Influence and mechanism of sodium-glucose cotransporter-2 inhibitors on the cardiac function: study protocol for a prospective cohort study.

Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.

New sorbicillinoid derivatives with GLP-1R and eEF2K affinities from a sponge-derived fungus Penicillium chrysogenum 581F1.

Two new sorbicillinoids, 13-hydroxy-dihydrotrichodermolide (1) and 10,11,27,28-tetrahydrotrisorbicillinone C (2), were isolated from the sponge-derived fungus Penicillium chrysogenum 581F1. Their structures were determined on the basis of spectroscopic analysis. Compounds 1 and 2 displayed high affinities to target proteins GLP-1R (diabetes) and eEF2K (cancer) with Kd values of 0.0285 µM, 0.0162 µM for GLP-1R and 0.118 µM, 0.0746 µM for eEF2K, respectively.

Trienic α-pyrone and ochratoxin derivatives from a sponge-derived fungus Aspergillus ochraceopetaliformis.

A new trienic α-pyrone derivative asteltoxin G (1) bearing a tetrahydrofuran ring and a new ochratoxin derivative named ochratoxin A1 (5), along with seven known compounds, were isolated from a sponge-derived fungus Aspergillus ochraceopetaliformis. The compounds (1-9) were evaluated on the basis of spectroscopic analyses and comparison with those of the reported data. The new compound ochratoxin A1 (5) exhibited anti-inflammatory activity against IL-6 and TNF-α expression of the LPS-induced THP-1 cells with inhibitory rates of 74.4 and 67.7% at concentration of 10 µM, respectively.