Navid Dashti; Forough Golsaz-Shirazi; Mahmood Jeddi-Tehrani; Amir-Hassan Zarnani; Mohammad Mehdi Amiri; Fazel Shokri
Abstract
Background: Since the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccine candidates have been developed within a short period of time. Although the potency of these vaccines was evaluated individually, their comparative potency was not comprehensively ...
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Background: Since the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several vaccine candidates have been developed within a short period of time. Although the potency of these vaccines was evaluated individually, their comparative potency was not comprehensively evaluated.Objective: To compare the immunogenicity and neutralization efficacy of four approved COVID-19 vaccines in Iran, including: PastoCovac Plus, Sinopharm, SpikoGen, and Noora in BALB/c mice.Methods: Different groups of female BALB/c mice were vaccinated with three doses of each vaccine. The serum levels of antibodies against the viral receptor binding domain (anti-RBD) and spike (anti-spike) protein as well as the vaccine formulation (anti-vaccine) were evaluated using enzyme-linked immunosorbent assay (ELISA). The neutralization efficacy of these four vaccines was assessed through four neutralization assays: conventional virus neutralization test (cVNT), pseudotype virus neutralization test (pVNT), surrogate virus neutralization test (sVNT), and inhibition flow cytometry.Results: All four vaccines induced seroconversion in vaccinated animals. All vaccines successfully induced high levels of anti-vaccine antibody; however, PastoCovac Plus and Sinopharm vaccines induced significantly higher levels of anti-RBD antibody titer compared to Noora and SpikoGen. Moreover, the results of the antibody response were corroborated by the virus neutralization tests, which revealed very weak neutralization potency by Noora and SpikoGen in all tests.Conclusion: Our results indicate significant immunogenicity and neutralization efficacy induced by PastoCovac Plus and Sinopharm, but not by Noora and SpikoGen. This suggests the need for additional comparative assessment of the potency and efficacy of these four vaccines in vaccinated subjects.
Amir Hossein Mansourabadi; Mona Sadeghalvad; Hamid-Reza Mohammadimotlagh; Aliakbar Amirzargar
Abstract
The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential ...
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The COVID-19 pandemic is probably the most devastating worldwide challenge in recent century. COVID-19 leads to a mild to severe respiratory disease and affects different organs and has become a global concern since December 2019. Meanwhile, molecular biology and diagnostic laboratories played an essential role in diagnosis of the disease by introducing serological and molecular tests. Molecular-based techniques are reliable detection tools for SARS-CoV-2 and used for diagnosis of patients especially in the early stage of the disease. While, serological assays are considered as additional tools to verify the asymptomatic infections, tracing previous contacts of individuals, vaccine efficacy, and study the seroprevalance. The average time of the appearance of anti-SARS-CoV-2 antibodies in the patient's serum is 3-6 days after the onset of symptoms for both IgM and IgA and 10-18 days for IgG. Following the outbreak of COVID-19, FDA has approved and authorized a series of serological laboratory tests for early diagnosis. Serological assays have low-cost and provide fast results but have poor sensitivity in the early stage of the viral infection. Although the serological tests may not play an important role in the active case of COVID-19, it could be effective to determine the immunity of health care workers, and confirm late COVID-19 cases during the outbreak. In this review, we compared various laboratory diagnostic assays for COVID-19.
Niwei Yan; Pingyin Lee; Huiying Jie; Canquan Zhou; Yuan Yuan
Abstract
Background: Immunotherapies targeting peripheral natural killer (pbNK) cells in unexplained recurrent miscarriage (uRM) remain controversial. We hypothesized that the change in pbNK cell count might be a result of innate immune responses rather than a cause.Objective: To explore whether the pbNK count ...
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Background: Immunotherapies targeting peripheral natural killer (pbNK) cells in unexplained recurrent miscarriage (uRM) remain controversial. We hypothesized that the change in pbNK cell count might be a result of innate immune responses rather than a cause.Objective: To explore whether the pbNK count is significantly different in women testing positive than those testing negative for commonly studied autoimmune markers.Methods: Peripheral blood samples were collected from 302 eligible patients with uRM for the antinuclear antibody (ANA) testing determined by the enzyme-linked immunosorbent assay (ELISA), anti-thyroid peroxidase antibody (TPO-Ab) testing and anti-thyroglobulin antibody (Tg-Ab) testing determined by the chemiluminescent immunoassay, and pbNK cell testing determined by flow cytometry. The patients were divided into two groups according to the pbNK normal range, and the comparative analysis entailed an examination of the prevalence rates of autoantibodies within the high pbNK group and the normal pbNK group, followed by a comprehensive investigation into the potential correlations between autoantibodies and pbNK cells.Results: There was a positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356–19.159), while there was a negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111-0.773). TPO-Ab-positive patients had a higher pbNK cell count compared with TPO-Ab-negative patients, while ANA-positive patients had a lower pbNK cell count compared with ANA-negative patients.Conclusion: The change in pbNK cell count may be a consequence of immune responses, and there should be careful consideration in applying it as an immunotherapeutic index.
Jian-Hua Lu; Xiao-Xiao Rui; Ting-Ting Wang; Xiao-Qin Wang; Yu-Ping Peng; Yi-Hua Qiu
Abstract
Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related ...
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Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related mechanisms on rheumatoid arthritis is unknown.Objective: To explore the effects of β2-AR in collagen-induced arthritis (CIA) on the imbalance of T helper (Th) 17/ regulatory T (Treg) cells.Methods: In DBA1/J mice, collagen type II was injected intradermally at the tail base to prepare the CIA model. The specific β2-AR agonist, terbutaline (TBL), was administered intraperitoneally beginning on day 31 and continuing until day 47 after primary vaccination, twice a day. Magnetic beads were used to sort CD3+ T cells subsets from spleen tissues.Results: In vivo, β2-AR agonist TBL alleviated arthritis symptoms in the CIA mice including histopathology of the ankle joints, four limbs’ arthritis score, the thickness of ankle joints, and rear paws. After TBL treatment, in the ankle joints, the levels of proinflammatory factors (IL-17/22) notably decreased and the levels of immunosuppressive factors (IL-10/TGF-β) significantly increased. In vitro, ROR-γt protein expression, Th17 cell number, mRNA expression and the releasing of IL-17/22 from CD3+ T cells reduced following TBL administration. Moreover, TBL enhanced the anti-inflammatory responses of Treg cells.Conclusion: These results suggest that β2-AR activation exerts anti-inflammatory effects through the amelioration of Th17/Treg imbalance in the CIA disease.
Haibai Sun; Jiaqing Liu; Ranran Feng; Chunyan Wang; Yuming Li; Xiao Wang
Abstract
Background: Follicular helper T lymphocyte (Tfh) promotes antibody production by B lymphocytes in various diseases, including Pulmonary Tuberculosis (PTB). Objective: To explore the potential role of Tfh cells and assess the expression level of PD-1, and IL-21 in PTB. Methods: 54 newly diagnosed ...
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Background: Follicular helper T lymphocyte (Tfh) promotes antibody production by B lymphocytes in various diseases, including Pulmonary Tuberculosis (PTB). Objective: To explore the potential role of Tfh cells and assess the expression level of PD-1, and IL-21 in PTB. Methods: 54 newly diagnosed smear-positive PTB, 27 people with latent tuberculosis (LTB) and 27 healthy controls (HC) were enrolled. The PTB group was further divided based on the range of lung field involved (focus number>=3, PTB-X3; <3, PTB-X2). After 6-month therapy, sputum smear (positive, PTB-SP; negative, PTB-SN) or imaging examinations (lesion reduction significant, PTB-os; insignificant, PTB-s) were used to evaluate the conditions of PTB patients. Blood samples were collected from PTB group at month six. CD4+CXCR5+Tfh, and its subsets, CD4+CXCR5+PD-1+Tfh and CD4+CXCR5+ICOS+Tfh in peripheral blood mononuclear cells (PBMCs) were detected. Serum IL-21 concentrations were measured. Results: The frequencies of CD4+CXCR5+Tfh, CD4+CXCR5+ICOS+Tfh and CD4+CXCR5+PD-1+Tfh were higher in PTB group than in HC. IL-21, IL-4 and IFNγ concentrations were significantly higher in PTB group than in HC. The proportion of CD4+CXCR5+Tfh in PTB-X2 was lower than in PTB-X3 group. CD4+CXCR5+PD-1+Tfh proportion in PTB-X2 was lower than that in the PTB-X3. After treatment, CD4+CXCR5+Tfh proportion was significantly lower in the PTB-SN group. CD4+CXCR5+Tfh was lower in the PTB-os group than in the PTB-s group. However, the CD4+CXCR5+PD-1+Tfh and cytokine concentrations of IL-21 were not different. Conclusions: CD4+CXCR5+Tfh level might predict the sputum results, and lesion decrease rate while CD4+CXCR5+PD-1+Tfh subset and IL-21 were not associated with sputum results or lesion decrease after treatment.
Maryam Rastin; Mahmoud Mahmoudi; Nafiseh Tabasi; Nadia Kia; Jafar Hajavi; Seyed-Alireza Esmaeili
Abstract
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 ...
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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.
Jing Sun; Jiabao Zhao; Chao Sun; Yu ting Zhu; Ping Zhou; Shu xian Gao; Ying-Ao Fan; Hao-Yuan Jiang; Qing-Wei Zheng; Jun-Chang Guan
Abstract
Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression ...
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Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. Methods: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. Results: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. Conclusion: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.
Mahdi Alimoradi Fard; Mehri Ghafourian; Abdolah Mousavi-Salehi; Farideh Moramazi; Nastaran Ranjbari
Abstract
Background: Endometriosis is a medical condition that can cause infertility in women. Women with endometriosis experience a decrease in NK cell cytotoxic activity against endometrial cells, ultimately contributing to the spread of these cells.Objective: To assess the frequency of NK cells and the expression ...
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Background: Endometriosis is a medical condition that can cause infertility in women. Women with endometriosis experience a decrease in NK cell cytotoxic activity against endometrial cells, ultimately contributing to the spread of these cells.Objective: To assess the frequency of NK cells and the expression of the NKP46 receptor in endometrial tissue from patients with endometriosis using immunohistochemistry.Methods: 30 endometrial tissue specimens were collected from three groups of cases with mild (n=11), moderate (n=10), and severe endometriosis (n=9), respectively. Additionally, 20 normal endometrial tissue specimens were collected as the control group. Immunohistochemical staining was carried out using specific human monoclonal antibodies against CD56 and NKP46 molecules.Results: Cases with severe endometriosis had a significantly higher number of CD56+ uterine NK cells (26.19±2.50) compared to fertile women (15.02±0.622) and women with mild to moderate endometriosis (p<0.001). However, there was no significant difference between the mild to moderate patients compared with the healthy women (p>0.05). Endometrial NKp46 expression was lower in women with severe endometriosis (0.447±0.0829) compared to fertile women (0.987±0.115, p=0.03). The NKp46+/CD56+ cell ratio was also lower in women with severe endometriosis (0.019±0.003) compared to fertile women (0.072±0.011, p=0.01).Conclusion: Women with severe endometriosis demonstrated an increased rate of infiltrated uterine NK cells and a significant decrease in NKP46 expression compared to fertile women. Therefore, NK cells and the NKp46 receptor may be involved in the development of endometriosis.
Mobina Fathi; Kimia Vakili; Fatemeh Sayehmiri; Ashraf Mohamadkhani; Reza Ghanbari; Mohammadreza Hajiesmaeili; Mostafa Rezaei-Tavirani
Abstract
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new global health threat. Objectives: To analyze the effectiveness of the measurement of specific antibodies to SARS-CoV2 (IgM and IgG) for the diagnosis of COVID-19 and to ...
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Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new global health threat. Objectives: To analyze the effectiveness of the measurement of specific antibodies to SARS-CoV2 (IgM and IgG) for the diagnosis of COVID-19 and to analyze the rate of SARS-CoV2 seroprevalence in the population. Methods: 11 relevant studies, published before June 5, 2020, were included in this meta-analysis. These studies were identified by searching the MEDLINE and Scopus databases. The final selected studies were analyzed using STATA version 14. Publication bias was examined using both Egger's test and Funnel plots. Moreover, the I² statistic has been used to evaluate and verify heterogeneity. Results: The 11 relevant studies selected for the present meta-analysis cover a total of 996 infection cases. According to the results, the average rate of positive cases for IgM (AU/mL) was 2.10 (95% CI: 1.65-2.55; I2=92.2%), and the sensitivity in individuals with positive IgM test was 63% (95% CI: 47-79; I2=94.9%). In addition, the average rate of positive cases for IgG (AU/mL) was 67.44 (95% CI: 28.79-106.09; I2=99.4%), and the sensitivity in individuals with positive IgG test was 79% (95% CI: 67-90; I2=89.5%). Conclusions: According to this analysis, detection of anti-SARS-CoV-2 IgM and IgG antibodies may assist early detection of SARS-CoV2 infection. Whether antibodies against SARS-CoV-2 confer protective immunity warrants further studies.
Hao Zheng; Qiaozhen Kang; Chenglong Zhang; Lu Yang; Xin Liu
Abstract
Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR ...
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Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR agonist.Objective: To explore the effect of the rMBP-NAP on the OXA-induced AD in a mouse model and clarify the possible action mechanism.Methods: The AD animal model was induced by repeated administration of oxazolone (OXA) in BALB/c mice. H&E staining was used to analyze the ear epidermis thickness and the number of infiltrating inflammatory cells. TB staining was used to detect mast cell infiltration in the ear tissue. ELISA was used to analyze the secretion of cytokines IL-4 and IFN-γ in peripheral blood. qRT-PCR was used to determine the expression levels of IL-4, IFN-γ, and IL-13 in ear tissue.Results: OXA induced the establishment of an AD model. After the rMBP-NAP treatment, the thickness of the ear tissue and the number of mast cells infiltrated in AD mice reduced, and the serum and ear tissue levels of IL-4 and IFN-γ increased, but the ratio of IFN-γ (rMBP-NAP group)/IL-4 (rMBP-NAP group) was greater than the ratio of IFN-γ (sensitized group)/IL-4 (sensitized group).Conclusion: The rMBP-NAP improved the disease symptoms including skin lesions in AD, alleviated the inflammation in ear tissue, and restored the Th1/2 balance by inducing a shift from the Th2 to the Th1 response. The results of our work support the use of rMBP-NAP as an immunomodulator for AD treatment in future investigations.
Lidan Luo; Yuan Fang; Qi Yuan; Jinmao Liao; Zheng Zhang
Abstract
Background: Pyroptosis is a programmed cell death related to caspase-1, accompanied by the secretion of pro-inflammatory cytokines. Objectives: To explore the effects of LPS on the P2X7R/NLRP3 pathway in macrophages, and hepatocytes pyroptosis in mice. Methods: LPS was used to establish an animal ...
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Background: Pyroptosis is a programmed cell death related to caspase-1, accompanied by the secretion of pro-inflammatory cytokines. Objectives: To explore the effects of LPS on the P2X7R/NLRP3 pathway in macrophages, and hepatocytes pyroptosis in mice. Methods: LPS was used to establish an animal model of the acute liver injury. The macrophage RAW264.7 was induced by LPS to establish a cell model. The P2X7R inhibitor A438079 and agonist BZATP were added. RAW264.7 was co-cultured with AML-12 cells. Pyroptosis and the ratio of CD11b+CD86+/CD11b+CD206+ were analyzed by flow cytometry. ELISA, WB, and qRT-PCR were applied to analyze factors involved in the P2X7R/NLRP3 pathway. Results: LPS induced liver damage in mice, promoted cell pyroptosis and increased the levels of IL-18, IL-1β, ALT, AST, and TBIL. P2X7R, GSDMD, and GSDMD-N expressions also increased in the LPS group. LPS induced macrophage activation in vivo. NLRP3, ASC, P2X7R, and caspase-1 expressions in vitro promoted. ELISA confirmed that the IL-1β and IL-18 levels repressed in the BZATP (P2X7R agonist) group, while the trend was opposite in the A438079 (P2X7R inhibitor) group. LPS activated the P2X7R/NLRP3 pathway in macrophages. After RAW264.7 was co-cultured with AML-12 cells, the pyroptosis of AML-12 cells promoted but the proliferation decreased in the BZATP group. GSDMD and GSDMD-N expressions promoted in the BZATP group, while the trend was opposite in the A438079 group. Conclusion: LPS activated macrophages via P2X7R activation of NLRP3 and induced hepatocyte pyroptosis, which provided novel potential targets for the liver injury treatment.
Ting Yi; Zhiyin Liu; Haokun Jia; Qiongzhi Liu; Jianjiao Peng
Abstract
Background: The imbalance between M1 and M2 macrophage activation is closely associated with the pathogenesis of inflammatory bowel diseases (IBDs). Sulforaphane (SFN) plays an important role in the treatment of inflammatory diseases.Objective: To investigate the effect of SFN on macrophage polarization ...
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Background: The imbalance between M1 and M2 macrophage activation is closely associated with the pathogenesis of inflammatory bowel diseases (IBDs). Sulforaphane (SFN) plays an important role in the treatment of inflammatory diseases.Objective: To investigate the effect of SFN on macrophage polarization and its underlying regulatory mechanism.Methods: Mouse bone marrow-derived macrophages (BMDMs) were treated with SFN and an Nrf2 inhibitor, Brusatol. M1 macrophages were induced by LPS and IFN-γ stimulation, whereas M2 macrophages were induced by stimulation with IL-4 and IL-13. LPS-stimulated BMDMs were co-cultured with Caco-2 cells. Flow cytometry, qRT-PCR, and Western blot were performed to assess macrophage polarization. Cell function was assessed using CCK8 assay, transepithelial electrical resistance (TEER) assay, and biochemical analysis.Results: Higher concentrations of SFN resulted in better intervention effects, with an optimal concentration of 10 μM. SFN decreased the levels of IL-12, IL-6, and TNF-α, as well as the percentages of CD16/32 in M1 BMDMs. At the same time, SFN increased the levels of YM1, Fizz1, and Arg1 as well as the percentages of CD206+ cells in M2 BMDMs. In addition, SFN enhanced the accumulation of Nrf2, NQO1, and HO-1 in M1 BMDMs, and the downregulation of Nrf2 reversed the regulatory effect of SFN on M1/M2 macrophages. LPS-stimulated BMDMs induced Caco-2 cell damage, which was partially alleviated by SFN.Conclusion: Our findings indicate that SFN may act as an Nrf2 agonist to regulate macrophage polarization from M1 to M2. Furthermore, SFN may represent a potential protective ingredient against IBD.
Yan Jiang; Linqiao Li; Qilu Pan; Xiaojing Du; Qian Han; Feixiang Ling; Rou Li; Lin Mai; Jianwei Huang; Shuyuan Chu; Libing Ma
Abstract
Background: Little is known about MBD2’s epigenetic regulation in the immune pathogenesis of CD4+T cell differentiation.Objective: This study attempted to explore the mechanism of methyl-cpg-binding domain protein 2 (MBD2) in CD4+T cell differentiation stimulated by environmental allergen ovalbumin ...
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Background: Little is known about MBD2’s epigenetic regulation in the immune pathogenesis of CD4+T cell differentiation.Objective: This study attempted to explore the mechanism of methyl-cpg-binding domain protein 2 (MBD2) in CD4+T cell differentiation stimulated by environmental allergen ovalbumin (OVA).Methods: Mononuclear cells were separated from the spleen tissues of male C57BL/6 mice. The OVA interfered with the differentiation of splenic mononuclear cells and CD4+T cells. The CD4+T cells were obtained by magnetic beads and identified by CD4 labeled antibody. CD4+T cells were transfected with lentivirus to silence MBD2 gene. A methylation quantification kit was used to detect 5-mC levels.Results: The purity of CD4+T cells reached 95.99% after magnetic beads sorting. Treatment with 200 μg/mL OVA stimulated the CD4+T cells differentiation to Th17 cells and promoted the secretion of IL-17. After being induced, the Th17 cell ratio increased. 5-Aza inhibited the Th17 cell differentiation and the IL-17 level in a dose-dependent manner. Under the intervention of the Th17 induction and 5-Aza, MBD2 silencing inhibited the differentiation of Th17 cell, and decreased the IL-17 and 5-mC levels in the cell supernatants. MBD2 silencing reduced the scale of the Th17 cell and IL-17 levels in the OVA-treated CD4+T cells.Conclusion: MBD2 affected IL-17 and 5-mC levels by mediating the Th17 cell differentiation in splenic CD4+T cells that were interfered with 5-Aza. OVA induced Th17 differentiation and increased IL-17 levels, inhibited by MBD2 silencing.
Danesh Hassani; Mohammad Mehdi Amiri; Faezeh Maghsood; Vahid Salimi; Gholam Ali Kardar; Omid Barati; Seyed Mohammad Reza Hashemian; Mahmood Jeddi-Tehrani; Amir-Hassan Zarnani; Fazel Shokri
Abstract
Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. Objective: To assess the cross-protection induced ...
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Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. Objective: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. Methods: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. Results: Our results revealed significant differences in anti-NP (p <0.0001) and anti-RBD (p <0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (p <0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (p <0.01). Conclusion: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.
Dijiao Tang; Qi Tang; Long Zhang; Hongxu Wang
Abstract
Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: ...
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Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: To evaluate the value of NLR in the diagnosis and pre-assessment of the disease severity of LN. Methods: This retrospective study included 88 patients with LN, 51 SLE patients without kidney involvement, 79 patients with primary chronic nephritis (CN), and 52 healthy controls (HC). The differences among these four groups and diagnostic value of NLR for patients with LN were evaluated. Results: The NLR of patients with LN before treatment was significantly higher than that of the other three groups. NLR positively correlated with C-reactive protein (CRP), complement 3(C3), C4, and serum creatinine (SCr) (CRP: r=0.337, p=0.007; C3: r=0.222, p=0.042; C4: r=0.230, p=0.035; SCr: r=0.408, p <0.0001) but negatively correlated with total serum IgG (r=-0.226, p=0.041). The level of NLR increased with the severity of renal dysfunction NLR (area under the curve: 0.785, 95% CI: 0.708-0.862) was useful for the diagnosis of LN, and its optimal cut-off value was 5.44 (sensitivity: 65.9%, specificity: 86.3%). Conclusions: NLR would be useful for the diagnosis of LN and reflects the severity of renal dysfunction Therefore, evaluating NLR before treatment could help clinicians to identify potential renal involvement in patients with SLE and distinguish LN from CN.
Heting Dong; Yinying Ren; Yiyi Song; Wei Ji; Yongdong Yan; Canhong Zhu; Li Huang; Meijuan Wang; Wenjing Gu; Xinxing Zhang; Huiming Sun; Chuangli Hao; Zhengrong Chen
Abstract
Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation.Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma.Methods: Female BALB/c ...
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Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation.Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma.Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically.Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice.Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.
Saeid Taghiloo; Mohsen Soltanshahi; Masoud Aliyali; Siavash Abedi; Hossein Mehravaran; Abolghasem Ajami; Hossein Asgarian-Omran
Abstract
Background: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. Objective: To investigate and compare the serum levels of ...
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Background: SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is recognized for the first time in Wuhan, China. The cytokine storm is a known factor causing major clinical symptoms leading to death in COVID-19 patients. Objective: To investigate and compare the serum levels of different cytokines in COVID-19 patients with different clinical severity. Methods: Concentrations of serum cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, and GM-CSF, were measured in 61 COVID-19 patients and 31 normal controls with ELISA. We investigated the correlation between the levels of these cytokines and clinical severity, CRP level, neutrophil and lymphocyte count in patients with COVID-19. Results: Our data indicated that the levels of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF, but not IL-10 were significantly increased in COVID-19 patients compared to normal controls. Statistical analysis showed that the level of IL-1β, IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF were higher in severe COVID-19 than those of mild cases. The concentrations of all mentioned cytokines were negatively associated with the absolute count of lymphocytes, and positively correlated with the CRP level and the absolute count of neutrophils. Conclusion: The current study suggests that high levels of various cytokines correlate with the disease severity and immunopathogenesis of COVID-19.
Liquan Yu; Jian Dai; Ziyao Fan; Liang Chen; Daolong Liu; Zhijun Wu; Hunan Sun; Chunyu Tong; Yongzhong Yu; Baifen Song; Jinzhu Ma; Yudong Cui
Abstract
Background: Staphylococcus aureus is an opportunistic pathogen responsible for various infections with diverse clinical presentation and severity. The α-hemolysin is a major virulence factor in the pathogenesis of S. aureus infections.Objective: To produce a chimeric fusion protein for hemolytic ...
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Background: Staphylococcus aureus is an opportunistic pathogen responsible for various infections with diverse clinical presentation and severity. The α-hemolysin is a major virulence factor in the pathogenesis of S. aureus infections.Objective: To produce a chimeric fusion protein for hemolytic detection of the S. aureus isolates and as a component of a multi-antigen vaccine.Methods: The fused strategy employed a flexible linker to incorporate the possible B cell and T cell determinants into one chimera (HlaD). The humoral and cellular response to the HlaD in mice was assessed to reveal a non-significant difference compared with the full-length α-hemolysin mutant (Hla H35L).Results: The results of the protective effect, the mimetic lung cell injury, and bacterial clearness demonstrated that the mice vaccinated with the HlaD alleviated the severity of the infection of the S. aureus, and the HlaD could similarly function with Hla H35L.Conclusion: The chimeric fusion (HlaD) provided a diagnostic antigen for hemolysis of the S. aureus strains and a potential vaccine component.
Saeid Taghiloo; Abolghasem Ajami; Reza Alizadeh-Navaei; Ehsan Zaboli; Hossein Asgarian-Omran
Abstract
Background: Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. Objectives: To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, ...
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Background: Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. Objectives: To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, and TLR7/8 agonist R848 on the expression and regulation of the immune inhibitory molecules in myeloid leukemia cells. Methods: WEHI-3 leukemia cells were incubated with dual PI3K and mTOR inhibitor BEZ235 and TLR7/8 agonist R848 for 48 hrs. Firstly, cell viability was assessed by MTT method. The semi-quantitative relative mRNA expression of Galectin-9 (Gal-9), PD-L1, PVR, and STAT3 was assessed according to HPRT as a housekeeping gene. Finally, the protein expression of phosphorylated STAT3 was evaluated by western blotting analysis. Results: WEHI-3 cells showed growth inhibition following treatment with BEZ235 and R848 whose combination exerted more proliferation arrest. The mRNA expression of Gal-9, PD-L1 and PVR immune checkpoint molecules significantly reduced in treated cells with BEZ235 and R848. Combined treatment indicated more reduction compared with the single treatment. Finally, the expression and phosphorylation of STAT3 were down-regulated after a single or dual treatment with BEZ235 and R848. Conclusion: Our results conclude that treatment with the combination of BEZ235 and R848 interferes with immune evasion mechanisms through STAT3-signaling pathway in WEHI-3 leukemia cells.
Zahra Bagheri-Hosseinabadi; Hamid Ostad Ebrahim; Fatemeh Bahrehmand; Gholamhosein Taghipour; Mitra Abbasifard
Abstract
Background: The role of cytokine storm in the immunopathogenesis of coronavirus disease 2019 (COVID-19) has been implicated. Objective: To determine the association of microRNA (miRNA)-10b and serum levels of IL-2 and IL-8 in patients with COVID-19. Methods: Blood samples were obtained from 33 COVID-19 ...
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Background: The role of cytokine storm in the immunopathogenesis of coronavirus disease 2019 (COVID-19) has been implicated. Objective: To determine the association of microRNA (miRNA)-10b and serum levels of IL-2 and IL-8 in patients with COVID-19. Methods: Blood samples were obtained from 33 COVID-19 patients and 29 healthy subjects. After RNA extraction and cDNA synthesis, the transcript level of miR-10b was determined by Real-time PCR. In addition, the serum levels of IL-2 and IL-8 were measured in subjects using ELISA. Results: The patient group comprised of 33 patients with COVID-19 (62.4 ± 3.7 years old), 13 (39%) males and 20 (61%) females. In the control group, 29 subjects (56.6 ± 1.6 years old), 9 (31%) males and 20 (69%) females, were included. The expression of miR-10b was significantly downregulated in the peripheral blood of COVID-19 patients in comparison to the healthy controls (fold change= 0.12, p < 0.0001). The levels of IL-2 (p < 0.001) and IL-8 (p < 0.001) were significantly increased in the serum samples of COVID-19 patients compared to the healthy subjects. The expression level of miR-10b was correlated significantly with the serum levels of IL-2 and IL-8 as well as with the age of patients, ESR and CRP levels. Conclusions: miR-10b is downregulated in the COVID-19 patients and might result in increased levels of IL-2 and IL-8, hence contributing to cytokine storm.
Mohammad Reza Haghshenas; Aida Khademolhosseini; Amirreza Dehghanian; Fereshteh Ghanipour; Hamid Ghaderi; Soolmaz Khansalar; Abdolreza Sotoodeh Jahromi
Abstract
Background: Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. ...
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Background: Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. However, its biological roles in brain tumors are not well defined.Objective: To assess the serum levels of IL-38 and the percentages of TILs in the tumor tissues of patients with primary brain tumors and to determine their associations with the pathological features of the disease.Methods: IL-38 was evaluated in sera using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E)-stained sections were scored to determine the percentages of TILs in four different areas: the invasive margin, central tumor, perivascular and perinecrotic areas.Results: IL-38 serum levels were significantly higher in low- and high-grade tumors than in healthy individuals, meanwhile, its levels remained consistent between these two grades. Although no significant difference was found in IL-38 serum levels between different histological subtypes of brain tumors, its levels were significantly higher in intra-axial brain tumors than in extra-axial ones. Additionally, a significant positive correlation was observed between serum levels of IL-38 and tumor size in patients with low-grade tumors. TILs were detected in at least one of the four examined areas; however, no statistically significant correlation was found between IL-38 levels and TILs.Conclusion: Our data may suggest a connection between IL-38 and immune suppression and tumor progression in primary brain tumors. Further investigation is needed to uncover the role of IL-38 in the brain tumor microenvironment.
Tao Wei; Wei-Hong Lv; Mei-Hua Gao; Shan-Juan Tan; Ling Li; Lei Zhang
Abstract
Background: The extent to which maternal antibodies against the hepatitis B surface antigen (HBsAb) acquired transplacentally affect the immune responses to the hepatitis B vaccine (HBVac) in infants is still uncertain.Objective: To explore the impact of the HBsAb on the immune response to the HBVac ...
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Background: The extent to which maternal antibodies against the hepatitis B surface antigen (HBsAb) acquired transplacentally affect the immune responses to the hepatitis B vaccine (HBVac) in infants is still uncertain.Objective: To explore the impact of the HBsAb on the immune response to the HBVac in a mouse model.Methods: According to the doses of the HBVac (2, 5 μg) injected, 267 BALB/c mice were divided into two groups. Each group was subdivided into 3 subgroups based on the doses of the hepatitis B immunoglobulin (HBIG) (0, 25, 50 IU) administered. The HBsAb titers were detected 4 weeks after completing the HepB vaccination. Results: Among all the mice, 40 had an HBsAb titer <100 mIU/mL (non- or low-response to the HBVac). The rates of the HBsAb titer <100 mIU/mL in 0, 25 and 50 IU HBIG groups were 1.1%, 23.1%, and 20.7%, respectively. Multivariate logistic regression analysis showed that the risk factors for low- or non-response to the HBVac were injection with the HBIG, low HBVac dose, and hypodermic injection. The mean HBsAb titers (log10) reduced gradually in the 0, 25 and 50 IU HBIG groups (P<0.001).Conclusion: The HBIG administration has negative impacts on the peak level of the HBsAb and the rate of an effective immune response. This implies that the maternal HBsAb acquired transplacentally might inhibit the immune responses to the HBVac in infants.
Zeinab Amirkhani; Mehrosadat Alavi; Mehdi Kalani; Ali Alavianmehr; Shirin Farjadian
Abstract
Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid ...
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Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer (DTC). Methods: A total of 85 patients with DTC were allocated into two groups based on RAI dosage after thyroidectomy. Patients in each group were randomly distributed into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Fifteen healthy individuals were included as controls. Serum cytokine levels including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, TNF-α and IFN-γ were determined by cytometric bead assay. Results: IL-4, IL-6, IL-21 and IL-22 levels in patients with DTC were higher than in the healthy controls. Regardless of RAI dosage, IL-6 showed an increasing trend after RAI ablation. IL-4, IL-22, and IL-17A remained at considerably higher levels than in the healthy controls after RAI ablation. Within-group comparisons showed a significant reduction in Th1+Th17/Th2+Th22 ratio in G2 patients 1 week after RAI ablation. Between-group comparisons showed increased IL-10 levels in G3 compared with G1 patients one week after high-dose RAI ablation. In G3, Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were remarkably lesser than in G2 patients 1 month after intermediate-dose RAI ablation. Conclusion: Our results showed better anti-inflammatory effects of omega-3 when it was used therapeutically after RAI ablation in patients with DTC than when it was used prophylactically before RAI.
Elahe Jandaghi; Maral Hemati; Maryam Mohammadlou; Jafar Jandaghi; Majid Mirmohammadkhani; Navid Danaei; Parviz Kokhaei
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) causing a human pandemic disease named COVID-19 has become a major global health concern. Iran as one of the most affected countries needs unprecedented effort for monitoring and evaluation of COVID-19. Objective: To determine ...
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Background: Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) causing a human pandemic disease named COVID-19 has become a major global health concern. Iran as one of the most affected countries needs unprecedented effort for monitoring and evaluation of COVID-19. Objective: To determine the seroprevalance of COVID-19 in Semnan province North-East of Iran. Methods: Six hundred people were randomly selected using the "SIB data-base". From 1 to 30 June, 2020, 153 participants of Semnan population were enrolled. Blood, nasopharyngeal and oropharyngeal samples were obtained. Prevalence of IgM and IgG antibodies were ascertained using ELISA and Real-Time PCR was conducted to evaluate viral load. Estimates of prevalence were standardized by age and sex, based on the 2015 national census of Semnan province. Results: Seroprevalence showed no difference between females and males and no significant association between age and seropositivity. Among total participants, the age and sex adjusted prevalence of SARS-CoV2 infection was 19.3% (95% CI, 14.0-26.7 per 100 persons). Approximately 10% of participants had detectable antibodies but showed a negative-PCR result. However, approximately 80% of participants did not show an evidence of infection. Conclusion: The majority of the population in Semnan province has no detectable antibodies to SARS-CoV-2. Therefore, Semnan is considered a SARS-CoV-2 susceptible area. These results emphasize the need for maintaining public health measures to tackle the new epidemic wave.
Wenjing Liu; Yiyao Zhang; Xia Chen
Abstract
Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils.Objective: To investigate ...
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Background: Pulmonary neutrophils may play a crucial role in the development of bronchiolitis obliterans (BO) following measles virus infection. IL-27 could potentially have a negative regulatory effect on the release of reactive oxygen species and cytotoxic granules in neutrophils.Objective: To investigate the levels of IL-27 in the bronchoalveolar lavage fluid (BALF) of children with post-infectious bronchiolitis obliterans (PIBO) and analyze the relationship between IL-27 levels and neutrophil proportions.Methods: A total of 24 children with PIBO were recruited for the experimental group, while 23 children with bronchial foreign bodies were included in the control group. Bronchoscopic alveolar lavage was performed in both groups. The levels of IL-27 in BALF were measured using enzyme-linked immunosorbent assay (ELISA). The proportions of neutrophils in BALF were determined by smear staining. The relationship between the levels of IL-27 in BALF and the neutrophil proportions was analyzed by the Pearson test.Results: The levels of IL-27 in BALF were significantly lower in children with PIBO compared to children with bronchial foreign bodies (p<0.05). Additionally, the proportions of neutrophils in BALF were significantly higher in children with PIBO compared to children with bronchial foreign bodies (p<0.05). The levels of IL-27 were negatively correlated with the neutrophil proportions in BALF in children with PIBO (p<0.05), but not in children with bronchial foreign bodies (p>0.05).Conclusion: The present study suggests that a decrease in IL-27 may be associated with an increase in neutrophils in BALF and may contribute to the pathogenesis of PIBO.
