Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 35440082 | Telemedicine application in patients with chronic disease: a systematic review and meta-an | 2022 Apr 19 | BACKGROUND: Telemedicine has been widely used for long-term care and self-management in patients with chronic disease, but there is no consensus regarding the effect of telemedicine on chronic disease management. The aim of this study is to review and analyse the effect of telemedicine on the management of chronic diseases such as hypertension, diabetes, and rheumatoid arthritis using a systematic review and meta-analysis. METHODS: We performed a comprehensive literature search of the Web of Science, PubMed, MEDLINE, EMBASE, CNKI (Chinese database), VIP (Chinese database), WanFang (Chinese database), and SinoMed (Chinese database) databases from their inception until December 31, 2021. The retrieved literature was screened and assessed independently by two authors. We used the risk-of-bias assessment tool recommended by the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2 for assessing literature quality and Revman 5.3 software to conduct the meta-analysis. RESULTS: Fifteen articles were included in this study. The results of the systematic review indicated that telemedicine consultation and telemonitoring are the most commonly used intervention methods. Telemedicine is helpful for improving self-management in patients with rheumatoid arthritis. The results of the meta-analysis showed patients' index of glycosylated hemoglobin (HbA1c) improved after 12 months of intervention (MD =  - 0.84; 95% CI =  - 1.53, - 0.16; Z = 2.42; P = 0.02), and no significant differences in fasting blood glucose (FBG) levels were observed after 6 months of intervention (MD =  - 0.35; 95% CI =  - 0.75,0.06; Z = 1.69; P = 0.09). The results also showed that systolic blood pressure (MD =  - 6.71; 95% CI =  - 11.40, - 2.02; Z = 2.81; P = 0.005) was reduced after 6 months of intervention. CONCLUSION: Telemedicine had a positive effect on the management of diabetes, hypertension, and rheumatoid arthritis, especially when telemedicine consultation and telemonitoring method were used. When telemedicine was used as a disease management tool for patients with diabetes, the optimal intervention time is 12 months. Telemedicine improved the systolic blood pressure in hypertensive patients while also reducing negative emotions and enhancing medication adherence in rheumatoid arthritis patients. | |
| 35566047 | Novel Small Molecule Inhibitors Targeting the IL-6/STAT3 Pathway or IL-1β. | 2022 Apr 22 | Development of small molecules that inhibit inflammatory cytokines is a desirable strategy for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). Following up a previous study, we synthesized 10 novel compounds with a 2,5-diaminobenzoxazole moiety and evaluated their biological activities. Among them, compound 3e showed potent inhibitory activity on Interleukin 6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling inhibition (71.5%), and 3a showed excellent inhibitory activity on Interleukin 1 (IL-1β) (92.1%). To test in vivo anti-inflammatory activity, compounds 3a and 3e were administered by intraperitoneal (IP) injection after subcutaneous (SC) injection of zymosan A into the right footpad of mice. Inflammation on the footpad was reduced after administration of compounds 3a and 3e. Especially, compound 3a showed a significant ameliorative effect on zymosan-induced inflammation. From the in vivo and in vitro test results, we confirmed that our synthesized compounds are effective on the RA animal model through inhibition of the IL-6/STAT3 signaling pathway. Since drugs developed with small molecule inhibitors have several advantages over biological drugs, further study on these compounds is needed for the development of potent SMI drugs on RA. | |
| 34968861 | A deep-learning framework for metacarpal-head cartilage-thickness estimation in ultrasound | 2022 Feb | OBJECTIVE: Rheumatoid arthritis (RA) is a chronic disease characterized by erosive symmetrical polyarthritis. Bone and cartilage are the main joint targets of this disease. Cartilage damage is one of the most relevant determinants of physical disability in RA patients. Cartilage damage is nowadays assessed by clinicians, which manually measure cartilage thickness in ultrasound (US) imaging. This poses issues relevant to intra-and inter-observer variability. Relying on the acquisition of metacarpal-head US images from 38 subjects, this work addresses the problem of automatic cartilage-thickness measurement by designing a new deep-learning (DL) framework. METHODS: The framework consists of a Convolutional Neural Network (CNN), responsible for regressing cartilage-interface distance fields, followed by a post-processing step to delineate the two cartilage interfaces from the predicted distance fields and compute the cartilage thickness. RESULTS: Our framework achieved encouraging results with a mean absolute difference (ADF) of 0.032 (±0.026) mm against manual thickness annotation by an expert clinician. When evaluating the intra-observer variability, we obtained an ADF = 0.036 (±0.028) mm. CONCLUSION: The proposed framework achieved an ADF against manual annotation that was comparable to the intra-observer variability, proving the potential of DL in the field. SIGNIFICANCE: This work is the first to address the problem of automatic cartilage-thickness estimation in US rheumatological images with DL, paving the way for future research in the field. From a clinical perspective, the proposed framework proved to be a valuable tool to support the clinical routine increasing the reproducibility of cartilage thickness measurements. | |
| 34013997 | Advances in Ultrasound Imaging in Rheumatology-What Do They Mean and What Challenges Do Th | 2022 Mar | Musculoskeletal ultrasound is an important tool for the monitorization of inflammatory rheumatic diseases, with subclinical synovitis being frequently detected in ultrasound scans of patients in clinical remission. It has been shown, for example, that the presence of Power Doppler signal synovial membrane has prognostic value for patients with rheumatoid arthritis. Microvascular imaging technologies significantly improve the sensitivity for slow-flow vessels and may potentially detect subclinical inflammation when Power Doppler fails to do so. The authors briefly discuss the implications of the use of such techniques in rheumatology setting and review available evidence. | |
| 35277211 | Vitamin D levels in patients with small and medium vessel vasculitis. | 2022 Mar | OBJECTIVES: To determine the prevalence of vitamin D deficiency in patients with small and medium vessel systemic vasculitis. METHODS: In this cross-sectional study, 25-hydroxy (OH) vitamin D3 levels were measured in adult patients with systemic small and medium vessel vasculitis including antineutrophil cytoplasmic antibody-associated vasculitis (AAV), cryoglobulinaemic vasculitis (CryV), IgA vasculitis (IgAV) and polyarteritis nodosa (PAN), and age- and sex-matched healthy subjects (HS) and patients with rheumatoid arthritis (RA) as control groups. 25OH vitamin D3 levels<30ng/ml and <20ng/ml were regarded as insufficiency and deficiency, respectively. RESULTS: Fifty-seven patients (42 AAV, 2 CryV, 8 IgA vasculitis, 5 PAN) with systemic vasculitis, 101 HS, and 111 RA patients were included. The mean 25OH vitamin D3 level was 21.8±14.2ng/mL in patients with vasculitis, 42.7±27.6ng/mL in HS (p<.001) and 20.1±18.47ng/mL in patients with RA (p=.54). Vitamin D insufficiency and deficiency were significantly higher in patients with systemic vasculitis compared to HS (75.4% vs 33.7%, p<.001; %50 vs 21.8%, p<.001, respectively). Vitamin D status was not different in patients with systemic vasculitis compared to RA. There was a negative correlation between vitamin D status and CRP levels (=-.364, p=.007). The multivariate logistic regression analysis showed that renal involvement was significantly associated with vitamin D deficiency/insufficiency in patients with vasculitis (OR 22.5 [95% CI 1.6-128.9]. CONCLUSION: Vitamin D deficiency and insufficiency are more frequent in patients with systemic small and medium vessel vasculitis and RA than HS. Renal involvement is one of the factors associated with vitamin D deficiency/insufficiency in patients with vasculitis. | |
| 35238807 | The safety of glucocorticoids in the treatment of inflammatory rheumatic disease: new evid | 2022 May 1 | PURPOSE OF REVIEW: Glucocorticoids justifiably remain a cornerstone in the treatment of many inflammatory rheumatic diseases but many are opposed to their use because of the side effects, most of them known to be dose-dependent. Most concerns regarding glucocorticoids stem from observational studies which are affected by several forms of bias, mainly confounding by indication, that may result in overestimation of harm. Solid evidence regarding the safety of low-dose glucocorticoids remains remarkably scarce. RECENT FINDINGS: Several observational studies showed heterogeneous results and two 6-month trials showed no increase of harm. The GLORIA trial of 5 mg/day prednisolone vs. placebo in patients aged 65+ is the first randomized control trial with glucocorticoids safety as coprimary outcome. The benefits of glucocorticoids in terms of symptoms and structural damage were confirmed, but the proportion of patients with at least one adverse event of special interest (serious or glucocorticoids-related) was increased by 24%, mostly due to nonsevere infections. SUMMARY: Based on current evidence the benefit-risk balance of low-dose glucocorticoids in rheumatoid arthritis, and probably in other rheumatic diseases is generally favourable. Physicians should be aware of the risks and mitigate them, but avoid the negative effects of unfounded fear. | |
| 34924117 | Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mic | 2022 Jan | Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA. | |
| 34530709 | Therapeutic Approaches for the Management of Autoimmune Disorders via Gene Therapy: Prospe | 2022 | BACKGROUND: Autoimmune diseases are the diseases that result due to the overactive immune response, and comprehend systemic autoimmune diseases like Rheumatoid Arthritis (RA), SjÓ§gren's Syndrome (SS), and organ-specific autoimmune diseases like type-1 diabetes mellitus (T1DM), Myasthenia Gravis (MG), and Inflammatory Bowel Disease (IBD). Currently, there is no long-term cure; but, several treatments exist which retard the evolution of the disease, embracing gene therapy, which has been scrutinized to hold immense aptitude for the management of autoimmune diseases. OBJECTIVE: The review highlights the pathogenic mechanisms and genes liable for the development of autoimmune diseases, namely T1DM, type-2 diabetes mellitus (T2DM), RA, SS, IBD, and MG. Furthermore, the review focuses on investigating the outcomes of delivering the corrective genes with their specific viral vectors in various animal models experiencing these diseases to determine the effectiveness of gene therapy. METHODS: Numerous review and research articles emphasizing the tremendous potential of gene therapy in the management of autoimmune diseases were procured from PubMed, MEDLINE, Frontier, and other databases and thoroughly studied for writing this review article. RESULTS: The various animal models that experienced treatment with gene therapy have displayed regulation in the levels of proinflammatory cytokines, infiltration of lymphocytes, manifestations associated with autoimmune diseases, and maintained equilibrium in the immune response, thereby compete with the progression of autoimmune diseases. CONCLUSION: Gene therapy has revealed prodigious aptitude in the management of autoimmune diseases in various animal studies, but further investigation is essential to combat the limitations associated with it and before employing it on humans. | |
| 35403627 | [Adaptation of Microarray Assay for Serum Amyloid A Analysis in Human Serum]. | 2022 Mar | Serum amyloid A is an inflammatory biomarker whose concentration changes during infectious and inflammatory diseases. SAA's tendency for aggregation and complex formation makes it difficult to determine its concentration in samples, especially when there is an increased level of it. Immunofluorescence SAA determination on a microarray was adapted for SAA quantification in human serum. Both the procedure and the diluent for the calibrator samples were chosen to obtain a dynamic range between 1 and 100 μg/mL. Mixtures of animal (rabbit, goat, mouse) sera with recombinant antigen diluted in certain concentrations were used for the calibrator samples. The method was tested using serum samples from 15 patients with rheumatoid arthritis or ankylosing spondylitis and 9 healthy donors. The results obtained on the microarray demonstrated a good correlation with the results determined by ELISA (Pearson's correlation coefficient is 0.93). The method developed could be a convenient tool for assessing SAA levels in a number of diseases, such as rheumatoid arthritis or infections of various etiologies, characterized by a significant increase in the level of this protein in the blood. The use of a microarray for the analysis allows the determination of the SAA concentration simultaneously with other inflammatory biomarkers. | |
| 34238651 | Using patient-generated health data in clinical practice: How timing influences its functi | 2022 Mar | OBJECTIVE: Utilizing patient-generated health data (PGHD) in clinical consultations and informing clinical and shared decision-making processes has the potential to improve clinical practice but has proven challenging to implement. Looking at consultations between people with rheumatoid arthritis (RA) and rheumatologists, this study examines when and how daily PGHD was discussed in outpatient consultations. METHODS: We conducted a secondary qualitative analysis of 17 audio-recorded research outpatient consultations using thematic and interactional approaches. RESULTS: Clinicians decided when to look at the PGHD and what symptoms to prioritise during the consultation. When PGHD was introduced early in consultations, it was usually used to invite patients to collaborate (elicit new information). When introduced later, PGHD was used to corroborate patient accounts and to convince the patient about proposed actions and treatments. Clinicians occasionally disregarded PGHD if it did not fit into their clinical assessment. CONCLUSION: The time that PGHD is introduced may influence how PGHD is used in consultations. Further research is needed to understand how best to empower patients to discuss PGHD. PRACTICE IMPLICATIONS: Educating patients and clinicians about the importance of timing and strategies when using PGHD in consultations may help promote shared decision-making. | |
| 34783974 | The Effect of α7nAChR Signaling on T Cells and Macrophages and Their Clinical Implication | 2022 Mar | Rheumatoid arthritis (RA) is one of the most common autoimmune disease and until now, the etiology and pathogenesis of RA is not fully understood, although dysregulation of immune cells is one of the leading cause of RA-related pathological changes. Based on current understanding, the priority of anti-rheumatic treatments is to restore immune homeostasis. There are several anti-rheumatic drugs with immunomodulatory effects available nowadays, but most of them have obvious safety or efficacy shortcomings. Therefore, the development of novel anti-rheumatic drugs is still in urgently needed. Cholinergic anti-inflammatory pathway (CAP) has been identified as an important aspect of the so-called neuro-immune regulation feedback, and the interaction between acetylcholine and alpha 7 nicotinic acetylcholine receptor (α7nAChR) serves as the foundation for this signaling. Consistent to its immunomodulatory functions, α7nAChR is extensively expressed by immune cells. Accordingly, CAP activation greatly affects the differentiation and function of α7nAChR-expressing immune cells. As a result, targeting α7nAChR will bring profound therapeutic impacts on the treatment of inflammatory diseases like RA. RA is widely recognized as a CD4(+) T cells-driven disease. As a major component of innate immunity, macrophages also significantly contribute to RA-related immune abnormalities. Theoretically, manipulation of CAP in immune cells is a feasible way to treat RA. In this review, we summarized the roles of different T cells and macrophages subsets in the occurrence and progression of RA, and highlighted the immune consequences of CAP activation in these cells under RA circumstances. The in-depth discussion is supposed to inspire the development of novel cell-specific CAP-targeting anti-rheumatic regimens. | |
| 33298811 | Preferred Strategies for Delivering Health Information to Patients With Musculoskeletal Di | 2022 Jan 1 | BACKGROUND: Patients' information needs may differ from what their care providers may perceive to be the patients' needs. This discordance needs to be recognized and addressed. OBJECTIVE: We conducted a qualitative study to explore the perceptions of patients with selected musculoskeletal disorders and those of rheumatologists, on their preferred strategies for delivery of disease management information. METHODS: Fifty-two patients diagnosed with either rheumatoid arthritis, knee osteoarthritis, or osteoporosis took part in 6 focus groups and 18 individual semistructured interviews. In addition, 11 rheumatologists participated in 2 focus groups and 4 semistructured individual interviews. Data were explored by thematic content analysis. Perceived preferences were identified and compared between patients and rheumatologists regarding (a) media, (b) setting, (c) messengers, and (d) key message content. RESULTS: Patients' preferred media for disease management information were electronic (television and videos delivered as digital optical discs or the Internet), group instruction, and printed material. Patients preferred the information to be delivered in the setting of their homes, doctor's offices, or clinic waiting areas by the rheumatologists and patients with disease experience, addressing healthy lifestyle changes, medication adherence, and consequences of noncompliance. For rheumatologists, the perceived preference for information delivery was through printed material (brochures, booklets, and pamphlets) delivered in waiting areas by nurses and physicians, addressing nature of the disease, complications, and treatment adverse effects. CONCLUSIONS: Provider perspectives on strategies for education may differ from those of patients. Our findings highlight the need for considering different stakeholder perspectives in designing educational tools and decision support materials for patients with chronic diseases. TAKEHOME MESSAGE: Rheumatologists' preferences on strategies for education (mode of delivery, delivery setting, messengers, and topics) differ from those of patients. For example, patients want to learn about lifestyle changes and consequences of compliance versus noncompliance, whereas rheumatologists considered more important for patients to understand their disease, treatment adverse effects, and consequences of noncompliance. | |
| 35122317 | Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted | 2022 Mar | BACKGROUND: Calprotectin is a calcium-binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed. METHODS: The protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared. RESULTS: The intra-day and inter-day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed-rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = -0.32 (95% CI: -0.65 - -0.05) +1.58 (95% CI: 1.42-1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices. CONCLUSIONS: The DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays. | |
| 32967487 | Serum 14-3-3η is a Marker that Complements Current Biomarkers for the Diagnosis of RA: Ev | 2022 Jan | OBJECTIVE: To systematically evaluate the diagnostic value of 14-3-3η protein for rheumatoid arthritis (RA). METHOD: Searched PubMed, Web of Science, Embase and China Biology Medicine (CBM) databases comprehensively from inception to May 2020. The evaluation index were the pooled sensitivity, specificity, diagnosis odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), as well as the area under the summary receiver operating characteristic (SROC) curves. Meta-Disc 1.4 and RevMan 5.3 were used to analyze all statistics. QUADAS-2 tool was applied to evaluate the quality of eligible studies. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. RESULTS: Nine articles containing eleven records were eligible for this meta-analysis. The pooled sensitivity of 14-3-3η was 0.63 (95% CI: 0.60 to 0.66), the pooled specificity was 0.90 (95% CI: 0.88 to 0.91). The pooled PLR and NLR was 6.10 (95% CI: 4.67 to 7.96) and 0.40 (95% CI: 0.33 to 0.48), respectively. The pooled DOR was 15.90 (95% CI: 11.15 to 22.68), and the area under the curve (AUC) was 0.8696. Compared with a single indicator (rheumatoid factor or anti-citrullinated protein antibodies), adding 14-3-3η can bring incremental benefits to the diagnosis of RA. The results of subgroup analysis and meta-regression suggested that the two factors (ethnicity, early vs established RA) we analyzed might not be the source of heterogeneity (P value were 0.0979 and 0.4298, respectively) and there was no publication bias among these articles (P = .42). CONCLUSION: Serum 14-3-3η protein is a supplementary biomarker in the diagnosis of RA. | |
| 34251313 | The role of musculoskeletal ultrasound in predicting the response to JAK inhibitors: resul | 2022 May | OBJECTIVES: In this longitudinal study, we assessed the role of musculoskeletal ultrasound (US) in predicting the efficacy of JAK inhibitors (JAKi) in rheumatoid arthritis (RA) patients. METHODS: We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by Disease Activity Score 28 (DAS28CRP); US examination in 22 joints (I-V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), scored through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I-V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score ranging from 0 to 22. RESULTS: We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). At multivariate analysis, PD and tenosynovitis score significantly correlated with changes in DAS28CRP. CONCLUSIONS: The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, we found that power Doppler and tenosynovitis scores could play a predictive role in response to treatment. | |
| 35627163 | Gene Expression Meta-Analysis of Potential Shared and Unique Pathways between Autoimmune D | 2022 Apr 27 | While anti-TNFα has been established as an effective therapeutic approach for several autoimmune diseases, results from clinical trials have uncovered heterogeneous patients' response to therapy. Here, we conducted a meta-analysis on the publicly available gene expression cDNA microarray datasets that examine the differential expression observed in response to anti-TNFα therapy with psoriasis (PsO), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Five disease-specific meta-analyses and a single combined random-effects meta-analysis were performed through the restricted maximum likelihood method. Gene Ontology and Reactome Pathways enrichment analyses were conducted, while interactions between differentially expressed genes (DEGs) were determined with the STRING database. Four IBD, three PsO and two RA datasets were identified and included in our analyses through our search criteria. Disease-specific meta-analyses detected distinct pro-inflammatory down-regulated DEGs for each disease, while pathway analyses identified common inflammatory patterns involved in the pathogenesis of each disease. Combined meta-analyses further revealed DEGs that participate in anti-inflammatory pathways, namely IL-10 signaling. Our analyses provide the framework for a transcriptomic approach in response to anti-TNFα therapy in the above diseases. Elucidation of the complex interactions involved in such multifactorial phenotypes could identify key molecular targets implicated in the pathogenesis of IBD, PsO and RA. | |
| 34983591 | miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targe | 2022 Jan 4 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. METHODS: The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. RESULTS: RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3'-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. CONCLUSION: In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway. | |
| 34796986 | Ratio of serum amyloid A to C-reactive protein is constant in the same patients but differ | 2022 Feb | C-reactive protein (CRP) is commonly monitored to track the activity of inflammation and has become the gold standard in the management of all inflammatory diseases. Indeed, serum amyloid A (SAA) have seemed to correlate moderately with CRP, but the discrepancy of CRP and SAA levels has often been reported, especially in rheumatoid arthritis. Then, we examined CRP reflects a real magnitude of inflammation in patients with rheumatic and infectious inflammatory diseases. A total of 414 patients with infectious and non-infectious inflammatory diseases were enrolled. At initial visit, each patient underwent a clinical assessment and had also laboratory tests such as SAA and CRP. In each patient, we carried out a longitudinal analysis of CRP and SAA levels. We determined the inter-individual correlation between SAA and CRP and also clarified intra-individual changes of SAA/CRP ratio. SAA and CRP levels changed approximately linearly over time within individuals irrespective of rheumatic and infectious inflammatory diseases. However, SAA/CRP ratios differed dramatically between patients (from 0.117 to 50.8, median 5.71). In patients with high SAA/CRP ratio (>8.44), SAA is a better predictor of inflammation than CRP. In contrast, CRP is a better predictor in patients with low ratio (<3.52). Our results suggest that the SAA/CRP ratio differed greatly between individuals but was constant in intra-individuals. Low CRP levels could be accompanied by SAA levels predicting any degree of inflammation, implying that CRP is not reflecting a real magnitude of inflammation. To evaluate the real magnitude of inflammation, to access the SAA/CRP ratio in advance is essential. | |
| 35418750 | Evaluating Triple Therapy Treatment Pathways in Chronic Obstructive Pulmonary Disease (COP | 2022 | PURPOSE: Inhaled triple therapy (TT) comprising a long-acting muscarinic antagonist, long-acting β(2) agonist, and inhaled corticosteroid is recommended for symptomatic chronic obstructive pulmonary disease (COPD) patients, or those at risk of exacerbation. However, it is not well understood which patient characteristics contribute most to future exacerbation risk. This study assessed patient predictors associated with future exacerbation time following initiation of TT. PATIENTS AND METHODS: This retrospective cohort study used data from the Optum™ Clinformatics™ Data Mart, a large health claims database in the United States. COPD patients who initiated TT between January 2008 and March 2018 (index) were eligible. Patients were required to be aged ≥18 years at index and have continuous enrollment for the 12 months prior to index (baseline) and the 12 months following index (follow-up). Patients who had received TT during baseline were excluded. Data from eligible patients were analyzed using a reverse engineering forward simulation machine learning platform to predict future COPD exacerbation time. RESULTS: Data from 73,625 patients were included. The model found that prior exacerbation was largely correlated with post-index exacerbation time; patients who had ≥4 exacerbation episodes during baseline had an average increase of 32.4 days post-index exacerbation, compared with patients with no exacerbations during baseline. Likewise, ≥2 inpatient visits (effect size 27.1 days), the use of xanthines (effect size 11.5 days), or rheumatoid arthritis (effect size 6.4 days) during baseline were associated with increased exacerbation time. Conversely, diagnosis of anemia (effect size -5.68 days), or oral corticosteroids in the past month (effect size -3.43 days) were associated with reduced exacerbation time. CONCLUSION: Frequent prior exacerbations, healthcare resource utilization, xanthine use, and rheumatoid arthritis were the strongest factors predicting the future increase of exacerbations. These results improve our understanding of exacerbation risk among COPD patients initiating triple therapy. | |
| 35149603 | Fractal analysis of perfusion imaging in synovitis: a novel imaging biomarker for grading | 2022 Feb | OBJECTIVES: The mutual and intertwined dependence of inflammation and angiogenesis in synovitis is widely acknowledged. However, no clinically established tool for objective and quantitative assessment of angiogenesis is routinely available. This study establishes fractal analysis as a novel method to quantitatively assess inflammatory activity based on angiogenesis in synovitis. METHODS: First, we established a pathophysiological framework for synovitis including fractal analysis of software perfusion phantoms, which allowed to derive explainability with a known and controllable reference standard for vascular structure. Second, we acquired MRI datasets of patients with suspected rheumatoid arthritis of the hand, and three imaging experts independently assessed synovitis analogue to Rheumatoid Arthritis MRI Scoring (RAMRIS) criteria. Finally, we performed fractal analysis of dynamic first-pass perfusion MRI in vivo to evaluate angiogenesis in relation to inflammatory activity with RAMRIS as reference standard. RESULTS: Fractal dimension (FD) achieved highly significant discriminability for different degrees of inflammatory activity (p<0.01) in software phantoms with known ground-truth of angiogenic structure. FD indicated increasingly chaotic perfusion patterns with increasing grades of inflammatory activity (Spearman's Ï=0.94, p<0.001). In 36 clinical patients, fractal analysis quantitatively and objectively discriminated individual RAMRIS scores (p≤0.05). Area under the receiver-operating curve was 0.84 (95% CI 0.7 to 0.89) for fractal analysis when considering RAMRIS as ground-truth. Fractal analysis additionally identified angiogenesis in cases where RAMRIS underestimated inflammatory activity. CONCLUSIONS: Based on angiogenesis and perfusion pathophysiology, fractal analysis non-invasively enables comprehensive, objective and quantitative characterisation of inflammatory angiogenesis with subjective and qualitative RAMRIS as reference standard. Further studies are required to establish the clinical value of fractal analysis for diagnosis, prognostication and therapy monitoring in inflammatory arthritis. |