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1.
Clin Rheumatol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385084

RESUMO

OBJECTIVE: To explore the long-term prognostic value of a simplified risk assessment strategy based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines in Chinese patients with connective tissue disease (CTD) associated with pulmonary arterial hypertension (PAH). METHODS: We identified 50 CTD-PAH patients diagnosed by right heart catheterization. A retrospective chart review was completed to assess their clinical presentation and laboratory test results. A simplified version of the risk stratification model proposed by the 2015 ESC/ERS PH guidelines was applied, which included the WHO functional class, the 6-minute walking distance test, N-terminal pro-B-type natriuretic peptide plasma levels, pericardial effusion, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO2). The risk grades were defined as follows: low risk = at least 3 low-risk variables and no high-risk variables; high risk = at least 2 high-risk variables, including SvO2 or CI; and intermediate risk = when the above definitions of low or high risk were not fulfilled. The study endpoint was 3-year all-cause mortality. RESULTS: Twenty patients were defined as a low-risk group, while 30 were classified into a combined intermediate-high-risk group at the baseline assessment. All 20 patients in the low-risk group remained in the low-risk group at follow-up, 20 patients in the intermediate-high-risk group were downgraded to the low-risk group, and eight patients remained in the intermediate-high-risk group at the follow-up assessment. Patients in the intermediate-high-risk group exhibited higher 3-year mortality than the low-risk group at baseline (26% vs 14%, P = 0.0384). Compared with patients who remained in the intermediate-high-risk group, patients who were downgraded to the low-risk group showed lower 3-year mortality (P = 0.0281). CONCLUSION: A simplified risk stratification model based on the 2015 ESC/ERS PH guidelines helped to identify CTD-PAH patients with poor long-term  prognosis , which was useful in evaluating the severity and treatment response of patients with CTD-PAH. Key Point •This study showed that the simplified version of the 2015 ESC/ERS risk stratification model could help identify Chinese CTD-PAH patients with poor prognosis at diagnosis and after treatment initiation.

2.
Clin Rheumatol ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414304

RESUMO

OBJECTIVE: Due to lack of comprehensive evaluation for various detection methods for antineutrophil cytoplasmic antibody (ANCA) in Chinese population, we evaluate the diagnostic performance of 12 established analysis methods in Chinese patients having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Sera were collected from 209 patients with GPA or MPA and 243 diseases controls from 15 centers. Twelve different reagents were employed for C-ANCA, P-ANCA, myeloperoxidase (MPO)-ANCA, and proteinase 3(PR3)-ANCA detection. The accuracy, sensitivity, and specificity of each method were analyzed. RESULTS: The accuracy of the two indirect immunofluorescence (IIF) and two line immunoassay (LIA) was 0.838 and 0.874, 0.869, and 0.862, respectively. The accuracy of the eight quantitative antigen-specific immunoassays was varied from 0.867 to 0.967. The sensitivity of ANCA-associated vasculitis (AAV) was 0.770 and 0.761 for the two IIF, 0.727 and 0.718 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the sensitivity varied from 0.79 to 0.967. The specificity was 0.897 and 0.971 for the two IIF, 0.992 and 0.988 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the specificity of AAV varied from 0.963 to 0.983. CONCLUSION: For Chinese patients suspected of having GPA and MPA, both the first-generation enzyme-linked immunosorbent assay (ELISA) and high-quality antigen-specific immunoassay can be used to detect MPO-ANCA and PR3-ANCA alone, without the combined detection with IIF to have good diagnostic performance. The chemiluminescent immunoassay (CLIA) seems to be a method worth recommending. Key points • Quantitative antigen-specific immunoassays can be used to detect MPO-ANCA and PR3-ANCA without IIF in Chinese. • CLIA has the maximum AUC value and the minimum LR (-) value, which seems to be a method worth recommending.

3.
Front Immunol ; 10: 884, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068949

RESUMO

Objectives: To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. Methods: CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analyses. The expression of osteoclasts (OCs), OCs-related cytokines, and immune cells in bone marrow were determined by flow cytometry, immunohistochemistry, immunofluorescence staining, and real-time PCR. The OCs formation was estimated using in vitro assays. Results: MRI detected BME could emerge at day 25 in 70% mice after the first immunization (n = 10), when there were not any arthritic symptoms, histological or MRI synovitis. At day 28, BME occurred in 90% mice whereas the arthritic symptom and histological synovitis were only presented in 30 and 20% CIA mice at that time (n = 10). The emergence of BME was associated with an increased bone marrow OCs number and an altered distribution of OCs adherent to subchondral bone surface, which resulted in increased subchondral erosion and decreased trabecular bone number during the CIA process. Obvious marrow environment changes were identified after BME emergence, consisting of multiple OCs related signals, including highly expressed RANKL, increased proinflammatory cytokines and chemokines, and highly activated T cells and monocytes. Conclusions: BME reflects a unique marrow "osteoclastic environment," preceding the arthritic symptoms and synovitis during the development of CIA.

4.
Clin Exp Rheumatol ; 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-31025923

RESUMO

OBJECTIVES: Rheumatoid arthritis (RA) is characterised by the overproduction of autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. T follicular helper (Tfh) cells are a specialised Th subset that provides signals to B cells, promoting the secretion of antibodies. Our previous studies showed that the frequency of circulating Tfh cells were markedly increased in RA patients and positively correlated with disease activity and the levels of anti-CCP autoantibody. Adiponectin (AD) is an adipokine secreted mainly by adipocytes. Our previous work has demonstrated that AD is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in RA patients. However, it remains unknown whether AD aggravates the severity of RA via modulating Tfh cells. This study aims to investigate whether AD exerts effect on Tfh cells in RA. METHODS: CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), and adiponectin receptor 1 (AdipoR1) expression on the surface of CD4+CXCR5+PD-1+ (Tfh) cells was detected by flow cytometry. Purified HC CD4+ T cells were cultured with different concentration fetal bovine serun (FBS) in the presence or absence of AD. The percentages of Tfh cells were analysed by flow cytometry. RA or osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) were stimulated with AD for 72h and then co-cultured with HC CD4+ T cells through cell-to-cell contact or in a transwell system. The percentages of Tfh cells were analysed by flow cytometry and the levels of soluble factors such as interleukin-(IL)-6, IL-21, IL-12 and IFNγ in the supernatants were determined by Human Magnetic Bead Panel or Enzyme linked immunosorbent assay (ELISA). Then anti-IL-6 antibody and/or anti-IL-21 antibody was added to the co-culture system, and the percentages of Tfh cells were analysed by flow cytometry. The frequency of Tfh cells in the joint tissue of collagen-induced arthritis (CIA) mice was examined by flow cytometry. The mRNA expression of Tfh cell transcription factors and functional molecules such as B-cell lymphoma 6 (Bcl-6), B lymphocyte maturation protein 1 (Blimp-1), IL-6, IL-21, IL-12 and IFNγ in the joints of CIA mice were detected by real time PCR (RT-PCR). RESULTS: Adiponectin receptor 1 (AdipoR1) expression was detected on the surface of Tfh cells. However, in the present study, we did not find that AD has a direct effect on Tfh cell generation in vitro. Nonetheless, AD-stimulated RA FLSs could promote Tfh cell generation, predominantly via IL-6 production. And this upregulated effect was partially abolished upon neutralising IL-6. Finally, intraarticular injection of AD aggravated synovial inflammation with increased frequency of Tfh cells in the joints of AD-treated CIA mice. CONCLUSIONS: Our study demonstrated that AD-stimulated RA FLSs promote Tfh cell generation, which is mainly mediated by the secretion of soluble factor IL-6. This finding reveals a novel mechanism for AD in RA pathogenesis.

5.
Int J Rheum Dis ; 22(5): 921-928, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30746850

RESUMO

AIM: Pulmonary arterial hypertension (PAH) is a complex and devastating complication of systemic lupus erythematosus (SLE). We sought to describe the baseline characteristics of right heart catheterization (RHC)-confirmed SLE-associated PAH and identify risk factors for PAH in SLE patients. METHODS: A multicenter, cross-sectional study was conducted using the Chinese SLE Treatment and Research group (CSTAR) registry. Baseline data for patients with SLE-associated PAH and SLE patients without PAH were collected and compared. Risk factors for PAH among patients with SLE were identified. RESULTS: A total of 292 patients with SLE-associated PAH were enrolled. RHC was used to reveal hemodynamic features, including mean pulmonary arterial pressure (46.2 ± 12.0 mm Hg), pulmonary arterial wedge pressure (7.84 ± 3.92 mm Hg), pulmonary vascular resistance (10.86 ± 5.57 Wood units), and cardiac index (2.77 ± 0.91 L/min × m2 ). A multivariate logistic regression analysis showed that serositis (odds ratio [OR] = 5.524, 95% CI 3.605-8.465, P < 0.001), anti-ribonucleoprotein (RNP) antibody positivity (OR = 13.332, 95% CI 9.500-18.710, P < 0.001), and diffusion capacity of carbon monoxide in the lung (DLCO)/%Pred <70% (OR = 10.018, 95% CI 6.619-15.162, P < 0.001) were independent predictors of PAH. We recommend using transthoracic echocardiography (TTE) to perform early screening of SLE patients who have serositis, anti-RNP antibody positivity, or DLCO/%Pred <70%. RHC is suggested for patients suspected of having PAH. Once a diagnosis of SLE-PAH is confirmed, evaluation and treatment should immediately begin. CONCLUSION: Overall, we recommend performing early screening using TTE in SLE patients with serositis, anti-RNP antibodies, or a DLCO/%Pred <70%, even for patients in a relatively stable condition according to SLE disease activity index.

6.
Eur Respir J ; 53(2)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30635295

RESUMO

This study aimed to identify the long-term clinical outcomes and prognostic factors of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) confirmed by right heart catheterisation.A multicentre prospective cohort of SLE-associated PAH was established. Baseline and follow-up records were collected. The primary end-point was death. The secondary exploratory end-point was treatment goal achievement (TGA), defined as an integrated outcome.In total, 310 patients were enrolled from 14 PAH centres. The 1-, 3- and 5-year survival rates were 92.1%, 84.8% and 72.9%, respectively. The 1-, 3- and 5-year TGA rates were 31.5%, 53.6% and 62.7%, respectively. Baseline serositis, 6-min walking distance >380 m and cardiac index ≥2.5 L·min-1·m-2 were identified as independent prognostic factors of TGA. Patients with baseline serositis were more likely to reach TGA after intensive immunosuppressive therapy. TGA was identified as a positive predictor of survival in patients with SLE-associated PAH.TGA was associated with long-term survival, which supports the treat-to-target strategy in SLE-associated PAH. Baseline heart function predicted both survival and treatment goal achievement in patients with SLE-associated PAH. Patients with serositis at baseline tended to benefit from intensive immunosuppressive therapy and have a better clinical outcome.

7.
Clin Rheumatol ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511293

RESUMO

The authors regret that the Fig. 1 in the original version of this article contained an error. In the left column, 211 cases in the TGP group should be followed up for 8 weeks before 12 weeks. The correct figure presented in this article.

8.
Medicine (Baltimore) ; 97(49): e13528, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544455

RESUMO

BACKGROUND: Helicobacter pylori has been proved as a risk factor of many diseases. There are some researches trying to find connection between H. pylori and Sjögren syndrome (SS). However, the conclusions of these studies are controversial. We conducted this meta-analysis to evaluate the association between H. pylori and SS. METHODS: We searched PubMed and Embase databases for researches which include the data of H. pylori infection rate in SS and control groups. A fixed-effects model was used to analyze the risk odds ratio (OR) with 95% confidence intervals (CIs) according to the heterogeneity across the selected studies. RESULTS: Nine studies with 1958 participants including 619 patients with SS met the inclusion criteria. The total infection rate of H. pylori was 53.83% (1054/1958). We found that the patients with SS had a significantly higher H. pylori infection rate than control groups (OR = 1.19, 95% CI: 1.01-1.41, P = .033). Subgroup analysis demonstrated a significantly higher H. pylori infection rate in patients with primary SS than controls (OR = 1.24, 95% CI: 1.03-1.50, P = .026). CONCLUSION: This meta-analysis is the 1st meta-analysis about the association between H. pylori and SS. The pooled data suggested a significantly higher H. pylori infection rate in patients with SS. More prospective or multicenter retrospective researches could be conducted in the future.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Síndrome de Sjogren/epidemiologia , Infecções por Helicobacter/complicações , Humanos , Síndrome de Sjogren/complicações
9.
Inflammopharmacology ; 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30343452

RESUMO

BACKGROUND: Dexamethasone (DEX) is an effective therapeutic option commonly used in the treatment of many inflammatory diseases. However, DEX could impair proliferation or differentiation of osteoblasts, suggesting a pivotal role of DEX in bone destruction. OBJECTIVE: To investigate whether intraarticular injection of DEX could exacerbate bone erosion during CIA development. SETTING: Collagen-induced arthritis (CIA) mice were divided into PBS-treated and DEX-treated groups (n = 5/group). Negative control group: DBA/1 mice (n = 5) were used as age-matched, healthy, untreated controls. METHOD: CIA was induced in male DBA/1 mice. Intraarticular injected DEX (0.01 mg/Kg, 10 µl) into the knee joint of CIA on Day 28, Day 35, Day 42 and Day 49 post the 1st immunization. RESULTS: The severity of the arthritic disease was ameliorated in DEX-treated mice, accompanied by the decreased expression of IL-6, IL-8 and TNF-α. However, DEX treatment accelerates bone erosion and osteoporosis during CIA development and triggers higher expression of RANKL, IL-17 in vitro and vivo. MAIN OUTCOME MEASURE: The effect of DEX on bone structure was analyzed using Haematoxylin & Eosin (H&E) staining and Micro-CT. The levels of receptor activator for nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) were investigated by real-time PCR, Western Blot and immunohistochemical analysis. RASFs were stimulated with Interleukin (IL)-1ß and then treated with different concentrations of DEX for 72 h. CONCLUSION: Intraarticular injection of DEX could exacerbate bone erosion in CIA model via up-regulation of RANKL expression.

10.
Clin Rheumatol ; 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30280368

RESUMO

To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p < 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.

11.
Clin Exp Rheumatol ; 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30183595

RESUMO

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

12.
Environ Sci Process Impacts ; 20(9): 1273-1284, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30140829

RESUMO

To explore the oxidation effects and mechanisms for the oxidation of alkanes by H2O2 in a Fenton system catalyzed by two types of iron bound to soil organic matter (Fe-SOM) in crude oil-contaminated soil, an oxidation experiment was performed in active Fe-SOM and Fe-SOM systems. The results showed that the TPH removal ability of active Fe-SOM (average 0.36 g TPH/g Fe-SOM) was 2.25-fold higher than the corresponding value of Fe-SOM. Active Fe-SOM contained both -NH2 and -OH functional groups, and had a higher content of iron with high binding energy, while Fe-SOM only contained -NH2 groups. Thus, a large yield of hydroxyl radicals (·OH) was generated (8.92 a.u.) by active Fe-SOM catalyzing the decomposition of H2O2, while the corresponding yield of ·OH in the Fe-SOM system was only 4.81 a.u. In addition, the removal efficiency of C17-C23 (70%) was comparable to that of C24-C30 (69%), not restricted by the hydrophobicity of different alkanes. The alkane removal by active Fe-SOM was higher than that by Fe-SOM, although the content of Fe-SOM was double that of active Fe-SOM. In summary, the active Fe-SOM formed in the soil sample containing humic acid-like and hydrophobic acid derivates could catalyze H2O2 decomposition to improve the removal efficiency of crude oil in contaminated soil.


Assuntos
Alcanos/química , Peróxido de Hidrogênio/química , Ferro/química , Poluição por Petróleo/prevenção & controle , Poluentes do Solo/química , Solo/química , Catálise , Fluorometria , Substâncias Húmicas/análise , Radical Hidroxila/análise , Oxirredução , Petróleo , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Clin Rheumatol ; 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30123930

RESUMO

To estimate the mortality and describe the causes of death in a large multicenter cohort of hospitalized patients with SLE in China. This was a retrospective study of a nationwide SLE cohort (10 centers, 29,510 hospitalized patients) from 2005 to 2014 in China. Standardized mortality ratios (SMRs) were calculated for all death and were stratified by sex and age. Chi-square test was used to determine whether the major causes of death vary in age, sex, duration of SLE, disease activity, or medications. Comparison between dead patients and survival controls was used to identify the risk factors for mortality. Logistic regression analysis was used to evaluate the risk factors for mortality. A total of 360 patients died during the study period, accounting for 1.22%. The overall SMR was 2.13 (95% CI 1.96, 2.30), with a particularly high SMR seen in subgroups characterized by younger age. Infection (65.8%) was the most common cause of death, followed by lupus nephritis (48.6%), hematological abnormality (18.1%), neuropsychiatric lupus/NPSLE (15.8%), and interstitial pneumonia (13.1%). Cardiovascular disease and malignancy contributed little to the causes of death. Infection, in particular severe pulmonary infection, emerged as the foremost risk factor for mortality, followed by lupus encephalopathy. However, lupus nephritis and hematological abnormalities occurred more frequently in survival patients. SLE patients at a younger age of diagnosis have a poorer prognosis. Infection dominated the causes of death in recent China. Ethnicity and medications might account for the differences in causes of death compared with western populations.

14.
Cytokine ; 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-30001863

RESUMO

Interleukin (IL)-29 is known to modulate immune functions of monocytes or macrophages. In this study, we investigated the effect and its underlying mechanism of IL-29 on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis using murine macrophage cell line RAW264.7 cells and bone-marrow-derived monocyte/macrophage precursor cells (BMMs), and human peripheral blood mononuclear cells (PBMCs). In response to human recombinant IL-29, cell viability and apoptosis were assessed by Cell Counting Kit-8 and flow cytometry; the osteoclast formation and activity by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assay, respectively; the expression and activation of molecules that associated with osteoclastogenesis by real time-PCR, immunoblotting or immunofluorescent analysis. IL-28 receptor α (IL-28Rα), a specific receptor of IL-29 was expressed on RAW264.7 cells. Although IL-29 did not affect the viability and apoptosis of RAW264.7 cells, it inhibited multinucleated cells in the differentiation of osteoclastogenesis, the bone-resorbing activity of mature osteoclasts and osteoclastic specific genes expression including TRAP, cathepsin K (CTSK), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), C-Fos and matrix metallopeptidase 9 (MMP-9). This inhibitory effect of IL-29 was confirmed on BMMs and PBMCs and mediated via IL-28Rα through the activation of Stat1 and 3 and the suppression of nuclear factor kappa B (NF-κB) and NFATc1 nuclear translocation in RAW264.7 cells. In conclusion, IL-29 inhibited osteoclastogenesis via activation of STAT signaling pathway, prevention of NF-κB activation and NFATc1 translocation, and suppression of downstream osteoclastogenic genes expression.

16.
Arthritis Res Ther ; 20(1): 125, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29898766

RESUMO

Unfortunately, after publication of this article [1], it was noticed that the panel for Fig. 4b was inadvertently obscured during the production process. The full, correct Fig. 4 can be seen below and the original article has been corrected to reflect this.

17.
Clin Exp Rheumatol ; 36(5): 911-919, 2018 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29745893

RESUMO

Rheumatoid arthritis (RA), an autoimmune disease, is characterised by a persistent synovitis in the joints and systemic inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are widely used to treat RA patients. However, a portion of patients still have inadequate response to traditional medications. Recently, cell-based therapies have become the focus, attracting more attention due to their potential for remission induction. Several immune-regulatory cell types, such as haematopoietic stem cells, mesenchymal stem cells and regulatory T cells have been defined as novel targets. In this paper, we have summarised and reviewed current clinical trials using cell-based therapeutic approaches for the treatment of RA.

18.
Front Immunol ; 9: 749, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29706965

RESUMO

Objectives: Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. Methods: The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Results: Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. Conclusion: SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

19.
Pharmacogenomics ; 19(5): 383-392, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29517409

RESUMO

Iguratimod (IGU) is a novel disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). Like other DMARDs, IGU exhibited significant differences in effectiveness and safety. AIM: The aim of this study was to identify genetic predictorsof efficacyand toxicity of IGU in patients with RA. MATERIALS & METHODS: Seven SNPs from IGU-metabolizing genes were genotyped in 272 IGU-treated patients with RA. Results: ABCG2 rs2231142 A allele conferred a higher response to IGU, while NAT2 rs1495742 G carriersconferred a lower response to IGU. CYP2C19*2 rs4244285 A carriers had higher risk for IGU-induced toxicity compared to the GG carriers. CONCLUSION: Our study suggests that the polymorphisms of ABCG2 (rs2231142), NAT2 (rs1495741)and CYP2C19*2 (rs4244285) may help to predict thetherapeutic effectiveness and toxicity of IGU in patients with RA.

20.
Clin Rheumatol ; 37(6): 1493-1502, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29442259

RESUMO

Metabolomics has been applied to explore altered metabolite profiles in disease and identify unique metabolic signatures in recent years. We aim to characterize the metabolic profile of rheumatoid arthritis patients and explore its underlying pathological processes using metabolomics approach. Serum samples from 30 rheumatoid arthritis (RA) patients, 30 primary Sjogren's syndrome (pSS) patients, and 32 healthy controls (HC) were collected. The sample was analyzed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Potential biomarkers were screened from orthogonal projection to latent structure discriminate analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). Compared with HC and pSS patients, the RA patients had increased serum levels of 4-methoxyphenylacetic acid, glutamic acid, L-leucine, L-phenylalanine, L-tryptophan, L-proline, glyceraldehyde, fumaric acid, and cholesterol as well as decreased capric acid, argininosuccinic acid, and billirubin. A total of eight potential biomarkers were screened and tentatively identified for RA. A panel of three metabolites (4-methoxyphenylacetic acid, L-phenylalanine, and L-leucine) was identified as specific biomarkers of RA. ROC analysis showed that the panel had a sensitivity of 93.30% with a specificity of 95.20% in discrimination RA from other groups. UPLC-HRMS-based quantification of circulating metabolites was a useful tool for identifying RA patients from pSS patients and healthy controls. The potential biomarkers indicated that the RA metabolic disturbance might be associated with inflammation injury, amino acid metabolism, oxidative stress, and phospholipid metabolism.


Assuntos
Artrite Reumatoide/sangue , Biomarcadores/sangue , Metaboloma , Síndrome de Sjogren/sangue , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Humanos , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Adulto Jovem
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