RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

A Real-World Study on the Effect of Imrecoxib for Patients with Axial Spondyloarthritis.

Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have generally been viewed as first-line therapy for axial spondyloarthritis (axSpA). Imrecoxib is a selective COX-2 inhibitor developed independently in China. At present, only one single-center RCT trial has shown that imrecoxib is equally effective as celecoxib in treating axSpA. Based on real-world data, our study aims to explore the efficiency of imrecoxib and TNF inhibitor (TNFi) combined with imrecoxib in treating axSpA. Patients and Methods: A total of 163 patients with axSpA who had more than two follow-up records in 6 months and treated with imrecoxib/celecoxib/TNFi combined with imrecoxib/TNFi combined with celecoxib from the First Affiliated Hospital of Anhui Medical University SpA Real World Database (AHSpA) were selected for analysis of our study. The linear mixed model was used to compare efficacy indexes before and after treatment and between different groups, adjust baseline measurement value and follow-up time. The Kaplan-Meier survival analysis was used to identify the differences in cumulative clinical remission rates between groups with different treatment at the follow-up period. Results: Results showed that after treatment ASDAScrp was slightly improved in imrecoxib group and celecoxib group within 6 months (p < 0.05). CRP, ESR, BASDAI, ASDAScrp, BASFI, occiput to wall distance and finger floor distance all significantly improved in TNFi combined with imrecoxib group and TNFi combined with celecoxib group within 6 months (all p < 0.05). According to the Kaplan-Meier survival curve and Log rank test analysis, the clinical remission rate was not significantly different between different treatment during 24-month follow-up (all p > 0.05). Conclusion: ASDAScrp improved slightly within 6 months after treatment with imrecoxib, and TNFi combined with imrecoxib significantly improved multiple effect indexes in axSpA patients. The efficacy of imrecoxib and celecoxib in the treatment of axSpA is equivalent. Also, they have the same efficacy after being combined with TNFi.

Presence of subclinical inflammation in axial spondyloarthritis patients with NSAID/anti-TNF-α drug-induced clinical remission.

OBJECTIVE: To investigate the rate of subclinical inflammation in patients with axial spondyloarthritis (axSpA) with nonsteroidal anti-inflammatory drug (NSAID)/anti-tumor necrosis factor (TNF)-α drug-induced clinical remission and to explore factors influencing clinical and imaging remission. METHODS: One hundred twenty-five patients with axSpA followed up for at least 6 months were enrolled in this prospective study and randomly divided into two groups. Ninety patients were treated with anti-tumor necrosis factor (TNF)-α or anti-TNF-α combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (anti-TNF-α treatment group), and thirty-five patients were treated with only NSAIDs (non anti-TNF-α treatment group). The improvements in the clinical remission rate, imaging remission rate, and disease parameters before and after the different treatments were compared. Risk factors for clinical and imaging remission were analyzed by multivariate logistic regression analysis. RESULTS: The clinical and imaging remission rate was increased after treatment especially in the anti-TNF-α group (P < 0.001). The remission rate of imaging in the group with clinical remission was higher than that in the group with clinical non-remission (P < 0.05). After treatment, the remission rates of imaging in the clinical remission and non-remission group were significantly higher than those before treatment (P < 0.0001). The results of multivariate logistic regression analysis showed that higher CRP was a risk factor for failure of clinical remission in axSpA (OR = 2.034, 95% CI:1.595 ~ 2.617, P < 0.001), while higher ASDAScrp was a risk factor for failure of imaging remission (OR = 1.306, 95% CI:1.026 ~ 1.688, P < 0.05). Anti-TNF-α treatment was a protective factor for both clinical (OR = 0.234, 95% CI:0.091 ~ 0.605, P < 0.05) and imaging remission (OR = 0.511, 95% CI:0.286 ~ 0.914, P < 0.05). CONCLUSION: Even after regular treatment, some clinical remission patients continued to have evidence of subclinical inflammation. Higher CRP and ASDAScrp are risk factors for clinical and imaging non-remission in axSpA respectively, Continuous NSAID treatment (more than 1 year) can effectively improve clinical and MRI inflammation in patients, but anti-TNF-α treatment is more beneficial for clinical and imaging remission. Key Points • Some patients achieving ASDAScrp remission status continue to have inflammation when assessed with objective imaging techniques. • MRI can sensitively measure bone marrow inflammation and may provide a more accurate assessment of remission. • Controlling inflammation, especially reducing CRP and ASDAScrp levels, is a key factor for achieving clinical and imaging remission in patients with axSpA.

The Potential Regulatory Mechanism of lncRNA 122K13.12 and lncRNA 326C3.7 in Ankylosing Spondylitis.

This work aims to analyze and construct a novel competing endogenous RNA (ceRNA) network in ankylosing spondylitis (AS) with bone bridge formation, lncRNA. Using RNA sequencing and bioinformatics, we analyzed expression profiles of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in whole blood cells from 5 AS patients and 3 healthy individuals. Next, we verified the expression levels of candidate lncRNAs in 97 samples using the ΔΔCt value of real-time quantitative polymerase chain reaction (qRT-PCR). We used multivariate logistic regression analysis to screen lncRNAs and clinical indicators for use in the prediction model. Both SPSS 24.0 and R software were used for data analysis and prediction model construction. The results showed that compared with the normal controls, 205 long noncoding RNAs (lncRNAs), 961 microRNAs (miRNAs), and 200 mRNAs (DEmRNAs) were differentially expressed in the AS patients. We identified lncRNA 122K13.12 and lncRNA 326C3.7 among 205 lncRNAs differentially expressed between AS patients and healthy humans. Then, we noted that 30 miRNAs and five mRNAs formed a ceRNA network together with these two lncRNAs. These ceRNA networks might regulate the tumor necrosis factor (TNF) signaling pathway in AS development. In addition, the expression level of lncRNA 122K13.12 and lncRNA 326C3.7 correlated with various structural damage indicators in AS. Specifically, the lncRNA 326C3.7 expression level was an independent risk factor in bone bridge formation [area under the ROC curve (AUC) = 0.739 (0.609-0.870) and p = 0.003], and the best Youden Index was 0.405 (sensitivity = 0.800 and specificity = 0.605). Moreover, we constructed a lncRNA-based nomogram that could effectively predict bone bridge formation [AUC = 0.870 (0.780-0.959) and p < 0.001, and the best Youden Index was 0.637 (sensitivity = 0.900 and specificity = 0.737)]. In conclusion, we uncovered a unique ceRNA signaling network in AS with bone bridge formation and identified novel biomarkers and prediction models with the potential for clinical applications.

[Immunogenicity of envelope glycoprotein gene of reticuloendotheliosis virus expressed in insect cell].

A recombinant baculovirus expressing reticuloendotheliosis virus env gene was constructed with Bac-to-Bac Baculovirus Expression Systems. After transfecting the recombinant virus into Sf9 cells for 3 days, REV env can be detected by indirect immunofluorescence antibody assay (IFA) and Western blot with specific monoclonal antibodies of REV. The oil-water emulsion vaccine was then produced using this infected Sf9 cells lycates and inoculated SPF chickens to validate the immunogenicity for REV. The results show that special anti-REV antibody can maintain more than 45 days and resist the infection of REV viruses. This is the first success to induce anti-REV antibody in chickens by none-live viruses.