The carbonyl nucleobase adduct MAde is a potent antigen for adaptive polyclonal MR1-restricted T cells.

The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.

Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups.

Introduction: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.

Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells.

MR1T cells are a recently found class of T cells that recognize antigens presented by the major histocompatibility complex-I-related molecule MR1 in the absence of microbial infection. The nature of the self-antigens that stimulate MR1T cells remains unclear, hampering our understanding of their physiological role and therapeutic potential. By combining genetic, pharmacological, and biochemical approaches, we found that carbonyl stress and changes in nucleobase metabolism in target cells promote MR1T cell activation.

Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.

Background: The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches.

Methods And Results: Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth.

Implication of metabolism in the polarization of tumor-associated-macrophages: the mass spectrometry-based point of view.

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients' prognosis.

EASY-FIA: A Readably Usable Standalone Tool for High-Resolution Mass Spectrometry Metabolomics Data Pre-Processing.

Flow injection analysis coupled with high-resolution mass spectrometry (FIA-HRMS) is a fair trade-off between resolution and speed. However, free software available for data pre-processing is few, web-based, and often requires advanced user specialization. These tools rarely embedded blank and noise evaluation strategies, and direct feature annotation.

NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2).

Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most common events in human cancers. Several efforts have been made toward the identification of selective PI3K pathway inhibitors. However, the success of these molecules has been partially limited due to unexpected toxicities, the selection of potentially responsive patients, and intrinsic resistance to treatments.

Plasmatic Hippuric Acid as a Hallmark of Frailty in an Italian Cohort: The Mediation Effect of Fruit-Vegetable Intake.

Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study.

DSM-5 Maladaptive Personality Domains among Treatment-Seeking Individuals with Alcohol Use Disorder: The Role of Disinhibition and Negative Affectivity.

Dimensional models of personality and personality disorders (PDs) have been widely investigated among individuals with alcohol use disorders (AUD). Nevertheless, DSM-5 maladaptive personality domains showed mixed associations with AUD. Furthermore, no studies have explored the role of DSM-5 maladaptive personality domains on the comorbidity between AUD and different PDs.

Mindful self-regulation of attention is a key protective factor for emotional dysregulation and addictive behaviors among individuals with alcohol use disorder.

Individuals with alcohol use disorder (AUD) and other substance use disorders (SUDs) frequently show co-occurrent behavioral addictions (BAs) (i.e., gambling and compulsive sex) and other inflexible behaviors (IBs) (i.

Dialectical behaviour therapy skills training for the treatment of addictive behaviours among individuals with alcohol use disorder: the effect of emotion regulation and experiential avoidance.

Backgrounds: Dialectical behavior therapy skills training (DBT-ST) is an effective treatment for alcohol use disorder (AUD). AUD frequently co-occurs with other addictive behaviors.

Objective: s: These secondary analyses of prior studies on the effectiveness of a 3-month DBT-ST program for AUD investigated pre- post-treatment changes in the severity of concurrent addictive behaviors.