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1.
Clin Exp Rheumatol ; 42(7): 1467-1473, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38757280

RESUMO

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.


Assuntos
Espondiloartrite Axial , Sistema de Registros , Uveíte Anterior , Humanos , Uveíte Anterior/epidemiologia , Uveíte Anterior/diagnóstico , Masculino , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , China/epidemiologia , Espondiloartrite Axial/epidemiologia , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/diagnóstico , Prevalência , Antígeno HLA-B27/sangue , Doença Aguda , Fatores de Risco , População do Leste Asiático
2.
Clin Exp Rheumatol ; 40(3): 544-550, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33938794

RESUMO

OBJECTIVES: The objective of this study is to describe the clinical features of patients with axial spondyloarthritis (axial SpA) in the ChinaSpA registry. METHODS: Patients with clinical diagnosis of ankylosing spondylitis (AS) or axial SpA were enrolled into the registry. Patients with a complete set of pelvis radiograph, pelvis MRI and HLA-B27 (Complete Set group, CS group) were further categorised based on classification criteria into AS, radiographic axial SpA (r-axSpA) and non-radiographic axial SpA (nr-axSpA). Early axial SpA was defined as symptom duration of less than three years. Descriptive statistics were used to describe clinical characteristics of enrolled patients. ANOVA analyses were used to compare patients in different groups. RESULTS: A total of 5270 patients were enrolled in the study, and 3223 patients had complete sets of pelvis radiographs, MRIs and HLA-B27 status. Among them, more than 80% patients met both the ASAS criteria for r-axSpA and the modified New York criteria for AS. Among those with early axial SpA, 92% of patients had sacroiliitis on pelvis radiograph, 3.8% had sacroiliitis only on pelvis MRI, and 3.8% were in the clinical arm without any sacroiliitis on imaging studies. Patients in nr-axSpA clinical arm had less diagnosis delay, lower inflammatory markers and ASDAS, compared topatients in the r-axSpA, nr-axSpA MRI arm. CONCLUSIONS: In the ChinaSpA registry, patients in nr-axSpA clinical arm had the shortest diagnostic delay, lower inflammatory markers and ASDAS, but no difference in extra-articular manifestation, compared to patients in the r-axSpA and nr-axSpA MRI arm.


Assuntos
Espondiloartrite Axial , Espondilartrite , Espondilite Anquilosante , Diagnóstico Tardio , Antígeno HLA-B27/genética , Humanos , Sistema de Registros , Espondilartrite/diagnóstico por imagem , Espondilartrite/epidemiologia
3.
Clin Exp Rheumatol ; 37(2): 227-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183595

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) in Chinese patients with active rheumatoid arthritis (RA) and an inadequate response to MTX. METHODS: This 24-week, phase 3, double-blind, placebo-controlled study was conducted in 30 centres across China. A total of 430 patients were randomised 3:1 to receive CZP 200 mg every 2 weeks (loading dose: 400 mg CZP at Weeks 0, 2 and 4) plus MTX or placebo (PBO) plus MTX. The primary endpoint was ACR20 response at Week 24, for which the superiority of CZP+MTX over PBO+MTX was evaluated. Additional parameters for clinical efficacy, health outcomes, immunogenicity and safety were assessed. RESULTS: At Week 24, 54.8% of CZP+MTX patients and 23.9% of PBO+MTX patients achieved ACR20 (odds ratio: 3.9, p<0.001). CZP+MTX patients also achieved greater improvements in HAQ-DI, higher ACR50/70 responses and higher DAS28(ESR) remission rate at Week 24. Rapid onset of response to CZP+MTX was observed as early as Week 1 for most of the clinical, functional and patient-reported outcomes. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment arms. Serious TEAEs were reported by 6.3% of CZP+MTX patients and 2.7% of PBO+MTX patients. No new safety signals were observed. CONCLUSIONS: CZP in combination with MTX showed an acceptable safety profile, a rapid onset of response and sustained effects in reducing the signs and symptoms of RA and improving physical function in Chinese patients with RA and an inadequate response to MTX.


Assuntos
Antirreumáticos , Artrite Reumatoide , Certolizumab Pegol/uso terapêutico , Metotrexato/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , China , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Indução de Remissão , Resultado do Tratamento
4.
Clin Exp Rheumatol ; 36 Suppl 111(2): 88-92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29465347

RESUMO

OBJECTIVES: The commonly adopted method of defining active disease in Takayasu's arteritis (TAK) is the definition used by the US National Institutes of Health (NIH). A gold standard in imaging techniques for assessing disease activity in TAK has not been clearly established and the creation of practical and valid tools represents a challenge. To assess whether 18F-FDG-PET/CT and NIH criteria show a good level of agreement in assessing disease activity of TAK patients. METHODS: 18F-FDG-PET/CT was performed in 17 patients with TAK. All 17 patients fulfilled the clinical criteria according to the American College of Rheumatology criteria. Two nuclear physicians visually assessed the degree of 18F-FDG uptake in the inflammatory vascular lesion. 18F-FDG-PET/CT and the inflammatory vascular lesion were evaluated by using the standardised uptake value (SUV) of 18F-FDG accumulation were interpreted as active vasculitic lesions. RESULTS: Of the 17 patients, 6 were in the active stage and 11 were in the inactive stage according to the level of disease activity as clinically assessed by the NIH criteria. No significant 18F-FDG accumulation was observed in the patients with inactive disease (SUV≤1.2). 18F-FDG-PET/CT localised 18F-FDG accumulation in the inflammatory lesion in the patients with TAK who had inactive disease (n=3) assessed by the NIH criteria. 18F-FDG PET/CT revealed intense 18F-FDG accumulation (SUV max 2.88) in the vasculature of 3 patients in the inactive stage of TAK. The other 8 patients in the active stage showed weak 18F-FDG accumulation (SUV ≤1.2). CONCLUSION: 18FDG-PET/CT appears to be a promising technique for the diagnosis and assessment of disease activity in patients of TAK, even those considered to be inactive by the NIH criteria. However, it needs to be validated in larger groups for cost-effectiveness and sensitivity to change.


Assuntos
Aortite/diagnóstico por imagem , Arterite de Takayasu/diagnóstico por imagem , Adulto , Aortite/etiologia , Cegueira/etiologia , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Tontura/etiologia , Fadiga/etiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , National Institutes of Health (U.S.) , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Arterite de Takayasu/complicações , Arterite de Takayasu/imunologia , Estados Unidos , Adulto Jovem
5.
Clin Exp Rheumatol ; 36(5): 836-840, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29600939

RESUMO

OBJECTIVES: To introduce the Chinese Registry of rhEumatoiD arthrITis (CREDIT), which is the first nationwide, multicentre, online rheumatoid arthritis (RA) registry in China, and to depict major cross-sectional data and treatment strategies of Chinese RA patients. METHODS: RA patients who fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis were recruited into the registry by their rheumatologists from 144 clinical centres in China. Data, including demographics, disease characteristics, co-morbidities, treatment, and adverse reactions, were collected and documented through the predefined protocol. RESULTS: 8071 registered patients (F:M = 4.03:1) were registered up to May 2017. Mean age at symptom onset and at diagnosis was 46.15±14.72y and 48.68±14.54y, respectively. Point prevalence of remission (95% CIs) was 14.88% (14.10-15.66%), 4.23% (3.79-4.66%), 4.25% (3.81-4.69%), and 4.27% (3.83-4.72%) according to DAS28-CRP, CDAI, SDAI, and the 2011 ACR/EULAR remission criteria, respectively. 38.84% and 38.11% of treatment-naïve patients (n=3262) were in moderate (3.25.1) disease activity, respectively. Among treatment-naïve patients, those who were initiated on treatment with bDMARDs had higher disease activity than those who were treated with csDMARDs (p<0.05). Three months after initiating bDMARDs, 19.29% (n=38) of patients achieved remission (DAS28-CRP<2.6). CONCLUSIONS: The CREDIT registry is an effective tool for real-world study of RA patients in China. By providing information for diagnosis and treatment regimen, the CREDIT registry can enhance the application of treat-to-target (T2T) strategy and improve patient outcomes in China.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sistema de Registros , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/tendências , Prevalência , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
6.
Med Sci Monit ; 23: 631-639, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-28157833

RESUMO

BACKGROUND Systemic lupus erythematosus (SLE) leads to renal lesions, which may be clinically silent in patients with little or no proteinuria. Early detection of these lesions may improve prognosis, but early markers are controversial. This study aimed to determine renal marker proteins associated with renal lesion severity in patients with lupus nephropathy (LN) and little or no proteinuria. MATERIAL AND METHODS Patients with LN and little or no proteinuria (<0.5 g/24 hours) (n=187) that underwent kidney biopsy were grouped according to: low severity (Class I or II; n=116) versus high severity (Class III, IV, or V; n=71). Disease status was determined according to the SLE disease activity index (SLEDAI). Renal marker proteins (serum ß2-macroglobulin, urinary ß2-macroglobulin, albumin, IgG, and α1-macroglobulin) were measured using radioimmunoassay. RESULTS Compared with the low severity group, patients in the high severity group had higher urinary albumin (11.60±8.94 versus 7.08±10.07 µg/mL, p=0.008) and urinary IgG (13.21±9.35 versus 8.74±8.90 µg/mL, p=0.007) levels. Multivariate conditional logistic regression analysis showed that urinary albumin (odds ratio (OR)=1.417, 95% confidence interval (95% CI): 1.145-1.895, p=0.001) and SLEDAI (OR=2.004, 95% CI: 1.264-3.178, p=0.003) were independently associated with severe renal lesions in these patients. Using an optimal cutoff point of urinary albumin of 7.53 µg/mL resulted in 67% sensitivity and 82% specificity for the detection of high severity renal lesions. CONCLUSIONS Urinary albumin levels and SLEDAI were independently associated with histological severity of renal lesions in patients with LN and little or no proteinuria. These parameters could be used to help select patients for renal biopsy.


Assuntos
Nefrite Lúpica/urina , Albumina Sérica/metabolismo , Adulto , Albuminúria/patologia , Albuminúria/urina , Biomarcadores/urina , Biópsia , China , Diagnóstico Precoce , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/urina , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Albumina Sérica Humana , Índice de Gravidade de Doença
7.
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
8.
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
9.
Inflamm Res ; 64(8): 637-45, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26115678

RESUMO

OBJECTIVE: The status of B10 cells in patients with rheumatoid arthritis (RA) has not been consistently reported. In this study, we observed the kinetic changes of the B10 cells in collagen-induced arthritis (CIA) mice and the influence of multiple cytokines on the B10 cells to investigate the potential mechanism underlying the changes of B10 cells. METHODS: The kinetic changes of frequency and function of the CD19(+)CD1d(hi)CD5(+) cells in splenic cells were observed during the complete progress of CIA mice. The kinetic changes of cytokines IL-4, IL-6, IL-17A, IL-18, TNF-α, IFN-γ and TGF-ß1 were also detected. Then influence of these cytokines on the status of B10 cells was investigated both in vitro and in vivo. RESULTS: The frequency and suppressive ability of the CD19(+)CD1d(hi)CD5(+) cells increased to its peak on the 14th day while gradually decreased subsequently. IFN-γ showed a similar tendency with the CD19(+)CD1d(hi)CD5(+) cells, whereas IL-6, IL-17A, IL-18, TNF-α, and TGF-ß1 reached its peak on the 28-35th day. In addition, IFN-γ up-regulated while TGF-ß1 down-regulated the frequency and function of the CD19(+)CD1d(hi)CD5(+) cells both in vitro and in vivo. CONCLUSION: The B10 cells in CIA mice could be regulated by IFN-γ and TGF-ß1, suggesting that the status of B10 cells in RA may be influenced by the balance of pro-inflammatory and anti-inflammatory factors, and the impaired B10 cells could be recovered in vitro by adequate treatment before being used for a therapeutic method in clinical practice.


Assuntos
Artrite Experimental/imunologia , Linfócitos B Reguladores/imunologia , Citocinas/imunologia , Animais , Antígenos CD19/imunologia , Antígenos CD1d/imunologia , Artrite Reumatoide/imunologia , Antígenos CD5/imunologia , Cinética , Masculino , Camundongos Endogâmicos DBA , Baço/citologia
10.
Rheumatol Int ; 35(11): 1925-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26248531

RESUMO

Granulomatosis with polyangiitis (GPA), formerly called Wegener's Granulomatosis, is characterized by necrotizing granulomatous inflammation and belongs to the family of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. The main clinical symptoms of GPA are vasculitis primarily involving upper and lower respiratory tracts, as well as kidneys. Gastrointestinal manifestations of GPA are less common (0-20 %), with gastric presentation mimicking a gastric cancer as an initial symptom. This is a descriptive case report of one patient, together with systematic review of the literature. We described a 31-year-old Chinese woman who presented with complaints of abdominal distention, anorexia for 2 months. Gastroscopy was carried out for three times, and stomach cancer was suspected. However, histopathology of gastric biopsy revealed a chronic inflammation with mucosal ulceration, frequent neutrophils and lymphocytes infiltration, and local granulomatous formation, whereas no sign of stomach carcinoma was observed. In view of the positive cANCA test, a diagnosis of GPA was considered. From the onset of the GPA in the patients, no other organs have been involved in the disease. The patient was successfully treated with corticosteroids and cyclophosphamide. As shown in the report, patients who present only with gastrointestinal manifestations represent challenges to diagnosis. ANCA testing can serve as a decisive diagnostic tool. Although uncommon, GI involvement may be a major feature in GPA, sometimes presenting as gastric tumor-like lesions. Diagnosis should be considered in patients presenting with GI symptoms accompanied by evidence of systemic vasculitis, and ANCA test should be used as a diagnostic measurement to clarify differential diagnosis.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Gastropatias/diagnóstico , Neoplasias Gástricas/patologia , Corticosteroides/uso terapêutico , Adulto , Anticorpos Anticitoplasma de Neutrófilos/análise , Biomarcadores/análise , Biópsia , Diagnóstico Diferencial , Feminino , Gastroscopia , Granulomatose com Poliangiite/tratamento farmacológico , Granulomatose com Poliangiite/imunologia , Humanos , Imunossupressores/uso terapêutico , Valor Preditivo dos Testes , Gastropatias/tratamento farmacológico , Gastropatias/imunologia , Resultado do Tratamento
11.
Environ Toxicol ; 30(6): 638-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24376112

RESUMO

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,ß-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,ß-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism.


Assuntos
Acroleína/toxicidade , Poluentes Ambientais/toxicidade , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Aldeídos , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 3/metabolismo , Glutationa/metabolismo , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular , Miocárdio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
12.
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
13.
Pharmacol Res ; 82: 40-50, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24705155

RESUMO

Recent evidence has suggested that cigarette smoking is associated with an increased prevalence of heart diseases. Given that cigarette smoking triggers proinflammatory response via stimulation of the capsaicin-sensitive transient receptor potential cation channel TRPV1, this study was designed to evaluate the effect of an essential α,ß-unsaturated aldehyde from cigarette smoke crotonaldehyde on myocardial function and the underlying mechanism with a focus on TRPV1 and mitochondria. Cardiomyocyte mechanical and intracellular Ca2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90), fura-2 fluorescence intensity (FFI), intracellular Ca2+ decay and SERCA activity. Apoptosis and TRPV1 were evaluated using Western blot analysis. Production of reactive oxygen species (ROS) and DNA damage were measured using the intracellular fluoroprobe 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and 8-hydroxy-2'-deoxyguanosine (8-OHdG), respectively. Our data revealed that crotonaldehyde interrupted cardiomyocyte contractile and intracellular Ca2+ property including depressed PS, ±dL/dt, ΔFFI and SERCA activity, as well as prolonged TR90 and intracellular Ca2+ decay. Crotonaldehyde exposure increased TRPV1 and NADPH oxidase levels, promoted apoptosis, mitochondrial injury (decreased aconitase activity, PGC-1α and UCP-2) as well as production of ROS and 8-OHdG. Interestingly, crotonaldehyde-induced cardiac defect was obliterated by the ROS scavenger glutathione and the TRPV1 inhibitor capsazepine. Capsazepine (not glutathione) ablated crotonaldehyde-induced mitochondrial damage. Capsazepine, glutathione and the NADPH inhibitor apocynin negated crotonaldehyde-induced ROS accumulation. Our data suggest a role of crotonaldehyde compromises cardiomyocyte mechanical function possibly through a TRPV1- and mitochondria-dependent oxidative stress mechanism.


Assuntos
Aldeídos/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Aconitato Hidratase/metabolismo , Animais , Cálcio/metabolismo , Caspase 3/metabolismo , Células Cultivadas , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica , Miócitos Cardíacos/fisiologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Fumar
14.
Artigo em Inglês | MEDLINE | ID: mdl-39305328

RESUMO

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease, which can result in disability in severe cases and endanger physical health. Two microarray datasets related to AS were selected from NCBI for bioinformatics analysis. Differentially expressed genes (DEGs) were screened and protein-protein interaction network was constructed to obtain hub genes. hSMSCs were injected with TNF-α to construct AS cell models. The hSMSCs were transfected with SIGLEC1 siRNA to silence SIGLEC1 expression. CCK-8, western blot, qRT-PCR, and ELISA were performed to detect the effects of SIGLEC1 knockdown on cell proliferation, osteogenic differentiation (ALP, BMP2, Osterix, and Runx2), inflammation (IL-23 and IL-6), and TGF-ß1/SMAD signaling pathway (SMAD3, SMAD7 and TGF-ß1). A TGF-ß1 activator was applied for feedback function assays. A total of 29 common DEGs were screened from GSE181364 and GSE221786, and the key gene SIGLEC1 was selected. Knockdown of SIGLEC1 promoted cell proliferation and inhibited ALP activity, the level of BMP2, Osterix and Runx2 in TNF-α-induced hSMSCs, as well as the decreased inflammatory factors IL-23 and IL-6. Furthermore, knockdown of SIGLEC1 inhibited the expression of TGF-ß1/SMAD signaling pathway related proteins, while the treatment of TGF-ß1 activator weakened the inhibiting effects of sh-SIGLEC1 on the osteogenic differentiation and inflammation in TNF-α-induced hSMSCs. In summary, knockdown of SIGLEC1 promoted cell proliferation and inhibited osteogenic differentiation and inflammation by inhibiting TGF-ß1/SMAD signaling pathway, thereby suppressing the development of AS.

15.
Int J Rheum Dis ; 27(10): e15354, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39352049

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. METHODS: The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. RESULTS: CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. CONCLUSION: Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.


Assuntos
Administração Intravenosa , Doenças do Tecido Conjuntivo , Ciclofosfamida , Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/fisiopatologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Masculino , Administração Oral , Estudos Retrospectivos , Pessoa de Meia-Idade , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/complicações , Resultado do Tratamento , Adulto , Fatores de Tempo , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Capacidade Vital , Recuperação de Função Fisiológica , Idoso , Capacidade de Difusão Pulmonar , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Sedimentação Sanguínea , Tolerância ao Exercício/efeitos dos fármacos , Teste de Caminhada , Proteína D Associada a Surfactante Pulmonar/sangue , Mucina-1/sangue
16.
RMD Open ; 10(3)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313305

RESUMO

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular and cerebrovascular events (CCEs). Furthermore, CCE was a significant factor contributing to mortality in patients with SLE. However, no clinical model exists that can predict which patients are at high risk. The purpose of this study was to develop a practical model for predicting the risk of CCE in people with SLE. METHODS: This study was based on the Chinese SLE Treatment and Research Group cohort. A total of 2399 patients, who had a follow-up period of over 3 years and were diagnosed with SLE for less than 1 year at the start of the study, were included. Cox proportional hazards regression and least absolute shrinkage and selection operator regression were used to establish the model. Internal validation was performed, and the predictive power of the model was evaluated. RESULTS: During the follow-up period, 93 patients had CCEs. The prediction model included nine variables: male gender, smoking, hypertension, age of SLE onset >40, cutaneous involvement, arthritis, anti-ß2GP1 antibody positivity, high-dose glucocorticoids and hydroxychloroquine usage. The model's C index was 0.801. Patients with a prognostic index over 0.544 were classified into the high-risk group. CONCLUSION: We have developed a predictive model that uses clinical indicators to assess the probability of CCE in patients diagnosed with SLE. This model has the ability to precisely predict the risk of CCE in patients with SLE. We recommended using this model in the routine assessment of patients with SLE.


Assuntos
Doenças Cardiovasculares , Transtornos Cerebrovasculares , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Feminino , Adulto , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , China/epidemiologia , Prognóstico , Medição de Risco , Modelos de Riscos Proporcionais , Seguimentos , População do Leste Asiático
17.
Rheumatol Ther ; 11(2): 397-409, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349593

RESUMO

INTRODUCTION: Anemia and malnutrition are recognized indicators of suboptimal physical condition in chronic inflammatory diseases. This study aimed to examine the association between anemia, low body mass index (BMI), and clinical outcomes in axial spondyloarthritis (axSpA). METHOD: This cross-sectional analysis utilized data from the multicenter ChinaSpA cohort. A total of 4146 participants with axSpA were categorized into four groups based on BMI and hemoglobin levels: those with both anemia and low BMI, those with anemia only, those with low BMI only, and those with neither condition. Logistic regression analyses were performed to analyze the association between anemia, low BMI, inflammation status, functional impairment, and disease activity. RESULTS: Anemia was present in 13.94%, low BMI in 11.99%, and both conditions in 2.15% of axSpA participants. Those with both anemia and low BMI showed significantly higher levels of inflammation (hypersensitive C-reactive protein [hsCRP] 30.60 mg/L vs. 8.44 mg/L), functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI] 3.80 vs. 2.10), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 4.52 ± 2.04 vs. 3.67 ± 2.21; Ankylosing Spondylitis Disease Activity Score calculated with C-reactive protein [ASDAS_CRP] 3.51 ± 1.10 vs. 2.62 ± 1.21) compared to those without these conditions. After adjusting for sex and age, significant associations were observed between elevated hsCRP levels and the presence of low BMI (odds ratio [OR] 1.44, 95% CI 1.17-1.78), anemia (OR 1.91, 95% CI 1.56-2.32), and their concurrent presence (OR 3.59, 95% CI 2.22-5.80). Similarly, increased BASFI was significantly associated with low BMI (OR 1.57, 95% CI 1.25-1.97), anemia (OR 1.47, 95% CI 1.19-1.80), and their combination (OR 3.11, 95% CI 2.02-4.78). CONCLUSION: All-cause anemia and low BMI are prevalent complications in patients with axSpA, exhibiting a significant correlation with elevated inflammation status and functional impairment. The simultaneous occurrence of anemia and low BMI particularly exacerbates clinical outcomes, emphasizing the critical role of comprehensive nutritional assessment and management in the therapeutic strategy for axSpA.

18.
Clin Exp Pharmacol Physiol ; 40(7): 398-403, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23590223

RESUMO

Dual antiplatelet therapy is essential for the management of acute coronary syndrome. In particular, combination therapy using aspirin with a platelet ADP (i.e. P2Y12 ) receptor inhibitor, such as clopidogrel, prasugrel or, more recently, ticagrelor, has been recommended for patients with acute coronary syndrome. Pharmacological agents that reversibly inhibit platelet aggregation without metabolic activation in the liver are believed to reduce cardiovascular mortality compared with the current drug of choice for antiplatelet therapy, namely clopidogrel. These findings are based on a multicentre, double-blind, double-dummy, randomized controlled trial. Numerous factors are postulated to contribute to the improved survival of patients who take ticagrelor compared with those taking clopidogrel, including the risk of myocardial infarction, heart failure, arrhythmia and bleeding. In addition, clopidogrel may lead to a much higher incidence of infection. Although ticagrelor has recently been approved for use in the US and exhibits superiority over other antiplatelet agents, certain concerns remain regarding its use, including lung injury and dyspnoea, thus raising the issue of its true superiority over clopidogrel or prasugrel. Recent studies into ticagrelor report conflicting data, with certain aspects of its mechanisms of action still not fully understood. Ticagrelor has beneficial effects following its clinical application, such as achieving overall higher reductions in mortality compared with the use of clopidogrel and prasugrel. Harmful effects associated with the use of ticagrelor include a higher incidence of dyspnoea and major bleeding compared with clopidogrel.


Assuntos
Adenosina/análogos & derivados , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Adenosina/efeitos adversos , Adenosina/uso terapêutico , Plaquetas/efeitos dos fármacos , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Ticagrelor
19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(3): 281-286, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36946354

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple tissues and organs. Frequent flare has been regarded as one of the main problems in the diagnosis and treatment of SLE, while the causes for frequent flare has remained to be unclear. We summarized the survival status and the situation of recurrence of SLE patients. The research progress regarding the recurrence and its mechanism will be reviewed from the aspects of genetic factors, environmental factors (i.e. infection, ultraviolet, vitamin D, chemical pollutants), drug and patient compliance, systemic damage and disease status, sex hormones and pregnancy, and social psychology. The implication is to explore effective clinical intervention to alleviate the SLE disease and improve the living quality of the patients.


Assuntos
Lúpus Eritematoso Sistêmico , Feminino , Humanos , Gravidez , Lúpus Eritematoso Sistêmico/diagnóstico , Recidiva
20.
Clin Rheumatol ; 42(5): 1327-1338, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36609932

RESUMO

OBJECTIVE: To identify the alterations of CD8+ T cells in blood and labial salivary glands (LSGs) of patients with Primary Sjögren's syndrome (pSS). METHODS: Blood samples from 24 pSS patients were assayed for CD38+ HLA-DR+ CD8+ (activated CD8+, aCD8+) T cells and serum IFN-γ and TNF-α, using flow cytometry and ELISA respectively, and compared with samples from 27 healthy controls. Immunohistochemistry was used to count CD8+ T cells in LSG tissues of 24 pSS patients and of 6 control patients with normal pathology. RESULTS: pSS patients had more aCD8+ T cells than aCD4+ T cells (medians 33.13% vs. 9.43%, p < 0.0001), and had an increased level of aCD8+ T cells (medians 33.13% vs. 16.48%, p < 0.0001) and serum IFN-γ (medians 1026 pg/mL vs. 0.00 pg/mL, p < 0.0001) compared to the healthy controls. The levels of aCD8+ T cells and IFN-γ were both significant positively correlated with European League Against Rheumatism Sjögren's Syndrome Disease Activity Index, IgG, anti-nuclear antibodies, rheumatoid factor. The LSGs focus score (FS) ≥1 group had more CD8+ T cell counts than 0≤ FS <1 group and control group (medians 256/mm2 vs. 126/mm2 and 256/mm2 vs. 64/mm2 respectively, both p < 0.05). CONCLUSION: The aCD8+ T cells and IFN-γ are positively correlated with each other, and predominantly elevated in the blood of pSS patients. In the LSG tissues of pSS, CD8+ T cell counts increase with severity of the lesions. CD8+ T cells may play crucial role in the pathogenesis of pSS. Key Points • Primary Sjögren's syndrome (pSS) is a chronic and systemic autoimmune disease. pSS patients had elevated blood levels of CD38 + HLA-DR+ CD8+ T cells and IFN-γ. • The CD38 + HLA-DR+ CD8+ T cells positively correlated with disease parameters and serum IFN-γ. • The salivary glands of pSS patients had appreciable CD8 + lymphocyte infiltration. CD8+ T cells may play crucial role in the pathogenesis of pSS.


Assuntos
Síndrome de Sjogren , Humanos , Linfócitos T CD8-Positivos , Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Antígenos HLA-DR
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