Objective: Circular RNAs (circRNAs) are a significant class of molecules involved in a wide range of diverse biological functions that are abnormally expressed in many types of diseases. The present study aimed to determine the circRNAs specifically expressed in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify their possible molecular mechanisms. Methods: To identify the circRNAs specifically expressed in RA, we started by sequencing the of PBMCs circRNA and microRNAs (miRNAs) from a RA group (n = 3) and a control group (n = 3). We constructed a network of differentially expressed circRNAs and miRNAs. Then, we selected differentially expressed circRNAs in PBMCs from 10 RA patients relative to 10 age-and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Spearman's correlation test was used to evaluate the correlation of circRNAs with biochemical measurements. Results: A total of 165 circRNAs and 63 miRNAs were differently expressed between RA patients and healthy people according to RNA-seq, including 109 circRNAs that were significantly up-regulated and 56 circRNAs that were down-regulated among the RA patients. RT-qPCR validation demonstrated that the expression levels of hsa circ 0001200, hsa circ 0001566, hsa circ 0003972, and hsa circ 0008360 were consistent with the results from the sequencing analysis. Then, we found that there were significant correlations between the circRNAs and disease severity. Conclusion: Generally, these results suggest that expression of hsa circ 0001200, hsa circ 0001566, hsa circ 0003972, and hsa circ 0008360 in PBMCs from RA patients may serve as potential biomarkers for the diagnosis of RA, and these circRNAs may influence the occurrence and development of RA.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in-house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.
Long noncoding RNAs (lncRNAs) are >200‐bp molecules that do not generally code for proteins. Human lncRNAs have well‐characterized roles in gene expression regulation, particularly with regard to protein‐coding genes, and their dysregulation has been linked to disease. Here, we set out to investigate changes in the expression of lncRNAs related to apoptosis and autophagy in the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA). In addition, we aimed to correlate lncRNA expression profiles with clinical indexes and self‐perception of patients (SPP). To this end, we employed RNA sequencing of lncRNAs in PBMCs from three patients with RA and three healthy controls. We used bioinformatics to screen several dysregulated lncRNAs related to apoptosis and autophagy. To validate key lncRNA candidates, we performed quantitative reverse transcriptase–PCR on 20 patients with RA and 20 healthy controls. We found the expression of seven lncRNAs (MAPKAPK5‐AS1, ENST00000619282, C5orf17, LINC01189, LINC01006, DSCR9 and MIR22HG) was significantly altered in PBMCs of patients with RA. Receiver operating characteristic curve analysis suggested that MIR22HG [area under the curve (AUC) = 0.846, P = 0.000], DSCR9 (AUC = 0.783, P = 0.005), LINC01189 (AUC = 0.677, P = 0.034), MAPKAPK5‐AS1 (AUC = 0.644, P = 0.025) and ENST00000619282 (AUC = 0.636, P = 0.043) are potential biomarkers of RA. Spearman's correlation analysis revealed selected lncRNAs correlated with clinical indexes and SPP. Therefore, we highlight that some lncRNAs related to apoptosis and autophagy may serve as potential biomarkers for diagnosis and monitoring of RA progression, which also correlate with several clinical indexes and SPP.
Rheumatoid arthritis (RA), recognized as a common chronic autoimmune disease, is characterized by the excessive proliferation and inflammatory infiltration of fibroblast‐like synoviocytes (FLS). In this study, our purpose is to elucidate the mechanisms of triptolide (TPL) in the treatment of RA by regulating the long non‐coding RNA (lncRNA) ENST00000619282, which promoted apoptosis and reduced inflammatory infiltration of FLS in RA (RA‐FLS). RA‐FLS was treated with different concentrations of TPL at different time points. CCK‐8 assay, ELISA, RT‐qPCR, immunofluorescence, TUNEL assay, and the transmission electron microscopy were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Next, the involvement of ENST00000619282 in TPL‐mediated protection against RA was explored. ENST00000619282 expression was significantly increased in the peripheral blood mononuclear cells (PBMCs) of RA patients. ENST0000061928 expression in RA PBMCs was positively associated with ESR, RF, CCP, and DAS28, while TPL treatment led to a downregulation of ENST00000619282. In addition, ENST00000619282 was significantly increased in RA‐FLS. Furthermore, overexpression of ENST00000619282 elevated the levels of pro‐apoptotic and pro‐inflammatory factors, while reduced the levels of anti‐apoptotic proteins and antiinflammatory factors. Besides, TPL treatment could reverse these effects by ENST00000619282 overexpression. The anti‐RA potential of TPL might be achieved by downregulating ENST00000619282, thereby promoting apoptosis, and reducing the inflammatory response in RA.
Objective. This study aimed to ascertain the immuno-inflammatory molecular targets of Xinfeng capsules (XFC) in the treatment of ankylosing spondylitis (AS) based on data mining, network pharmacology, and molecular docking. Methods. The efficacy of XFC in the treatment of AS was assessed by clinical data mining. Network pharmacology was utilized to establish a network of the targets for XFC active ingredients in the treatment of AS. The binding mode and affinity of XFC active ingredients to the key targets for AS were predicted using molecular docking. Results. XFC significantly diminished immuno-inflammatory indicators of AS. In total, 208 targets of XFC were obtained from the TCMSP database and 629 disease targets of AS were screened from the GeneCards database, which were intersected to yield 57 targets of XFC in the treatment of AS. Protein-protein interaction, gene ontology, and Kyoto genome encyclopedia analyses showed that XFC might activate TNF and NF-κB signaling pathways. Quercetin, kaempferol, triptolide, and formononetin had free binding energies < -9 kcal/mol to inflammatory targets (TNF and PTGS2) in the molecular docking analysis of XFC-active ingredients, indicating that TNF and PTGS2 might be the targets of the action of XFC. Conclusions. Collectively, XFC had a significant therapeutic effect on AS. Specifically, the active ingredients of XFC, including quercetin, kaempferol, triptolide, and formononetin, inhibited the inflammatory response in AS by downregulating TNF and PTGS2 in the TNF and NF-κB signaling pathways.
Background Abnormal expression of long noncoding RNAs (lncRNAs) is involved in several autoimmune diseases including rheumatoid arthritis (RA). In this study, we intended to explore the expression of lncRNA LINC00638 in RA and its potential mechanism of action related to inflammation and oxidative stress. Methods The level of LINC00638 in the peripheral blood mononuclear cells (PBMCs) obtained from 45 RA patients and 30 normal controls was analyzed and its correlation with clinical indicators was investigated. In vitro, we used tumor necrosis factor‐α to stimulate fibroblast‐like synoviocytes (FLS) of RA patients for cell based experiments. Subsequently, the overexpressed plasmid and small interfering RNA of LINC00638 were designed. Furthermore, we further analyzed the potential effects of LINC00638 on the proliferation and migration of RA‐FLS and the nuclear factor erythrocyte derived 2 related factor 2 (Nrf2)/heme oxygenase 1 (HO‐1) pathway. Results LINC00638 expression was found to be significantly decreased in PBMCs of RA patients, and it was negatively correlated with erythrocyte sedimentation rate, interleukin (IL)‐17, reactive oxygen species (ROS), and disease activity scores for 28 joints (DAS28). Overexpression of LINC00638 activated the Nrf2/HO‐1 pathway, markedly decreased the expressions of IL‐6, IL‐17, IL‐23, ROS, as well as malondialdehyde, increased the total antioxidant capacity, and attenuated the proliferation and migration of RA‐FLS, while silencing of LINC00638 reversed these manifestations. Conclusions LINC00638 was found to be expressed at low levels in RA patients and was associated with immune inflammation, oxidative stress, and disease activity. Overexpression of LINC00638 can reduce the proliferation as well as migration of RA‐FLS, and activate the Nrf2/HO‐1 pathway to inhibit the inflammation and oxidative stress.
Self-perception in patients is their self-response to sensory stimuli. It is an important aspect of the existence and quality of life among patients. However, the inherent relationship between self-perception and the cellular activity at the molecular level is elusive. In this study, we aimed to explore the association of self-perception with RNA expression profile in patients with rheumatoid arthritis (RA) through computational analysis. We recruited 30 patients clinically diagnosed with RA and to age-and sex-matched controls without previous clinical history. In total, 5 self-perception measures and 30 RNA expression measures were derived from RA patients and control groups. A correlation analysis based on Spearman correlation and Logistic-regression methods was adopted to assess the correlation between self-perception and RNA expression. Quantitative analysis revealed that RA patients with poor self-perception were closely associated with RNAs expression, In addition, 3 key molecules including AC019117.2, LINC00638, and hsa_circ_0003972 could be used to predict self-perception changes in RA patients. Herein, our results will provide new insights in RA diagnosis however, the underlying mechanisms need to be further explored.
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