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Introduction: Immunological processes are most important in recurrent spontaneous abortion(RSA). According to studies T lymphocytes and natural killer cells(NK cells) are two effective cell groups in RSA. The aim of this study was to investigate the percentage and absolute number of natural killer(NK) cells in women with RSA with unknown etiology. Methods: 24 Women with a history of recurrent pregnancy losses with unknown etiology. We compared the percentage of peripheral blood NK cells with a group of fertile patients. Lymphocytes from peripheral blood were isolated by ficoll paque density centrifugation. Lymphocytes were stained using anti CD56 and(FITC)-anti CD16 and CYQ-CD3 monoclonal antibodies for identification of NK cells and was used anti CD56 and(FITC)-anti CD69 for detection of activated NK cells. We used BD FACS calibure flow cytometry for data analysis. Results: On the basis of the obtained results, absolute number of CD16+56+ cells showed significant increases in Recurrent spontaneous abortion(RSA) in comparison with control group(P= 0.43). Also absolute number of CD16+56bright cells had significant increase in RSA(P=0.00). There was no significant difference(P= 0.08) of CD16+56dim cells between RSA and control group. In RSA, the absolute number of CD69+cells significantly increased(P=0.02). Also, results showed significant increase in the absolute number of CD56+/CD69+ cells in RSA(P=0.04). Conclusion: The results suggested that the higher percentage of NK cells in peripheral blood of RSA patients compared to control group may indicate the same increase in number and cytotoxicity of uterin NK cells.

Introduction: Undoubtedly, reproduction is a necessity for survival and successful pregnancy is an immunological paradox. In the present study, we investigated the proportional changes of CD4+CD25bright T cells, CD4+CD25dim T cells in peripheral blood in unexplained recurrent spontaneous abortions (URSA) and compared it with normal pregnant women by antibody monoclonal method. Methods: The study group comprised of women with miscarriages of unexplained etiology who had normal karyotypes, anticardiolipin antibodies, prolactin levels and normal spousal spermograms. They did not have polycystic ovaries and also did not receive any drugs at the time of the study. PBLs lymphocytes were isolated, then FITC-conjugated and anti-CD4 and PE-conjugated anti-CD25 antibody levels were measured. Then results of the study and control group were analyzed and compared. Results: The absolute number of CD25 bright cells in the CD4‏+T cells in peripheral blood was statistically significantly lower in the study group as compared to the control group(P=0.000). The absolute number of CD4+CD25dimT cells in peripheral blood was statistically significantly higher in the study group as compared to the control group (P=0.000). Conclusion: As decrease in the number of CD4+CD25+Tcells or their functional deficiency may be linked with miscarriage, CD4+CD25+‏ Tells could serve as a novel biomarker for monitoring in URSA patients, but more studies are needed in this field.

The reduction of biodiversity and its adverse effects on plant and animal species is one of the consequences of global warming. The wide spread of non-native species has inherent negative effects on other species and ecosystems and may pose a double and more serious threat to biodiversity in the future due to climate change. Knowing the future distribution of these species can be used for biodiversity conservation. In the current study, the distribution of non-native stone moroko fish was predicted under two optimistic and pessimistic (RCP 2.6 and RCP 8.5) scenarios for the years 2050 and 2080 by the MaxEnt model. The results showed that the performance of the model in predicting species distribution was excellent (0.988) based on the Area Under the Curve (AUC) criterion. In addition, it is predicted that the distribution of the species is likely to increase significantly (more than 100%) in all years and optimistic and pessimistic scenarios. Therefore, managers and decision-makers should consider the significant expansion of this species in the future as well as, its potential effects on biodiversity and take necessary and appropriate management actions.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease recognized by elevated activity of autoimmune cells, loss of tolerance, and decreased regulatory T cells producing inhibitory cytokines. Despite many efforts, the definitive treatment for lupus has not been fully understood. Curcumin (CUR) and berberine (BBR) have significant immunomodulatory roles and anti-inflammatory properties that have been demonstrated in various studies. This study aimed to investigate the anti-inflammatory properties of CUR and BBR on human monocyte-derived dendritic cells (DCs) with an special focus on the maturation and activation of DCs., Methods: Human monocytes were isolated from the heparinized blood of SLE patients and healthy individuals, which were then exposed to cytokines (IL-4 and GM-CSF) for five days to produce immature DCs. Then, the obtained DCs were characterized by FITC-uptake assay and then cultured in the presence of CUR, BBR, or lipopolysaccharide (LPS) for 48 h. Finally, the maturation of DCs was analyzed by the level of maturation using flow cytometry or real-time PCR methods., Results: The results showed promising anti-inflammatory effects of CUR and BBR in comparison with LPS, supported by a significant reduction of not only co-stimulatory and antigen-presenting factors such as CD80, CD86, CD83, CD1a, CD14, and HLA-DR but also inflammatory cytokines such as IL-12., Conclusion: CUR and BBR could arrest DC maturation and develop a tolerogenic DC phenotype that subsequently promoted the expression of inhibitory cytokines and reduced the secretion of proinflammatory markers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: This study aimed to assess the ex vivo impact of Lactobacillus delbrueckii (L. delbrueckii) and Lactobacillus rhamnosus (L. rhamnosus) on inflammatory and anti-inflammatory cytokines as well as their related molecules on the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients., Patients and Methods: This study was conducted with 20 newly diagnosed SLE patients (18 females, 2 males; mean age: 33.3±12.4 years; range, 18 to 68 years) between September 2017 and September 2018. Extracted PBMCs from each patient were divided into 4 cell groups in our study. Three cell groups act as treatment groups receiving L. rhamnosus (10 7 CFU/mL), L. delbrueckii (10 5 CFU/mL) or a mixture of both, and one group act as our untreated control group in the absence of any probiotic agents. All cell groups were cultured in RPMI 1460 medium for 48 h. Then, total RNA was extracted, and cDNA was synthesized., Results: The gene expression levels of forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), interleukin (IL)-6, IL-10, and IL-2 were evaluated by a quantitative real-time polymerase chain reaction. The results revealed that expression levels of FOXP3, TGF-β, IL-10, and IL-2 increased and the level of IL-6 decreased in probiotics-receiving groups compared to the control group. Lactobacillus delbrueckii and L. rhamnosus enhanced the expression of regulatory T cell-related molecules such as FOXP3 and IL-2 and also increased the expression of IL-10. These probiotics also reduced the expression of IL-6 as proinflammatory cytokines in the PBMCs of SLE patients., Conclusion: The results of the present study show that these probiotics could be effective in regulating the balance of cytokine gene expression ex vivo , and due to their beneficial effects, they can be an intriguing option in the production of new complement drugs for SLE., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

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.

Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune-mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG 35-55 , and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor-β (TGF-β), interleukin-10 (IL-10), IL-6, IL-23 and IL-17 were assessed with a real-time polymerase chain reaction technique. Furthermore, secretion of TGF-β and IL-17 cytokines were determined by enzyme-linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p < .001). Our results showed a significant decrease in IL-17, as well as an increase in TGF-β cytokine in the treatment group compared to the EAE control group (p < .01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease-associated cytokines decreased and the mRNA expression of the anti-inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS., (© 2022 John Wiley & Sons Ltd.)

Introduction: Sulfur mustard (SM) intoxication produces local and systemic changes in the human body. In this study, the relationship between tear and serum matrix metalloproteinase (MMP)-9 and serum tissue inhibitors of metalloproteinases (TIMPs) are assessed in serious eye-injured SM-exposed casualties., Methods: A group of 128 SM-exposed patients with serious ocular injuries in three subgroups (19 mild, 31 moderate, and 78 severe cases) is compared with 31 healthy controls. Tear and ocular status and serum MMPs and MMP-9/TIMPs complex levels were evaluated using enzyme-linked immunosorbent assay (ELISA)., Results: Serum level of MMP-9 was significantly higher in the SM-exposed group compared to the control group (P = 0.009). Mean serum MMP-9 level in the SM-exposed group with ocular abnormalities was significantly higher than that in the SM-exposed group without ocular abnormalities. SM-exposed people with corneal calcification had significantly higher serum MMP-9/TIMP-1 level compared to the SM-exposed ones without this problem (P = 0.045). The SM-exposed group with severe ocular injuries had significantly higher MMP-9/TIMP-1 than the controls (P = 0.046). The SM-exposed group had significantly lower levels of MMP-9/TIMP-4 complex than the controls (P < 0.001). The SM-exposed group with tear meniscus and fundus abnormality had significantly higher MMP-9/TIMP-4 levels than the SM-exposed group without these problems (P = 0.009 and P = 0.020)., Conclusion: Serum MMP-9 level had increased in SM-exposed groups with ocular problems, while TIMP-1 and TIMP-2 levels had remained unchanged. Serum TIMP-4 drastically decreased in SM-exposed group, which clearly explains the severity of the systemic and ocular damages., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane-induced lupus mice model. Fifty-four female BALB/c mice (3-5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE-induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble-stranded DNA (anti-dsDNA), antiribonucleoprotein (anti-RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL-6), IL-10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti-dsDNA, and anti-RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti-dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL-6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE-induced mice., (© 2018 Wiley Periodicals, Inc.)

Background: The majority of patients with multiple sclerosis (MS) suffer from central neuropathic pain (CNP). Using experimental autoimmune encephalomyelitis (EAE) model, only a few experiments were performed to assess pain behaviors in MS. To address this issue, complete Freund's adjuvant (CFA) was replaced with an acylated triterpene glycoside saponin adjuvant named quillaja saponin-21 (QS-21) to develop CNP in the EAE mouse model. The deacylated form of QS-21, named QT-0101, has been suggested to have an immunomodulatory effect. Thus, QT-0101 was used as a vaccine adjuvant to modulate the immune system against myelin oligodendrocyte glycoprotein (MOG35-55) antigen., Methods: In this study, C57BL/6 mice, except for mice in the negative control (PBS) and MOG groups, were divided into three groups and immunized by MOG35-55 emulsified with CFA, QS-21, or QT-0101 adjuvants, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, through the Hot Plate test and the clinical signs, was assessed for 60 days after immunization. On days 21 and 60, mice were sacrificed and the frequency of TCD4 + , TCD8 + , IL-17 + , IL-4 + , and CD25 + /FoxP3 + cells population in the total splenocytes population was assessed by flow cytometry. Infiltration of Leukocytes into the brain and demyelination of white matter were also evaluated by histopathologic studies., Results: Our results revealed that unlike the MOG+QT-0101 group, the MOG+QS-21 and MOG+CFA groups represented clinical symptoms that mimic the mild relapsing-remitting and monophasic models, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, developed in the bilateral hind paws in the MOG+CFA and MOG+QS-21 mice groups during the onset of neurologic deficits, but it is maintained until completion of the study only in MOG+QS-21 mice group. The frequency of TCD4 + , TCD8 + and IL-17 + cells population in the MOG+QS-21 and MOG+CFA mice groups, as well as IL-4 + and CD25 + /Foxp3 + cells population in the MOG+QT-0101 mice group, significantly increased in comparison with the PBS mice group. Infiltration of inflammatory cells increased significantly in the MOG+QS-21 and MOG+CFA mice groups compared with the PBS mice group. Demyelination of white matter was identified significantly only in the MOG+CFA mice group compared with the PBS mice group., Conclusion: These results showed that QS-21 is a suitable adjuvant for the establishment of a mild relapsing-remitting EAE model for CNP development and open a new avenue to future pre-clinical and clinical research studies related to CNP treatment. Nevertheless, QT-0101 seems to have the potential to act as a vaccine adjuvant with immunomodulatory property against auto-antigens., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM-CSF and IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase (IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis., (© 2018 Wiley Periodicals, Inc.)

Uncontrolled inflammation in systemic lupus erythematosus (SLE) could cause dysfunction in multiple organs. T helper 17 (Th17) cells are a main branch of inflammatory responses in the pathogenesis of SLE, and by producing interleukin 17 (IL-17), represent a major functional tool in the progression of inflammation. Animal models provide a special field for better studies of the pathogenesis of diseases. Tolergenic probiotics could decrease inflammation in autoimmune diseases by modulating the immune system and maintaining homeostasis. The aim of this project was to evaluate the effects of Lactobacillus rhamnosus and Lactobacillus delbrueckii on Th17 cells and their related mediators in a pristane-induced BALB/c mice model of SLE. The mice were divided into pretreatment groups, which received probiotics or prednisolone at Day 0, and treatment groups, which received probiotics and prednisolone 2 months after injection. The presence of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-ribonucleoprotein (anti-RNP) and lipogranuloma was evaluated; also, the population of Th1-Th17 cells as well as interferon γ (IFN-γ), IL-17, and IL-10 levels, and the expression of RAR-related orphan related receptor gamma (RORγt) and IL-17 were determined. We observed that probiotics and prednisolone could delay SLE in pretreatment and treatment mice groups, with a reduction in ANA, anti-dsDNA, anti-RNP, and mass of lipogranuloma. Probiotics and prednisolone decreased the population of Th1-Th17 cells and reduced IFN-γ and IL-17 as inflammatory cytokines in the pretreatment and treatment groups in comparison with SLE-induced mice. Our results indicated that, due to their anti-inflammatory properties and reduction of Th17, Th1, and cytotoxic T lymphocyte (CTL) cells, the use of these probiotics could probably represent a new tool for the better management of SLE., (© 2018 Wiley Periodicals, Inc.)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of inflammatory cytokines and autoreactive antibodies due to the loss of immune tolerance. Recognition of self-nucleic acids by intracellular Toll-like receptors (TLRs) can overactivate immune responses and this abnormal activation of TLRs contributes to the pathogenesis of the disease. In recent years, anti-inflammatory and immunomodulatory effects of 1,25-dihydroxyvitamin D3 (VitD3) on the immune system has received particular attention. The present study investigated the effects of vitamin D3 on the expression of TLR3, TLR7, and TLR9 in SLE patients. Study participants included 20 SLE patients and 20 age- and sex-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured in the presence or absence of vitamin D3 (50 nM). Then RNA was extracted, cDNA was synthesized and gene expression levels of TLR3, TLR7, and TLR9 were assessed using real-time PCR. Up-regulated expression levels of TLR7 and TLR9 were observed in the PBMCs of SLE patients in comparison with controls. Culturing PBMCs with vitamin D3 significantly down-regulated the expression of TLR3 (8.86 ± 4.2 for SLE patients vs. 45.34 ± 18.6 for control; P = 0.03), TLR7 (17.91 ± 7.7 for SLE patients vs. 242.37 ± 89.6 for controls; P = 0.0001) and TLR9 (4.67 ± 1.9 for SLE patients vs. 8.9 ± 1.5 for controls; P = 0.007) in SLE patients in comparison with healthy controls. The results of the current study suggest that vitamin D3 could exert some of its immunomodulatory effects in SLE patients via affecting the expression levels of some TLRs. J. Cell. Biochem. 118: 4831-4835, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Recent reports have shown that probiotics can induce immunomodulatory activity with promising effects in inflammatory diseases. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of Lactobacillus plantarum A7, which comprises human commensal bacteria, and Bifidobacterium animalis, a potential probiotic strain, on alleviation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS., Methods: To evaluate the therapeutic effects of probiotic strains, female C57BL/6 mice (8-10 wks old) received Lactobacillus plantarum A7, Bifidobacterium animalis PTCC 1631or a mixture of both strains through oral administration daily for 22days beginning simultaneous with induction of EAE. The clinical parameters were recorded daily. On Day 22, each mouse was bled, and their spinal cord was removed for histology analysis. The effects of the treatments on regulatory T (Treg) cells level were evaluated using flow cytometry, and T-cell proliferation was assessed using a BrdU incorporation assay. The supernatants of spleen and lymph nodes cultured and mononuclear cells were collected for quantification of different panel of pro and anti-inflammatory cytokines by ELISA. The analysis of gene expression was performed at RNA level for transcription factors by real-time PCR., Results: The results showed that treatment with a mixture of the two strains caused a more significant delay in the time of disease onset and clinical score compared to when the strains were used alone. The pathological features of the disease, such as mononuclear infiltration into the CNS, were also inhibited more significantly by the combinational approach. The results also revealed that treatment with combination of both strains enhanced the population of CD4 + CD25 + Foxp3 + -expressing T-cells in the lymph nodes and the spleen., Treatment: with our probiotic strains markedly inhibited disease associated cytokines while increased anti-inflammatory cytokines. Additionally, L. plantarumA7 and B. animalis ameliorated EAE condition by favoring Th2 and Treg differentiation via up-regulation of Foxp3 and GATA3 in the brain and spleen as well as inhibited the differentiation of Th1 and Th17 cells., Conclusions: The current research provided evidence that probiotic therapy with L. plantarum and B. animalis can effectively attenuate EAE progression as well as reinforce the polarization of regulatory T-cells., (Copyright © 2017. Published by Elsevier Masson SAS.)

Background & Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects females more than males. Gender affects the manifestations of SLE and men with lupus show more severe symptoms and worse prognosis. This study was aimed to compare clinical and immunological features in female and male lupus patients in Iran., Methods: Demographic, clinical and laboratory data from 78 women and 20 men with lupus were collected. Autoantibodies (against nRNP, Sm, SSA, SSB, Ro-52, CENP, Jo-1, Scl-70, nucleosome, anti-dsDNA, histone and Rib-p protein) were determined using immunoblotting technique., Results: Men with lupus had less anti-SSA (21.1 vs 48.1%) and anti-Ro52 (10.5 vs 44.3%) antibodies when compared to women and none of the male patients had anti-SSB antibodies. Kidney damage was more frequent in men (68.4% in men vs 36.7% in women). In men with kidney involvement, anti-dsDNA increased significantly (84.6 vs 20.0%) in comparison to males without nephritis. Anti-SSA (7.7 vs 50.0%) and anti-nRNP (0.0 vs 33.8%) on the other hand, decreased. Women with renal involvement had no anti-SSB antibodies., Interpretation & Conclusions: In male patients, SLE appeared with more severe features, and kidney damage was more frequent in males. The frequency of some autoantibodies was different between females and males. In males with kidney damage anti-dsDNA increased significantly, while anti-SSA and anti-nRNP decreased. Anti-SSB was not detected in males and females with nephritis.

The effects of isoquinoline alkaloid berberine (BER) on spleen tissue CD4 + CD25 + Foxp3 + regulatory T (T reg ) cells were evaluated in BALB/c mice. Here, BER was administered daily by intraperitoneal injection at doses of 5 mg/kg and 10 mg/kg for 14 days. Following the exposure, mice spleen cellularities, IL-10 production by splenocytes, and spleen T reg /CD4 + cell profiles were studied in all the test groups of animals. The results showed that a high dose of BER (10 mg/kg) could decrease both the absolute and relative percentages of spleen T reg cells as well as decrease the production of IL-10 by splenocytes in the treated mice (p<0.05). BER at 5 mg/kg did not appear to affect any of these parameters. Based on the finding here, it would seem that BER has effective immunostimulatory properties, which contradicts the results from other studies indicating immunosuppressive effects of BER. Depending on the doses of BER used, it might have a broad spectrum from immunosuppressive to stimulatory effects. Further studies, including more doses, are required to better evaluate the effects of this natural product. Mechanistic studies are required, particularly in case of redox state of the immune cells, to elucidate and determine how BER functions to impart the toxicity effects demonstrated here and in other studies., (Copyright © 2017 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and anti-inflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG35-55 and then administered different doses of hyperforin or HPE post-immunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (Treg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased Treg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of Treg cell and could eventually be considered as a potential candidate for use in the treatment of MS.

Introduction: Lupus nephritis is a serious organ involvement with unknown etiology, and glomerulonephritis class IV is one of the most severe forms of the disease which correlates with poor prognosis and death. Immunological abnormalities are implicated in the expression of lupus nephritis. In this study, we examined some T helper 17 and regulatory T-related cytokines and molecules in systemic lupus erythematosus patients with glomerulonephritis class IV., Materials and Methods: The study group comprised of 20 glomerulonephritis class IV SLE patients and 20 sex- and age-matched SLE patients without kidney involvement as control group. Blood samples was collected from each participant, lymphocytes were isolated, and RNA was extracted from lymphocytes. Then cDNA was synthesized using reverse transcription enzyme, and finally using specific primers and probes, the expression levels of forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, interferon (IFN)-γ, interleukin (IL)-6, and IL-17 genes were analyzed by real-time polymerase chain reaction based on the TaqMan method., Results: The expression levels of IL-6, IL-17, IFN-γ, and Foxp3 genes were significantly higher in SLE patients with glomerulonephritis class IV than those with non-nephritis SLE. However, the expression of TGF-β was not significantly different between the SLE patients with and without glomerulonephritis class IV involvement., Conclusions: According to our results, it seems that in class IV glomerulonephritis patients, increased Foxp3-producing regulatory T cells has an imperfect capacity to control the pathogenic IL-17- and IFN-γ-producing cells.

Objectives: Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL-23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE., Materials and Methods: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits., Results: The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL-23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer., Conclusion: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE.

The immunotoxic effects of the isoquinoline alkaloid berberine (BBR) were investigated in Balb/c mice. Here, BBR was administered daily by intraperitoneal injection at doses of 5 and 10 mg/kg for 14 days. Following the exposure, host spleen weight, cellularity and histopathology, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), spleen cell subtype profiles, splenocyte cytokine production and lymphocyte proliferation were studied in all of the test groups of animals. The results showed that the high dose of BBR (10 mg/kg) could suppress both cellular and humoral immune functions in the treated hosts. BBR at 5 mg/kg only appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that BBR has effective immunosuppressive properties. Mechanistic studies are required to determine exactly how this material is acting to impart many of the immunotoxic effects demonstrated here. At the same time, further research should also be performed on BBR to further develop its potential use as an effective immunosuppressant or co-adjuvant for the treatment of diseases caused by an exaggerated or unwanted immune response.

Objectives: Genetic and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE). Autoreactive lymphocytes are cleared through apoptosis and any disturbance in the apoptosis or clearance of apoptotic cells may disturb tolerance and lead to autoimmunity. Vitamin D has anti-proliferative effects and controls cell cycle progression. In this study we investigated the effects of vitamin D on cell cycle and apoptosis induction in lupus patients., Materials and Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 25 SLE patients were cultured in the presence of 50 nM of 1,25(OH)2D3; then one part of the cells were stained with FITC labeled Annexin V and PI and were analyzed for apoptosis determination. For gene expression assessment of FasL, Bcl-2 and Bax, RNA was extracted from one another part of the cells, cDNA was synthesized and gene expression analysis was performed using Real time PCR. An additional part of the cells were treated with PI and the cell cycle was analyzed using flowcytometer., Results: The mean number of early apoptotic cells in vitamin D treated cells decreased significantly (18.48±7.9%) compared to untreated cells (22.02±9.4%) (P=0.008). Cell cycle analysis showed a significant increase in G1 phase in vitamin D treated cells (67.33±5.2%) compared to non treated ones (60.77±5.7%) (P =0.02). Vitamin D up-regulated the expression levels of Bcl-2 by (18.87 fold increase), and down-regulated expression of Bax (23%) and FasL (25%)., Conclusion: Vitamin D has regulatory effects on cell cycle progression, apoptosis and apoptosis related molecules in lupus patients.

Agents that destroy tumor cells and simultaneously boost host anti-tumor immunity are of keen interest in cancer therapy. In the present study, the effect of carnosol on anti-tumor immunity in a Balb/c mouse model of fibrosarcoma was evaluated. Carnosol was administered intraperitoneally daily (at 5 or 10 mg/kg/day, for 7 days) to tumor-bearing mice (i.e. 7 days after initial injection of tumor cells). Another group of tumor-bearing mice was treated with 20 mg cyclophosphamide/kg/d (positive control); a final group received vehicle only (vehicle control). After an initial measure on Day 0, tumor size was measured twice during the 7-day treatment period. One day after the final treatment with vehicle/carnosol (i.e. Day 7), the mice had their tumors measured and then were euthanized to permit their spleen and tumor to be harvested for isolation of, respectively, splenocytes and tumor-associated lymphocytes. Using these materials, spontaneous and mitogen-induced release of interleukin (IL)-4, IL-10, and interferon (IFN)-γ, lymphocyte proliferation, and the absolute numbers/relative percentages of splenic and tumor-associated T-regulatory (Treg) and other T-lymphocyte sub-sets were evaluated. The results showed that carnosol at both doses significantly suppressed tumor growth and caused depletion of splenic and tumor-associated Treg cells. It also caused relative (vs control mouse cell values) decreases in splenocyte spontaneous/inducible production of IL-4 and IL-10 and increases in IFNγ and cell proliferation. Carnosol at either dose did not cause changes in the percentages of CD4(+) or CD8(+) lymphocytes in the spleen or in tumor-associated lymphocyte populations. The observed increases in IFNγ, decreases in IL-10 and IL-4 production, and reductions in splenic/tumor-associated Treg cell levels might be signs reflecting the potential anti-tumor activity of carnosol. Based on the findings here, it is asserted that carnosol is a likely candidate - after more complete toxicologic evaluation - for eventual use as an anti-cancer therapeutic.

Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate immunomodulatory/anti-inflammatory properties of this plant and elucidate potential underlying mechanisms for the actions. Effects of the SLAK on mitogen-induced murine splenocyte proliferation and interleukin (IL)-4 and interferon (IFN)-γ secretion were evaluated. To assess anti-inflammatory activities, levels of inducible of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in peritoneal macrophages was examined. The results showed that SLAK noticeably was capable of suppressing PHA/LPS-stimulated splenocyte proliferation and of up-regulating production of the T-helper (TH)-2 cell cytokine IL-4 while down-regulating formation of TH1 IFNγ. In addition, while SLAK caused negligible proliferation inhibition, peritoneal macrophages displayed considerable decrease in NO and PGE2 production along with iNOS and COX-2 expression. The current experiment shows Artemisia khorasanica - a traditionally used herb - may have immunomodulatory and anti-inflammatory effects. It is anticipated that the ingredients may be employed as therapeutic candidates in the regulation of some immune responses implicated in various conditions and ailments.

Background: Differential diagnosis between complete hydatidiform mole, partial hydatidiform mole and hydropic abortion, known as hydropic placentas is still a challenge for pathologists but it is very important for patient management., Objective: We analyzed the nuclear DNA content of various types of hydropic placentas by flowcytometry., Materials and Methods: DNA ploidy analysis was performed in 20 non-molar (hydropic and non-hydropic spontaneous abortions) and 20 molar (complete and partial moles), formalin-fixed, paraffin-embedded tissue samples by flow cytometry. The criteria for selection were based on the histopathologic diagnosis., Results: Of 10 cases histologically diagnosed as complete hydatiform mole, 9 cases yielded diploid histograms, and 1 case was tetraploid. Of 10 partial hydatidiform moles, 8 were triploid and 2 were diploid. All of 20 cases diagnosed as spontaneous abortions (hydropic and non-hydropic) yielded diploid histograms., Conclusion: These findings signify the importance of the combined use of conventional histology and ploidy analysis in the differential diagnosis of complete hydatidiform mole, partial hydatidiform mole and hydropic abortion.

Context: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention., Objective: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model., Materials and Methods: Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund's adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks after disease establishment. Ten weeks after the last injection the mice were killed and spleens were studied for Treg percentages and expression of cytokine genes., Results: We found that treatment with 1,25-dihydroxyvitamin D3 reduces IL-6 and IL-10 mRNA expression and increases TGF-β and Foxp3 mRNA expression levels, and also enhances spleen Treg percentage., Conclusions: The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-β and Foxp3 gene expressions, along with an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE.

Ursolic acid (UA) is plentifully present in fruits, foods, and medicinal plants, and has anti-cancer activity on many cancer cell lines. However, the effects of UA on some melanoma cells and the mechanisms of action have not been reported. The effect of UA on isolated human melanoma and fibroblast cell lines has been investigated using the MTT assay, and cell death was determined using Annexin-V/PI staining. To explore whether the activation of caspases was required for apoptosis induction, cells were treated with pan-caspase inhibitor and UA. Changes in apoptosis pattern were analyzed by flow cytometry. Activation of caspases was detected by western blot analysis. A significant concentration-dependent suppression of cell proliferation was seen after 24 and 48 h in the presence of UA. Apoptosis was considerably increased by UA, indicated by enhancement of an Annexin-V positive population and a sub-G1 peak. UA induced proteolytic processing of caspase-3. The results confirm the anti-cancer properties of UA on cultured human melanoma cells, possibly mediated through the induction of apoptosis following activation of caspases., (© 2014 International Federation for Cell Biology.)

Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects., Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting., Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c., Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.

Background: Well-documented studies reported several pharmacological properties for crocin, the active compound of Crocus sativus, such as its antitumor, radical scavenging, antidepressant, and memory-enhancing effects., Objectives: We aimed to evaluate the possible cytotoxic activity of crocin on B lymphocytes in human myeloma (U266 cell line) after 24- and 48-hour treatment., Materials and Methods: For this purpose, cell viability was determined by the colorimetric MTT assay and cell death pattern was evaluated using Annexin V-FITC/propidium iodide (PI) apoptosis detection kit. ROS (reactive oxygen species) production and DNA fragmentation were assessed using 2',7'-dichlorofluorescein diacetate (DCFH-DA) kit and PI staining, respectively., Results: The highest concentration of crocin significantly decreased ROS production after 48 hours of treatment. However, crocin had no effect on the expression level of HSP (Heat shock protein). Additionally, its administration caused a mild decline in cell viability and a mild increase in the population of DNA fragmented cells as well as apoptosis., Conclusions: In our study, no prominent effect was seen; therefore, in order to have a better perspective of crocin activity against cancerous cell lines, further studies are highly recommended.

Rose Bengal (RB) has been used as a safe agent in clinical diagnosis. In addition, it is used as a photodynamic sensitizer for removing microorganisms and cancer cells. Recently, its preferential toxicity after direct exposure to cancer cells was proven. The present study focuses on anti-cancer and anti-inflammatory activities of RB. The toxicity of RB against AGS gastric cancer and NIH 3T3 fibroblast cell lines was studied using an MTT assay. Patterns of any cell death among the AGS cells were defined using Annexin-V and PI staining. In addition, the effect of RB on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production induced by lipopolysaccha-ride in J774A.1 macrophages was determined. Modulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressions in the macrophages was also evaluated by Western blots. The results showed that AGS cells exhibited significant concentration-dependent decreases in growth in response to RB; these cells showed a greater growth inhibition than did non-malignant 3T3 cells, suggesting that anti-growth activity of RB could be cell-specific. Moreover, AGS cells exposed to RB exhibited a significant increase in apoptosis; only at high RB doses did the cells display significant levels of necrosis. While RB also caused a modest decrease in the growth of J774A.1 macrophages, the cells displayed remarkable decreases in NO production and iNOS expression without significant concurrent modulation in PGE(2) production or COX-2 expression. The data from this study appears to suggest that RB differentially impacts on transformed cell lines, preferentially suppresses growth of a gastric cancer cell line through induction of apoptosis, and induces changes in cells that could reflect potential anti-inflammatory effects that might be induced in situ.

Purpose: Six major hepatitis C virus genotypes have been characterised, which vary in their geographical distribution. The prevalence of hepatitis C virus (HCV) in an area is not constant, and depends on the changes in route of infection, which may change over time. In this study, the distribution of HCV genotypes in Mashhad, the capital of Razavi Khorasan province in north-east of Iran was investigated. Mashhad is a holy city of Shiate Moslems, which attracts more than 20 million tourists and pilgrims every year., Materials and Methods: Two hundred and seventy-eight HCV infected subjects (227 males and 51 females) were included in this study. HCV genotypes were analysed by type specific reverse transcriptase polymerase chain reaction (RT-PCR)., Results: Genotype 3a was detected in 49.6%, 1a in 36.3%, 1b in 12.6% and 2a in 0.4%. Two HCV genotypes were detected in 1.1% cases; 1a +3a in 1%, 3a + 1b in 0.4%. Genotypes 2b and 3b were not detected in any samples., Conclusion: We demonstrated that despite the previous reports on the frequency of HCV genotypes in Iran, 3a is the predominant genotype in Mashhad.

Objective(s): Apoptosis is a tightly regulated process and plays a crucial role in autoimmune diseases. Because abnormalities in apoptosis are considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE), in present study we studied the apoptosis in T lymphocytes from Iranian SLE patients at protein and gene expression levels for some molecules which are involved in apoptosis pathways., Materials and Methods: Thirty five SLE patients (23 female, 12 male), and 20 age matched controls (10 female, 10 male) participated in this study. T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) using MACS method. Apoptosis rate was studied at protein level by flow cytometer using Annexin V, and at gene expression level using semi-quantitative RT-PCR method for detection of Fas, FasL, Bcl-2, caspase 8, and caspase 9 genes., Results: The percentage of apoptotic cells in SLE patients was not different in comparison with controls (20.2% ± 1.4 vs 21.1% ± 1.0), but the expression levels of FasL, caspase 8, and caspase 9 genes in all SLE patients and in female patients were significantly lower than controls; 0.45R vs 0.78R for FasL, 0.74R vs 1.0R for caspase 8, and 0.76R vs 1.26R for caspase 9 in all SLE patients and 0.37R vs 0.82R for FasL, 0.45R vs 1.6R for caspase 8, and 0.63R vs 1.56R for caspase 9 in female patients., Conclusion: The expression levels of FasL, caspase 8 and caspase 9 molecules involved in apoptosis decreased in female, but not in male SLE patients.

Background: Among various naturally occurring compounds which have been extracted from Crocus sativus, crocin has shown different pharmacological effects i.e. neuroprotection and anti-tumor activity., Methods: Here, crocin effects on human T-cell leukemia cell line, MOLT-4, were evaluated. In this study, we examined the effects of 24 and 48 h of crocin treatment (50, 250 and 500 µM) on the viability of MOLT-4 cell line. Moreover, probable apoptotic/necrotic outcomes, reactive oxygen species (ROS) production variations along with crocin treatment consequences on DNA, were investigated., Results: Results from MTT assay demonstrated that 48-h crocin treatment at 500 µM, significantly reduced cell viability (p<0.01). DNA fragmentation was recorded to be significantly increased at higher doses of crocin following 24 and 48 h (p<0.01). According to our results, while apoptosis was detected at all concentrations, necrosis detected at the highest dose, only. In comparison with control, ROS production was reduced at 50 and 250 µM., Conclusions: In accordance with previous reports, crocin exhibited mild cytotoxic effects on a leukemia cell line which might be mediated through the increase of DNA fragmentation.

Objective(s): Non-Hodgkin's lymphoma (NHL) is a lymphoproliferative malignancy in which cells undergo microscopic changes with unknown etiology, and risk factors such as age, sex, genetic and environmental factors are involved. The relationship between the presence of infectious agents and the development of lymphoproliferative diseases has been an interesting research topic. HTLV-I (Human T Cell Lymphotropic Virus Type-1) predisposes the infected individulas to opportunistic neoplasms and lymphoid malignancies. HCV (Hepatitis C Virus) the etiologic agent of hepatitis C, is hepatotropic, and long-term infection with HCV can continuously stimulate and expand lymphocyte clones, resulting in further transformation and finally aggressive malignancies., Materials and Methods: 54 tissue samples diagnosed with NHL were selected to be studied for the presence of HTLV-I and HCV viruses. DNA and RNA were extracted from samples, cDNA was synthesized and using specific primers presence of HTLV-I and HCV viruses were investigated by PCR and nested RT-PCR methods., Results: In 10 out of 54 (18.8%) samples (7 men and 3 women), HTLV-I was present, and 4 out of 54 (7.4%) samples (3 men and one woman) were positive for HCV., Conclusion: Based on our results, it is recommended that in patients with NHL, infection with HTLV-I and HCV viruses need to be screened.

Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

The toxic effect of paraquat (PQ), an herbicide that has been used widely in agriculture, on some parameters of the immune system was investigated. PQ was administered to Balb/c mice as intraperitoneal doses of 0.01, 0.1, or 1.0 mg PQ/kg body weight (BW) for a total of 28 days. Besides the histopathological examination of each host?s vital organs, measures of their splenic and bone marrow cellularity, blood macrophage/granulocyte phagocytic activity, total serum immunoglobulin M (IgM) and IgG, complement C3, and splenic CD49b (natural killer) cell levels, as well as of serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase and complement-mediated lytic activity (CH₅₀), activities, were then performed following the respective final treatments. The results indicate that high and medium doses of PQ (i.e., 1 and 0.1 mg/kg) could lead to suppressed phagocytic activity by circulating macrophages/granulocytes. The data also revealed that the high PQ dose induced a significant decrease (p<0.05) in spleen cellularity and splenic CD49b cell levels, along with numerous histopathological changes in the spleen. However, at none of the doses tested did PQ produce changes in serum levels of C3, total IgG or IgM, or in the CH₅₀. At 0.01 mg PQ/kg/day, no histopathological or functional disturbances were detected. These results indicate that PQ at doses more than 0.1?mg/kg has toxic effects on the cellular components of the innate immune system of Balb/c mice. The present results, however, indicate that at an exposure level below the recommended acceptable daily intake limit of 0.005 mg/kg, no observable immunotoxicity effect might be expected.

The immunotoxic effect of paraquat (PQ), a herbicide that has been used widely in agriculture was investigated using Balb/c mice. Paraquat was administered at doses of 1, 0.1, and 0.01 mg/kg for 21 days. Body weight, organ weight, cellularity of spleen, delayed type of hypersensitivity (DTH) response, plaque-forming cell (PFC) assay, hemagglutination titer (HA), quantitative hemolysis of SRBC (QHS) assay, spleen cell subtypes, cytokine production and lymphocyte proliferation assay were studied in various groups of animals. Results showed that high dose of PQ (1mg/kg) could suppress both cellular and humoral activity of the immune system. PQ at medium dose (0.1 mg/kg) did not show any changes in organ weight, body weight and spleen cellularity but significantly decreased the proliferation response to PHA and the production of IFNgamma. PQ at low dose (0.01 mg/kg) did not produce any significant changes in humoral or cellular responses of the immune system. In conclusion, paraquat at high dose has an inhibitory effect on the cell-mediated and humoral immunity. It seems that PQ has no adverse effects on mice immune system at low doses of 0.01 mg/kg, which is two times the PQ allowed daily intake (ADI) limit., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Systemic Lupus Eyrythematosus (SLE) is an autoimmune disease characterized by antibodies to nuclear antigens, particularly anti-dsDNA. Imbalance between production and destruction of immune cells causes cytopenia. Sex hormones have immunomodulatory effects; estrogen increases the production of autoantibodies in SLE prone NZB/NZW mice., Objective: To investigate the relationship between sex hormones, anti-dsDNA, and lymphocyte subsets in Iranian patients with SLE., Methods: 38 SLE patients (28 females and 10 males) meeting 4 of 11 ACR revised criteria for SLE classification, and 20 age and sex matched healthy individuals (10 females and 10 males) participated in this study. Lymphocyte subsets were analyzed using flow cytometric analysis. Serum anti-dsDNA levels and sex hormones concentrations were determined using commercial ELISA and RIA kits, respectively., Results: The absolute count of white blood cells, lymphocytes, T lymphocytes (CD3+), T helper cells (CD3+CD4+), B cells (CD19+) and Nk cells (CD3- CD16+CD56+) in SLE patients diminished significantly in comparison to control group (p<0.05). IgG anti-dsDNA antibody levels were significantly higher in patients compared to controls as expected (p<0.05). Prolactin increased significantly, while DHEAS showed a significant decrease in SLE patients compared with the controls (p<0.05), however the level of estrogen did not have any significant difference in SLE patients in comparison to controls., Conclusion: Increased concentration of prolactin together with a simultaneous decrease in serum DHEAS in SLE patients are associated with anti-dsDNA elevation and a decrease in almost all lymphocyte subsets.