the secretory epithelium of prostate and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a transporter protein or a putative channel between cancer cells while it has limited expression in normal human tissues. This protein has been suggested as an attractive target for prostate cancer immunotherapy. Objective: This study aimed at the development of a specific single chain fragment variable (scFv) antibody against STEAP-1 epitope and testing the inhibitory effect of the selected scFv antibody in blocking gap junctions between tumor cells. Method: In the current study, a phage library was used and a specific scFv antibody was isolated against STEAP-1 epitope using panning process. Results: PCR and DNA fingerprinting of the obtained clones demonstrated a dominant pattern of a specific clone. Binding of the selected scFv to the corresponding target on PC3 and LNCaP cell lines was tested using ELISA and flow cytometry techniques. The inhibitory effect of the selected scFv antibody in blocking gap junctions between the cells was tested using intercellular communication assay. The selected antibody reacted with the corresponding epitope in ELISA and bound to prostate cancer cells with an intensity of 44.6% (PC3 cells) and 73.4% (LNCap cells) as shown by FACS analysis. Intercellular communication assay indicated that dye transfer between the cells in PC3 and LNCaP cell lines treated with 1000 scFv/cell was significantly inhibited (80-90%). Conclusion: Our results suggested that the selected specific anti-STEAP1 scFv highly inhibited intercellular communication between prostate cancer cells and has the potential to be used as a new effective agent in prostate cancer immunotherapy.