Eukaryotic translation initiation factor 6-mediated ribosome biogenesis promotes synovial aggression and inflammation by increasing the translation of SP1 in rheumatoid arthritis.

Introduction: Fibroblast-like synoviocytes (FLSs) play critical roles in synovial inflammation and aggression in rheumatoid arthritis (RA). Here, we explored the role of eukaryotic translation initiation factor 6 (eIF6) in regulating the biological behaviors of FLSs from patients with RA.

Methods: FLSs were isolated from the synovial tissues of RA patients.

FTO-mediated RNA mA methylation regulates synovial aggression and inflammation in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (mA) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the mA demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients.

NAT10 promotes synovial aggression by increasing the stability and translation of N4-acetylated PTX3 mRNA in rheumatoid arthritis.

Objective: Recent studies indicate that N-acetyltransferase 10 (NAT10)-mediated ac4C modification plays unique roles in tumour metastasis and immune infiltration. This study aimed to uncover the role of NAT10-mediated ac4C in fibroblast-like synoviocytes (FLSs) functions and synovial immune cell infiltration in rheumatoid arthritis (RA).

Methods: FLSs were obtained from active established patients with RA.

Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis.

Objective: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s).

Response to belimumab among patients with refractory lupus nephritis: a real-world observational retrospective multicenter study.

Objectives: Belimumab is a biological agent approved for the treatment of active lupus nephritis (LN), but its efficacy on refractory lupus nephritis (LN) is unknown. This study aims to evaluate the efficacy and safety of belimumab in Chinese patients with refractory LN.

Methods: This multicenter, observational, and retrospective study enrolled patients with refractory LN who failed induction therapy with steroids, cyclophosphamide, mycophenolate, and calcineurin inhibitors and received 24-week belimumab treatment before data analysis.

ALKBH5-Mediated RNA m A Methylation Regulates the Migration, Invasion, and Proliferation of Rheumatoid Fibroblast-Like Synoviocytes.

Objective: Fibroblast-like synoviocytes (FLSs) are critical for promoting joint damage in rheumatoid arthritis (RA). N -methyladenosine (m A) modification plays key roles in various diseases, but its role in the pathogenesis of RA is largely unknown. Here, we investigate increased demethylase ALKBH5 promotion of proliferation, migration, and invasion of RA FLSs via regulating JARID2 expression.

Schisandrin treatment suppresses the proliferation, migration, invasion, and inflammatory responses of fibroblast-like synoviocytes from rheumatoid arthritis patients and attenuates synovial inflammation and joint destruction in CIA mice.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease causing joint dysfunction. As disease-modifying anti-rheumatic drugs (DMARDs) have poor efficacy in 20% to 25% of RA patients, additional novel RA medications are urgently needed. Schisandrin (SCH) has multiple therapeutic effects.

SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C.

Fibroblast-like synoviocytes (FLSs), play a key role in perpetuating synovial inflammation and bone erosion in rheumatoid arthritis (RA), however, the underlying mechanism(s) of RA FLSs activation and aggression remain unclear. Identifying endogenous proteins that selectively target FLSs is urgently needed. Here, we systematically identified that secreted modular calcium-binding protein 2 (SMOC2), was significantly increased in RA FLSs and synovial tissues.

Long Noncoding RNA HAFML Promotes Migration and Invasion of Rheumatoid Fibroblast-like Synoviocytes.

The aggressive phenotype exhibited by fibroblast-like synoviocytes (FLSs) is critical for the progression of joint destruction in rheumatoid arthritis (RA). Long noncoding RNAs (lncRNAs) have crucial roles in the pathogenesis of diverse disorders; however, few have been identified that might be able to control the joint damage in RA. In this study, we identified an lncRNA, ENST00000509194, which was expressed at abnormally high levels in FLSs and synovial tissues from patients with RA.

Myricitrin inhibits fibroblast-like synoviocyte-mediated rheumatoid synovial inflammation and joint destruction by targeting AIM2.

To explore the effect and underlying mechanism of Myricitrin (Myr) in regulating fibroblast-like synoviocyte (FLS)-mediated synovitis and joint destruction in RA. FLSs were isolated from synovial tissues from patients with RA. Gene expression was measured using quantitative RT-qPCR.

signaling in the regulation of rheumatoid synovial aggression.

Background: Fibroblast-like synoviocytes (FLSs) play a critical role in promoting synovial aggression and joint destruction in rheumatoid arthritis (RA). Cyclic GMP-AMP synthase ()/stimulator of interferon gene () signaling plays an important role in controlling a series of cellular biological processes. However, it is still unclear whether signaling regulates rheumatoid synovial aggression.

The suppression of Brd4 inhibits peripheral plasma cell differentiation and exhibits therapeutic potential for systemic lupus erythematosus.

The mechanisms that control B cell terminal differentiation remain undefined. Here, we investigate the role of bromodomain-containing protein 4 (Brd4) in regulating B cell differentiation and its therapeutic potential for B cell-mediated autoimmune diseases including systemic lupus erythematosus (SLE). We showed that Brd4 inhibitor PFI-1 suppressed plasmablast-mediated plasma cell differentiation in healthy human CD19 B cells.

Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression.

Fibroblast-like synoviocytes (FLSs) play a key role in controlling synovial inflammation and joint destruction in rheumatoid arthritis (RA). The contribution of long noncoding RNAs (lncRNAs) to RA is largely unknown. Here, we show that the lncRNA LINK-A, located mainly in cytoplasm, has higher-than-normal expression in synovial tissues and FLSs from patients with RA.

Nitidine chloride inhibits fibroblast like synoviocytes-mediated rheumatoid synovial inflammation and joint destruction by targeting KCNH1.

Objective: Nitidine chloride (NC), a natural small molecular compound from traditional Chinese herbal medicine zanthoxylum nitidum, has been shown to exhibit anti-tumor effect. However, its role in autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we investigate the effect of NC in controlling fibroblast-like synoviocytes (FLS)-mediated synovial inflammation and joint destruction in RA and further explore its underlying mechanism(s).

Increased SUMO-activating enzyme SAE1/UBA2 promotes glycolysis and pathogenic behavior of rheumatoid fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLSs) are critical to joint inflammation and destruction in rheumatoid arthritis (RA). Increased glycolysis in RA FLSs contributes to persistent joint damage. SUMOylation, a posttranslational modification of proteins, plays an important role in initiation and development of many diseases.

Accumulation of cytosolic dsDNA contributes to fibroblast-like synoviocytes-mediated rheumatoid arthritis synovial inflammation.

The accumulation of cytosolic dsDNA plays important roles in the regulation of cellular processes. However, whether cytosolic dsDNA is involved in the pathogenesis of rheumatoid arthritis (RA) is not clear. Therefore, the present study investigated the roles of cytosolic dsDNA in the modulation of inflammatory responses of fibroblast-like synoviocytes (FLS) in patients with RA.

Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation.

Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (lowly expressed in rheumatoid fibroblast-like synoviocytes), that negatively regulates the migration, invasion, and proliferation of FLSs through interaction with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q).

Attenuation of antimalarial agent hydroxychloroquine on TNF-α-induced endothelial inflammation.

Objective: Hydroxychloroquine (HCQ) is an antimalarial drug that is widely used in the treatment of some autoimmune diseases. In the present study, we explore the role of HCQ in regulating endothelial inflammation and its underlying mechanism.

Methods: Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords.

Glycogen Metabolism and Rheumatoid Arthritis: The Role of Glycogen Synthase 1 in Regulation of Synovial Inflammation Blocking AMP-Activated Protein Kinase Activation.

Objective: To investigate the role of glycogen metabolism in regulating rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and its underlying mechanism.

Methods: FLSs were separated from synovial tissues (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was determined by periodic acid Schiff staining.

Piperlongumine inhibits the proliferation, migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Objectives: Recent studies have indicated that piperlongumine (PLM) may exert anti-inflammatory effects. In the present study, we determined the effect of PLM on the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) (referred to herein as RA FLS). We further explored the mechanisms by which the studied compound inhibits the functions of RA FLS.

Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis.

Background And Purpose: Abnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA.

Experimental Approach: A specific inhibitor of PFKFB3, PFK15, and siRNA were used to evaluate the role of PFKFB3.

Halofuginone inhibits TNF-α-induced the migration and proliferation of fibroblast-like synoviocytes from rheumatoid arthritis patients.

Fibroblast-like synoviocytes (FLSs) display an aggressive phenotype that is a critical factor in cartilage destruction in rheumatoid arthritis (RA). Increased FLS migration and proliferation are essential to the pathology of RA. Halofuginone has been found to inhibit cell migration and proliferation in cancer cells.

Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway.

Triptolide, a primary active ingredient extracted from a traditional Chinese herb, Tripterygium wilfordii Hook F, has been demonstrated to have a positive therapeutic effect on patients with rheumatoid arthritis (RA); however, its mechanism of action against RA is not well established. Therefore, in the present study, we observed the effect of triptolide on the aggressive behavior of RA fibroblast-like synoviocytes (RA FLSs), and we explored its underlying signal mechanisms. We found that triptolide treatment significantly reduced the migratory and invasive capacities of RA FLSs in vitro.

The suppression of bromodomain and extra-terminal domain inhibits vascular inflammation by blocking NF-κB and MAPK activation.

Background And Purpose: There is increasing evidence indicating that bromodomain and extra-terminal domain (BET) proteins play a critical role in the regulation of immune and inflammatory responses; however, their contribution to vascular inflammation has not yet been elucidated. In this study, we investigated the effect of inhibiting BET bromodomain on vascular inflammation and the underlying mechanisms.

Experimental Approach: HUVECs were isolated from fresh umbilical cords.