Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis.
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ABSTRACT:
SUBMITTER: Khodadust F
PROVIDER: S-EPMC9267012 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInterleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools.MethodsIL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (Kd) and half maximal inhibition constant (IC50) were estimated for phage clones and synthesized peptides by ELISA. We used 5-Aza-2'-deoxycytidine (ADC)-stimulated Jurkat cells and human synovial tissue from patients with RA for in vitro characterization of peptides. For molecular imaging studies performed by magnetic resonance imaging (MRI), experimental arthritis was induced in DBA/1 male mice by immunization with an emulsion of complete Freund's adjuvant and type II collagen from chicken sternal cartilage.ResultsAfter several steps of phage display and peptide screening, two IL-7Rα-specific heptapeptides (P258 and P725) were selected from the initial library, based on their affinity for the target (extracellular domain of IL-7Rα, which contains a fibronectin type III repeat-like sequence). P258 (a linear peptide obtained by removing the Cys-constraint) had the lowest affinity for fibronectin itself and was therefore proposed for molecular imaging. After grafting to ultra-small superparamagnetic particles of iron oxide (USPIO), P258 produced a strong negative contrast on MRI in mice with collagen-induced arthritis (CIA), even at 2 hours post injection. The co-localization of USPIO-P258 with IL-7Rα-expressing cells in the synovial tissue from CIA mice and its ability to discriminate the level of IL-7R expression and the disease severity confirmed its efficacy as an in vivo IL-7Rα imaging agent. Interestingly, the cyclic peptide (P725), which was less adequate for molecular imaging because of higher affinity for fibronectin, had a strong ability to compete with IL-7 for the IL-7Rα binding sites, making it a potential candidate for blocking applications. Accordingly, P725 prevented the signal transducer and activator of transcription 5 (STAT5) activation induced by IL-7 in ADC-stimulated Jurkat cells.ConclusionsThe two peptides identified in this work demonstrate that IL-7Rα targeting in RA presents potential applications for in vivo molecular imaging and putative blocking purposes.
| S-EPMC5059943 | biostudies-literature
Project description:Background: Rheumatoid arthritis (RA) is a highly prevalent, chronic inflammatory condition of the synovial joints that affects approximately 1% of the global population. The pathogenesis of RA is predominantly inflammatory in nature, thereby accelerating the co-occurrence of other immunoinflammatory conditions such as atherosclerosis. Apart from traditional cardiovascular risk factors, RA patients possess a multitude of other factors that predispose them to early atherosclerotic disease. The aim of this systematic review is to assess the prevalence of premature atherosclerosis in RA patients and elucidate the role that proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction play in the pathophysiology of RA-mediated atherosclerosis. We also discussed novel biomarkers that can be used to predict early atherosclerosis in RA and current guidelines used to treat RA. Methods: This review followed the PRISMA guidelines to select and analyze relevant articles. A literature search for articles was performed on February 25, 2022, through three research databases including PubMed, ProQuest, and ScienceDirect. The query used to identify relevant publications was "Rheumatoid arthritis and atherosclerosis" and the search duration was set from 2012-2022. Relevant articles were selected based on the inclusion and exclusion criteria. Results: Our initial search generated 21,235 articles. We narrowed our search according to the inclusion and exclusion criteria. After assessing eligibility based on the full content of the articles, 73 articles were ultimately chosen for this review. Conclusion: There is an increased prevalence of accelerated atherosclerosis among RA patients. We found evidence to explain the role of proinflammatory cytokines, RA-related autoantibodies, and endothelial dysfunction in the pathophysiology RA-mediated atherosclerosis. Therapies targeting either the inflammatory load or traditional CV risk-factors seem to improve vascular outcomes in RA patients. Novel markers of atherosclerosis in RA may be useful in predicting premature atherosclerosis and serve as new targets for therapeutic intervention.
| S-EPMC9551388 | biostudies-literature
Project description:The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.
| S-EPMC6525860 | biostudies-literature
Project description:1backgroundRheumatoid Arthritis (RA) is a heterogeneous autoimmune disease with multiple unidentified pathogenic factors. The inconsistency between molecular subgroups poses challenges for early diagnosis and personalized treatment strategies. In this study, we aimed to accurately distinguish RA patients at the transcriptome level using bioinformatics methods.2methodsWe collected a total of 362 transcriptome datasets from RA patients in three independent samples from the GEO database. Consensus clustering was performed to identify molecular subgroups, and clinical features were assessed. Differential analysis was employed to annotate the biological functions of specifically upregulated genes between subgroups.3resultsBased on consensus clustering of RA samples, we identified three robust molecular subgroups, with Subgroup III representing the high-risk subgroup and Subgroup II exhibiting a milder phenotype, possibly associated with relatively higher levels of autophagic ability. Subgroup I showed biological functions mainly related to viral infections, cellular metabolism, protein synthesis, and inflammatory responses. Subgroup II involved autophagy of mitochondria and organelles, protein localization, and organelle disassembly pathways, suggesting heterogeneity in the autophagy process of mitochondria that may play a protective role in inflammatory diseases. Subgroup III represented a high-risk subgroup with pathological processes including abnormal amyloid precursor protein activation, promotion of inflammatory response, and cell proliferation.4conclusionThe classification of the RA dataset revealed pathological heterogeneity among different subgroups, providing new insights and a basis for understanding the molecular mechanisms of RA, identifying potential therapeutic targets, and developing personalized treatment approaches.
| S-EPMC11365346 | biostudies-literature
Project description:Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor ?B and its ligand, chemokine receptors, vascular cell adhesion molecule-1, ?V?? integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.
| S-EPMC4061725 | biostudies-literature
Project description:BackgroundMobile devices such as smartphones and tablets have surged in popularity in recent years, generating numerous possibilities for their use in health care as mobile health (mHealth) tools. One advantage of mHealth is that it can be provided asynchronously, signifying that health care providers and patients are not communicating in real time. The integration of asynchronous mHealth into daily clinical practice might therefore help to make health care more efficient for patients with rheumatoid arthritis (RA). The benefits have been reviewed in various medical conditions, such as diabetes and asthma, with promising results. However, to date, it is unclear what evidence exists for the use of asynchronous mHealth in the field of RA.ObjectiveThe objective of this study was to map the different asynchronous mHealth interventions tested in clinical trials in patients with RA and to summarize the effects of the interventions.MethodsA systematic search of Pubmed, Scopus, Cochrane, and PsycINFO was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies were initially screened and later assessed by two independent researchers. Disagreements on inclusion or exclusion of studies were resolved by discussion.ResultsThe literature search yielded 1752 abstracts. After deduplication and screening, 10 controlled intervention studies were included. All studies were assessed to be at risk for bias in at least one domain of the Cochrane risk-of-bias tool. In the 10 selected studies, 4 different types of mHealth interventions were used: SMS reminders (to increase medication adherence or physical activity; n=3), web apps (for disease monitoring and/or to provide medical information; n=5), smartphone apps (for disease monitoring; n=1), and pedometers (to increase and track steps; n=1). Measured outcomes varied widely between studies; improvements were seen in terms of medication compliance (SMS reminders), reaching rapid remission (web app), various domains of physical activity (pedometer, SMS reminders, and web apps), patient-physician interaction (web apps), and self-efficacy (smartphone app).ConclusionsSMS reminders, web apps, smartphone apps, and pedometers have been evaluated in intervention studies in patients with RA. These interventions have been used to monitor patients or to support them in their health behavior. The use of asynchronous mHealth led to desirable outcomes in nearly all studies. However, since all studies were at risk of bias and methods used were very heterogeneous, high-quality research is warranted to corroborate these promising results.
| S-EPMC7677027 | biostudies-literature
Project description:The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization. As such, a literature review was conducted to better understand the economic value of remission. Despite the large heterogeneity found in RA-related economic outcomes across studies, patients in remission consistently had lower direct medical and indirect costs, less healthcare resource utilization, and greater productivity compared to those without remission. Remission was associated with 19-52% savings in direct medical costs and 37-75% savings in indirect costs. The economic value of remission should thus be considered in economic analyses of RA therapies to inform treatment and reimbursement decisions.
| S-EPMC8799574 | biostudies-literature
Project description:Photoacoustic tomography (PAT) combines optical and acoustic imaging to generate high-resolution images of microvasculature. Inherent sensitivity to hemoglobin permits PAT to image blood vessels but precludes discriminating neovascular from maturing microvasculature. ?(v)?(3)-Gold nanobeacons (?(v)?(3)-GNBs) for neovascular molecular PAT were developed, characterized, and demonstrated in vivo using a mouse Matrigel-plug model of angiogenesis. PAT results were microscopically corroborated with fluorescent ?(v)?(3)-GNB localization and supporting immunohistology in Rag1(tm1Mom) Tg(Tie-2-lacZ)182-Sato mice. ?(v)?(3)-GNBs (154 nm) had 10-fold greater contrast than blood on an equivolume basis when imaged at 740 nm to 810 nm in blood. The lowest detectable concentration in buffer was 290 nM at 780 nm. Noninvasive PAT of angiogenesis using a 10-MHz ultrasound receiver with ?(v)?(3)-GNBs produced a 600% increase in signal in a Matrigel-plug mouse model relative to the inherent hemoglobin contrast pretreatment. In addition to increasing the contrast of neovessels detected at baseline, ?(v)?(3)-GNBs allowed visualization of numerous angiogenic sprouts and bridges that were undetectable before contrast injection. Competitive inhibition of ?(v)?(3)-GNBs with ?(v)?(3)-NBs (no gold particles) almost completely blocked contrast enhancement to pretreatment levels, similar to the signal from animals receiving saline only. Consistent with other studies, nontargeted GNBs passively accumulated in the tortuous neovascular but provided less than half of the contrast enhancement of the targeted agent. Microscopic studies revealed that the vascular constrained, rhodamine-labeled ?(v)?(3)-GNBs homed specifically to immature neovasculature (PECAM(+), Tie-2(-)) along the immediate tumor periphery, but not to nearby mature microvasculature (PECAM(+), Tie-2(+)). The combination of PAT and ?(v)?(3)-GNBs offered sensitive and specific discrimination and quantification of angiogenesis in vivo, which may be clinically applicable to a variety of highly prevalent diseases, including cancer and cardiovascular disease.
| S-EPMC3042842 | biostudies-other
Project description:IntroductionThis systematic review aims to analyse the trial data on the effects of bee venom acupuncture (BVA) for rheumatoid arthritis (RA).Methods and analysisThe following 14 databases will be searched from their inception to March 2014: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, CINAHL, six Korean medical databases (OASIS, Korean Traditional Knowledge Portal, Korean Studies Information Service System, KoreaMed, Korean Medical Database and DBPIA) and three Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang and VIP. The methodological quality will be assessed using the Cochrane risk of bias tool.DisseminationThe systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print.Trial registration numberPROSPERO 2013: CRD42013005853.
| S-EPMC4010843 | biostudies-literature
Project description:PurposeGiven the poor soft-tissue quality in rheumatoid arthritis patients, many believe that rheumatoid arthritis should be treated with reverse total shoulder arthroplasty (rTSA). The purpose of this paper is to systematically assess outcomes of anatomic total shoulder arthroplasty (aTSA) in rheumatoid arthritis to determine if aTSA remains a viable option.MethodsA comprehensive literature search was conducted identifying articles relevant to aTSA in the setting of rheumatoid arthritis with intact rotator cuff. Outcomes include clinical outcomes and rates of complication and revision.ResultsTen studies were included with a total of 279 shoulders with mean follow-up of 116 ± 69 months. The mean age was 68 ± 10 years. Survivorship was 97%, 97% and 89% at 5, 10 and 20 years, respectively. The overall complication rate was 9%. Radiolucency was present in 69% of patients, of which 34% were at risk of loosening at 79 months. The overall rate of revision was 8.4%. Studies generally reported clinically significant improvements in range of motion, Constant score and ASES score.ConclusionaTSA in the rheumatoid patient results in improvements in range of motion and patient-reported outcomes. Rates of complications and survivorship are generally good in this population. However, it should be noted that there is significant heterogeneity in outcome reporting amongst the literature on this topic and that many studies fail to adequately report complication and revision rates. When compared to rTSA in patients with rheumatoid arthritis, evidence suggests that aTSA is still a viable treatment option despite the shift in utilization to rTSA.
| S-EPMC8899319 | biostudies-literature