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ID PMID Title PublicationDate abstract
30952846 The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflamm 2019 Apr 5 The human immune system has evolved in the context of our colonisation by bacteria, viruses, fungi and parasitic helminths. Reflecting this, the rapid eradication of pathogens appears to have resulted in reduced microbiome diversity and generation of chronically activated immune systems, presaging the recent rise of allergic, autoimmune and metabolic disorders. Certainly, gastrointestinal helminths can protect against gut and lung mucosa inflammatory conditions by modulating the microbiome and suppressing the chronic inflammation associated with dysbiosis. Here, we employ ES-62, an immunomodulator secreted by tissue-dwelling Acanthocheilonema viteae to show that helminth-modulation of the gut microbiome does not require live infection with gastrointestinal-based worms nor is protection restricted to mucosal diseases. Specifically, subcutaneous administration of this defined immunomodulator affords protection against joint disease in collagen-induced arthritis, a mouse model of rheumatoid arthritis, which is associated with normalisation of gut microbiota and prevention of loss of intestinal barrier integrity.
31890833 The Masquelet technique for septic arthritis of the small joint in the hands: Case reports 2020 Feb Septic arthritis in distal interphalangeal (DIP) joints sometimes occurs in association with mucous cysts or after the surgical treatment of mallet fingers. Recently, several studies have demonstrated the effectiveness of the Masquelet technique in the treatment of bone defects caused by trauma or infection. However, only few studies have reported the use of this technique for septic arthritis in small joints of the hand, and its effectiveness in treating septic arthritis in DIP joints remains unclear. We report the clinical and radiological outcomes of three patients who were treated with the Masquelet technique for septic arthritis in DIP joints. One patient had uncontrolled diabetes and another had rheumatoid arthritis treated with methotrexate and prednisolone. The first surgical stage involved thorough debridement of the infection site, including the middle and distal phalanx. We placed an external fixator from the middle to the distal phalanx and then packed the cavity of the DIP joint with antibiotic cement bead of polymethylmethacrylate (40 g) including 2 g of vancomycin and 200 mg of minocycline. At 4-6 weeks after the first surgical stage, the infection had cleared, and the second surgical stage was performed. The external fixator and cement bead were carefully removed while carefully preserving the surrounding osteo-induced membrane. The membrane was smooth and nonadherent to the cement block. In the second surgical stage, an autogenous bone graft was harvested from the iliac bone and inserted into the joint space, within the membrane. The bone graft, distal phalanx, and middle phalanx were fixed with Kirschner wires and/or a soft wire. Despite the high risk of infection, bone union was achieved in all patients without recurrence of infection. Although the Masquelet technique requires two surgeries, it can lead to favorable clinical and radiological outcomes for infected small joints of the hand.
30959746 Lactobacillus fermentum PC1 has the Capacity to Attenuate Joint Inflammation in Collagen-I 2019 Apr 5 Lactobacillus strains have shown efficacy in attenuating inflammation. This study evaluated the potential of Lactobacillus fermentum PC1 for the treatment of rheumatoid arthritis (RA) using a murine model of collagen-induced arthritis. On Day 1, healthy DBA/1 mice (six to eight weeks of age) were immunized, with 100 μg of Chicken Type 11 collagen emulsified in complete Freund's adjuvant (CFA) by intradermal injection, at the base of the tail. On Day 21, the mice were immunized intraperitoneally with 100 μg of Bovine Type11 collagen in phosphate buffered saline (PBS). On Day 28, the mice were immunized intraperitoneally with 50 μg of lipopolysaccharide (LPS). Viable L. fermentum PC1 (1 × 10⁸ colony forming units) was given daily from Day two until the end of the experiment. From Day 21 onwards, the mice were monitored daily for clinical signs of arthritis. On Day 44, the experiment was terminated. Paws were obtained for histology and serum for cytokine assays. L. fermentum PC1-fed mice had significantly reduced paw inflammation as well as decreased synovial infiltration and less cartilage damage. Circulating serum cytokine profiles revealed decreased IL-12 and increased anti-inflammatory cytokines, namely IL-4 and IL-10. Thus, early administration of L. fermentum PC1 could prove to be a valuable therapeutic agent in the management of RA.
31356425 Thumb Metacarpophalangeal Joint Arthritis. 2019 Dec 1 Arthritis of the thumb metacarpophalangeal joint can be debilitating whether in isolation or in conjunction with degenerative disease at the adjacent joints. Despite its crucial role in fluid and dexterous motion of the thumb axis, little is known about the isolated incidence of pathology at this joint. Etiologies include primary, posttraumatic, and inflammatory arthritis. For early, isolated degenerative disease, arthroscopic synovectomy has been shown to yield satisfactory results. For more advanced disease, fusion is the benchmark. The literature suggests that increased flexion angles may mitigate development of trapeziometacarpal arthritis. In case of advanced arthropathy of the entire thumb axis, arthroplasty is a viable option to reduce pain, preserve motion, and thus limit progression of adjacent joint disease. Special considerations should be given to the rheumatoid thumb because a select combination of treatments for each deformity is thought to best address the unique pathomechanics.
31835888 Porphyromonas gingivalis, Periodontal and Systemic Implications: A Systematic Review. 2019 Dec 11 In recent scientific literature, oral infections and systemic manifestations, or correlations between oral health and systemic diseases are a topic of discussion. Porphyromonas gingivalis is one of the bacteria implicated in the biofilm formation of bacterial plaque, and plays an important role in the progression of periodontal disease. In this systematic review authors have evaluated the literature of the last 10 years on P. gingivalis and all the systemic implications proven. This study therefore evaluates all the districts of the organism in which this bacterium may have implications. From the results it emerges that P. gingivalis has implications in the onset of different systemic pathologies, including rheumatoid arthritis, cardiovascular pathologies, and neurodegenerative pathologies. Surely, understanding the mechanisms of diffusion of this bacterium, it would be possible to prevent a series of pathologies. Thus, putting the dentist clinician at the center of prevention for these diseases.
30996010 Sicca Syndrome Associated with Immune Checkpoint Inhibitor Therapy. 2019 Sep BACKGROUND: The objective of this study was to characterize the clinicopathologic features of sicca syndrome associated with immune checkpoint inhibitor (ICI) therapy. SUBJECTS, MATERIALS, AND METHODS: Consecutive patients with new or worsening xerostomia in the setting of ICI treatment for benign or malignant neoplastic disease were evaluated, including labial salivary gland biopsy (LSGB). RESULTS: Twenty patients (14 male; median age 57 years) had metastatic melanoma (n = 10), metastatic carcinoma (n = 6), or recurrent respiratory papillomatosis (n = 4) and were being treated with avelumab (n = 8), nivolumab (n = 5), pembrolizumab (n = 4), nivolumab/ipilimumab (n = 2), and M7824, a biologic targeting programmed cell death ligand 1 (PD-L1) and transforming growth factor ß (n = 1). Four had pre-existing autoimmune disease. Nineteen had very low whole unstimulated saliva flow; six had new dry eye symptoms. The median interval between ICI initiation and dry mouth onset was 70 days. Rheumatoid factor and anti-Sjögren's Syndrome-related Antigen A (Anti-SSA) were both positive in two subjects. LSGB showed mild-to-severe sialadenitis with diffuse lymphocytic infiltration and architectural distortion. There were lymphocytic aggregates in eight patients, composed mainly of CD3(+) T cells with a slight predominance of CD4(+) over CD8(+) T cells. ICI targets (e.g., programmed cell death 1 and PD-L1) were variably positive. In direct response to the advent of the sicca immune-related adverse event, the ICI was held in 12 patients and corticosteroids were initiated in 10. Subjective improvement in symptoms was achieved in the majority; however, salivary secretion remained very low. CONCLUSION: ICI therapy is associated with an autoimmune-induced sicca syndrome distinct from Sjögren's syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular injury. Improvement can be achieved with a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary flow deficits may be long term. IMPLICATIONS FOR PRACTICE: Sicca syndrome has been reported as an immune-related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies demonstrated mild-to-severe sialadenitis distinct from Sjögren's syndrome, with diffuse T-cell lymphocytic infiltration and acinar injury. Recognition of the cardinal features of ICI-induced sicca will spur appropriate clinical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine specialists better identify patients that develop ICI-induced sicca to initiate appropriate clinical evaluation and therapy to reduce the likelihood of permanent salivary gland dysfunction.
31484917 Pleuroparenchymal Fibroelastosis in association with Connective Tissue Disease: a new inte 2019 Aug 7 Pleuroparenchymal fibroelastosis (PPFE) is a rare and recently described interstitial pneumonia. It consists of progressive fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes, with defined and reproducible clinical, radiological and histopathological criteria. No effective treatment has yet been shown to modify the natural course of the disease, which vary greatly in the literature. Several conditions have been associated with PPFE, including connective tissue diseases (CTD). The authors present two cases of female patients with a CTD (rheumatoid arthritis and limited cutaneous systemic sclerosis, respectively) who presented with typical bilateral upper lobe thickening in chest-HRCT. In the first case, diagnosis was based on "definite" radiological and histopathological criteria for PPFE, while in the second case diagnosis was established on clinical grounds after discussion in a multidisciplinary team meeting. The authors present these cases of CTD-associated PPFE in order to raise awareness of this entity among clinicians.
31374539 Severe idiopathic pneumoparotitis: Case report and study review. 2019 Oct Parotitis is a frequent disease in general pediatrics. Pneumoparotitis is a rare affection that belongs to differential diagnoses of parotitis, along with infections, lymphadenitis, autoimmune disorders, inflammatory conditions, vascular malformations or neoplasms. It is usually described in musicians using wind instruments or in other situations involving a Vasalva maneuver. We report the case of a 12 years old boy with severe idiopathic pneumoparotitis without any of these well-known causes and whose autoimmune familial background of Sjögren syndrome might be relevant.
31523050 Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic In 2020 Jun 1 OBJECTIVE: An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls. METHODS: We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively. RESULTS: SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons). CONCLUSION: The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.
30647188 Association of Smoking and Obesity on the Risk of Developing Primary Sjögren Syndrome: A 2019 Jul OBJECTIVE: To explore the role of smoking and obesity in primary Sjögren syndrome (pSS). METHODS: Olmsted County (Minnesota, USA) residents (n = 106) diagnosed with pSS from 2000 to 2015 were compared to 3 controls without pSS and matched for age and sex who were randomly selected from Olmsted County residents. RESULTS: Current smokers were less likely to be pSS cases (OR 0.34, 95% CI 0.14-0.85), while there was no association between former smoking and case/control status (OR 1.27, 95% CI 0.80-2.03) compared to never smokers. Smoking status was not associated with antinuclear antibody, anti-SSA, anti-SSB, or rheumatoid factor positivity (p > 0.05). OR for obesity was 0.79 (95% CI 0.48-1.30). CONCLUSION: In this population-based study, current smoking was inversely associated with case/control status, while body mass index lacked any association.
30475093 Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca 2019 May AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of β(2)-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.
31192933 Th17/Treg cell level and clinical characteristics of peripheral blood of patients with Sjo 2019 Jun This study aims at analyzing the Th17/Treg cell level and clinical characteristics of the peripheral blood of patients with Sjogren's syndrome (SS) complicated with primary biliary cirrhosis (PBC) so as to deepen the understanding of this disease and seek for its possible onset mechanism.A retrospective analysis was conducted on the clinical data of 24 patients [8 (33%) males and 16 (67%) females] with SS complicated with primary biliary cirrhosis, 50 patients with primary SS and 93 healthy volunteers. These patients were divided into 3 groups: experimental group (SS+PBC), control group (SS) and healthy group. Then, peripheral blood was collected and flow cytometry was conducted to detect level of Th17 cells and Treg cells. A fully automatic biochemical detector was used to detect the corresponding liver function index. The correlation analysis was made based on the clinical manifestations and biochemical characteristics.Compared with the healthy group and control group, the experimental group had the highest Th17/Treg cell ratio, and Th17 cell frequency was significantly increased (P <.05). Furthermore, ALT, AST, ALP, γ-GT, TBIL, and other indexes were positively correlated to the Th17/Treg ratio (P <.05).Th17/Treg cell level and its ratio in peripheral blood of patients with SS complicated with primary biliary cirrhosis were significantly unbalanced, indicating that Th17 cells participate in the onset of this disease to a large extent. Furthermore, the Th17/Treg ratio has a certain correlation with some of the liver function indexes, on which a stratified analysis could be made furtherly according to the seriousness of the conditions.
31365332 A two-phase cohort study of the sleep phenotype within primary Sjögren's syndrome and its 2019 May OBJECTIVES: To characterise the sleep profile of patients with primary Sjögren's syndrome (pSS) and its relationship between hyper-somnolence and other clinical parameters. METHODS: In phase one of the study, we utilised cross-sectional data on daytime hyper-somnolence from the United Kingdom Primary Sjögren's Syndrome Registry (UKPSSR) cohort (n=857, female=92.7%). Phase two relied on clinical data from a cohort of patients (n=30) with PSS, utilising symptom assessment questionnaires and sleep diaries. RESULTS: Within the UKPSSR, daytime hyper-somnolence was prevalent (ESS, 8.2±5.1) amongst pSS patients with a positive correlation between daytime hyper-somnolence and fatigue (Spearman's rs = 0.42, p<0.0001). Amongst the clinical cohort, 100% of patients had problematic sleep. Participants with pSS awoke frequently (NWAK, 2.2±1.3), had difficulty in returning back to sleep (WASO, 59.9±50.2 min vs. normal of <30min) and a reduced sleep efficiency (SE, 65.7±18.5% vs. >85%). Fatigue (FIS, 82.4 ±33.5) and orthostatic symptoms (OGS, 6.7 ±3.7) remained high in these patients. CONCLUSIONS: Sleep disturbances are a problem in pSS, comprising difficulty in maintaining sleep, frequent awakenings throughout the night and difficulties in returning back to sleep. As such, the total time in bed without sleep is much greater and sleep efficiency greatly reduced. These patients in addition have a high symptomatic burden possibly contributing to and/or contributed by poor and disordered sleep.
31141241 Sjögren's syndrome and ranula development. 2019 Sep OBJECTIVES: We hypothesized that the extravasation of saliva from damaged ducts with lymphocytic infiltration in patients with Sjögren's syndrome causes ranulas. There are too many uncertainties to support this hypothesis. The aim of this study was to investigate whether there is an association between Sjögren's syndrome and ranulas. MATERIALS AND METHODS: We observed three cases of patients with ranulas who were also diagnosed with Sjögren's syndrome at the same facility. These cases led to the question of whether there are other such cases, and thus, an exhaustive literature search was conducted. RESULTS: Three cases in two case reports of mucocele of the floor of the mouth associated with adult Sjögren's syndrome were noted. Including our cases, until now, there have been six cases of ranula with adult Sjögren's syndrome. CONCLUSIONS: It could be useful to investigate whether patients presenting with a ranula are also affected by Sjögren's syndrome and, conversely, investigate patients with Sjögren's syndrome longitudinally to see whether they develop ranulas.
30299247 Prevalence of sicca syndrome in the Peruvian population. 2019 May OBJECTIVES: Sjögren's syndrome is a complex and heterogeneous autoimmune disease characterised by ocular and oral dryness (1), which mainly affects the exocrine glands. The objective of this study was to determine the prevalence of sicca syndrome (SS) in the Peruvian population. The age and gender of patients with SS and their national prevalence and in each of the departments were defined. METHODS: This was a cross-sectional prevalence study. All the people for whom the Ministry of Health (MINSA) in Peru covered health treatments from January to December 2016 were taken into account. The patients with SS were either newly or previously diagnosed with sicca syndrome (Sjögren's) according to the international classification of diseases version 10 (ICD-10) of the World Health Organization (WHO). The prevalence was determined considering the number of cases of SS in the total population registered by the Ministry of Health (MINSA). RESULTS: 1,301 cases of SS were observed in a total population of 15,417,345 people served in 25 territories. The prevalence of SS in this population was 0.0084%, the prevalence rate was 8.4 cases per 100,000 persons (95% CI: 7.99-8.91). The prevalence of SS was higher in the territories of Tacna, Lima, La Libertad, Arequipa, Callao, and Apurímac. CONCLUSIONS: The results of this study show the prevalence of SS in the Peruvian population and serve to strengthen the health strategies of rheumatology, ophthalmology, and oral health to improve the diagnosis, treatment, follow-up of the disease, and the quality of life of patients with SS.
31464667 Sjögren's syndrome is not a risk factor for periodontal disease: a systematic review. 2019 May OBJECTIVES: Sjögren's syndrome (SS) is an autoimmune disorder causing irreversible damage to the exocrine glands. Evidence whether SS patients are at a higher risk to develop periodontal disease is conflicting. Therefore, we systematically reviewed the literature on the prevalence of periodontal disease in patients with SS. METHODS: Searches were performed in MEDLINE and CENTRAL databases on prevalence of periodontal diseases in SS. Meta-analyses were performed for gingival index (GI), plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), DMFT and DMFS (Decayed Missing Filled Teeth, respectively, Surfaces). RESULTS: Out of 512 studies, 10 studies were eligible for quantitative synthesis. Meta-analyses of the data indicated that in SS patients CAL, GI, PPD and PI are comparable to controls. DMFT and DMFS values were higher in SS patients than controls. CONCLUSIONS: No significant differences in the GI, PI, CAL, and PPD were observed in patients with SS compared to controls. These results indicate that there is no evidence of a higher risk for periodontal disease in patients with SS, while SS patients are more susceptible to caries compared to non-SS patients.
30836075 Discrepancies in Interpretation of the Minor Salivary Gland Biopsy in the Diagnosis of Sjà 2019 Aug PURPOSE: Although the minor salivary gland biopsy (MSGB) is a major criterion for the diagnosis of Sjögren syndrome (SS), multiple studies have outlined difficulties in standardization. The purpose of this study was to answer the following question: in all patients referred for MSGB, did strict application of focus scoring criteria alter the sensitivity of and predictive value of the MSGB in the diagnosis of SS compared with the initial interpretation? MATERIALS AND METHODS: The authors designed a cross-sectional study of patients referred to the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery (Boston, MA) over a 5-year period for MSGB. The primary predictor variable was the MSGB focus score. The primary outcome variable was the SS diagnosis. The newly established SS diagnosis status results were compared with the initial SS diagnoses. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. Other relevant variables of interest, such as size of glandular tissue harvested and associated signs and symptoms, also were documented. The primary predictor variable was the MSGB focus score and the primary outcome variable was the SS diagnosis (positive or negative). RESULTS: Seventy-three patients met the inclusion criteria. The mean age was 48.5 years (range, 19 to 71 yr) and 64 were women (87.6%). The authors' previous study using initial pathology reports yielded 80.0% sensitivity, 87.5% specificity, 57.1% PPV, and 95.5% NPV. The present review of the MSGB using strict focus scoring guidelines yielded 95.4% sensitivity, 76.4% specificity, 63.6% PPV, and 97.5% NPV. CONCLUSIONS: The MSGB is an important major criterion in establishing a diagnosis of SS. Application of strict focus scoring guidelines when reviewing the MSGB yielded a sensitivity far greater than initially reported in this group. Difficulties with interpretation are discussed. Future studies will focus on improvement of interpretation and immunohistochemical aids in diagnosis.
30320957 Prospective Determination of the Incidence and Risk Factors of New-Onset Uveitis in Juveni 2019 Nov OBJECTIVE: Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors. METHODS: Data were reported every 6 months for 2 years, then yearly to 5 years. Incidence was determined by Kaplan-Meier estimators with time of JIA diagnosis as the reference point. Univariate log-rank analysis identified risk factors and Cox regression determined independent predictors. RESULTS: In total, 1,183 patients who enrolled within 6 months of JIA diagnosis met inclusion criteria, median age at diagnosis of 9.0 years (interquartile range [IQR] 3.8-12.9), median follow-up of 35.2 months (IQR 22.7-48.3). Of these patients, 87 developed uveitis after enrollment. The incidence of new-onset uveitis was 2.8% per year (95% confidence interval [95% CI] 2.0-3.5) in the first 5 years. The annual incidence decreased during follow-up but remained at 2.1% (95% CI 0-4.5) in the fifth year, although confidence intervals overlapped. Uveitis was associated with young age (<7 years) at JIA diagnosis (hazard ratio [HR] 8.29, P < 0.001), positive antinuclear antibody (ANA) test (HR 3.20, P < 0.001), oligoarthritis (HR 2.45, P = 0.002), polyarthritis rheumatoid factor negative (HR 1.65, P = 0.002), and female sex (HR 1.80, P = 0.02). In multivariable analysis, only young age at JIA diagnosis and ANA positivity were independent predictors of uveitis. CONCLUSION: Vigilant uveitis screening should continue for at least 5 years after JIA diagnosis, and priority for screening should be placed on young age (<7 years) at JIA diagnosis and a positive ANA test.
31180523 Resveratrol alleviates inflammatory injury and enhances the apoptosis of fibroblast‑like 2019 Jul Resveratrol, a bioactive compound predominantly found in grapes and red wine, provides a wide range of properties that are beneficial for health, including anticancer and anti‑inflammatory activities. Previously published studies have addressed the potential therapeutic effects of resveratrol on rheumatoid arthritis (RA); however, the subcellular mechanism remains to be fully elucidated. In the present study, the therapeutic effects of resveratrol on adjuvant arthritis (AA) in Sprague‑Dawley rats were investigated, and the mechanisms of resveratrol‑induced apoptosis in fibroblast‑like synoviocytes (FLSs) were further examined. Based on the findings, resveratrol treatment over a 12‑day period led to a reduction in paw swelling and arthritis scores at the macroscopic level, and an attenuation of inflammatory cell infiltration and synovial hyperplasia, upon a histopathological examination of the AA rats. Furthermore, the administration of resveratrol triggered decreases in the expression of interleukin (IL)‑1, IL‑6, IL‑8 and tumor necrosis factor‑α (TNF‑α) and an increase in the expression of IL‑10, alleviating inflammatory injury in AA rats in a dose‑dependent manner. In addition, resveratrol was revealed to induce the apoptosis of FLSs when administered with 5 µM H2O2 as determined by elevated levels of Bax, caspase‑3, caspase‑12 and C/EBP‑homologous protein, and the downregulation of B‑cell lymphoma 2 (Bcl‑2), suggesting that resveratrol is able to induce apoptosis in FLSs via the mitochondrial pathway and endoplasmic reticulum (ER) stress in a milieu containing 5 µM H2O2. Furthermore, JC‑1 was used as a fluorescent probe to detect the mitochondrial membrane potential (Δψm), and resveratrol was shown to reduce the Δψm in FLSs in the presence of 5 µM H2O2. However, resveratrol was not able to trigger intracellular calcium overload, although it did suppress ATP‑ and thapsigargin‑induced calcium release from the ER. In conclusion, the present study revealed that resveratrol was able to alleviate inflammatory injury in AA rats, triggering the apoptosis of FLSs via the mitochondrial pathway and ER stress. These results provide a theoretical basis for future treatments using resveratrol for RA.
31240234 Chlorogenic Acid Inhibits BAFF Expression in Collagen-Induced Arthritis and Human Synovioc 2019 B cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) family, plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Chlorogenic acid (CGA) is a phenolic compound and exerts antiarthritic activities in arthritis. However, it is not clear whether the anti-inflammatory property of CGA is associated with the regulation of BAFF expression. In this study, we found that treatment of the collagen-induced arthritis (CIA) mice with CGA significantly attenuated arthritis progression and markedly inhibited BAFF production in serum as well as the production of serum TNF-α. Furthermore, CGA inhibits TNF-α-induced BAFF expression in a dose-dependent manner and apoptosis in MH7A cells. Mechanistically, we found the DNA-binding site for the transcription factor NF-κB in the BAFF promoter region is required for this regulation. Moreover, CGA reduces the DNA-binding activity of NF-κB to the BAFF promoter region and suppresses BAFF expression through the NF-κB pathway in TNF-α-stimulated MH7A cells. These results suggest that CGA may serve as a novel therapeutic agent for the treatment of RA by targeting BAFF.