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1.
J Assoc Physicians India ; 68(2): 18-22, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009356

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic inflammatory connective tissue disorder with wide spectrum of presentation from polyarthritis to multisystem involvement. Apart from bones, muscles and other soft tissues, Vitamin D receptors have been found on many immune cells and tissues. The most vital function of Vitamin D is calcium and phosphorus absorption but it can also act as an immune-modulator hormone, which can affects both innate and adaptive immune responses leading to autoimmune diseases. Objectives: To study the relationship of vitamin D insufficiency with disease activity and functional disability in patients of Rheumatoid Arthritis. Material and Methods: The present study was an observational, cross sectional study done in a tertiary care hospital in New Delhi, India. The inclusion criteria comprised of patients attending the inpatient (IPD) and outpatient department (OPD), age above 18 years and fulfilling 1987 American college of Rheumatology (ACR) criteria for RA. The exclusion criteria was patients suffering from any other connective tissue disorder (CTD) and patients who were taking vitamin D supplements for past 6 months. Thirty patients were enrolled in the study after satisfying inclusion and exclusion criteria and appropriate clinical data and blood sample were collected after informed consent. Joint examination were performed and swollen joint count (SJC), tender joint count (TJC), patient global assessment (PGA) and evaluator global assessment (EGA) scores were recorded. Disease activity using DAS28ESR, DAS28CRP and CDAI were calculated and disability index was assessed using Short Fries Health Assessment Questionnaire. Results: In our study mean vitamin D level was 18.93 ng/ml (S.D. 6.64 ng/ml). Mean DAS28 ESR was 4.57±1.48. Mean Disability Index was 0.52±0.89. All the study population had low Vitamin D level (100%), while 50% patients had vitamin D level in deficiency range (<20ng/ml). On analysis by student t-test, statistically higher PGA (p value 0.024) and Disability Index (p value < 0.001) in vitamin D deficient patients, compared to vitamin D insufficient patient group was observed, however there was no significant difference in disease activity between the groups. Conclusion: Low Vitamin D levels are common in Indian rheumatoid arthritis patients. Mean PGA significantly increased, and disability index significantly increased in Vitamin D deficient group compared to insufficient group suggesting vitamin D deficient patients poor wellbeing and more disability.


Assuntos
Artrite Reumatoide/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/metabolismo , Artrite Reumatoide/metabolismo , Estudos Transversais , Humanos , Índia/epidemiologia , Índice de Gravidade de Doença
2.
Gene ; 722: 144105, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31521702

RESUMO

BACKGROUND: Caulophyllum robustum Maxim (CRM) is a medicinal compound of the Northeast and is commonly used in China for the treatment of rheumatic pain and rheumatoid arthritis (RA). A preliminary study found that CRM has good anti-inflammatory, analgesic and immunosuppressive effects. However, the specific links and targets for its function remain unclear. Our study aimed to provide a mechanism for the action of Caulophyllum robustum Maxim extraction (CRME) against RA and to establish a method for studying disease treatment using Chinese medicine. METHODS: The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method was used to detect the toxicity of CRME in L929 cells, and the concentration ranges of the blank, model, and CRME drug groups were determined. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were identified between the three groups. Gene Ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways of the differentially expressed genes. Expression of Hist1h2bj, Hist1h2ba, Zfp36, Ccl3, Cxcl2 and Egr1 in the blank, model and drug groups was detected by quantitative real-time PCR (qRT-PCR), and the role of CRME on the above factors was determined to ensure consistency with the chip data. RESULTS: A total of 329 significantly upregulated genes and 141 downregulated genes were identified between the blank and model groups. A total of 218 significantly upregulated genes and 191 downregulated genes were identified between the CRME drug group and model group. CRME has a significant role in multiple pathways involved in the occurrence and development of RA. Additionally, Hist1h2bj, Hist1h2ba, Zfp36, Ccl3, Cxcl2, and Egr1 were observed in modules of the lncRNA-mRNA weighted co-expression network, consistent with the chip data. CONCLUSIONS: CRME has regulatory effects on inflammatory factors, the histone family, chemokines and their ligands that are related to RA-related cytokines, the RA pathway, the TNF signaling pathway, the Toll receptor-like signaling pathway, the chemokine signaling pathways and other pathways are related to the course of RA.


Assuntos
Artrite Reumatoide/genética , Caulophyllum , Medicamentos de Ervas Chinesas/farmacologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Animais , Artrite Reumatoide/metabolismo , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas
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
4.
Clin Ter ; 170(6): e472-e477, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696912

RESUMO

Monokine induced by interferon (IFN)-γ (MIG) and its receptor chemokine (C-X-C motif) receptor 3 (CXCR)3 seem to play an important role in the pathogenesis of rheumatoid arthritis (RA). MIG expression has been observed in sera, synovial fluid (SF) and synovial tissue of RA patients; it is highly expressed in RA synovium by infiltrating macrophage-like cells and fibroblast-like synoviocytes. A Type-1 helper-response orientated disease was suggested because of the high expression of CXCR3 in SF T cells and the presence of elevated IFN-γ levels. It has been observed a decrease of the inflammation by anti-CXCR3, and anti-MIG molecules, in fact they inhibit CXCR3-enhanced cell migration and pro-inflammatory cytokine expression, leading to an amelioration of the arthritis progression. These findings suggest a possible therapeutic role of these molecules in humans.


Assuntos
Artrite Reumatoide/metabolismo , Quimiocina CXCL9/metabolismo , Humanos , Receptores CXCR3/metabolismo , Líquido Sinovial/metabolismo , Linfócitos T/metabolismo
6.
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
7.
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
8.
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
9.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 85-90, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31472052

RESUMO

To investigate the effect of gentiopicrin on the expressions of inflammatory factors in human fibroblast-like synoviocytes (HFLS) and the underlying mechanism. Human fibroblast-like synoviocytes (HFLS) were cultured in vitro at 37 °C in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5 % fetal bovine serum (FBS) in a humidified incubator containing 5 % CO2. Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide (MTT) assay, while real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expressions of interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) mRNAs. The expressions of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) were determined using Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-1ß and IL-6 in cell lysate. Treatment with 5-25 µM gentiopicrin did not significantly affect the number of viable cells, when compared with control group (p > 0.05). However, at 50 and 100 µM gentiopicrin, the number of viable cells were significantly increased, relative to control group (p < 0.05). Results of qRT-PCR showed that the expression levels of IL-1ß and IL-6 mRNAs were significantly higher in TNF-α group than in control group (p < 0.05). However, treatment with gentiopicrin significantly and dose-dependently decreased their expression levels compared with TNF-α group (p < 0.05). Western blotting results showed that the expressions of p-p38MAPK and NF-κB-p65 proteins were significantly upregulated in TNF-α group, when compared with control group (p < 0.05). However, treatment with gentiopicrin significantly and dose-dependently down-regulated the expression of these proteins compared with TNF-α group (p < 0.05). The levels of IL-1ß and IL-6 in cell lysate were significantly higher in TNF-α group than in control group (p < 0.05). However, treatment with gentiopicrin, and p38MAPK/NF-κB pathway inhibitors (SB203580 and BAY11-7082) significantly reduced the levels of these inflammatory factors compared with TNF-α group (p < 0.05).  Gentiopicrin has therapeutic potential for Rheumatoid arthritis (RA  ) through a mechanism involving the inhibition of p38MAPK/NF-κB pathway.


Assuntos
Fibroblastos/metabolismo , Glucosídeos Iridoides/farmacologia , NF-kappa B/antagonistas & inibidores , Extratos Vegetais/farmacologia , Sinoviócitos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Artrite Reumatoide/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Imidazóis/farmacologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Glucosídeos Iridoides/administração & dosagem , NF-kappa B/metabolismo , Nitrilos/farmacologia , Extratos Vegetais/administração & dosagem , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
J Enzyme Inhib Med Chem ; 34(1): 1615-1622, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31480869

RESUMO

The highly aggressive fibroblast-like synoviocytes (FLSs) are inflammatory mediators involved in synovial joint destruction. Membrane channels and transporters are essential components of the cell migration apparatus and are involved in various cellular functions. Although evidence is emerging that cell migration is a physiological/pathological process, the mechanism of highly dynamic synoviocytes linked to the membrane channels and carbonic anhydrases (CAs) in inflamed joints is only partially understood. In this review, topics covered will give a brief overview of CAs and the membrane channels of synoviocytes. We have also systematically focused on the role of FLS channels and transporters under various conditions, including rheumatoid arthritis (RA), to understand the pathophysiology of the migration of synoviocytes as inflammatory mediators in joints.


Assuntos
Artrite Reumatoide/metabolismo , Anidrases Carbônicas/metabolismo , Mediadores da Inflamação/metabolismo , Membrana Sinovial/metabolismo , Sinoviócitos/metabolismo , Animais , Humanos
11.
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
12.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491989

RESUMO

Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.


Assuntos
Artrite Reumatoide/metabolismo , Biomarcadores , Espectrometria de Massas , Proteoma , Proteômica , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Biologia Computacional/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Proteômica/métodos
13.
Phytomedicine ; 63: 153036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401534

RESUMO

BACKGROUND: Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA. PURPOSE: This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms. METHODS: The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis. RESULTS: Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats. CONCLUSION: Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Flavonas/farmacologia , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Masculino , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
14.
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
15.
J Immunol Res ; 2019: 4080735, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428656

RESUMO

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints. The inflammation of the synovium can be observed in both of the two diseases. Synovial fibroblasts (SFs) play an important role in the inflammatory process of the synovium. The functional states of synovial fibroblasts are heterogeneous, and the detailed transition process of their functional states is still unclear. By using transcriptomic data of SFs at a single-cell level, we found a similar transition process for SFs in RA and OA. We also identified the potential regulatory effects of the WNT signaling pathway, the TGF-ß signaling pathway, the FcεRI signaling pathway, and the ERBB signaling pathway on modifying the SFs' functional state. These findings indicate potentially overlapped pathogenic mechanisms in these two diseases, which may help uncover new therapeutic targets to ameliorate disease progression.


Assuntos
Artrite Reumatoide/metabolismo , Fibroblastos/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/citologia , Artrite Reumatoide/imunologia , Progressão da Doença , Fibroblastos/imunologia , Genes erbB , Humanos , Osteoartrite/imunologia , Análise de Célula Única , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt
16.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443349

RESUMO

Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.


Assuntos
Adipocinas/metabolismo , Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Adipocinas/genética , Animais , Artrite Reumatoide/patologia , Biomarcadores , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Leptina/genética , Leptina/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Resistina/genética , Resistina/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
17.
Cell Biochem Funct ; 37(7): 474-485, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31365139

RESUMO

The effect of quercetin was assessed in rats induced with complete Freund adjuvant (CFA). Arthritis scores, paw oedema, latency, activities of myeloperoxidase (MPO), ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), and ectoadenosine deaminase (E-ADA) in lymphocytes were determined. Furthermore, nucleotide and nucleoside levels as well as the secretion of pro- and anti-inflammatory cytokines were evaluated. Animals were treated with saline and quercetin in doses of 5, 25, and 50 mg/kg for 45 days. The result revealed that quercetin (50 mg/kg) reduced arthritis score and paw oedema, and increased the latency in the thermal hyperalgesia test. Histopathological analysis showed that all the doses of quercetin reduced infiltration of inflammatory cells. MPO activity was increased in the arthritis group; however, quercetin reduced this activity. E-NTPDase activity was increased in lymphocytes of arthritis rats, and treatment with quercetin reversed this increase. However, E-ADA activity was reduced in the arthritis group, and treatment with quercetin modulated the activity of this enzyme in arthritis rat groups. Serum adenosine levels were increased in arthritis, and the levels were lowered with quercetin treatment. Quercetin treatment in arthritis groups decreased the elevated levels of cytokines in the arthritis control group. Thus, quercetin demonstrated an anti-inflammatory effect, and this flavonoid may be a promising natural compound for the treatment of arthritis. SIGNIFICANCE OF THE STUDY: Quercetin may represent a potential therapeutic compound in the treatment of rheumatoid arthritis. Findings from this study indicate that quercetin suppresses swelling and attenuates the underlying inflammatory responses. This is the first report where quercetin was shown to modulate the immune response to arthritis via attenuation of the purinergic system (E-NTPDase and E-ADA activities) and the levels of IFN-gamma and IL-4. Thus, this work is relevant to basic research and may be translated into clinical practice.


Assuntos
AMP Desaminase/antagonistas & inibidores , Adenosina Trifosfatases/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Reumatoide/tratamento farmacológico , Citocinas/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Quercetina/farmacologia , AMP Desaminase/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Feminino , Adjuvante de Freund , Ratos , Ratos Wistar
18.
Chem Biodivers ; 16(9): e1900294, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381811

RESUMO

Bawei Longzuan granule (BLG) is a representative Zhuang medicine preparation. The present work aims to characterize the chemical constituents of BLG and evaluate its anti-arthritic activity. The major chemical constituents of BLG were tentatively identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), which revealed the presence of some alkaloids (e. g., magnoflorine, sinomenine and nitidine) and flavonoids (e. g., hesperidin, diosmin and sinensetin) that may be partly responsible for the anti-arthritic effect of BLG. In addition, the collagen-induced arthritis (CIA) model in rats was induced by intradermal injection of bovine collagen-II in complete Freund's adjuvant at the base of tail. The CIA rats received oral administration of BLG (1.25, 2.5 and 5 g/kg) for 30 days. Then, various indicators were determined to evaluate its anti-arthritic activity, including paw swelling, arthritic score, body weight, knee joint pathology, thymus index and spleen index. Additionally, the serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-4 and IL-10 were measured to determine the underlying mechanisms. The results showed that BLG efficiently ameliorated the severity of arthritis in CIA rats by decreasing paw swelling and arthritis score and improving the histological lesions of knee joint. Moreover, the serum levels of several pro-inflammatory cytokines (i. e., IL-1ß, TNF-α, IL-6 and IFN-γ) were downregulated, whereas two anti-inflammatory factors (i. e., IL-4 and IL-10) were upregulated after BLG administration. These results indicated that BLG possessed promising therapeutic effect on collagen-induced arthritis by inhibiting inflammatory responses. BLG can be used as a complementary or alternative traditional medicine to treat rheumatoid arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Citocinas/antagonistas & inibidores , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Colágeno , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Inflamação/metabolismo , Masculino , Medicina Tradicional Chinesa , Ratos , Ratos Wistar
19.
Mol Cell Biochem ; 459(1-2): 141-150, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297660

RESUMO

Migration and invasion are important characteristics of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), which are involved in joint damage and contribute to rheumatoid arthritis (RA) pathology. However, the underlying mechanisms remain unclear. Because epithelial-mesenchymal transition (EMT) is a key mechanism related to migration and invasion in cancer cells, we investigated the relationship between EMT and RA-FLSs and explored whether the transforming growth factor ß1 (TGF-ß1)/Smad signaling pathway is involved. In vivo, fibroblast-like synoviocytes (FLSs) were isolated from the synovium of RA or osteoarthritis (OA) patients and cultured for 4-8 passages. EMT markers were detected by immunofluorescence and Western blotting. RA-FLSs were treated with TGF-ß1 or Smad2/3 small interfering RNA (siRNA), EMT markers were detected, and migration and invasion were assessed by Transwell assays. EMT markers could be detected in FLSs; when compared with osteoarthritis fibroblast-like synoviocytes (OA-FLSs), E-cadherin and vimentin decreased, while N-cadherin and α-smooth muscle actin (α-SMA) increased in RA-FLSs. Furthermore, TGF-ß1 enhanced migration and invasion by inducing EMT via activating Smad2/3 in RA-FLSs. Phosphorylation of Smad2/3 was accompanied by degradation of Smad3. Silencing Smad2/3 blocked EMT and inhibited the migration and invasion induced by TGF-ß1. Matrix metalloproteinase 9 (MMP9) and vimentin were not affected when cells were treated with TGF-ß1 or Smad2/3 siRNA. The TGF-ß1/Smad signaling pathway is involved in EMT and contributes to migration and invasion in RA-FLSs. Interestingly, vimentin decreased in RA-FLSs, but there is no correlation between vimentin and TGF-ß1/Smad signaling pathway. Thus, further research on vimentin should be conducted.


Assuntos
Artrite Reumatoide/metabolismo , Movimento Celular , Fibroblastos/metabolismo , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Sinoviócitos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Artrite Reumatoide/patologia , Células Cultivadas , Feminino , Fibroblastos/patologia , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Sinoviócitos/patologia
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