RESUMO
Hydrogen sulfide is a biologically important molecule and developing chemical tools that enable further investigations into the functions of H2 S is essential. Fluorescent turn-on H2 S probes have been developed for use in cellulo and inâ vivo, but the membrane permeability of these probes can lead to probe leakage and signal attenuation over time. Here we report a cell trappable fluorescent probe for H2 S, CT-MeRhoAz, which is based on a methylrhodolazide scaffold derivatized with an acetoxymethyl ester group. Prior to ester cleavage, the CT-MeRhoAz probe generates a 2500-fold turn-on response to H2 S, which is enhanced to a 3000-fold response for the carboxylic acid form of the probe. Additionally, the probe is highly selective for H2 S over other biologically relevant sulfur, oxygen, and nitrogen-based analytes. Live cell imaging experiments confirmed the biocompatibility of CT-MeRhoAz and also that it is cell trappable, unlike the parent MeRhoAz scaffold.
Assuntos
Sulfeto de Hidrogênio , Xantonas , Ésteres , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/metabolismoRESUMO
We aimed to determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular (CV) events and all-cause mortality. We conducted a retrospective double cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection (COVID-19+ cohort) and its documented absence (COVID-19- cohort). The study investigators drew a simple random sample of records from all patients under the Oregon Health & Science University Healthcare (n = 65,585), with available COVID-19 test results, performed March 1, 2020 to September 13, 2020. Exclusion criteria were age <18 years and no established Oregon Health & Science University care. The primary outcome was a composite of CV morbidity and mortality. All-cause mortality was the secondary outcome. The study population included 1,355 patients (mean age 48.7 ± 20.5 years; 770 women [57%], 977 White non-Hispanic [72%]; 1,072 ensured [79%]; 563 with CV disease history [42%]). During a median 6 months at risk, the primary composite outcome was observed in 38 of 319 patients who were COVID-19+ (12%) and 65 of 1,036 patients who were COVID-19- (6%). In the Cox regression, adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk for primary composite outcome (hazard ratio 1.71, 95% confidence interval 1.06 to 2.78, p = 0.029). Inverse probability-weighted estimation, conditioned for 31 covariates, showed that for every patient who was COVID-19+, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19-: average treatment effect on the treated -65.5 (95% confidence interval -125.4 to -5.61) days, p = 0.032. In conclusion, either symptomatic or asymptomatic SARS-CoV-2 infection is associated with an increased risk for late CV outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.
Assuntos
COVID-19 , Doenças Cardiovasculares , Adolescente , Adulto , Idoso , Teste para COVID-19 , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2RESUMO
In an effort to expand the availability of simple polysulfides for H2S donation, we report here the synthesis and H2S release profiles of bis(aryl) and bis(alkyl) tetrasulfides. The tetrasulfide donors release H2S in a first-order dependence on reduced glutathione (GSH) and release more H2S than the commonly used trisulfide DATS.