Safe and Orally Bioavailable Inhibitor of Serine Palmitoyltransferase Improves Age-Related Sarcopenia.

The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide synthesis, serine palmitoyltransferase (SPT).

Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow.

Background: Immunothrombosis is the process by which the coagulation cascade interacts with the innate immune system to control infection. However, the formation of clots within the brain vasculature can be detrimental to the host. Recent work has demonstrated that Toxoplasma gondii infects and lyses central nervous system (CNS) endothelial cells that form the blood-brain barrier (BBB).

Temporal epidemiological profile of oral potentially malignant disorders in southern Brazil.

The study aimed to investigate oral potentially malignant disorders (OPMDs) diagnosed in an Oral Pathology service in southern Brazil over a span of 56 years and to assess the factors influencing their severity and outcomes. A retrospective analysis of histopathological records from 1965 to 2021 was performed. Lesions diagnosed as leukoplakia, erythroplakia, leukoerythroplakia, or actinic cheilitis were included.

Maternal Low-Protein Diet During Nursing Leads to Glucose-Insulin Dyshomeostasis and Pancreatic-Islet Dysfunction by Disrupting Glucocorticoid Responsiveness in Male Rats.

Both perinatal malnutrition and elevated glucocorticoids are pivotal triggers of the growing global pandemic of metabolic diseases. Here, we studied the effects of metabolic stress responsiveness on glucose-insulin homeostasis and pancreatic-islet function in male Wistar offspring whose mothers underwent protein restriction during lactation. During the first two weeks after delivery, lactating dams were fed a low-protein (4% protein, LP group) or normal-protein diet (22.