Anti-inflammatory effects of Solanum procumbens on a low dose complete Freund's adjuvant-induced arthritis rat model

Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsoluble Solanum procumbens extract(SP)with anti-inflammatory effects,including ursolic acid,β-sitosterol,hexadecanoic acid,cisvaccenic acid,and vanillic acid.Additionally,we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms,including paw volumes,local temperatures,withdrawal latency,and mechanical withdrawal threshold at the hind paw and white blood cell(WBC)number from complete Freund’s adjuvant-induced arthritis rat models.Results:We have successfully established a complete Freund’s adjuvant-induced arthritis rat model at a low dose(1 mg/mL).SP extract significantly reduced paw volumes(P<0.05),prolonged withdrawal latencies(P<0.05),decreased local temperature,and increased the mechanical withdrawal threshold(P<0.05),but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers.Conclusions:SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis,but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.

Paeoniflorin-6′-O-benzene sulfonate ameliorates progression of adjuvant-induced arthritis by inhibiting interaction between Ahr and GRK2 of fibroblast-like synoviocytes

OBJECTIVE Aryl hydrocarbon receptor(Ahr)is thought to be a crucial factor that regulates immune responses,which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis(RA).The results of our group in recent years have shown that CP-25,a novel ester derivative of paeoniflorin,has a good effect on improving RA animal models.However,whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear.METHODS CP-25 treatment ameliorated adjuvant-induced arthritis(AA),a mouse model of RA,by inhibiting Ahr-related activities in fibroblasts like synoviocytes(FLS).AA rats were treated with CP-25 or paroxetine from day 17 to 33 after immunization.RESULTS CP-25 alleviated arthritis symptoms and the pathological changes,decreased the expression of Ahr in the synovium and FLS of AA rats.Besides,treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation.In addition,we also demonstrated that CP-25 down-regulated the co-expression and co-localization of Ahr and G protein-coupled receptor kinase 2(GRK2)in MH7A.CONCLUSION The data presented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA,which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.

The effects of Fumaderm~ on immunological function and cytokines in a rat model of adjuvant-induced arthritis

Objective To study the therapeutic effect of Fumaderm in Freund’s complete adjuvant-induced arthritis(AIA)in Spraque-Dawley rats.Methods Adjuvant-induced arthritis(AIA)was established by intradermal injection of 0.1 mL of Freund’s complete adjuvant(CFA)in the palmar surface of the right hindpaw and Fumaderm was delivered by oral gavage for 28 days.After CFA injection,the edema of the hindpaw was determined every two days.On 28 days after CFA injection,the lymphocyte subsets of peripheral blood and the cytokines were determined by flow cytometry,meanwhile the histopathological examination of ankle-joints of the animals was performed.Results Fumaderm had a significant therapeutic effect on AIA.The hindpaw swelling was reduced significantly in a dose-dependent manner.The ratio of peripheral blood T lymphocytes was improved obviously.Multiparameter cytokine analysis from peripheral blood CD4+ T cells showed a decrease of proinflammatory cytokines and an increase of anti-inflammatory cytokines in Fumaderm treated animals.A strongly reduced inflammatory response in the joint synovium was observed.Conclusion Fumaderm has potential anti-inflammatory effects on AIA rats.Further investigation is needed to elucidate the molecular mechanism involved in the clinical effect observed in the AIA model.

Ginsenoside Rb1 attenuates adjuvant-induced arthritis in rats through inactivation of NF-κB signaling pathway

OBJECTIVE To investigate the anti-arthritic effect and mechanism of action of ginsenoside Rb1 on adju⁃vant-induced arthritis(AIA)in rats.METHODS Male SD rats were received 0.1 mL injections of FCA(10 g·L^-1)emulsion into the right hind metatarsal foot pad for arthritis induction.After that,rats were randomly divided into six groups,namely control group,untreated group,dexamethasone(DEX,2.5 mg·kg^-1)group,low(5 mg·kg^-1),medium(10 mg·kg^-1)and high(20 mg·kg^-1)doses of ginsenoside Rb1 groups,and treated intraperitoneally at the above dosage once a day for 2 weeks.After treatment,paw swelling and arthritis indexes were evaluated,the thymus and spleen index were calculated as well.HE staining were used to observe the joint histopathology in rats.Rat ELISA kits were used to determinate the TNF-α,IL-1βand IL-6 levels.Western blotting were used to detect the related protein expression of NF-κB signaling pathway in the tissues of inflamed joints.RESULTS Rb1 significantly decreased the paw swelling and arthritis index,Compared with AIA group.HE staining results revealed that medium and high doses of Rb1 significantly reduced synovial inflammatory cell infiltration,synovial lining hyperplasia and bone destruction,compared with AIA group.Elisa results showed that Rb1 significantly decreased the TNF-α,IL-1β and IL-6 levels(P<0.05,P<0.01).Western blotting results revealed that the expression of p-IκB and p-P65 were significantly reduced in 20 mg·kg^-1 of Rb1 group,compared with AIA group(P<0.05,P<0.01).CONCIUSION Rb1 manifests therapeutic anti-inflammatory effects on rats with AIA,poten⁃tially through a mechanism of inhibiting activation of the NF-κB.

Changes in mRNA Expression and Activity of Xenobiotic Metabolizing Enzymes in Livers from Adjuvant-Induced Arthritis Rats

Pathophysiological changes in human patients and in animal models of infection or inflammation are associated with alterations in the production of numerous liver-derived proteins including metabolizing enzymes. In this study, the effects of adjuvant-induced arthritis (AA) in rats on the levels of mRNA and activity of hepatic xenobiotic metabolizing enzymes were determined during the inflammatory response. The mRNA levels of cytochrome P450 (CYP) 1A2, CYP2C12, CYP2D1, CYP2D2, and CYP3A1 were significantly decreased compared with control levels in almost all phases of inflammation. A reduction in the activity of CYP2C and CYP3A, which are abundantly expressed in the liver, was also observed. For phase II metabolizing enzymes, mRNA levels of uridine 5’-diphospho-glucuronosyltransferase (UGT) 1A1, UGT1A6, sulfotransferase (SULT) 2A1, and glutathione S-transferase 2 were significantly decreased compared with control levels. However, the mRNA levels of UGT2B and SULT1A1 returned to control levels during the subacute (7 d after adjuvant treatment) and chronic (21 d after adjuvant treatment) phases although these levels decreased during the acute (3 d after adjuvant treatment) phase. These results suggest that the effects of inflammation on the expression of xenobiotic metabolizing enzymes differ depending on the isoform of the enzyme and could affect the pharmacokinetics of each substrate.

The petroleum ether fraction of Celastrus paniculatus Willd. seeds demonstrates antiarthritic effect in adjuvant-induced arthritis in rats

Objective:Celastrus paniculatus(CP)Willd.is a plant indigenous to India with medicinal properties.It is used in the ayurvedic treatment of inflammatory ailments such as rheumatoid arthritis.The present study was designed to investigate the therapeutic efficacy of the petroleum ether fraction(PCP)obtained from CP seeds on adjuvant-induced arthritis in rats.Methods:Arthritis was induced in SpragueeDawley rats by immunization with Freund’s complete adjuvant(FCA).Arthritis severity was evaluated by arthritis score,paw volume,tibiotarsal joint thickness,body weight,dorsal flexion pain,motility test,stair climbing ability and index of thymus and spleen.Moreover,histopathology of knee joints supported by haematological analysis was used to assess the anti-arthritic action of PCP.The levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT),nitric oxide(NO)and malondialdehyde(MDA)in liver were also assessed.Serum samples were collected for estimation of aspartate transaminase(AST),alanine transaminase(ALT)and alkaline phosphatase(ALP).In addition,cytokines such as tumour necrosis factor-alpha(TNF-a)and interleukin-6(IL-6)were estimated in plasma.Results:PCP significantly alleviated arthritic progression with regards to paw swelling,arthritic score,immune organ indices,hyperalgesic effect and body weight.This phenomenon was correlated with significant suppression of overproduction of inflammatory cytokines(TNFa and IL-6),oxidant stress markers(MDA and NO)and cellular enzyme(AST,ALT and ALP)levels versus arthritic rats without treatment.Moreover,PCP restored the decreased levels of SOD,CAT and GSH.Conclusion:Our results suggest that the anti-arthritic properties of PCP may be due to immunosuppressive effects,cytokine regulation,antioxidant effects and bone-protective activities.

Effect of Ethanolic Extract of Pereskia aculeata Miller on Joint Swelling in Rats with Adjuvant-induced Arthritis

[Objectives]To explore the effect of ethanolic extract of Pereskia aculeata Miller(EEPA)on joint swelling in adjuvant arthritis rats.[Methods]60 SD rats were randomly selected.Except for the blank group,the remaining animals were injected with complete Freund's adjuvant to establish the adjuvant arthritis rat models,which were divided into 6 groups:blank group,positive group,model group,and EEPA high-dose(64 mg/kg),EEPA medium-dose(32 mg/kg),EEPA low-dose(16 mg/kg)groups,10 in each group.The changes of ankle joint swelling diameter and arthritis index score were observed,and the spleen index was calculated.The serum prostaglandin E2(PGE2)level was detected by enzyme-linked immunosorbent assay(ELISA).[Results]The degree of ankle swelling diameter,arthritis index score,expression of serum inflammatory factors,and spleen index in the model group were significantly higher than those in the blank group,indicating that there was an inflammatory reaction and abnormal immune organs,and the modeling was successful.Under the intervention of EEPA drugs,the degree of ankle swelling diameter and arthritis index score of EEPA group with different doses were significantly lower than that of the model group(P<0.05),and the level of serum inflammatory factors was also lower than that of the model group(P<0.05).The index was lower than the model group and close to the normal group(P<0.05),and the higher the EEPA dose,the lower the index expression level(P<0.05).[Conclusions]EEPA can reduce joint swelling and inhibit the level of inflammatory factors to some extent in adjuvant arthritis rats.

Gentiopicroside, originated from Gentiana macrophylla Pall, possesses antiarthritic efficacy in adjuvant-induced arthritis rats

OBJECTIVE This work aimed to investigate the anti-rheumatoid arthritic effect of gentio.picroside from Gentiana macrophylla Pall using an animal model of adjuvant induced arthritis.METH.ODS Adjuvant arthritis was induced in fifty SD male rats,which were randomly divided into five groups(n=10):control(0.5% CMC-Na) group,AIA(rats with CFA) group,dexamethasone(1 mg·kg^(-1)) group,gentiopicroside(50 mg·kg^(-1)) group,and gentiopicroside(100 mg·kg^(-1)) group.Rats were administered intragastrically with drugs or CMC-Na once a day for a period of 2 weeks.Paw swelling,arthritic index,histological changes were assessed to evaluate the anti-arthritic effect.Weight growth,spleen and thymus indexes were also investigated in.RESULTS Gentiopicroside at dose of 100 mg·kg^(-1) significantly inhibited the secondary paw swelling(P<0.05) and arthritis index(P<0.05),decreased synovial inflammatory infil.tration,synovial hyperplasia and bone erosion.Furthermore,gentiopicroside showed no immunosup.pressive adverse effects in body weight,index of spleen and thyums compared with dexamethasone administration(P<0.05,P<0.01).CONCLUSION Gentiopicroside possessed anti-arthritic efficacy in AIA rats without immunosuppressive effects.

Effect of Cornus officinalis glycoside on adjuvant-induced arthritis in rats

The aim of this study was to explore the effect of Cornus officinalis glucosides (COG) on adjuvant-induced arthritis in rats and its mechanism. Seventy-two rats were divided into six groups of normal, model, Dexasone (0.125 mg/kg), high-dose COG (240 mg/kg), mid-dose COG (120 mg/kg), and low-dose COG (60 mg/kg). Rat arthritis was induced by injection of Freund's complete adjuvant in the hind paws. All treatment started from the day the arthritis was induced. The edema degree of the adjuvant injection location was determined on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 20, 23 and the opposite side was observed on days 11, 13, 15, 17, 20, 23 after the injection of adjuvant. All rats were sacrificed on day 24 after the injection of adjuvant for microscopic examination of the ankle, and for the study of the immunological molecular mechanism. The results showed that the COG significantly suppressed both the primary and secondary edema, improved pathological injuries of adjuvant arthritis (AA) rat ankles, significantly suppressed the proliferation of T lymphocytes and DTH reaction. It significantly suppressed IL-1, IL-6 and TNF-αproduction from peritoneal macrophages and PGE2 in plasma. In conclusion, the Cornus officinalis glucosides (COG) is able to prevent and cure the rat adjuvant-induced arthritis, and can suppress the production of pro-inflammatory cytokine IL-1, IL-6, TNF-αand PGE2.

Tripterygium hypoglaucum extract ameliorates adjuvant-induced arthritis in mice through the gut microbiota

Traditionally,Tripterygium hypoglaucum(Levl.)Hutch(THH)are widely used in Chinese folk to treat rheumatoid arthritis(RA).This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota.The main components of prepared THH extract were identified by HPLC-MS.C57BL/6 mice with adjuvant-induced arthritis(AIA)were treated with THH extract by gavage for one month.THH extract significantly alleviated swollen ankle,joint cavity exudation,and articular cartilage destruction in AIA mice.The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways.THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice,featuring the increases of Bifidobacterium,Akkermansia,and Lactobacillus and the decreases of Butyricimonas,Parabacteroides,and Anaeroplasma.Furthermore,the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota.In addition,antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora.Strikingly,THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice,which validates the indispensable role of the intestinal flora.For the first time,we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway.Therefore,THH extract may serve as a microbial modulator to recover RA in clincial practice.verRAinclincial practice.

Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway

Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.

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.

Acute Lymphoblastic Leukemia Presenting as Systemic Juvenile Idiopathic Arthritis: Experience from Bangladesh

Background: Acute lymphoblastic leukemia (ALL), the most common paediatric malignancy, is a heterogeneous hematologic disease. ALL patients may present with isolated and persistent osteo-articular complaints, lower incidence of hepatomegaly, splenomegaly or lymphadenopathy without clear laboratory features, and misdiagnosed as systemic juvenile idiopathic arthritis (sJIA). Methods: This was a single center cross sectional study over a period of 4 years. Clinic laboratory profiles of 39 ALL children were compared with 39 age and sex-matched sJIA cases. Result: Among 39 ALL patients 89.7% were initially misdiagnosed as sJIA upon clinical presentation. Majority (66.7%) of ALL patients had oligo-articular joint involvement. In sJIA, small joints of the hands were most commonly involved. The total WBC count was significantly higher in ALL patients (p-value 0.0065). CRP and LDH values between the two groups showed significant differences (p-value 0.00006 and 0.00001 respectively). Conclusion: The presentation of leukemia with arthralgia or arthritis makes the diagnosis difficult for the physicians. The diagnosis of sJIA must be made with caution keeping the possibility of haematological malignancy in mind.

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.

Serum Zinc and Copper Level in Juvenile Idiopathic Arthritis (JIA) Patients and Its Correlation with Disease Duration-A Tertiary Hospital Study

Background: Juvenile Idiopathic Arthritis (JIA) is the most prevalent rheumatic disease in children. It is associated with abnormal levels of serum zinc (Zn) and copper (Cu) as during inflammation serum copper concentration increases and zinc decreases. Objective: To assess the serum Zn and Cu levels in different sub-types of JIA patients and their correlation with the disease duration. Methods: This cross-sectional study was conducted over twelve months at the Pediatric Rheumatology Division, Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University. Sixty-nine JIA cases that fulfilled the International League of Association for Rheumatology (ILAR) criteria were taken as cases and age and sex-matched healthy children were considered as controls. The serum Zn and Cu tests were done using the spectrophotometric method with INDIKO PLUS Drug Analyzer. Data were recorded in a pre-designed questionnaire. Data were checked, verified and analyzed manually where continuous variables were analyzed using unpaired t-test and categorical variables using the ANOVA test. Pearson’s correlation coefficient test was used to see the correlation of serum zinc and copper levels with disease duration. Results: Boys were predominant in both case and control groups, with the majority within the 10 to 16-year-age group. Enthesitis-related arthritis (ERA) was the most common subtype followed by sJIA, Oligo JIA, Poly JIA (RF-) and unclassified subtypes. Disease duration was found less than 12 months in 30.4% of JIA patients. Serum analysis revealed a statistically significant reduction in mean zinc levels and increased copper levels in JIA patients compared to controls. This study observed a negative correlation between serum zinc levels and disease duration, whereas serum copper levels exhibited a positive correlation with disease duration. Conclusion: In conclusion, this study revealed that JIA patients exhibit alterations in serum zinc and copper levels. Serum copper levels showed a positive correlation and serum zinc levels showed a negative correlation with the duration of the disease.

Case Report: Rhupus (The Association of Systemic Lupus Erythematosus and Rheumatoid Arthritis): About 2 Cases

Introduction: The association of systemic lupus erythematosus and rheumatoid arthritis (rhupus) is a rare clinical condition. Throughout the world, 287 cases of Rhupus have been described. We report two new observations of two patients who presented predominantly distal erosive polyarthritis with positive anti-Sm antibodies in one case and SmRNP in the other case. Observations: Case 1: 37 years old patient, with a recent diagnosis of pulmonary tuberculosis. She has since 8 months an inflammatory, bilaterally and symmetrical polyarthralgia without deformation or ankylosing synovitis, associated with malar erythema without other abnormalities. Immunological tests showed: positive Rheumatoid factor at 158 IU/ml, positive Anti-CCP at 550 IU/ml, and positivity of antinuclear at 1/1280 nuclear fluorescence with a strong presence of anti-Sm >8 IU/ml. The diagnosis of rhupus was concluded, without serious visceral involvement. Case 2: A 28-year-old patient, married with 3 children, with bilateral, symmetrical, deforming and chronic polyarthritis affecting large and small joints, which had been evolving for over 5 years without cutaneous abnormality associated. Paraclinical investigations showed: a biological inflammatory syndrome. Immunology was positive, with rheumatoid factors at 78 IU/ml, anti-CCP at 561 IU/ml, antinuclear antibodies at 1/1280 with positive anti-SmRNP and anti-SSA/Ro52, and a positive direct Coombs test. Joint ultrasound revealed tenosynovitis of the extensors and common flexors of the fingers, erosions and synovitis of multiple PPIs. The diagnosis of rhupus was based on the presence of 10 ACR criteria for RA and 8 ACR/EULAR 2019 criteria for SLE. Conclusion: Rheumatoid arthritis is a rare autoimmune disease combining features of both systemic lupus erythematosus and rheumatoid arthritis in the same patient, often sequentially. Despite a growing number of case reports and series, a consensus on the classification of SLE arthritis is still lacking, and diagnostic criteria for rhupus do not exist. These cases of rhupus must be recognized, as the vital and/or functional prognosis may be different from SLE alone or isolated RA.

Interleukin 6 and Bone Erosions in Rheumatoid Arthritis in an African Hospital

Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.

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.