Pharmacology & Biotechnology
A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptakeOur study identified a first multi-targeted compound (GM1869) inhibiting RyR2-mediated Ca2+ leak together with activating SERCA2a function that may represent a critical breakthrough for treatment of diastolic Ca2+ leak in heart failure.
Rapid and precise genotyping of transgene zygosity in mice using an allele-specific methodA novel, precise, rapid, and generalizable method to determine transgene zygosity in mice by allele-specific restriction enzyme digestion of PCR products from transgenes or homologous endogenous genes.
Cell death and barrier disruption by clinically used iodine concentrationsClinically used concentrations of povidone-iodine (PVP-I) are toxic to eukaryotic cells by attacking the lipid bilayer and tight junctions with fast kinetics and urge the reappraisal of PVP-I use.
Vasopressin V1a receptor and oxytocin receptor regulate murine sperm motility differentlyEpididymal vasopressin V1a receptor is involved in the regulation of sperm motility, and its antagonist may be a therapeutic agent for male-type reproductive dysfunction.
PACSIN2 as a modulator of autophagy and mercaptopurine cytotoxicity: mechanisms in lymphoid and intestinal cellsThis study evaluates the role of PACSIN2 in autophagy modulation and its impact on mercaptopurine cytotoxicity in lymphoid and intestinal models.
Visualized procollagen Iα1 demonstrates the intracellular processing of propeptidesProcollagen Iα1 with two tags reveals the different fates of processed propeptides, the rate-limiting step in collagen secretion, and a link between defects in intracellular processing and diseases.
Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19This proof-of-concept study shows that plitidepsin, a marine peptide that inhibits SARS-CoV-2 replication, has a favorable safety profile and may be an efficacious treatment for patients with COVID-19.
TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degenerationThis study identifies the endolysosomal two-pore channel TPC2 as a potential novel drug target for age-related macular degeneration (AMD). Inhibition of TPC2 reduces two key clinical hallmarks of the AMD, retinal inflammation and formation of leaky choroi.
BRD2 regulation of sigma-2 receptor upon cholesterol deprivationUpon cholesterol deprivation, epigenetic bookmark reader BRD2 and master transcription factor SREBP2 form a complex at bookmarked chromatin (H3K27ac), thereby activating the transcription of the sigma-2 receptor—a recently unveiled player in cholesterol homeostasis.
The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancerUsing patient-derived organoids the authors show how a specialized polarity pathway protects our gut barrier from stress-induced collapse. Findings highlight both diagnostic and therapeutic potential of the pathway for treating gut barrier dysfunction in aging, cancer, and dysbiosis.