Ami To investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells （DCs） and the effect of CP-25. Method Bone marrow DCs were isolated and stim- ulated ...Ami To investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells （DCs） and the effect of CP-25. Method Bone marrow DCs were isolated and stim- ulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha- TRADD-TRAF2-NF-KB in DCs were analyzed. Result Both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 （ 10 -5, 10 -6 , 10 -7 mol/L ） decreased significantly the ex- pressions of CD40, CD80, CD83, CD86 and MHC- ]I , increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-KB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-KB expression of DCs. CP-25 （10^-5, 10^-6, 10^-7 mol/L） decreased the expressions of EP4 and NF-KB, increased cAMP level in DCs stimulated by PGE2. CP-25 （10^-5 10^-6 10^-7 mol/L） also could down-regulate significantly TNFR1 TRADD TRAF2 and NF-KB expression in DCs stimulated by TNF-alpha. Conclusion PGE2 and TNF-alpha could enhance DCs func- tions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-KB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD- TRAF2-NF-KB pathways.展开更多
Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischem...Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and-8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 μg/kg;1 μg/kg and 3 μg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and-8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 μg/kg and 1 μg/ kg as compared to the placebo group. In contrast, the 3 μg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and-8 is reduced in the ischemic region in groups 0.1 and 1 μg/ kg as compared to the placebo group whereas activity in the 3 μg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.展开更多
Objective:To explore the changes of serum TNF-alpha, IL-2 and IL-13 in patients with rheumatoid arthritis (RA).Methods: A total of 60 patients with rheumatoid arthritis admitted to our hospital from December 2016 to D...Objective:To explore the changes of serum TNF-alpha, IL-2 and IL-13 in patients with rheumatoid arthritis (RA).Methods: A total of 60 patients with rheumatoid arthritis admitted to our hospital from December 2016 to December 2017 were selected as the observation group, and another 60 healthy people in the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) double antibody sandwich method was used to detect the changes of serum TNF-α, IL-2 and IL-13 in the observation group before and after treatment, and was correlated with rheumatoid arthritis disease activity index, plasma ESR, CRP level and DAS28 score.Results:before treatment, serum TNF-α, IL-2 alpha and IL-13 were significantly higher than those in the control group, the observation group of serum TNF-α, IL-2 and IL-13 levels were significantly lower than those before treatment, and compared with the control group, the difference was not statistically significant. Before treatment, the changes of serum TNF-α alpha, IL-2 and IL-13 during the onset of rheumatoid arthritis were positively correlated with the level of plasma ESR, CRP and DAS28.Conclusions:the serum levels of TNF-α, IL-2 and IL-13 in rheumatoid arthritis patients are significantly increased, and are closely related to the activity of rheumatoid arthritis. Patients can be effectively improved after treatment, which is worthy of clinical reference.展开更多
Using a rabbit model leading to myositis in response to exercise-induced muscle overuse, we have previously observed that TNF-alpha is involved in the exercised muscle in early developing myositis as well as both ipsi...Using a rabbit model leading to myositis in response to exercise-induced muscle overuse, we have previously observed that TNF-alpha is involved in the exercised muscle in early developing myositis as well as both ipsiand contralaterally in the myositis which develops in response to a lengthened period of overuse. It is unknown if TNF-alpha can also be engaged contralaterally in early stages of myositis. The hypothesis was that this is the case. It was therefore evaluated whether the TNF-alpha system is early involved contralaterally. An experimental model of 1 week of overuse of the soleus muscle on one side leading to myositis was used, and in situ hybridization and immunohistochemistry were applied to study the expression patterns of TNF-alpha in the soleus muscle in the contralateral side. TNF-alpha was expressed in the myositis process which occurred contralaterally. There were thus TNF-alpha mRNA reactions in the cells of the inflammatory infiltrates, in blood vessel walls and in certain of the muscle fibers. Parts of the latter were necrotic fibers, whereas others were interpreted to be in a regenerative stage. TNF-alpha immunoreactions were seen for infiltrating white blood cells. The observations show that the TNF-alpha system is early involved in the cross-over effects that occur in response to unilateral muscle overuse leading to myositis bilaterally. TNF-alpha is likely to have pro-inflammatory and destructive effects but also to have effects in the muscle regenerative processes. The occurrence of an early involvement of the TNF-alpha system contralaterally to the injury side shows a new aspect of importance of this system in inflammation.展开更多
OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) o...OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) of normal human were isolated using magnetic cell separation(MACS) by a positive selection.B cells(107 cells·mL^(-1)) were stimulated by BAFF(100 ng·mL^(-1))or TNF-alpha(100 ng·mL^(-1)) for two hours,and then were treated with CP-25(10-5 mol·L^(-1)) or Rituximab(5 μg·mL^(-1)) or Etanercept(10 μg·mL^(-1)).B cell proliferation was detected by CCK-8.B cell subsets and BAFF receptors(BAFFR,BCMA and TACI) were analyzed by flow cytometry.The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry.The expression of MKK3,MKK6,P-p38,P-p65,TRAF2 and p100/52 was analyzed by Western blotting.RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept reduced the percentage and numbers of CD19^+B cells,CD19^+CD20^+B cells,CD19^+CD27^+B cells and CD19^+CD20^+CD27^+B cells induced by BAFF or TNF-alpha.CP-25 down-regulated the high expression of BAFFR,BCMA and TACI stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated the expression of MKK3,P-p38,P-p65,TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha.CONCLUSION CP-25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway.This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.展开更多
Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. ...Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.展开更多
Activation-induced cytidine deaminase(AID)is required for the generation of antibody diversity through initiat-ing both somatic hypermutation(SHM)and class switch recombination.A few research groups have success-fully...Activation-induced cytidine deaminase(AID)is required for the generation of antibody diversity through initiat-ing both somatic hypermutation(SHM)and class switch recombination.A few research groups have success-fully used the feature of AID for generating mutant li-braries in directed evolution of target proteins in B cells in vitro.B cells,cultured in suspension,are not con-venient for transfection and cloning.In this study,we established an AID-based mutant accumulation and sorting system in adherent human cells.Mouse AID gene was first transfected into the human non-small cell lung carcinoma H1299 cells,and a stable cell clone(H1299-AID)was selected.Afterwards,anti-hTNF-αscFv(ATscFv)was transfected into H1299-AID cells and ATscFv was displayed on the surface of H1299-AID cells.By 4-round amplification/flow cytometric sorting for cells with the highest affinities to hTNF-alpha,two ATscFv mutant gene clones were isolated.Compared with the wild type ATscFv,the two mutants were much more efficient in neutralizing cytotoxicity of hTNF-alpha.The results indicate that directed evolution by somatic hypermutation can be carried out in adherent non-B cells,which makes directed evolution in mammalian cells easier and more efficient.展开更多
目的探讨肿瘤坏死因子(TNF)-α拮抗剂治疗自身免疫性疾病患者诱发或加重银屑病的临床特征、治疗和预后。方法计算机检索Medline、Springerlink、Sciencedirect、Wiley、Web of Science、CNKI、万方数据库和CBM数据库,纳入国内外文献中...目的探讨肿瘤坏死因子(TNF)-α拮抗剂治疗自身免疫性疾病患者诱发或加重银屑病的临床特征、治疗和预后。方法计算机检索Medline、Springerlink、Sciencedirect、Wiley、Web of Science、CNKI、万方数据库和CBM数据库,纳入国内外文献中公开发表的TNF-α拮抗剂治疗中诱发或加重银屑病患者的临床资料进行荟萃分析。结果本研究纳入27篇文献,共78例患者[33例类风湿关节炎、18例克罗恩病、9例银屑病性关节炎、9例强直性脊柱炎、2例adamantiades-beh?et病和2例幼年特发性关节炎,血清阴性脊柱关节病、溃疡性结肠炎、血清阴性脊柱关节病合并克罗恩病,白塞病、SAPHO综合征各1例]。临床特征如下:(1)女性多见;以中老年为主;(2)临床常用的TNF-α拮抗剂依那西普、英夫利昔单抗和阿达木单抗均可诱发银屑病皮损;(3)出现不良反应时间差异较大,4 d~72个月,但大多数患者在治疗的第1年内出现银屑病皮损。(4)新发银屑病类型主要是脓疱性银屑病,其中掌跖脓疱病最常见,其次为寻常性银屑病;(5)以局部使用糖皮质激素治疗为主,多数患者皮损可改善,少数严重者需要全身治疗,也有少数患者需更换为另外一种TNF-α拮抗剂或中止TNF-α拮抗剂治疗;(6)多数患者皮损的临床特点与组织病理学特点相符;(7)少数患者有个人及家族银屑病史;(8)少数患者有吸烟史。结论在自身免疫性疾病患者中,TNF-α拮抗剂可诱发或加重银屑病。临床上应该密切观察可能出现的不良反应,根据患者具体情况,选择最佳治疗方法。展开更多
目的:观察穴位贴敷治疗气滞血瘀型带状疱疹后遗神经痛(PHN)的临床疗效及对患者血清炎性因子和5-羟色胺(5-HT)的影响。方法:将136例PHN患者随机分为观察组(68例,脱落6例)和对照组(68例,脱落5例)。观察组给予消肿止痛贴+中药细粉穴位贴敷...目的:观察穴位贴敷治疗气滞血瘀型带状疱疹后遗神经痛(PHN)的临床疗效及对患者血清炎性因子和5-羟色胺(5-HT)的影响。方法:将136例PHN患者随机分为观察组(68例,脱落6例)和对照组(68例,脱落5例)。观察组给予消肿止痛贴+中药细粉穴位贴敷治疗,穴取三阴交(双侧)、神阙、阿是穴,三阴交每次贴敷30 min,7 d 1次,神阙、阿是穴每次贴敷6~8 h,1 d 1次;对照组在支配相应痛区神经节段的夹脊穴注射甲钴胺注射液,每次1 mL,1 d 1次。均7 d为一疗程,共治疗4个疗程。观察两组患者治疗前后疼痛视觉模拟量表(VAS)评分、健康状况调查简表(SF-36)评分、中医证候积分和血清炎性因子[单核细胞趋化蛋白-1(MCP-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)]、5-HT含量,并评定两组临床疗效。结果:治疗后,两组患者VAS评分、中医证候积分及血清MCP-1、IL-6、TNF-α、5-HT含量均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05);两组患者SF-36评分较治疗前升高(P<0.05),且观察组高于对照组(P<0.05)。观察组总有效率为74.2%(46/62),高于对照组的52.4%(33/63,P<0.05)。结论:消肿止痛贴+中药细粉穴位贴敷治疗气滞血瘀型PHN疗效较好,能减轻患者症状,提高生活质量,并降低血清MCP-1、IL-6、TNF-α、5-HT含量。展开更多
文摘Ami To investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells （DCs） and the effect of CP-25. Method Bone marrow DCs were isolated and stim- ulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha- TRADD-TRAF2-NF-KB in DCs were analyzed. Result Both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 （ 10 -5, 10 -6 , 10 -7 mol/L ） decreased significantly the ex- pressions of CD40, CD80, CD83, CD86 and MHC- ]I , increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-KB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-KB expression of DCs. CP-25 （10^-5, 10^-6, 10^-7 mol/L） decreased the expressions of EP4 and NF-KB, increased cAMP level in DCs stimulated by PGE2. CP-25 （10^-5 10^-6 10^-7 mol/L） also could down-regulate significantly TNFR1 TRADD TRAF2 and NF-KB expression in DCs stimulated by TNF-alpha. Conclusion PGE2 and TNF-alpha could enhance DCs func- tions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-KB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD- TRAF2-NF-KB pathways.
文摘Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and-8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 μg/kg;1 μg/kg and 3 μg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and-8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 μg/kg and 1 μg/ kg as compared to the placebo group. In contrast, the 3 μg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and-8 is reduced in the ischemic region in groups 0.1 and 1 μg/ kg as compared to the placebo group whereas activity in the 3 μg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.
文摘Objective:To explore the changes of serum TNF-alpha, IL-2 and IL-13 in patients with rheumatoid arthritis (RA).Methods: A total of 60 patients with rheumatoid arthritis admitted to our hospital from December 2016 to December 2017 were selected as the observation group, and another 60 healthy people in the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) double antibody sandwich method was used to detect the changes of serum TNF-α, IL-2 and IL-13 in the observation group before and after treatment, and was correlated with rheumatoid arthritis disease activity index, plasma ESR, CRP level and DAS28 score.Results:before treatment, serum TNF-α, IL-2 alpha and IL-13 were significantly higher than those in the control group, the observation group of serum TNF-α, IL-2 and IL-13 levels were significantly lower than those before treatment, and compared with the control group, the difference was not statistically significant. Before treatment, the changes of serum TNF-α alpha, IL-2 and IL-13 during the onset of rheumatoid arthritis were positively correlated with the level of plasma ESR, CRP and DAS28.Conclusions:the serum levels of TNF-α, IL-2 and IL-13 in rheumatoid arthritis patients are significantly increased, and are closely related to the activity of rheumatoid arthritis. Patients can be effectively improved after treatment, which is worthy of clinical reference.
基金Financial support has been obtained from the Faculty of Medicine,Umea University,and the J.C.Kempe and Seth M.Kempe Memorial Foundations,Ornskoldsvik
文摘Using a rabbit model leading to myositis in response to exercise-induced muscle overuse, we have previously observed that TNF-alpha is involved in the exercised muscle in early developing myositis as well as both ipsiand contralaterally in the myositis which develops in response to a lengthened period of overuse. It is unknown if TNF-alpha can also be engaged contralaterally in early stages of myositis. The hypothesis was that this is the case. It was therefore evaluated whether the TNF-alpha system is early involved contralaterally. An experimental model of 1 week of overuse of the soleus muscle on one side leading to myositis was used, and in situ hybridization and immunohistochemistry were applied to study the expression patterns of TNF-alpha in the soleus muscle in the contralateral side. TNF-alpha was expressed in the myositis process which occurred contralaterally. There were thus TNF-alpha mRNA reactions in the cells of the inflammatory infiltrates, in blood vessel walls and in certain of the muscle fibers. Parts of the latter were necrotic fibers, whereas others were interpreted to be in a regenerative stage. TNF-alpha immunoreactions were seen for infiltrating white blood cells. The observations show that the TNF-alpha system is early involved in the cross-over effects that occur in response to unilateral muscle overuse leading to myositis bilaterally. TNF-alpha is likely to have pro-inflammatory and destructive effects but also to have effects in the muscle regenerative processes. The occurrence of an early involvement of the TNF-alpha system contralaterally to the injury side shows a new aspect of importance of this system in inflammation.
基金supported by National Natural Science Foundation of China(81330081,81473223and 81673444)Anhui Province Postdoctoral Science Foundation(2016B134)
文摘OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) of normal human were isolated using magnetic cell separation(MACS) by a positive selection.B cells(107 cells·mL^(-1)) were stimulated by BAFF(100 ng·mL^(-1))or TNF-alpha(100 ng·mL^(-1)) for two hours,and then were treated with CP-25(10-5 mol·L^(-1)) or Rituximab(5 μg·mL^(-1)) or Etanercept(10 μg·mL^(-1)).B cell proliferation was detected by CCK-8.B cell subsets and BAFF receptors(BAFFR,BCMA and TACI) were analyzed by flow cytometry.The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry.The expression of MKK3,MKK6,P-p38,P-p65,TRAF2 and p100/52 was analyzed by Western blotting.RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept reduced the percentage and numbers of CD19^+B cells,CD19^+CD20^+B cells,CD19^+CD27^+B cells and CD19^+CD20^+CD27^+B cells induced by BAFF or TNF-alpha.CP-25 down-regulated the high expression of BAFFR,BCMA and TACI stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated the expression of MKK3,P-p38,P-p65,TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha.CONCLUSION CP-25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway.This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.
基金supported by National Natural Science Foundation(No.81260315)Foundation of the Education Department of Guangxi Province,China(No.201010LX375)the Foundation of the Nature Science Fund,Guangxi Province,China(No.2012GXNSFBA053121)
文摘Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.
基金funded by grants from the Ministry of Science and Technology of People’s Republic of China(Nos.2011CBA00906 and 2011YQ03013404).
文摘Activation-induced cytidine deaminase(AID)is required for the generation of antibody diversity through initiat-ing both somatic hypermutation(SHM)and class switch recombination.A few research groups have success-fully used the feature of AID for generating mutant li-braries in directed evolution of target proteins in B cells in vitro.B cells,cultured in suspension,are not con-venient for transfection and cloning.In this study,we established an AID-based mutant accumulation and sorting system in adherent human cells.Mouse AID gene was first transfected into the human non-small cell lung carcinoma H1299 cells,and a stable cell clone(H1299-AID)was selected.Afterwards,anti-hTNF-αscFv(ATscFv)was transfected into H1299-AID cells and ATscFv was displayed on the surface of H1299-AID cells.By 4-round amplification/flow cytometric sorting for cells with the highest affinities to hTNF-alpha,two ATscFv mutant gene clones were isolated.Compared with the wild type ATscFv,the two mutants were much more efficient in neutralizing cytotoxicity of hTNF-alpha.The results indicate that directed evolution by somatic hypermutation can be carried out in adherent non-B cells,which makes directed evolution in mammalian cells easier and more efficient.
文摘目的探讨肿瘤坏死因子(TNF)-α拮抗剂治疗自身免疫性疾病患者诱发或加重银屑病的临床特征、治疗和预后。方法计算机检索Medline、Springerlink、Sciencedirect、Wiley、Web of Science、CNKI、万方数据库和CBM数据库,纳入国内外文献中公开发表的TNF-α拮抗剂治疗中诱发或加重银屑病患者的临床资料进行荟萃分析。结果本研究纳入27篇文献,共78例患者[33例类风湿关节炎、18例克罗恩病、9例银屑病性关节炎、9例强直性脊柱炎、2例adamantiades-beh?et病和2例幼年特发性关节炎,血清阴性脊柱关节病、溃疡性结肠炎、血清阴性脊柱关节病合并克罗恩病,白塞病、SAPHO综合征各1例]。临床特征如下:(1)女性多见;以中老年为主;(2)临床常用的TNF-α拮抗剂依那西普、英夫利昔单抗和阿达木单抗均可诱发银屑病皮损;(3)出现不良反应时间差异较大,4 d~72个月,但大多数患者在治疗的第1年内出现银屑病皮损。(4)新发银屑病类型主要是脓疱性银屑病,其中掌跖脓疱病最常见,其次为寻常性银屑病;(5)以局部使用糖皮质激素治疗为主,多数患者皮损可改善,少数严重者需要全身治疗,也有少数患者需更换为另外一种TNF-α拮抗剂或中止TNF-α拮抗剂治疗;(6)多数患者皮损的临床特点与组织病理学特点相符;(7)少数患者有个人及家族银屑病史;(8)少数患者有吸烟史。结论在自身免疫性疾病患者中,TNF-α拮抗剂可诱发或加重银屑病。临床上应该密切观察可能出现的不良反应,根据患者具体情况,选择最佳治疗方法。
文摘目的:观察穴位贴敷治疗气滞血瘀型带状疱疹后遗神经痛(PHN)的临床疗效及对患者血清炎性因子和5-羟色胺(5-HT)的影响。方法:将136例PHN患者随机分为观察组(68例,脱落6例)和对照组(68例,脱落5例)。观察组给予消肿止痛贴+中药细粉穴位贴敷治疗,穴取三阴交(双侧)、神阙、阿是穴,三阴交每次贴敷30 min,7 d 1次,神阙、阿是穴每次贴敷6~8 h,1 d 1次;对照组在支配相应痛区神经节段的夹脊穴注射甲钴胺注射液,每次1 mL,1 d 1次。均7 d为一疗程,共治疗4个疗程。观察两组患者治疗前后疼痛视觉模拟量表(VAS)评分、健康状况调查简表(SF-36)评分、中医证候积分和血清炎性因子[单核细胞趋化蛋白-1(MCP-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)]、5-HT含量,并评定两组临床疗效。结果:治疗后,两组患者VAS评分、中医证候积分及血清MCP-1、IL-6、TNF-α、5-HT含量均较治疗前降低(P<0.05),且观察组低于对照组(P<0.05);两组患者SF-36评分较治疗前升高(P<0.05),且观察组高于对照组(P<0.05)。观察组总有效率为74.2%(46/62),高于对照组的52.4%(33/63,P<0.05)。结论:消肿止痛贴+中药细粉穴位贴敷治疗气滞血瘀型PHN疗效较好,能减轻患者症状,提高生活质量,并降低血清MCP-1、IL-6、TNF-α、5-HT含量。
