Aspirin is associated with improved outcomes in patients with sepsis-induced myocardial injury: An analysis of the MIMIC-IV database.

BACKGROUND: The effectiveness of aspirin treatment in septic patients remains a subject of debates. OBJECTIVE: To explore the association between aspirin usage and the prognosis of patients with sepsis-induced myocardial injury (SIMI), as well as the timing of aspirin administration. METHODS: Patients with SIMI were screened in the MIMIC-IV database and categorized into aspirin and non-aspirin groups based on their medications during intensive care unit (ICU) stay, and propensity matching analysis (PSM) was subsequently performed to reduce bias at baseline between the groups. The primary outcome was 28-day all-cause mortality. Cox multivariate regression analysis was conducted to evaluate the impact of aspirin on the prognosis of patients with SIMI. RESULTS: The pre-PSM and post-PSM cohorts included 1170 and 1055 patients, respectively. In the pre-PSM cohort, the aspirin group is older, has a higher proportion of chronic comorbidities, and lower SOFA and SAPS II scores when compared to the non-aspirin group. In the PSM analysis, most of the baseline characterization biases were corrected, and aspirin use was also associated with lower 28-day mortality (hazard ratio [HR] = 0.51, 95 % confidence interval [CI]: 0.42-0.63, P < 0.001), 90-day mortality (HR = 0.58, 95 % CI: 0.49-0.69, P < 0.001) and 1-year mortality (HR = 0.65, 95 % CI: 0.56-0.76, P < 0.001), irrespective of aspirin administration timing. A sensitivity analysis based on the original cohort confirmed the robustness of the findings. Additionally, subsequent subgroup analysis revealed that the use of vasopressin have a significant interaction with aspirin's efficacy. CONCLUSION: Aspirin was associated with decreased mortality in SIMI patients, and this beneficial effect persisted regardless of pre-ICU treatment.

Endothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice.

Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells. Tamoxifen-induced deletion of endothelial Sp1 and Sp3 in male mice decreases the serum nitrite/nitrate level, impairs endothelium-dependent vasodilation, and causes hypertension and cardiac remodeling. The beneficial actions of captopril are abolished by endothelial-specific deletion of Sp1/Sp3, indicating that they may be targets for ACEIs. Captopril increases Sp1/Sp3 protein levels by recruiting histone deacetylase 1, which elevates deacetylation and suppressed degradation of Sp1/Sp3. Sp1/Sp3 represents innovative therapeutic target for captopril to prevent cardiovascular diseases.

Stimulatory G-Protein α Subunit Modulates Endothelial Cell Permeability Through Regulation of Plasmalemma Vesicle-Associated Protein.

Endothelial cell leakage occurs in several diseases. Intracellular junctions and transcellular fashion are involved. The definite regulatory mechanism is complicated and not fully elucidated. The alpha subunit of the heterotrimeric G-stimulatory protein (Gsα) mediates receptor-stimulated production of cyclic adenosine monophosphate (cAMP). However, the role of Gsα in the endothelial barrier remains unclear. In this study, mice with knockout of endothelial-specific Gsα (GsαECKO) were generated by crossbreeding Gsαflox/flox mice with Cdh5-CreERT2 transgenic mice, induced in adult mice by tamoxifen treatment. GsαECKO mice displayed phenotypes of edema, anemia, hypoproteinemia and hyperlipoproteinemia, which indicates impaired microvascular permeability. Mechanistically, Gsα deficiency reduces the level of endothelial plasmalemma vesicle-associated protein (PLVAP). In addition, overexpression of Gsα increased phosphorylation of cAMP response element-binding protein (CREB) as well as the mRNA and protein levels of PLVAP. CREB could bind to the CRE site of PLVAP promoter and regulate its expression. Thus, Gsα might regulate endothelial permeability via cAMP/CREB-mediated PLVAP expression.

Responsive Janus Cage Reactor.

A Janus silica cage was synthesized by selectively grafting an ionic liquid (IL) and poly-N-isopropylacrylamide (PNIPAM) (lower critical solution temperature (LCST)≈32 °C) onto the exterior and interior sides of the mesoporous SiO2 shell. The paramagnetic core inside the cavity is responsible for magnetic collection. The PW12 O40 3- anion is further conjugated onto the IL side by anion exchange. The Janus cage acts as a thermal-responsive reactor for catalytic oxidization of dibenzothiophene (DBT) in the presence of H2 O2 . The sulfide in the model oil can be completely decomposed at 25 °C, whilst the oxidative products are more dissoluble in water and preferentially captured inside the Janus cage. The Janus cage reactor could be regenerated at high temperature above 32 °C after releasing the products.

Phosphomolybdic acid-responsive Pickering emulsions stabilized by ionic liquid functionalized Janus nanosheets.

A type of ionic liquid functionalized high-aspect-ratio Janus SiO2 nanosheets (IL-Janus nanosheets), which possesses a side terminated by imidazolin salt groups and the opposite side terminated by phenyl groups, was prepared and its emulsification performance was investigated. The surface wettability of ionic liquid functionalized side could be tailored via simple anion exchanging, giving the amphiphilic or totally hydrophobic Janus nanosheets. The influence of several parameters including surface wettability, particle concentration, oil composition, oil-water ratio as well as initial location of the nanosheets on the stability, morphology and type of the Pickering emulsions (O/W or W/O) stabilized by the amphiphilic IL-Janus nanosheets was evaluated. The research results revealed that average emulsion droplets size was decreased with increase of nanosheets concentration below a concentration value but had almost no change beyond the concentration; catastrophic phase inversion phenomenon occurred by varying volume fraction of water phase in the oil-water systems, and transitional phase inversion could be achieved by in-situ exchanging Cl- anion of the IL-Janus nanosheets with phosphomolybdate H2PMo12O40-. The responsiveness of Pickering emulsions towards phosphomolybdic acid is resulted from irreversible anion exchanging of Cl- by H2PMo12O40- and the variation of surface wettability of the nanosheets.

Ionic liquid functionalized Janus nanosheets.

Ionic liquid functionalized Janus nanosheets are synthesized by selective treatment of the imidazolin terminated side of Janus nanosheets while the other side is preserved. The Janus performance of the nanosheets and thus emulsion stability are reversibly triggered by anion exchange.