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Abstract As the treatment of infectious and parasitic diseases improved, the prevalence of these conditions declined. However, with the expansion of the use of immunobiologicals, opportunistic infections have emerged, especially under atypical presentations. The present study reports the case of a patient treated with infliximab for Crohn's disease, who presented diarrhea, weight loss, abdominal pain, fever, and subcutaneous erythematous nodules that evolved with spontaneous fluctuation and ulceration. With the finding of alcohol-resistant bacilli and Mycobacterium tuberculosis DNA in a cutaneous fragment, through polymerase chain reaction, the diagnosis of gummatous tuberculosis was confirmed, probably secondary to hematogenous dissemination from an intestinal focus.
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Humans , Tuberculosis, Cutaneous/diagnosis , Tuberculosis, Cutaneous/chemically induced , Tuberculosis, Cutaneous/drug therapy , Crohn Disease/drug therapy , Syphilis , Skin , Infliximab/adverse effectsABSTRACT
Objective@#To investigate the clinical efficacy of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of rheumatoid arthritis (RA).@*Methods@#Forty adult RA patients (12 males, 28 females) aged from 36 to 79 were selected in Department of Rheumatology of the Second People′s hospital of Datong from February 2016 to February 2018.The patients were randomly divided into the observation group and the control group according to the digital table, with 20 cases in each group.The observation group was treated by intra-articular injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein and sodium hyaluronate, and the control group was only treated with recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein.The joint swelling, joint pain, joint mobility, morning stiffness, X-ray grade and total effective rate of the two groups were statistically analyzed before and after treatment.@*Results@#Before treatment, there were no statistically significant differences in joint swelling, joint pain, joint mobility, morning stiffness, clinical score and X-ray grade between the two groups (all P>0.05). After treatment, the symptoms and signs of the two groups were obviously improved.The joint pain, joint pressure pain, joint activity, morning stiffness and clinical score in the observation group were (1.2±1.2)points, (0.8±0.7)points, (0.5±0.4)points, (0.7±0.7)points and (4.5±2.6)points, respetively, which were significantly better than those in the control group [(2.2±1.4)points, (1.5±0.9)points, (1.5±0.9)points, (1.5±0.6)points and (8.6±4.6)points, U=125, 111, 68, 89 and 97, all P<0.05]. The total effective rate of the observation group was 100% (20/20), while that of the control group was 75% (15/20), there was statistically significant difference between the two groups (χ2=14.10, P<0.01).@*Conclusion@#The injection of recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein combined with sodium hyaluronate in the treatment of RA can effectively improve the clinical symptoms of RA patients, and it is more effective than single use.It is worthy of popularizing in clinic.
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Objective To evaluate the role of spinal cord tumor necrosis factor receptor-associated factor 6 (TRAF6)/nuclear factor kappa B (NF-κB)signaling pathway in the development of diabetic neuropathic pain (DNP)in rats.Methods Clean-grade healthy adult male Sprague-Dawley rats,aged 2 months,weighing 180-230 g,in which IT catheters were implanted,were used in this study.Streptozotocin 60 mg/kg was intraperitoneally injected after IT catheterization to establish the model of DNP.Twelve DNP rats were divided into 2 groups (n =6 each) by a random number table method:DNP group and DNP plus TRAF6 inhibitor group (group DTR).Another 6 age-matched Sprague-Dawley rats were used as normal control group (group NC).The rats in group DC and group DTR received IT injection of dimethyl sulfoxide 10 μl and TRAF6 inhibition 10 μg,respectively,once a day for 7 consecutive days starting from day 21 after establishing the model.The mechanical paw withdrawal threshold (MWT) was determined before establishing the model (T1),on 7,14 and 21 days after establishing the model (T2-4),and on 1,4 and 7 days after IT injection (T5-7).The rats were sacrificed after the last MWT measurement,and the L3-5 segments of the spinal cord were removed for determination of the expression of TRAF6 and NFκB p65 by Western blot.Results Compared with group NC,the MWT at T3-7 in group DC and at T3-6 in group DTR was significantly decreased,and the expression of spinal TRAF6 and NF-κB p65 was up-regulated in DC and DTR groups (P＜0.05).Compared with group DC,the MWT was significantly increased at T6-7,and the expression of spinal TRAF6 and NF-κB p65 was down-regulated in group DTR (P ＜ 0.05).Conclusion Spinal cord TRAF6/NF-κB signaling pathway is involved in the development of DNP in rats.
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ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.
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Humans , Skin Diseases/etiology , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Inflammation/complications , Inflammation/diagnosis , Skin Diseases/immunology , Inflammation/immunologyABSTRACT
Objective To investigate the expression and clinical significance of tumor necrosis factor recep-tor associated factor 6(TRAF6)in human esophageal cancer.Methods The clinical data of 72 patients with esopha-geal cancer were collected.Immunohistochemistry method was used to determine TRAF6 expression in esophageal carcinoma and its adjacent normal tissue,and its relationship with clinical pathological features was explored.Results The TRAF6 positive expression rate in esophageal cancer tissue was 66.13%,which was significantly higher than that of normal tissue (13.89%),the difference between the two groups was statistically significant(χ2 =56.850,P <0.01).And TRAF6 expression level was significantly correlated with esophageal cancer clinical staging,lymph node metastasis(χ2 =6.818,4.428,all P <0.05),but TRAF6 expression was not correlated with age,sex,tumor differenti-ation.Conclusion The expression level of TRAF6 in esophageal carcinoma was significantly increased,and there was a significant correlation between the TRAF6 expression level and clinical pathological characteristics.
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Objective To investigate the effect of elemene on mRNA expressions of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) and caspase-8 in tumor tissues of mice bearing hepatoma H22.Methods Forty BALB/c mice models bearing hepatoma H22 were established by subcutaneous inoculating tumor cells.Forty BALB/c mice were randomly divided into 4 groups:model group,low-and high-elemene dosage groups,and cisplatin group.The tumors after executing mice were weighted.The mRNA expressions of TRAF6 and caspase-8 in tumor tissues were detected by quantitative real-time reversetranscription polymerase chain reaction (RT-PCR).Results The dosage of elemene could inhibit tumor growth.The inhibition ratio of cancer in the low-and high-elemene dosage and cisplatin group was 24.2％,27.4％,and 28.2％,respectively.It reduced significantly tumor weights(P ＜0.01).Compared to the model group,the expression level of TRAF6 mRNA on tumors was decreased significantly,while the expression level of caspase-8 mRNA was increased significantly in the other groups(P ＜ 0.05).Conclusions The present results indicated that molecular mechanism of inhibition of liver cancer growth treated by elemene might be through down-regulating mRNA expressions of TRAF6 and caspase-8,promoting tumor cells apoptosis,and achieving the anti-tumor effect.
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Objective To investigate the expression of micro RNA-146a (miR-146a),TNF receptorassociated factor 6 (TRAF6) gene and IL-1 receptor-associated kinase 1 (IRAK1) gene in the peripheral mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and their relationship with the disease activity.The role of miR-146a,TRAF6,IRAK1 in the pathogenesis of AS was explored.Methods Expression of miR-146a,TRAF-6 and IRAK-1 in peripheral blood mononuclear cells was studied using realtime polymerase chain reaction (qRT-PCR) in 45 AS patients and 22 healthy controls.The indicators of disease activity adopted in this study were Bath ankylosing spondylitis disease activity index (BASDAI),erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) level,and immunoglobulin (Ig).The relationship was analyzed in AS patients between the relative expression levels miR-146a,TRAF6,IRAK1 and BASDAI,ESR,CRP,Ig concentration.Non-parametric test,t test,One-way ANOVA,Pearson's and Spearman's correlation analysis were used for statistical analysis.Results ①The relative expression level of miR-146a which was observed in PBMCs of AS patients was significantly higher than that in normal control group [1.46(0.39,4.79)and 0.81(0.17,1.90),P＜0.05].The expression of miR-146a was significantly higher in active AS patients group than that in inactive patients [2.93(0.95,7.95) and 0.54(0.28,1.69),P＜0.05],there was no difference between the treatment group and without treatment group [1.28(0.31,2.37) and 2.22(0.49,7.71),P＞0.05].② There was significant difference in the relative expression level of IRAK-1 between AS patients and the normal control group.IRAK1 was significantly higher in AS patients than that in normal control group (1.4±0.7,1.1±0.4,P＜0.05).However,there was not difference between active AS patients group and inactive patients group as well as treated group and untreated group (1.5±0.9,1.4±0.5; 1.6±0.7,1.3±0.7,P＞0.05).③ TRAF6 expression was obviously lower in AS patients than that in normal control group (1.3±0.6,1.7±0.8,P＜0.05),and that was also significantly lower in the untreated group and active group than that in the normal control group (1.1±0.7,1.7±0.8; 1.1±0.5,1.7±0.8,P＜0.05).④ Signi-ficant positive correlation was observed between the miR-146a level and BASDAI,as well as duration of morning stiffness (r=0.557,P=0.000; r=0.363,P=0.018).The expression level of IRAK1 was significantly negative correlated with IgM (r=-0.313,P=0.046).Conclusion ① miR-146a expression is up-regulated in patients with AS,and it may be a potential useful marker for disease activity in AS patients; ② The abnormal expression of IRAK1,TRAF6 in AS patients may play a role in the pathogenesis of AS.
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Objective To explore the role of Toll-like receptor 7 (TLR7) and related signal transduction molecules in mechanisms underlying human papilloma virus (HPV) infection and condyloma acuminatum (CA) recurrence.Methods Peripheral blood was obtained from 30 healthy controls,35 patients with primary CA,32 patiens with recurrent CA and 30 patients with recurrent CA treated by imiquimod and ALA-PDT.Two-color flow cytometric analysis was used to detect TLR7 expression in different peripheral blood T cell subsets,Western blot to determine the expression levels of an adapter protein myeloid differentiation primary response gene 88 (MyD88),and signaling molecules including tumor necrosis factor receptor-associated factor (TRAF6),phosphatidylinositol3-kinase (PI3K),protein kinase B (AKT),p42/44 and nuclear factor-kappa B (NF-κB) in peripheral blood CD3+ T cells,from these subjects.Statistical analysis was carried out by Student's t test using the software SPSS 13.0.Results TLR7 was expressed in peripheral blood CD3+CD4+ T cells and CD3+CD8+ T cells from the healthy controls.Compared with the healthy controls,the patients with primary and recurrent CA showed no significant changes in TLR7 expression in CD3+CD8+ T cells,but a statistical increase in TLR7 expression in CD3+CD4+ T cells (23.3％ ± 8.4％ and 32.8％ ± 8.9％ vs.12.6％ ± 6.3％,t =4.72,10.76,both P ＜ 0.01).Decreased expression of TLR7 in CD3+CD4+ T cells was observed in patients treated with imiquimod and ALAPDT compared with the patients with recurrent CA (20.3％ ± 5.7％ vs.32.8％ ±8.9％,t =5.41,P ＜ 0.01).The protein expressions of MyD88,TRAF6,PI3K,p42/44 and NF-κB were significantly increased in CD3 + T cells,while the AKT protein expression experienced no significant changes in patients with primary or recurrent CA compared with the healthy controls.A significant decrease was observed in the protein expression of MyD88,TRAF6,p42/44 and NF-κB in the treated patients compared with those with recurrent CA.Conclusions TLR7,which is highly expressed in peripheral blood CD3+CD4+ T cells in patients with CA,may take part in the host immune response against HPV and serve as a recognition receptor for HPV infection.
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Objective: To observe the effect of bortezomib (Btzmb) on the differentiation and function of osteoclasts from patients with multiple myeloma (MM) during their maturation in vitro and investigate the influence of Btzmb on the expression of tumor necrosis factor receptor-associated factor (TRAF6), one of the key signaling molecules on the upstream of osteoclasts differentiation. Methods: Osteoclast precursor mononuclear cells were isolated from peripheral blood of MM patients and cultured with receptor activator of NF-κB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) and different concentrations of Btzmb. The number of tartrateresistan acid phosphatase (TRAP)-positive osteoclasts was counted. The TRAP activity in the supernatant was tested. The extent of the ivory slice resorption was observed. The effects of Btzmb on the mRNA and protein expressions of TRAF6 were determined by RT-PCR and Western blotting, respectively. Results: After Btzmb 2.5 and 5 nmol/L treatment, the number of osteoclasts were reduced compared with the control group [(157 ±21) and (98 ± 15) vs (307 ± 25), P < 0.05]. The number of the ivory slice resorption decreased [(53 ± 24)% and(29 ± 7)% of the control, P < 0.05]. The TRAP activity in the supernatant was inhibited [(86 ± 24)% and(60 ± 25)% of the control, P < 0.05]. The activity of TRAF6 protein gradually declined and the levels of TRAF6 mRNA also decreased at 24 h after Btzmb treatment. Conclusion: Btzmb can inhibite the differentiation and function of osteoclasts. The action of Btzmb may be related with TRAF6.