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ID PMID Title PublicationDate abstract
30007097 Relationship of MR imaging of submandibular glands to hyposalivation in Sjögren's syndrom 2019 Jan OBJECTIVE: We analysed the correlation between magnetic resonance images of the parotid and submandibular glands and the salivary flow rate in patients with Sjögren's syndrome. METHODS: We retrospectively reviewed magnetic resonance images (heterogeneous signal-intensity distribution and gland volume on T1- and fat-suppressed T2-weighted images, and multiple high-signal-intensity spots on magnetic resonance sialograms in the parotid and submandibular glands) obtained from 66 patients who were diagnosed with Sjögren's syndrome. We evaluated the relationship between these imaging features and their salivary flow rates in stimulated and unstimulated conditions. RESULTS: We found that as the disease progressed, both the heterogeneous signal-intensity distribution and the volumes of the parotid and the submandibular glands were significantly related to the stimulated and the unstimulated salivary flow rate. These imaging features were more highly correlated in assessments of the submandibular gland than in those of the parotid gland for both stimulated and unstimulated salivary flow rates. CONCLUSIONS: Magnetic resonance image features of heterogeneity and smaller volume in the submandibular gland are reliable for predicting hyposalivation related to the progression of Sjögren's syndrome.
31612760 Type I renal tubular acidosis caused by Sjögren's syndrome with hypokalemia as the first 2020 Feb Sjögren's syndrome is a chronic inflammatory autoimmune disease characterized by exocrine gland involvement and marked lymphocytic infiltration. Numerous reports of patients with Sjögren's syndrome have described kidney damage, mainly involving distal tubule dysfunction, severe renal calcification, kidney stones, and rickets. We herein describe a patient with primary Sjögren's syndrome who developed type I renal tubular acidosis with hypokalemia as the first symptom. This case highlights the possibility that an underlying autoimmune disorder should be considered in a patient presenting with distal tubular acidosis or recurrent hypokalemic periodic paralysis because treatment of the primary disease improves the outcome.
31555987 Survival analysis of patients with Sjögren's syndrome in Turkey: a tertiary hospital-base 2020 Jan OBJECTIVES: This study was conducted to determine long-term survival rates and the factors associated with mortality in Turkish primary Sjögren syndrome (pSS) patients. METHODS: All patients diagnosed with pSS between 2004 and 2014 were included in this study. By January 2019, all subjects still living by the end of the study, as well as any death, were identified. Survival rates and standard mortality rates (SMRs) using general population mortality data were calculated. Mortality-related factors were determined by univariate and multivariate analysis. RESULTS: During follow-up, 33 cases of 372 pSS patients resulted in death (8.9%). Of those patients, they were typically older at disease onset, at recruitment, and had shorter follow-up times (p < 0.001 for all). The overall SMR of all pSS patients compared with the general population was 2.11 (95% confidence interval (CI) 1.39-2.83). Male pSS patients had a higher SMR than that of general male patients. Overall survival rates were 97.8% at five years, 90.2% at 10 years, and 87.1% at 15 years in patients with pSS. The survival rate of pSS patients was significantly lower than the general Turkish population (p = 0.011). Multivariate Cox regression analysis showed that older age at disease onset and the presence of interstitial lung disease (ILD) were independent risk factors for mortality. CONCLUSIONS: Based on these data, mortality rates of Turkish pSS patients are higher compared with the general population. Survival significantly decreased in the pSS patients with ILD, especially in older male patients at disease onset. Male gender and malignancy may also be associated with a worse prognosis in pSS patients.Key Point• Mortality in Sjögren's syndrome.
30539582 Detection of SSA and SSB Antibodies Associated with Primary Sjögren's Syndrome Using Enzy 2019 Antibodies to Ro52/Ro60 (SSA) and La (SSB) are strongly associated to the autoimmune disease primary Sjögren's syndrome and are important in the serologic diagnosis of the disease. Several methods for detection of these antibodies exist such as indirect immunofluorescence, commercial western blot kits, in-house assays, and numerous commercial enzyme-linked immunosorbent assays (ELISAs). Dependent on the type of assay, sensitivity and specificity may vary notably. Especially ELISAs, where the antibody reactivity to synthetic peptides, recombinant or native proteins are determined, are often applied. This chapter describes detection of SSA and SSB antibodies by ELISA.
30830076 [Oxidative stress correction in the treatment of severe keratoconjunctivitis sicca in pati 2019 PURPOSE: To evaluate the antioxidative effect of artificial tears in the treatment of keratoconjunctivitis sicca (KCS). MATERIAL AND METHODS: The study included 43 patients (60 eyes) with severe KCS: 38 women (50 eyes) and 5 men (10 eyes) aged from 27 to 76 years (in average 52 years). Patients were randomly divided into 2 groups; all patients used therapeutic silicone hydrogel soft contact lens (SCL) and instillations of 0.05% Cyclosporin A (CyA) 2 times a day. Patients of the first group (22 people, 30 eyes) used 0.15% hyaluronic acid. In the second group, patients (21 people, 30 eyes) used a tear substitute with similar surface-active component, but with antioxidant properties. The results of the treatment were evaluated using basic and additional research methods at 1, 3, 6 and 12 months. RESULTS: Corneal epithelialization was achieved after 1 month of conservative treatment in all patients who wore SCLs and were treated with instillations of 0.05% CyA and artificial tears. Then the lenses were removed and the patients were switched to instillations of CyA and artificial tears. Comparative analysis of the results showed that higher functional indicators were achieved in the second group, where patients used Artelac Rebalance drops with antioxidant properties. CONCLUSION: Improvement of clinical and functional parameters in the treatment of severe forms of KCS was achieved by direct action on both links of pathogenesis with minimal amounts of the drugs and the frequency of their use. Subsequent supportive therapy contributed to stabilization of the results and further increase of the functional parameters.
30561129 Effects of Xerostom(®) products on xerostomia in primary Sjögren's syndrome: A randomize 2019 Apr OBJECTIVES: To assess the effects of Xerostom(®) toothpaste and mouthwash in primary Sjögren's syndrome (pSS) patients with xerostomia. SUBJECTS AND METHODS: A double-blinded, randomized study where patients were assigned at baseline test or control products. Patients used the products 3 times/day/28 days. We used a visual analogue scale (VAS) for xerostomia and an Oral Health Impact Profile-14 (OHIP-14), baseline and after treatment, to assess possible improvement. RESULTS: A total of 28 patients with pSS were included in this study, but only 24 finished it (all women, mean age 55.21 ± 11.87), and 13 patients received the test and 11 the control. VAS and OHIP-14 scores decreased in both groups after treatment but significant differences between groups were not found. We do not detect VAS intragroup significant differences before and after treatment in test and control groups. A significant improvement in OHIP-14 was identified in the treatment group, while no significant differences were observed in the control group. No adverse effects were present. CONCLUSIONS: Xerostom(®) toothpaste and mouthrinse may alleviate and improve quality of life without associated side effects, but further research with a larger number of participants and follow-up are necessary to establish the positive efficacy of these topical products in pSS patients.
29781867 ACCELERATED ONSET OF RETINAL TOXICITY FROM HYDROXYCHLOROQUINE USE WITH CONCOMITANT BREAST 2019 Spring PURPOSE: To report a case of accelerated retinal toxicity due to hydroxychloroquine (HCQ) use for treatment of Sjögren syndrome in a patient treated with concomitant chemotherapy for breast cancer. METHODS: Observational case report. RESULTS: A 56-year-old white woman using 400 mg HCQ (7.1 mg/kg real body weight) daily for a total of 2 years and 10 months for treatment of Sjögren syndrome with concomitant use of docetaxel and cyclophosphamide therapy (21-day cycle, 4 cycles) followed by anastrozole for breast cancer, presented with visual complaints and findings of severe HCQ toxicity. CONCLUSION: Concomitant breast cancer therapy may have a synergistic effect with HCQ leading to accelerated retinal toxicity. As such potential acceleration is poorly understood, patients on HCQ who are treated with concomitant chemotherapy should be considered for more frequent retinal screenings to maximize safety and preservation of vision.
31621565 Patient questionnaires in osteoarthritis: what patients teach doctors about their osteoart 2019 Sep A patient history generally provides the most important information in diagnosis and management of patients with most rheumatic diseases, including osteoarthritis (OA). Patient history components can be expressed as quantitative, structured, "scientific" data, rather than "subjective" narrative descriptions, using patient self-report questionnaires. The Western Ontario McMaster (WOMAC) questionnaire is used in all OA clinical trials, and the health assessment questionnaire (HAQ) in all rheumatoid arthritis (RA) clinical trials, as "disease-specific" questionnaires. However, both questionnaires include scores for physical function function and pain; physical function scores are correlated highly significantly at r=0.78 in both RA and OA patients, while WOMAC pain scores are correlated with HAQ visual analogue scale (VAS) pain scores at r=0.73 in OA and r=0.71 in RA. Therefore, the WOMAC and HAQ may be regarded as largely "generic" questionnaires, at least for people with arthritis. Since it is not feasible to ask patients with different diagnoses to complete different care questionnaires in busy clinical settings, a single multidimensional HAQ (MDHAQ), derived from the HAQ and largely similar and informative in all rheumatic diseases, has been used in all rheumatology patients in several settings. The MDHAQ also has been incorporated into two OA clinical trials, with virtually identical results to the WOMAC. In routine clinical care, MDHAQ scores have documented that the disease burden of OA is comparable to RA in terms of scores for pain, physical function, and RAPID3 (routine assessment of patient index data) an index of pain, function and patient global assessment. Further observations indicate capacity of the MDHAQ to recognise fibromyalgia similarly to formal fibromyalgia criteria, as well as the ineffectiveness of opioids in OA, and similar prevalence of depression and other psychological issues in OA to RA. These findings also illustrate the value of a database of MDHAQ data for retrospective analysis of serendipitous observations from routine clinical care.
31172311 Emerging Immunomodulatory Therapies and New Treatment Paradigms for Axial Spondyloarthriti 2019 Jun 6 PURPOSE OF REVIEW: The purpose of this review is to educate the reader about the evolving classification of axial spondyloarthritis (AxSpA) and describe recent treatment data from clinical trials of medications with mechanisms of action other than TNF inhibition. The review will also address emerging treatment strategies for AxSpA. RECENT FINDINGS: New and more sensitive classification schema for AxSpA find that the prevalence of the disease is more than twice that of the historic definition of ankylosing spondylitis (AS), when patients without radiographically observable damage to the sacroiliac joints are included. TNF inhibitors have shown efficacy in the full spectrum of disease. IL-17 inhibitors, e.g., secukinumab and ixekizumab and janus kinase (JAK) inhibitors, have shown good efficacy and relatively good safety in radiographically defined AxSpA and are being tested in non-radiographic (nr) AxSpA. Several immunomodulatory medicines approved for psoriasis, psoriatic arthritis, and rheumatoid arthritis have not shown efficacy in AxSpA, highlighting the importance of conducting good-quality, placebo-controlled trials in this condition. Treatment strategies such as "treat to target" and tapering therapy are being studied. There remains a large unmet need to identify and adequately treat the full spectrum of AxSpA. The use of TNF inhibitors has improved our ability to achieve remission or low disease activity in AxSpA. Newer medicines with different mechanisms of action, e.g., IL-17 or JAK inhibition, are also showing similar ability. Continued research, including identification of new targets of treatment, is critical.
31090589 Treat-to-target in axial spondyloarthritis: gold standard or fools' gold? 2019 Jul PURPOSE OF REVIEW: Treat-to-target (T2T) is an emerging management strategy in axial spondyloarthritis (axSpA). The concept was originally based on evidence from other chronic conditions, such as hypertension, diabetes and hypothyroidism, as well as some rheumatic diseases, such as rheumatoid arthritis and gout. The purpose of this review is to discuss the arguments against and in favour of adopting a T2T strategy in the management of axSpA. RECENT FINDINGS: International groups have recommended a T2T strategy in axSpA. Inactive disease according to the Ankylosing Spondylitis Disease Activity Score (ASDAS) has been suggested as a potential target. Achievement of ASDAS inactive disease has been associated with less progression of radiographic damage in several studies. Evidence for the benefit of a T2T approach has been published in psoriatic arthritis, a form of spondyloarthritis. SUMMARY: Observational evidence suggests that a T2T approach might be beneficial in axSpA. However, data from a prospective randomized study proving the efficacy of a T2T strategy compared to routine care are still lacking. Moreover, the cost-effectiveness of such strategy in clinical practice also needs to be tested. The target will need to be useful and feasible in both clinical practice and clinical trials.
31126876 Role of osteopontin in dendritic cell shaping of immune responses. 2019 Dec Osteopontin (OPN) is a pleiotropic cytokine produced both by immune and non-immune cells and active on different cellular targets. OPN production has been associated with several pathological conditions, including autoimmune diseases (e.g. lupus, multiple sclerosis and rheumatoid arthritis) and cancer. Emerging evidence suggests that the role of OPN has been underestimated, as it seems to be working at multiple levels of immune regulation, such as the shaping of T cell effector responses, the regulation of the tumor microenvironment, and the functional interaction with mesenchymal stromal cells. In this context, dendritic cells (DCs) play a crucial role being both an important source and a cellular target for OPN action. DC family is composed by several cell subsets endowed with specific immune functions. OPN exerts its biological functions through multiple receptors and is produced in different intracellular and secreted forms. OPN production by DC subsets is emerging as a crucial mechanism of regulation in normal and pathological conditions and starts to be exploited as a therapeutic target. This review will focus on the role of DC-derived OPN in shaping immune response and on the complex role of this cytokines in the regulation in immune response.
31081558 MSC Therapy for Osteoarthritis: An Unfinished Story. 2019 Jun Mesenchymal stromal cells (MSCs) have firmly occupied the attention of orthopedic clinicians and scientists for most of the last 25 years. Hundreds of laboratories worldwide have carried out research aimed at unraveling the biological characteristics of these cells and probing the manner in which they potentially contribute to cartilage and bone repair. Clinical trials registries indicate that they are also being tested in patient studies for a wide range of conditions such as osteoarthritis, rheumatoid arthritis, fracture repair, regeneration of articular cartilage, tendon repair, and for treatment of degenerative disc disease. Despite these efforts, the effectiveness of MSCs as a treatment modality for these conditions is still uncertain and market authorizations have been limited. In addition, critical and clear phenotypic parameters for defining MSCs are uncertain and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available. Added to this, cell manufacturing protocols are complex and costly and present substantial challenges in terms of regulatory oversight and standardization. Despite these obstacles, MSCs still remain at the forefront of efforts in Regenerative Medicine, based on a conviction that this technology can provide an effective treatment paradigm for major diseases where there is still an unmet need. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1229-1235, 2019.
31118734 Evaluating tofacitinib citrate in the treatment of moderate-to-severe active ulcerative co 2019 The etiology of ulcerative colitis (UC) is complex and involves a host of genetic, epigenetic and environmental factors. Over the last thirty years, signaling pathways like the Janus kinase (JAK) signaling pathway have been implicated in its pathogenesis. Pharmacologic blockade of this pathway is available through several small molecule inhibitors, including tofacitinib. Tofacitinib is an orally administered pan-JAK inhibitor that was first approved by the Food and Drug Administration (FDA) for use in rheumatologic disorders such as rheumatoid arthritis and psoriatic arthritis. The FDA approved its use in moderate-to-severe active ulcerative colitis in 2018. The aim of this review will be to discuss the role of tofacitinib in ulcerative colitis. We will discuss the role of JAK-STAT signaling, clinical data available for tofacitinib, and the safety profile for this therapy. Tofacitinib's place in the UC management algorithm is currently being debated. This effective oral therapy is poised to be a mainstay of UC therapeutics. This review will highlight the key clinical features and detail the UC experience to date.
30872671 Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative 2019 Mar 14 Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.
30385646 Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features. 2019 Nov BACKGROUND: Copa syndrome is a rare autosomal dominant disorder with abnormal intracellular vesicle trafficking. The objective of this work is to expand the knowledge about this disorder by delineating phenotypic features of an unreported COPA family. METHODS AND RESULTS: A heterozygous missense variant (c.698 G>A, p.Arg233His) in COPA was identified in four members of a three-generation kindred with lung, autoimmune and malignant disease of unknown aetiology. Ages of onset were 56, 26, 16 and 1 year, with earlier age of onset in successive generations. Presenting symptoms were cough and dyspnoea. Findings included small lung cysts, follicular bronchiolitis, interstitial lung disease, neuroendocrine cell hyperplasia, rheumatoid arthritis, avascular necrosis and select abnormal autoimmune serologies. Neither alveolar haemorrhage nor glomerular disease were present. Features not previously associated with Copa syndrome included neuromyelitis optica, pulmonary carcinoid tumour, clear cell renal carcinoma, renal cysts, hepatic cysts, nephrolithiasis, pyelonephritis and meningitis. Longitudinal evaluations demonstrated slow progression of lung disease and extrapulmonary cysts. CONCLUSIONS: Worsening severity with successive generations may be observed in Copa syndrome. Extrapulmonary cysts, malignancies, autoimmune neurological disorders and infections are clinical features that may be associated with Copa syndrome. Further studies are indicated to fully define the phenotypic spectrum of this disorder.
31031776 IgG and Fcγ Receptors in Intestinal Immunity and Inflammation. 2019 Fcγ receptors (FcγR) are cell surface glycoproteins that mediate cellular effector functions of immunoglobulin G (IgG) antibodies. Genetic variation in FcγR genes can influence susceptibility to a variety of antibody-mediated autoimmune and inflammatory disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). More recently, however, genetic studies have implicated altered FcγR signaling in the pathogenesis of inflammatory bowel disease (IBD), a condition classically associated with dysregulated innate and T cell immunity. Specifically, a variant of the activating receptor, FcγRIIA, with low affinity for IgG, confers protection against the development of ulcerative colitis, a subset of IBD, leading to a re-evaluation of the role of IgG and FcγRs in gastrointestinal tract immunity, an organ system traditionally associated with IgA. In this review, we summarize our current understanding of IgG and FcγR function at this unique host-environment interface, from the pathogenesis of colitis and defense against enteropathogens, its contribution to maternal-fetal cross-talk and susceptibility to cancer. Finally, we discuss the therapeutic implications of this information, both in terms of how FcγR signaling pathways may be targeted for the treatment of IBD and how FcγR engagement may influence the efficacy of therapeutic monoclonal antibodies in IBD.
30724039 Diagnosis of Fibromyalgia: Disagreement Between Fibromyalgia Criteria and Clinician-Based 2019 Mar OBJECTIVE: Recent studies have suggested that fibromyalgia is inaccurately diagnosed in the community, and that ~75% of persons reporting a physician diagnosis of fibromyalgia would not satisfy published criteria. To investigate possible diagnostic misclassification, we compared expert physician diagnosis with published criteria. METHODS: In a university rheumatology clinic, 497 patients completed the Multidimensional Health Assessment Questionnaire (MD-HAQ) and the 2010 American College of Rheumatology preliminary diagnostic criteria modified for self-administration during their ordinary medical visits. Patients were evaluated and diagnosed by university rheumatology staff. RESULTS: Of the 497 patients, 121 (24.3%) satisfied the fibromyalgia criteria, while 104 (20.9%) received a clinician International Classification of Diseases (ICD) diagnosis of fibromyalgia. The agreement between clinicians and criteria was 79.2%. However, agreement beyond chance was only fair (κ = 0.41). Physicians failed to identify 60 criteria-positive patients (49.6%) and incorrectly identified 43 criteria-negative patients (11.4%). In a subset of 88 patients with rheumatoid arthritis (RA), the kappa value was 0.32, indicating slight to fair agreement. Universally, higher polysymptomatic distress scores and criteria-based diagnosis were associated with more abnormal MD-HAQ clinical scores. Women and patients with more symptoms but fewer pain areas were more likely to receive a clinician's diagnosis than to satisfy fibromyalgia criteria. CONCLUSION: There is considerable disagreement between ICD clinical diagnosis and criteria-based diagnosis of fibromyalgia, calling into question ICD-based studies. Fibromyalgia criteria were easy to use, but problems regarding clinician bias, meaning of a fibromyalgia diagnosis, and the validity of physician diagnosis were substantial.
30713571 Water Extract of Acori Graminei Rhizoma Attenuates Features of Rheumatoid Arthritis in DBA 2019 The dry rhizome of Acorus gramineus Solander, known as Acori Graminei Rhizoma, is used to treat dementia, stroke, eczema, and indigestion in traditional Chinese medicine, traditional Korean medicine, and traditional Japanese Kampo medicine. Previous studies have reported that Acori Graminei Rhizoma extract ameliorated cognitive impairment in Aβ1-42 injected mice. However, the effect of Acori Graminei Rhizoma on type II collagen induced arthritis (CIA) has not been elucidated. Thus, we evaluated the water extract of Acori Graminei Rhizoma (WAG) in CIA mice models. Male DBA/1 mice were separated into five groups (NOR; n=10, CON; n=10, CIA + methotrexate (MTX); n=10, CIA + 100 mg/kg WAG; n=10, CIA + 500 mg/kg WAG; n=10). CIA was induced by injecting the mice with bovine type II collagen, after which the mice were treated with WAG and/or MTX. Hematological parameters and liver and kidney serum toxicity markers were analyzed. Further, serum levels of interleukin (IL)-6, TNF-α, and type II collagen IgG were analyzed via enzyme-linked immunosorbent assay (ELISA). Treatment with 500 mg/kg WAG decreased serum levels of IL-6, TNF-α, and collagen IgG in a CIA model. Moreover, WAG treatment decreased CIA-induced swelling of mouse hind legs, infiltration of inflammatory cells into the synovial membrane, and blood neutrophil levels. WAG administration did not influence hematological parameters or kidneys and liver toxicity markers. WAG may be used to treat arthritis by reducing the inflammation indicators. However, further experiments are required to determine how WAG affects inflammation mechanisms in vitro and in vivo.
31652577 Oral-Gut Microbiota and Arthritis: Is There an Evidence-Based Axis? 2019 Oct 22 The gut microbiome appears to be a significant contributor to musculoskeletal health and disease. Recently, it has been found that oral microbiota are involved in arthritis pathogenesis. Microbiome composition and its functional implications have been associated with the prevention of bone loss and/or reducing fracture risk. The link between gut-oral microbiota and joint inflammation in animal models of arthritis has been established, and it is now receiving increasing attention in human studies. Recent papers have demonstrated substantial alterations in the gut and oral microbiota in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). These alterations resemble those established in systemic inflammatory conditions (inflammatory bowel disease, spondyloarthritides, and psoriasis), which include decreased microbial diversity and a disturbance of immunoregulatory properties. An association between abundance of oral Porphyromonas gingivalis and intestinal Prevotella copri in RA patients compared to healthy controls has been clearly demonstrated. These new findings open important future horizons both for understanding disease pathophysiology and for developing novel biomarkers and treatment strategies. The changes and decreased diversity of oral and gut microbiota seem to play an important role in the etiopathogenesis of RA and OA. However, specific microbial clusters and biomarkers belonging to oral and gut microbiota need to be further investigated to highlight the mechanisms related to alterations in bones and joints inflammatory pathway.
31117504 Enhanced Antiarthritic Efficacy by Nanoparticles of (-)-Epigallocatechin Gallate-Glucosami 2019 Jun 12 This work aims to improve the antiarthritic activity of (-)-epigallocatechin gallate (EGCG) and glucosamine (GA) through fabrication and optimization of casein protein nanoparticles (EGC-NPs). Optimized EGC-NPs were obtained with a EGCG/GA/casein ratio of 1:2:8 (w/w/w). The EGC-NPs gave a mean size of 186 ± 3.5 nm and an entrapment efficiency of 86.8 ± 2.7%, and they exhibited a greater inhibitory activity against human fibroblast-like synoviocytes-osteoarthritis cells and human fibroblast-like synoviocytes-rheumatoid arthritis cells compared with that of the EGCG-GA mixture by 33.5% and 20.8%, respectively. Freeze-dried EGC-NPs stored at 25 °C during 12 months showed high dispersion stability. Moreover, the redispersion of the freeze-dried EGC-NPs produced almost no significant changes in their physicochemical properties and bioactivity. Rat experiments demonstrated that the antiarthritis effect of the EGC-NPs was significantly higher than that of EGCG-GA mixture, as assessed through an analysis of anti-inflammatory efficacy, radiographic images and histopathological assessments of paw joints, and immunohistochemical changes in serum cytokines. The enchanced antiarthritic activity in vivo was consistent with that in vitro. The EGC-NPs demonstrate potential as a food supplement for the treatment of arthritis.