The Causal Association between Alcohol, Smoking, Coffee Consumption, and the Risk of Arthritis: A Meta-Analysis of Mendelian Randomization Studies.

Objective: To evaluate the genetic causality between alcohol intake, smoking, coffee consumption, and arthritis. Methods: Mendelian randomization (MR) studies with alcohol, smoking, and coffee consumption behaviors as exposures, and osteoarthritis (OA) and rheumatoid arthritis (RA) as outcomes were retrieved from up to July 2023. Two researchers with relevant professional backgrounds independently assessed the quality and extracted data from the included studies. Meanwhile, we applied MR analyses of four lifestyle exposures and five arthritis outcomes (two for OA and three for RA) with gene-wide association study (GWAS) data that were different from the included studies, and the results were also included in the meta-analysis. Statistical analyses were performed using Stata 16.0 and R software version 4.3.1. Results: A total of 84 studies were assessed. Of these, 11 were selected for meta-analysis. As a whole, the included studies were considered to be at a low risk of bias and were of high quality. Results of the meta-analysis showed no significant genetic causality between alcohol intake and arthritis (odds ratio (OR): 1.02 (0.94-1.11)). Smoking and arthritis had a positive genetic causal association (OR: 1.44 (1.27-1.64)) with both OA (1.44 (1.22-1.71)) and RA (1.37 (1.26-1.50)). Coffee consumption and arthritis also had a positive genetic causal association (OR: 1.02 (1.01-1.03)). Results from the subgroup analysis showed a positive genetic causality between coffee consumption and both OA (OR: 1.02 (1.00-1.03)) and RA (OR: 1.56 (1.19-2.05)). Conclusion: There is positive genetic causality between smoking and coffee consumption and arthritis (OA and RA), while there is insufficient evidence for genetic causality between alcohol intake and arthritis.

Effect of chrono-moxibustion and its influence on circadian rhythm for rheumatoid arthritis: A study protocol for a randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease which is characterized by a circadian variation of key clinical symptoms and findings, with prominent joint swelling, stiffness and pain occurring in the early morning and light clinical symptoms during the day. Chrono-moxibustion is carried out at different time, which could result in dissimilar therapeutic effects. However, its efficacy has seldom been systematically demonstrated and few studies have reported that Chrono-moxibustion may regulate the circadian rhythm of RA. We therefore designed a randomized trial to explore the effective difference of Chrono-moxibustion in RA treatment, as well as to study its influence on circadian rhythm of RA patients. METHODS: This study is a randomized controlled trial involving 120 participants, and a total of 90 eligible RA patients will be randomly allocated to three groups in a 1:1:1 ratio as moxibustion at 7 to 9 am, moxibustion at 5 to 7 pm, and waiting list group, meanwhile, 30 healthy people will be divided into the control group. Patients in moxibustion groups will be treated for 30 minutes per session, 3 times a week, lasting 6 weeks. All of RA patients will be evaluated with questionnaires and laboratory tests before treatment, as well as 3 weeks, 6 weeks, and 3 months after treatment. One way analysis of variance (ANOVA) with multiple comparisons will be applied to identify differences more than two groups. Halberg cosiner software will be used to analysis the circadian rhythm. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide evidence-based evidence for the effective difference of Chrono-moxibustion in RA treatment and its influence on circadian rhythm of RA patients.

Association between work physical activity, dietary factors, and risk of rheumatoid arthritis.

OBJECTIVE: We aimed to determine the association of physical activity and dietary factors on RA risk. METHODS: This case-control study within the Mayo Clinic Biobank matched incident RA cases (two codes plus disease-modifying anti-rheumatic drug, PPV 95%) to controls 1:3 on age, sex, and recruitment year/location. A baseline questionnaire assessed activity and dietary exposures. Logistic regression models calculated adjusted odds ratios (aOR) with 95% confidence intervals (CI) of RA for each of 45 activity/dietary exposures. RESULTS: We identified 212 incident RA cases and 636 controls (mean age 64, 70% female). Active work physical activity was associated with elevated risk of RA (aOR 3.00, 95% CI 1.58-5.69 vs. sedentary); leisure activity was not (aOR 0.96, 95% CI 0.64-1.42 sedentary vs. active). Three or more servings high-fat food and 5+ servings fruits/vegetables daily showed non-significant associations with RA (aOR 1.22, 95% CI 0.74-2.00 vs. 0-1 time; aOR 0.75, 95% CI 0.51-1.11 vs. 0-3 times), especially in sensitivity analyses with at least five years between questionnaire and RA (aOR 1.80, 95% CI 0.69-4.71; aOR 0.54, 95% CI 0.27-1.08). Alcohol binging was not associated with RA risk (aOR 1.28, 95% CI 0.56-2.96). Finally, sensitivity (versus primary) analyses showed a nonsignificant increase in RA risk for most vitamins and supplements. CONCLUSION: Active work physical activity and some nutritional profiles (increased high-fat, reduced fruit/vegetable consumption) may be associated with increased risk of RA. Confirmatory studies are needed.

Investigation of the association between coffee and risk of RA-results from the Swedish EIRA study.

BACKGROUND: Studies on the association between coffee, a modifiable lifestyle factor, and rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, have been conflicting. The aim of the present study was to study the association between coffee consumption and risk of RA in the context of different lifestyle factors. METHODS: We included 2184 cases (72% women, mean age 55 years) newly diagnosed with RA during 2005-2018 in Sweden and 4201 controls matched on age, sex, and residential area. Data on coffee consumption was collected through a food frequency questionnaire and categorized into < 2 (reference), 2-< 4, 4-< 6, and ≥ 6 cups/day. We calculated odds ratios (OR) with 95% confidence intervals (CI) for coffee consumption and risk of RA, in a crude model (taking matching factors into account), and then adjusted first for smoking and further for BMI, educational level, alcohol consumption, and physical activity. We also stratified analyses on sex, smoking, rheumatoid factor, and anti-CCP2 status. RESULTS: In the crude model, high coffee consumption was associated with increased risk of RA (OR = 1.50, 95% CI 1.20-1.88 for ≥ 6 cups/day compared to < 2 cups). After adjusting for smoking, the OR decreased and was no longer statistically significant (OR = 1.16, 95% CI 0.92-1.46) and decreased further in the full model (OR = 1.14 95% CI 0.89-1.45). This pattern held true in all strata. CONCLUSION: The findings from this large, population-based case-control study did not support a significant association between coffee consumption and risk of RA as a whole nor within different subgroups.

Nutrition and Rheumatoid Arthritis Onset: A Prospective Analysis Using the UK Biobank.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the joints. The multifactorial etiopathogenesis of RA has been heavily investigated, but is still only partially understood. Diet can represent both a risk factor and a protective factor, based on some evidence that suggests specific properties of certain foods and their ability to increase/reduce inflammation. To date, the studies done on this topic provide discordant results and are heterogeneous in terms of design and cohort size. In this work, we investigated for the first time the relationship between nutrition and the risk of RA onset using a sample size of about half a million subjects from one of the largest publicly available biobanks that is the UK biobank. Results showed that oily fish, alcohol, coffee and breakfast cereals have protective roles in RA; whereas, tea can increase the risk of RA. In conclusion, the obtained results confirm that diet plays key roles in RA, either by promoting or by preventing RA onset and development. Future research should focus on unravelling the effects of dietary habits on immune-mediated diseases to establish better preventive strategies.

Increased Ratio of CD14++CD80+ Cells/CD14++CD163+ Cells in the Infrapatellar Fat Pad of End-Stage Arthropathy Patients.

Objectives: This study sought to identify the ratio of M1/M2 cells in the infrapatellar fat pads (IFP) and subcutaneous fat tissues (SC) of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. The clinical features of OA and RA patients treated with or without biological disease-modifying anti-rheumatic drugs (bDMARDs) were also assessed. Methods: IFP and SC were collected from patients with OA and RA who are undergoing total knee arthroplasty (TKA). CD14-positive cells were then isolated from these samples. Flow cytometry was used to determine the number of CD14++CD80+ cells and CD14++CD163+ cells. The expression levels of lipid transcription factors, such as sterol regulatory element-binding protein 1 (SREBP1) and liver X receptor alpha (LXRA), and inflammatory cytokines were also evaluated. Results: Twenty OA patients and 22 RA patients were enrolled in this study. Ten of the RA patients (45.4%) received bDAMRDs before TKA. On average, a fivefold increase in the number of CD14-positive cells and lower expression levels of SREBP1C and LXRA were observed in OA IFP relative to OA SC; however, these results were not obtained from the RA samples. The median ratio of CD14++CD80+ cells/CD14++CD163+ cells of OA IFP was 0.87 (0.76-1.09, interquartile range), which is higher to that of OA SC with a lower ratio (p = 0.05835). Conclusions: The quantity and quality of CD14-positive cells differed between IFP and SC in arthropathy patients. To our knowledge, this is the first study to characterize the ratio of M1/M2 cells in the IFP and SC of end-stage OA and RA patients. The increased ratio of CD14++CD80+ cells/CD14++CD163+ cells in the IFP from patients with OA and RA treated with bDMARDs indicated that inflammation was localized in the IFP. As adipose tissue-derived innate immune cells were revealed as one of the targets for regulating inflammation, further analysis of these cells in the IFP may reveal new therapeutic strategies for inflammatory joint diseases.

LncRNA HOTTIP from synovial fibroblast-derived exosomes: A novel molecular target for rheumatoid arthritis through the miR-1908-5p/STAT3 axis.

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. HOTTIP, a long noncoding RNA (lncRNA), participates in cell proliferation and invasion. However, the correlation between HOTTIP and RA remains unclear. Therefore, this study aimed to clarify how HOTTIP works in RA and to investigate its role in the development of RA. Flow cytometry was used to analyze cell cycle progression. Binding between HOTTIP, signal transducer and activator of transcription 3 (STAT3) and miR-1908-5p was demonstrated by dual-luciferase assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of T cell differentiation-related proteins. We found that HOTTIP was upregulated in rheumatoid arthritis synovial fibroblasts (RASFs). HOTTIP directly bound to miR-1908-5p and negatively modulated miR-1908-5p expression while positively regulating STAT3. The effects of HOTTIP overexpression on regulating the balance of the Th17/Treg cell ratio were partly reversed by miR-1908-5p overexpression. In addition, in vivo experiments demonstrated that overexpression of HOTTIP aggravated inflammation in RA mice, which was demonstrated by hematoxylin and eosin (HE) staining and the increased expression levels of CD4+ interleukin (IL)-17+, forkhead Box P3 (FOXP3) and retinoid-related orphan receptor gamma-t (RORγt). In summary, our study suggests that HOTTIP plays a damaging role in RA by promoting inflammation, which may be related to the regulation of miR-1908-5p expression and the STAT3 signaling pathway. These results suggest that the regulation of HOTTIP may be a promising therapeutic strategy for RA.

Critical Role of Synovial Tissue-Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation.

Rheumatoid arthritis (RA) is a chronic prototypic immune-mediated inflammatory disease which is characterized by persistent synovial inflammation, leading to progressive joint destruction. Whilst the introduction of targeted biological drugs has led to a step change in the management of RA, 30-40% of patients do not respond adequately to these treatments, regardless of the mechanism of action of the drug used (ceiling of therapeutic response). In addition, many patients who acheive clinical remission, quickly relapse following the withdrawal of treatment. These observations suggest the existence of additional pathways of disease persistence that remain to be identified and targeted therapeutically. A major barrier for the identification of therapeutic targets and successful clinical translation is the limited understanding of the cellular mechanisms that operate within the synovial microenvironment to sustain joint inflammation. Recent insights into the heterogeneity of tissue resident synovial cells, including macropahges and fibroblasts has revealed distinct subsets of these cells that differentially regulate specific aspects of inflammatory joint pathology, paving the way for targeted interventions to specifically modulate the behaviour of these cells. In this review, we will discuss the phenotypic and functional heterogeneity of tissue resident synovial cells and how this cellular diversity contributes to joint inflammation. We discuss how critical interactions between tissue resident cell types regulate the disease state by establishing critical cellular checkpoints within the synovium designed to suppress inflammation and restore joint homeostasis. We propose that failure of these cellular checkpoints leads to the emergence of imprinted pathogenic fibroblast cell states that drive the persistence of joint inflammation. Finally, we discuss therapeutic strategies that could be employed to specifically target pathogenic subsets of fibroblasts in RA.

Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

Vitamin D deficiency: concern for rheumatoid arthritis and COVID-19?

Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.

Linalyl acetate as a potential preventive agent against muscle wasting in rheumatoid arthritis rats chronically exposed to nicotine.

Cigarette smoking has detrimental effects on rheumatoid arthritis (RA), characterized by muscle wasting. Linalyl acetate (LA), the main component of Lavandula angustifolia Mill (lavender) oil, has anti-inflammatory properties. We investigated the detrimental effects of chronic nicotine exposure in rats with RA, as well as the abilities of lavender oil and LA to prevent muscle wasting. Rats with RA induced by type II collagen were exposed to nicotine for 22 days from day 1. Lavender oil or LA was administered twice a week during the experiment. Compared with control, collagen-induced arthritis (CIA) and chronic nicotine exposure plus CIA (NicoCIA) showed increases in hind paw thickness and serum interleukin (IL)-6 and decreases in body weight and serum insulin-like growth factor (IGF)-1 levels. Moreover, weight and fiber cross-sectional area of the gastrocnemius muscle were much lower, and mitochondrial membrane potential of the gastrocnemius muscle was higher, in the NicoCIA than in the CIA. These alterations in the NicoCIA were prevented by lavender oil and LA. Importantly, LA showed greater activity than lavender oil in preventing IGF-1 reduction in the NicoCIA. These findings suggest that lavender oil and LA may have preventive benefit in RA by counteracting muscle wasting associated with chronic nicotine exposure.

Prevotella histicola Protects From Arthritis by Expansion of Allobaculum and Augmenting Butyrate Production in Humanized Mice.

Bacterial therapeutics are the emergent alternatives in treating autoimmune diseases such as Rheumatoid Arthritis [RA]. P. histicola MCI 001 is one such therapeutic bacterium that has been proven to treat autoimmune diseases such as RA and multiple sclerosis [MS] in animal models. The present study characterized P. histicola MCI 001 isolated from a human duodenal biopsy, and evaluated its impact on the gut microbial and metabolic profile in a longitudinal study using the collagen-induced arthritis model in HLA-DQ8.AEo transgenic mice. P. histicola MCI 001 though closely related to the type strain of P. histicola, DSM 19854, differed in utilizing glycerol. In culture, P. histicola MCI 001 produced vitamins such as biotin and folate, and was involved in digesting complex carbohydrates and production of acetate. Colonization study showed that duodenum was the predominant niche for the gavaged MCI 001. A longitudinal follow-up of gut microbial profile in arthritic mice treated with MCI 001 suggested that dysbiosis caused due to arthritis was partially restored to the profile of naïve mice after treatment. A taxon-level analysis suggested an expansion of intestinal genus Allobaculum in MCI001 treated arthritic mice. Eubiosis achieved post treatment with P. histicola MCI 001 was also reflected in the increased production of short-chain fatty acids [SCFAs]. Present study suggests that the treatment with P. histicola MCI 001 leads to an expansion of Allobaculum by increasing the availability of simple carbohydrates and acetate. Restoration of microbial profile and metabolites like butyrate induce immune and gut homeostasis.

Nutri-epigenetics: the effect of maternal diet and early nutrition on the pathogenesis of autoimmune diseases.

Autoimmune diseases comprise a wide group of diseases involving a self-response of the immune system against the host. The etiopathogenesis is very complex involving disease-specific factors but also environmental factors, among which the diet. Maternal diet during pregnancy as well as early nutrition recently attracted the interest of the scientists as contributing to the immune programming. In this paper, we reviewed the most recent literature on the effect of maternal diet and early nutrition in modulating the immune system in a selected subset of autoimmune diseases: type 1 diabetes, celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis and rheumatoid arthritis. Particularly, we focused our narrative on the role of maternal and perinatal nutrition in the epigenetic mechanisms underlying the auto-immune response. Maternal diet during pregnancy as well as breastfeeding and early nutrition play a big role in many epigenetic mechanisms. Most of the nutrients consumed by the mother and the infant are known exerting epigenetic functions, such as folate, methionine, zinc, vitamins B12 and D, fibers, casein and gliadin, and they were linked to gene expression changes in the immune pathways. Despite the common role of maternal diet, breastfeeding and early nutrition in almost all the autoimmune diseases, each disease seems to have specific diet-driver epigenetic mechanisms that require further investigations. The research in this field is opening new routes to establishing a precision nutrition approach to the auto-immune diseases.

Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications.

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

The Influence of Menopause and Inflammation on Redox Status and Bone Mineral Density in Patients with Rheumatoid Arthritis.

Although oxidative stress is considered to be one of the key pathogenic factors in rheumatoid arthritis (RA), there is insufficient knowledge regarding the impact of menopause on redox status in this population. Thus, this study is aimed at assessing the influence of menopause within healthy women and within RA patients as well as the impact of RA in premenopausal and postmenopausal women on redox status, with special reference to bone mineral density (BMD). A total of 90 women were included in the study, 42 with RA and 48 age-matched healthy controls. They were divided into subgroups according to the presence of menopause. Following oxidative stress parameters were measured spectrophotometrically: index of lipid peroxidation (measured as TBARS), nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). BMD was assessed by using a dual-energy X-ray absorptiometry scanner. Comorbidities and drug history were recorded. The levels of H2O2 and TBARS were elevated in patients with RA, while NO2 - and O2 - increased in healthy women, both in premenopausal and postmenopausal groups. SOD activity decreased in postmenopausal RA patients. BMD was reduced in postmenopausal RA women. There was a correlation between NO2 - and O2 - with Health Assessment Questionnaire (HAQ) index in RA patients. Given that postmenopausal state was associated with elevated oxidative stress within healthy women and that menopausal state did not affect redox homeostasis within RA patients, but the redox homeostasis was altered in both RA groups compared to healthy women, it can be presumed that impaired redox status in RA occurred due to presence of the disease, irrespective of age. Moreover, menopause attenuates BMD reduction in women with RA. These results may indicate the need for therapeutic use of antioxidants in the form of supplements in women with RA, regardless of age.

Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4/NF-κB/MAPK Pathway.

Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor α (TNF-α). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg/kg/d each), the anti-RA effect and inhibitory activity on the TLR4/NF-κB/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4/NF-κB/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA.

Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis.

SCOPE: Previous work reported that dietary supplementation with resveratrol lowers synovial hyperplasia, inflammatory and oxidative damage in an antigen-induced arthritis (AIA) model. Here, it is investigated whether resveratrol can regulate the abnormal synovial proliferation by inducing autophagy and controlling the associated inflammatory response. METHODS AND RESULTS: Animals treated with resveratrol 8 weeks before AIA induction show the highest significant signal for microtubule-associated protein 1 light chain 3 by confocal microscopy. Besides, resveratrol significantly reduces p62 expression, but it does not increase the signal of beclin-1. Also, active caspase-3 expression, as well as poly(ADP-ribose) polymerase, is upregulated in the AIA group, and is significantly reduced in resveratrol-treated AIA group. Resveratrol also mitigates angiopoietin-1 and vascular endothelial growth factor signals. Finally, resveratrol significantly reduces the serum levels of IL-1ß, C reactive protein, and prostaglandin E2, as well as nuclear factor κB synovial tissue expression, which shows a significant correlation with p62 expression. CONCLUSION: Dietary supplementation with resveratrol induces the noncanonical autophagy pathway and limits the cross-talk with inflammation, which in consequence modulates the synovial hyperplasia. Preventive strategies that incorporate dietary intervention with resveratrol may offer a potential therapeutic alternative to drugs to influence the risk of rheumatoid arthritis and influence its course.

Galuteolin suppresses proliferation and inflammation in TNF-α-induced RA-FLS cells by activating HMOX1 to regulate IKKß/NF-κB pathway.

OBJECTIVE: Galuteolin (Galu) is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the effects of Galu on the TNF-α-induced RA-FLS cells (synoviocytes) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis and anti-inflammation. METHODS: After TNF-α stimulation, cell proliferation of RA-FLS was assessed by CCK-8 assay. TUNEL staining was used to detect the apoptosis. Western blot was used to detect the expressions of Iκκß, p-p65, p65, p-IκB, IκB, Cleaved-caspase3, Caspase-3, Bcl-2, and Bax. HO-1 were determined by RT-PCR. The contents of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and MMP-1 were determined by ELISA. RESULTS: Galu significantly suppressed cell proliferation in a dose-dependent manner. Additionally, Galu obviously promotes cell apoptosis rate of RA-FLS cells and elevated the expression levels of HO-1, caspase-3, and Bax, while reducing the expression level of Bcl-2. Furthermore, Galu apparently inhibited the levels of Iκκß, p-p65, and p-IκB. Moreover, Galu also significantly reduced the levels of pro-inflammatory factors IL-1ß, IL-6, IL-8, and MMP-1 in RA-FLS cells. CONCLUSION: Galuteolin exerts protective effects against TNF-α-induced RA-FLS cells by inhibiting apoptosis and inflammation, which can guide the clinical use of rheumatoid arthritis.

Beverages in Rheumatoid Arthritis: What to Prefer or to Avoid.

BACKGROUND: The role of nutrition in the pathogenesis of rheumatic diseases, including rheumatoid arthritis (RA), has gained increasing attention in recent years. A growing number of studies have focussed on the diverse nutritional contents of beverages, and their possible role in the development and progression of RA. Main body: We aimed to summarise the current knowledge on the role of a range of beverages in the context of RA. Beverages have a key role within the mosaic of autoimmunity in RA and potential to alter the microbiome, leading to downstream effects on inflammatory pathways. The molecular contents of beverages, including coffee, tea, and wine, have similarly been found to interfere with immune signalling pathways, some beneficial for disease progression and others less so. Finally, we consider beverages in the context of wider dietary patterns, and how this growing body of evidence may be harnessed by the multidisciplinary team in patient management. CONCLUSIONS: While there is increasing work focussing on the role of beverages in RA, integration of discussions around diet and lifestyle in our management of patients remains sparse. Nutrition in RA remains a controversial topic, but future studies, especially on the role of beverages, are likely to shed further light on this in coming years.

The mechanism of Chinese herbal formula HQT in the treatment of rheumatoid arthritis is related to its regulation of lncRNA uc.477 and miR-19b.

Rheumatoid arthritis (RA) pathogenesis has been associated with dysregulation of long noncoding RNA (lncRNA) and microRNA (miRNA) expression in serum and in lesioned tissue. In this study, a microarray assay was performed to study the profile of lncRNAs in the serum of RA patients and healthy donors, and a set of novel lncRNAs associated with RA was identified. For the remainder of the study, focus is on the top hit, lncRNA uc.477. The upregulation of lncRNA uc.477 and downregulation of miR-19b were validated in the serum of RA patients compared to that of healthy donors, and similar results were further confirmed by quantitative real-time PCR analysis of a cell line: RA-derived human fibroblast-like synoviocytes (HFLS-RA). LncRNA uc.477 could interfere with the processing of pri-miR-19b to produce its mature form and thereby played a pro-inflammatory role. In addition, Huayu Qiangshen Tongbi formula (HQT), a traditional Chinese medicine (TCM), has been shown to exert a promising therapeutic effect on RA and to exhibit long-term safety in our previous clinical retrospective study. Importantly, HQT treatment normalized the levels of lncRNA uc.477 and miR-19b in HFLS-RA in vitro and in mouse models of collagen-induced arthritis. HQT treatment, knockdown of lncRNA uc.477, and overexpression of miR-19b resulted in a comparable inhibition of pro-inflammatory cytokine gene expression in HFLS-RA cells. Together, these data suggest that the therapeutic effects of HQT on RA are closely related to its modulation of lncRNA uc.477 and miR-19b.