TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

Deciphering the Therapeutic Potential of Novel Pentyloxyamide-Based Class I, IIb HDAC Inhibitors against Therapy-Resistant Leukemia.

Histone deacetylase inhibitors (HDACi) are established anticancer drugs, especially in hematological cancers. This study aimed to design, synthesize, and evaluate a set of HDACi featuring a pentyloxyamide connecting unit linker region and substituted phenylthiazole cap groups. A structural optimization program yielded HDACi with nanomolar inhibitory activity against histone deacetylase class I/IIb enzymes.

YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12.

Background And Objectives: Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.

Effect of Valve Type and Anesthesia Strategy for TAVR: 5-Year Results of the SOLVE-TAVI Trial.

Background: In the randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial comparing newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV), as well as conscious sedation (CS) and general anesthesia (GA), clinical outcomes were similar both for valve and anesthesia comparison at 30 days and 1 year.

A focus shift in the evaluation of misinformation interventions.

The proliferation of misinformation has prompted significant research efforts, leading to the development of a wide range of interventions. There is, however, insufficient guidance on how to evaluate these interventions. Here, we argue that researchers should consider not just the interventions' primary effectiveness but also ancillary outcomes and implementation challenges.