Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF.

Comparison of the single-cell and single-nucleus hepatic myeloid landscape within decompensated cirrhosis patients.

Background And Aims: A complete understanding of disease pathophysiology in advanced liver disease is hampered by the challenges posed by clinical specimen collection. Notably, in these patients, a transjugular liver biopsy (TJB) is the only safe way to obtain liver tissue. However, it remains unclear whether successful sequencing of this extremely small and fragile tissue can be achieved for downstream characterization of the hepatic landscape.

Adipose tissue macrophage dysfunction is associated with a breach of vascular integrity in NASH.

Background & Aims: In non-alcoholic fatty liver disease (NAFLD), monocytes infiltrate visceral adipose tissue promoting local and hepatic inflammation. However, it remains unclear what drives inflammation and how the immune landscape in adipose tissue differs across the NAFLD severity spectrum. We aimed to assess adipose tissue macrophage (ATM) heterogeneity in a NAFLD cohort.

Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity.

Objective: Acute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.

Design: Following phenotypic characterisation, we performed RNA sequencing on CD14CD16 monocytes from patients with ACLF and decompensated alcoholic cirrhosis.

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally.

Toxicity of the amphetamine metabolites 4-hydroxyamphetamine and 4-hydroxynorephedrine in human dopaminergic differentiated SH-SY5Y cells.

Amphetamine (AMPH) is a psychostimulant used worldwide by millions of patients in the clinical treatment of attention deficit hyperactivity disorder, narcolepsy or even obesity, and is also a drug of abuse. 4-Hydroxynorephedrine (4-OHNE) and 4-hydroxyamphetamine (4-OHAMPH) are two major metabolites known to persist in the brain longer than AMPH. The contribution of AMPH metabolites for its neurotoxicity is undetermined.

"Ecstasy" toxicity to adolescent rats following an acute low binge dose.

Background: 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a worldwide drug of abuse commonly used by adolescents. Most reports focus on MDMA's neurotoxicity and use high doses in adult animals, meanwhile studies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral organs using a binge dose scheme that tries to simulate human adolescent abuse.

Mitochondria: key players in the neurotoxic effects of amphetamines.

Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects.

The neurotoxicity of amphetamines during the adolescent period.

Amphetamine-type psychostimulants (ATS), such as amphetamine (AMPH), 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations.