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ID PMID Title PublicationDate abstract
34712426 Anti-arthritic activity of Ricinus communis L. and Withania somnifera L. extracts in adjuv 2021 Jul OBJECTIVES: This study aimed to evaluate the anti-arthritic activity of Ricinus communis leaves' and Withania somnifera roots' hydroalcoholic extracts in Complete Freund's adjuvant-induced arthritis in Wistar rats. MATERIALS AND METHODS: HPLC and FT-IR analysis detected pharmacologically important phytocompounds in both plant extracts. Oral treatments including methotrexate (MTX; 3 mg/kg twice a week) and extracts at 250 and 500 mg/kg/day were initiated after arthritis induction. Changes in paw swelling, arthritic score, body weight, organ indices (thymus and spleen), hematological and biochemical parameters, and pro-/anti-inflammatory cytokine expression using qRT-PCR were assessed. Oxidative stress markers in hepatic tissue were determined. Histopathological and radiological examinations were also performed. RESULTS: RCE (R. communis extract) and WSE (W. somnifera extract) demonstrated a reduction in paw swelling, arthritic score, and restoration of body weight and organ indices. Hematological parameters, serum inflammatory markers such as CRP and RF, and liver function markers of arthritic rats were significantly (P<0.01) ameliorated with RCE and WSE treatment. Both plants persuasively down-regulated IL-1β, IL-6, IL-17a, TNF-α, and RANKL and up-regulated IL-4, INF-γ, and OPG relative expression as well as alleviating hepatic oxidative stress parameters. Histopathological and radiological findings revealed a marked reduction in tissue inflammation and bone erosion in extracts treated groups. CONCLUSION: The study findings suggest that R. communis leaves and W. somnifera roots have markedly subsided inflammation and improved health through modulating pro-/anti-inflammatory cytokine expression and reducing oxidative stress.
34277343 Inflammatory arthritis and the elbow surgeon. 2021 Sep The treatment of inflammatory arthritis with disease modifying drugs and biological agents had reduced the number of patients needing surgical treatment. Surgical treatment of patients with inflammatory arthritis is challenging not only due to the factors such as bone stock and status of soft tissue but also due to the comorbidities associated with inflammatory arthritis. Multidisciplinary approach to these patients is recommended to deal with the complex poly-articular involvement and systemic physiological impairment especially when planning surgery. This review will cover the key articular and peri-articular pathologies that can affect the elbow in inflammatory arthritis and discuss the treatment strategies available to the orthopaedic surgeon in their management. From surgical point of view, the rheumatoid elbow can be classified into 4 types: 1) classic soft tissue type with increased joint laxity, malalignment and instability; 2) osteoarthritic type with stiffness, hypertrophic joints (hypertrophic) and preserved alignment; 3) nodular type with subcutaneous nodules and enthesopathies but preserved jointly; 4) mutilans with bone and joint destruction. Surgical managements of the articular problem in each of the subtypes are discussed in this review. On the other hand, the seronegative arthritis such as psoarisis, gout and lupus seems to affect the peri-articular tissue of the elbow more than the joint itself and the disease specific management of the peri-articular soft tissue problems, such as enthesopathies and inflammatory nodules, are also outlined.
33770421 Development and validation of rheumatoid arthritis disease activity indices including Hand 2021 Mar 26 OBJECTIVES: To develop and validate a composite RA disease activity index using optical spectral transmission (OST)-scores obtained with the HandScan replacing tender and swollen joint counts. METHODS: RA patients from a single centre routinely undergoing HandScan measurements and at least one concurrent OST-score and DAS28 were included. Data was extracted from medical records. Linear regression analyses with DAS28 as outcome were performed to create a disease activity index (DAS-OST). OST-score, ESR and patient global assessment (PGA-)VAS, gender, age, disease duration and RF-status were evaluated as independent variables. Final models were derived, based on statistical significance of coefficients and model fit. Of the data, 2/3 was used for development and 1/3 for validation; external validation was performed in a cohort from another centre. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intra-class correlation coefficient (ICC). Diagnostic value of DAS-OST was determined for established definitions of remission, and low (L), and high (H) disease activity (DA). RESULTS: Data of 3358 observations from 1505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + PGA-VAS*0.03. The ICC between DAS-OST and DAS28 were 0.88 (95%CI 0.87-0.90) and 0.82 (95%CI 0.75-0.86) and measurement errors 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA and HDA were 79%, 91%, 43%, and specificity 92%, 80%, 96% in external validation. CONCLUSION: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PGA-VAS and gender into a disease activity index (DAS-OST).
33510894 Rheumatoid arthritis CD14(+) monocytes display metabolic and inflammatory dysfunction, a p 2021 INTRODUCTION: This study investigates the metabolic activity of circulating monocytes and their impact on pro-inflammatory responses in RA and explores whether this phenotype is already primed for inflammation before clinical manifestations of disease. METHODS: Blood was collected and CD14(+) monocytes isolated from healthy control donors (HC), individuals at-risk (IAR) and RA patients. Monocyte frequency in blood and synovial tissue was assessed by flow cytometry. Inflammatory responses and metabolic analysis ± specific inhibitors were quantified by RT-PCR, Western blot, migration assays, Seahorse-XFe-technology, mitotracker assays and transmission electron microscopy. Transcriptomic analysis was performed on HC, IAR and RA synovial tissue. RESULTS: CD14(+) monocytes from RA patients are hyper-inflammatory following stimulation, with significantly higher expression of cytokines/chemokines than those from HC. LPS-induced RA monocyte migratory capacity is consistent with increased monocyte frequency in RA synovial tissue. RA CD14(+) monocytes show enhanced mitochondrial respiration, biogenesis and alterations in mitochondrial morphology. Furthermore, RA monocytes display increased levels of key glycolytic enzymes HIF1α, HK2 and PFKFB3 and demonstrate a reliance on glucose consumption, blockade of which abrogates pro-inflammatory mediator responses. Blockade of STAT3 activation inhibits this forced glycolytic flux resulting in metabolic reprogramming and resolution of inflammation. Interestingly, this highly activated monocytic phenotype is evident in IAR of developing disease, in addition to an enhanced monocyte gene signature observed in synovial tissue from IAR. CONCLUSION: RA CD14(+) monocytes are metabolically re-programmed for sustained induction of pro-inflammatory responses, with STAT3 identified as a molecular regulator of metabolic dysfunction. This phenotype precedes clinical disease onset and may represent a potential pathway for therapeutic targeting early in disease.
34956106 Oral and Gut Microbial Carbohydrate-Active Enzymes Landscape in Health and Disease. 2021 Inter-individual variability in the microbial gene complement encoding for carbohydrate-active enzymes (CAZymes) can profoundly regulate how the host interacts with diverse carbohydrate sources thereby influencing host health. CAZy-typing, characterizing the microbiota-associated CAZyme-coding genes within a host individual, can be a useful tool to predict carbohydrate pools that the host can metabolize, or identify which CAZyme families are underrepresented requiring supplementation via microbiota transplantation or probiotics. CAZy-typing, moreover, provides a novel framework to search for disease biomarkers. As a proof of concept, we used publicly available metagenomes (935) representing 310 type strain bacterial genomes to establish the link between disease status and CAZymes in the oral and gut microbial ecosystem. The abundance and distribution of 220 recovered CAZyme families in saliva and stool samples from patients with colorectal cancer, rheumatoid arthritis, and type 1 diabetes were compared with healthy subjects. Based on the multivariate discriminant analysis, the disease phenotype did not alter the CAZyme profile suggesting a functional conservation in carbohydrate metabolism in a disease state. When disease and healthy CAZyme profiles were contrasted in differential analysis, CAZyme markers that were underrepresented in type 1 diabetes (15), colorectal cancer (12), and rheumatoid arthritis (5) were identified. Of interest, are the glycosyltransferase which can catalyze the synthesis of glycoconjugates including lipopolysaccharides with the potential to trigger inflammation, a common feature in many diseases. Our analysis has also confirmed the expansive carbohydrate metabolism in the gut as evidenced by the overrepresentation of CAZyme families in the gut compared to the oral site. Nevertheless, each site exhibited specific CAZyme markers. Taken together, our analysis provides an insight into the CAZyme landscape in health and disease and has demonstrated the diversity in carbohydrate metabolism in host-microbiota which can be a sound basis for optimizing the selection of pre, pro, and syn-biotic candidate products.
33197425 Analysis on the expression and value of CCL2 and CCL3 in patients with osteoarthritis. 2021 Feb In this study, we investigated the clinical value of CC chemokine ligand 2 (CCL2) and CC chemokine ligand 3 (CCL3) in osteoarthritis (OA). A prospective analysis was performed on 126 patients with rheumatoid arthritis of the knee (observation group (OG)) who admitted to Qilu hospital from August 2016 to August 2018 and 135 healthy controls (control group (CG)) who underwent physical examinations during the same period. The concentrations of CCL2 and CCL3 in peripheral blood were compared between the two groups, and the predictive value of the two on the occurrence, efficacy and prognosis of recurrence of OA were analyzed. In addition, an OA rat model was established to detect the relative protein levels of CCL2 and CCL3 in rat knee joint tissues. There were no statistically significant differences between the two groups in baseline data such as age, body mass index (BMI), gender, smoking, drinking, educational level, family medical history and living environment (P > 0.05). CCL2 and CCL3 increased in peripheral blood of patients in the OG (P < 0.05), both of which were positively correlated with rheumatoid factor (RF) (P < 0.001). CCL2 and CCL3 were of good predictive value for the occurrence, efficacy and prognosis of recurrence of OA (P < 0.001). The relative protein levels of CCL2 and CCL3 in bone and joint tissues of OA rats were significantly higher than those of normal rats (P < 0.001). CCL2 and CCL3 are elevated in peripheral blood of OA patients, which have good predictive value for the occurrence, efficacy and prognosis of recurrence of OA, indicating their potential roles as excellent markers for diagnosis and treatment of OA in the future.
35110824 Joint Protection Programmes for People with Osteoarthritis and Rheumatoid Arthritis of the 2021 Winter Purpose: Joint protection has been introduced as a self-management strategy for people with rheumatoid arthritis (RA) and osteoarthritis (OA) of the hand. The purpose of this study was to conduct an overview of systematic reviews (SRs) and critically appraise the evidence to establish the current effectiveness of joint protection for people with hand RA and OA. Method: A comprehensive search was conducted of six databases from January 2008 to May 2018. SRs that evaluated the effectiveness of joint protection for people with hand arthritis were eligible for inclusion. The A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 checklist was used to assess the methodological quality of each SR. Results: Nine SRs were included: two were rated as high quality, and seven were rated as low quality. Seven of the nine did not take into account risk of bias when interpreting or discussing their findings, six did not assess publication bias, and five did not register their protocol. The high-quality reviews found no clinically important benefit of joint protection for pain, hand function, and grip strength levels. The low-quality reviews reported improvements in function, pain, grip strength, fatigue, depression, self-efficacy, joint protection behaviours, and disease symptoms in people with RA. Conclusions: High-quality evidence from high-quality reviews found a lack of any clinically important benefit of joint protection programmes for pain, hand function, and grip strength outcomes, whereas low-quality evidence from low-quality reviews found improvements in these outcomes.
33426782 Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic 2021 Jan IMPORTANCE: Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis. BACKGROUND: Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States. DESIGN: This work involved a consensus survey and a panel meeting. PARTICIPANTS: The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work. METHODS: The Delphi technique was used to achieve consensus. MAIN OUTCOME MEASURES: This work yielded consensus statements. RESULTS: The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis. CONCLUSIONS AND RELEVANCE: Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA.
33551802 Artocarpus tonkinensis Extract Inhibits LPS-Triggered Inflammation Markers and Suppresses 2020 Artocarpus tonkinensis (At) leaf decoction, a traditional remedy prepared in North Vietnam by the Hmong ethnic group, is a tea extract rich in bioactive compounds that may have therapeutic effects in arthritis and backache. Indeed, it has been demonstrated that At is able to inhibit Th17 lymphocytes development and to protect mice in an experimental model of collagen-induced arthritis. By resorting to macrophage in vitro models of inflammation and osteoclastogenesis, we showed that At extract significantly reduced nitric oxide synthase 2 (NOS2) activity and IL-6 production by RAW 264.7 murine cells. Moreover, At demonstrated an anti-osteoclastogenic effect, as revealed by complete inhibition of TRAP-positive osteoclast formation and decreased expression of key osteoclast-related genes. This At activity likely relies on the inhibition of RANK downstream signaling pathway, as the activation of non-receptor tyrosine kinase Src is reduced upon RANKL-At exposure. Protective effect of At against bone loss was also enlightened in vivo by collagen-induced arthritis (CIA) experiment demonstrating that, although paw edema was only weakly opposed by drinking At decoction, bone and cartilage were well preserved in CIA+At mice and joint tissue expressed decreased levels of osteoclast marker genes respect to CIA control group. Maesopsin 4-O-β-D-glucoside (i.e., TAT-2, one of the main decoction bioactive components) was capable to contrast NOS2 activity, IL-6 expression and osteoclast formation, too, albeit to a lesser extent when compared to At decoction. Overall, this study enlightens another At cell target, macrophages, beside Th17 lymphocytes, and suggests that the anti-arthritic beneficial effects of At decoction largely derives from its ability to counteract not only inflammation, but also osteoclastogenesis.
34422862 The Crucial Questions on Synovial Biopsy: When, Why, Who, What, Where, and How? 2021 In the majority of joint diseases, changes in the organization of the synovial architecture appear early. Synovial tissue analysis might provide useful information for the diagnosis, especially in atypical and rare joint disorders, and might have a value in case of undifferentiated inflammatory arthritis, by improving disease classification. After patient selection, it is crucial to address the dialogue between the clinician and the pathologist for adequately handling the sample, allowing identifying histological patterns depending on the clinical suspicion. Moreover, synovial tissue analysis gives insight into disease progression helping patient stratification, by working as an actionable and mechanistic biomarker. Finally, it contributes to an understanding of joint disease pathogenesis holding promise for identifying new synovial biomarkers and developing new therapeutic strategies. All of the indications mentioned above are not so far from being investigated in everyday clinical practice in tertiary referral hospitals, thanks to the great feasibility and safety of old and more recent techniques such as ultrasound-guided needle biopsy and needle arthroscopy. Thus, even in rheumatology clinical practice, pathobiology might be a key component in the management and treatment decision-making process. This review aims to examine some essential and crucial points regarding why, when, where, and how to perform a synovial biopsy in clinical practice and research settings and what information you might expect after a proper patient selection.
34808732 Gram stain microscopy in septic arthritis. 2021 Sep Septic arthritis is a serious condition that can lead to rapid destruction of joint if it is not rapidly diagnosed and treated appropriately. The reported annual incidence is 10 in 100 000 although this increases to 70 in 100 000 in those with risk factors for developing septic arthritis mainly rheumatoid arthritis and immune-compromised patients. The aim of this study is to examine the sensitivity and specificity, and thus the clinical usefulness, of gram stain results. This was a single centre, retrospective case series. All joint aspirates over a three year period from May 2015 to April 2018 were reviewed. The gram stain and final culture results noted. 830 samples were included from both native and replaced joints. Native joints accounted for a total of 701 cases (84%) of the aspirates, whilst those obtained from prosthetic joints 129 (16%). In 74 (9%) cases there was a discrepancy between the gram stain and culture results. The sensitivity of the gram stain in this case series is 22% and the specificity of the test is 99.6%. The clinician should have a low threshold for overlooking a negative gram stain result and place greater emphases on the clinical findings in conjunction with biochemical markers.
34970568 The Effect of Ketogenic Diet on Inflammatory Arthritis and Cardiovascular Health in Rheuma 2021 The principle of ketogenic diet (KD) is restriction of carbohydrates to a maximum of 5-10% of the total daily caloric intake, aiming at shifting body metabolism toward ketone bodies. Different studies suggested promising results of KD to help patients to lose weight, to reduce insulin requirements in diabetes, to supplement cancer protocols, to treat neurological conditions and to optimize control of metabolic and cardiovascular diseases. However, literature about the anti-inflammatory properties of KD in rheumatic diseases is still limited. The beneficial effects of weight loss in patients with inflammatory arthritis can be explained by biomechanical and biochemical factors. Obesity is associated with macrophage activation and production of pro-inflammatory cytokines including TNF-α, IL-1b, and IL-6. The clinical effect of KD may be primarily attributed to improvement of insulin sensitivity. Insulin resistance is associated with an increase of TNF-α, IL-1α, IL-1β, IL-6, and leptin. Moreover, reduction of body's adipose tissue and weight loss account for part of the anti-inflammatory effects and for the impact of KD on cardiovascular health. In rheumatoid arthritis, fasting was shown to be effective in reducing disease symptoms, possibly through the production of β-hydroxybutyrate (BHB), the main ketone body. BHB may exert inhibitory effects also on IL-17 and intermittent fasting improved the clinical manifestations of psoriatic arthritis. In ankylosing spondylitis, current literature doesn't allow to draw conclusion about the effects of KD. Future prospective studies will be needed to elucidate the potential beneficial effects of KD on specific domains and clinical outcomes in patients with inflammatory arthritis.
34639772 Combination of Modified Scarf Osteotomy and Metatarsal Shortening Offset Osteotomy for Rhe 2021 Oct 5 With the progress of medical treatment for rheumatoid arthritis (RA), several joint-preserving forefoot surgical procedures have been established and performed. In this situation, we have been choosing the combined surgery: modified scarf osteotomy for the great toe and metatarsal shortening offset osteotomy for the lesser toes in RA cases. A retrospective observational study of 53 RA patients (mean follow-up period: 4.6 years) who underwent the surgery was completed. RA foot ankle scores were assessed, using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a self-administered foot evaluation questionnaire (SAFE-Q) was also checked to evaluate clinical outcomes. For radiological evaluations, deformity parameters were measured using radiographs of the feet with weight-bearing. JSSF hallux and lesser toes scores and the SAFE-Q score showed significant improvement in all indices. HVA, M1-M2A, M1-M5A, M2-M5A, and sesamoid position were significantly improved after surgery. At the final follow-up, the hallux valgus deformity had recurred in 4 feet (7.5%), and hallux varus deformity had developed in 8 feet (15.1%). No case of recurrent hallux valgus deformity required revision surgery. Recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint was seen in 6 feet (11.3%) after surgery. A combination of modified scarf osteotomy for the great toe and modified metatarsal shortening offset osteotomy for the lesser toes is one of the novel surgical procedures for rheumatoid forefoot deformity. Preoperative disease activity of RA negatively affected the clinical score of the hallux. The spread of M2-M5A was a risk factor for resubluxation of the lesser toe MTP joint.
35424296 Folate receptor-targeting mesoporous silica-coated gold nanorod nanoparticles for the syne 2021 Jan 14 The synergy of photothermal therapy (PTT) and chemotherapy is widely regarded as an effective treatment for complex diseases, such as cancer and inflammation. In this paper, we report the synthesis of a nanoscaled drug delivery system, which was composed of a gold nanorod (GNR) as the photothermal agent and a mesoporous silica shell as the methotrexate (MTX) reservoir, named FAGMs. Due to folate modification on the surface, FAGMs targeted specifically activated macrophages in rheumatoid arthritis (RA). Under 808 nm laser irradiation, FAGMs could kill macrophages by reaching sufficient local hyperthermia with excellent efficiency in the photothermal conversion of GNRs. Meanwhile, internal heating caused hydrogen bond fracture; thus, MTX released rapidly from FAGMs for localized synergistic PTT and chemotherapy. The FAGMs had a mean particle size of about 180 nm and a zeta potential of 14.36 mV. The release rate of MTX from FAGMs in vitro increased markedly under 808 nm laser irradiation. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages when treated with FAGMs, suggesting that folic acid molecules enabled the enhancement of endocytosis into activated macrophages. In rats with adjuvant-induced arthritis, synergistic treatment excellently inhibited the progression of RA. These results demonstrated that FAGMs could be promising for the treatment of RA.
34644224 Perceived challenges at work and need for professional support among people with inflammat 2021 Oct 13 BACKGROUND: People with inflammatory arthritis (IA) often experience low work ability, and up to 38% lose their jobs during the initial years after the diagnosis of IA. AIM: We explore the perceived challenges at work and identify the need for professional support among Danish people with IA. MATERIALS/METHODS: Individual explorative interviews based on a hermeneutic approach. We used Graneheim and Lundman's qualitative content analysis. RESULTS: Eleven women and four men with IA (aged 36-68 years) who worked full or part time, or were on short-term sick leave, participated. The analysis revealed one main theme, Balancing work as part of everyday life, and four sub-themes: 1) Working despite challenges, 2) Prioritising energy for work, 3) Fatigue leading to lack of control, and 4) Need for flexibility and recognition. CONCLUSIONS: People with IA prioritise staying at work despite experiencing challenges with fatigue and balancing their work and energy in everyday life. They need recognition, support and flexibility at work to be able to continue in their jobs. SIGNIFICANCE: The study highlights the need to be aware of occupational balance and, thus, to include other aspects in life apart from just work. It points at occupational therapists as relevant partners in vocational rehabilitation.
34722047 Impact of Change in Lifestyle and Exercise on Cognitive Function in Patients With Rheumato 2021 Sep Rheumatoid arthritis (RA) is a chronic destructive type of arthritis. It has a high prevalence in females as compared to the male population globally. It mainly affects the synovium of peripheral joints and leads to the destruction of joints with time. Patients with RA usually have a high burden of inflammation which may lead to certain physical disabilities and debilitating effects on mental health and cognitive ability. The question we investigated here in this systematic review is how changing lifestyles and increasing exercise or physical activities affects one's cognitive abilities. This article adheres to preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. We used different databases such as PubMed, MEDLINE, and ScienceDirect to find relevant articles. To ensure the quality of the finally selected 12 studies, we followed different quality appraisal tools.  Based on our review, we found out that increasing physical activities and aerobic exercises positively increase overall well-being and decrease the inflammatory load, which will ultimately positively impact cognitive function in this subgroup of patients. We also discover certain key players affecting motivation, perception, and adherence to physical activities. We encourage future studies to be done on this topic to help in increasing quality of life and increasing independence in this group of patients. Counseling and addressing patient concerns are very important and keep disease activity well controlled so that physical activities become feasible.
34875039 Paternal inflammatory arthritis is associated with a higher risk of miscarriage: results o 2021 Dec 7 OBJECTIVES: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA. METHODS: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyze the impact of IA on pregnancy outcomes, pregnancies were classified into two groups; pregnancies conceived after the diagnosis of IA and before the diagnosis of IA. RESULTS: In total 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, p = <0.05). This increased risk was still present after adjusting for confounders (OR 2.03 [95%CI 1.12-3.69], p= 0.015). CONCLUSIONS: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.
33967784 Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Cornus Officinalis a 2021 Cornus officinalis Sieb et. Zucc and Paeonia lactiflora Pall. have exhibited favorable therapeutic effects against rheumatoid arthritis (RA), but the specific mechanisms of their active compounds remain unclear. The aim of this study was to comprehensively analyze the therapeutic mechanisms of selected active compounds in Cornus officinalis (loganin, ursolic acid, and morroniside) and Paeonia lactiflora (paeoniflorin and albiflorin) via network pharmacology. The pharmacological properties of the five active compounds were evaluated and their potential target genes were identified by database screening. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analysis were performed to determine the enriched molecular pathways associated with the active compounds. Using network pharmacology tools, eight genes (IL1β, VEGFA, STAT3, TP53, IL6, TNF, FOS, and LGALS3) were identified as common targets between RA and the five active compounds. Molecular docking simulation revealed the compound-target relationship between the five active compounds and three selected targets from the eight common ones (LGALS3, STAT3, and VEGFA). The compound-target relationships were subsequently validated via preliminary in vivo experiments in a rat model of collagen-induced arthritis. Rats subjected to collagen-induced arthritis showed increased protein expression of LGALS3, STAT3, and VEGFA in synovial tissues. However, treatment using Cornus officinalis or/and Paeonia lactiflora, as well as their most drug-like active compounds (ursolic acid or/and paeoniflorin, respectively, identified based on pharmacological properties), attenuated the expression of these three targets, as previously predicted. Collectively, network pharmacology allowed the pharmacological and molecular roles of Cornus officinalis and Paeonia lactiflora to be systematically revealed, further establishing them as important candidate drugs in the treatment and management of RA.
34309834 CD4(+) LAG-3(+) T cells are decreased in active psoriatic arthritis patients and their res 2021 Nov Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte-activation gene (LAG)-3 is one of the regulatory receptors expressed on T cells in a soluble form. LAG-3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non-MDA) and healthy controls. In cultured in-vitro peripheral blood mononuclear cells (PBMCs), LAG-3 expression on CD4(+) T cells was similar in both MDA PsA patients (7.5 ± 0.9) (n = 14) and healthy controls (7.8 ± 0.6) (n = 15), but significantly lower in non-MDA PsA patients (3.1 ± 0.3) (n = 13) (p < 0.0001). An inverse correlation between PsA clinical disease activity and %CD4(+) LAG-3(+) T cells in vitro was observed (composite psoriatic disease activity index r = -0.47, p < 0.02 and psoriatic arthritis disease activity score, r = -0.51, p < 0.008). In-vitro co-culture of CD4(+) T cells with anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-17A had no effect on LAG-3(+) expression in MDA PsA patients and healthy controls. In non-MDA patients, anti-TNF, but not anti-IL-17A, restored the %CD4(+) LAG-3(+) T cells (7.9 ± 0.9 and 3.2 ± 0.4, respectively) (p < 0.0004). Lower soluble LAG-3 levels were found in sera of naive to biological PsA patients (n = 39) compared to healthy controls (n = 35) (p < 0.03). Impaired LAG-3 on CD4(+) T cells may reflect active PsA disease state. Anti-TNFs have potency to up-regulate the CD4(+) LAG-3(+) T cells in vitro.
33602797 'SMASH' recommendations for standardised microscopic arthritis scoring of histological sec 2021 Feb 18 Animal models for inflammatory arthritides such as rheumatoid arthritis (RA) and psoriatic arthritis are widely accepted and frequently used to identify pathological mechanisms and validate novel therapeutic strategies. Unfortunately, many publications reporting on these animal studies lack detailed description and appropriate assessment of the distinct histopathological features of arthritis: joint inflammation, cartilage damage and bone erosion. Therefore, the European consortium BeTheCure, consisting of 38 academic and industrial partners from 15 countries, set as goal to standardise the histological evaluation of joint sections from animal models of inflammatory arthritis. The consensual approach of a task force including 16 academic and industrial scientists as well as laboratory technicians has resulted in the development of the Standardised Microscopic Arthritis Scoring of Histological sections ('SMASH') recommendations for a standardised processing and microscopic scoring of the characteristic histopathological features of arthritis, exemplified by four different rodent models for arthritis: murine collagen-induced arthritis, collagen-antibody-induced arthritis, human tumour necrosis factor transgenic Tg197 mice and rat pristane-induced arthritis, applicable to any other inflammatory arthritis model. Through standardisation, the SMASH recommendations are designed to improve and maximise the information derived from in vivo arthritis experiments and to promote reproducibility and transparent reporting on such studies. In this manuscript, we will discuss and provide recommendations for analysis of histological joint sections: identification of the regions of interest, sample preparation, staining procedures and quantitative scoring methods. In conclusion, awareness of the different features of the arthritis pathology in animal models of inflammatory arthritis is of utmost importance for reliable research outcome, and the standardised histological processing and scoring methods in these SMASH recommendations will help increase uniformity and reproducibility in preclinical research on inflammatory arthritis.