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ID PMID Title PublicationDate abstract
30773535 [Clinicopathological characteristics and diagnosis of IgG4related sialadenitis]. 2019 Feb 18 Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated disease and one of immunoglobulin G4-related diseases (IgG4-RD). Our multidisciplinary research group investigated the clinicopathological characteristics and diagnosis of IgG4-RS during the past 10 years. Clinically, it showed multiple bilateral enlargement of major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands. The comorbid diseases of head and neck region including rhinosinusitis, allergic rhinitis, and lymphadenopathy were commonly seen, which could occur more early than enlargement of major salivary glands. Internal organ involvements, such as autoimmune pancreatitis, sclerosing cholangitis, and interstitial pneumonia could also be seen. Thirty-five (38.5%) patients had the symptom of xerostomia. Saliva flow at rest was lower than normal. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in almost all the cases and the majority of the patients had increased IgE levels. CT, ultrasonography, and sialography showed their imaging characteristics. Histologically it showed marked lymphoplasmacytic inflammation, large irregular lymphoid follicles with expanded germinal centers, prominent cellular interlobular fibrosis, eosinophil infiltration, and obliterative phlebitis. Their immunohistological examination showed marked IgG-positive and IgG4-positive plasma cell infiltration and high IgG4/IgG ratio. The disease could be divided into three stages according to severity of glandular fibrosis. The serum IgG4 level was higher and the saliva secretion lower as glandular fibrosis increased. IgG4-RS should be differentiated from other diseases with enlargement of major salivary gland and lacrimal gland, such as primary Sjögren syndrome, chronic obstructive submandibular sialadenitis, and eosinophilic hyperplastic lymphogranuloma.
31096705 Microneedle-Assisted Transdermal Delivery of Etanercept for Rheumatoid Arthritis Treatment 2019 May 15 Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.
30891627 The pathogenicity of Th17 cells in autoimmune diseases. 2019 May IL-17-producing T helper (Th17) cells have been implicated in the pathogenesis of many inflammatory and autoimmune diseases. Targeting the effector cytokines IL-17 and GM-CSF secreted by autoimmune Th17 cells has been shown to be effective for the treatment of the diseases. Understanding a molecular basis of Th17 differentiation and effector functions is therefore critical for the regulation of the pathogenicity of tissue Th17 cells in chronic inflammation. Here, we discuss the roles of proinflammatory cytokines and environmental stimuli in the control of Th17 differentiation and chronic tissue inflammation by pathogenic Th17 cells in humans and in mouse models of autoimmune diseases. We also highlight recent advances in the regulation of pathogenic Th17 cells by gut microbiota and immunometabolism in autoimmune arthritis.
30094684 M2 macrophages and their role in rheumatic diseases. 2019 May As a component of the innate immune system, macrophages play a crucial role in host defense against a variety of microbes. Conventionally, macrophages have been classified as M1 and M2 depending on their phenotype and role in immune regulation. M1 macrophages are generally pro-inflammatory, while M2 (also known as alternatively activated macrophages) are anti-inflammatory. M1 macrophages release pro-inflammatory cytokines, reactive nitrogen, and oxygen intermediates, and kill pathogens, whereas their M2 counterparts participate in the resolution of inflammation, remodeling of tissue, angiogenesis, and tissue repair. Macrophages are also crucial in the pathogenesis of immune-inflammatory disorders, such as, arthritis. In this review, we discuss the markers of human M2 macrophages, the role played by them in inflammation or progression of rheumatic diseases, their potential to act as biomarkers, and, finally, therapeutic strategies aiming at altering/enhancing the macrophage phenotype.
30484004 Metabolomics Analysis Reveals Therapeutic Effects of α-Mangostin on Collagen-Induced Arth 2019 Apr α-Mangostin (MAN) is a bioactive compound isolated from pericarp of mangosteen (Garcinia mangostana Linn.) with significant anti-rheumatic potentials. The purpose of this study was to explore the mechanisms underlying its therapeutic effects on collagen-induced arthritis (CIA) in rats with metabolomics approaches. Therapeutic effects of MAN on CIA were assessed by radiographic, histological, and immunohistochemical methods. Metabolic profiles of rats were characterized based on UPLC-MS/MS analysis of urine samples, followed by verification in HFLS-RA cells using a variety of toxicological and biochemical assays. We found that MAN treatment protected joint structures in CIA rats and caused a decrease of nicotinamide mononucleotide (NMN) in urine. The levels of nicotinamide phosphoribosyltransferase (NAMPT) were reduced in fibroblast-like synoviocytes by MAN both in vivo and in vitro, which was accompanied with a decline in nicotinamide adenine dinucleotide (NAD) production. Secretion of extracellular NAMPT (eNAMPT) in HFLS-RA cells was also decreased upon MAN treatment, which lagged behind the changes of its intracellular counterpart (iNAMPT). Co-treatment with NMN raised the secretion of eNAMPT and restored the decline of p-p65 and TNF-α induced by MAN in vitro. Sirt1 expression was down-regulated under MAN treatments too. These results suggest that MAN treatment suppressed NAD production by inhibiting iNAMPT expression, which in turn decreased eNAMPT secretion and alleviated NF-κB-mediated inflammations in CIA rats.
31103432 Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment 2021 Apr Therapeutic advances in rheumatoid arthritis require periodic review of treatment guidelines. OBJECTIVE: To update the Mexican College of Rheumatology guidelines on the pharmacological treatment of rheumatoid arthritis. METHOD: Board certified rheumatologists from different health institutions and regions of the country participated. Work teams were formed that reviewed the previous guidelines, elaborated new questions, reviewed the literature, and scored the evidence that was presented and discussed in plenary session. The conclusions were presented to infectologists, gynaecologists and patients. Recommendations were based on levels of evidence according to GRADE methodology. RESULTS: Updated recommendations on the use of available medications for rheumatoid arthritis treatment in Mexico up to 2017 are presented. The importance of adequate and sustained control of the disease is emphasized and relevant safety aspects are described. Bioethical conflicts are included, and government action is invited to strengthen correct treatment of the disease. CONCLUSIONS: The updated recommendations of the Mexican College of Rheumatology on the pharmacological treatment of rheumatoid arthritis incorporate the best available information to be used in the Mexican health care system.
30259249 Increasing incidence and shifting profile of idiopathic inflammatory rheumatic diseases in 2019 Feb To explore the trends in the incidence of idiopathic inflammatory rheumatic diseases (IIRDs) after the turn of the millennium. From a nationwide register maintained by the Social Insurance Institution of Finland, we collected all adult patients with IIRDs granted a new special reimbursement for anti-rheumatic drugs between 2000 and 2014. Temporal trends in the incidences of various IIRDs were estimated in three 5-year intervals. A total of 58,405 adult patients were identified. Between 2000-2004 and 2010-2014, the age-adjusted incidence rate of IIRDs increased from 114 to 116/100000 [incidence rate ratio (IRR) 1.03 (95% CI 1.01 to 1.06)] in women and from 67 to 69/100,000 [IRR 1.10 (95% CI 1.06-1.14)] in men. The incidence of seropositive rheumatoid arthritis (RA) remained stable while that of seronegative RA decreased. For other diagnoses, the incidences either increased (unspecified arthritis, psoriatic arthritis, spondyloarthritis), remained stable (reactive arthritis), or decreased (SLE and the group of diseases with the ICD-10 code M35). The gender difference in spondyloarthritis leveled as the incidence in women increased at a higher rate than in men. Mean age at IIRD diagnosis decreased among women. The total age-adjusted incidence of IIRDs has gradually increased, due to the increase in unspecified arthritis, psoriatic arthritis, and spondyloarthritis. This, in addition to the ascending number of individuals at risk in the population, translates into a growing burden to the health care system.
31929822 Effect of Jiawei Fengshining on Synovial Cell Apoptosis and TGF-β1/Smad Signaling Pathway 2019 BACKGROUND/AIMS: Jiawei Fengshining (JWFSN) is a new formula originated from Fengshining, a classic formula for the treatment of rheumatoid arthritis (RA). The mechanism of JWFSN in the treatment of RA is still unclear. The aim of this study was to evaluate the effect of JWFSN formula on the inflammatory mediator levels in the serum and the TGF-β1/Smad pathway in the synovium and to explore the underlying mechanisms of JWFSN formula to ameliorate synovial hyperplasia and apoptosis inhibition of synovium in rats with RA. METHOD: SPF female Wistar rats were randomly divided into 6 groups: the blank control group, the model control group, the positive drug group, and the low-, medium-, and high- dose JWFSN groups, with 8 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory mediators, anti-inflammatory mediators, and rheumatoid factor (RF). The pathological condition and apoptosis of the synovial tissue were detected by hematoxylin and eosin (HE) and TUNEL staining, respectively. TGF-β1, p-Smad2, p-Smad3, and Smad7 protein expressions in synovial tissue were measured by western blot assay. In addition, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was treated with 20% JWFSN-containing serum to obtain in vitro data. RESULT: The administration of JWFSN was found to ameliorate synovial hyperplasia and promote apoptosis; increase the serum contents of anti-inflammatory mediators; reduce inflammatory mediators and RF contents; and inhibit the TGF-β1/Smad signaling pathway in CIA rats. In vitro JWFSN treatment increased the apoptosis of MH7A cells and decreased cell viability. Additionally, JWFSN treatment inhibited the TGF-β1/Smad signaling pathway in MH7A cells. Interestingly, kartogenin (TGF-β1/Smad pathway activator) treament reversed the effects of JWFSN treatment. CONCLUSION: JWFSN may ameliorate inflammatory factors' abnormality, synovial hyperplasia, and apoptosis inhibition of synovium via the TGF-β1/Smad signaling pathway.
30611783 Nicorandil abates arthritic perturbations induced by complete Freund's adjuvant in rats vi 2019 Feb 1 BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease which poses a need to explore effective yet safe pharmacotherapeutic options. The current work aimed to study the therapeutic role of nicorandil in controlling RA. EXPERIMENTAL APPROACH: Complete Freund's adjuvant (CFA)-induced arthritis model was applied by injecting 400 μL of CFA in the right hind paw at day 0 and day 7. Four groups of rats were used as follows: normal-control (CTRL), CFA-induced arthritis (ART), CFA-induced arthritis treated with diclofenac (DIC) and CFA-induced arthritis treated with nicorandil (NIC). Both NIC and DIC were administered at day 14 for two weeks. Paw volume, knee joint diameter, pain behavior assessment as well as body weight were all periodically recorded throughout the experimental period. Following the sacrifice of animals at day 28, gene expressions of TLR-4, MyD88 and TRAF6 as well as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), nuclear factor Kappa B (NF-κB) were quantified in hind paws tissue. Finally, the serum levels of the inflammatory biomarkers (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) together with the histopathological examination of sections in the rat hind paw were recorded. RESULTS: Both NIC and DIC proved promising anti-arthritic potential mediated, at least in part through switching off TLR4-MyD88-TRAF6 axis as well as downstream TRAF6 dependent activated MAP kinases and NF-κB. CONCLUSION AND IMPLICATIONS: Nicorandil, via interfering with TLR4 signaling, sheds light on a potential clinical role of the drug in pursuit for safe and effective regimens for RA.
35030696 Combinatorial, Microparticle-Based Delivery of Immune Modulators Reprograms the Dendritic 2019 Jun 17 Safe, effective, antigen-specific therapy for rheumatoid arthritis (RA) remains an elusive clinical goal with a few lasting, viable options on the horizon. Existing therapeutic interventions are indiscriminate and inconsistently immunosuppressive, often leaving patients susceptible to infection. Herein, we investigate the use of a dual-sized, microparticle "regulatory vaccine" (REGvac) that passively targets dendritic cells for antigen-specific biomaterial-based immunotherapy of RA. This REGvac employs poly(d,l-lactic-co-glycolic-acid) (PLGA) microparticles (MPs) encapsulating (i) a dendritic cell chemoattractant, (ii) potent immunosuppressive molecules, (iii) and an RA-relevant autoantigen to provide a multifaceted approach for the treatment of collagen-induced arthritis (CIA), the primary mouse model of RA. Subcutaneous administrations of the REGvac after mice had developed moderate clinical symptoms markedly diminished overt inflammation in the paws, halted cartilage degradation, and restored gait parameters within 56 days after initial treatment. Positron emission tomography imaging corroborated reduction of inflammation in the paws of REGvac-treated mice. In-depth immunological assessments showed a decreased expression of CD80, CD86, and MHC II on CD11c(+) dendritic cells in joint-associated lymph nodes. Further, we observed significant increases in conventional regulatory CD25(+)FOXP3(+) T cells, as well as programmed cell death protein-1 (PD-1)-expressing CD4(+) T cells in joint-proximal lymph nodes and the spleen. Real-time PCR analysis of joint tissues from treated mice revealed significant decreases in inflammatory cytokine expression (IL-6), while IL-10 mRNA levels were significantly increased. These observations strongly hint toward the induction of multiple tolerogenic mechanisms by administration of this MP regulatory vaccine. With regards to antigen specificity, ex vivo antigen recall assays revealed a lack of response to collagen by CD4(+) T cells from the popliteal and inguinal lymph nodes of REGvac-treated mice, contrasting with the proliferative response of CD4(+) T cells from CIA+ mice. Taken altogether, our results strongly support the application of this MP regulatory vaccine as a potent, biomaterial-based, antigen-specific therapy for RA.
31030710 [Heiguteng Zhuifenghuoluo capsule inhibits the expression of NF-κB in synovial tissues of 2019 Mar Objective To investigate the effect of Heiguteng Zhuifenghuoluo Capsule (HZC) on nuclear factor kappa B (NF-κB)-related protein in rheumatoid arthritis rats, and to analyze the expression of IκBα, NF-κBp65, phospho-nuclear factor kappa B p65 (p-NF-κBp65), receptor activator of nuclear factor κB ligand (RANKL), transforming growth factor activated kinase 1(TAK1), transforming growth factor β activated kinase binding protein 1(TAB1), monocyte chemoattractant protein 1 (MCP-1), C-X-C motif chemokine ligand 1 (CXCL1), macrophage inflammatory protein-1 (MIP-1) of plasma in rheumatoid arthritis rats. Methods Male SD rats were randomly divided into control group, model group, HZC (0.315 g/kg) group, and HZC (0.315 g/kg) plus ammonium pyrrolidinedithiocarbamate (PDTC, 0.01 g/kg) group. The model was constructed in all groups except the control group. Five weeks after modeling, the plantar thickness and spleen organ coefficient (spleen/body weight ratio) were measured in all rats. The TAK1 and TAB1 proteins were detected by immunohistochemical method in the spleen. Western blot analysis was used to detect the expression of IκBα, NF-κBp65, p-NF-κBp65 and RANKL proteins in the synovium of joint and plantar tissue. MCP-1, CXCL1, MIP-1 expression in the plasma was detected by ELISA. Results Compared with the model group, the swelling degree of plantar and the spleen organ coefficient in the control group, HZC group and combined administration group decreased significantly. The immunohistochemistry showed that the expression of TAK1 and TAB1 proteins in the spleen were down-regulated in the control group, HZC group and combined administration group. Western blotting showed that the expression of IκBα protein was up-regulated in the synovium of joint tissue of the control group, HZC group and combined administration group, but the expression of NF-κBp65, p-NF-κBp65, RANKL proteins were down-regulated in the control group, HZC group and combined administration group. ELISA showed that the expression of plasma MCP-1, CXCL1, MIP-1 were down-regulated in the control group, HZC group and combined administration group. Conclusion HZC inhibits the inflammatory response of rheumatoid arthritis rats by regulating NF-κB-related proteins.
31555285 Matured Tolerogenic Dendritic Cells Effectively Inhibit Autoantigen Specific CD4(+) T Cell 2019 Tolerogenic dendritic cells (tolDCs) are a promising treatment modality for diseases caused by a breach in immune tolerance, such as rheumatoid arthritis. Current medication for these diseases is directed toward symptom suppression but no real cure is available yet. TolDC-based therapy aims to restore immune tolerance in an antigen-specific manner. Here we used a mouse model to address two major questions: (i) is a maturation stimulus needed for tolDC function in vitro and in vivo and is maturation required for functioning in experimental arthritis and (ii) can tolDCs modulate CD4(+) T cell responses? To answer these questions, we compared matured and immature dexamethasone/vitamin D3-generated tolDCs in vitro. Subsequently, we co-transferred these tolDCs with naïve or effector CD4(+) T cells to study the characteristics of transferred T cells after 3 days with flow cytometry and Luminex multiplex assays. In addition, we tested the suppressive capabilities of tolDCs in an experimental arthritis model. We found that tolDCs cannot only modulate naïve CD4(+) T cell responses as shown by fewer proliferated and activated CD4(+) T cells in vivo, but also effector CD4(+) T cells. In addition, Treg (CD4(+)CD25(+)FoxP3(+)) expansions were seen in the proliferating cell population in the presence of tolDCs. Furthermore, we show that administered tolDCs are capable to inhibit arthritis in the proteoglycan-induced arthritis model. However, a maturation stimulus is needed for tolDCs to manifest this tolerizing function in an inflammatory environment. Our data will be instrumental for optimization of future tolDC therapies for autoimmune diseases.
31623278 Comment from the Editor to the Special Issue: "Periodontitis: From Dysbiotic Microbial Imm 2019 Oct 16 The human oral cavity contains a large number of different microbial habitats. When microbes from the oral indigenous flora colonize the interspace between the tooth and the connective tissue, they induce an inflammatory response. If the microbes are in sufficient numbers, and release components that cause an imbalance in the host inflammatory response, degenerative processes in the surrounding tissues are induced, ultimately resulting in periodontal disease. The disease progress depends on bacterial load, the composition of the microbial community, and host genetic factors. The two most studied periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans express virulence factors, including proteases and exotoxins. Periodontal infections are also linked to the risk pattern of several systemic diseases. We would like to shed light on the mechanisms behind periodontitis and the associations of periodontal infections with systemic inflammation. Seven articles are included in this Special Issue and cover several pathogenic processes in the periodontal infection with capacity to cause imbalance in the host response. Highlights from each of the published papers are summarized and discussed below.
31334206 Arthritis in Two Patients With Partial Recombination Activating Gene Deficiency. 2019 Autoimmunity is becoming an increasingly recognized complication in patients with primary immunodeficiencies (PIDs), including a variety of combined immune deficiencies such as Recombination Activating Gene (RAG) defects. The approach to treating autoimmunity in PID patients is complex, requiring a balance between immunosuppression and susceptibility to infection. Inflammatory arthritis is a feature of immune dysregulation in many PIDs, and the optimal treatment may differ from first line therapies that usually consist of disease-modifying anti rheumatic drugs (DMARDs). An example of mechanism-based therapy of arthritis in PID uses blockade of IL-6 signaling with tocilizumab for patients with STAT 3 gain-of-function (GOF) mutation and augmented IL-6 pathway. Herein, we describe two PID cases with arthritis who were found to have defects in RAG. One patient with refractory inflammatory arthritis experienced remarkable improvement in symptoms with tocilizumab therapy. Arthritis can be a clinical feature of immune dysregulation in RAG deficiency, and tocilizumab therapy has been suggested to have utility in treatment of arthritis in RAG deficiency.
31921569 Fluorometric Imaging for Early Diagnosis and Prognosis of Rheumatoid Arthritis. 2020 Jan Early diagnosis and monitoring of disease progress are of significant importance in the effective treatment of rheumatoid arthritis (RA), because the continuing inflammation can lead to irreversible joint damage and systemic complications. However, applying imaging modalities for the prognosis of RA remains challenging, because no tissue-specific guidelines are available to monitor the progressive course of RA. In this study, fluorometric imaging of RA is reported using bioengineered targeted agents of the blood vessel, bone, and cartilage in combination with the customized optical fluorescence imaging system. Separate but simultaneous tissue-specific images of synovitis, cartilage destruction, and bone resorption are obtained from a mouse model of RA, which allows quantification of the prognosis of diseases at each stage. Thus, the fluorometric imaging of RA by using tissue-specific contrast agents plays a key role in the systemic treatment of RA by monitoring structural damage and disease progression.
30508140 The level of synovial AXL expression determines the outcome of inflammatory arthritis, pos 2019 Mar 1 OBJECTIVE: To investigate the role of AXL, a member of the anti-inflammatory TYRO3, AXL MER (TAM) receptor family, in arthritis. METHODS: KRN serum transfer arthritis was induced in Axl-/- and wild-type mice. Knee and ankle joints were scored macro- and microscopically. Synovial gene and protein expression of Axl was determined in naïve and TGF-β1-overexpressing joints. AXL expression was determined in M1-like or M2-like macrophages and RA synovium. Human macrophages, fibroblasts and synovial micromasses were stimulated with TGF-β1 or the AXL inhibitor R428. RESULTS: Ankle joints of Axl-/- mice showed exacerbated arthritis pathology, whereas no effect of Axl gene deletion was observed on gonarthritis pathology. To explain this spatial difference, we examined the synovium of naïve mice. In contrast to the knee, the ankle synovial cells prominently expressed AXL. Moreover, the M2-like macrophage phenotype was the dominant cell type in the naïve ankle joint. Human M2-like macrophages expressed higher levels of AXL and blocking AXL increased their inflammatory response. In the murine ankle synovium, gene expression of Tgfb1 was increased and Tgb1 correlated with Axl. Moreover, TGFB1 and AXL expression also correlated in human RA synovium. In human macrophages and synovial micromasses, TGF-β1 enhanced AXL expression. Moreover, TGF-β1 overexpression in naïve murine knee joints induced synovial AXL expression. CONCLUSION: Differences in synovial AXL expression are in accordance with the observation that AXL dampens arthritis in ankle, but not in knee joints. We provide evidence that the local differences in AXL expression could be due to TGF-β1, and suggest similar pathways operate in RA synovium.
30981578 Design, synthesis and structure-activity relationship study of aminopyridine derivatives a 2019 Jun 15 Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC(50) = 27 nM). Then we carried out structure-based drug design and synthesized a series of compounds with an aminopyridine scaffold. Finally, compound 12k and 12l were identified as the promising inhibitors of JAK2, which exhibited high inhibitory activity (IC(50) = 6 nM and 3 nM, respectively) and selectivity for JAK2 over JAK1 and JAK3, and showed potent antiproliferative activities toward HEL human erythroleukemia cells. Moreover, 12k suppressed symptoms of the collagen-induced arthritis (CIA) model in rats.
31303891 Long non-coding RNA PVT1 knockdown suppresses fibroblast-like synoviocyte inflammation and 2019 BACKGROUND: As a type of chronic autoimmune joint disease, rheumatoid arthritis (RA) is a disorder, characterized by a variety of physical symptoms as well as RA fibroblast-like synoviocyte (RA-FLS) proliferation. More recently, long non-coding RNAs (lncRNAs) have been implicated in the progression of various diseases including the progression of RA. Hence, the aim of the current study was to investigate the role by which the lncRNA, plasmacytoma variant translocation 1 (PVT1), influences RA-FLSs and its ability to modulate the methylation of sirtuin 6 (sirt6). METHODS: RA rat models were initially established to determine the expression of PVT1 and sirt6 in synovial tissues and RA-FLSs. Elevation or depletion of PVT1 or sirt6 was achieved by means of transformation with plasmids in order to investigate their effects on RA-FLS proliferation, inflammation and apoptosis. The localization of PVT1 and its binding ability to the sirt6 promoter region were also explored in an attempt to elucidate the correlation between PVT1 and sirt6 methylation. RESULTS: High expression of PVT1 and low expression of sirt6 were detected in the synovial tissues and RA-FLSs of the rat models. RA-FLSs treated with sh-PVT1 or oe-sirt6 exhibited suppressed cell proliferation, inflammation and induced apoptosis. PVT1 was predominately localized in the nucleus while evidence was obtained indicating that it could bind to the sirt6 promoter to induce sirt6 methylation, thus inhibiting sirt6 transcription. PVT1 knockdown was observed to restore sirt6 expression through decreasing sirt6 methylation, thereby alleviating RA. CONCLUSION: The key findings of the study provide evidence suggesting that, PVT1 knockdown is able to restrain RA progression by inhibiting sirt6 methylation to restore its expression.
31750389 Use of Tofacitinib for the Treatment of Arthritis Associated With Ulcerative Colitis. 2019 Sep Tofacitinib is a Janus kinase 1-3 inhibitor initially approved for the treatment of rheumatoid arthritis and now approved for the treatment of moderately to severely active ulcerative colitis (UC). We present the case of a patient with UC and seronegative inflammatory arthritis in whom arthritis progressed while on vedolizumab and was successfully treated with tofacitinib. This case provides insight into the use of tofacitinib for the treatment of UC and a concomitant extraintestinal manifestation of joint involvement.
30324883 Selenium and Autoimmune Diseases: A Review Article. 2019 BACKGROUND: Selenium is an essential trace element with fundamental effects on human biology. Trace elements deficiency is not an uncommon finding in autoimmune diseases. This deficiency may be a consequence of autoimmune diseases or may contribute to their etiology. With regard to evidence showing the association between selenium deficiency and generation of reactive oxygen species and subsequent inflammation, reviewing the role of selenium in collagen vascular diseases could help researchers to devise strategies for managing these diseases. OBJECTIVE: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases. DATA SOURCES: PubMed, Scopus, Science Direct, and Google Scholar. STUDY ELIGIBILITY CRITERIA: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study. DATA EXTRACTION: In this systematic review, articles were evaluated through searching following keywords in combination with selenium: "autoimmune rheumatic diseases "or "scleroderma" or "systemic sclerosis" or "Behcet's disease" or "Sjögren syndrome" or "systemic lupus erythematosus" or "musculoskeletal diseases" or "rheumatoid arthritis" or "vasculitis" or "seronegative arthritis" or "antiphospholipid antibody syndrome". RESULTS: Of 312 articles, 280 were excluded and 32 articles were entered in this study. Based on the majority of studies assessing selenium level in patients with collagen vascular diseases, lower selenium levels were observed in these patients. Moreover, the majority of articles showed an improvement in clinical symptoms of collagen vascular diseases compared to controls after the treatment of patients with different dosages of L-selenomethionine. CONCLUSION: A decrease in the serum level of selenium was noted in patients with autoimmune diseases, which may be a risk factor for inflammation and initiation of autoimmunity in these patients. A sufficient quantity of selenium has been shown to contribute to the management of complications of autoimmune diseases and even improved survival in patients with autoimmune diseases, which may be due to the anti-inflammatory effects of selenium. Since this issue is of clinical importance, it can be considered in potential nutrition interventions and have beneficial effects on some autoimmune diseases.