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1.
J Cell Mol Med ; 24(2): 1658-1669, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821687

RESUMO

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)-associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR-7 expression was down-regulated in lung tissue of PM group than control group, and NETs further decreased miR-7 expression. TLR9 and Smad2 were up-regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA-treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR-7 and Smad2 in LF. Finally, miR-7-Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM-related ILD, and TLR9-miR-7-Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.

2.
Int J Clin Pharmacol Ther ; 57(10): 500-505, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426902

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of low-dose rituximab in the treatment of hematologic abnormalities in patients with connective tissue disease. MATERIALS AND METHODS: A total of 13 patients with connective tissue disease who did not respond to prednisolone and multiple immunosuppressive agents, or their disease recurred after treatment, were given 100 mg of rituximab only combined with prednisolone once a week for 4 weeks. Then, the therapeutic effects and adverse reactions were respectively observed in the 13 patients. RESULTS: Rituximab showed good and rapid efficacy in the treatment of refractory thrombocytopenia and autoimmune hemolytic anemia caused by systemic lupus erythematosus, Sjögren's syndrome, and mixed connective tissue disease. Only 1 patient had urinary tract infection. During 24-month follow-up, disease recurred in 7 patients who still responded to azathioprine/Tripterygium wilfordii. CONCLUSION: Low-dose rituximab has good efficacy and safety in the treatment of hematologic abnormalities in patients with connective tissue disease.


Assuntos
Doenças do Tecido Conjuntivo/tratamento farmacológico , Rituximab/uso terapêutico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/etiologia , Anticorpos Monoclonais Murinos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Sjogren/complicações , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(32): e16682, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393368

RESUMO

Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ±â€Š20.7 mg/day to 55.0 ±â€Š11.1 mg/day after 2-week treatment, and to 3.3 ±â€Š2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Metotrexato/administração & dosagem , Doença de Still de Início Tardio/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Antirreumáticos/farmacologia , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Resultado do Tratamento
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(8): 1118-1122, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28871954

RESUMO

Objective To detect the serum levels of IL-25 and IL-17 in rheumatoid arthritis (RA) patients and investigate the potential relationship with bone erosion and concomitant interstitial lung disease (ILD). Methods The study enrolled a total of 117 RA patients and 56 healthy subjects as controls. The serum levels of IL-25 and IL-17 were determined by ELISA, and rheumatoid factor (RF) was detected by turbidimetric immunoassay, anticyclic citrullinated peptide (anti-CCP) antibody as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also tested. ILD was identified on high-resolution computed tomography (HR-CT), the degree of bone erosion was inspected by musculoskeletal ultrasonography, and radiographic grade was graded by Sharp-van der Heijde Score (SHS). Disease activity in RA was scored with the DAS28 and visual analogue scale (VAS). Correlation analysis was used to evaluate the correlations of IL-25 and IL-17 in different groups. Results Compared with healthy control group, the serum levels of IL-25 and IL-17 increased significantly in the patients with RA. Compared with bone erosion negative group, the serum level of IL-25 was higher significantly in bone erosion group. The level of IL-25 was higher in the ILD group of RA patients than the non-ILD group. In addition, there were positive correlations between the serum level of IL-25 and RF-IgG (r=0.285), RF-IgA (r=0.314), RF-IgM (r=0.380). Meanwhile, the serum level of IL-17 had the positive correlations with RF-IgG (r=0.198) and RF-IgM (r=0.273). Both of them had no correlations with anti-CCP antibody. Conclusion The serum level of IL-25 is raised in RA patients with bone erosion and ILD.


Assuntos
Artrite Reumatoide/imunologia , Doenças Ósseas/imunologia , Interleucina-17/sangue , Doenças Pulmonares Intersticiais/imunologia , Adulto , Idoso , Anticorpos Anti-Proteína Citrulinada/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangue
5.
J Zhejiang Univ Sci B ; 18(7): 605-614, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28681585

RESUMO

OBJECTIVE: Low-density granulocytes (LDGs) can form neutrophil extracellular traps (NETs) spontaneously and excessively. When peripheral blood mononuclear cells (PBMCs) are used for studying T lymphocytes, LDGs contained in the PBMCs may decrease the threshold of activating T lymphocytes by forming NETs. This study focused on the profiles of LDGs in common autoimmune diseases and methods for removing LDGs from PBMCs. METHODS: The percentages of LDGs in PBMCs from 55 patients with dermatomyositis (DM), 15 with polymyositis (PM), 42 with rheumatoid arthritis (RA), 25 with systemic lupus erythematosus (SLE), and 19 healthy controls were determined by flow cytometry. Three methods of removing LDGs were explored and compared. After removal, PBMCs from six patients with positive T-SPOT.TB were tested again to find out if LDGs contained in the PBMCs could influence T lymphocyte reactions. RESULTS: Significantly higher LDG percentages were found in PBMCs from patients with DM ((8.41±10.87)%, P<0.0001), PM ((8.41±10.39)%, P<0.0001), RA ((4.05±6.97)%, P=0.0249), and SLE ((7.53±11.52)%, P=0.0006), compared with the controls ((1.28±0.73)%). The T-SPOT.TB values significantly decreased after LDGs were removed. Increasing relative centrifugal force (RCF) within a limited range can decrease the LDG percentage from an initial high level, but not markedly increase the LDG clearance rate. Compared with the whole blood sediment method, the PBMC adherence method can significantly remove LDGs yet scarcely influence the T lymphocyte percentage in PBMCs. CONCLUSIONS: The LDG percentage in PBMCs is significantly increased in patients with SLE, DM, PM, and RA. The influence of LDGs on T lymphocytes cannot be ignored in PBMC cultures. The adherence method is a simple and easy-to-use method for removing LDGs and purifying T lymphocytes from PBMCs.


Assuntos
Separação Celular/métodos , Granulócitos/citologia , Leucócitos Mononucleares/citologia , Linfócitos T/citologia , Adulto , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Adesão Celular , Dermatomiosite/sangue , Feminino , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos , Polimiosite/sangue
6.
Mod Rheumatol ; 27(1): 122-129, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27171278

RESUMO

OBJECTIVE: We previously found that neutrophil extracellular traps (NETs) were associated with interstitial lung disease (ILD) in dermatomyositis (DM) patients. However, it is unclear whether low-density granulocytes (LDGs), endowed with enhanced NET formation capabilities, contribute to the pathogenesis of ILD. This study aims to elucidate the relationship between LDGs and DM-associated ILD. METHODS: We recruited 48 DM patients (28 with ILD) as well as 19 healthy volunteers for this study. The percentage of LDGs in peripheral blood mononuclear cells (PBMCs) was ascertained by flow cytometry. Plasma cfDNA was measured by using the Quant-iT PicoGreen dsDNA Kit and plasma LL-37 was tested by using the LL-37 ELISA kit. RESULTS: The percentage of LDGs was 7.1 times higher in DM patients than in healthy controls. LDG percentage was 2.7 times higher in DM patients with ILD than in DM patients without ILD. Additionally, LDG percentage positively correlated with MYOACT lung disease activity scores, and NET/neutrophil-related marker levels (LL-37, cfDNA, MPO, and MMP-8) in the DM group were significantly higher than those in the control group. CONCLUSION: The abnormal increase of LDGs may exacerbate abnormal NET regulation and further contribute to the pathogenesis of ILD in DM patients by abnormally forming NETs.


Assuntos
Dermatomiosite/sangue , Granulócitos/patologia , Leucócitos Mononucleares/patologia , Doenças Pulmonares Intersticiais/sangue , Adulto , Biomarcadores/sangue , Dermatomiosite/complicações , Feminino , Citometria de Fluxo , Humanos , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade
7.
Zhongguo Gu Shang ; 30(6): 576-580, 2017 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29424183

RESUMO

During choosing non-steroidal anti-inflammatory drugs(NSAIDs), risk factors should be evaluated in elder patients with rheumatoid arthritis. The present study focused on biological therapies, and elderly patients should be more concerned about the risk of infection when used it. Traditional Chinese medicine has advantages of obvious curative effect, especially for tripterygium wilfordii, large clinical trial on western and Chinese medical accurate drug strategies for old patients with rheumatoid arthritis. Old patients are easier to suffer from cardiac diseases and interstitial lung disease, rheumatoid arthritis could be controlled along with the treatment for coexistent disease. The incidence of rheumatoid arthritis in old patients is the same with other RA, and need to treat to target based on the aim of relieve pain and reduce activity of diseases, while the clinical charteristic and treatment target in elder patients with rheumatoid arthritis were not similar with other aged patient, so treatment standard target would vary with aging. Resent clinical studies excluded old patients, lead to lack of evidence-based medicine data. Clinical study for elder patients with rheumatoid arthritis are energetically carrying out, and could provide base and guide for clinical treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/terapia , Medicina Tradicional Chinesa , Tripterygium , Fatores Etários , Idoso , Humanos
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(9): 1204-1208, 2016 08 20.
Artigo em Chinês | MEDLINE | ID: mdl-27687651

RESUMO

OBJECTIVE: To investigate the potential role of deoxyribonuclease I (DNase I) in the pathogenesis of rheumatoid arthritis (RA). METHODS: DNase I activity was measured by radial enzyme-diffusion method in serum samples from 83 RA patients and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and 38 patients with other inflammatory arthritis. SF cfDNA level was measured with Pico Green Kit, and the correlation among DNase I activity, cfDNA level and clinical parameters of RA patients was analyzed. RESULTS: Serum DNase I activity was significantly lower in RA patients than in the healthy control subjects (0.3065∓0.1436 vs 0.4289∓0.1976 U/mL, P<0.001), and was negatively correlated with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in RA patients was significantly higher than that in patients with osteoarthritis (100.81∓142.98 vs 18.98∓31.40 µg/mL, P=0.002), but similar to that in patients with AS (45.85∓47.67 µg/mL, P=0.428) and GA (162.95∓97.49 µg/mL, P=0.132). In patients with inflammatory arthritis, SF cfDNA level was positively correlated with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002). CONCLUSION: Impairment of DNase I activity may be responsible for the enhanced NETs generation and plays a role in the pathogenesis of RA.


Assuntos
Artrite Reumatoide/enzimologia , Desoxirribonuclease I/sangue , Desoxirribonuclease I/metabolismo , Líquido Sinovial/enzimologia , Artrite Gotosa/sangue , Artrite Gotosa/enzimologia , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Humanos , Osteoartrite/sangue , Osteoartrite/enzimologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/enzimologia
9.
J Biopharm Stat ; 24(3): 600-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24697196

RESUMO

For paired binary data, McNemar's test is widely used to test marginal homogeneity or symmetry for a 2 by 2 contingency table. In this article, we extend McNemar's test by considering a series of paired binary data in which the series is defined by a stratification factor. We provide a test for testing homogeneous stratum effects. For illustration, we apply our test to a cancer epidemiology study. Finally, we conduct simulations to show that our test preserves the nominal type I error level and evaluate the power of our test under various scenarios.


Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Simulação por Computador , Análise por Pareamento , Modelos Estatísticos , Biomarcadores/análise , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Razão de Chances
10.
Brain Res ; 1449: 38-45, 2012 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-22373650

RESUMO

Previous studies have indicated that central sensitization is a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation and astrocytes play an important role in the central sensitization. The current study investigated the role of amino acid transport system A in central sensitization and hyperalgesia induced by intraplantar injection of formalin in rats. Formalin (5%, 50µl) injected subcutaneously into the unilateral hindpaw pad induced typical biphase nociceptive behaviors, including licking/biting and flinching of the injected paw and an increase of glial fibrillary acid protein (GFAP, an activated astrocyte marker) expression in spinal dorsal horn, and these effects could be attenuated by intrathecal injection of the competitive inhibitor of amino acid system A transporter, methylaminoisobutyric acid (MeAIB, 0.1, 0.3, 0.5, and 0.7mmol), in a dose-dependent manner. Intrathecal injection of vehicle (PBS) had no effect on the formalin-induced nociceptive behaviors and increase of the GFAP. These findings suggest that amino acid transport system A is involved in inflammation-induced nociception, and inhibition of this transporter system results in inhibition of the central sensitization and hyperalgesia.


Assuntos
Sistema A de Transporte de Aminoácidos/metabolismo , Sensibilização do Sistema Nervoso Central/fisiologia , Dor Nociceptiva/metabolismo , Células do Corno Posterior/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/metabolismo , Masculino , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Medição da Dor/efeitos dos fármacos , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , beta-Alanina/análogos & derivados , beta-Alanina/farmacologia
11.
Cell Biol Int ; 36(3): 229-36, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21954859

RESUMO

Mechanotransduction is a complicated process, of which mechanosensation is the first step. Previous studies have shown that the cytoskeleton plays a crucial role in mechanosensation and the mediation of intracellular signal transduction. However, the mechanism of mechanotransduction in the bone remains elusive. Here, we investigated the potential involvement of a novel MAPK (mitogen-activated protein kinase) member, ERK5 (extracellular-signal-regulated kinase 5), in the response of osteoblastic cells to FSS (fluid shear stress). Our results demonstrated that ERK5 was rapidly phosphorylated in pre-osteoblastic MC3T3-E1 cells upon FSS, and the integrity and reorganization of the cytoskeleton were critical in this process, in which the cytoskeleton-dependent activation of FAK (focal adhesion kinase) may be involved in the activation of ERK5 induced by FSS. Moreover, we found that cytoskeletal disruption led to significant down-regulation of ERK5 phosphorylation, but had no effect on ERK5 nuclear localization. Furthermore, the cytoskeleton rapidly reorganized in response to FSS, but long-time fluid load, even at a physiological level, led to cytoskeletal disruption, suggesting that other pathways may be involved in long-term mechanotransduction. Taken together, our data provide new insight into the mechanisms of mechanosensation by highlighting the link between ERK5 activation and cytoskeletal reorganization in osteoblasts undergoing FSS.


Assuntos
Citoesqueleto/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Osteoblastos/metabolismo , Estresse Mecânico , Animais , Células Cultivadas , Regulação para Baixo , Mecanotransdução Celular , Camundongos , Proteína Quinase 7 Ativada por Mitógeno/genética
12.
Arch Orthop Trauma Surg ; 130(3): 357-61, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19387669

RESUMO

INTRODUCTION: Due to atypical clinical presentation, wide use of antibiotics and lack of specificity in diagnosis, misdiagnosis is common, and diagnosis of tubercular infection in a joint is increasingly difficult. The use of arthroscopy for the diagnosis and treatment of early-stage knee TB has rarely been reported. Through this case series we describe the usefulness of arthroscopy for the management of synovial tuberculosis of the knee joint. MATERIALS AND METHODS: Synovectomy and synovial membrane biopsy were performed using arthroscopy in ten subjects suffering from synovial tuberculosis. This was combined with intra-articular isoniazid injection and systemic antituberculosis drugs. RESULTS: In all cases, continuous passive motion exercise was started 2 days after operation and they were followed up from 6 months to 3 years. The flexion angles 90 degrees +/- 5 degrees preoperatively increased to 120 degrees +/- 14 degrees in nine patients following surgery, the extension limit angle also improved from an average 20 degrees +/- 3 degrees preoperatively to 5 degrees +/- 1 degrees postoperatively. There was a significant difference in knee function index between preoperation and postoperation (t = 6.9, t = 6.3, P < 0.01). Japanese Institute of Plastic Surgery synovial disease treatment success criteria was also improved from 44.4 +/- 8.4 points before surgery to 81.5 +/- 10.4 following surgery (t = 8.749, P < 0.01). The joint swelling disappeared or was relieved after 2 months. No relapse of tuberculosis was found at the time of follow-up. CONCLUSION: Combined use of arthroscopy and antituberculosis medication appears to be advantageous for the management of early-stage synovial tuberculosis of the knee joint. Arthroscopic removal of the pannus allows better nutrition of the cartilage and thus greatly improves the joint function.


Assuntos
Artroscopia , Articulação do Joelho/cirurgia , Tuberculose Osteoarticular/diagnóstico , Adolescente , Adulto , Antituberculosos/administração & dosagem , Biópsia , Terapia por Exercício , Feminino , Humanos , Injeções Intra-Articulares , Isoniazida/administração & dosagem , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sinovectomia , Membrana Sinovial/patologia , Tuberculose Osteoarticular/terapia
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