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1.
Rheumatol Ther ; 9(5): 1347-1359, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35867262

RESUMO

INTRODUCTION: Non-specific chronic sialadenitis (NSCS) is a common pathology of labial salivary glands (LSGs), and NSCS with positive anti-SSA/SSB antibodies is common in clinical practice. Previous studies have evaluated the associations of high focus score (FS) with clinical manifestations in primary Sjögren's syndrome (pSS) patients extensively, but the characteristics of pSS with NSCS have seldom been investigated. We here analyzed the characteristics of pSS patients with NSCS. METHODS: Among 425 patients who underwent LSG biopsies, 217 had pSS and 37 non-SS sicca patients had NSCS without other diseases (i.e., sicca controls). We categorized these 217 pSS patients into three groups based on the pathology of LSGs: FS ≥ 1 (n = 104), 0 ≤ FS < 1 (n = 76), and NSCS (n = 37). We then compared the three groups while focusing on the NSCS group. Multivariate logistic regression analysis was performed to identify variables that influenced NSCS. RESULTS: The mean age of pSS patients with NSCS (58.3 ± 11.0 years) was significantly higher than those with FS ≥ 1 (48.5 ± 14.9 years) and 0 ≤ FS < 1 (45.3 ± 13.7 years), but other clinical characteristics were similar. NSCS had a significant positive correlation with age (OR = 7.282, 95% CI 2.085-25.44 and OR = 13.130, 95% CI 3.368-51.189 for patients aged 45-64 years and > 65 years, respectively). Significantly higher levels of lymphocytic infiltration were found in the pSS NSCS group than in the sicca NSCS controls (48.6 vs. 10.8%, respectively). CONCLUSIONS: The pSS patients with NSCS were older than corresponding non-NSCS pSS individuals, but they had similar clinical features. NSCS is associated with age and seldom occurred below the age of 45 years, regardless of the presence or absence of pSS. NSCS may be a subtype of pSS in elderly patients.

2.
Chin Med J (Engl) ; 133(8): 892-898, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32187053

RESUMO

BACKGROUND: Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income. METHODS: This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients' treatment satisfaction. RESULTS: When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological disease-modifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032). CONCLUSION: Higher disease severity and higher financial burden were associated with lower patient satisfaction.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Adulto , Antirreumáticos/uso terapêutico , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Índice de Gravidade de Doença , Inquéritos e Questionários
3.
J Clin Rheumatol ; 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389685

RESUMO

BACKGROUND: Intra-articular (IA) injections are an integral part of the management of rheumatoid arthritis (RA). However, there are few reports regarding the association between drug effectiveness and cost. OBJECTIVES: The aim of this study was to assess the cost-effectiveness of various combinations of IA injections of betamethasone, hyaluronic acid (HA) or etanercept for oligoarthritis in RA. METHODS: Seventy RA patients were assigned to 4 groups according to the IA injection drug(s): betamethasone alone, betamethasone + etanercept, betamethasone + HA, or etanercept alone. Data for the following were collected before and after IA injection: erythrocyte sedimentation rate, C-reactive protein (CRP), disease activity score in 28 joints calculated with CRP, and patient global visual analog scale. In addition, power Doppler ultrasonography and gray-scale ultrasonography scores were obtained for synovitis, and passive range of motion of joints was measured. RESULTS: Sixty-eight RA patients completed the trial. Compared with patients given etanercept alone, the visual analog scale, power Doppler ultrasonography, and gray-scale ultrasonography scores of each of the other groups were significantly better at each time point. At 1 month, the passive range of motion of joints in patients given betamethasone + HA was significantly better than that of each of the other groups. Synovial hyperplasia improved significantly in all groups, but less so in those given etanercept alone. All other clinical parameters of the 4 groups were similar. The costs per joint for the betamethasone-alone, betamethasone + etanercept, betamethasone + HA, and etanercept-alone groups were, respectively, $7.55, $181.77, $42.68, and $174.22. CONCLUSIONS: Intra-articular injection of betamethasone alone was the most cost-effective treatment for oligoarthritis of RA. Betamethasone combined with HA injection resulted in the best improvement in joint function.

4.
Curr Drug Targets ; 19(9): 1009-1017, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27550202

RESUMO

Autophagy is an evolutionarily conserved degradation process in triggered by metabolic stress or environmental changes. Autophagy involves formation of autophagosomes, which fuse with lysosomes and degrade encapsulated intracellular components, such as long-lived and misfolded proteins, as well as intracellular organelles. Autophagy has been implicated in a wide variety of physiological and pathological conditions, and was recently implicated in the regulation of immunity and inflammation. Rheumatic diseases are a group of disorders characterized by immune system malfunctions in which the body attacks its own tissues. These diseases can seriously threaten human health if untreated. Although the underlying pathophysiology of autoimmune diseases has not yet been fully elucidated, autophagy has been implicated in their progression. In this article, we review the basics of autophagy, and the functional role of autophagy in the pathogenesis of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Crohn's disease and ankylosing spondylitis (AS). Moreover, we reviewed the role of autophagy and autophagy-related genes (Atgs) in innate and adaptive immunity, as well as the pathogenic crosstalk between autophagy and apoptosis. Our findings should provide valuable insights into the role of autophagy in the pathogenesis of rheumatic diseases. In addition, identification of novel autophagy-associated target proteins may offer a promising target for drugs treating human rheumatic disorders.


Assuntos
Antirreumáticos/farmacologia , Autofagia/imunologia , Doenças Reumáticas/fisiopatologia , Imunidade Adaptativa/imunologia , Animais , Apoptose/imunologia , Desenho de Fármacos , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Terapia de Alvo Molecular , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia
5.
Biochem Biophys Res Commun ; 473(2): 442-8, 2016 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-26970310

RESUMO

Abnormal perpetual inflammatory response and sequential cytokine-induced prostaglandin E2 (PGE2) play important roles in the pathogenesis of rheumatoid arthritis (RA). The underlying regulatory mechanism, however, remain largely unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), an important chromatin modifier that plays a critical role in transcriptional regulation by modifying DNA accessibility for cofactors, was upregulated in human rheumatoid synovial tissues. Furthermore, a knockdown of MTA1 by siRNA in the human fibroblast-like synovial cell line MH7A was found to impair the 4-hydroxynonenal (4-HNE)-induced transcriptional expression levels of certain proinflammatory cytokines including IL-1ß, TNF-α and IL-6. Moreover, endogenous MTA1 was required for the cytokines-induced PGE2 synthesis by rheumatoid synoviocytes. Collectively, the coordinated existence of MTA1 inside distinct cascade loops points to its indispensable role in the modulation of the integrated cytokine network along the pathogenesis of RA. Further exploration of the functional details of this master transcriptional regulator should be an attractive strategy to identify novel therapeutic target for RA and warrants execution.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Dinoprostona/imunologia , Histona Desacetilases/imunologia , Proteínas Repressoras/imunologia , Transdução de Sinais , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Aldeídos/imunologia , Artrite Reumatoide/genética , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , Regulação da Expressão Gênica , Histona Desacetilases/análise , Histona Desacetilases/genética , Humanos , Proteínas Repressoras/análise , Proteínas Repressoras/genética , Membrana Sinovial/metabolismo , Transativadores
6.
Clin Rheumatol ; 34(6): 1073-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25896532

RESUMO

Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). We aimed to investigate the potential of ultrasound to detect early changes after TNF-a antagonist therapy of Achilles enthesitis of AS patients. One hundred AS patients with active disease, requiring TNF-a antagonist therapy, were included (etanercept n = 25, infliximab n = 25, adalimumab n = 25, non-biologic disease-modifying antirheumatic drugs (DMARDs) n = 25). Physical examination was performed to evaluate disease activity and detect Achilles enthesitis and/or retrocalcaneal bursitis. Ultrasound of the Achilles enthesitis was performed bilaterally. Follow-up examinations were performed 3 months after the initiation of therapy. Gray scale (GS) scores, Power Doppler (PD) scores, and total additive scores (TS) decreased significantly during TNF-a antagonist therapy but not in traditional non-biologic traditional DMARDs group. The bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis metrology index (BASMI), bath ankylosing spondylitis functional index (BASFI), and Maastricht ankylosing spondylitis enthesitis score (MASES) all showed significant improvements. When three different TNF-a antagonists were analyzed separately, no significant difference was observed in GS, PD, and total scores. Subclinical Achilles enthesitis, detected only with GS ultrasound, is present in a subset of AS patients and a significant improvement can be demonstrated after 3 months of TNF-a antagonist therapy. Doppler ultrasound provides a reliable estimation to monitor the therapeutic response to TNF antagonists in AS patients with Achilles enthesitis. TNF-a antagonists have been shown to be effective in decreasing ultrasound signs of enthesitis after 3 months of therapy in AS patients.


Assuntos
Tendão do Calcâneo/diagnóstico por imagem , Antirreumáticos/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Adalimumab/uso terapêutico , Adulto , Bursite/diagnóstico por imagem , Estudos de Coortes , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Doenças Reumáticas/diagnóstico por imagem , Doenças Reumáticas/tratamento farmacológico , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico por imagem , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ultrassonografia Doppler
7.
Biol Reprod ; 92(1): 6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25395675

RESUMO

Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol in green tea, exerts antiapoptotic activity and prevents tissue damage against different stimuli. Herein, we investigated the effects of EGCG treatment to simultaneously improve spermatogenesis following ionizing radiation (IR) (at a dose of 2 Gy). Mice were intraperitoneally injected with 50 mg/kg EGCG or vehicle control 3 days prior to the irradiation, and the treatment lasted intermittently for 24 days. Supplement with exogenous EGCG protected against short-term germ cell loss and attenuated IR-elicited testicular oxidative stress. Mechanistically, prosurvival effects of EGCG treatment upon IR stress were regulated, at least in part, via the mitogen-activated protein kinase/BCL2 family/caspase 3 pathway. Consistently, at post-IR Day 21, histological analyses revealed tubule damage, desquamation of germ cells, and impairment of caudal parameters in irradiated testis, which could be significantly improved by intermittent EGCG treatment. In addition, long-term EGCG application ameliorated the IR-induced blood-testicular barrier permeability and suppressed testicular steroidogenesis, thus exerting a stimulatory effect on the spermatogenic recovery. Collectively, EGCG appeared to efficiently prevent germ cells from radiation-induced cell death via multiple mechanisms. Employment of this bioactive polyphenol should be an attractive strategy to preserve fertility in males exposed to conventional radiation therapy and warrants further investigation.


Assuntos
Catequina/análogos & derivados , Lesões por Radiação/prevenção & controle , Radiação Ionizante , Protetores contra Radiação/farmacologia , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Catequina/farmacologia , Citoproteção/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espermatogênese/efeitos da radiação , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Espermatozoides/efeitos da radiação , Testículo/citologia , Testículo/fisiologia , Testículo/efeitos da radiação
8.
Int J Immunogenet ; 42(1): 4-10, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25545293

RESUMO

Human leucocyte antigen (HLA)-B27 expression is correlated with spondyloarthritis (SpA), but its role in disease pathogenesis remains unclear. The aim of the study was to determine whether HLA-B27 free heavy chain (FHC) contributes to SpA pathogenesis. Flow cytometry was used to analyse the FHC expression on CD3+ and CD14+ cells in the peripheral blood (PB) and synovial fluid (SF) from SpA patients, healthy controls, and rheumatoid arthritis (RA) patients. Human monocytic U937 cell lines stably expressing enhanced green fluorescence protein (EGFP)/HLA-B27, EGFP/HLA-A2 or EGFP alone were created to further investigate the relation between HLA-B27 and FHC expression. The relative FHC level on CD14+ PB cells was significantly higher in SpA patients than in controls, but lower than on the SF cells of SpA patients. No significant correlation was found for relative FHC expression with HLA-B27 or ß2-microglobulin expression. HLA-B27-transfected U937 cells expressed higher FHC levels than either EGFP/HLA-A2- or EGFP-transfected cells. HLA class I FHC expression was significantly increased on monocytes of SpA patients and HLA-B27-transfected cells, implying that FHC, perhaps mostly derived from HLA-B27, plays an important role in SpA pathogenesis.


Assuntos
Antígeno HLA-B27/imunologia , Antígenos de Histocompatibilidade Classe I/biossíntese , Cadeias Pesadas de Imunoglobulinas/biossíntese , Monócitos/imunologia , Espondiloartropatias/imunologia , Adolescente , Adulto , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Complexo CD3/metabolismo , Linhagem Celular Tumoral , Feminino , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Antígeno HLA-B27/genética , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Espondiloartropatias/patologia , Líquido Sinovial/citologia , Transfecção , Células U937 , Adulto Jovem , Microglobulina beta-2/biossíntese
9.
Arthritis Res Ther ; 16(6): 478, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25404518

RESUMO

INTRODUCTION: Activated platelets exert a proinflammatory action that can be largely ascribed to their ability to interact with monocytes. However, the mechanisms that promote dynamic changes in monocyte subsets in rheumatoid arthritis (RA) have not been clearly identified. The aim of this study was to determine whether platelet activation and the consequent formation of monocyte-platelet aggregates (MPA) might induce a proinflammatory phenotype in circulating monocytes in RA. METHODS: The surface phenotype of platelets and the frequencies of monocyte subpopulations in the peripheral blood of RA patients were determined using flow cytometry. Platelets were sorted and co-cultured with monocytes. In addition, monocyte activation was assessed by measuring the nuclear factor κB (NF-κB) pathway. The disease activity was evaluated using the 28-joint disease activity score. RESULTS: Platelet activation, circulating intermediate monocytes (Mon2) and MPA formation were significantly elevated in RA, especially in those with active disease status. Furthermore, Mon2 monocytes showed higher CD147 expression and responded to direct cell contact with activated platelets with higher cytokine production and matrix metallopeptidase 9 (MMP-9) secretion, which increased the expression of CD147. After the addition of specific antibodies for CD147, those effects were abolished. Furthermore, the NF-κB-driven inflammatory pathway may be involved in this process. CONCLUSION: These findings indicate an important role of platelet activation and the consequent formation of MPA in the generation of the proinflammatory cytokine milieu and for the promotion and maintenance of the pathogenically relevant Mon2 monocyte compartment in RA, which is likely to play an important role in the pathogenesis of autoimmunity.


Assuntos
Artrite Reumatoide/metabolismo , Basigina/metabolismo , Plaquetas/metabolismo , Mediadores da Inflamação/metabolismo , Monócitos/metabolismo , Fenótipo , Adulto , Idoso , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Basigina/genética , Basigina/imunologia , Plaquetas/imunologia , Técnicas de Cocultura , Feminino , Humanos , Mediadores da Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Transdução de Sinais/fisiologia , Adulto Jovem
10.
Rheumatology (Oxford) ; 53(12): 2288-96, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25053832

RESUMO

OBJECTIVES: We aimed to investigate whether CD147 can up-regulate the chemotactic, adhesive and invasive properties of human neutrophils and to determine the mechanism underlying this process. METHODS: Human promyelocytic leukaemia cells (HL-60) cells and peripheral blood or synovial fluid neutrophils were isolated from RA patients. Under cyclophilin A (CypA) stimulation, chemotaxis, adhesion potential and invasion ability were assessed using chemotaxis, adhesion and invasiveness assays. Lipid raft isolation and western blot were used to determine the mechanism underlying the effects of CypA stimulation. RESULTS: CD147 up-regulates the calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils in RA patients. Transient receptor potential melastatin 7 may be responsible for this phenomenon. CONCLUSION: These findings suggest that in RA patients, abundant CypA up-regulates the calcium-induced chemotactic, adhesive and invasive properties of neutrophils via direct binding to CD147. Cyclophilin-CD147 interactions might contribute to the destruction of cartilage and bone in RA.


Assuntos
Artrite Reumatoide/imunologia , Basigina/imunologia , Cálcio/imunologia , Neutrófilos/imunologia , Canais de Cátion TRPM/imunologia , Adulto , Idoso , Basigina/genética , Adesão Celular/imunologia , Diferenciação Celular/imunologia , Células Cultivadas , Quimiotaxia de Leucócito/imunologia , Feminino , Células HL-60 , Humanos , Masculino , Microdomínios da Membrana/imunologia , Pessoa de Meia-Idade , Infiltração de Neutrófilos/imunologia , Proteínas Serina-Treonina Quinases , Interferência de RNA , Canais de Cátion TRPM/genética , Regulação para Cima/imunologia , Adulto Jovem
11.
Curr Pharm Des ; 19(27): 4893-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23343120

RESUMO

This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell (hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. The hUCB-MSCs were directly injected into the quadriceps thigh muscles in patients with foot disease (cell quantity at 2 x 106 per point). Physical attributes, blood cytokines, blood glucose and insulin dosage were evaluated before treatment and 1, 2, 4, 8, and 12 weeks thereafter. The ratios of Treg/Th17, Treg/Th1, and Th17/Th1 cells were measured using flow cytometry and their correlation with various cytokines (FoxP3, IL-17, INF-γ, C-RP, TNF-α, and VEGF) was scrutinized. Levels of blood glucose and insulin dosage were significantly reduced in all 15 patients following hUCB-MSC transplantation. The ratios of CD4⁺CD25(hi)FoxP3⁺ Treg/Th17 and CD4⁺CD25(hi)FoxP3⁺ Treg/Th1 cells were significantly increased 4 weeks after transplantation (p < 0.01), while the ratio of Th17/Th1 cells remained unchanged. Serum levels of VEGF peaked at 4 weeks following transplantation. Levels of C-RP and TNF-α were significantly reduced 4 weeks after transplantation. Intriguingly, the ratios of Treg/Th17 were positively correlated with VEGF levels, and were inversely correlated with plasma IL-6 levels. Our data indicated that immune disorders are associated with the development of type 2 diabetes and its complications. Levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied with improved clinical profiles in diabetic patients. These data favor a role for Treg cells in the onset and progression of T2D.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/terapia , Transplante de Células-Tronco Mesenquimais , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Citocinas/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pé Diabético/sangue , Pé Diabético/imunologia , Monitoramento de Medicamentos , Feminino , Humanos , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Injeções Intramusculares , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Coxa da Perna
12.
Mol Med Rep ; 6(5): 1183-9, 2012 11.
Artigo em Inglês | MEDLINE | ID: mdl-22923041

RESUMO

Improved knowledge of the immunological properties of mesenchymal stem cells (MSCs) creates a potential cell-mediated immunotherapeutic approach for arthritic diseases. The low frequency of MSCs necessitates their in vitro expansion prior to clinical use. As sequential passage has been used as the most popular strategy for expansion of MSCs, the effect of long-term culture on the immunological properties of MSCs is not clear. In this study, we observed that the morphology of MSCs showed the typical characteristics of the Hayflick model of cellular aging during sequential expansion. The growth kinetics of MSCs decreased while the number of MSCs staining positive for SA ß-gal (senescence marker) increased in long-term culture. Although long-term culture exerts less of an effect on the immunophenotype of MSCs, the immunosuppressive effects of MSCs on the allogeneic T-cell proliferation, activation-antigen expression (CD69 and CD25) and cytokine production (IFN-γ, TNF-α, IL-10) were significantly impaired following stimulation with phytohemagglutinin (PHA).


Assuntos
Células-Tronco Mesenquimais/citologia , Linfócitos T/citologia , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Senescência Celular , Feminino , Humanos , Imunofenotipagem , Interferon gama/metabolismo , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
13.
Biochem Biophys Res Commun ; 422(2): 238-44, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22575453

RESUMO

The blood CD4(+) CXCR5(+) T cells, known as "circulating" Tfh, have been shown to efficiently induce naïve B cells to produce immunoglobulin. They play an important role in certain autoimmune diseases. In the present study, we show for the first time that the frequency of CD4(+) CXCR5(+) T cells is increased in pSS patients and positively correlated with autoantibodies in the blood. The concentration of Th17-like subsets (CD4(+) CXCR5(+) CCR6(+)) in pSS patients was found to be significantly higher than in healthy controls. Functional assays showed that activated Th17-like subtypes in the blood display the key features of Tfh cells, including invariably coexpressed PD-1, ICOS, CD40L and IL-21. Th17 subsets were found to highly express Bcl-6 protein and Th1 and Th2 were not. Bcl-6 is believed to be a master transforming factor for Tfh cell differentiation and facilitate B cell proliferation and somatic hypermutation within the germinal center. These data indicate that Th17 subsets of CD4(+) CXCR5(+) T cells in the blood may participate in the antibody-related immune responses and that high frequency of CD4(+) CXCR5(+) CCR6(+) Tfh cells in blood may be suitable biomarkers for the evaluation of the active immune stage of pSS patients. It might provide insights into the pathogenesis and perhaps help researchers identify novel therapeutic targets for pSS.


Assuntos
Autoimunidade , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/imunologia , Receptores CCR6/imunologia , Receptores CXCR5/imunologia , Síndrome de Sjogren/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Proteínas de Ligação a DNA/biossíntese , Feminino , Humanos , Interleucinas/biossíntese , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-6 , Síndrome de Sjogren/sangue , Subpopulações de Linfócitos T/efeitos dos fármacos
14.
Int J Radiat Oncol Biol Phys ; 65(2): 435-44, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16690431

RESUMO

PURPOSE: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab'2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. METHODS AND MATERIALS: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. RESULTS: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). CONCLUSION: Iodine (131I) metuximab injection is safe and active for HCC patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Basigina/imunologia , Carcinoma Hepatocelular/radioterapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/radioterapia , Radioimunoterapia/métodos , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Combinação de Medicamentos , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/farmacocinética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade
15.
Arthritis Res Ther ; 8(2): R44, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16507143

RESUMO

Macrophage-like synoviocytes and fibroblast-like synoviocytes (FLS) are known as the most active cells of rheumatoid arthritis (RA) and are close to the articular cartilage in a position enabling them to invade the cartilage. Macrophage-like synoviocytes and FLS expression of matrix metalloproteinases (MMPs) and their interaction has aroused great interest. The present article studied the expression of CD147, also called extracellular matrix metalloproteinase inducer, on monocytes/macrophages and FLS from RA patients and its potential role in enhancing MMPs and the invasiveness of synoviocytes. Expression of CD147 on FLS derived from RA patients and from osteoarthritis patients, and expression of CD147 on monocytes/macrophages from rheumatic synovial fluid and healthy peripheral blood were analyzed by flow cytometry. The levels of CD147, MMP-2 and MMP-9 mRNA in FLS were detected by RT-PCR. The role of CD147 in MMP production and the cells' invasiveness in vitro were studied by the co-culture of FLS with the human THP-1 cell line or monocytes/macrophages, by gel zymography and by invasion assay. The results showed that the expression of CD147 was higher on RA FLS than on osteoarthritis FLS and was higher on monocytes/macrophages from rheumatic synovial fluid than on monocytes/macrophages from healthy peripheral blood. RT-PCR showed that the expressions of CD147, MMP-2 and MMP-9 mRNA was higher in RA FLS than in osteoarthritis FLS. A significantly elevated secretion and activation of MMP-2 and MMP-9 were observed in RA FLS co-cultured with differentiated THP-1 cells or RA synovial monocytes/macrophages, compared with those co-cultured with undifferentiated THP-1 cells or healthy control peripheral blood monocytes. Invasion assays showed an increased number of invading cells in the co-cultured RA FLS with differentiated THP-1 cells or RA synovial monocytes/macrophages. CD147 antagonistic peptide inhibited the MMP production and the invasive potential. Our studies demonstrated that the CD147 overexpression on monocytes/macrophages and FLS in RA patients may be responsible for the enhanced MMP secretion and activation and for the invasiveness of synoviocytes. These findings suggest that CD147 may be one of the important factors in progressive joint destruction of RA and that CD147 may be a potential therapeutic target in RA treatment.


Assuntos
Artrite Reumatoide/metabolismo , Basigina/metabolismo , Metaloproteinases da Matriz/biossíntese , Membrana Sinovial/metabolismo , Adulto , Idoso , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Basigina/genética , Células Cultivadas , Técnicas de Cocultura , Ativação Enzimática/efeitos dos fármacos , Humanos , Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Monócitos/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Peptídeos/farmacologia , RNA Mensageiro/metabolismo , Membrana Sinovial/patologia , Membrana Sinovial/fisiopatologia
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 21(5): 631-3, 2005 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-16143073

RESUMO

AIM: To observe the effects of Compound Muji Powder (CMJP) on chronic patients with hepatitis B. METHODS: 28 chronic patients with hepatitis B were chosen as therapy group who took CMJP and general protecting liver medicine, another 31 patients taking general protecting liver medicine only were taken as control group. Clinic symptom, liver function, serum fibrosis items, parts of immunological items, blood routine test and ultrasound alteration were observed before, after and 3 months after ending of treatment and compared between the two groups. RESULTS: Many detecting items including ALT, AST, r-GT, HA, LN, PCIII, IgG, r-globin, AFP, PLT, thickness of spleen and echogenicity of liver had changed obviously after CMJP application, and parts of these alteration maintained rather long time. CONCLUSION: Since CMJP could play the role of protecting the liver cells, inhibiting liver fibrosis, decreasing AFP level and reducing the enlargement of spleen, it had good curative effects to chronic hepatitis B patients.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Feminino , Hepatite B Crônica/diagnóstico por imagem , Hepatite B Crônica/patologia , Humanos , Masculino , Estudos Retrospectivos , Ultrassonografia
17.
BMC Cell Biol ; 6(1): 25, 2005 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-15904490

RESUMO

BACKGROUND: During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. RESULTS: By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 +/- 31.63) was higher than that of the undifferentiated THP-1 cells (205.1 +/- 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. CONCLUSION: The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1 cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.


Assuntos
Basigina/fisiologia , Diferenciação Celular/fisiologia , Movimento Celular , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Monócitos/citologia , Basigina/genética , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação Enzimática , Regulação da Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Regulação para Cima
18.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 21(1): 120-2, 2005 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15629100

RESUMO

AIM: To observe the positive rate and its clinical significance of serum antibody to ribosomal P protein (anti-P) in patients with systemic lupus erythematosus (SLE). METHODS: Anti-P protein antibody was detected by EURO blot with synthetic full-length ribosomal proteins, and then correlation between anti-P antibody, other autoantibodies and clinical characters was analysed . RESULTS: In 150 SLE patients 36 cases (24%) were positive for anti-P antibody. The incidence of renal and central nervous system lesions in anti-P antibody-positive patients was notably higher than that in anti-P antibody-negative group. The positive rate of anti-P antibody was correlated with that of anti-dsDNA, anti-Sm and anti-RNP antibodies, but had no correlation with the lesions of skin, joint, blood and liver, nor indexes of disease's activity (DAI). CONCLUSION: There is correlation between anti-P antibody level with renal and CNS lesions in SLE patients.


Assuntos
Anticorpos/sangue , Anticorpos/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Proteínas Ribossômicas/imunologia , Adolescente , Adulto , Idoso , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Criança , Feminino , Humanos , Rim/imunologia , Rim/patologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 25(9): 753-5, 2004 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-15555354

RESUMO

OBJECTIVE: To investigate the prevalence and epidemiologic characteristics of seronegative spondyloarthritis (SpAs) in Chinese army force in different areas. METHODS: 4-phase survey was conducted in 21 750 Chinese army, including: face-to-face interviews with standardized COPCORD questionnaires (Phase I screening); further examination on the suspected cases; identification of inflammatory joint and spinal diseases (Phase II); identification of SpAs (AS and uSpA) by more than two experienced specialists in rheumatology; further examination with X-rays and laboratory detection of HLA-B27 (Phase III); and data analysis (Phase IV). RESULTS: Among 21 750 army men, 21 cases of RA, 106 cases of SpAs were identified, with prevalence rates of 0.966 per thousand, 4.87 per thousand respectively. In 106 cases of SpAs, there were 46 cases of ankylosing spondylitis (AS), 52 cases of undifferentiated SpAs (uSpAs) with the prevalence rates of 2.11 per thousand and 2.39 per thousand respectively. Few cases of reactive arthritis (ReA) and Reiter's syndrome (RS) were identified (6 and 1 cases respectively). The prevalence of AS, uSpAs were higher in navy than that in the ground force or the air force. Soldiers in cold and damp areas had higher prevalence rates than that in the plain and drought areas. CONCLUSION: The prevalence of SpA (especially AS and uSpA) in Chinese army force was similar to that in the civilians. SpA (AS and uSpA) was more prevalent seen in the Navy. The incidence of SpA (AS and uSpA) was influenced by environmental factors such as coldness and dampness.


Assuntos
Vértebras Lombares , Militares , Sacro , Espondilartrite/epidemiologia , Adulto , China/epidemiologia , Humanos , Masculino , Prevalência , Proibitinas , Espondilartrite/etiologia
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