Increased FURIN expression in rheumatoid arthritis patients and its anti-inflammatory effect.

BACKGROUND: FURIN belongs to the proprotein convertase family that processes proproteins and is involved in many diseases. However, the role of FURIN in rheumatoid arthritis (RA) remains unknown. In this study, we investigated the association between circulating FURIN and disease activity in patients with RA and the effect of FURIN in THP-1-derived macrophages. METHODS: A total of 108 RA patients and 39 healthy controls participants were included in this study. RA patients were divided into four disease activity groups determined by the Disease Activity Score of 28 joints (DAS28). FURIN expression in peripheral blood mononuclear cells (PBMCs) and serum was detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Western blotting and qRT-PCR were used to detect cytokines level after interfering FURIN expressed in THP-1-derived macrophages. RESULTS: Both FURIN mRNA and protein levels were significantly higher in RA patients than in healthy controls participants (P < .001). No significant difference in FURIN expression was observed among the four RA groups (P > .05). Spearman correlation revealed that FURIN positively correlated with transforming growth factor-ß1(TGF-ß1), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP). Moreover, the inhibition of FURIN in THP-1-derived macrophages promoted the caspase-1 and IL-1ß expression (P < .05). CONCLUSION: FURIN levels were significantly increased in the peripheral blood of RA patients and were not associated with disease activity. The inhibition of FURIN in THP-1-derived macrophages with elevated IL-1ß levels shows that FURIN may have an anti-inflammatory effect.

Erratum to "Increased Expression of TLR10 in B Cell Subsets Correlates with Disease Activity in Rheumatoid Arthritis".

[This corrects the article DOI: 10.1155/2018/9372436.].

The association between albumin-dNLR score and disease activity in patients with rheumatoid arthritis.

BACKGROUND: Recently, clinical studies have described an association between albumin and the derived neutrophil to lymphocyte ratio (dNLR) with several diseases. This study was aimed to investigate the albumin-dNLR (ALB-dNLR) score in rheumatoid arthritis (RA) patients and assess its relationship with clinical and laboratory parameters of RA. METHODS: We retrospectively enrolled 127 RA patients, 155 osteoarthritis (OA) patients, and 155 healthy controls. The ALB-dNLR score was based on serum albumin level, neutrophil count, and white cell count. The Spearman's rank test was used to measure the correlations between ALB-dNLR score and disease activity as well as laboratory indexes. RESULTS: The ALB-dNLR score was significantly higher in RA patients than in OA patients (P < 0.001) and in healthy controls (P < 0.001). The proportion of higher ALB-dNLR score has been raised along with increased disease activity (P < 0.001). The Spearman's rank test showed that ALB-dNLR score was positively associated with DAS28 score, CRP, ESR, IgA, and platelet count. Moreover, the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of ALB-dNLR was 0.693 (95% CI: 0.631-0.755), which was higher than that of albumin (AUC: 0.625, 95% CI: 0.559-0.692) and dNLR (AUC: 0.680, 95% CI: 0.617-0.743) alone. CONCLUSIONS: The results demonstrate that the ALB-dNLR score increased in RA patients. The ALB-dNLR score may be a useful marker to estimate the disease activity of RA patients.

Increased Expression of TLR10 in B Cell Subsets Correlates with Disease Activity in Rheumatoid Arthritis.

Toll-like receptor (TLR) 10, mainly expressed on B cells, has emerged as a modulatory receptor in inflammation. Nonetheless, the clinical significance of TLR10 in rheumatoid arthritis (RA) remains unclear. In this study, we explored the expression of TLR10 in B cells and B cell subsets in RA subjects and healthy controls (HCs) and determined its relevance to disease activity and inflammatory biomarkers. TLR10 levels in B cells and B cell subsets (CD19+CD27+, CD19+CD27-, CD27+IgD-, CD27+IgD+, CD27-IgD+, D27-IgD-, CD19+CD5+, and CD19+CD5-) and inflammatory biomarker concentrations in peripheral blood (PB) obtained from RA subjects and HCs were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations of TLR10 expression with disease activity and inflammatory biomarkers were then analysed. Similar levels of TLR10 in all CD19+ B cells were observed in the RA subjects and HCs. Compared to that in the HCs, TLR10 was elevated significantly in the CD19+CD27-IgD- and CD19+CD5+ subsets in the RA subjects. In addition, almost all subsets expressing TLR10 were increased with disease activity. The present study reveals that enhanced TLR10 in B cell subsets is positively correlated with disease activity in RA subjects.

Estradiol inhibits NLRP3 inflammasome in fibroblast-like synoviocytes activated by lipopolysaccharide and adenosine triphosphate.

OBJECTIVE: Nucleotide binding domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome is known for activating pro-inflammatory cytokines in knee osteoarthritis (OA). This study was performed to identify whether NLRP3 inflammasome can be triggered by lipopolysaccharides (LPS) and adenosine triphos adenine (ATP), which are positively related with knee OA severity in joint-spaces, in human fibroblast-like synoviocytes (FLS), and to identify whether estrogen would inhibit the activation of NLRP3 inflammasome. METHODS: In the present study, human FLS were isolated from the knee OA in patients during arthroplasty, and were treated with LPS and ATP in the presence or absence of estradiol (E2). The messenger RNA (mRNA) and protein levels of NLRP3 components were analyzed by real-time polymerase chain reaction and western blotting, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to examine interleukin (IL)-1ß and IL-18 content in the supernatant. Estrogen receptor α inhibitor MPP and ß inhibitor PHTPP were used to explore how E2 works. RESULTS: Our results demonstrated that treatment with LPS and ATP increased significantly both in mRNA and protein levels of all the NLRP3 inflammasome components, and triggered the NLRP3 inflammasome, followed by upregulated IL-1ß and IL-18 in the cell supernatant. E2 appeared to inhibit the activation of NLRP3 inflammasome by diminishing mRNA and protein levels of NLRP3 through estrogen receptor ß, and decreased the expression of IL-1ß and IL-18 as well. CONCLUSION: These results suggested the increased LPS and ATP in joint-space may promote knee OA by NLRP3 inflammasome and E2 may exert a protective effect by inhibiting the activation of NLRP3 inflammasome in FLS.

Prognostic significance of pre-resection albumin/fibrinogen ratio in patients with non-small cell lung cancer: A propensity score matching analysis.

BACKGROUND: Nutrition and coagulation play important roles in cancer progression. This study was aimed to investigate the value of the albumin/fibrinogen ratio (AFR) in non-small cell lung cancer (NSCLC) patients, through a propensity score matching (PSM) method. METHODS: We retrospectively analyzed 529 NSCLC patients underwent surgical resection from 2010 to 2015. PSM was used to eliminate possible biases. A Cox proportional hazards regression model was performed to evaluate the prognostic value of AFR in NSCLC. RESULTS: The optimal value was 9.67 for the AFR by ROC (receiver operating characteristic) curve. The AFR was statistically significantly associated with age, sex, smoking history, histological subtype, tumor size, pathological stage and adjuvant therapy (p < 0.05). Multivariate analysis indicated that the pathological stage and pre-resection AFR were independent prognostic factors for patients with NSCLC. Additionally, elevated AFR indicated a better outcome, and patients with higher AFR had lower risk for overall death (OS) (HR 0.512, 95% CI 0.316-0.829, p = 0.006) as well as disease-free death (DFS) (HR 0.561, 95% CI 0.399-0.787, p = 0.001). The propensity score model identified 120 patients from each group that were balanced for age, sex, smoking history, histological subtype, tumor size, stage distribution and adjuvant therapy. In multivariable regression analysis of PSM groups, the result indicated that the AFR was predictive for OS (HR 0.392, 95% CI 0.225-0.683, p < 0.001) and DFS (HR 0.526, 95% CI 0.344-0.805, p = 0.003). CONCLUSIONS: Pre-resection AFR can be considered as an independent prognostic factor in NSCLC patients, and higher AFR may enhance OS and DFS of NSCLC patients.

Corrigendum to "Serum Sclerostin Levels in Patients with Ankylosing Spondylitis and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis".

[This corrects the article DOI: 10.1155/2017/9295313.].

Serum Sclerostin Levels in Patients with Ankylosing Spondylitis and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Objective. Current studies of serum sclerostin levels in AS and RA patients are inconsistent. This meta-analysis was performed to identify the association of serum sclerostin level with AS and RA patients. Methods. Embase, PubMed, MEDLINE, and Cochrane Library databases (up to 25 January 2017) were used to collect all relevant published articles. Studies were pooled and standard mean difference (SMD) with 95% confidence interval (CI) was calculated. All data analyses were performed using RevMan 5.3. Results. Totally eight studies of AS including 420 AS patients and 317 healthy controls (HC) and three studies of RA including 145 RA patients and 127 HC were finally included in this meta-analysis. The results revealed that the serum sclerostin levels in both AS patients (SMD = -0.14; 95% CI = [-0.39,0.11]; P = 0.28) and RA patients (SMD = -0.10; 95% CI = [-0.34,0.15]; P = 0.43) were not significantly different from those in HC. Conclusion. The difference of serum sclerostin levels in AS and RA patients was not significantly different from HC, indicating that the sclerostin may not associate with the development of AS and RA.

The association between the lymphocyte-monocyte ratio and disease activity in rheumatoid arthritis.

The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory marker for prediction of disease development, progress, and survival. Recently, a genome-wide association study identified genetic variations in ITGA4 and HLA-DRB1 that affect the LMR levels and were widely believed to be susceptibility genes for autoimmune diseases, including rheumatoid arthritis (RA). However, the role of LMR in RA patients remains unclear. The LMR level and other laboratory data of 66 RA patients, 163 osteoarthritis (OA) patients, and 131 healthy controls (HC) were compared using binary logistic regression. The correlations between LMR and disease activity and other inflammatory markers were measured using the Spearman rank test. ROC curve analyses assessed the diagnostic accuracy of LMR in RA. The LMR and lymphocyte count were significantly lower in RA patients, whereas the monocyte count was significantly higher relative to the HC group/OA patients (p < 0.01). A decreased LMR has been associated with increased disease activity (p = 0.012). In addition, the DAS28 and traditional inflammatory markers, including ESR, CRP, RDW, PLR, and NLR, and immune-related factors, such as C4, IgA, and IgM, were inversely correlated with LMR, while hemoglobin and albumin were positively correlated with LMR. The ROC curve showed that the area under the curve of LMR was 0.705 (95%CI = 0.630-0.781). The corresponding specificity and sensitivity were 82.82 and 45.45%, respectively. The present study shows that the LMR is an important inflammatory marker which could be used to identify disease activity in RA patients and to distinguish RA from OA patients.