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OBJECTIVE: Previous studies have reported that the inappropriate use of allopurinol may increase the risk of cerebrovascular accidents, but some studies have also confirmed that allopurinol is a protective factor against stroke. To clarify whether there is a relevant causal relationship between allopurinol and cerebral infarction, we conducted a two-sample Mendelian randomization (MR) study. METHODS: Data on single nucleotide polymorphisms (SNPs) associated with allopurinol and genome-wide association studies of cerebral infarction were obtained from the genome-wide association study (GWAS) web site. Five basic MR analyses were performed using MR-Egger regression, weighted median (WM1), inverse variance weighting (IVW), weighted mode (WM2), and simple mode. Sensitivity analysis was subsequently performed to detect horizontal pleiotropy, heterogeneity, and potential outliers. The final analysis results were mainly based on the IVW estimates. RESULTS: A total of 10 SNPs were used as instrumental variables (IVs). MR analysis [(IVW: odds ratio (OR) = 1.053, 95% confidence interval (CI): 1.019-1.088, P = 0.002), (WM1: OR = 1.053, 95% CI: 1.009-1.098, P = 0.017), (WM2: OR = 1.050, 95% CI: 1.008-1.095, P = 0.044), (MR Egger: Q = 4.285, P = 0.830)] showed a positive causal association between allopurinol and the risk of cerebral infarction. Sensitivity analysis such as horizontal pleiotropy and heterogeneity increased the reliability of this result. CONCLUSION: The results of this study provide direct evidence that there is a causal relationship between allopurinol and cerebral infarction and that allopurinol may increase the risk of cerebral infarction.
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Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.
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BACKGROUND: Previous studies have reported low serum 25-hydroxyvitamin D [25(OH)D] levels in dermatomyositis (DM) patients, but the exact causal relationship between them remains elusive. Our aim is to confirm the causal relationship between 25(OH)D and DM risk through a Mendelian randomization study. METHODS: Retrieve genome-wide association study (GWAS) data on 25(OH)D (n = 441 291) and DM (n cases = 201, n controls = 172 834) from the GWAS database (https://gwas.mrcieu.ac.uk/). Select single-nucleotide polymorphisms (SNPs) strongly correlated with 25(OH)D as instrumental variables (IVs). The primary analytical approach involves the use of the inverse-variance weighted method (IVW), supplemented by MR-Egger regression and weighted median methods to enhance the reliability of the results. Heterogeneity and sensitivity analyses were conducted using Cochran's Q and leave-one-out approaches, respectively. RESULTS: The IVW analysis confirmed a positive causal relationship between genetic variation in 25(OH)D levels and DM (OR = 2.36, 95% CI = 1.01-5.52, p = .048). Although not statistically significant (all p > .05), the other methods also suggested a protective effect of 25(OH)D on DM. Based on MR-Egger intercepts and Cochran's Q analysis, the selected SNPs showed no horizontal pleiotropy and heterogeneity. Sensitivity analysis demonstrated the robustness of the results against individual SNPs. CONCLUSION: We provide the first evidence of a causal relationship between 25(OH)D levels and DM. Our findings support the importance of measuring serum 25(OH)D levels and considering vitamin D supplementation in clinical practice for patients with DM.
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Dermatomiositis , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Vitamina D , Humanos , Vitamina D/análogos & derivados , Vitamina D/sangre , Dermatomiositis/genética , Dermatomiositis/sangre , Dermatomiositis/diagnóstico , Dermatomiositis/epidemiología , Factores de Riesgo , Predisposición Genética a la Enfermedad , Biomarcadores/sangre , Medición de Riesgo , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Estudios de Casos y Controles , Fenotipo , Bases de Datos GenéticasRESUMEN
INTRODUCTION: Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. METHODS: We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. RESULTS: Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362-0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. CONCLUSION: The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.
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OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.
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Anticuerpos Monoclonales Humanizados , Lupus Eritematoso Sistémico , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estudios Retrospectivos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Resultado del Tratamiento , Trombocitopenia/tratamiento farmacológico , Inmunosupresores/efectos adversos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The main subtypes of idiopathic inflammatory myopathies (IIMs)-polymyositis (PM) and dermatomyositis (DM)-are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. METHODS: Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. RESULTS: A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti-mda5 antibody, mortality, gene 5 antibody, IIMs, double-blind, and prognostic factors, among others, may be new hot topics. CONCLUSION: This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Polimiositis , Humanos , Dermatomiositis/epidemiología , Dermatomiositis/complicaciones , Estudios Retrospectivos , Polimiositis/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Pronóstico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.
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Artritis Experimental , Artritis Reumatoide , Ácido Gálico/análogos & derivados , MicroARNs , Animales , Ratones , Vía de Señalización Hippo , Microtomografía por Rayos X , Artritis Reumatoide/metabolismo , Artritis Experimental/inducido químicamente , MicroARNs/genética , Inflamación/metabolismo , Luciferasas/metabolismo , Luciferasas/farmacología , Luciferasas/uso terapéutico , Proliferación Celular , Fibroblastos , Células CultivadasRESUMEN
OBJECTIVES: In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. METHODS: A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. RESULTS: Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). CONCLUSIONS: Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.
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Gota , Inhibidores de la Bomba de Protones , Persona de Mediana Edad , Humanos , Masculino , Femenino , Inhibidores de la Bomba de Protones/efectos adversos , Estudios de Casos y Controles , Esomeprazol , Gota/inducido químicamente , Gota/diagnóstico , Gota/tratamiento farmacológico , Seguro de Salud , Factores de RiesgoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint swelling, pain, and deformation. RA patients have an increased risk of thyroid dysfunction, and drugs of RA treatment may have potential effects on thyroid function. METHODS: This is a single-center cross-sectional study including 281 inpatients with RA in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The purpose of this study is to explore the correlation between RA therapeutic drugs and thyroid function. The medical records of 281 inpatients with RA were collected, including general data, laboratory examination, complications, and RA treatment. Spearman correlation analysis was used to explore the association of independent variables with thyroid function and antibodies in RA patients. Multinomial logistics and binary logistic regression were used for multivariate analysis. The statistically significance level was set as P < 0.05. SPSS 22.0 was used for statistical analysis. RESULTS: Patients taking methotrexate (OR = 0.067, 95%CI: 0.008-0.588, P = 0.015) had lower levels of total thyroxine (TT4) (TT4 < 78.38 nmol/L). There was a negative correlation between glucocorticoids (r = - 0.153, P = 0.010) and total triiodothyronine (TT3) level (TT3 ≥ 1.34 nmol/L), but it was not significant in the multivariate regression model of TT3, although the regression model was statistically significant (P = 0.001). CONCLUSION: Methotrexate is associated with decreased TT4 levels in RA patients, and glucocorticoids is associated with decreased TT3 levels. Drugs of RA treatment may affect the thyroid function of patients while treating RA, which may be one of the causes of secondary thyroid diseases in RA patients.
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Artritis Reumatoide , Tiroxina , Humanos , Metotrexato/efectos adversos , Estudios Transversales , Glucocorticoides , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
Dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of rheumatoid arthritis (RA). Our previous studies confirmed that Duanteng Yimu decoction (DTYMT) effectively inhibits RA fibroblast-like synoviocyte (FLS) proliferation. In this study, we investigated the influence of DTYMT on miR-221 in RA individuals. Hematoxylin-eosin (HE) staining was performed to assess histopathological alterations in collagen-induced arthritis (CIA) mice. The expression of miR-221-3p and TLR4 in PBMC, FLS, and cartilage was measured by RT-qPCR. In the in vitro experiments, DTYMT-containing serum was incubated with FLS-transfected miR-221 mimic or inhibitor. CCK-8 was performed to determine FLS proliferation, and the secretion of IL-1ß, IL-6, IL-18, and TNF-α was quantified by ELISA assay. In addition, the regulation of miR-221 expression on FLS apoptosis was assessed using flow cytometry. Finally, western blot was employed to reflect TLR4/MyD88 protein levels. HE results showed that DTYMT effectively reduced synovial hyperplasia in the joints of CIA mice. RT-qPCR assay of FLS and cartilage of the model group showed that miR-221-3p and TLR4 significantly increased compared with those in the normal group. All outcomes were improved by DTYMT. The miR-221 mimic reversed the inhibitory effect of DTYMT-containing serum on FLS proliferation, the release of IL-1ß, IL-18, IL-6, and TNF-α, and FLS apoptosis, as well as TLR4/MyD88 protein levels. The results showed that miR-221 promotes the activity of RA-FLS by activating TLR4/MyD88 signaling, and DTYMT treats RA by reducing miR-221 in CIA mice.
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Artritis Experimental , Artritis Reumatoide , MicroARNs , Sinoviocitos , Animales , Ratones , Interleucina-18/metabolismo , Receptor Toll-Like 4/metabolismo , Hiperplasia/tratamiento farmacológico , Hiperplasia/metabolismo , Hiperplasia/patología , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Leucocitos Mononucleares/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Proliferación Celular , Artritis Reumatoide/metabolismo , Sinoviocitos/metabolismo , MicroARNs/metabolismo , Artritis Experimental/patología , Fibroblastos/metabolismo , Membrana Sinovial/patología , Células CultivadasRESUMEN
Background: Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. Methods: Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1ß, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. Results: Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1ß, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. Conclusions: These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.
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INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Lupus nephritis (LN) is a common type of organ damage which occurs in SLE patients and is characterized by recurrent proteinuria. Activation of B lymphocytes can lead to refractory LN, which is an important pathogenic factor in SLE. B lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL) are predominantly produced by myeloid cells (monocytes, dendritic cells, neutrophils, etc) to regulate B lymphocyte function. Telitacicept was the first dual-targeting biological drug which targeted both BLyS and APRIL. Telitacicept has passed a phase II clinical trial and has since been approved for the treatment of SLE. CASE PRESENTATION: We report a case of SLE confirmed by renal biopsy as proliferative lupus nephritis (PLN) with massive proteinuria, which was treated with telitacicept (European League Against Rheumatism / American College of Rheumatology 2019 standard). During the 19 months of follow-up, the patient's renal function was stable, massive proteinuria was relieved, and creatinine and blood pressure did not increase. CONCLUSIONS: During the 19 months of telitacicept treatment (160 mg once weekly), PLN reduced blood system damage and proteinuria without increasing the risk of infection.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , BlancoRESUMEN
OBJECTIVE: Typically, Jaccoud arthropathy (JA) is characterized by joint deformation without bone erosion. However, some recent studies have shown that bone erosion also occurs in JA; however, this remains controversial. To date, there have been no unified diagnostic standards for JA. Herein, we report a case of systemic lupus erythematosus complicated with JA without bone erosion. METHODS: A 27-year-old woman was admitted to our department with a 2-year history of pain, swelling, and progressive deformities of her hands and feet. She was diagnosed with systemic lupus erythematosus and class V lupus nephritis 5 years prior. Upon examination, her erythrocyte sedimentation rate and C-reactive protein levels were found to be increased. She was positive for antinuclear antibodies, antidouble stranded DNA antibodies, and antiextractable nuclear antigen antibodies, with a decreased complement C3 and C4. Radiography and magnetic resonance imaging revealed no bone erosion. The patient was diagnosed with JA. She was treated with oral prednisone (10 mg daily), tofacitinib (5 mg twice daily), methotrexate (10 mg weekly), and celecoxib (0.2 g twice daily). RESULTS: The patient's joint symptoms improved after treatment. No further progress was observed during the 4-month follow-up period. CONCLUSION: We believe that bone erosion is the key to distinguish rhupus syndrome from JA. However, this needs to be confirmed with further long-term follow-up studies. We found that the use tofacitinib, MTX, and celecoxib in combination with prednisone may be an effective regimen for the treatment of JA.
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Artritis Reumatoide , Lupus Eritematoso Sistémico , Adulto , Anticuerpos Antinucleares , Antígenos Nucleares , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Proteína C-Reactiva , Celecoxib , Complemento C3 , ADN , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metotrexato , PrednisonaRESUMEN
Quercetin is widely found in natural plants, especially Chinese herbal plants. It has been used to treat arthritis in China for thousands of years. However, the effects and mechanisms of quercetin in the treatment of gout arthritis (GA) remain unclear. We aimed to verify the treatment of GA with quercetin and investigate the underlying mechanism. A combination of network pharmacology and experiments was used to reveal the mechanism of quercetin in the treatment of GA. Potential targets of quercetin and gout were identified. Then, the protein-protein interaction network for the common targets between quercetin and gout was constructed and the core targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the common targets were performed to elucidate the pharmacological functions and mechanisms associated with quercetin treatment in GA. Finally, a monosodium urate-induced GA rat model was used to validate the predicted mechanisms in network pharmacology. Seventy-two common targets were identified. KEGG analysis revealed that treatment of GA with quercetin predominantly involved the interleukin (IL)-17, tumor necrosis factor (TNF), mitogen-activated protein kinase, and phosphoinositide 3-kinase-Akt signaling pathways. In an experimental validation, quercetin attenuated ankle joint inflammation-induced bone destruction and histological lesions. It also diminished the expression of IL-6, IL-17A, and IL-17F in the IL-17 pathway, and regulated the release of RAR-related orphan receptor gamma t,IL-17E, IL-1ß, IL-6, TNF-α, Foxp3, and transforming growth factor-beta 1. The collective findings implicate quercetin as a valuable alternative drug for the treatment of GA.
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Artritis Gotosa , Medicamentos Herbarios Chinos , Gota , Animales , Artritis Gotosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Gota/tratamiento farmacológico , Interleucina-6/uso terapéutico , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Quercetina/uso terapéutico , RatasRESUMEN
Rheumatoid arthritis (RA) is a heterogeneous chronic disease. RA patients should start disease modifying anti-rheumatic drugs (DMARDs) therapy immediately after diagnosis. If first-line treatment with conventional synthetic DMARDs does not relieve the disease, biology and targeted synthetic DMARDs are options for patients. Patients can switch to different types of biological and targeted synthetic DMARDs if remission is not achieved. However, for patients with difficult-to-treat RA, achieving disease stabilization after the failure of multiple biological and targeted synthetic DMARDs is a clinical challenge that needs to be addressed. As distinct cytokine pathways, the benefits and challenges of dual therapy are worth discussing. As the most extensively used biologic DMARDs, adalimumab is an anti-tumor necrosis factor monoclonal antibody used to treat RA. Tofacitinib, as a Janus Kinase inhibitor, is an orally administered targeted synthetic DMARDs that involved in the regulation of immune responses by directly or indirectly inhibiting cytokine pathways. This report describes a successful case of a 48-year-old woman with difficult-to-treat RA who treated with Tofacitinib combined with adalimumab. She had been on glucocorticosteroid for a long time, but had persistent joint pain and fatigue. At more than one year of follow-up, her Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-ESR) remained in complete remission, and she discontinued her glucocorticosteroid medications. Also, she did not develop a mycobacterial tuberculosis infection, herpes zoster, and new-onset cardiovascular events.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Femenino , Persona de Mediana Edad , Metotrexato/uso terapéutico , Adalimumab/uso terapéutico , Productos Biológicos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Antirreumáticos/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: Previous studies have shown that increased neutrophils, as a manifestation of oxidative stress, may be involved in the progression of kidney disease. To our knowledge, little is known about the relationship between neutrophils and renal impairment in rheumatoid arthritis (RA). Therefore, we aim to investigate whether neutrophil is associated with renal impairment in RA patients. METHODS: We retrospectively investigated the renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (eGFR) from September 2018 and September 2019. The exposure variable was neutrophils, and the main outcome was eGFR. General data (gender, age, duration, hypertension, diabetes, hobbies, and medication history), whole blood markers, lipid indexes, and inflammatory indexes were collected as much as possible. We used multivariable logistic regression analysis to evaluate the association between neutrophils and renal impairment in RA participants. RESULTS: A total of 89 cases (14.8%) had renal impairment with eGFR < 60 ml/min/1.73 m2 , and 75 cases (84.3%) were female. Subgroup analysis showed that female (odds ratio [OR] = 0.523, 95% confidence interval [CI]: 0.318-0.867, p = .011), neutrophils greater thsn 7.5 × 109 /L (OR = 2.314, 95% CI: 1.310-4.087, p = .004), NLR > 3.53 (OR = 1.757, 95% CI: 1.104-2.799, p = .018), hemoglobin less than 120 g/L (OR = 2.413, 95% CI: 1.418-4.118, p = .001), and UA > 360 µmol/L (OR = 6.052, 95% CI: 3.708-9.878, p < .001) was related to renal damage in RA. Adjusted for several confounders, the multivariable analysis indicated that neutrophils greater than 7.5 × 109 /L (OR = 1.784, 95% CI: 1.164-3.288, p = .031) was independently associated with an increased risk of renal impairment in RA. CONCLUSION: Our study demonstrated that neutrophils greater than 7.5 × 109 /L was associated with a high risk of renal impairment in RA, suggesting that neutrophil may be a biomarker for renal impairment in RA.
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Artritis Reumatoide , Neutrófilos , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Estudios RetrospectivosRESUMEN
Background: Uveitis refers to inflammation in the uvea, retina, retinal blood vessels, and vitreous, which can lead to irreversible eye damage and permanent vision loss. Glucocorticoid drugs are the first-line treatment, but side effects, such as obesity and hyperglycemia, can occur. Therefore, biologics have become a new treatment choice. Case Presentation: A 18-year-old girl developed eye pain and was diagnosed with binocular uveitis. Prednisone 50 mg was administered once a day, and the redness and pain in both eyes improved. Later, the prednisone dose was gradually reduced, and treatment was discontinued 3 years ago. Two years ago, the patient's condition relapsed, with both eyes becoming red and painful. She was administered prednisone 20 mg once daily and adalimumab. Visual acuity in both eyes continued to progressively decrease, accompanied by cataracts. At the same time, the patient experienced complications, including obesity and hyperglycemia. Subsequently, a new treatment regimen, oral prednisone 20 mg once a day, tofacitinib 5 mg twice a day, and methotrexate 10 mg once a week, as well as the use of insulin to control blood sugar, was initiated. One month later, the patient's redness and eye pain eased, and her vision gradually improved. The dosage of prednisone was gradually reduced to 5 mg once daily. At the same time, her blood sugar returned to normal, and insulin was stopped. Outcomes: The patient was treated with tofacitinib for 10 months. Subsequently, her best-corrected visual acuity of the right eye rose from 0.06 to 0.075, and the best-corrected visual acuity of the left eye rose from CF/30 cm to CF/100 cm. Redness and eye pain were relieved, her glucocorticoid consumption reduced from 15 to 2.5 mg, and her blood sugar gradually normalized. Conclusion: This case study shows that tofacitinib relieves ocular inflammation in patients with uveitis and improves eyesight. We believe that JAK inhibitors could be another treatment option for noninfectious uveitis in patients who do not respond to conventional anti-TNF-α inhibitors (such as adalimumab).
RESUMEN
Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that ß-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear. Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining. Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2'-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression. Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.