Symptoms Of Arthritis Research Articles

Agreement between child- and parent-reported orofacial symptoms in patients with juvenile idiopathic arthritis

Objective To assess the agreement between child- and parent-reported orofacial symptoms in the Danish version of the patient questionnaire Assessment of Orofacial Symptoms in Juvenile Idiopathic Arthritis. Method This cross-sectional study was conducted at Aarhus University in March 2023. Eligible candidates were consecutive subjects with juvenile idiopathic arthritis (JIA) and temporomandibular joint involvement accompanied by a parental proxy for examination in the Craniofacial Clinic. After obtaining written informed consent, the questionnaire was completed individually and separately by the child and the parent without any communication between them. The level of agreement was analysed using Cohen’s (weighted) kappa for nominal and ordinal outcome variables (orofacial pain frequency, pain location, jaw function, orofacial symptoms, and changes since last visit) and the intraclass correlation coefficient for linear outcome variables (orofacial pain intensity and functional disability of the jaw). Results The 34 included dyads had an overall ‘poor’ to ‘moderate’ child–proxy reporting agreement on the questionnaire for the assessment of JIA-related orofacial symptoms. After dividing the children into two age groups, < 13 and ≥ 13 years old, we found substantial agreement on pain frequency and moderate to excellent agreement on pain intensity for the older group. The child–proxy agreement for children aged < 13 years was slight on pain frequency and poor to moderate on pain intensity. Conclusion The child–proxy reporting agreement on JIA-related orofacial symptoms is inconsistent. We suggest collecting information from both children and parents, especially when assessing orofacial pain and symptoms in children < 13 years of age.

The mediating role of kinesiophobia in pain intensity, physical function, and physical activity level in inflammatory arthritis.

Pain is the main symptom of inflammatory arthritis and it can impair physical functional performance and physical activity level. Some individuals can develop kinesiophobia and experience a vicious circle of worsening health. This study aimed to investigate the association between pain and physical functional performance/physical activity and determine whether kinesiophobia mediates this association. This was a cross-sectional study with individuals diagnosed with inflammatory arthritis (rheumatoid arthritis or spondyloarthritis) treated at a Rheumatology Outpatient Clinic. We assessed pain (Visual Analogue Scale), physical activity (International Physical Activity Questionnaire - long form), kinesiophobia (Tampa Scale for Kinesiophobia), and physical functional performance (Handgrip Strength Dynamometry, 30-second Sit-to-Stand test, Static Muscular Endurance test, and Timed Up and Go test). The mediating effect of kinesiophobia on the relationship between pain intensity and physical functional performance/physical activity was analyzed, and the significance of the mediating effect (kinesiophobia) was tested through a bootstrap approach. Thirty-three individuals with inflammatory arthritis (mean age: 48 ± 12 years) participated in the study. Kinesiophobia mediates the relationship between pain intensity and physical functional performance analyzed by the 30-second Sit-to-Stand test [indirect effect (IE)overall = -0.343, bootstrap 95% confidence interval (CI): -0.698 to -0.002] and by knee flexion at 90º of the dominant limb (IEoverall = -1.55, bootstrap 95% CI: -3.43 to -0.237). In conclusion, pain intensity can affect physical functional performance through kinesiophobia in individuals with inflammatory arthritis.

The impact of residential winter HVAC usage behavior on arthritis in older adults: A PLS-SEM analysis

Environmental factors like temperature and humidity have been shown to influence arthritis symptoms in older adults, and HVAC equipment can regulate indoor environmental parameters. This study aimed to explore the pathways and effectiveness of residential HVAC usage behavior during winter on arthritis conditions. Conducted across four major climate zones in China, this cross-sectional study involved 3579 older adults aged 60–74 years and collected data on demographics, residential environments, lifestyles, and health outcomes. Utilizing Partial Least Squares - Structural Equation Modeling (PLS-SEM), a complex structural equation model (SEM) and an HVAC-Health mediation model was developed to analyze the relationships among influencing factors and health outcomes. Results revealed that socio-economic status, building characteristics, lifestyles, HVAC usage behavior, and indoor environmental exposure significantly affect the frequency of arthritis flare-ups (p < 0.05). Specifically, lifestyles, indoor wet and cold exposures have strong direct effects on health outcomes, with path coefficients of 0.178, 0.155 and 0.143, respectively. Moreover, HVAC usage indirectly influences health through mediators, with cold exposure (β = 0.045, p < 0.001), air pollution (β = 0.025, p < 0.001), and wet exposure (β = 0.012, p = 0.001) ranked in terms of their mediating effects. This research underscores the crucial role of HVAC systems in mitigating arthritis symptoms in older adults, advocating for enhanced implementation of HVAC technologies in senior housing to promote health and well-being. The originality of this study lies in employing the PLS-SEM method to elucidate how the indoor environment—particularly under the premise of HVAC usage—affect arthritis symptoms in older adults.

Career duration and later-life health conditions among former professional American-style football players

ObjectivesCareer duration is often used as a metric of neurotrauma exposure in studies of elite athletes. However, as a proxy metric, career length may not accurately represent causal factors, and...

Efficacy and safety of 10mg versus 30mg of oral prednisolone for acute CPP crystal arthritis: findings of a randomized controlled trial.

The optimal prednisolone dose for managing acute calcium pyrophosphate (CPP) crystal arthritis remains unclear. We compared the efficacy and safety of 10- and 30-mg daily doses of prednisolone for acute CPP crystal arthritis. This randomized, controlled, open-label trial included patients with acute CPP crystal arthritis and symptoms that had begun less than 72h earlier. Patients without CPP crystals, those with septic arthritis, and those with uncontrolled infections were excluded. Participants received either 10 or 30mg of prednisolone daily for 7days. The primary outcome was time until complete resolution of symptoms; secondary outcomes included time until clinical resolution, recurrence rates, laboratory profiles, and adverse events, adjusted for confounders. Seventy-nine patients participated. Baseline characteristics were comparable, except that the 30-mg recipients had more initial inpatient visits (p = 0.03). The median time until complete resolution was 7days in both groups (p = 0.73). The 30-mg recipients exhibited faster clinical resolution (1 vs. 3days; p = 0.03), but adjusted analyses revealed no significant differences in time until complete resolution (6.2 vs. 6.5days; p = 0.68) or clinical resolution (2.4 vs. 2days; p = 0.27). The overall recurrence rate was 14.3%; the 30-mg recipients experienced slightly more recurrences (p = 0.08). The other secondary outcomes did not differ significantly. The 10- and 30-mg daily doses of prednisolone were equally effective in treating acute symptoms of CPP crystal arthritis, with no significant differences in resolution time, recurrence rates, or safety outcomes.

Wutou decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway

Ethnopharmacological relevanceIn traditional Chinese medicine (TCM), Wutou Decoction (WTD) has long been used to alleviate arthritis. Emerging studies have reported that WTD could improve the symptoms of rheumatoid arthritis (RA). However, the mechanism by which WTD is involved in the treatment of RA remains elusive, posing a challenge to the worldwide acceptance of WTD as an efficient RA therapy. Aim of the studyThis study investigated the antiarthritic efficacy of WTD in a collagen-induced arthritis (CIA) rat model and explored silent information regulator 1 (SIRT1)-mediated deacetylation of the high mobility group box 1 (HMGB1)/NF-κB pathway. Materials and methodsA rat CIA model was used to evaluate the antiarthritic activity of WTD. Clinical arthritis score assessment, left ankle thickness assessment, micro-CT, histopathological staining, immunofluorescence staining, and ELISA were conducted to elucidate the anti-inflammatory effects of WTD. The M1 macrophage polarization state, cell viability, and invasion were also determined to assess the effects of WTD on macrophage proliferation and invasion in vitro. Additionally, in vivo and in vitro HMGB1 nuclear translocation and NF-κB activation were analysed. Finally, deacetylase activity was assessed by Western blot, NAD+/NADH analysis, and co-immunoprecipitaion. ResultsWTD significantly alleviated arthritis in CIA rats and inhibited pathological changes in joint lesions while concurrently suppressing TNF-α, IL-6, and IL-1β release. Mechanistically, WTD suppressed M1 infiltration in ankle tissues and their invasion in vitro. Furthermore, WTD downregulated HMGB1/p65 nuclear translocation and acetylation, which may be associated with SIRT1 upregulation. ConclusionsOverall, WTD potentially alleviates RA through SIRT1-mediated downregulation of HMGB1 and NF-κB acetylation.

A comparative randomised clinical trial of Amrutadi kwath and Vasadi kath in the management of Vatarakta (Gout)

Vatarakta specially occurs in Madhyavastha which is Parihanikala in which Dhatukshaya takes place. Khavaigunya (Rikta srotas) occurs in Asthi which is responsible for the production of Vatarakta. Vatarakta is a disease related with khavaigunya found in raktavaha strotas which include vitiated vata and rakta, so termed as vatarakta. Due to properties of sukshmatva and saratva of vayu, dravatva and saratva of rakta they spread all over the body. Symptoms of Vatarakta are shool, toda, daha, vaivarnya described by various acharya. Symptoms of Gouty arthritis are similar as of vatarakta Joint pain, Swelling, stiffness, disability and crepitations over small joint. Gouty arthritis is the most common form of arthritis, which occurs in middle age. Amrutadi Kwath and Vasadi Kwath have most of contents are snigdha, guru and mrudu. By virtue of these properties, this alleviates vata and pitta. Hence these are used in diseases which arise due to vitiation of vata and pitta. in vatarakta by its vatapittashamaka prabhav and snigddha, mrudu gunas by vatanulomana kriya. Amrutadi kwath is very effective in relieving the symptoms of vatarakta. Materials and Method: Total 80 patients of the age group 25-60 years presenting with signs and symptoms of vatarakta were selected randomly from OPD of the department of kayachiktsa. The 40 patients of trial group were treated with Amrutadi kwath and 40 patients of control group were subjected to vasadi kwath. Conclusion: Amrutadi Kwath showing significant results than Vasadi Kwath in symptoms of Vatarakta (Gout).

Design, Synthesis of Flurbiprofen Based 1,3,4-Oxadiazoles and Constrained Anticancer, Antioxidant Agents: In silico Docking Analysis.

Flurbiprofen, a primary component of a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis, and is a considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. The synthesized series (6a-k) was characterized using a combination of spectroscopic techniques, including FT-IR, mass, 1H NMR, and 13C NMR, physical data. In the series, analogues 6c, 6e, 6h, and 6k showed excellent inhibitory activity against MCF-7 cells in the range of IC50 values of 9.10 to 13.67 µg. mL-1 compared to DXN (IC50 = 9.24 µg. mL-1). In this series, analogues 6c, 6f, 6h, and 6j show remarkable H2O2 radical scavenging inhibition IC50 of 48.25 ± 0.21, 47.33 ± 0.15, 51.10 ± 0.25, and 44.40 ± 0.07 μM by using ascorbic acid as a standard, whose IC50 is 49.90 ± 0.27 μM. According to the docking results, the most potent cytotoxic compounds have a stronger binding affinity with the Flurbiprofen complex (PDB: 1R9O) because of their interactions with residues such as Arg416(A), Trp103(A), Phe97(A), Gly279(A), Ile188(A), Glu283(A), Thr287(A), Val462(A), Phe459(A), Leu345(A), Ile417(A), and Cys418(A). Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability.

Study protocol: process and outcome evaluation of the Walk with Ease program for fall prevention

BackgroundFalls are the leading cause of injury related morbidity and mortality in older adults. Primary and secondary prevention strategies that address modifiable risk factors are critically important to reduce the number of falls and fall related injuries. A number of evidence-based fall prevention programs are available, but few offer potential for broad dissemination and public health impact due to implementation barriers, such as a need for trained program leaders and clinicians.MethodsThe study will use a randomized controlled trial design to evaluate incorporating physical therapy exercises (primary prevention strategy) within an existing intervention called Walk with Ease. While Walk with Ease has an established evidence-base related to the management of arthritis pain and symptoms, the present study will determine the potential to also reduce falls and fall risk in community-dwelling older adults. The integrated process and outcome evaluation will determine the relative effectiveness of individually-prescribed exercises (compared to standardized exercises) as well as the potential of ‘habit training’ resources (relative to generic behavior prompts) to improve compliance with exercises in this population.DiscussionThe study, conducted through a local clinical-community partnership will advance both the science and practice of community-based fall prevention programming, while also informing implementation strategies needed to promote broader dissemination.Trial registrationClinicalTrials.gov, NCT05693025, Registered January 20, 2023, Updated March 1, 2023.

Overview of the Mechanism of Action of Gentiana Scabra in the Treatment of Rheumatoid Arthritis

Objective: To provide a comprehensive review of the research on the analgesic, anti-inflammatory, anti-swelling and analgesic effects of Radix Gentiana Macrophylla. Methods: Gentiana macrocephala has an analgesic effect in modern research, commonly used in various rheumatism and paralysis, numbness, contracture and soreness of the muscles and bones and other diseases of the pain treatment, can be extracted from the sterol glycoside salts and other medicinal components, its anti-inflammatory and analgesic and treatment of acute arthritis episodes of the clinical effect of the performance of the particularly unique and significant. The results can make the joint swelling, pain and other symptoms can be reduced, and the risk of reoccurrence can also be reduced after the introduction of the drug. Conclusion: In the treatment of rheumatoid arthritis, Gentiana Macrophyllae alone and in combination can improve joint symptoms such as stiffness, swelling, pain, distension and deformity as well as other systemic symptoms of rheumatoid arthritis.

Microbial chaperonin 60 inhibits osteoclast differentiation by interfering with RANK/RANKL binding and overexpression of lipocalin2

Osteoclasts play a crucial role in bone destruction in rheumatoid arthritis (RA). This study aimed to investigate the inhibitory effects of chaperonin 60 (CPN60), identified in the surface proteins of Propionibacterium freudenreichii MJ2, on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation, and elucidate the underlying mechanisms. Treatment with CPN60 inhibited RANKL-induced osteoclast differentiation by decreasing the expression of osteoclast differentiation-related genes and proteins. CPN60 interfered with the binding of RANKL to RANK, as elucidated using surface plasmon resonance (SPR) and immunofluorescence. In silico molecular docking analysis further supported the interference of CPN60 with the binding of RANKL and RANK. CPN60 suppressed the expression of molecules linked to the calcium-dependent pathway in RANKL-induced osteoclast differentiation at both mRNA and protein levels. Microarray analysis showed elevated expression of lipocalin 2 (Lcn2), which was closely linked to the inhibition of osteoclast differentiation in CPN60-treated RAW 264.7 cells. Inhibition of Lcn2 decreased the inhibitory effect of CPN60 on osteoclast differentiation, indicating that increased expression of Lcn2 by CPN60 contributes to the inhibition of osteoclastogenesis. In addition, CPN60 treatment alleviated arthritis symptoms in collagen-induced arthritis mice by reducing the generation of collagen-specific antibodies and inhibiting osteoclast differentiation. In conclusion, CPN60 of P. freudenreichii MJ2 interfered with RANKL–RANK binding, reduced the expression of genes and proteins related to osteoclast differentiation and upregulated Lcn2 expression, thereby inhibiting RANKL-induced osteoclast differentiation, which might contribute to ameliorate collagen-induced arthritis.

Omalizumab-Induced Arthralgias in a Patient with Chronic Idiopathic Urticaria

Background: Omalizumab (Xolair) is a recombinant DNA-derived humanized IgG1 κ monoclonal antibody that selectively binds to the high-affinity IgE receptor on the surface of mast cells and basophils, limiting release of mediators of the allergic response. It is the first monoclonal antibody approved for the treatment of refractory chronic idiopathic urticaria in patients over the age of 12 and has been shown to result in clinically significant improvement of itching and wheal formation in these patients. Rarely, inflammatory arthralgias can be a severe side effect of omalizumab. Clinical Case: We report a case of a 38-year-old female patient with chronic idiopathic urticaria who responded well on a therapeutic dosage of omalizumab, but subsequently developed severe inflammatory arthralgias. We decreased her dosage and added methotrexate for complete resolution of her urticarial and arthritic symptoms. Conclusion: In patients with concern for medication-induced inflammatory arthralgias, physicians should consider reducing or discontinuing omalizumab with consideration of patient goals for the treatment of chronic idiopathic urticaria. This article highlights the occurrence of inflammatory arthralgias as a side effect of omalizumab, the importance of eliciting patient goals and preferences for treatment, and proposes a solution to manage these arthralgias while appropriately treating symptoms in patients with chronic idiopathic urticaria.

Complex transmission epidemiology of neglected Australian arboviruses: diverse non-human vertebrate hosts and competent arthropod invertebrate vectors.

More than 75 arboviruses are indigenous to Australia, of which at least 13 are known to cause disease in humans. Alphaviruses are the most common arboviruses, notably including Ross River and Barmah Forest viruses, which contribute a significant public health and economic burden in Australia. Both can cause febrile illness with arthritic symptoms. Each circulates nationally across diverse climates and environments, and has multi-host, multi-vector dynamics. Several medically important flaviviruses also circulate in Australia. Infection with Murray Valley encephalitis or Kunjin viruses is less common but is associated with brain inflammation. Key research priorities for Australian arboviruses aim to understand clinical manifestations, develop timely diagnostics, and identify transmission cycles that permit the maintenance of arboviruses. While these can now be answered for a handful of notifiable alpha- and flaviviruses there are others for which non-human vertebrate hosts and competent arthropod invertebrate vectors are still to be identified and/or whose role in transmission is not well understood. One or more of these 'neglected' arboviruses may be the causative agent of a proportion of the many thousands of fever-related illnesses reported annually in Australia that at present remain undiagnosed. Here, what is known about enzootic cycling of viruses between arthropod vectors and mammalian and avian reservoir hosts is summarised. How and to what extent these interactions influence the epidemiology of arbovirus transmission and infection is discussed.

New Highly Selective Antivirals for Chikungunya Virus identified from the Screening of a Drug-Like Compound Library.

Chikungunya fever is a mosquito-borne disease caused by Chikungunya virus (CHIKV). Treatment of CHIKV infections is currently supportive and does not limit viral replication or symptoms of persistent chronic arthritis. Although there are multiple compounds reported as antivirals active against CHIKV in vitro, there are still no effective and safe antivirals. Thus, active research aims at the identification of new chemical structures with antiviral activity. Here, we report the screen of the Pandemic Response Box library of small molecules against a fully infectious CHIKV reporter virus. Our screening approach successfully identified previously reported CHIKV antiviral compounds within this library and further expanded potentially active hits, supporting the use of reporter-virus-based assays in high-throughput screening format as a reliable tool for antiviral drug discovery. Four molecules were identified as potential drug candidates against CHIKV: MMV1634402 (Brilacidin) and MMV102270 (Diphyllin), which were previously shown to present broad-spectrum antiviral activities, in addition to MMV1578574 (Eravacycline), and the antifungal MMV689401 (Fluopicolide), for which their antiviral potential is uncovered here.

The Effects of Peloid and Balneotherapy on Arthritis: A Systematic Review

Background: Over the decades, the prevalence of arthritis in the United States has skyrocketed. Arthritis is the most common cause of disability in the United States. According to the National Arthritis Data Workgroup, more than 22% of American adults (which is equivalent to over 52.5 million people) suffer from arthritis or a rheumatic condition. Of those diagnosed with arthritis, 7.3% of people are aged 18-44, 30.3% are 45-64 years old, and 49.7% are over the age of 65. Women are also more prone to developing this disease than men; 26% of women have been diagnosed with arthritis whereas 19.1% of men have been diagnosed with arthritis. Researchers estimated that by 2030, the number of people who will be diagnosed with arthritis will increase to 67 million. There are three most common types of arthritis, two of which will be the focus of this systematic literature review, these include osteoarthritis and rheumatoid arthritis. Osteoarthritis is characterized by degeneration of cartilage as well as bony overgrowth while rheumatoid arthritis, while rheumatoid arthritis is an autoimmune and inflammatory disease affecting the joints of the body. Peloid and balneotherapy dates to the ancient past. Humans searching for healing remedies in the surrounding nature, discovered the healing effects of heat, cold and radiation solar and mineral waters. Instinct and observation of the world paved the way for natural but effective ways to treat pain. This literature review will be focused on the effects of peloid and balneotherapy on reducing the symptoms of arthritis and thus improving quality of life. Purpose: The purpose of this targeted systematic literature review is to examine the relationship between the treatment of peloid and balneotherapy on patients with arthritis in reducing pain, arthritic symptoms and increasing their quality of life. Methodology: A literature search was conducted using PubMed, Google Scholar, CINAHL, Science Direct databases. The search terms included balneotherapy, peloid therapy, arthritis, rheumatoid arthritis, osteoarthritis, quality of life, rehabilitation, physical activity, and pain management. Inclusion criteria: 18-65 years, published within the last 10 years, interventions related to peloid and balneotherapy, or both. An evidence level of 2b or higher was required for the inclusion criteria. Exclusion criteria includes not evaluating interventions of interest and therapeutic interventions for arthritis which are not peloid or balneotherapy related. A total of five articles (n = 5) were included in this systematic literature review. The original search criteria yielded 61 research articles related to the topic, which were then screened with the inclusion criteria with a remaining of five articles which were utilized in this review. Results: A systematic literature review of five studies was performed. Five clinical studies measured the effectiveness of balneotherapy and/or peloid therapy and there was significant difference between the groups in WOMAC pain, stiffness, and function scores and in the VAS. Discussion: This review indicates that balneotherapy and peloid therapy were effective in reducing pain, stiffness, improving function as assessed by the WOMAC and VAS scores.

51569 Bimekizumab treatment resulted in sustained improvements in nail psoriasis and signs and symptoms of psoriatic arthritis in patients with baseline nail disease: 1-year pooled results from two phase 3 studies

51569 Bimekizumab treatment resulted in sustained improvements in nail psoriasis and signs and symptoms of psoriatic arthritis in patients with baseline nail disease: 1-year pooled results from two phase 3 studies

Metabolomics Reveals Disturbed Amino Acid Metabolism During Different Stages of RA in Collagen-Induced Arthritis Mice.

Rheumatoid arthritis (RA) is an autoimmune disease featured by chronic synovitis and progressive joint damage. Early treatment before the onset of clinical symptoms (also known as the pre-RA stage) may slow or stop the progression of the disease. We sought to discover the dynamic metabolic changes during the evolution of collagen-induced arthritis (CIA) to better characterize the disease stages. Untargeted metabolomics analysis using gas chromatography-mass spectrometry revealed that the metabolic profiles of CIA mice gradually differed from that of the control group with the progression of the disease. During the induction phase, the CIA group showed some metabolic alterations in galactose metabolism, arginine biosynthesis, tricarboxylic acid cycle (TCA cycle), pyruvate metabolism, and starch/sucrose metabolism. During the early inflammatory phase, no joint swelling was observed in CIA mice, and metabolites changed mainly involving amino acid metabolism (arginine biosynthesis, arginine/proline metabolism, phenylalanine/tyrosine/tryptophan biosynthesis), and glutathione metabolism. During the peak inflammatory phase, severe arthritis symptoms were observed in CIA mice, and there were more extensive metabolic alterations in valine/leucine/isoleucine biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, TCA cycle, galactose metabolism, and arginine biosynthesis. Moreover, the reduction of specific amino acids, such as glycine, serine, and proline, during the early stages may result in an imbalance in macrophage polarization and enhance the inflammatory response in CIA mice. Our study confirmed that specific perturbations in amino acid metabolism have occurred in CIA mice prior to the onset of joint symptoms, which may be related to autoimmune disorders. The findings could provide insights into the metabolic mechanism and the diagnosis of pre-RA.

Effects of resveratrol on rheumatic symptoms and hepatic metabolism of arthritic rats.

Resveratrol has been studied as a potential agent for treating rheumatic conditions; however, this compound suppresses glucose synthesis and glycogen catabolism when infused in perfused livers of both arthritic and healthy rats. This study investigated the effects of oral administration of resveratrol on inflammation and liver metabolism in rats with arthritis induced by Freund's adjuvant, which serves as rheumatoid arthritis model. Holtzman rats, both healthy and exhibiting arthritic symptoms, were orally treated with resveratrol atdoses varying from 25 to 500 mg/kg for a 5-day period preceding arthritis induction, followed by an additional 20-day period thereafter. Paw edema, arthritic score and hepatic myeloperoxidase activity were assessed to evaluate inflammation. Glycogen catabolism and gluconeogenesis from lactate were respectively evaluated in perfused livers from fed and fasted rats. Resveratrol decreased the liver myeloperoxidase activity at doses above 100 mg/kg, and decreased the paw edema and delayed the arthritic score at doses above 250 mg/kg. The hepatic gluconeogenesis was decreased in arthritic rats and resveratrol did not improve it. However, resveratrol did not negatively modify the gluconeogenesis inlivers of healthy and arthritic rats. Glycogen catabolism was in part and slightly modified by resveratrol in the liver of arthritic and healthy rats. It is improbable that resveratrol negatively affects the liver metabolism, especially considering that gluconeogenesis is highly fragile to changes in cellular architecture. The findings suggest that resveratrol could serve as alternative for treating rheumatoid arthritis. Nevertheless, prudence is advised regarding its transient effects on liver metabolism.

Exploring the pathogenesis of RA through the gut-articular axis-dysbiosis a potential factor.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. It has been suggested that the pathogenesis of RA begins in the mucosa and then transitions to the joints when many factors interact, including microbial dysbiosis, inflammatory responses, and immune abnormalities at the mucosal site. Data from RA animals and patients suggest there are changes in the mucosal microflora before the onset of RA, and that dysbiosis of the mucosal ecology continues to play a role in the development of arthritis. Microbial dysbiosis of the mucosa reduces the normal barrier function of the intestinal tract, promotes inflammatory reactions in the mucosal areas of the intestines, and then activates the intestinal immune cells abnormally to produce a large number of auto-reactive antibodies that exacerbate arthritis. Current findings do not clarify whether dysbiosis is only a potential trigger for the development of RA. If it is possible to intervene in such microbial changes before the onset of RA, could the clinical symptoms of arthritis be prevented or reduced? Finding new ways to regulate gut flora composition to maintain gut barrier function is an ongoing challenge for the prevention and treatment of RA.

Gelsolin alleviates rheumatoid arthritis by negatively regulating NLRP3 inflammasome activation.

Despite numerous biomarkers being proposed for rheumatoid arthritis (RA), a gap remains in our understanding of their mechanisms of action. In this study, we discovered a novel role for gelsolin (GSN), an actin-binding protein whose levels are notably reduced in the plasma of RA patients. We elucidated that GSN is a key regulator of NLRP3 inflammasome activation in macrophages, providing a plausible explanation for the decreased secretion of GSN in RA patients. We found that GSN interacts with NLRP3 in LPS-primed macrophages, hence modulating the formation of the NLRP3 inflammasome complex. Reducing GSN expression significantly enhanced NLRP3 inflammasome activation. GSN impeded NLRP3 translocation to the mitochondria; it contributed to the maintenance of intracellular calcium equilibrium and mitochondrial stability. This maintenance is crucial for controlling the inflammatory response associated with RA. Furthermore, the exacerbation of arthritic symptoms in GSN-deficient mice indicates the potential of GSN as both a diagnostic biomarker and a therapeutic target. Moreover, not limited to RA models, GSN has demonstrated a protective function in diverse disease models associated with the NLRP3 inflammasome. Myeloid cell-specific GSN-knockout mice exhibited aggravated inflammatory responses in models of MSU-induced peritonitis, folic acid-induced acute tubular necrosis, and LPS-induced sepsis. These findings suggest novel therapeutic approaches that modulate GSN activity, offering promise for more effective management of RA and a broader spectrum of inflammatory conditions.