Case Report: gene mutation resulting in central conducting lymphatic anomaly facilitates group A sepsis.

Background: Central conducting lymphatic anomaly (CCLA) is a heterogeneous disorder characterized by structural anomalies in the main collecting lymphatic vasculature. These anomalies result in chronic chylous leaks, causing issues such as congenital hydrothorax and potentially impairing the normal immune response. Recently, mutations in the MyoD family inhibitor domain-containing () gene have been identified as a cause of CCLA.

Cellular pyrimidine imbalance triggers mitochondrial DNA-dependent innate immunity.

Cytosolic mitochondrial DNA (mtDNA) elicits a type I interferon response, but signals triggering the release of mtDNA from mitochondria remain enigmatic. Here, we show that mtDNA-dependent immune signalling via the cyclic GMP-AMP synthase‒stimulator of interferon genes‒TANK-binding kinase 1 (cGAS-STING-TBK1) pathway is under metabolic control and is induced by cellular pyrimidine deficiency. The mitochondrial protease YME1L preserves pyrimidine pools by supporting de novo nucleotide synthesis and by proteolysis of the pyrimidine nucleotide carrier SLC25A33.

Mitochondrial Proteases: Multifaceted Regulators of Mitochondrial Plasticity.

Mitochondria are essential metabolic hubs that dynamically adapt to physiological demands. More than 40 proteases residing in different compartments of mitochondria, termed mitoproteases, preserve mitochondrial proteostasis and are emerging as central regulators of mitochondrial plasticity. These multifaceted enzymes limit the accumulation of short-lived, regulatory proteins within mitochondria, modulate the activity of mitochondrial proteins by protein processing, and mediate the degradation of damaged proteins.

PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis.

Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum.

A simple clinical score predicts high risk for upper gastrointestinal hemorrhages from varices in patients with chronic liver disease.

Objective: Upper gastrointestinal (GI) bleeding from esophageal or gastric fundus varices is a common complication of portal hypertension in liver cirrhosis and carries a high mortality rate of 20-35%. Stratifying high-risk patients for variceal bleeding is mainly based on endoscopic scoring. The purpose of this study was to develop a simple clinical score to assess the bleeding risk.

Clinical and prognostic role of plasma coagulation factor XIII activity for bleeding disorders and 6-year survival in patients with chronic liver disease.

Background/aims: Alterations of plasma coagulation factor XIII may contribute to bleeding disorders in patients with liver cirrhosis. As standard clotting tests such as prothrombin time or activated thromboplastin time (aPTT) cannot detect factor XIII deficiency, this may often be overlooked in clinical practice. We aimed to define factor XIII's clinical and prognostic role in chronic liver disease.