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1.
Int J Oral Sci ; 12(1): 5, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32024813

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/BxN mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint (TMJ) inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging (µMRI) and micro-computed tomography (µCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/BxN animals, which was also evidenced by µCT but was less pronounced than that seen in the knee joints. µMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes (FLSs) isolated from the TMJ of K/BxN mice secreted inflammatory cytokines (IL-6 and IL-1ß) and expressed degradative mediators such as matrix metalloproteinases (MMPs). K/BxN mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.


Assuntos
Artrite Experimental/patologia , Artrite Reumatoide/patologia , Osso e Ossos/diagnóstico por imagem , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/lesões , Microtomografia por Raio-X/métodos , Animais , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Modelos Animais de Doenças , Humanos , Imagem por Ressonância Magnética , Metaloproteinase 8 da Matriz/imunologia , Camundongos , Camundongos Transgênicos , Articulação Temporomandibular/metabolismo , Tomografia Computadorizada por Raios X
2.
Gene ; 724: 144144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629819

RESUMO

BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1ß, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS: miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION: MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.


Assuntos
Artrite Reumatoide/genética , Citocinas/metabolismo , MicroRNAs/genética , Sirtuína 1/genética , Membrana Sinovial/patologia , Regiões 3' não Traduzidas , Artrite Reumatoide/patologia , Proliferação de Células/genética , Citocinas/genética , Feminino , Fibroblastos/patologia , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Sirtuína 1/metabolismo , Membrana Sinovial/metabolismo
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(11): 1030-1034, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31879000

RESUMO

Objective To detect the mRNA and protein expression of microtubule-associated protein 1 light chain 3 (LC3) in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA), and to investigate its relationship with RA. Methods Twenty-two patients with RA and 16 healthy subjects with matching gender and age as controls were included in the study. PBMCs were isolated by density gradient centrifugation. The level of LC3 mRNA in PBMCs was detected by real-time fluorescent quantitative PCR. The protein level of LC3 in PBMCs was detected by Western blot analysis. The expression of LC3 protein in PBMCs was detected by immunofluorescence staining. Pearson analysis was used to analyze the correlation between LC3 expression and clinical parameters of RA patients. Results Compared with the normal control group, the levels of LC3 mRNA and protein in PBMCs of RA patients went up significantly, and the expression of LC3 significantly increased in PBMCs. The mRNA expression level of LC3 was obviously positively correlated with erythrocyte sedimentation rate (ESR, r=0.7480), 28 joint disease activity (DAS28, r=0.5016), C-reactive protein (CRP, r=0.6518), and rheumatoid factor (RF, r=0.7232). Conclusion The expression of LC3 is up-regulated in RA patients and is associated with ESR, DAS28, CRP and RF.


Assuntos
Artrite Reumatoide/metabolismo , Leucócitos Mononucleares/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Artrite Reumatoide/patologia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Humanos , RNA Mensageiro , Fator Reumatoide/análise
5.
Medicine (Baltimore) ; 98(47): e17968, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764801

RESUMO

To identify the risk factors for destruction of large joints in the lower extremities in patients with rheumatoid arthritis (RA) during a 4-year follow-up period in a prospective study.We enrolled consecutive patients who participated in both 2012 and 2016. Clinical data, disease activity, and types of medication were collected in 2012. Standard anteroposterior radiographs of weight-bearing joints (hips, knees, and ankles) were taken in 2012 and 2016. Radiographic progression was defined as progression in the Larsen grade or the need for joint arthroplasty or arthrodesis. The association between baseline characteristics and the incidence of radiographic progression was statistically assessed.A total of 213 patient were enrolled, and, after exclusion, 186 patients were analyzed. Sixty 9 patients (37.1%) showed radiographic progression in 1 of the large joints in the lower extremities. Multivariate regression analysis showed that radiographic progression was associated with older age, higher disease activity, and the presence of radiographic destruction at the baseline. The lower dosage of oral prednisolone was a significant risk factor compared with higher dosage when used.Patients with the risk factors should be followed closely to limit the progression of large joint destruction in the lower extremities.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Glucocorticoides/administração & dosagem , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Prednisolona/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fatores de Risco
6.
Expert Opin Investig Drugs ; 28(12): 1113-1123, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31738612

RESUMO

Introduction: Rheumatoid arthritis (RA) is a chronic, refractory disorder caused by autoimmunity in the synovial joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biologicals offer remission in only two-thirds of RA patients within 3 months, hence new therapeutic approaches are necessary. Tyrosine kinase inhibitors (TKIs) are newly developed small molecule drugs which have demonstrated encouraging results in this disease.Areas covered: The key findings from phase I and II clinical trials that have investigated the use of novel TKIs in the treatment of RA are discussed. We examined the literature published between January 2014 to January 2019 using electronic databases including PubMed, Web of Science, Medline, Embase, and Google Scholar. Additional information about phase I and II trials on the ClinicalTrial.gov website up to January 2019 was also retrieved.Expert opinion: JAK inhibitors are promising drugs with sound efficacy and acceptable safety and may be beneficial to patients who do not respond to DMARDs and biologicals. The response rates among RA patients to TKIs are diverse; genetic and environmental factors may be involved in the varying responses which are closely related to the pathogenesis of RA. Future studies may reveal the underlying mechanisms of resistance and non-response.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Desenvolvimento de Medicamentos , Humanos , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/farmacologia , Inibidores de Proteínas Quinases/efeitos adversos
7.
Clin Exp Rheumatol ; 37 Suppl 120(5): 7-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621569

RESUMO

Osteoarthritis (OA) may be associated with substantial work disability, morbidity, costs, and increased mortality rates, often similar to rheumatoid arthritis (RA), documented in many published reports over the last 4 decades. However, OA generally has been viewed as less severe than RA. This discrepancy may be explained in part by:a) RA may have been considerably more severe in the past, prior to effective therapies.b) most older individuals have radiographic joint damage, which often is not associated with clinical symptoms.c) RA is associated with abnormal laboratory tests, which are regarded as conveying greater significance than symptoms of pain and disability according to a "biomedical model," the dominant paradigm of modern medicine.d) Most reports of OA and RA have emphasised differences between the 2 diseases even beyond laboratory abnormalities in pathogenesis, physical findings, and imaging.e) Even pain and functional disability seen in both diseases are assessed using different patient self-report questionnaires, a WOMAC (Western Ontario McMaster Universities osteoarthritis index) in OA, and HAQ (health assessment questionnaire) in RA.An identical measure is required for optimal direct comparisons, which has been used in 8 studies performed between 1979 and 2019 at 8 sites in North America, Europe, and Australia. These studies were primarily based on retrospective analyses at sites which collected a patient questionnaire in routine clinical care by all patients at all visits to inform clinical decisions. A pain visual analogue scale (VAS) was higher in OA compared to RA in 11/12 patient groups, while physical function on a HAQ (health assessment questionnaire) or derivative MDHAQ (multidimensional HAQ) and RAPID3 (routine assessment of patient index data) were slightly higher in RA before 2013 and higher in OA in later reports. Furthermore, a study of population-based data from the 1978 US Health Interview Survey indicated similar levels of disability and earnings losses according to surrogate variables for OA and RA. Therefore, at least over the last 40 years, pain and functional disability in OA have appeared to be severe and similar to RA. These observations also-illustrate the potential value of using an identical patient questionnaire in all patients at all visits in routine care settings, analogous to using the same laboratory tests such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in all rheumatic diseases, and maintaining a database of the results for later analyses.


Assuntos
Artrite Reumatoide , Osteoartrite , Artrite Reumatoide/patologia , Humanos , Osteoartrite/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários
8.
Scand J Rheumatol ; 48(5): 353-361, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31631790

RESUMO

Objective: To elucidate the roles of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in cell cycle regulation and proliferation of rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). Methods: Under stimulation with IL-6/soluble interleukin-6 receptor (sIL-6R) and TNF-α, we examined the expression of cell cycle regulators [p16INK4a, p21Cip1, p27Kip1, cyclin-dependent kinase-4 (CDK4), CDK6, Cyclin D, Cyclin E, and retinoblastoma protein (pRB)] by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining. The expression of pRB, with or without 10% foetal bovine serum, was examined by Western blotting. DNA synthesis and cell viability were examined by the BrdU assay and WST-8 assay, respectively. After transfection with siRNA/p16INK4a, siRNA/p21Cip1, siRNA/p27Kip1, siRNA/CDK4, or siRNA/CDK6, RA-FLSs were successively stimulated with or without IL-6/sIL-6R or TNF-α to determine cell viability. Results: IL-6/sIL-6R significantly decreased the expression of p16INK4a, and increased p21Cip1, Cyclin E1, CYCLIN D, and pRB. TNF-α decreased the expression of CDK4, and significantly increased p27Kip1, CDK6, Cyclin E1/E2, CYCLIN D, CYCLIN E, pRB, and phosphorylated pRB (phospho-pRB). By immunofluorescence staining, CYCLIN D and phospho-pRB were simultaneously stained in the single cell. In serum-free culture, the expression of pRB was apparently decreased. DNA synthesis and cell viability were significantly increased by IL-6/sIL-6R and TNF-α. Silencing of CDK6 attenuated the cell viability induced by IL-6 and TNF-α. Conclusion: The results indicate that IL-6 and TNF-α interact with each other in regulating the cell cycle and accelerate the proliferation of RA-FLSs.


Assuntos
Artrite Reumatoide/genética , Regulação da Expressão Gênica , Interleucina-6/genética , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Western Blotting , Ciclo Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Interleucina-6/biossíntese , RNA/genética , Sinoviócitos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
9.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
10.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 641-648, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537249

RESUMO

Objective To investigate the expression of programmed cell death 1 (PD-1) and inducible costimulatory molecules (ICOS) on peripheral T lymphocytes of patients with rheumatoid arthritis (RA) and to determine its relationship with disease severity. Methods The study included 30 RA patients and 26 healthy people. Flow cytometry was used to detect the ratio of CD3+CD8+ effector memory T cells (Tem) and follicular helper T (Tfh) cells in peripheral blood, and then to detect the proportion of PD-1 and ICOS-positive cells in lymphocyte subsets. Correlation between them and 28 joint disease activity scores (DAS28) was assessed by Spearman correlation analysis. Results The absolute number of Tem and Tfh cells in the RA group was higher than that in the healthy group. The expression of ICOS and PD-1 in the RA group was higher than that in the healthy group. There was a positive correlation between the expression of ICOS and PD-1 on peripheral CD3+CD8+ Tem and Tfh cells and DAS28 in RA group. Conclusion PD-1 and ICOS on peripheral CD3+CD8+ Tem and Tfh cells may be involved in the development of RA and may be an indicator of RA activity.


Assuntos
Artrite Reumatoide/patologia , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Artrite Reumatoide/metabolismo , Humanos
11.
Eur Cytokine Netw ; 30(2): 67-73, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486401

RESUMO

OBJECTIVE: To detect the effect of interleukin (IL)-34 on the secretion of Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) and Matrix metalloproteinase (MMP)-3 by fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and to investigate whether the effect is mediated by IL-17. METHOD: RA-FLS and RA-PBMCs were stimulated with recombinant human (rh) IL-34, with or without the IL-17 inhibitor Plumbagin. The supernatant of the culture medium was collected and the levels of RANKL, OPG, and MMP-3 were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: RhIL-34 promoted RANKL secretion and inhibited OPG secretion in RA-FLS. The effect was weakened by the addition of the IL-17 inhibitor. In contrast, rhIL-34 had no significant effect on MMP-3 secretion by FLS. RhIL-34 elevated the secretion of RANKL by RA-PBMCs but not by healthy-PBMCs. Furthermore, the secretion of RANKL by RA-PBMCs reduced after the addition of the IL-17 inhibitor. OPG secretion by both RA-FLS and FLS from healthy controls was inhibited by rhIL-34, but were elevated after the addition of the IL-17 inhibitor. RhIL-34 had no significant effect on MMP-3 secretion by both RA-PBMCs and healthy-PBMCs. CONCLUSION: IL-34 enhances RANKL/OPG expression by RA-FLS and RA-PBMCs, and this effect is, indirectly, mediated by IL-17. This cytokine is therefore likely to to play an important role in local joint destruction and systemic osteoporosis in RA, and is therefore a potential therapeutic target for the treatment of this disease.


Assuntos
Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Interleucinas/farmacologia , Leucócitos Mononucleares/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Sinoviócitos/metabolismo , Artrite Reumatoide/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Sinoviócitos/efeitos dos fármacos
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 556-561, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484621

RESUMO

Exosomes are 30-100 nm vesicles secreted from almost all types of cells.They contain various molecular constituents,including proteins,lipids,and RNA.As important mediators of cell-to-cell communication,exosomes are involved in a variety of physiological and pathological processes such as inflammatory reaction,cell proliferation and differentiation,tissue repair,immune signal transduction,and stress response.Exosomes can regulate and maintain the initiation and progression of many autoimmune diseases,especially rheumatoid arthritis.Meanwhile,exosomes may be a new biomarker for the diagnosis of rheumatoid arthritis and a potential treatment vector for this disease.


Assuntos
Artrite Reumatoide/patologia , Exossomos , Comunicação Celular , Humanos , Transdução de Sinais
13.
Cochrane Database Syst Rev ; 9: CD012958, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31476270

RESUMO

BACKGROUND: Chronic inflammatory joint diseases (IJDs) affect 1% to 2% of the population in developed countries. IJDs include rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA). Tobacco smoking is considered a significant environmental risk factor for developing IJDs. There are indications that smoking exacerbates the symptoms and worsens disease outcomes. OBJECTIVES: The objective of this review was to investigate the evidence for effects of smoking cessation interventions on smoking cessation and disease activity in smokers with IJD. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library; PubMed/MEDLINE; Embase; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and three trials registers to October 2018. SELECTION CRITERIA: We included randomised controlled trials testing any form of smoking cessation intervention for adult daily smokers with a diagnosis of IJD, and measuring smoking cessation at least six months after baseline. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included two studies with 57 smokers with a diagnosis of rheumatoid arthritis (RA). We identified no studies including other IJDs. One pilot study compared a smoking cessation intervention specifically for people with RA with a less intensive, generic smoking cessation intervention. People included in the study had a mean age of 56.5 years and a disease duration of 7.7 years (mean). The second study tested effects of an eight-week cognitive-behavioural patient education intervention on cardiovascular disease (CVD) risk for people with RA and compared this with information on CVD risk only. The intervention encouraged participants to address multiple behaviours impacting CVD risk, including smoking cessation, but did not target smoking cessation alone. People included in the study had a mean age of 62.2 years (intervention group) and 60.8 years (control group), and disease duration of 11.6 years (intervention group) and 14.1 years (control group). It was not appropriate to perform a meta-analysis of abstinence data from the two studies due to clinical heterogeneity between interventions. Neither of the studies individually provided evidence to show benefit of the interventions tested. Only one study reported on adverse effects. These effects were non-serious, and numbers were comparable between trial arms. Neither of the studies assessed or reported disease activity or any of the predefined secondary outcomes. We assessed the overall certainty of evidence as very low due to indirectness, imprecision, and high risk of detection bias based on GRADE. AUTHORS' CONCLUSIONS: We found very little research investigating the efficacy of smoking cessation intervention specifically in people with IJD. Included studies are limited by imprecision, risk of bias, and indirectness. Neither of the included studies investigated whether smoking cessation intervention reduced disease activity among people with IJD. High-quality, adequately powered studies are warranted. In particular, researchers should ensure that they measure disease markers and quality of life, in addition to long-term smoking cessation.


Assuntos
Artrite Infecciosa/patologia , Artrite Reumatoide/patologia , Artropatias/patologia , Abandono do Hábito de Fumar/métodos , Fumar/efeitos adversos , Terapia Cognitivo-Comportamental , Humanos , Osteoartrite/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilartrite/patologia
14.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491879

RESUMO

The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Medicamentos Biossimilares/uso terapêutico , Articulações/patologia , /uso terapêutico , Artrite Reumatoide/metabolismo , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , Humanos , Articulações/metabolismo , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , /efeitos adversos
15.
Gene ; 720: 144081, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473322

RESUMO

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA. When comparing the four groups (ANOVA P < 0.01, fold change > 4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways. Moreover, ROC analysis showed values of AUC 0.76 and P < 0.05 for miR 361-5p, identifying this miRNA as a potential biomarker of disease. We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.


Assuntos
Artrite Reumatoide/genética , Biomarcadores/análise , Genoma Humano , MicroRNAs/genética , Adulto , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Curva ROC
16.
Sensors (Basel) ; 19(16)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394720

RESUMO

A recent review of thermography studies in rheumatoid arthritis shows limited data about disease activity and mostly focuses on differences between the thermography of rheumatoid arthritis patients and typical subjects. A retrospective study compared patients with high disease activity (n = 50), moderate disease activity (n = 16), and healthy participants (n = 42), taking into account demographic, clinical, laboratory, and thermography parameters. We applied an infrared thermography sensor and a fingers examination protocol. Outcomes included the mean temperature of five fingers of a hand: In static, post-cooling, post-rewarming, the total change in mean temperature of fingers due to cold provocation, the total change in mean temperature of fingers due to rewarming, the area under the cooling curve, the area under the heating curve, the difference between the area under the rewarming and the cooling curve, and temperature intensity distribution maps. For patients with high disease activity, a lower area under the heating curve and a lower difference between the area under the rewarming curve and the cooling curve were observed, as well as a smaller total change in mean temperature due to rewarming, compared to patients with moderate disease activity (p < 0.05). Our study findings could be helpful in patients with an equivocal clinical examination.


Assuntos
Artrite Reumatoide/patologia , Raios Infravermelhos , Termografia/métodos , Temperatura Baixa , Estudos Transversais , Feminino , Dedos/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reaquecimento , Índice de Gravidade de Doença , Temperatura Cutânea
17.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370159

RESUMO

Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm "one disease, one drug".


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Psoríase/tratamento farmacológico , Idoso , Envelhecimento/genética , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Contagem de Células , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Modelos Animais de Doenças , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Idoso Fragilizado , Homeostase/efeitos dos fármacos , Homeostase/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Comunicação Parácrina/efeitos dos fármacos , Psoríase/genética , Psoríase/metabolismo , Psoríase/patologia
18.
Inflamm Res ; 68(10): 889-900, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372663

RESUMO

OBJECTIVE: To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ). MATERIALS AND METHODS: Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1ß, NF-κB, RANKL, Wnt-10b, ß-catenin and DKK1. RESULTS: The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1ß and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear ß-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections. CONCLUSION: Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Hiperalgesia/imunologia , NF-kappa B/imunologia , Articulação Temporomandibular/imunologia , Via de Sinalização Wnt , Animais , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Adjuvante de Freund , Hiperalgesia/patologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-1beta/imunologia , Lipídeos , Masculino , Ligante RANK/imunologia , Ratos Wistar , Soroalbumina Bovina , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Articulação Temporomandibular/patologia , Fator de Necrose Tumoral alfa/imunologia , Proteínas Wnt/imunologia
19.
Int J Mol Sci ; 20(16)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430907

RESUMO

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.


Assuntos
Artrite Reumatoide/patologia , Galectinas/imunologia , Granulócitos/patologia , /imunologia , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Células Cultivadas , Feminino , Galectinas/sangue , Granulócitos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fagocitose
20.
Bratisl Lek Listy ; 120(8): 586-592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379182

RESUMO

OBJECTIVE: In recent years, neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) are reported to be increasing in plenty of rheumatological diseases and the latter rates to be disease activity indicators. In our study, we aimed to search for the difference in NLR and PLR before and after the treatment, their relationship with the disease activity and their seasonal differences in patients using anti-TNF medication for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) while. METHOD: Sixty-eight RA and 203 AS patients using anti-TNF medication for at least 6 months were included in the study. Patients with acute infection, diabetes, hypertension, cancer, renal failure and liver failure were excluded from the study. NLR, PLR, seasonal differences and the disease activities of the patients were evaluated retrospectively. RESULTS: We determined that NLR and PLR are strongly correlated with disease activity, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). In addition, we determined that disease activity, thrombocytes and PLR are increased in spring and winter, especially in patients with RA. CONCLUSION: NLR and PLR are simple, cheap, and easily accessible parameters which can be used to evaluate disease activity and treatment response before and after anti-TNF treatment. Further studies are needed to enlighten the effect of seasonal differences on disease activity (Tab. 2, Fig. 2, Ref. 43).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Estações do Ano , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/patologia , Plaquetas/citologia , Contagem de Células , Humanos , Linfócitos/citologia , Neutrófilos/citologia , Estudos Retrospectivos , Espondilite Anquilosante/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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