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ID PMID Title PublicationDate abstract
32851371 Does Abatacept Induce Testicular Toxicity? 2020 Jun OBJECTIVES: This study aims to demonstrate the effect of subcutaneous injections of abatacept on the histology of testes in mice. MATERIALS AND METHODS: The study included 20 male BALB/c mice (average weight, 25 g; aged 12-14 weeks). Ten mice received subcutaneous (SC) injections of abatacept [0.25 mg per 25 g body weight per 0.03 mL normal saline (NS)] at zero, two, four and eight weeks. As the control group, 10 mice received SC injections of NS (0.03 mL). At the post-injection 10(th) week, the mice were sacrificed, and histopathological studies were conducted. RESULTS: The results showed that 3/10 mice died of the abatacept-treated group. Testicular histology for the abatacept-treated group showed that 7/7 displayed no histopathological changes. CONCLUSION: To our knowledge, this is the first control-blinded study of BALB/c mice suggesting that abatacept may not have testicular toxicity. Further fertility and testicular toxicology evaluations including semen analysis and gonadal hormones should be performed to clarify our findings.
32353105 Atypical clinical presentation of distal renal tubular acidosis: a case report registered 2020 Jul We report an unusual case of a 24-year-old girl with a history of recurrent hypokalemic paralysis episodes and skin lesions on the lower limbs and buttocks, both of which had an acute evolution. In subsequent investigations, the patient also had nephrocalcinosis, nephrolithiasis, hyperchloremic metabolic acidosis and persistent alkaline urinary pH. The findings were consistent with distal renal tubular acidosis as the cause of hypokalemic paralysis. Clinical findings, immunological tests and the result of skin biopsy suggested primary Sjögren's syndrome as an underlying cause. The patient developed azotemia due to obstructive nephrolithiasis. All the features presented in this case are an unusual manifestation of distal renal tubular acidosis; so far, we are not aware of a similar report in the literature.
32896265 Omega-3 and omega-6 fatty acids in primary Sjögren's syndrome: clinical meaning and assoc 2020 Jul OBJECTIVES: Lipid mediators derived from polyunsaturated fatty acids (FA), have been related to inflammation and immune response regulation. Herein we evaluated the intake and serum levels of ω-3 and ω-6 FA among patients with primary Sjögren's syndrome (pSS), and correlated with ocular/oral sicca symptoms, disease activity and a panel of chemokines/cytokines. METHODS: We included 108 patients and 100 controls. Dietary information was obtained from a food questionnaire of one-day reminder and processed using a nutritional software. Among the SS group, we measured serum ω-3 (α-linolenic acid [α-LN], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and ω-6 (linoleic acid [LA], arachidonic acid [AA]) by gas chromatography flame ionization. We scored the ESSDAI, ESPRI, Schirmer-I test and NSWSF. In a subsample, we assessed the OSDI, ophthalmologic staining scores and measured CXCL8, CXCL10, CCL2, IL-22 and IL-21 in saliva, and CXCL8, CXCL10, CCL2 and CXCL9 in tears by Luminometry. RESULTS: ω-3 and ω-6 intake was lower in SS patients than controls, and did not correlate with serum levels. We found a negative correlation between α-LN and the OSDI and ESSDAI, as well as DHA and ESSDAI. In tears, AA positively correlated with CXCL9, whereas in saliva, α-LN, DHA and the ω3 sum negatively correlated with CCL2. We observed a negative correlation between the ω6 sum and IL-21. CONCLUSIONS: pSS patients had deficient omega intake. Lower ocular symptoms, ESSDAI scores and salivary CCL2 correlated with higher ω-3 levels, possible suggesting a role in chronic inflammation. Further studies are warranted to deepen in the knowledge of this association.
32104943 Hypergammaglobulinemic purpura of Waldenström in children. 2020 May BACKGROUND: Hypergammaglobulinemic purpura of Waldenström (HGPW), a rare cutaneous eruption characterized by the triad of recurrent episodes of lower extremity petechiae, symptoms of stinging and burning, and lower extremity edema, is poorly described in children. Some children have been reported to follow a benign course, while others are eventually diagnosed with fulminant rheumatologic disease. OBJECTIVES: To determine the distinguishing features of HGPW including the spectrum of disease manifestations and clinical outcomes. METHODS: This is a multicenter, retrospective case series of six children with HGPW combined with a literature review of 45 previously published pediatric cases. RESULTS: Most children were eventually diagnosed with systemic disease (63%) or developed autoantibody accumulation suggestive of evolving disease (71%). The most common diagnoses were Sjogren's syndrome and systemic lupus erythematosus. The mean duration between onset of cutaneous eruption and diagnosis of systemic disease was 5.6 years, underscoring that HPGW patients often present with a rash that precedes the development of systemic symptoms. CONCLUSIONS: Diagnosis of HGPW should prompt initial screening for rheumatologic disease with long-term rheumatology follow-up, as the majority of patients present with evolving manifestations of systemic disease.
33489063 Time-averaged disease activity of rheumatoid arthritis associated with long-term bone mine 2020 BACKGROUND: Rheumatoid arthritis (RA) is associated with poor bone mineral density (BMD). We designed the current study owing to the lack of long-term prospective studies regarding whether a high disease activity leads to increased bone loss. METHODS: We have continually enrolled patients with RA. According to the average disease activity score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) during follow-up, the patients were classified into remission, low disease activity, and moderate or high disease activity groups. Patients were examined with dual-energy X-ray absorptiometry at baseline and after 3 years of follow-up. BMD changes were compared among the groups. RESULTS: We have studied 477 patients. Overall BMD was significantly reduced from baseline to the 3-year follow-up (p < 0.05). After stratifying according to the time-averaged DAS28-ESR levels and use of anti-osteoporosis treatment (AOT), the BMD values of the femur and spine significantly increased in patients in the remission group with AOT. The BMD changes of different DAS28-ESR patients were further compared using the generalized estimation equation model. For the patients on AOT, the negative change in femoral BMD values of the moderate or high activity group was significant when compared with the remission group with positive BMD changes (regression coefficient, -0.038; 95% confidence interval, -0.055 to -0.021). CONCLUSION: For RA patients, if remission is achieved, AOT can better improve BMD, especially in the femur. In addition, moderate or high disease activity will lead to significant bone loss; therefore, disease activity must be actively controlled.
33447265 Methotrexate at middle and high accumulative doses might be associated with lower risk of 2020 BACKGROUND: We investigated whether taking methotrexate (MTX) is associated with a lower risk of new-onset cancers in patients with rheumatoid arthritis (RA). METHODS: We conducted a 12-year retrospective cohort study from a population-based National Health Insurance Research Database in Taiwan. A total of 21,699 patients with newly diagnosed RA were enrolled during 2000-2009. The overall cancer rate was compared between 10,352 new users of MTX and 11,347 non-users. We used the WHO Defined Daily Dose (DDD) as a tool to assess drug exposure. Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of disease after controlling for demographics and other comorbidities. RESULTS: After adjusting for age, sex, cancer-related comorbidities, and RA-combined medication, the HR of cancer risk was 0.87 (95% CI = 0.74-1.02) for the MTX user group compared with the MTX non-user group. The cumulative incidence of cancer in the MTX non-user group was significantly higher than that of the MTX user group (log-rank test p < 0.001). In the low accumulative dose group [cumulative dose <1125 mg, cumulative defined daily dose (cDDD) <450], the HR of cancer risk for MTX users was 1.20 (95% CI = 1.01-1.42) compared with the MTX-non-user group. However, the adjusted HR of cancer risk was reduced to 0.66 (95% CI = 0.49-0.87) in MTX middle-dose users (cumulative dose 1125-2250 mg, cDDD: 450-899) and 0.33 (95% CI = 0.23-0.48) for the MTX high-dose group (cumulative dose ⩾2250 mg, cDDD ⩾900), respectively (p for trend < 0.0001). CONCLUSION: MTX at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with RA.
33292831 Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admi 2020 Dec 4 BACKGROUND: Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs). METHODS: This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU. RESULTS: Upon admission, the median age was 70 (range, 33-96) years, and RA duration was 10 (range, 0-61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson's comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission. CONCLUSION: Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.
32851365 Efficacy and Safety of Opinercept Tumor Necrosis Factor Inhibitor Therapy for Drug-Refract 2020 Jun OBJECTIVES: This study aims to evaluate the efficacy and safety profile of opinercept for rheumatoid arthritis (RA) patients undergoing disease- modifying anti-rheumatic drugs (DMARDs) therapy. PATIENTS AND METHODS: A total of 98 patients with active RA (17 males, 81 females; mean age 58.6±12.2 years; range, 24.3 to 85.3 years) were randomized into opinercept plus DMARDs (OD group) or placebo plus DMARDs (PD group), in a 24-week treatment period. Primary outcome was American College of Rheumatology score (ACR20) at week 24. Other exploratory endpoints included ACR50, ACR70 and disease activity score-28 (DAS28) at week 12 and 24, tender/swollen joint counts, pain, Health Assessment Questionnaire-Disability Index, erythrocyte sedimentation rate, and C-reactive protein level. Incidence of adverse events (AEs), vital signs and physical findings, and laboratory test results were also evaluated. RESULTS: Patients in OD group showed significantly higher achievement percentage of ACR20 at week 24 than the PD group (76.6% vs. 30.3%, p<0.001). The evaluation of DAS28 was significantly improved in OD patients compared to PD patients at weeks 12 and 24. Most of the occurred AEs were mild or moderate and considered unrelated to study treatments. CONCLUSION: Opinercept concurrent with DMARDs was superior to DMARDs alone in slowing RA progression and ameliorating symptoms, with well- tolerated and acceptable safety profile.
32336980 Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with me 2020 BACKGROUND: Biqi capsule is a traditional Chinese medicine widely used as a complementary and alternative treatment for rheumatoid arthritis (RA). The objective is to understand the efficacy, safety and mechanism of Biqi combined with methotrexate (MTX) in RA. METHODS: We present a randomized, controlled pilot trial on Biqi combined with MTX against patients with active RA. Seventy patients were randomized 1:1 to receive Biqi + MTX or Leflunomide (LEF) + MTX for 24 weeks, and were assessed at baseline, 4, 12 and 24 weeks. Serum and urine samples were collected for metabolomics. RESULTS: Overall, 81.2% patients in Biqi group achieved ACR20 at 24 weeks. No statistically significant differences were observed in primary or secondary outcomes between the two groups. A better safety profile was observed for Biqi with significantly fewer adverse effects reported (11.4%) compared to LEF group (40%, P < 0.05). Comparison between treatment responders and non-responders indicated a unique urine metabolic profile of enriched fatty acids and decreased acylcarnitines associated with Biqi responders, indicating a restored energy homeostasis in response to Biqi. The gene targets of these metabolites were significantly enriched in interleukin-4 and interleukin-13 pathways, implying that Biqi could ameliorate Th2-derived inflammatory response. Multivariate network analysis indicated that patient morning stiffness and SJC were key factors associated with metabolomics in Biqi-treated patients, whereas CRP was the main factor in LEF group. Therefore, Biqi and LEF likely work by influencing different patient clinical parameters. CONCLUSIONS: Our study suggests that Biqi capsule can be a promising alternative option in combination with MTX for RA treatment, and demonstrates the capability of using metabolomics to interrogate mechanism of action for traditional Chinese medicine.Trial registration This trial is registered with ChiCTR, No. ChiCTR-IPR-16009029. Registered August 15, 2016. http://www.chictr.org.cn/showprojen.aspx?proj=15034.
32175525 Nutrition in RMDs: is it really food for thought? Focus on rheumatoid arthritis. 2020 BACKGROUND: The relationship between food and health is known since the antiquity and in the field of rheumatic and musculoskeletal diseases (RMDs), mainly rheumatoid arthritis (RA), a large number of studies has been published over the last 50 years encompassing different aspects of nutrition. This led to postulate a role of nutrients for both primary prevention of RMDs in the general population and secondary prevention of disease flares and complications in patients with an established RMD. MAIN BODY OF ABSTRACT: We aimed to summarise and critically discuss current evidence on the role of different nutrients and dietary regimens in RMDs with a focus on RA. Over the last years, some seminal papers proved that some compounds, such as salt, can directly modulate the immune system and large epidemiological studies have been linking dietary patters with the risk to develop RMDs. However, physicians' knowledge about the role of diet in disease prevention and treatment is often poor and ultimately diet is rarely perceived as a companion of pharmacological treatment. CONCLUSIONS: Based on the currently available evidence, we are not (yet?) in the phase of putting diet on the same level as pharmacological treatment in RMDs and in particular, RA, but future studies will likely shed additional light on this controversial topic and at least might suggest a value as dietary prevention of risk factors.
32161847 Racial disparities in pre-operative pain, function and disease activity for patients with 2020 BACKGROUND: Black and Hispanic patients with osteoarthritis have more pain and worse function than Whites at the time of arthroplasty. Whether this is true for patients with rheumatoid arthritis (RA) is unknown. METHODS: This cross-sectional study used data on RA patients acquired between October 2013 and November 2018 prior to elective total knee (TKA) or hip arthroplasty (THA). Pain, function, and disease activity were assessed using the visual analogue scale (VAS), the Multidimensional Health Assessment Questionnaire (MDHAQ), and the Disease Activity Score (DAS28-ESR). We linked the cases to census tracts using geocoding to determine the community poverty level. Race, education, income, insurance and medications were collected via self-report. Using multivariable linear and logistic models we examined whether minority status predicted pain, function and RA disease activity at the time of arthroplasty. RESULTS: Thirty seven (23%) of the 164 patients were Black or Hispanic (minorities). The MDHAQ and DAS28-ESR were not significantly worse while VAS pain score was significantly worse in minority patients (p = 0.03). There was no significant difference in education between the groups. Insurance varied significantly; 29% of minority patients had Medicaid vs. 0% of Whites (p < 0.0001). In the multivariable analyses minority status was not significantly associated with DAS28-ESR [p = 0.66], MDHAQ [p = 0.26], or VAS pain [p = 0.18]. CONCLUSIONS: For Black and/or Hispanic patients with RA undergoing THA or TKA at a high-volume specialty hospital, unlike Black or Hispanic patients with osteoarthritis (OA), there was no association with worse pain, function, or RA disease activity at the time of elective arthroplasty.
33339369 The Performance of Vascular Age in the Assessment of Cardiovascular Risk of Patients with 2020 Dec 16 Background. Cardiovascular (CV) disease risk prediction models developed for use in the general population have suboptimal performance in patients with rheumatoid arthritis (RA). Vascular age (VA) is a new concept that has been proposed as a measure of CV 'relative' risk instead of the 'absolute' risk that current prediction models provide. In the present study we aim to study the performance of vascular age (VA) in the assessment of CV risk in patients with RA. We additionally aimed to analyze its relation with subclinical atherosclerosis as measured through carotid plaque ultrasound. Methods. A total of 1173 non-diabetic RA patients without previous CV events were included. Disease characteristics, SCORE, VA determined on SCORE and on carotid intima media thickness (cIMT), and the presence of plaque through carotid ultrasound were assessed. The interrelations of VA with SCORE, and its associations with subclinical carotid atherosclerosis were studied. Results. On average, RA patients had both a SCORE determined VA (4.7 years) and a cIMT-based VA (2.4 years) significantly higher than the chronological age. When these differences were analyzed in different age intervals, while VA based on SCORE was significantly higher compared to chronological age in all age ranges, VA determined on cIMT was significantly elevated only in RA patients younger than 60 years. The area under the curve analysis for the association of SCORE and VA with the presence of carotid plaque disclosed no differences between both parameters. VA was associated with the presence of carotid plaque after multivariable regression analysis in patients younger than 60 years old. Conclusion. VA is significantly higher than chronological age in patients with RA. The performance of VA in its relation to carotid plaque is similar to that of the SCORE.
32922525 Reduced skeletal muscle independently predicts 1-year aggravated joint destruction in pati 2020 BACKGROUND: Numerous cross-sectional studies have reported the associations between rheumatoid arthritis (RA) and reduced skeletal muscle. We firstly explored the dynamic change of skeletal muscle and its effect on RA clinical outcomes in a real-world prospective cohort. METHODS: Consecutive RA patients were treated according to the treat-to-target strategy and completed at least 1-year follow up. Clinical data and muscle index (assessed by bioelectric impedance analysis) were collected at baseline and visits at 3, 6, 9 and 12 months. Myopenia was defined by appendicular skeletal muscle mass index ⩽7.0 kg/m(2) in men and ⩽5.7 kg/m(2) in women. A 1-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ⩾0.5 units. RESULTS: Among 348 recruited patients, 315 RA patients (mean age 47.9 years, 84.4% female) completed 1-year follow up. There were 143 (45.4%) RA patients showing myopenia at baseline. Compared with those without baseline myopenia, RA patients with baseline myopenia had higher rate of 1-year radiographic progression (43.4% versus 21.5%, all p < 0.05). Baseline myopenia was an independent risk factor for 1-year radiographic progression with adjusted odds ratio (AOR) of 2.5-fold, especially among RA patients in remission at baseline both defined by Disease Activity Score in 28 joints (DAS28) including C-reactive protein (DAS28-CRP) or erythrocyte sedimentation rate (DAS28-ESR) with AOR of 18.5~42.9-fold. Further analysis of six subtypes of dynamic skeletal muscle change showed that newly acquired myopenia at endpoint was associated with radiographic progression (AOR of 5.4-fold). CONCLUSIONS: Reduced skeletal muscle is an independent predicting factor for 1-year aggravated joint destruction, especially in remission RA. The importance of dynamic monitoring of skeletal muscle and muscle improvement therapy are worth exploration.
32752190 GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomar 2020 Aug 1 This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p < 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p < 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response.
32650513 Anti-atherogenic Modification of Serum Lipoprotein Function in Patients with Rheumatoid Ar 2020 Jul 8 Lipid metabolism derangement contributes to increased cardiovascular risk in Rheumatoid Arthritis (RA). It is still debated whether and how tocilizumab, an interleukin-6 receptor inhibitor used in active RA, impacts cardiovascular risk. We studied the effect of tocilizumab on the regulation of macrophage cholesterol homeostasis, measuring patient serum ability to respectively load (cholesterol loading capacity, CLC) and discharge (cholesterol efflux capacity, CEC) cells with cholesterol. Patients with RA (n = 8) were studied before and after 4 and 12 weeks of tocilizumab treatment. CLC was measured by a fluorimetric assay of intracellular cholesterol content in human macrophages and CEC was measured for the three main pathways, mediated by the transporters Scavenger Receptor class B-type I (SR-BI), ATP binding cassette-G1 (ABCG1) and -A1 (ABCA1) in specific cell models. After 12 weeks of tocilizumab treatment, serum LDL cholesterol levels were increased, while CLC was reduced. HDL cholesterol levels were unchanged, but CEC was significantly ameliorated for the SR-BI and ABCG1 pathways with respect to baseline. Tocilizumab reduces LDL pro-atherogenic potential despite increasing their serum levels and increases HDL protective activity in RA. The data of our pilot study suggest that tocilizumab regulates lipoprotein function in selected patient populations and lay the groundwork for future larger studies.
32299258 Exosomes Represent an Immune Suppressive T Cell Checkpoint in Human Chronic Inflammatory M 2020 Oct Background: T cells present in chronic inflammatory tissues such as nasal polyps (from chronic rhinosinusitis patients) have been demonstrated to be hypo-responsive to activation via the TCR, similar to tumor-specific T cells in multiple different human tumor microenvironments. While immunosuppressive exosomes have been known to contribute to the failure of the tumor-associated T cells to respond optimally to activation stimuli, it is not known whether they play a similar role in chronic inflammatory microenvironments. In the current study, we investigate whether exosomes derived from chronic inflammatory microenvironments contribute to the immune suppression of T cells. Methods: Exosomes were isolated by ultracentrifugation and characterized by size and composition using nanoparticle tracking analysis, scanning electron microscopy, antibody arrays and flow exometry. Immunosuppressive ability of the exosomes was measured by quantifying its effect on activation of T cells, using nuclear translocation of NFκB as an activation endpoint. Results: Exosomes were isolated and characterized from two different types of chronic inflammatory tissues - nasal polyps from chronic rhinosinusitis patients and synovial fluid from rheumatoid arthritis patients. These exosomes arrest the activation of T cells stimulated via the TCR. This immune suppression, like that which is seen in tumor microenvironments, is dependent in part upon a lipid, ganglioside GD3, which is expressed on the exosomal surface. Conclusion: Immunosuppressive exosomes present in non-malignant chronic inflammatory tissues represent a new T cell checkpoint, and potentially represent a novel therapeutic target to enhance the response to current therapies and prevent disease recurrences.
33223115 Ethyl acetate extract of Tibetan medicine Rhamnella gilgitica ameliorated type II collagen 2021 Mar 1 ETHNOPHARMACOLOGICAL RELEVANCE: Rhamnella gilgitica Mansf. et Melch. (སེང་ལྡེང་།, RG) is a traditional Tibetan medicinal plant that is currently grown throughout Tibet. According to the theory of Tibetan medicine, RG is efficient for removing rheumatism, reducing swelling, and relieving pain. Hence, it has been used for the treatment of rheumatoid arthritis (RA) in Tibet for many years. However, there are no previous reports on the anti-RA activities of ethyl acetate extract of RG (RGEA). AIM OF THE STUDY: This study aimed to explore the anti-RA effect and mechanism of RGEA on collagen-induced arthritis (CIA) in rats. MATERIALS AND METHODS: The CIA model was established in male Wister rats by intradermal injection of bovine type II collagen and Complete Freund's Adjuvant at the base of the tail and left sole, respectively. The rats were orally administered with RGEA (9.71, 19.43, or 38.85 mg/kg) for 23 days. The body weight, swelling volume, arthritis index score, thymus and spleen indices, and pathological changes were observed to evaluate the effect of RGEA on RA. Furthermore, the inflammatory cytokines in serum, such as interleukin1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin6 (IL-6), interleukin17 (IL-17), interferon-γ (INF-γ), interleukin4 (IL-4), and interleukin10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA) to explore the anti-inflammatory effects of RGEA. The terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was used to examine apoptosis. Finally, the protein and gene expression of B-cell lymphoma-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), Caspase3, janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling1 (SOCS1), and 3 (SOCS3) in synovial tissue were detected using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: After the treatment with RGEA, the body weight of rats was restored, both the arthritis index and paw swelling were suppressed, and spleen and thymus indices were decreased. RGEA reduced the inflammatory cells and synovial hyperplasia in the synovial tissue of the knee joint, and suppressed bone erosion. Meanwhile, RGEA decreased the levels of IL-1β, IL-6, IL-17, TNF-α, and INF-γ, while increased the levels of IL-4 and IL-10. TUNEL fluorescence apoptosis results confirmed that RGEA obviously promoted the apoptosis of synovial cells. Further studies showed that RGEA inhibited the proteins and mRNAs expression of JAK2 and STAT3 as well as increased the proteins and mRNAs expression of SOCS1 and SOCS3. In addition, RGEA upregulated the expression of Bax and Caspase3, and downregulated the expression of Bcl-2. CONCLUSION: The anti-RA effectof RGEA might be related to the promotion of apoptosis and inhibition of inflammation, which regulated the JAK-STAT pathway.
32838587 Interferon gamma/interleukin-4 modulation, anti-inflammatory and antioxidant effects of he 2020 Oct BACKGROUND: This study sought to assess the effect of hesperidin on serum inflammatory cytokines and oxidative damage in liver of complete Freund's adjuvant (CFA)-induced arthritic rats. METHOD: Fifty-six adult female Wistar rats (220-250 g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14th day prior to oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days. RESULT: The result showed that treatment with both doses of hesperidin and dexamethasone in the joint of arthritic rats significantly (p < .05) diminished paw swelling/edema and arthritis score as well as enhanced latency in thermal hyperalgesia test. In addition, hesperidin treatment in arthritis rats showed significant (p < .01) improvement in red blood cells and platelets counts as well as hemoglobin and hematocrit compared to the arthritis control rat group. Furthermore, hesperidin treatment significantly (p < .05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < .05) decreased the liver of thiobarbituric acid reactive species and reactive oxygen species levels but raised the levels of total and non-protein thiols of rat induced with CFA. The reduced activities of liver δ-aminolevulinate dehydratase, catalase, glutathione-S transferase in arthritic rats were significantly (p < .05) increased with hesperidin treatment in arthritic rats. This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of serum IFN-γ and IL-4 levels as well as protection against oxidative damage. CONCLUSION: Hence, hesperidin could be a potential immune-modulatory, anti-inflammatory and anti-oxidant agent.
32889506 Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients w 2020 Nov OBJECTIVES: The diagnosis of primary Sjogren's syndrome (pSS) continues to be difficult and several patients keep symptomatic for years with different diagnoses before confirmation of pSS. Since the IL-23-IL-17 axis is involved in the etiopathogenesis of pSS we evaluated by immunohistochemistry and morphometric methods the presence of IL-17 as well as IL-23 within minor salivary glands (MSG) obtained from patients with uncertain diagnosis of pSS. MATERIALS AND METHODS: 42 patients, with symptoms attributable to pSS, and 8 patients used as a control, were enrolled for the study. Autoantibody detection, histological analysis for the presence of Germinal Centers (GC+), immunohistochemistry to detect IL-23 and IL-17 were performed. RESULTS: The detection of GC + anti-SSA and anti-SSB antibody in parallel with the detection of IL-17 and IL-23, displays only a diagnostic reinforcement value. Instead, the detection of a positive reaction for both IL-17 and IL-23 without GC + or autoantibody within minor salivary glands, as detected in 36 % of patients with uncertain diagnosis, may be hold as a sensitive and specific marker to identify those patients who are likely to evolve into pSS. CONCLUSION: we suggest to use the IL-17/ IL-23 immunohistochemical detection to improve the identification of patients with a possible diagnosis in all cases which do not fully meet the American-European criteria for pSS, in particular when the GC + are not present at histopathological analysis and anti-SSA and anti-SSB antibody are undetectable in the serum.
33135351 Inferences of individual differences in response to tripterysium glycosides across patient 2020 Oct BACKGROUND: To identify biomarkers for guiding therapy and predicting clinical response of Tripterysium Glycosides Tablets (TGT) treatment is an urgent task due to individual differences in TGT response across rheumatoid arthritis (RA) patients. Competing endogenous RNA (ceRNA) regulatory system may influence drug response with involvement in diverse biological processes. Herein, we aimed to identify a TGT response-related ceRNA axis. METHODS: A TGT response-related ceRNA axis was screened according to clinical cohort-based RNA expression profiling, lncRNA-mRNA coexpression, and ceRNA network analyses. Its clinical relevance was evaluated by computational modeling. Regulatory mechanisms of ceRNA axis were also experimentally investigated. RESULTS: The ceRNA regulatory axis combined with lncRNA ENST00000494760, miR-654-5p, and C1QC was identified as a candidate biomarker for RA patients' response to TGT. Both ENST00000494760 and C1QC mRNA expression were significantly lower, while miR-654-5p expression was dramatically higher in TGT responders than nonresponders. Its clinical relevance was verified by computational modeling based on both independent clinical validation cohort and collagen-induced arthritis (CIA) mice. Mechanistically, miR-654-5p directly bound to the 3'-untranslated region of both ENST00000494760 and C1QC mRNA to inhibit their expression. Moreover, miR-654-5p suppressed C1QC mRNA expression, but ENST00000494760 bound to miR-654-5p and relieved its repression on C1QC mRNA, leading to RA aggressive progression and weak TGT response. CONCLUSIONS: LncRNA ENST00000494760 overexpression may sponge miR-654-5p to promote C1QC expression in RA patients. This novel ceRNA axis may serve as a biomarker for screening the responsive RA patients to TGT treatment, which will allow improved personalized healthcare.