Distinct Expression of Chemokine-like Factor 1 in Synovium of Osteoarthritis, Rheumatoid Arthritis and Ankylosing Spondylitis

Chemokine-like factor 1（CKLF1） is a newly cloned chemotactic cytokine with CCR4 being its functional receptor. Recent evidence demonstrates a role of CKLF1 in arthritis. The aim of this study was to quantify the expression of CKLF1 as well as assess the correlation between CKLF1 and plasma acute-phase markers. Synovium was obtained from 16 osteoarthritis（OA）, 15 rheumatoid arthritis（RA） and 10 ankylosing spondylitis（AS） patients undergoing total joint arthroplasty, with other 11 patients treated for meniscal tears during sport accidents serving as normal controls. Levels of CKLF1 and CCR4 m RNA were detected by q RT-PCR, and the expression of CKLF1 was investigated by immunohistochemistry staining, subsequently analyzed with semiquantitative scores. Plasma acute-phase markers of inflammation were determined by ELISA. CKLF1 was found with a particularly up-regulated expression in synovim from AS and RA patients, and CCR4 m RNA levels increased in RA patients, not in OA or AS patients. Elevated levels of plasma markers of inflammation including CRP, ESR and Ddimer were observed in RA. Further, significantly positive correlations between relative expression levels of CKLF1 and CRP/ESR in RA patients and a positive correlation between CKLF1 and ESR in AS patients were found. There was no detectable correlation between CKLF1 and plasma D-dimer. This study confirms an increased but different level of CKLF1 in RA, OA and AS patients, all significantly higher than that in controls. Additionally, the significant positive correlations between CKLF1 levels and CRP/ESR in RA and between CKLF1 and ESR suggest that CKLF1 might contribute to the inflammation state and clinical symptoms in these rheumatic diseases. Further studies are required to investigate the utility of targeting specific CKLF1 for symptom control or disease modification in RA and AS.

Flare up of rheumatoid arthritis associated with VogtKoyanagi-Harada syndrome treated with leflunomide

Dear Editor,We present a case of"Flare up of rheumatoid arthritis associated with Vogt-Koyanagi-Harada(VKH)syndrome treated with leflunomide".To our knowledge,this is the first case of uveitis and arthritis inflammation active at the same time and no treatment for this condition has been described in the literature.

Expression of CC Chemokine Ligand 5 in Patients with Rheumatoid Arthritis and Its Correlation with Disease Activity and Medication

Objective To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. Methods CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. Results CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P<0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P<0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r=0.3329, P<0.05), erythrocyte sedimentation rate (r=0.4001, P<0.05), and C reactive protein (r=0.3735, P<0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. Conclusions In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.

Naringenin nanocrystals for improving antirheumatoid arthritis activity

Naringenin(NAR)is recognized for its anti-inflammatory activity.However,the clinical application of NAR is limited by low bioavailability,which is attributed to its poor aqueous solubility.In this study,we aimed to improve the therapeutic efficacy of NAR by formulating it into nanocrystals(NCs)via wet milling.The obtained NARNCs exhibited superior dissolution behaviors,increased cellular uptake,and enhanced transcellular diffusion relative to those of bulk NAR.Oral administration of NARNCs also significantly improved bioavailability in rats.In addition,the NARNCs effectively improved rheumatoid arthritis treatment in collagen-induced arthritic rats by reducing inflammatory cell infiltration and synovial damage.These results indicate that NARNCs provides a promising strategy for rheumatoid arthritis treatment.

Effect of family caregiver nursing education on patients with rheumatoid arthritis and its impact factors:A randomized controlled trial

BACKGROUND Rheumatoid arthritis(RA)is a common autoimmune disease.Nursing education for family caregivers is considered a workable and effective intervention,but the validity of this intervention in RA has not been reported.AIM To explore whether family caregiver nursing education(FCNE)works on patients with RA and the factors that influence FCNE.METHODS In this randomized controlled study,a sample of 158 pairs was included in the study with 80 in the intervention group and 78 in the control group.Baseline data of patients and caregivers was collected.The FCNE intervention was admi-nistered to caregivers,and inflammation level indicators,disease activity indicators and mood disorder indicators of patients were followed up and analyzed.RESULTS Baseline characteristics of the intervention and the control groups had no significant difference.Indicators were significantly reduced in the intervention group compared to the control group.The intervention group showed significant differences in stratification of relationship,education duration and age.CONCLUSION The effect of FCNE on RA is multifaceted,weakening inflammation level,alleviating disease activity and relieving mood disorder.Relationship between caregiver and patient,caregiver’s education level and patient’s age may act as impact factors of FCNE.

Transcranial Direct Current Stimulation Combined with Peripheral Neuromuscular Stimulation Improves Quality of Life, Fatigue, and Pain in a Patient with Rheumatoid Arthritis and Refractory Radicular Pain Related to Spinal Stenosis

Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.

High Remission Rates in a Brazilian Cohort of Initial Rheumatoid Arthritis after 15 Years of Follow-Up

Introduction: Rheumatoid arthritis (RA) is a chronic systemic rheumatic disease which is usually treated with corticosteroids and immunobiologicals. The goal of this article is to carry out an assessment of disease activity indices in a cohort of patients with rheumatoid arthritis. Patients and Methods: This is a prospective cohort study. Individuals from the Initial Rheumatoid Arthritis Brasília Cohort, which is an incident cohort of early RA diagnosed patients, were monitored at the Rheumatology Service of the Hospital Universitário de Brasília (HUB), University of Brasília (UnB), Brazil. A cross-sectional analysis was carried out from 2017 to 2018 to evaluate patients with 15 or more years of follow-up, through a direct interview and review of medical records. The main focus of the study is on the assessment of disease activity, based on the indices: 28-joint Disease Activity Score based on Creactive protein (DAS 28 CPR) and based on erythrocyte sedimentation rate (DAS 28 ESR), Clinical Disease Activity Index (CDAI), and Simple Disease Activity Index (SDAI). The reference remission criteria used were the Composite Disease Activity Indices. Results: 107 patients were evaluated, mostly women, mean age of 55.1 years. Concerning the disease characteristics, 75.5% of the patients were positive for rheumatoid factor and 12 (11.3%) had documented erosive disease. The mean Health Assessment Questionnaire (HAQ) at the time of assessment was 0.6 (median 0.35). The indices analyzed showed: DAS28-ESR 48.6% of patients were in remission and 12.1% had low activity levels, DAS28-CRP 55.1% and 11.2%, SDAI 42% and 26.1%, CDAI 41.1% and 27.1%. These remission and low disease activity levels are higher than those generally found in the literature. Conclusion: This study presents a cohort of patients with RA who started treatment at an early stage of the disease and who achieved higher rates of remission and lower disease activity than those reported in the literature.

Comparative study for cardiovascular risk factors of rheumatoid arthritis and osteoarthritis

Objective： To compare the difference of cardiovascular risk factors in patients with rheumatoid arthritis （RA） and osteoarthritis （OA）. Methods： A retrospective analysis was performed to compare the difference of cardiovascular factors between 44 patients with RA and 36 patients with OA in terms of their gender, age, body mass index, course of disease, carotid ultrasound related indicators, homocysteine, blood lipid levels, inflammation index, echocardiographic index, etc. Results： （1） General situation： there was no significant difference between two groups in terms of gender and age （P 〉 0.05）. However, body mass index of OA group was significantly higher than that of RA group and the course of disease of RA group was significantly longer than that of OA group （P = 0.024）. （2） Laboratory index： the level of homocysteine of RA group was significantly higher than that of OA group （P = 0.002）. Though there was no significant difference between these two groups in terms of total cholesterol, triglyceride, low density lipoprotein, apolipoprotein B and high density lipoprotein （P 〉 0.05）, the level of apolipoprotein A1 of RA group was significantly lower than that of OA group （P 〈 0.001） and the level of lipoprotein A of RA group was significantly higher than that of OA group （P 〈 0.001）. The levels of erythrocyte sedimentation rate and C reactive protein of group RA were significantly higher than those of OA group （P 〈 0.001）. （3） Stroke volume and ejection fraction of echocardiography of RA patients were significantly lower than those of OA patients （P = 0.022, P = 0.009）. However, there was no significant difference between two groups in terms of aortic diameter, left atrial diameter, left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular posterior wall thickness, left ventricular fractional shortening, right ventricular diameter, right atrial diameter, and interventricular septum thickness （P 〉 0.05）. Though significant difference in carotid artery plaque incidence between the two groups was not observed （P 〉 0.05）, the incidence of carotid artery thickening and carotid artery middle thickness were significantly different between the two groups （P 〈 0.001）. Conclusion： The rate for the occurrence of cardiovascular events in patients with RA was higher than those with OA. Additionally, effective control of RA patients’ conditions has the potential to reduce the risk of cardiovascular events.

Rheumatoid arthritis and ankylosing spondylitis occurring together: a case report

Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are two different rheumatoid immune diseases. It is not common that the two diseases occur simultaneously in the same patient in clinical practice. Here, we reported a case of meeting the diagnostic criteria for both AS and RA, who was treated with integrated traditional Chinese and Western medicine and received apparent improvement.

Joint Angle Correction in Rheumatoid Arthritis and Its Reliability Analysis Based on Phase Dispersion Quantification

Background: Rheumatoid arthritis is a form of autoimmune disease characterized by synovitis that can ultimately cause joint deformities and impaired functioning. The cartilage destruction is one of the most important indicators for diagnosis and treatment of rheumatoid arthritis, and it is radiographically manifested as joint space narrowing. Issue: In the literature, the joint space narrowing progression between a baseline and its follow-up finger joint images can be quantified by using image registration algorithm. We found that the inconsistencies of joint angles may lead to characteristic mismatches and thus severely affect the accuracy of joint space narrowing quantifications. Methods: In this work, we introduce a rotation invariant phase only correlation in joint space narrowing quantification for the joint angle correction. Further, we propose a confidence index to quantify the quantification reliability of phase only correlation based on phase dispersion in phase difference spectrum. Conclusion: In our clinical experiments, the proposed quantification method can effectively overcome and manage the mismatch due to the inconsistency of joint angles. Additionally, the confidence index shows a high consistency with the joint space narrowing progression examinations manually done by a trained radiologist and one radiological technologist.

SDC1 acts as a novel molecular marker and prevents rheumatoid arthritis and modulates inflammatory response by targeting the miR-4531/SDC1 axis

Objective:Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by chronic erosive arthritis.Due to the lack of effective biomarkers for diagnosis and treatment,RA patients have many complications in the later stage,seriously affecting their quality of life.Thus,this study was conducted to investigate new therapeutic targets and to discover diagnostic biomarkers in RA.Methods:In this study,the expression profiles of GSE55235 and GSE55457 were downloaded from the Gene Expression Omnibus database to obtain DEGs between RA and healthy samples.Genetic Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the common genes existing in the RA-related modules.Additionally,we used the STRING database to construct the protein‒protein interaction network.Furthermore,we established the interaction analysis of Hub Genes and microRNA(miRNA)and verified the 10 Hub genes through the GSE77298 dataset and quantitative real-time polymerase chain reaction Results:276 and 69 DEGs were screened from the GSE55235 dataset and GSE55457 dataset,respectively.Then,we obtained 42 up-regulated genes in two chip datasets intersection.Genetic Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the 42 up-regulated genes showed that they were mainly concentrated in immune response-activating cell surface receptor signaling pathway,etc.Furthermore,the protein-protein interaction network indicated that 10 hub genes are closely related to RA,including MS4A1,CD27,LCK,CD79A,SDC1,CXCL9,CXCL10,CXCL13,IGLL5,and IGJ.In addition,we found that miR-4531 is the same target miRNAs between MS4A1 and SDC1 through messenger RNA-miRNA co-expression network.Finally,the GSE77298 gene chip and quantitative real-time polymerase chain reaction verified the expression of 10 Hub genes.The six Hub genes of CD27,SDC1,CXCL9,CXCL10,CXCL13,and IGJ are significantly increased.Conclusions:We found that SDC1 may be a novel molecular marker for the prevention and treatment of RA.The miR-4531/SDC1 regulatory axis may play a key role in this process.In conclusion,our study not only provides potential biomarkers for the diagnosis and treatment of RA,but also provides a basis and new targets for further revealing the potential mechanism of RA occurrence and development and discovering targeted drugs.

Generalized lymphadenopathy as an atypical initial clinical manifestation in rheumatoid arthritis and a possible hypothetical mechanism

Objective:To describe a 60-year-old male with diffuse generalized lymphadenopathy preceding a diagnosis of rheumatoid arthritis.Case presentation:The patient was admitted on suspicion of lymphoma.Chest positron emission/computed tomography showed enlarged lymph nodes bilaterally,mediastinum in the perihilar,retroperitoneum,and inguinal regions,with normal hematopoiesis of bone marrow.Lymph node biopsy revealed reactive follicular lymphadenopathy.Polyarthritis was present,and a rheumatoid factor test was positive eight months after the initial medical evaluation.A diagnosis of rheumatoid arthritis associated with generalized lymph node involvement was made.The patient was treated with leflunomide and corticosteroids and showed complete recovery without recurrence at 18 months of follow-up.Conclusions:Once histological findings of reactive lymph node hyperplasia are established as primarily related to rheumatic disease activity,clinicians should consider a possible diagnosis of rheumatoid arthritis.

Dystrophic Calcinosis in the Hands of a Patient with Rheumatoid Arthritis and Secundary Sjogren’s Syndrome

Salts of calcium phosphate and inorganic phosphate are normally found in serum and extracellular fluids, balancing through poorly understood factors that prevent abnormal tissue deposition of these minerals. However, in those tissues that are injured, especially due to chronic inflammatory processes, a predisposition to the deposition of these minerals is developed, triggering what has been called Dystrophic Calcinosis (DC), common in different Connective Tissue Diseases (CTD), especially dermatomyositis and scleroderma, but there is no a frecuent association with diseases like Rheumatoid Arthritis (RA) and Sj?gren Syndrome (SS). We report a case of a female patient of 63 years old with RA and Secundary SS who presents with DC in the hands and no evidence of other connective tissue.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Development of biomedical hydrogels for rheumatoid arthritis treatment

Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

Concomitant atypical knee gout and seronegative rheumatoid arthritis:A case report

BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.