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ID PMID Title PublicationDate abstract
34918140 Foot and ankle functions and deformities focus on posterior tibial tendon dysfunction usin 2021 Oct 6 OBJECTIVES: Posterior tibial tendon dysfunction (PTTD) affects the support of the medial longitudinal arch and stability of the hindfoot. The purpose of this study was to assess the relationships of PTTD with foot and ankle functions and foot deformities in patients with rheumatoid arthritis (RA). METHODS: A total of 129 patients (258 feet) who underwent magnetic plain and contrast-enhanced magnetic resonance imaging were enrolled in this study. Positive magnetic resonance imaging findings were defined as tenosynovitis and incomplete and complete rupture of the posterior tibial tendon. Foot and ankle functions were assessed using the Japanese Society for Surgery of the Foot standard rating system for the RA foot and ankle scale (JSSF-RA) and self-administered foot evaluation questionnaire. Plain radiographs were examined for the hallux valgus angle, first metatarsal and second metatarsal angle, lateral talo-first metatarsal angle, and calcaneal pitch angle. RESULTS: PTTD was associated with motion in the JSSF-RA (p = .024), activities of daily living in JSSF-RA (p = .017), and pain and pain-related factors in the self-administered foot evaluation questionnaire (p = .001). The calcaneal pitch angle was significantly lower in the feet with PTTD than in those without PTTD (median: 16.2° vs. 18.0°; p = .007). CONCLUSIONS: The present study shows that PTTD was associated with foot and ankle functions and flatfoot deformity. Thus, a better understanding of PTTD in patients with RA is important for the management of foot and ankle disorders in clinical practice.
34869276 A Three-Dimensional Co-Culture Model for Rheumatoid Arthritis Pannus Tissue. 2021 Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.
34703497 Targeting the resolution pathway of inflammation using Ac2-26 peptide-loaded PEGylated lip 2021 Jul Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2-26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2-26 peptides hinders their efficacy in vivo. In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l-ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG(2k)) to encapsulate and deliver Ac2-26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2-26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.
34685413 Ischemic Heart Disease and Rheumatoid Arthritis-Two Conditions, the Same Background. 2021 Oct 3 Rheumatoid arthritis (RA) is one of the most frequent inflammatory rheumatic diseases, having a considerably increased prevalence of mortality and morbidity due to cardiovascular disease (CVD). RA patients have an augmented risk for ischemic and non-ischemic heart disease. Increased cardiovascular (CV) risk is related to disease activity and chronic inflammation. Traditional risk factors and RA-related characteristics participate in vascular involvement, inducing subclinical changes in coronary microcirculation. RA is considered an independent risk factor for coronary artery disease (CAD). Endothelial dysfunction is a precocious marker of atherosclerosis (ATS). Pro-inflammatory cytokines (such as TNFα, IL-1, and IL-6) play an important role in synovial inflammation and ATS progression. Therefore, targeting inflammation is essential to controlling RA and preventing CVD. Present guidelines emphasize the importance of disease control, but studies show that RA- treatment has a different influence on CV risk. Based on the excessive risk for CV events in RA, permanent evaluation of CVD in these patients is critical. CVD risk calculators, designed for the general population, do not use RA-related predictive determinants; also, new scores that take into account RA-derived factors have restricted validity, with none of them encompassing imaging modalities or specific biomarkers involved in RA activity.
34429668 Patterns of Response to Different Treatment Strategies in Seropositive Rheumatoid Arthriti 2021 PURPOSE: To study the pattern of response to different treatment strategies in seropositive rheumatoid arthritis (RA) patients and to describe our clinical practice in RA management. PATIENTS AND METHODS: Over a period of two years from April 2018 to April 2020, we conducted a retrospective analysis of data for 288 consecutive seropositive RA patients attending rheumatology clinics and the daycare unit at Aseer Central Hospital. Data were collected on patient demographics, disease duration, extraarticular manifestations, comorbidities and treatment. Disease activity was assessed using the clinical disease activity index (CDAI). RESULTS: Out of the total 288 patients, 42% (120) are on csDMRADs, while 54% (162) are on bDMRADs and 4% (6) are on tsDMARDs. Of the patients on csDMARDS, 51%, 43% and 7% of them were on remission, low and moderate disease activity, respectively. However, of the patients on non-csDMARDS, 36.3%, 49.4% and 14.3% of them were on remission, low and moderate disease activity, respectively. Failure of csDMARDs was affected by the presence of high disease activity at baseline, extraarticular lung manifestations and coexistent fibromyalgia, with a significant effect of the latter on remission rate. Among patients on non-csDMARDs, 42 (25%) showed one or more therapy changes. Tumor necrosis factor inhibitors were the predominant first-line agents in biologically naive patients (65%) followed by abatacept (18%). Abatacept was the most frequently prescribed second biologic in 52% of cases followed by tocilizumab in 19%. CONCLUSION: The current clinical practice in our hospital is consistent with the latest American College of Rheumatology (ACR)/The European League Against Rheumatism (EULAR) guidelines. Treat-to-target strategy was achieved in the vast majority of our patients, while remission was observed in almost half of the patients.
34362073 Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005-2018. 2021 Jul 26 Rheumatoid arthritis (RA) trends among US adults and disparities in RA patients in recent years have not been well described. We aimed to examine the trend of RA prevalence and disparities among US adults. Data from the National Health and Nutrition Examination Survey (NHANES) of the years 2005-2018 were analyzed to examine the self-reported RA prevalence trend. Age-adjusted RA prevalence stratified by race/ethnicity and socioeconomic status (SES), as well as associated linear trends, were calculated for both genders. The multivariable adjustment was used to evaluate the association between race, SES, and RA. During 2005-2018, there was no significant linear trend in the age-adjusted self-reported RA prevalence among men and women, but significant differences among people from different races, educational levels, and family poverty income ratio (PIR) groups were observed. The RA rate difference was significant for both genders and between Non-Hispanic Caucasians and Non-Hispanic African Americans (both p-value ≤ 0.001). Both men and women with a higher educational level and a higher PIR had a lower age-adjusted RA rate. Age-adjusted RA prevalence fluctuated for both men and women during 2005-2018. Non-Hispanic African Americans and people with low SES had significantly higher age-adjusted RA prevalence and RA risk.
35087406 Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatm 2021 The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.
34955646 iTRAQ and PRM-Based Proteomic Analysis Provides New Insights into Mechanisms of Response t 2021 BACKGROUND: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study. METHODS: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs. RESULTS: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis. CONCLUSION: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.
34727347 Subcutaneous Infliximab, CT-P13 SC: A Profile of Its Use in the EU. 2021 Dec CT-P13 (Remsima(®); Inflectra(®)), a biosimilar of reference infliximab (Remicade(®)), provides a useful alternative for patients requiring infliximab therapy and, as with other biosimilar agents, has the potential to reduce treatment costs. Furthermore, the availability of CT-P13 in a subcutaneous formulation (CT-P13 SC), with the possibility (after adequate training) of self-administration at home, has the potential to both improve patient convenience and reduce the burden on the healthcare system. The initial approval of CT-P13 SC, for use in the treatment of rheumatoid arthritis in adults, was based on the findings of a randomised, double-blind phase I/III trial which demonstrated the non-inferiority of CT-P13 SC administered once every 2 weeks to intravenous CT-P13 (CT-P13 IV) administered once every 8 weeks in reducing disease activity in patients with active rheumatoid arthritis. Subsequently, based on pharmacokinetic data in patients with inflammatory bowel disease, CT-P13 SC has also been approved in the EU for use in the treatment of Crohn's disease, ulcerative colitis and, by extrapolation, ankylosing spondylitis, psoriatic arthritis and psoriasis, in adults.
33667534 Rheumatoid pannus presenting as a large epidural mass in the subaxial cervical spine: A ca 2022 Jan Rheumatoid arthritis (RA) is a debilitating inflammatory condition characterised by joint damage that affects the cervical spine most commonly at the atlantoaxial joint resulting in neck pain and myelopathy. The pathogenesis of RA involves the formation of a hyperplastic synovial tissue, termed pannus, which invades the local bone and causes osseous erosion. Here, we describe a case of rapid onset quadriparesis due to spinal cord compression at C5-C6 secondary to vertebral subluxation and mass effect from a large inflammatory pannus in the subaxial spine. Surgical decompression and resection of the subaxial pannus were performed, and the patient regained strength in all extremities. Histopathologic evaluation of the resected tissue confirmed the diagnosis of pannus over other more common epidural masses. Pannus formation commonly occurs in the peri-odontoid region; however, its presentation as a large soft tissue mass in the subaxial spine is not described in the current literature. Therefore, pannus should be considered in the differential diagnosis of epidural masses in the spine of RA patients. We use this case to discuss the pathology and radiological findings relevant to rheumatoid pannus formation in the subaxial cervical spine, as well as emphasise the importance of treatment in the context to severe degenerative disease.
33816157 Clinical utility of F-18 sodium fluoride PET/CT for estimating disease activity in patient 2021 Apr BACKGROUND: The present study aimed to investigate the clinical implication of F-18 sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) for assessing the disease activity of rheumatoid arthritis. METHODS: Seventeen patients with rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria were prospectively enrolled. All enrolled patients underwent F-18 NaF PET/CT along with physical examination, blood test, and ultrasonography. On PET/CT images, two quantitative parameters, F-18 NaF uptake of the joint (joint SUV) and joint-to-bone uptake ratio, were measured for each of the 28 joints included in calculating the disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between PET/CT parameters and clinical factors and the predictive values of PET/CT parameters for joints with synovitis and high disease activity were evaluated. RESULTS: Tender joints (joint SUV, 13.6±8.4; joint-to-bone uptake ratio, 1.70±1.02) and both tender and swollen joints (joint SUV, 13.9±5.4; joint-to-normal bone uptake ratio, 1.81±0.76) had significantly higher joint SUV and joint-to-bone uptake ratio than joints without synovitis (joint SUV, 6.0±2.4; joint-to-bone uptake ratio, 0.74±0.31; P<0.001). On correlation analysis, summed joint SUV (P=0.002, correlation coefficient=0.705) and summed joint-to-bone uptake ratio (P<0.001, correlation coefficient=0.861) of 28 joints showed strong positive correlation with DAS28-ESR after adjustment for age and body mass index. Summed joint SUV showed significant positive correlations with ultrasonography findings (grey scale ultrasonography: P=0.047, correlation coefficient =0.468; power Doppler ultrasonography: P=0.045, correlation coefficient =0.507). On the receiver operating characteristic curve analysis, the sensitivity and specificity for predicting synovitis were 83.2% and 92.7%, respectively, for joint SUV and 81.5% and 90.7%, respectively, for joint-to-bone uptake ratio. Moreover, the summation of both PET/CT parameters of 28 joints showed a diagnostic accuracy of 100.0% for predicting high disease activity in rheumatoid arthritis. CONCLUSIONS: Summed joint uptake on F-18 NaF PET/CT had a strong positive correlation with DAS28-ESR and accurately predicted high disease activity. F-18 NaF PET/CT parameters might be used as an imaging biomarker for disease activity in rheumatoid arthritis. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service of the Korea (CRIS, http://cris.nih.go.kr/cris/en; registry number, KCT0002597; registered November 2017).
33386441 Is there a role of tranexamic acid in rheumatoid arthritis with total knee arthroplasty? F 2021 Mar BACKGROUND: Tranexamic acid (TXA) has proven to be effective in reducing the blood loss associated with total knee arthroplasty (TKA) in patients with osteoarthritis. However, there still exists a paucity of evidence regarding the effectiveness of intravenous TXA in patients with rheumatoid arthritis. The aim of this study was to explore the efficacy and safety of intravenous TXA on blood loss after TKA in Chinese patients with rheumatoid arthritis. MATERIALS AND METHODS: A total of 405 patients with rheumatoid arthritis who had undergone TKA were categorized into two groups based on the protocol of TXA use. TXA group (n = 248): patients received 15 mg/kg TXA prior to operation. Control group (n = 157): patients received no TXA. The outcome measurements such as, total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), transfusion, drainage, the timing of first ambulation, the length of stay (LOS), total hospitalization costs, the results of 12-Item Short Form Survey (SF-12), the incidence of thromboembolic events and other complications were recorded and compared. RESULTS: The mean TBL, IBL, HBL, volume of transfusion and drainage were significantly lower in TXA group than in Control group. The rate of transfusion was significantly lower in TXA group than in Control group. There was a favorable effect in early ambulation for patients in TXA group, compared with patients in Control group. In addition, TXA group had shorter LOS, lower hospitalization costs and higher postoperative SF-12 score than Control group. The incidence of deep venous thrombosis and other complications did not differ between the two groups. CONCLUSION: TXA can effectively diminish blood loss, reduce transfusion, shorten LOS and decrease hospitalization costs after TKA in Chinese patients with rheumatoid arthritis, without increasing the risk of complications.
34101054 Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Es 2021 Oct BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. METHODS: We performed genome-wide association analyses in an entire JIA case-control sample (All-JIA) and in a case-control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. RESULTS: We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10(-6)), LTBP1 (P = 9,45 × 10(-6)), and ELMO1 (P = 1,05 × 10(-5)). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10(-6)), LTBP1 (P = 9,95 × 10(-6)), MX1 (P = 1,65 × 10(-5)), and CD200R1 (P = 2,59 × 10(-5)). CONCLUSION: This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.
33360828 DiR-labeled tolerogenic dendritic cells for targeted imaging in collagen- induced arthriti 2021 Feb Tolerogenic dendritic cells (tolDCs) are immunosuppressive cells and play an important role in rheumatoid arthritis (RA) as immunotherapeutic tools. We aimed to investigate whether allogeneic tolDCs (allo-tolDCs) and autologous tolDCs (auto-tolDCs) had long-time tolerogenic potential in vivo and improve arthritis in collagen-induced arthritis (CIA) rats. TolDCs were induced by NF-κB Decoy ODN, and loaded with Bovine Type II collagen (CII- loaded tolDCs) and identified by flow cytometry, and labeled with DiR and injected into CIA rats. The biodistribution of DiR-labeled tolDCs was monitored by IVIS imaging at different time points. Major organs were harvested and analyzed by ex-in vivo cell imaging. The tolDCs were successfully constructed, along with expressing low levels of CD80 and CD86 compared to DCs. The fluorescent signals of all DiR (+) groups were observed at least 25 days, and as long as 35 days. DiR (+) CII- loaded allo-and auto-tolDCs at post injection mainly distributed in the chest and abdomen and gradually moved to limb joints over time. The allo- and auto-tolDCs decreased the expression of IFN-γ and IL-2 in CIA rats with different severity compared to CIA rats without tolDCs treatment, while significantly increased the expression of IL-4 and IL-10. Additionally, these tolDCs ameliorated the ankle joints injury in CIA rats with different severity. The both allo- and auto-tolDCs showed long-time tolerogenic potential in vivo and ameliorated arthritis in CIA rats with different severity.
34271433 Effects of hydroxysafflor yellow A on rats with collagen-induced arthritis. 2021 Sep 17 Hydroxysafflor yellow A (HSYA) from safflower (Carthamus tinctorius L.) possesses several medicinal properties. However, it is unknown whether HSYA is effective in the treatment of rheumatoid arthritis (RA). Hence, we investigated the effects of HSYA on the inflammation and synovial damage in rats with collagen-induced arthritis (CIA) by subjecting them to treatment with different doses of HSYA. Our results revealed that HSYA could significantly reduce paw swelling, pathological manifestations, and serum cytokine levels in rats with CIA. The HSYA-treated groups showed increased antioxidant enzyme activity in the serum and decreased expression of inflammatory mediators in the synovial tissues. Furthermore, HSYA treatment inhibited extracellular signal-regulated kinase (ERK) signalling pathway activation. Notably, the highest dose of HSYA (20 mg/kg) exhibited the best effects against RA symptoms. Therefore, our findings suggest that HSYA alleviates the inflammatory response and synovial damage in rats with CIA by inhibiting the ERK signalling pathway.
33746759 Repurposing of Pirfenidone (Anti-Pulmonary Fibrosis Drug) for Treatment of Rheumatoid Arth 2021 Clinical studies have shown that pirfenidone (PFD) effectively relieves joint pain in rheumatoid arthritis (RA) patients. However, the detailed mechanisms underlying the anti-RA effects of PFD have not been investigated. This study was undertaken to investigate the repurposing of PFD for the treatment of RA, and explore its anti-rheumatic mechanisms. A collagen-induced arthritis (CIA) rat model was used to observe joint pathological changes following PFD treatment. Based on bioinformatics to predict the mechanism of PFD anti-RA, using EA. hy926 and TNF-α-induced MH7A cells to establish in vitro model to explore its biological mechanism from the perspectives of synovial inflammation and angiogenesis. PFD significantly relieved pathological changes, including joint swelling, synovial hyperplasia, inflammatory cell infiltration and joint destruction. PFD was also associated with reduced expression of MMP-3 and VEGF in articular chondrocytes and synovial cells of CIA rats (p < 0.05). Using bioinformatic methods, we predicted that PFD inhibits cell inflammation and migration by interfering with the JAK2/STAT3 and Akt pathways. These results were verified using in vitro models. In particular, PFD effectively reduced the expression of pro-inflammatory, chondrogenic, and angiogenic cytokines, such as IL-1β, IL-6, IL-8, MMP-1/3/2/9 and VEGF (p < 0.05), in TNF-α-induced MH7A cells. In addition, PFD significantly reduced the production of MMP-2/9 and VEGF in EA. hy926 cells, thereby weakening migration and inhibiting angiogenesis (p < 0.05). These findings suggest that PFD may alleviate the pathological process in CIA rats, by inhibiting inflammation and angiogenesis through multiple pathways, and serve as a potential therapeutic drug for RA.
35224306 The protein corona modulates the inflammation inhibition by cationic nanoparticles via cel 2022 Jul A central paradigm in nanomedicine is that when synthetic nanoparticles (NPs) enter the body, they are immediately cloaked by a corona of macromolecules (mostly proteins) that mediates the role of the physico-chemical properties in the NP biological functions (the "coronation paradigm"). In this work, we focused on the assessment of the "coronation paradigm" for cationic NPs (cNPs) used as rheumatoid arthritis (RA) drugs due to their ability to scavenge cell-free DNA (cfDNA). We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis (CIA) rats than the non-hydroxylated analogues. Especially, the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested cNPs. Proteomic analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones, which may provide a mechanistic explanation for the different biodistribution profiles of cNPs. Thus, this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.
33897712 Immunomodulatory Effects of Dopamine in Inflammatory Diseases. 2021 Dopamine (DA) receptor, a significant G protein-coupled receptor, is classified into two families: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptor families, with further formation of homodimers, heteromers, and receptor mosaic. Increasing evidence suggests that the immune system can be affected by the nervous system and neurotransmitters, such as dopamine. Recently, the role of the DA receptor in inflammation has been widely studied, mainly focusing on NLRP3 inflammasome, NF-κB pathway, and immune cells. This article provides a brief review of the structures, functions, and signaling pathways of DA receptors and their relationships with inflammation. With detailed descriptions of their roles in Parkinson disease, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, this article provides a theoretical basis for drug development targeting DA receptors in inflammatory diseases.
34874828 Adherence to the Mediterranean diet and the impact on clinical features in primary Sjögre 2021 Nov OBJECTIVES: The relationship between dietary patterns, including the Mediterranean diet, and rheumatic and musculoskeletal diseases (RMDs) has been increasingly assessed but data on patients with established primary Sjögren's syndrome (pSS) is lacking. The aim of the study was to explore the adherence to the Mediterranean diet and its relationship with metabolic and inflammatory features in a cohort of patients with pSS. METHODS: Demographic, clinical and serological data, including anthropometric parameters and cardiovascular (CV) disease risk factors/events among others were collected from 91 pSS patients. Adherence to the Mediterranean diet over the previous 12 months was assessed with the 14-item PREvencion con DIeta MEDiterranea (PREDIMED) tool and the 28-item Mediterranean Lifestyle (MEDLIFE) index. RESULTS: According to the PREDIMED score 29 (31%) patients had a good adherence to the Mediterranean Diet, 57 (61%) a medium adherence and only 7 (8%) a poor adherence. No difference could be identified across groups with regard to demographic data, disease activity, CV risk factors or other parameters. With regard to the MEDLIFE, the total of blocks 1 and 2, that are related to Mediterranean foods and dietary habits, did not correlate with the total of block 3 (related to other healthy habits such as physical activity), meaning that the patients adhering the most to the Mediterranean Diet not necessarily had an overall healthy lifestyle. The PREDIMED score was inversely correlated with disease activity, as measured by ESSDAI (Spearman's rho=-0.27, p=0.009) and ClinESSDAI (Spearman's rho=-0.26, p=0.01). Fish consumption was associated with lower prevalence of hypertension. CONCLUSIONS: Adherence to the Mediterranean diet, with particular attention to fish consumption, may be beneficial on various domains in pSS, such as the CV system and the inflammatory environment, and as such should be recommended to patients with this disease.
34665711 Searching for the "X factor" in Sjögren's syndrome female predilection. 2021 Nov Sjögren's syndrome is typified by a strong female predilection which is also observed in other systemic autoimmune diseases. Although many factors may be contributing to this phenomenon, the exact underlying mechanisms remain unclear. Apart from the traditionally considered hormonal and environmental factors, lately the role of sex chromosomes and especially of the X chromosome has drawn much attention. In the current review, we focus on the inherent genetic imbalance between the sex chromosomes and their influence and role on gender-discordant disease presentation. To compensate for this imbalance, nature has created a defective epigenetic mechanism to silence the second rich in immune related genes X chromosome. Genes escaping silencing, transfer the genetic imbalance into the transcriptional and protein level, contributing to gender differences as reflected in functions of the innate and adaptive immunity. Under this prism, recent research data on SS, regarding specific immune X-linked loci are being presented and analysed. The "X Factor" in the search for an explication of women's predilection in autoimmunity, may lie behind these unique properties of the X chromosome.