Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Corrigendum: Deep sequencing of plasma exosomal microRNA level in psoriasis vulgaris patients.

[This corrects the article DOI: 10.3389/fmed.2022.895564.].

In silico analysis of serum miRNA profiles in seronegative and seropositive rheumatoid arthritis patients by small RNA sequencing.

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA.

Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis.

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Attenuates Rheumatoid Arthritis through Upregulating miR-125b to Suppress NF-κB-Induced Inflammation by Targeting CK2.

The Huayu-Qiangshen-Tongbi (HQT) decoction, a Chinese medical formula, has been identified to show a potent therapeutic effect on rheumatoid arthritis (RA). However, the specific molecular mechanism of HQT in RA has not been well studied. In the present study, LPS-treated human rheumatoid fibroblast-like synoviocyte (FLS) MH7A cells and collagen-induced arthritis (CIA) mice were utilized as in vitro and in vivo models. Our results demonstrated that HQT could efficiently inhibit RA-induced inflammation by reducing the production of cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6). Moreover, HQT significantly upregulated the expression of miR-125b. Besides, analysis of bioinformatics suggested casein kinase 2 (CK2) was a potential target of miR-125b. Luciferase reporter assay was performed and revealed that miR-125b suppressed CK2 expression in MH7A cells. Furthermore, miR-125b inhibited LPS-induced NF-kappa-B (NF-κB) activation, which is a downstream target of CK2. In addition, the NF-κB inhibitor ammonium pyrrolidinedithiocarbamate (PDTC) and NF-kappa-B inhibitor alpha (IkB-α) enhanced the inhibitory effect of miR-125b on the expression of TNF-α, IL-1ß, and IL-6. Taken together, our study revealed that HQT could attenuate RA through upregulating miR-125b to suppress NF-κB-induced inflammation by targeting CK2. The findings of this study should facilitate investigating the mechanism of HQT on RA and discovering novel therapeutic targets for RA.

Deep Sequencing of Plasma Exosomal microRNA Level in Psoriasis Vulgaris Patients.

Psoriasis is a chronic skin disease affecting 1% to 3% of the world population. Psoriasis vulgaris (PV) is the most common form of psoriasis. PV patients suffer from inflamed, pruritic and painful lesions for years (even a lifetime). However, conventional drugs for PV are costly. Considering the need for long-term treatment of PV, it is urgent to discover novel biomarkers and therapeutic targets. Plasma exosomal miRNAs have been identified as the reliable biomarkers and therapy targets of human diseases. Here, we described the levels of serum exosomal miRNAs in PV patients and analyzed the functional features of differently expressed miRNAs and their potential target genes for the first time. We identified 1182 miRNAs including 336 novel miRNAs and 246 differently expressed miRNAs in serum exosomes of healthy people and PV patients. Furthermore, the functional analysis found differently expressed miRNA-regulated target genes enriched for specific GO terms including primary metabolic process, cellular metabolic process, metabolic process, organic substance metabolic process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway containing cellular processes, human diseases, metabolic pathways, metabolism and organismal systems. In addition, we found that some predicted target genes of differentially expressed miRNAs, such as CREB1, RUNX2, EGFR, are both involved in inflammatory response and metabolism. In summary, our study identifies many candidate miRNAs involved in PV, which could provide potential biomarkers for diagnosis of PV and targets for clinical therapies against PV.

The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review.

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.

Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.

BACKGROUND: Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to be the biomarkers for a number of immune disorders. OBJECTIVE: This study was conducted to identify the common mechanisms among psoriatic arthritis (PsA), psoriasis vulgaris (PV), rheumatoid arthritis (RA), and gouty arthritis (GA). The common expressed plasma exosomal microRNAs in these diseases were determined. METHODS: The expression of microRNAs derived from plasma exosome of patients with PsA (n=30), PV (n=15), RA (n=15), GA (n=15), and healthy controls (n=15) was evaluated via sequencing. Function analysis of common expressed microRNAs was conducted by the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Coexpression analysis was conducted to identify novel and significant genes and proteins by using the Search Tool for the Retrieval of Interacting Genes (STRING). A systematic literature review was conducted to uncover the role of the common microRNAs in the pathogenesis of PsA, PV, RA, and GA. RESULTS: A total of 36 common expressed microRNAs were detected in patients with PsA, PV, RA, and GA. The most significantly enriched biological processes, cellular components, and molecular functions were "homophilic cell adhesion via plasma membrane adhesion molecules," "CCR4-NOT complex," and "calcium ion binding," respectively. "Antigen processing and presentation" was the most significantly enriched pathway. A total of 91 validated coexpressed gene pairs were identified and 16 common expressed microRNAs and 85 potential target genes were screened based on Cytoscape. Of 36 common expressed microRNAs, 5 microRNAs, including hsa-miR-151a-3p, hsa-miR-199a-5p, hsa-miR-370-3p, hsa-miR-589-5p, and hsa-miR-769-5p, were considered to be connected with the common pathogenesis of PsA, PV, RA, and GA. Systemic review revealed that the roles of these 5 microRNAs are related to immune disorder and bone injury, which matches the conclusion from GO and KEGG analyses. CONCLUSION: (1) Both immune disorder and bone metabolic dysregulation could be the shared mechanism in the development of PsA, PV, RA, and GA. (2) Immune dysfunction is involved in GA. Our study may shed new light on the diagnosis and treatment strategy of these autoimmune diseases and GA, which warrants further studies.

The Bone-Protecting Efficiency of Chinese Medicines Compared With Western Medicines in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: Rheumatoid Arthritis (RA) is a systemic autoimmune disease leading to joint destruction. The prevention of bone and cartilage destruction has received increased attention in recent years. Objective: To evaluate the current evidences regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA. Methods: We comprehensively searched PubMed, Embase, the Cochrane Library (www.thecochranelibrary.com), the China National Knowledge Infrastructure (CNKI), the Database for Chinese Technical Periodicals (VIP), and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the two therapy methods. Results: Sixteen studies including 1,171 patients were included in the final analysis. The results showed that Chinese medicine could significantly improve the bone mineral density (BMD) (mean difference [MD] = 0.05 /g·cm-2, 95% CI [0.03, 0.08], P < 0.00001), and decrease the serum matrix metalloproteinase 3 (MMP-3) ([SMD] = -2.84, 95% CI [-4.22, -1.47], P < 0.0001). Conclusions: Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency. Given the inherent limitations of the included studies, future well-designed RCTs are required to confirm and update the findings of this analysis.

Systematic review and meta-analysis of the efficacy and safety of Biqi capsule in rheumatoid arthritis patients.

Biqi capsule is a Traditional Chinese Medicine preparation for treating rheumatoid arthritis (RA), and clinical studies have indicatedthat its effect may be more beneficial than that of Western medicine. The present study aimed to estimate the efficacy and safety of Biqi capsule alone or combined with methotrexate (MTX) compared with MTX alone for treating RA by performing a meta-analysis of randomized controlled trials and controlled clinical trials. A systematic literature search of studies published until March 2017 was performed. References from relevant studies were screened to obtain additional articles. The results were independently evaluated for relevance, and full-text studies were assessed for eligibility. The risk of bias was assessed using the Cochrane collaboration tool for assessing risk of bias. Out of 558 citations that were initially retrieved, a total of 5 studies comprising 522 patients met the inclusion criteria. The risk of bias of these trials was generally unclear or high. Meta-analysis indicated that Biqi capsule had better effects on C-reactive protein [standardized mean difference (SMD), -7.05; 95% CI -(10.77-3.33)] and tender joint count [SMD, -3.02; 95% CI, -(3.81-2.22)] and fewer adverse effects (AEs) than MTX [relative risk (RR), 0.19; 95% CI, 0.08-0.43]. Biqi capsule plus MTX was superior to MTX in terms of the total effect (RR, 1.17; 95% CI, 1.06-1.28), rheumatoid factor [SMD, -12.54; 95% CI, -(16.87-8.20)], swollen joint count [SMD, -1.50; 95% CI, -(1.99-1.01)], score of joint swelling [SMD -2.07; 95% CI, -(2.76-1.38)], tender joint count [SMD, -2.16; 95% CI, -(2.86-1.47)] and score of joint tenderness [SMD, -4.69; 95% CI, -(5.92-3.47)]. There was no difference in AEs between Biqi capsule plus MTX and MTX (RR, 0.71; 95% CI, 0.34-1.50). In conclusion, the present study indicated that compared with MTX, Biqi capsule plus MTX appeared to have more benefits but that Biqi capsule alone was not better for RA patients than MTX. In the other words, Biqi capsule plus MTX is more effective and has fewer AEs compared to MTX. However, the trials selected in the present meta-analysis have various limitations, including the lack of blinding and the short duration of the treatment; therefore, the conclusions are not sufficiently definitive. More randomized controlled trials are necessary to evaluate the use of Biqi capsule for managing RA.

The differential profiles of long non-coding RNAs between rheumatoid arthritis and gouty arthritis.

OBJECTIVE: This study was designed to determine the differential profiles of long non-coding RNAs (lncRNAs) between rheumatoid arthritis (RA) and gouty arthritis (GA), which may lead to the discovery of specific biomarkers for RA diagnosis and treatment in the future. METHODS: The profiles of lncRNAs were determined by Agilent microarray. Bioinformatics analyses, including Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, of the large dataset obtained from microarray experiments were performed. RESULTS: A total of 765 lncRNAs and 2,808 mRNAs were significantly and differentially expressed in RA samples as compared to GA samples. Moreover, of 2,808 differentially expressed mRNAs, 178 upregulated mRNAs and 21 downregulated mRNAs were identified to be strongly correlated with lncRNAs examined in this study. Bioinformatics analyses revealed the tumor-like phenotype of synovial cells in RA and the involvement of immune system process in GA. In addition, this study demonstrated the significantly different molecular origins of two Chinese Medicine syndrome patterns of RA patients -- blood stasis and non-blood stasis. CONCLUSIONS: Our study showed for the first time the differentially expressed lncRNA profiles in synovial tissues between RA and GA and between two clinical phenotypes of RA patients differentiated by Chinese Medicine. This study helps achieving personalized medicine in RA. Larger-scale studies are required to validate the data presented.

Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma.

BACKGROUND: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. METHODS: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. RESULTS: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. CONCLUSIONS: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.

Role of an imbalanced miRNAs axis in pathogenesis of psoriasis: novel perspectives based on review of the literature.

BACKGROUND: Specific profile of microRNAs (miRNAs, miR) expressed in psoriasis has been identified in the past few years, while the studies on roles and molecular mechanisms of these miRNAs are still on the way. In our previous study, four specific miRNAs (miR-31, miR-203, hsa-miR-99a and miR-125b) were found to be specifically altered in psoriatic lesions.We therefore conducted a systematic literature review in this study to reveal the role of these miRNAs in the pathogenesis of psoriasis in order to inform future research. METHODS: The related articles indexed in PubMed (MEDLINE) database were searched and analyzed. We identified eligible studies related to the mechanism research of miR-31, miR-203, hsa-miR-99a and miR-125b in psoriasis or psoriatic lesional skin from inception up to July 2016. The experts in the field of miRNAs and Psoriasis were involved in analysis process. RESULTS: Both miR-31 and miR-203 are dramatically upregulated in psoriatic lesions. The former plays the pro-proliferative, pro-differentiative and pro-inflammatory roles and the latter holds the potentials for anti-proliferation, pro-inflammation and pro-differentiation in psoriatic keratinocytes. Conversely, both hsa-miR-99a and miR-125b are significantly downregulated in psoriatic skin. These two miRNAs are able to inhibit proliferation while promote differentiation of psoriatic keratinocytes, and miR-125b can also suppress inflammation in psoriatic lesions. By analyzing the contexts related to these miRNAs, we found that each of them does not act alone but rather work in concert with other miRNAs. The imbalance between miR-31/miR-203and hsa-miR-99a/miR-125b may contribute to the intense proliferation and abnormal differentiation of psoriatic keratinocytes, which is a characteristic of pathogenesis of psoriasis. CONCLUSION: An imbalanced miRNAs axis was for the first time outlined. Apparently, upregulation of miR-31/miR-203 and downregulation of hsa-miR-99a/miR-125b work together in concert to facilitate the development of psoriasis pathogenesis. Further work in this field holds the potentials to open a new way to study psoriasis.

Adult onset Still's disease accompanied by acute respiratory distress syndrome: A case report.

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder characterized by rash, leukocytosis, fever and arthralgia/arthritis. The most common pulmonary manifestations associated with AOSD are pulmonary infiltrates and pleural effusion. The present study describes a 40-year-old male with AOSD who developed fever, sore throat and shortness of breath. Difficulty breathing promptly developed, and the patient was diagnosed with acute respiratory distress syndrome (ARDS). The patient did not respond to antibiotics, including imipenem, vancomycin, fluconazole, moxifloxacin, penicillin, doxycycline and meropenem, but was sensitive to glucocorticoid treatment, including methylprednisolone sodium succinate. ARDS accompanied by AOSD has been rarely reported in the literature. In conclusion, in a patient with ARDS who does not respond to antibiotic treatment, the involvement of AOSD should be considered.

Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

OBJECTIVES: This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. METHODS: The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. RESULTS: The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. CONCLUSIONS: The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA.

An Exploration of the Role of MicroRNAs in Psoriasis: A Systematic Review of the Literature.

Psoriasis is recently characterized by a specific microRNAs (miRNAs) expression profile, which guides the researchers' efforts to explore the therapeutic targets and objective biomarkers that reflect the diagnosis and disease activity in clinical use for psoriasis.The paper presents a state-of-the-art review of expression and function of miRNAs in psoriasis along with its clinical implications.We analyzed all literature searched by keywords "microRNA" and "psoriasis" in PubMed (Medline) from inception up to July 2015, and the references in the literature searched were also considered.Relevant literature was chosen according to the objective of this review. Relevant literature was searched by 3 independent investigators, and experts in the field of miRNAs and psoriasis were involved in analyzing process.We included any study in which role of miRNAs in psoriasis was examined in relation to disease pathogenesis, diagnosis, and treatment.The specific miRNAs profile has been identified from human psoriatic skin, blood, and hair samples. It is found that genetic polymorphisms related to some of specific miRNAs, miR-146a for example, are associated with psoriasis susceptibility. Key roles of several unique miRNAs, such as miR-203 and miR-125b, in inflammatory responses and immune dysfunction, as well as hyperproliferative disorders of psoriatic lesions have been revealed. Moreover, circulating miRNAs detected from blood samples have a potential of clinic application to be the biomarkers of diagnosis, prognosis, and treatment responses. Additionally, a new layer of regulatory mechanisms mediated by miRNAs is to some extent revealed in pathogenesis of psoriasis.The dramatically altered mRNA expression profiles are displayed in psoriasis, and some of these may become disease markers and therapeutic targets. Herein, this work underscores the potential importance of miRNAs to diagnosis, prognosis, and treatment of psoriasis. However, further study in this field is worth doing in the future, as the exact roles of miRNAs in psoriasis have not been fully elucidated.Systematic review registration number is not registered.

Determination of role of thromboxane A2 in rheumatoid arthritis.

INTRODUCTION: To date, the etiology of rheumatoid arthritis (RA) remains largely unknown, and the therapies are still unsatisfactory. The biosynthesis of thromboxane A2 (TxA2) is increased in RA patients, suggesting a role of TxA2 in RA pathology. METHODS: RA patients were divided into two groups, DMARDs and non-DMARDs, according to their use of disease-modifying antirheumatic drugs (DMARDs). Sera from RA patients and healthy controls were extracted and subjected to enzyme immunoassays for measurement of the thromboxane B2 (TxB2) level. The statistical correlations between serum TxB2 levels and disease activity score of 28 joints (DAS28), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) were calculated. Moreover, the effects of dual TxA2 modulator BM567 on cell proliferation as well as protein expression of α-actinin and NF-κB2 in RA fibroblast-like synovial (FLS) cells MH7A were determined by MTS assays and Western blot analysis, respectively. The effects of BM567 on mRNA expression of cyclooxygenase (COX)-2, a downstream product of NF-κB2 and an upstream enzyme of TxA2, was examined by real-time quantitative PCR experiments. RESULTS: Serum TxB2 level was significantly higher in RA patients as compared to healthy controls. Both DAS28 score and serum TxB2 levels were slightly lower in the DMARDs group than the non-DMARDs group, without statistical significance, and there was positive correlation between these two factors. BM567 significantly suppressed cell proliferation as well as expression of α-actinin, NF-κB2, p52, and COX-2 in MH7A. CONCLUSION: TxA2 plays an important role in RA pathology, synovial cell proliferation in particular, through an auto-regulatory feedback loop. Thus, targeting TxA2 may represent a promising add-on therapy in the treatment of RA.