Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.

Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood.

A Comprehensive Metabolomic and Microbial Analysis Following Dietary Amino Acid Reduction in Mice.

Nutritional metabolomics provides a comprehensive overview of the biochemical processes that are induced by dietary intake through the measurement of metabolite profiles in biological samples. However, there is a lack of deep phenotypic analysis that shows how dietary interventions influence the metabolic state across multiple physiologic sites. Dietary amino acids have emerged as important nutrients for physiology and pathophysiology given their ability to impact cell metabolism.

Metabolic regulation of the mitochondrial immune checkpoint.

Disrupting mitochondrial function in malignant cells is a promising strategy to enhance anticancer immunity. We have recently demonstrated that depriving colorectal cancer cells of serine results in mitochondrial dysfunction coupled with the cytosolic accumulation of mitochondrial DNA and consequent activation of CGAS- and STING-dependent tumor-targeting immune responses.

Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling.

Serine is critical for supporting cancer metabolism, and depriving malignant cells of this nonessential amino acid exerts antineoplastic effects, in large part, through disrupting metabolic pathways. Given the intricate relationship between cancer metabolism and the immune system, the metabolic defects imposed by serine deprivation might impact tumor-targeting immunity. In this study, we demonstrated that restricting endogenous and exogenous sources of serine in colorectal cancer cells results in mitochondrial dysfunction, leading to mitochondrial DNA (mtDNA) accumulation in the cytosol and consequent cGAS-STING1-driven type I IFN secretion.

Over 30 years of STEP: The Pittsburgh experience with first-episode psychosis.

Aims: For over 30 years, combined research and treatment settings in the US have been critical to conceptualizing care for first-episode psychosis (FEP). Here we describe an early example of such a context, the Services for the Treatment of Early Psychosis (STEP) clinic, which is affiliated with the University of Pittsburgh.

Methods: We describe STEP's historical roots and establishment in the early 1990s; STEP's research and treatment contributions, alongside its growth and ongoing leadership.