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Background: Dental amalgam, a mixture of approximately 50% mercury with silver, tin, zinc and copper in varying ratios, is a major source of mercury pollution in the general population not occupationally exposed. The toxicity of mercury is enhanced because it is so readily absorbed, with around 90-100% of mercury vapor being absorbed through the oral mucosa. The aim of the current study is to examine the mercury levels in hair and nails in subjects with amalgam fillings.Methods: For a sample of forty university students reporting infrequent fish consump-tion, with their only known exposure to mercury from amalgam fillings, mercury levels were measured in hair and nail samples using the LECO AMA 254 Advanced Mercury Analyzer (USA), according to the ASTM standard No. D-6722 test method.Results: Mercury concentration in hair ranged from 0.09 to 3.11 mg/kg, and in nail from zero to 1.35 mg/kg. We found that subjects with five or more amalgam fillings had significantly higher levels in their hair than subjects with zero to 5 amalgam fillings (CI 95% P=0.003). However, the number of amalgam fillings had no effect on the mercury concentration in nails in these two groups (P=0.26). There was no significant difference between the levels of mercury of males and that of females tested (P=0.26 for nail and P=0.15 for hair).Conclusion: The mercury amount in hair was 1.5 times as much as that of the nail samples, may be due to the differences in the chemical compounds, particularly those with sulfur, or the deposition of those compounds that would be affected by blood circulation during formation of hair and nails. Although the amounts of mercury found in this study were below the WHO maximum acceptable level of 6 mg/kg for mercury in human hair, the levels were sufficient to warrant the use of other dental materials such as composites in order to decrease the overall rate of exposure to mercury.

Background: Inflammatory bowel disease (IBD) is a persistent inflammation of the digestive system, and Mesenchymal Stem Cells (MSCs) and their exosomes have demonstrated potential as treatments for this condition. The objective of this research was to examine the possible effectiveness of intraperitoneal injection of umbilical cord-MSCs (UC-MSCs) and their exosomes through a two-time injection regimen in a mouse model., Method: In this study, an animal model of a specific type of IBD in C57BL/6 mice, induced by dextran sulfate sodium (DSS), was utilized. The mice were treated with MSCs, exosomes, Mesalazine, and a combination of them. Upon sacrificing the mice, colon and spleen tissues were isolated to assess the changes in the mice's weight, colon length, spleen weight, and colitis' pathological symptoms. IL-10 and IL-17 levels were measured, and Treg and Th17 cell percentages were determined as well. Furthermore, colon tissue was stained to investigate histopathological changes., Results: In the groups that received MSCs, there was a significant reduction in the disease activity index and their combinations with exosomes and Mesalazine compared to the colitis group. Colon length increased in all groups except the exosome group. Histological measures were notably reduced in the MSC groups and their combinations. Significant increases in the IL-10 level of colon tissue and the proportion of Treg present in the spleen were observed in the groups receiving MSC and combination treatment. Furthermore, these groups showed a notable reduction in the percentage of spleen Th17 cells. However, IL17A decreased non-significantly in all groups., Conclusion: The results showed that intraperitoneal injection of UC-MSCs and their combination with exosome and Mesalazine in a murine colitis model improved the disease's symptoms. Therefore, MSCs and their combination with exosomes can be a promising therapeutic approach along with other common drugs for IBD, but exosomes alone could not significantly reduce the symptoms of colitis., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed following the Declaration of Helsinki Ethical Principles and approved by the Ethics Committee of the Mashhad University of Medical Sciences, Mashhad, Iran (IR. MUMS. RES.1401.133). (1) Title of the approved project: Evaluation of the effectiveness of umbilical cord mesenchymal stem cells along with the synergistic effect of the Exosomes derived from them on the immune response of an IBD mouse model. (2) Name of the institutional approval committee: the Ethics Committee of the Mashhad University of Medical Sciences, Mashhad, Iran. (3) Approval number: IR. MUMS. RES.1401.133. (4) Date of approval: 06/08/2022. After filling out the informed consent letter, human umbilical cords (H-UC) were obtained from Imam Reza hospital from full-term pregnancy mothers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Mesenchymal stem cell (MSC) therapy has been considered a promising approach for the treatment of Parkinson's disease (PD) for several years. PD is a globally prevalent neurodegenerative disease characterized by the accumulation of Lewy bodies and the loss of dopaminergic neurons, leading to severe motor and non-motor complications in patients. As current treatments are unable to halt the progression of neuronal loss and dopamine degradation, MSC therapy has emerged as a highly promising strategy for PD treatment. This promise is due to MSCs' unique properties compared to other types of stem cells, including self-renewal, differentiation potential, immune privilege, secretion of neurotrophic factors, ability to improve damaged tissue, modulation of the immune system, and lack of ethical concerns. MSCs have been employed in numerous pre-clinical and clinical studies for PD treatment with promising results. However, certain aspects of their efficacy in treating PD may benefit from various genetic and epigenetic modifications. In this review article, we assess these approaches to improving MSCs for specialized treatment of PD., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethical approval and consent to participate: Not applicable. Consent for publication: All authors listed on the manuscript have agreed for publication., (© 2024. The Author(s).)

Inflammatory bowel disease (IBD) significantly diminishes an individual's quality of life and increases the risk of colorectal cancer. Recent clinical and experimental findings suggest that infection with parasitic helminths may suppress the development of certain inflammatory conditions. The objective of this study was to evaluate the immunoregulatory effects of Dicrocoelium eggs on experimentally induced colitis in C57BL/6 mice using dextran sulfate sodium (DSS). C57BL/6 mice received 3.5% DSS orally for 7 days to induce colitis, during which they were treated intraperitoneally with Dicrocoelium eggs. The severity of colitis was assessed through parameters such as body weight, stool consistency or bleeding, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, colon gene expression levels, and serum cytokine levels. Our results indicated that Dicrocoelium eggs administration significantly reduced the severity of colitis and disease activity. Histopathological scores improved, correlating with downregulation of IFN-γ and upregulation of IL-4 expression. This findings suggest the therapeutic potential of Dicrocoelium eggs in treating colitis. Immunotherapy involving Dicrocoelium eggs primarily induces a Th2 response and modulates IFN-γ, contributing to reduced inflammation in colitis. Thus, this approach could be a promising therapeutic strategy for alleviating inflammation in IBD., (© 2024. The Author(s).)

Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)-induced arthritis in rats was investigated. The extract was characterized using liquid chromatography-electrospray mass spectrometry (LC-ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor-alpha (TNF-α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF-α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE-treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Objective: The SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), leads to severe pathogenicity and high mortality among different communities around the world. Therefore, it is important to understand the mechanisms of virus pathogenesis and the immune system's response to prevent the further spread of this virus. This study was aimed to evaluate the relationship between the serum level of interleukin 6 and positive IgG and IgM antibody levels in patients with COVID-19 to investigate inflammation and disease progression., Methods & Materials: In this study, 10 ml of EDTA blood samples were taken from 414 COVID-19 patients. Then, the plasma was separated and the levels of IgM and IgG antibodies and interleukin 6 cytokine were evaluated by ELISA and chemiluminescence methods, respectively. All data were analyzed by SPSS 22 and GraphPad prism 9 software at the significance level of P < 0.05., Results: The results of this study showed that there was no significant difference in the expression of IgM and IgG antibodies between men and women. Also, a significant increase in the mean expression of IL-6 was observed only in the high concentration range (100-〉1000 pg/ml) in men compared to women (P < 0.001). In addition, in the female population, all three concentration ranges (negative, medium, and high) of IL-6 have the highest correlation with high titers (>10 U/ml) of IgM and IgG antibodies. While, in men, all three concentration ranges of IL-6 had the highest correlation with > 10 U/ml IgM antibody titers, but in the case of IgG, the highest correlation between different concentrations of IL-6 was observed with the negative or moderate titers of this antibody and there was an inverse relationship with the high titers of IgG (>10 U/ml)., Conclusion: As a result, the relationship between different serum levels of cytokine IL-6 with different titers of IgM and IgG antibodies was observed in both male and female populations. In general, it can be concluded that the correlation between different concentrations of IL-6 with different IgM titers was similar in both men and women, but in the case of different IgG titers, this correlation was higher in women than men., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

It is well known that systemic lupus erythematosus (SLE) is an auto-inflammatory disease that is characterized by chronic and widespread inflammation. The exact pathogenesis of SLE is still a matter of debate. However, it has been suggested that the binding of autoantibodies to autoantigens forms immune complexes (ICs), activators of the immune response, in SLE patients. Ultimately, all of these responses lead to an imbalance between anti-inflammatory and pro-inflammatory cytokines, resulting in cumulative inflammation. IL-35, the newest member of the IL-12 family, is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. Structurally, IL-35 is a heterodimeric cytokine, composed of Epstein-Barr virus-induced gene 3 (EBI3) and p35. IL-35 appears to hold therapeutic and diagnostic potential in cancer and autoimmune diseases. In this review, we summarized the most recent associations between IL and 35 and SLE. Unfortunately, the comparative review of IL-35 in SLE indicates many differences and contradictions, which make it difficult to generalize the use of IL-35 in the treatment of SLE. With the available information, it is not possible to talk about targeting this cytokine for the lupus treatment. So, further studies would be needed to establish the clear and exact levels of this cytokine and its related receptors in people with lupus to provide IL-35 as a preferential therapeutic or diagnostic candidate in SLE management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Berberine is a benzylisoquinoline alkaloid found in such plants as Berberis vulgaris, Berberis aristata, and others, revealing a variety of pharmacological properties as a result of interacting with different cellular and molecular targets. Recent studies have shown the immunomodulatory effects of Berberine which result from its impacts on immune cells and immune response mediators such as diverse T lymphocyte subsets, dendritic cells (DCs), and different inflammatory cytokines. Multiple sclerosis (MS) is a chronic disabling and neurodegenerative disease of the central nervous system (CNS) characterized by the recruitment of autoreactive T cells into the CNS causing demyelination, axonal damage, and oligodendrocyte loss. There have been considerable changes discovered in MS regards to the function and frequency of T cell subsets such as Th1 cells, Th17 cells, Th2 cells, Treg cells, and DCs. In the current research, we reviewed the outcomes of in vitro, experimental, and clinical investigations concerning the modulatory effects that Berberine provides on the function and numbers of T cell subsets and DCs, as well as important cytokines that are involved in MS., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease., Methods: Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons., Results: Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation., Conclusions: Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties., (© 2023. The Author(s).)

Macrophage polarization is a dynamic process determining the outcome of various physiological and pathological situations through inducing pro-inflammatory responses or resolving inflammation via exerting anti-inflammatory effects. The miRNAs are epigenetic regulators of different biologic pathways that target transcription factors and signaling molecules to promote macrophage phenotype transition and regulate immune responses. Modulating the macrophage activation, differentiation, and polarization by miRNAs is crucial for immune responses in response to microenvironmental signals and under various physiological and pathological conditions. In term of clinical significance, regulating macrophage polarization via miRNAs could be utilized for inflammation control. Also, understanding the role of miRNAs in macrophage polarization can provide insights into diagnostic strategies associated with dysregulated miRNAs and for developing macrophage-centered therapeutic methods. In this case, targeting miRNAs to further regulate of macrophage polarization may become an efficient strategy for treating immune-associated disorders. The current review investigated and categorized various miRNAs directly or indirectly involved in macrophage polarization by targeting different transcription factors and signaling pathways. In addition, prospects for regulating macrophage polarization via miRNA as a therapeutic choice that could be implicated in various pathological conditions, including cancer or inflammation-mediated injuries, were discussed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Maintenance of immune system integrity is a vital requirement to protect human body against pathogens/cancers. Natural compounds have long been used due to their benefits for the immune system. One of which is bee venom that contains a peptide called melittin having antimicrobial and anticancer effects. Since a limited number of studies regarding the effects of melittin on the immune system have been carried out, we aimed to evaluate the effects of melittin on BALB/c mice immune system parameters., Methods: Female BALB /c mice were treated intraperitoneally (i.p) with 0.75 and 1.5 mg/kg doses of melittin for 14 days (5 doses per week). The negative control group received i.p normal saline whereas the positive controls received i.p 20 mg/kg cyclophosphamide (CYP). Immunological parameters such as hematological parameters, delayed-type hypersensitivity (DTH), hemagglutination titer (HA), spleen cellularity, splenocytes proliferation, as well as spleen and bone marrow histopathological assessment were evaluated., Results: Our findings showed that melittin has no gross pathological effect on the spleen and bone marrow. It was also demonstrated that melittin has no any significant effect on hematological parameters. Melittin did not cause any significant changes to proliferation response of splenocytes to PHA and LPS, spleen cellularity, DTH response, as well as the production of anti-SRBC antibodies. According to our results, melittin at 0.75 and 1.5 mg/kg doses could not induce significant changes on immune parameters and as a result, melittin was found to be safe for the mice immune system., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: This study aimed to determine whether syzygium aromaticum (clove) could help polycystic ovary syndrome (PCOS) rats., Materials and Methods: In this experimental study, forty adult female Wistar rats (weighing 250 ± 10 g) were divided randomly into five groups; G1: control, G2: PCOS group, G3: PCOS+clove (30 mg/kg/ orally/daily) group, G4: PCOS+clove (60 mg/kg/orally/daily) group, and G5: PCOS+gonadectomy group. The PCOS was induced by a single dose injection of estradiol valerate (16 mg/kg/IM). Following PCOS induction, the rats were treated for 14 days. Histological parameters, follicle apoptosis, mRNA expression of autophagy markers ( Lc3, Beclin1 ), oxidative stress markers, insulin and blood glucose levels, as well as serum levels of aromatase and testosterone were evaluated in these rats. Finally, the ratio of serum luteinizing hormone (LH) to follicle-stimulating hormone (FSH) levels was also calculated., Results: The autophagy markers ( Lc3, Beclin1 ), histological parameters, oxidative stress, insulin, and hormone levels changed significantly in the PCOS rats (G2). In G3 and G5 groups, it was observed that the levels of LH/FSH and testosterone decreased significantly in comparison to the PCOS group, and inhibition of autophagy was also observed in these groups. Treatment with cloves in the G3 group significantly improved oxidative stress, histological parameters, and insulin levels., Conclusion: These findings demonstrated that oxidative stress, apoptosis, and excessive autophagy could be improved by treatment with low doses of clove and gonadectomy. Cloves may help to improve these parameters by regulating and inhibiting excessive autophagy. However, discovering the direct role of this extract in regulating the parameters such as oxidative stress, insulin, and androgens requires further investigation. In the present study, P<0.05 was considered statistically significant.

Background: Dendritic cells, (DCs) as one of the important immune cell populations, are responsible for the initiation, development, and control of acquired immune responses. Myeloid dendritic cells can be used as a vaccine for several autoimmune diseases and cancers. Tolerogenic probiotics with regulatory properties can affect the maturation and development of immature dendritic cells (IDC) into mature DCs with certain immunomodulatory effects., Objective: To assess the immunomodulatory effect of Lactobacillus rhamnosus and Lactobacillus delbrueckii, as two tolerogenic probiotics, in the differentiation and maturation of myeloid dendritic cells., Methods: The IDCs were derived from the healthy donors in GM-CSF and IL 4 medium. Mature DCs (MDC) were produced with L. delbrueckii, L. rhamnosus, and LPS from IDCs. Real-Time PCR and flow cytometry were used to confirm the DC maturation and to determine DC markers as well as IDO, IL10, and IL12 expression levels, respectively., Results: Probiotic-derived DCs showed a significant reduction in the level of HLA-DR (P≤0.05), CD86 (P≤0.05), CD80 (P≤0.001), CD83 (P≤0.001), and CD1a. Also, the expression of IDO (P≤0.001) and IL10 increased while IL12 expression decreased (P≤0.001)., Conclusion: Our findings revealed that tolerogenic probiotics could induce regulatory DCs by reducing co-stimulatory molecules along with increasing the expression of IDO and IL10 during the differentiation process. Therefore, the induced regulatory DCs probably can be used in the treatment of various inflammatory diseases.

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases., Competing Interests: The authors declare no competing financial or non-financial interests.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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 + and CD8 + T cells, leading to the loss of self-tolerance. However, there is a scarcity of evidence defining the precise molecular interaction between the virus and the immune system to elicit autoreactivity. Here, we present a review of the relevant immunological findings in Covid-19 and the current reports of autoimmune disease associated with the disease., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: 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., Objectives: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (Copyright: © 2021 The Author(s); Published by Iranian Journal of Biotechnology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Keyvani, Riahi, Yousefi, Esmaeili, Shafabakhsh, Moradi Hasan-Abad, Mahjoubin-Tehran, Hamblin, Mollazadeh and Mirzaei.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The present in vitro study aimed to evaluate whether Lactobacillus delbrueckii and Lactobacillus rhamnosus treatments can induce regulatory phenotype, together with modulating the expression of chemokine receptors (CRs) in dendritic cells (DCs). The CRs of DCs have been found to be involved in the pathogenesis of Systemic lupus erythematosus (SLE) through directing recruitment and migration of immune cells., Materials and Methods: In brief, monocytes of patients with SLE and healthy donors were isolated and differentiated to regulatory or inflammatory mature DCs through treatment with L. delbrueckii , L. rhamnosus , mixed probiotics, and LPS., Results: FACScan analysis showed that the expression of CRs including CXCR3, CCR5, CCR4, and CCR3, was significantly reduced in all probiotic-treated groups of SLE and healthy (control) donors when compared with the LPS treated group., Conclusion: The results demonstrated that tolerogenic probiotics could prevent or decrease the expression of inflammatory CRs on the surface of tolerogenic DCs during the maturation process., Competing Interests: The authors declare that they have no conflicts of interest.

Follicle-stimulating hormone receptor (FSHR) plays an essential role as one of the most important molecules in response to some of infertility related medications. Impaired ovarian reserve and poor response to such treatments are partially dependent on the FSHR molecule itself. However, the function and drug sensitivity for this receptor may change due to various allele and polymorphisms in the FSHR gene. Studies indicated some of the FSHR-mediated treatments utilized in clinical centers display different outcomes in specific populations, which may arise from FSHR altered genotypes in certain patients. To support the increased demands for reaching the personalized drug and hormone therapy in clinics, focusing on actionable variants through Pharmacogenomic analysis of this receptor may be necessary. The current study tries to display a perspective view on genetic assessments for Pharmacogenomic profiling of the FSHR gene via providing a systematic and critical overview on the genetics of FSHR and its diverse responses to ligands for infertility treatment in females with impaired ovarian responses and show the potential effects of the patient genetic make-up on related binding substances efficacy. All identified functional drug-related alleles were selected through a comprehensive literature search and analyzed. Advanced technologies for the genetic evaluation of them are also discussed properly.

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.

Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest.