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Mast cells, autoantibodies, inflammatory cells, coagulation cascade, complement system and nervous system are all involved in the complex pathogenesis of chronic spontaneous urticaria (CSU) , while mast cells play a pivotal role in it. With deeper understanding of the pathogenesis of CSU, cutting-edge therapeutic methods are gradually being used in clinical practice. Nowadays, pharmacotherapyeutic studies are more focused on accurately modulating the pathological state of mast cells. This review summarizes recent advances in the pathogenesis of and medicines for CSU.
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Studies have shown that the type 2 inflammatory response and related cytokines such as interleukin-4 and -13, play a key role in atopic dermatitis (AD) . Th2 cells and type 2 cytokines are the core factors in the type 2 inflammatory response, which is mainly involved in the pathogenesis of AD through 3 pathways: aggravating skin barrier defects; activating and strengthening the itching response; pathologically reprograming regulatory T cells into Th2-like regulatory T cells to amplify the type 2 inflammatory response. This review explores the relationship between the type 2 inflammatory response and AD, aiming to help optimize treatment regimens and provide new treatment options for patients with AD.
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The breast cancer is a usual and serious malignant tumor which threatens the women′s health.Molecular subtyping bases on the molecular level, and provides a new classification method for the breast cancer pathology classification, and plays an important guidance significance for the clinical treatment.At present, the breast cancer molecular subtyping is mainly divided into the following subtypes: the Luminal A type and Luminal B type, HER-2 overexpression and the triple negative breast cancer.Different molecular subtyping has different characteristics in treatment reaction, prognosis and the clinical application situation.
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Objective:To illuminate a method for establishment of a cost-efficient atopic dermatitis (AD) mouse model by topical application of ovalbumin (OVA),super-antigen staphylococcal enterotoxin B (SEB),and calcipotriene ointment (CO) on the back of BALB/c mice.Methods:Experimental mice were topically treated with OVA/SEB or OVA/SEB/CO every other day during 15 days of induction.Clinical alterations on the skin area were monitored every other day.Epidermal thickness were measured by reflectance confocal microscope (RCM) before harvest.Inflammatory cells in skin biopsies were marked by hematoxylin-eosin (HE) staining.Blood sample and skin biopsies were measured by ELISA and quantitative real-time PCR to detect the expression of IL-2,IL-4,IL-31,interferon (IFN)-γ,tumor necrosis factor (TNF)-α pruritus-associated nerve growth factor (NGF),and serum IgE.Results:Human AD-like cutaneous local inflammatory reaction was characterized by the accumulation of inflammatory cells,increased epidermal thickness and serum IgE levels as well as Th1 cell-associated cytokines (IFN-γ,TNF-α),Th2 cell-associated cytokines (IL-4,IL-31),and NGF in the OVA/SEB/CO group compared with that in the normal control group or the OVA/ SEB group.Conclusion:OVA/SEB/CO can induce an AD-like mouse model with lower economic and time consumption.
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Atopic dermatitis (AD) is an allergic skin disease with a genetic predisposition.The pathogenesis is complex,including environment stimulation,epidermal barrier deficiency,and autoimmune disorders.The destruction of epidermal barrier stimulates the inflammatory response.In acute period,Th2 cells are activated to produce IL-4 and induce B lymphocytes to secrete IgE.Thus leads to degranulation of mast cells and basophils.After acute period,epidermis is thickened,accompanied with increasing expression levels of several chemokines and cytokines.In chronic phase,the cellular infiltration includes mainly Th1 and Th2 cells,and less Th17 and Th22 cells.The latter two cells together with their specific cytokines and chemokines are derived from keratinocytes and fibroblasts,which can produce tissue remodeling and fibrosis.So far,the treatment of AD contains allergens exposure avoid,anti-inflammatory,anti-infection,phototherapy,and immune therapy,etc.
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OBJECTIVE@#To construct a special luciferase reporter to detect DNA methylation regulatory activity in FCER1G gene promoter regulatory element.@*METHODS@#We constructed special full and mock methylated FCER1G gene promoter regulatory luciferase reporters by patch-methylation, and detected DNA methylation regulatory activity by comparing the luciferase activity of full-methylated luciferase reporters with mock-methylated reporters.@*RESULTS@#We successfully constructed the full and mock methylated FCER1G gene promoter regulatory luciferase reporters. The ratio of luciferase activity between the full methylated and the mock methylated was (0.36±0.07):1 (P<0.001).@*CONCLUSION@#FCER1G promoter activity is methylation-sensitive and is regulated by DNA methylation.
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Humans , Base Sequence , DNA Methylation , Gene Expression Regulation , Genes, Reporter , Luciferases , Genetics , Molecular Sequence Data , Promoter Regions, Genetic , Genetics , Receptors, IgE , Genetics , MetabolismABSTRACT
Objective:To explore the mechanisms by which DNA methylation regulates miR-126 and its host gene EGFL7 in CD4+T cells from patients with systemic lupus erythematosus (SLE). Methods:We analyzed the expression and the DNA methylation status within promoter region of EGFL7 and miR-126 by real-time qPCR and bisulifte genomic sequencing analysis. Results:miR-126 and EGFL7 mRNA expression was upregulated in CD4+T cells from SLE compared with that from healthy controls (P Conclusion:hTe upregulation of miR-126 and its host gene EGFL7 expression in CD4+T cells from SLE is associated with the hypomethylation of the EGFL7 promoter.
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Objective To evaluate the efficacy and safety of total glucosides of paeony combined with ebastine for the treatment of chronic idiopathic urticaria.Methods A randomized,open-labeled,positive drugcontrolled,parallel-group study was carried out.Sixty patients with chronic idiopathic urticaria were randomly divided into two groups using a random digit table:combined group treated with total glucosides of paeony 600 mg thrice daily combined with ebastine 10 mg per day,control group treated with ebastine 10 mg per day only.The treatment lasted 12 weeks followed by a four-week follow-up.Adverse reactions were recorded and treatment efficacy was evaluated by using urticaria activity score over seven days (UAS7).Results The UAS7 was 9.28 ±4.59,5.83 ± 4.44 and 7.52 ± 5.57 in the combined group on week 8,12 after the initiation of treatment and week 4 after the withdrawal of treatment,respectively,significantly lower than that in the control group at the three time points (13.29 ± 4.72,P ＜ 0.05; 9.86 ± 5.46,P ＜ 0.01; 16.21 ± 5.34,P ＜ 0.01).Significant differences were observed in the response rate between the combined group and control group at the end of the 12-week treatment (75.9％ vs.42.9％,x2 =4.56,P ＜ 0.05).There was a decreased recurrence rate in the combined group combined with the control group at the end of the follow-up (13.6％ vs.50.0％,x2 =3.90,P ＜0.05).No obvious adverse reactions were noted in either of the two groups.Conclusion Total glucosides of paeony could markedly enhance the efficacy of ebastine for the treatment of chronic idiopathic urticaria with a reduction in recurrence rate.
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BACKGROUND:The skin lesions, pathological and immunological characteristics of Nc/Nga mice are consistent with human atopic dermatitis, and as an atopic dermatitis animal model, it has great research value. But there are no reports on the physiological and biochemical parameters of Nc/Nga mice in China. OBJECTIVE:To observe the growth and reproduction and blood physiological and biochemical parameters of atopic dermatitis model of NC/Nga mice METHODS:The data of reproductive performance of NC/Nga mice from the first to the third generation was analyzed, including mean litter size, weaning rate, pregnancy rate and generation interval. The body mass of 60 Nc/Nga mice with 1-56 days old was measured, 30 mice of female and male, then the growth curve was draw. The blood samples from the infraorbital vessels were col ected to detect the blood physiological and biochemical parameters in the mice. RESULTS AND CONCLUSION:The mean delivery interval of Nc/Nga mice was (25.8±3.1) days, mean litter size was (7.5±2.5) mice, mean weaning rate was (97.2±1.2)%, the mean pregnancy rate was (97.0±1.4)%, and there was no significant difference among the three generations of these mice (P>0.05). The body mass of Nc/Nga mice was increased with the time increasing of days, the body mass of the mice was maximal within 1-2 weeks post-weaning, and there was no significant difference in body mass between males and females at 6 weeks post-weaning (P>0.05). Comparison of the blood physiological and biochemical parameters of mice at the same age between males and females showed that the levels of red blood cells and hemoglobin in female mice were significantly higher than those in the male mice;the platelet count in the male mice was significantly higher than that in the female mice (P<0.05);the triglycerides and albumin levels in the female mice were higher than those in the male mice (P<0.05). The results indicate that the gender and age may influence the blood physiological and biochemical parameters of Nc/Nga mice.
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OBJECTIVE@#To observe the demethylation effect of demethylation inhibitor 5-azacytidine (5-Zac) on programmed death receptor 1 (PD-1) in Molt-4 cells (T lymphocyte cell line) and to investigate the relationship between DNA demethylation and expression of PD-1.@*METHODS@#Molt-4 cells were cultured in the medium containing different concentrations of 5-Zac(0, 5, 10 μmol/L) for 72 h. According to the concentrations of 5-Zac, the Molt-4 cells were divided into a 0 μmol/L 5-Zac group, a 5 μmol/L 5-Zac group, and a 10 μmol/L 5-Zac group. The expression of PD-1 in Molt-4 cells was detected by flow cytometry and the apoptosis rate was calculated. The mRNA transcription level of PD-1 was detected by real-time polymerase chain reaction; Molt-4 cell DNA in all groups were treated by sodium bisulfite. The PD-1 promoter fragment was amplified by PCR, the amplification fragments were transformed into E. coli., the positive clones were selected for equencing, and the methylation status of the fragments of PD-1 promoter was examined. RESULTS Seventy-two hours after the 5-Zac treatment, the expression rate of PD-1 in the Molt-4 cells in the 0 μmol/L 5-Zac group, the 5 μmol/L 5-Zac group, and the 10 μmol/L 5-Zac group was (1.13 ± 0.01)%, (18.96 ± 1.87)%, and (63.09 ± 6.25)% respectively, in a low concentration-dependent way. The PD-1 mRNA expression level was increased significantly with the 5-Zac treatment. Cells apoptosis showed that:compared with the 0 μmol/L 5-Zac group, the apoptosid rate in the 5 μmol/L 5-Zac group and 10 μmol/L 5-Zac group was signficantly increased, which was (1.9 ± 0.06)%, (8.89 ± 1.36)%, and (24.50 ± 3.68)% in the 0 μmol/L 5-Zac group, the 5 μmol/L 5-Zac group, and the 10 μmol/L 5-Zac mol/L group respectively. The bisulfite genomic sequencing showed that the demethylation probability of CpG points on -601 bp and -553 bp was significantly increased in the 5-Zac treated cells compared with those untreated.@*CONCLUSION@#5-Zac can result in the increase of PD-1 expression in the human lymphoid cell series Molt-4 in vitro, and the apoptosis rate increases, which is related to PD-1 gene promoter demethylation.
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Humans , Apoptosis , Genetics , Azacitidine , Pharmacology , Cell Line , CpG Islands , Genetics , DNA Methylation , Genetics , Enzyme Inhibitors , Pharmacology , Programmed Cell Death 1 Receptor , Genetics , Metabolism , Promoter Regions, Genetic , Genetics , RNA, Messenger , Genetics , Metabolism , T-Lymphocytes , Cell Biology , MetabolismABSTRACT
Objective To investigate the demethylation and changes in gene expression of programmed death receptor-1 ( PD-1) caused by methylation inhibitor 5- azacytidine (5-Zac) in lymphocyte series Molt-4 cells and its mechanism. Methods Molt-4 cells were cultured in different concentrations of 5-Zac(0, 5, 10 Umol/L)for 72 h, ratio of cell expressing PD-1 and apoptosis rate were detected by FCM, transcription of PD-1 gene mRNA was detected by RT-PCR. Molt-4 cell DNA of all groups were disposed by sodium bisulfite, PD-1 gene promoter fragment binded with transcription factor Brn-2 was amplified by PCR,these amplification fragments were transformed into E. coli. Positive clones were selected by sequencing,methylation status of the fragments binded with transcription factor Brn-2 was examined. Results S-Zac could increase the PD-1 expression of Molt-4 cells. PD-1 expression rate in 0 μmol/L 5-Zac( 1. 13%±0.01% ) treated cells was found more lower than that in both 5 μmol/L and 10 μmol/L 5-Zac treated cells (18. 96% ±1. 87% , 63. 09% ± 6. 25% , P < 0. 05 ) , and they showed concentration-dependent (P <0.01). Cells apoptosis rate and PD-1 mRNA expression were also observed increased significantly with 5-Zac treating. Demethylation probability of CG points showed significant difference between transcription factor Brn-2 binding site and other four locations (P < 0.05 ). Conclusion 5 -Zac inhibits cell grouth in human lymphoid cell series Molt-4 by inducing PD-1 gene expression and promoter demethylation. PD-1 gene promoter binding transcription factor Brn-2 fragment CG point demethylation may be one of the important mechanisms in 5-Zac treated Molt-4 cells.
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Objective To investigate the efficacy of combined high-dose intravenous immunoglobulin (IVIG) pulse therapy in patients with severe systemic lupus erythematosus (SLE). Methods Thirty-six patients were enrolled into this study, and randomly classified into WIG group (n=17) and methylprednisolone (MP) group (n=19). The treatment of patients in MG group began with a 3-day intravenous MP followed by intravenous WIG 400 mg per kilogram of body weight per day for 3-5 days, then was switched to oral prcdnisone and cyclophosphamide at routine dose. Intravenous MG was given repeatedly with an interval of 1 month for 2-5 sessions. Patients in MP group were treated with the same corticosteroids and immunosuppressants as used in WIG group but without IVIG. Patients were followed up for 3-12 months.The clinical efficacy, related serum parameters, and systemic lupus activity measurement (SLAM) were evaluated and compared between the two groups. Results Most patients in both groups showed a remission of symptoms and reduction in disease activity after treatment. The decrease in SLAM, positivity rates of antinuclear antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies as well as the increase in platelets were faster in IVIG group than those in MP group (all P<0.05), but the long-term efficacy of the two groups was similar (P>0.05). Infections occurred in 11.8% of patients in WIG group and 36.8% of patients in MP group. Conclusions High-dose intravenous immunoglobulin may serve as an effective aid in the treatment of severe SLE, and is particularly beneficial to patients resistant to corticosteroids and immunosuppressants of routine dose and those accompanied by severe infections and intolerable to high dose of corticosteroids and immunosuppressants.