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Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): -0.70; 95% confidence interval (CI): -1.25, -0.15; P = 0.01) and 3rd month (SMD: -1.47; 95% CI: -2.77, -0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: -0.38; 95% CI: -0.72, -0.05; P = 0.03) and 6th months (SMD: -0.81; 95% CI: -1.32, -0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels.

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ZNF503 antisense RNA 1 (ZNF503-AS1) is a newly identified long non-coding RNA (lncRNA) that regulates retinal pigment epithelium differentiation. To study its role in diabetic retinopathy, we performed RT-qPCR to measure plasma ZNF503-AS1 levels of 298 diabetic patients immediately after the diagnosis, during the follow-up, and at the end of follow-up. Plasma lncRNA ZNF503-AS1 expression in 96 healthy participants was also detected by RT-qPCR. Transforming growth factor beta 1 (TGF-ß1) expression after ZNF503-AS1 overexpression was detected by Western blot. Cell proliferation and apoptosis were detected by cell proliferation and apoptosis assays, respectively. We found that ZNF503-AS1 was not differentially expressed in healthy participants and diabetic patients. High plasma lncRNA ZNF503-AS1 level was correlated with a high incidence of diabetic retinopathy. Plasma lncRNA ZNF503-AS1 level was higher in patients with diabetic retinopathy than in patients with other complications (p < 0.05). ZNF503-AS1 overexpression inhibited proliferation, promoted cell apoptosis, and upregulated TGF-ß1 expression (p < 0.05). We concluded that ZNF503-AS1 might participate in diabetic retinopathy by activating TGF-ß signaling.

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BACKGROUND: Cross-sectional studies suggest an association between metabolic syndrome (MetS) and knee osteoarthritis (KOA). We performed a meta-analysis to evaluate whether MetS is an independent risk factor for KOA. METHODS: Prospective cohort studies evaluating the association between MetS and KOA in general population were retrieved from PubMed and Embase. Only studies with multivariate analyses were included. Data were pooled with a random-effect model, which is considered to incorporate heterogeneity among the included studies. RESULTS: Five studies including 94,965 participants were included, with 18,990 people with MetS (20.0%). With a mean follow-up duration of 14.5 years, 2,447 KOA cases occurred. Pooled results showed that MetS was not significant associated with an increased risk of KOA after controlling of factors including body mass index (adjusted risk ratio [RR]: 1.06, 95% CI: 0.92~1.23, p = 0.40; I2 = 33%). Subgroup analysis showed that MetS was independently associated with an increased risk of severe KOA that needed total knee arthroplasty (RR = 1.16, 95% CI: 1.03~1.30, p = 0.02), but not total symptomatic KOA (RR = 0.84, 95% CI: 0.65~1.08, p = 0.18). Stratified analyses suggested that MetS was independently associated with an increased risk of KOA in women (RR = 1.23, 95% CI: 1.03~1.47, p = 0.02), but not in men (RR = 0.90, 95% CI: 0.70~1.14, p = 0.37). CONCLUSIONS: Current evidence from prospective cohort studies did not support MetS was an independent risk factor of overall KOA in general population. However, MetS may be associated with an increased risk of severe KOA in general population, or overall KOA risk in women.

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The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene-gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case-control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40-2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38-2.13). GMDR analysis suggested a potential gene-gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67-3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.

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Fucoidan is a sulfated polysaccharide found mainly in various species of brown algae and brown seaweed. Here, we investigated the effects of low-molecular-weight (LMW) fucoidan (4 kDa) on interleukin-1beta (IL-1ß)-stimulated rheumatoid arthritis fibroblast-like synoviocyte (RAFLS). 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and annexin V/propidium iodide assay were used to assess cell viability and apoptosis, respectively. Transwell assay was performed to evaluate cell invasion. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay analysis was done to measure gene expression and secretion. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined by electrophoretic mobility shift assay. LMW fucoidan dose-dependently inhibited the viability and induced apoptosis of IL-1ß-treated RAFLS. Fucoidan attenuated IL-1ß-induced invasion of RAFLS and decreased the expression and secretion of metalloproteinase (MMP)-1, MMP-3, and MMP-9. Fucoidan suppressed NF-κB binding activity, p65 nuclear translocation, and IκB-α degradation in IL-1ß-stimulated RAFLS. Additionally, IL-1ß-induced phosphorylation of p38 but not ERK or JNK was significantly impaired by fucoidan treatment. LMW fucoidan reduces the viability, survival, and invasiveness of IL-1ß-treated RAFLS, which is associated with inhibition of NF-κB and p38 activation. LMW fucoidan may have therapeutic potential in the treatment of rheumatoid arthritis.

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