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Rapid Response Fluorescence Probe Enabled In Vivo Diagnosis and Assessing Treatment Response of Hypochlorous Acid-Mediated Rheumatoid Arthritis.

ABSTRACT: Diagnosis and early assessment of the treatment response of rheumatoid arthritis (RA) necessitates a reliable bioanalytical method for rapid, sensitive, and specific detection of the hypochlorous acid (HOCl) biomarker in inflammatory diseases. Herein, two fluorescence probes, Probe-1 and Probe-2 are developed for quantitative monitoring and visualization of inflammatory response-related HOCl levels in vitro and in vivo. In the presence of HOCl, fluorescence "OFF-ON" response is obtained for both the probes as a result of specific HOCl-triggered C=N bond cleavage reaction. Probe-1 and Probe-2 feature rapid response (<4 s), a high degree of sensitivity and selectivity toward HOCl, which allow them to be used for quantification of HOCl in a simulated physiological condition. Using Probe-2 as the probe, fluorescence imaging and flow cytometry analysis of HOCl levels in lysosome of inflammatory mimic cells, visualization of HOCl generation in endotoxin-induced inflammation of adult zebrafish and RA of mice are possible. Probe-2 exhibits high effectiveness for early assessment of the treatment response of HOCl-mediated RA in mice with an antiarthritic drug, methotrexate (MTX). The results demonstrate that Probe-2 is a powerful tool for future studies on diagnosis and monitoring treatment efficiency in a broad range of inflammatory diseases, including RA.

SUBMITTER: Feng H

PROVIDER: S-EPMC6096987 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionLimited data are available to explain nonadherence to methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA). Better understanding of patterns of MTX use and reasons for nonadherence may help identify patients who would benefit from alternative RA treatments and potentially aid in developing strategies to increase overall adherence. The purpose of this study was to assess patients' self-reported adherence to MTX and to identify reasons for nonadherence.MethodsPatient panel members in the US self-reporting a diagnosis of RA of ?3 months' and current MTX use of ?4 weeks' duration, with or without concomitant use of another RA prescription medication, participated in this cross-sectional, web-based survey.ResultsThe sample population (251 MTX monotherapy, 250 MTX combination therapy) was predominantly female, white, non-Hispanic, and educated; 48% were 18-44 years-old, 47% had medical comorbidities, 66% were first diagnosed with RA ?5 years earlier, 51% reported MTX use of <1 year, and 83% reported oral MTX use. Forty-two percent reported not taking MTX exactly as prescribed. Reasons for nonadherence included forgetting to take it (33%), not needing it when feeling well (24%), and concern about long-term safety (24%). Among nonadherent patients, 53% took smaller doses, 52% skipped doses, and 6% reported other nonprescribed ways of taking MTX. Younger age, male sex, and shorter duration of MTX use were associated with poorer self-reported adherence. Compared with monotherapy patients, combination therapy patients, particularly those taking ?2 other RA prescriptions, were less likely to report high adherence.ConclusionNearly half the sample reported poor MTX adherence because they forgot to take it, thought it was not needed when they felt well, or had long-term safety concerns. Patients taking ?2 other RA prescription medications were less likely to report good adherence. Reducing treatment burden without sacrificing efficacy may be a strategy worth evaluating.

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Rapid Response Fluorescence Probe Enabled In Vivo Diagnosis and Assessing Treatment Response of Hypochlorous Acid-Mediated Rheumatoid Arthritis.

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