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CD20 is a classic marker expressed by B cells. However, recent studies have found that CD20 is also dimly expressed on a small subset of CD3 +T cells, and the CD20 +T cells play an important proinflammatory role in multiple sclerosis (MS). Anti-CD20 monoclonal antibodies selectively deplete CD20 +T cells and effectively suppress inflammatory disease activity. Although CD20 +T cells have received increasing attention, the understanding of these cells is currently still in its infancy. This article provides an overview of the current knowledge about advanced progress of CD20 +T cells as well as their roles in MS.
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@#Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P<0.01), indicating the successful establishment of ASO. Moreover, the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased (P<0.05), while the IL-10 level was significantly decreased (P<0.05). In addition to increased IL-6 and IL-17 levels, the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group. The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased (P<0.05). These alternations were also observed in ASO patients. After endovascular surgery (such as percutaneous transluminal angioplasty and arterial stenting), all these changes were significantly improved (P<0.05). Conclusions: The Th17/Treg and M1/M2 ratios were significantly increased in ASO, and surgery can effectively improve the balance of Th17/Treg, and reduce the ratio of M1/M2, and the expression of inflammatory factors.
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Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.
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AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P<0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P<0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P<0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P<0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P<0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P<0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P<0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.
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Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.
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Abstract The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.
الموضوعات
Humans , Female , Flow Cytometry/methods , Lupus Erythematosus, Systemic/pathology , Patients/classification , Biomarkers/analysis , Natural Killer T-Cellsالملخص
Abstract Background The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail. Methods PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/−cells and PD-L1+/−cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA. Results The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1− cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1− cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs. Conclusions Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1− and PD-1− cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.
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Objective: We documented the immunological profile of neonates and mothers, and lymphocyte subsets at birth. Methods: Consecutively born preterm neonates (26 to 31 weeks gestation) at our level III neonatal unit, fulfilling the inclusion criteria were enrolled. Immunoglobulin levels were assessed in maternal blood and in cord blood along with T cell subsets. Results: A total of 115 neonates were enrolled. The mean cord levels for IgG, IgM and IgA, respectively were 5.34, 0.10 and 0.04 g/L and of B, T, NK and NK-T cells were 14%, 71%, 10% and 1%, respectively of total lymphocyte population. Cord IgG and IgA levels showed a significantly rising trend with increasing gestation (P=0.005 and 0.02, respectively) but not IgM and T cell subsets. Maternal immunoglobulins were similar in all gestations. Conclusion: The cord IgG and IgA increased with increasing gestation but not IgM in neonates.
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B cells are very crucial part of our immune system. They protect us from various infections by secreting antigen-specific antibodies, which neutralize the infectious agents. It is important for a clinical hematologist to know about the B cell development, function and the diseases developing from the quantitative or qualitative defects in B cells. This simple and short review is focused on the basic understanding and clinical hematologist’s perspective of B cells.
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B lymphocyte is an important component of the human immune system and it has a role in the process of the body's specific immunity. In recent years, the research on B cells and tumor immune escape has rapidly progressed. Studies have shown that different types of B cells play different roles in tumor microenvironment through a variety of mechanisms. B cells in the tertiary lymphatic structure promote anti-tumor immunity, while regulatory B cells promote tumor immune escape. Antibody drugs targeting B cells are a promising direction for tumor immunotherapy.
الموضوعات
Humans , B-Lymphocytes/pathology , Immunotherapy , Neoplasms/therapy , Tumor Escape , Tumor Microenvironmentالملخص
Regulatory B cells (Bregs) are a group of cells with immunoregulatory function. They can regulate the progression of diseases by inhibiting excessive inflammatory responses and serve as critical protective cells in immune disorders and other conditions. This article reviewed the source, function and mechanism of Bregs and its role in autoimmune diseases, infection and tumor.
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Myasthenia gravis is mainly acetylcholine receptor antibody-mediated, T cells-dependent and complement participated acquired autoimmune disease characterized by impairment of the neuromuscular transmission. The main clinical feature of the disease is the presence of fatigability or muscle weakness. Most patients can be successfully managed with nonspecific immunotherapies such as corticosteroid and non-steroidal immunosuppressants. However, the side effects caused by long-term corticosteroid therapy are still a hurdle in the treatment of myasthenia gravis (MG). Oral non-steroidal immunosuppressants, as add-on therapy, can greatly reduce the relapse of the disease, but some drugs have a slow onset of action and the potential for significant toxicity, and even increase the risk of infection and neoplasms with long-term treatment. Despite these therapies, a minority of patients can be refractory because of incompletely responding or not well tolerated to available therapies. Thus, the need to avoid the use of corticosteroids, or at least reduce their use as much as possible should concern all patients with MG. Targeted immunotherapy is a therapeutic monoclonal antibody or antibody fragment targeting immune cells, complement, neonatal Fc receptor and cytokines. Recently, targeted immunotherapy has completed phase Ⅱ and Ⅲ clinical trials in patients with MG, and some of them have been approved by Food and Drug Administration. These promising biologics showed efficacy in symptoms persistent improvement, steroids reduction and were well tolerated, now evolving into powerful tools changing the algorithm of MG. This paper summarizes the results of clinical trials of new biologics in MG and looks forward to the prospect of MG treatment.
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RESUMEN Introducción: Las inmunodeficiencias primarias son enfermedades genéticas. Están constituidas por más de 200 enfermedades que tienen en común las infecciones recurrentes. La inmunodeficiencia combinada se caracteriza por episodios de sepsis recurrentes del aparato respiratorio, digestivo y de piel sobre todo por gérmenes oportunistas. El cuadro clínico es muy variable y se conocen múltiples fenotipos clínicos. Objetivo: Evaluar las manifestaciones clínicas e inmunológicas de la inmunodeficiencia primaria combinada no grave a través de un caso. Presentación de caso: Se trata un lactante de 8 meses de edad, masculino, blanco, que presentó múltiples infecciones respiratorias y digestivas, intolerancia a la leche, asociado a sibilancias recurrentes y manifestaciones exantemáticas. Tuvo varios ingresos incluso en terapia intensiva por sepsis grave y cumplió tratamientos con penicilinas, cefalosporinas, sulfas, fosfocina, vancomicina y metronidazol. El estudio inmunológico reveló una marcada disminución de las subpoblaciones linfocitarias y concentraciones disminuidas de la subclase de IgG4. Se estableció el diagnóstico de inmunodeficiencia primaria del tipo combinada no grave. El tratamiento utilizado incluyó gammaglobulina endovenosa y el factor de transferencia. Se confirmó una mejoría clínica evidente. Conclusiones: Las infecciones recurrentes junto con los resultados de los estudios permitieron diagnosticar esta inmunodeficiencia primaria. El diagnóstico precoz y el tratamiento oportuno mejoran la calidad de vida del paciente.
ABSTRACT Introduction: Primary immunodeficiencies are genetic diseases. They are made up of more than 200 diseases that have recurrent infections in common. Combined immunodeficiency is characterized by recurrent episodes of sepsis of the respiratory, digestive and skin system, especially opportunistic germs. The clinical picture is highly variable and multiple clinical phenotypes are known. Objective: Assess the clinical and immunological manifestations of non-severe combined primary immunodeficiency through a case. Case presentation: 8-month-old male, white infant who presented multiple respiratory and digestive infections, milk intolerance, associated with recurrent wheezing and exanthematic manifestations. He had several hospitalizations even in the intensive care service due to severe sepsis and completed treatments with penicillins, cephalosporins, sulfas, phosphocin, vancomycin and metronidazole. The immunological study revealed a marked decrease in lymphocyte subpopulations and decreased concentrations of the IgG4 subclass. The diagnosis of primary immunodeficiency of the non-severe combined type was established. The treatment used included intravenous gamma globulin and transfer factor. An evident clinical improvement was confirmed. Conclusions: The recurrent infections together with the results of the studies allowed to diagnose this primary immunodeficiency. Early diagnosis and timely treatment improve the patient's quality of life.
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Objective To explore the effect of budesonide suspension for inhalation in the treatment of childhood asthma and its influence on growth and development in 1-2 years. Methods The 68 children with asthma admitted to our hospital from October 2016 to January 2017 were selected. Every patient had acute attacks and received continued medication. 34 patients treated with salbutamol sulfate inhaled aerosol were used as the control group. 34 patients treated with budesonide suspension combined with salbutamol sulfate aerosol were classified as the observation group. The interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), high-sensitivity-C-reactive protein (hs-CRP), maximum respiratory flow, IS maximum expiratory volume, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, wet rales disappearing time, cough disappearing time, and the two year follow-up indicators of growth and development were compared. Results After medication, IL-6, TNF-α, hs-CRP, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, moist rales disappearance time, and cough disappearance time were lower in the observation group(P<0.05). The maximum respiratory flow and IS maximum expiratory volume in the observation group were higher than those in the control group (P<0.05). The GH level, height, and weight obtained from two year follow up in the observation group were lower than those in the control group (P<0.05). Conclusion Budesonide suspension combined with salbutamol sulfate aerosol inhalation therapy can alleviate the inflammatory reaction, improve the lung function and immune function of children, and accelerate the disappearance of clinical symptoms, but it will affect the growth and development of children to a certain extent.
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Objective:To investigate the changes in peripheral blood and liver-infiltrating natural killer-like B (NKB) cells in patients with primary hepatocellular carcinoma (HCC), and to assess the influence of IL-18 on NKB cells in vitro and the underlying mechanism. Methods:Forty-three HCC patients and 21 normal controls (NC) were enrolled in the study. Peripheral blood samples were collected to isolate plasma and peripheral blood mononuclear cells (PBMC). Intrahepatic lymphocytes (IHL) were isolated from tumor tissues and para-tumor tissues obtained from 16 HCC patients who received surgery. IL-12, IL-18 and IL-18 binding protein (IL-18BP) levels in plasma were measured by enzyme linked immunosorbent assay. The percentages of CD3 -NKp46 + CD19 + NKB cells and IL-18 + NKB cells in PBMC and IHL were analyzed by flow cytometry. Changes in the percentages of NKB cells and IL-18 + NKB cells were measured after stimulating PBMC and IHL with recombinant human IL-18 (1 ng/ml and 10 ng/ml). Changes in IL-18BP levels in the culture supernatants and phosphorylated nuclear factor-κB (NF-κB) in NKB cells were also assessed. Student′s t test, one-way analysis of variance or LSD-t test was used for statistical analysis. Results:There was no significant difference in plasma IL-12 level between HCC patients and NC ( P=0.245). Compared with NC, HCC patients had decreased IL-18 level in plasma [(224.3±58.89) pg/ml vs (327.0±52.27) pg/ml, P<0.000 1], but increased IL-18BP level [(4.421±0.97) ng/ml vs (0.92±0.18) ng/ml, P<0.000 1]. The percentages of peripheral blood NKB cells and IL-18 + NKB cells were lower in HCC patients than in NC [(2.68±1.23)% vs (8.88±2.95)% and (54.42±12.60)% vs (69.74±12.65)%, both P<0.000 1]. The percentage of NKB cells in IHL was reduced in tumor tissues as compared with that in para-tumor tissues [(2.89±0.86)% vs (4.66±1.17)%, P<0.000 1]. Moreover, the percentage of IL-18 + NKB cell was also down-regulated in tumor tissues as compared with that in para-tumor tissues [(51.50±13.18)% vs (62.13±9.24)%, P=0.013]. Recombinant human IL-18 stimulation reduced the IL-18BP level in the culture supernatants ( P<0.05). IL-18 stimulation at 1 ng/ml did not affect NKB cell percentage, IL-18 + NKB cell percentage or NF-κB phosphorylation in NKB cells from PBMC or IHL ( P>0.05), while 10 ng/ml of IL-18 not only elevated NKB cell percentage and IL-18+ NKB cell percentage, but also promoted NF-κB phosphorylation in NKB cells ( P<0.01). Conclusions:In vitro stimulation with high concentration of IL-18 might promote NF-κB phosphorylation by inhibition of IL-18BP expression. This process might play a positive feedback role to induce the activation of NKB cells and IL-18 secretion.
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The human immune system represents a dynamic multiscale system with high complexity in biology. Humoral immunity, as the main branch of adaptive immunity, is characterized by differentiated stages of the B lymphocytes, producing the final product of antibodies that has a diversity of the tuning mechanisms within genetic and epigenetic levels in confrontation with environmental exposures. Disorders because of disturbed humoral immunity are linked with dysregulation of feedback-regulated signaling and the dynamic of immune components that determine the overall response. Food products, mainly herbal components have a significant role in tailoring the immune system micro-ecosystem which can diversify the adaptive nature of humoral immunity. Herein, we review the current evidence-based approaches for the impact of medicinal herbs on humoral immunity signaling and antibody production with a focus on immunotherapeutic applications.
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Cigarette smoking is a major risk factor for chronic respiratory inflammatory diseases. Nicotine is the most important ingredient in tobacco smoke. The incidence rate of chronic respiratory diseases associated with nicotine is increasing rapidly. Therefore, it is urgent to find potential targets for nicotine-related chronic respiratory inflammatory diseases. This article hereby aims to investigate the effect of nicotine on apoptosis of BEAS-2B cells and its potential mechanism. The expressions of apoptosis, autophagy and PI3K/ Akt/ mTOR pathway-related proteins were detected by Western blotting. Flow cytometry and CCK-8 were used to detect cell apoptosis rate and cell viability. The results showed that nicotine induced apoptosis of BEAS-2B cells at 1, 2 and 4 mmol/ L, and the cell viability decreased with the increase of concentration. Compared with the control group, the expression of autophagy-related protein LC3Ⅱ and P62 increased significantly after nicotine treatment (P0. 05). Compared with the nicotine group, rapamycin pretreatment significantly decreased cell apoptosis and increased cell activity (P<0. 05). Compared with the nicotine group, the expression of p-Akt and p-mTOR decreased significantly and apoptosis decreased significantly after LY294002 pretreatment (P<0. 05). Furthermore, nicotine induces apoptosis of BEAS-2B cells by inhibiting autophagy may be via PI3K/ Akt/ mTOR pathway, which may be a potential target for the prevention and treatment of chronic respiratory inflammatory diseases.
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Objective:To observe the analgesic effect of Panlongqi tablet（PLQT） on rats with chronic inflammatory pain， and to explore mechanism of the action preliminarily from the perspective of the nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB）and mitogen-activated protein kinase（MAPKs） signaling pathways. Method:Rats were induced to establish model of chronic inflammatory pain by complete Freund adjuvant（CFA）， which was divided into normal group， model group， the PLQT 0.16，0.32，0.64 g·kg-1 group， and the ibuprofen 0.05 g·kg-1 group（also positive group）， give the medicine once a day by gavage. Standard Von Frey fiber was used to evaluated the mechanical pain threshold， acetone was used to stimulated rats inflammatory foot to get the cold-induced response score， with the mechanical pain threshold and cold-induced response score to be observed at 1， 2， 3， 4 and 6 h before and after administration on day 1， and at 4 h after administration on day 3-7. The content of PGE2， IL-1， TNF-α in serum， inflammatory foot and 4-5 lumbar spinal cord was detected by enzyme-linked immunosorbent assay（ELISA）. The protein level of MAPKs （p-p38， p-ERK， p-JNK） in lumbar spinal cord 4-5 was detected by Western blot. The expression of NF-κB p65 in the lumbar spinal cord was detected by IFA. Result:Model group had lower mechanical pain threshold and higher cold-induced response score than these in normal group（P<0.01）， while the mechanical pain threshold and cold-induce response score of the model rats were dose-dependent better regulated after administration of PLQT 0.16， 0.32， 0.64 g·kg-1·d-1（P<0.05，P<0.01）， these effect lasted 6 h， of which PLQT groups get the most significant effect on 4 h， however the effect of IBP was similar to that of PLQT medium dose group. In addition， PLQT reduced the abnormal increase of PGE2， IL-1 and TNF-α contents in serum， inflammatory foot and spinal cord of rats in model group， decreased the protein phosphorylation levels of ERK and JNK in spinal cord， and decreased the protein expression of NF-κB p65， that was significant in the PLQT high-dose group（P<0.01）. Conclusion:PLQT had significant analgesic effect on chronic inflammatory pain model rats， which may be related to the inhibition of NF-κB and MAPKs signaling pathways in spinal cord.
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Functional cure of chronic hepatitis B (CHB) marks sustained virological inhibition and immunological control and is the ideal treatment goal recommended by the latest guidelines for the prevention and treatment of CHB in China and foreign countries. CHB patients can achieve virological inhibition with the help of long-term direct antiviral therapy, and only a small number of patients can achieve functional cure, suggesting that there is an urgent need for the combination of direct antiviral therapy and immunotherapy. At present, the best treatment strategy is targeted precise clearance of HBV-infected hepatocytes to reduce liver injury, which depends on HBV-specific immune cells in the liver. Therefore, restoring or enhancing the function of HBV-specific T cells and B cells is the key strategy for functional cure of CHB.
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BACKGROUND: Heart transplantation is an important treatment for end-stage heart disease. The use of immunosuppressive drugs is indispensable for the maintenance of transplantation. Given the enormous side effects of immunosuppressive drugs, it may even have a significant impact on the quality of life of patients. People began to explore new ways to induce transplantation tolerance to avoid the use of immunosuppressive drugs. The immunomodulation characteristics of mesenchymal stem cells have attracted the attention of researchers and a large number of related researches have been carried out. OBJECTIVE: To summarize and investigate the characteristics of immune regulation of mesenchymal stem cells and immune tolerance induction in heart transplantation and their relationship. METHODS: We searched relevant literature in PubMed database. Key words were “stem cell; mesenchymal stem cells; MSC; MSCs; heart transplantation; cardiac allograft; heart allograft; immune tolerance; tolerance; immunological rejection”. The repetitive studies were excluded after screening, and the related literature was arranged and summarized. RESULTS AND CONCLUSION: On one hand, mesenchymal stem cells have different effects on a variety of immune cells. On the other hand, mesenchymal stem cells regulate or directly produce a large number of biological active factors so as to constitute a complex network, creating a microenvironment conducive to immune regulation. The application of mesenchymal stem cells in heart transplantation is limited to animal experiments, and the results are relatively optimistic. Researchers’ exploration of induction of immune tolerance in heart transplantation will help people to understand the field further and provide more inspiration to relevant clinicians.