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ID PMID Title PublicationDate abstract
34646275 Effects of Mesenchymal Stem Cell-Derived Exosomes on Autoimmune Diseases. 2021 Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials of inflammatory and autoimmune diseases. Emerging evidence indicates that the immunomodulatory effect of MSCs is primarily attributed to the paracrine pathway. As one of the key paracrine effectors, mesenchymal stem cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm in diameter that play an important role in cell-to-cell communication by carrying bioactive substances from parental cells. Recent studies support the finding that MSC-EXOs have an obvious inhibitory effect toward different effector cells involved in the innate and adaptive immune response. Moreover, substantial progress has been made in the treatment of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSC-EXOs are capable of reproducing MSC function and overcoming the limitations of traditional cell therapy. Therefore, using MSC-EXOs instead of MSCs to treat autoimmune diseases appears to be a promising cell-free treatment strategy. In this review, we review the current understanding of MSC-EXOs and discuss the regulatory role of MSC-EXOs on immune cells and its potential application in autoimmune diseases.
34460071 Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis. 2021 Aug 30 Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.
34371695 Recent Advances in Liposomal-Based Anti-Inflammatory Therapy. 2021 Jul 1 Liposomes can be seen as ideal carriers for anti-inflammatory drugs as their ability to (passively) target sites of inflammation and release their content to inflammatory target cells enables them to increase local efficacy with only limited systemic exposure and adverse effects. Nonetheless, few liposomal formulations seem to reach the clinic. The current review provides an overview of the more recent innovations in liposomal treatment of rheumatoid arthritis, psoriasis, vascular inflammation, and transplantation. Cutting edge developments include the liposomal delivery of gene and RNA therapeutics and the use of hybrid systems where several liposomal bilayer features, or several drugs, are combined in a single formulation. The majority of the articles reviewed here focus on preclinical animal studies where proof-of-principle of an improved efficacy-safety ratio is observed when using liposomal formulations. A few clinical studies are included as well, which brings us to a discussion about the challenges of clinical translation of liposomal nanomedicines in the field of inflammatory diseases.
34229081 TNF-α: The shape of small molecules to come? 2022 Jan In 2020, the anti-tumor necrosis factor (TNF) monoclonal antibody Humira® generated US$165.8 billion in cumulative sales and snatched the crown for the industry's most successful drug from Lipitor (atorvastatin). TNF-α is a major component in beneficial and disease-related inflammation and TNF-α-inhibitor biologics have gained widespread use in autoimmune diseases, such as rheumatoid arthritis (RA). Many more diseases could benefit from TNF-α inhibitors, such as Alzheimer's disease (AD) or major depression. However, the nature of TNF-α-inhibitor biologics prohibits central nervous system (CNS) applications. Moreover, high drug production costs and pricing, together with antidrug immune reactions and insufficient patient coverage, argue for the development of small-molecule drugs. Recently, drug-like orally available small molecules were described with high activity in animal disease models with activities comparable to those of antibodies.
34175144 [Thrombin generation assay in autoimmune disease]. 2021 Dec Thrombin generation assay (TGA) is a useful tool to evaluate the initiation, propagation and inhibition of coagulation. TGA is a global test that is used to assess hemorrhagic risk in hemophilia patients, but it can also be used to study hypercoagulable states. The interest of TGA is to screen for cardiovascular risk, which is regularly associated with autoimmune disease (AID) such as antiphospholipid syndrome. Indeed, TGA has been used to evaluate hypercoagulability in patients with antiphospholipid syndrome treated with rivaroxaban versus warfarin. In other AIDs without thrombotic events, TGA measurement is elevated, mainly in rheumatoid arthritis (RA), systemic lupus erythematosus and Behçet's disease. These findings in RA are correlated with the inflammatory activity of the disease. In systemic lupus erythematosus and Behçet's disease, TGA appears to reflect disease activity. In conclusion, TGA remains relatively under used in the clinical evaluation of AID, but it could play a greater role in the evaluation of certain potentially thrombogenic treatments in AID. Finally, TGA helps measuring AID activity, due to the clearlink between coagulation and inflammation, despite some limitations of interpretation mainly due to a lack of standardization.
34159624 Anti-inflammatory activity of ginger modulates macrophage activation against the inflammat 2021 Jun 22 Monosodium glutamate (MSG) has been traditionally used as a flavor enhancer and is added to many foods. The chronic consumption of MSG has been suggested as causing toxicity, inflammation, obesity, type 2 diabetes, and pre-malignant changes. The use of medicinal plants and their products, such as ginger, against the effects of MSG has been suggested to have a protective effect. To evaluate the anti-inflammatory activity of ginger against the effects of MSG, we conducted a serial inflammatory analysis of MSG- and ginger-treated rats, focusing particularly on liver pathology. The consumption of ginger as an unconventional therapy against the effects of MSG resulted in significant anti-inflammatory activity. We found that it was possible to diagnose MSG-associated inflammatory pathogenesis using inflammatory mediators. Ginger consumption produced protective effects on health, minimized adverse effects, and may be applicable for food development and the treatment of many inflammatory diseases. PRACTICAL APPLICATIONS: The chronic administration of monosodium glutamate (MSG) as a flavor enhancer has been suggested to produce toxicity, inflammation, and pre-malignant changes in organs. Ginger has protective effects, with potent anti-inflammatory and anti-fibrotic activity against MSG administration. This study is the first to report that ginger modulated the inflammatory and fibrotic effects of MSG and improved immunological indices reflecting the involvement of inflammatory and fibrotic markers and polysaccharide content in the activation of macrophages. These findings support the further use of ginger as a supplement for food enhancement and as an anti-fibrotic, anti-inflammatory, and therapeutic agent in pharmaceutical therapies against autoimmune and inflammatory diseases, such as rheumatoid arthritis, lupus, and ulcerative colitis, as well as MSG-associated inflammatory diseases.
34040516 The Analyses of Chemical Components From Oldenlandia hedyotidea (DC.) Hand.-Mazz and Antic 2021 Oldenlandia hedyotidea (DC.) Hand.-Mazz (OH), also known as sweet tea, is a valuable functional food with medicinal properties and is used for the treatment of cold, cough, gastroenteritis, heatstroke, herpes zoster, and rheumatoid arthritis. The phytochemicals in plant-based foods are responsible for the occurrence of these diseases to some extent. However, there is a scarcity of information on the chemical components of OH. We, therefore, aimed to investigate the phytochemical components of OH using ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and UHPLC triple time-of-flight mass spectrometry (UHPLC-Triple-TOF-MS). The main component of the OH extract, asperulosidic acid, was additionally quantified using UHPLC with ultraviolet detection (UHPLC-UV). The anticancer activity of the OH extract was assessed by a cell proliferation assay and a scratch assay using an esophageal cancer cell line. Ten compounds were tentatively identified in the aqueous extract of OH, including five iridoids, two anthraquinones, and one phenolic acid. The content of asperulosidic acid in the aqueous extract of OH was approximately 42 μg ml(-1), and the extract exerted definite in vitro anticancer effects. The results can be used for quality control and assessment of the OH extract, which can serve as a promising source of functional ingredients for potential use in the food and drug industries.
33777473 Winning the Battle after Three Years of Suffering: A Case of a Refractory Pyoderma Gangren 2021 Pyoderma gangrenosum is an uncommon inflammatory disorder characterized by neutrophilic infiltration of the skin. It can present as skin papules or pustules that progress into painful ulcers. 30-40% of the cases are associated with other systemic diseases such as inflammatory bowel diseases, rheumatoid arthritis, and proliferative hematological disorders. Uniquely, this condition has been associated with systemic lupus erythematosus (SLE). The rarity of this disorder poses a diagnostic and therapeutic challenge. We present a case of a 55-year-old female with a history of SLE and chronic right leg ulcer, presented with increased pain from the ulcer associated with a mild flare of her cutaneous lupus; examination revealed circumferential skin ulcer measuring about 25 cm extending around the right leg above the ankle with prominent fibrinous material and surrounding erythema. Blood work showed elevated WBC with neutrophilic predominance. Serology revealed a positive ANA, elevated RNP, smith, and SSA/Ro antibodies with normal anti-CCP level. Skin biopsy was taken, and it showed a diffuse neutrophilic and lymphocytic infiltrate consistent with the diagnosis of pyoderma gangrenosum. The patient was then treated with topical and systemic steroids and sequentially with dapsone, methotrexate, mycophenolate, and cyclosporine for over a two-year period but failed to show any improvement. Therefore, a trial of intravenous immunoglobulin (IVIG) therapy was attempted and produced a dramatic response after two-month infusions characterized by shrinking in the size of the ulcer and resolving pain. We believe that refractory PG poses a therapeutic challenge, and despite a lack of specific guidelines, IVIG can be attempted if initial suppressive treatment fails to show signs of improvement.
33733998 Innate Lymphoid Cells and Adaptive Immune Cells Cross-Talk: A Secret Talk Revealed in Immu 2021 The inflammatory immune response has evolved to protect the host from different pathogens, allergens, and endogenous death or damage-associated molecular patterns. Both innate and adaptive immune components are crucial in inducing an inflammatory immune response depending on the stimulus type and its duration of exposure or the activation of the primary innate immune response. As the source of inflammation is removed, the aggravated immune response comes to its homeostatic level. However, the failure of the inflammatory immune response to subside to its normal level generates chronic inflammatory conditions, including autoimmune diseases and cancer. Innate lymphoid cells (ILCs) are newly discovered innate immune cells, which are present in abundance at mucosal surfaces, including lungs, gastrointestinal tract, and reproductive tract. Also, they are present in peripheral blood circulation, skin, and lymph nodes. They play a crucial role in generating the pro-inflammatory immune response during diverse conditions. On the other hand, adaptive immune cells, including different types of T and B cells are major players in the pathogenesis of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc.) and cancers. Thus the article is designed to discuss the immunological role of different ILCs and their interaction with adaptive immune cells in maintaining the immune homeostasis, and during inflammatory autoimmune diseases along with other inflammatory conditions (excluding pathogen-induced inflammation), including cancer, graft-versus-host diseases, and human pregnancy.
33678483 Acute idiopathic thenar and hypothenar compartment syndrome. 2021 Sep Compartment syndrome (CS) is a condition associated with intra-compartment pressures exceeding the perfusion pressure of the tissue. This condition can occur in any body compartment surrounded by fascia, however CS of some regions like the thenar and hypothenar is extremely rare. Acute CS is often caused by major trauma and idiopathic acute CS is sparsely reported in literature. We present a case report of a 39-year-old male, with a medical history of rheumatoid arthritis (RA) for which he uses adalimumab and low-dose prednisone, with idiopathic acute CS of thenar and hypothenar compartments. Unexplained tremendous pain, paresthesia and swelling of his hand were the only symptoms observed. Due to direct recognition of the condition there was no delay in time to treatment. Treatment involved a fasciotomy of the thenar and hypothenar compartments as well as a release of the carpal tunnel. This direct surgical approach resulted in retaining excellent function and appearance of the hand. We hypothesized several causes for the etiology of the condition (e.g. rhabdomyolysis, rheumatologic disease-related condition, other systemic diseases, trauma, infection), but all could be rejected based on laboratory or clinical findings. Remarkable is that the patient experienced a comparable episode in his other hand two years earlier. Although the acute CS is of unknown origin in the presented case, the development of acute CS in both hands over time suggests a predisposing factor in idiopathic acute CS that is far from being elucidated.
33663910 Use of Parenteral Methotrexate in Rheumatic Diseases: A Systematic Review. 2021 Mar 1 OBJECTIVE: To analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases. METHODS: A systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies. RESULTS: Out of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data. CONCLUSIONS: Parenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.
33532840 Motif-Raptor: A Cell Type-Specific and Transcription Factor Centric Approach for Post-GWAS 2021 Feb 3 MOTIVATION: Genome-wide association studies (GWAS) have identified thousands of common trait-associated genetic variants but interpretation of their function remains challenging. These genetic variants can overlap the binding sites of transcription factors (TFs) and therefore could alter gene expression. However, we currently lack a systematic understanding on how this mechanism contributes to phenotype. RESULTS: We present Motif-Raptor, a TF-centric computational tool that integrates sequence-based predictive models, chromatin accessibility, gene expression datasets and GWAS summary statistics to systematically investigate how TF function is affected by genetic variants. Given trait associated non-coding variants, Motif-Raptor can recover relevant cell types and critical TFs to drive hypotheses regarding their mechanism of action. We tested Motif-Raptor on complex traits such as rheumatoid arthritis and red blood cell count and demonstrated its ability to prioritize relevant cell types, potential regulatory TFs and non-coding SNPs which have been previously characterized and validated. AVAILABILITY: Motif-Raptor is freely available as a Python package at: https://github.com/pinellolab/MotifRaptor. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
33243604 The role of the cholinergic anti-inflammatory pathway in septic cardiomyopathy. 2021 Jan Septic cardiomyopathy (SCM)is common in septic patients and results in cardiovascular failure. The pathogenesis of SCM is complicated, and patients with SCM have high mortality because current treatment methods are limited. The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through vagus nerve stimulation that leads to the release of acetylcholine (ACh), which binds to the alpha7 nicotinic acetylcholine receptor (α7nAChR). Moreover, α7nAChR activation by its agonists at the tissue level inhibits inflammatory mediators and regulates the function of immune cells in sepsis. Therefore, the α7nAChR can maintain balance of the inflammatory-immune response in sepsis. CAP has been elucidated as a critical regulator of anti-inflammation in many diseases, including rheumatoid arthritis, inflammatory boweldisease and SCM. Additionally, some clinical and preclinical trials show therapeutic potential via regulating CAP. There are excellent studies regarding the beneficial role of CAP activation, especially α7nAChR, in experimental SCM. This review aims to discuss the CAP in attenuating inflammation and the potential role of α7nAChR activation in regulating immune and reducing inflammation in SCM.
32935861 Interleukin-17 and ischaemic stroke. 2021 Feb Interleukin-17 (IL-17) is a cytokine family that includes 6 members, IL-17A through IL-17F, most of them are reported to have pro-inflammatory role. Through binding to their receptors (IL-17Rs), IL-17 activates the intracellular signalling pathways to play an important role in autoimmune diseases, including rheumatoid arthritis (RA) and multiple sclerosis (MS). Ischaemic stroke is a complex pathophysiological process mainly caused by regional cerebral ischaemia. Inflammatory factors contribute to the physiological process of stroke that leads to poor prognosis. IL-17 plays a crucial role in promoting inflammatory response and inducing secondary injury in post-stroke. Though immune cells and inflammatory factors have been reported to be involved in the damage of stroke, the functions of IL-17 in this process need to be elucidated. This review focuses on the pathological modulation and the mechanism of IL-17 family in ischaemic stroke and seeking to provide new insights for future therapies.
34847389 Specialized pro-resolving receptors are expressed in salivary glands with Sjögren's syndr 2022 Feb Our previous studies demonstrated that resolvin D1 (RvD1) and its aspirin-trigged (AT) form AT-RvD1, are effective in decreasing inflammation while restoring saliva flow rates in a Sjögren's syndrome (SS)-like mouse model before and after disease onset. Resolvins are specialized pro-resolving mediators (SPM) that actively regulate inflammation. However, we only have extensive data within the salivary glands for RvD1 and AT-RvD1, both of which bind to the receptor ALX/FPR2. As such, the presence of other SPM receptors is unknown within salivary glands. Therefore, the goal of this study was to determine the expression of SPM receptors in non-SS and SS patients. For this purpose, six human minor salivary glands from female subjects were analyzed by H&E using the Chisholm and Mason classification to determine the degree of lymphocytic infiltration. Next, confocal immunofluorescence analysis was performed to determine the presence and distribution of different SPM receptors in mucous acini and striated ducts. We observed diffuse presence of lymphocytic infiltration and clinical data were consistent with SS diagnosis in three patients. Moreover, confocal immunofluorescence analysis indicated the presence of the receptors ALX/FPR2, BLT1 and CMKLR1 in the mucous acini and striated ducts of both non-SS and SS patients. GPR32 was absent in SS and non-SS minor salivary glands. In summary, our results showed that various SPM receptors are expressed in non-SS and SS minor salivary glands, all of which may pose as potential targets for promoting pro-epithelial and anti-inflammatory/pro-resolution signaling on SS patients.
33468262 Abdominal symptoms during Sjogren's syndrome: a pilot study. 2021 Jan 19 BACKGROUND: Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease. METHODS: One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected. RESULTS: Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each). CONCLUSIONS: The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms. TRIAL REGISTRATION: NCT03157011 . Date of registration: July 17, 2017.
33592902 SS-A52 antigen expression in thymic carcinoma accompanied with Sjögren syndrome: A case r 2021 Feb 5 RATIONALE: The relationship between thymic tumors and Sjögren syndrome (SjS) is unknown, and surgical resection has not been optimized. Especially, thymic carcinoma with autoimmune disease is rare. Analysis of SS-A52, germinal centers, plasma cells, and Foxp3+ Treg in thymic carcinoma has never been reported, and their pathological roles in causing SjS have not been studied. PATIENT CONCERNS: A 78-year-old man presented with sputum production and xerostomia while asleep. Chest computed tomography showed a homogeneous and hypodense mass in the anterosuperior mediastinum. Serum levels of the antinuclear antibody, antibody to SS-A, and antibody to SS-B were positive. DIAGNOSES: Thymic carcinoma (squamous cell carcinoma) and SjS. INTERVENTIONS: Video-assisted thoracoscopic resection of the mediastinal tumor and postoperative radiation therapy was performed. OUTCOMES: The histological diagnosis was thymic squamous cell carcinoma. Histologically, the squamous carcinomatous cells were arranged in nests and cords in the fibrohyaline stroma with capsular invasion. In the stroma, dense lymphoid tissues containing large reactive germinal centers and many plasma cells were also noted. In the involuted thymus, CD20-positive mature lymphocytes infiltrated, and germinal centers were noted. Double immunohistochemical staining revealed that SS-A52 antigen was positive in both the carcinoma component and CD20-positive mature B cells. Postoperatively, the xerostomia persisted, and serum SS-A and SS-B remained positive. No evidence of carcinoma recurrence with chest computed tomography scan was observed at 18-months follow-up. LESSONS: In the surgical treatment of thymic tumors with SjS, extended thymectomy might be worth considering to stop the progressive destruction of the targets of SjS-specific autoantibodies. However, the postoperative symptoms may not dramatically improve because the target organs might have changed irreversibly, and memory B cells might persist. This is the first report that demonstrated the SS-A52 antigen presentation in a thymic tumor to the best of our knowledge.
32721173 Ultra-High Frequency Ultrasound, A Promising Diagnostic Technique: Review of the Literatur 2021 Aug OBJECTIVES: Ultra-high frequency ultrasonography (UHFUS) is a recently introduced diagnostic technique which finds several applications in diverse clinical fields. The range of frequencies between 30 and 100 MHz allows for high spatial resolution imaging of superficial structures, making this technique suitable for the imaging of skin, blood vessels, musculoskeletal anatomy, oral mucosa, and small parts. However, the current clinical applications of UHFUS have never been analyzed in a consistent multidisciplinary manner. The aim of this study is to revise and discuss the current applications of UHFUS in different aspects of research and clinical practice, as well as to provide some examples of the current work-in-progress carried out in our center. MATERIALS AND METHODS: A literature search was performed in order to retrieve articles reporting the applications of UHFUS both in research and in clinical settings. Inclusion criteria were the use of frequencies above 30 MHz and study design conducted in vivo on human subjects. RESULTS: In total 66 articles were retrieved. The majority of the articles focused on dermatological and vascular applications, although musculoskeletal and intraoral applications are emerging fields of use. We also describe our experience in the use of UHFUS as a valuable diagnostic support in the fields of dermatology, rheumatology, oral medicine, and musculoskeletal anatomy. CONCLUSION: Ultra-high frequency ultrasonography application involves an increasing number of medical fields. The high spatial resolution and the superb image quality achievable allow to foresee a wider use of this novel technique, which has the potential to bring innovation in diagnostic imaging.
33628297 Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulati 2021 OBJECTIVE: Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats. MATERIALS AND METHODS: SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting. RESULTS: Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues. CONCLUSIONS: This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.
34384858 The effect of association of aspirin and omega 3 in rat temporomandibular joint with induc 2022 Jan This study aimed to evaluate the effects of omega-3 (ω3) polyunsaturated fatty acids, in association with aspirin (AA), on the morphology of cytokine release in the temporomandibular joint (TMJ) of rats induced with rheumatoid arthritis (IR) by injecting 100 μL of complete Freund's adjuvant with bovine type II collagen at the tail base. Thirty-two adult male rats were divided into treatment groups: Sham, treated with 0.9% sodium chloride (NaCl) p.o.; IR-control, treated with 0.9% NaCl p.o.; IR-ω3 treated with ω3 PUFAS (85 mg/kg/day p.o.); and IR-ω3 + AA treated with ω3 (85 mg/kg/day p.o.) + AA (20 mg/kg/day i.p.). After maintained treatment for seven days, the animals were euthanized. Bilateral TMJs from each rat were removed and one was subjected to histological immunoassays and enzyme-linked immunosorbent assays to assess interleukin (IL)-1β, tumor necrosis factor-α, and IL-10 levels. Data analysis was performed using the Kruskal-Wallis and Dunn tests. In the IR-ω3 and IR-ω3 + AA groups, the TMJ was greater than in the IR-control group (P < 0.0001). The addition of AA did not improve the effects of ω3 (P = 0.0698). Similarly, the addition of AA conferred no additional effects on the cytokine levels (P > 0.05); however, it increased the proteoglycan density, compared with ω3 alone. We found that ω3 exhibited anti-inflammatory activity in arthritic rats, and the addition of AA increased proteoglycan density, but did not affect cytokine expression.