Thermoneutral housing worsens MASLD and reveals defective brown adipose tissue response to β3-adrenergic stimulation.

Metabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis and evaluate therapeutic approaches. The majority of the lipids accumulating in the liver upon MASLD originate from adipose tissue and appropriate models to study the liver-adipose tissue dialog are also needed.

Orange peel extract and hesperidin attenuate myeloperoxidase activity and oxidative stress in vitro, with anti-inflammatory effects in vivo: a natural approach to gingival protection.

Periodontal inflammation, such as gingivitis, involves neutrophil infiltration and elevated myeloperoxidase (MPO) activity, leading to excessive reactive oxygen species (ROS) that damage cellular structures, including proteins and lipids. In the oral cavity, oxidative stress may worsen due to local iron release from microbleeding, promoting tissue destruction and gingival recession. This study evaluated the protective effects of orange peel aqueous extract (OPE) and hesperidin (HSP) against iron-induced oxidative damage in human plasma.

Uncovering an antifibrotic Prrx1-lineage mesenchymal cell subpopulation in fibrotic lungs.

Idiopathic pulmonary fibrosis (IPF) is a rare and fatal lung disease caused by progressive damage to alveolar epithelial cells, leading to abnormal activation of mesenchymal cells. The PRRX1 transcription factor (TF) has been found to be reactivated in IPF and was previously identified as a key mesenchymal TF in pulmonary fibrosis. In this study, we utilized the Prrx1:CreERT2; Rosa26iTomato murine transgenic line to further characterize the Prrx1-positive cell lineage in healthy and fibrotic lungs.

GDF15 is associated with hepatocellular senescence and correlates with mortality in patients with alcohol-associated hepatitis.

Background & Aims: Cellular senescence is characterized by the loss of proliferative capacity, cell cycle arrest, and the acquisition of a proinflammatory senescence-associated secretory phenotype (SASP). Senescence is frequently present in advanced chronic liver diseases; however, the impact of hepatocellular senescence in alcohol-associated liver disease (ALD) progression and alcohol-associated hepatitis (AH) is poorly understood.

Methods: Senescence was evaluated in transcriptomic data from patients at different ALD stages: advanced fibrosis (n = 10), cirrhosis (n = 10), and AH (n = 29).

FedECA: federated external control arms for causal inference with time-to-event data in distributed settings.

External control arms can inform early clinical development of experimental drugs and provide efficacy evidence for regulatory approval. However, accessing sufficient real-world or historical clinical trials data is challenging. Indeed, regulations protecting patients' rights by strictly controlling data processing make pooling data from multiple sources in a central server often difficult.

Euglycemic diabetic ketoacidosis associated with a sodium-glucose co transporter 2 inhibitor use in a trauma patient: a case report.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), like empagliflozin, are widely prescribed for managing type 2 diabetes mellitus. However, they carry a rare but serious risk: euglycemic diabetic ketoacidosis (EDKA). EDKA's atypical presentation, characterized by metabolic acidosis and ketosis despite normal blood glucose levels, often delays diagnosis, posing significant challenges in intensive care.

The Fibrosis-4 score is associated with overall mortality and severe haematological toxicity in older patients with cancer: Analysis of two prospective cohort studies.

The management of older adults with cancer is complicated. Although the liver metabolizes most chemotherapy agents, the predictive value of the liver status in older patients with cancer remains unclear. Here, we evaluated the association of the Fibrosis-4 (FIB-4) score with overall mortality and toxicity in older patients with cancer.

The proline isomerase Pin1 inhibitors PiB and juglone protect rats against lipopolysaccharide-induced respiratory inflammation.

The peptidyl-prolyl cis/trans-isomerase, NIMA-interacting 1 (Pin1), is involved in several cellular functions by changing the conformation and activity of phosphorylated proteins. Its key role in cellular signalling makes Pin1 an appealing target for the development of pharmacological agents to treat diseases such as inflammation. Pulmonary inflammation is a major disease resulting from the activation of immune cells by microbes or pollutants.

Telomere biology disorders in lung transplantation: Clinical challenges and management strategies.

Telomeres, repetitive DNA sequences at the ends of chromosomes, play a crucial role in maintaining genomic stability. In recent years, their significance in lung transplantation has gained growing attention. Shortened telomeres-whether due to inherited telomeropathies or acquired attrition-have emerged as a risk factor for various pulmonary diseases, particularly pulmonary fibrosis, which is a leading indication for lung transplantation.

PTEN Inactivation in Mouse Colonic Epithelial Cells Curtails DSS-Induced Colitis and Accelerates Recovery.

: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. : In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis.

Performance of the China-CLIF framework in acute-on-chronic liver failure: a multicohort study across all aetiologies.

Background: Acute-on-chronic liver failure (ACLF) of various aetiologies is a complex syndrome with high short-term mortality and significant global burden.

Objective: To explore easily applicable diagnostic criteria and an accurate prognostic score for ACLF.

Design: Clinical data from 5288 patients (after exclusions from 7388 screened) with acute deterioration of chronic liver disease across various aetiologies were used to evaluate the performance of European Chronic Liver Failure (CLIF) and Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria.

EASL postgraduate course report: Vascular biology in chronic liver disease and clinical management implications.

This article reviews the content of the EASL Congress 2024 postgraduate course on vascular biology in chronic liver disease and its clinical management. It focuses on haemostasis in patients with cirrhosis, vascular liver diseases including porto-sinusoidal vascular disorder and portal vein thrombosis, and portal hypertension and its extrahepatic complications in cirrhosis. Haemostatic changes in cirrhosis coincide with complex shifts between the risks of bleeding and thrombosis, making management decisions challenging.

APEX2-based quantitative proteomics of LAT and CD3ζ interactomes in living human Jurkat T cells unveils new interactors.

T cell receptor (TCR) stimulation induces a signaling cascade that starts with the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) present in the TCR-CD3 complex. This is followed by the phosphorylation of proteins including LAT, which once phosphorylated interacts with multiple proteins allowing signal diversification and amplification. We take advantage of APEX2-based peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track the formation and dynamics of CD3ζ (also known as CD247) and LAT interactomes in TCR-activated Jurkat T cells.

Pregnancy-acquired memory CD4 regulatory T cells improve pregnancy outcome in mice.

Subsequent pregnancies are generally less prone to obstetric complications. A successful pregnancy outcome requires pivotal immunological adaptation to ensure immune tolerance towards the foetus. Thus, the lower risk for pregnancy complication during subsequent pregnancies may be attributable to immune memory mounted during first pregnancies.

LRO biogenesis and function: what can we learn from mast cells?

Lysosome-related organelles (LROs) are specialized compartments with cell type-specific roles. In mast cells (MCs), which are tissue-localized hematopoietic effector cells, LROs refer to secretory lysosomes also known as secretory granules (SGs) containing numerous pre-formed inflammatory mediators including proteases, proteoglycans, lysosomal enzymes, histamine and serotonin. Their release during MC activation is responsible for allergic, inflammatory manifestations, the fight against parasitic agents or the neutralization of toxins.

Sunitinib as Second-Line Treatment in Advanced Intrahepatic Cholangiocarcinoma: Results From the SUN-CK GERCOR Phase II Trial.

Background & Aims: Angiogenesis is critical in intrahepatic cholangiocarcinoma (ICC), a highly lethal cancer with limited treatment options. Sunitinib, a multi-receptor tyrosine kinase inhibitor, has strong antiangiogenic and antitumor effects. We aimed to evaluate the efficacy and tolerability of sunitinib as a second-line treatment in chemotherapy-pretreated patients with advanced ICC.

Revisiting Hepatic Small Vessel Neoplasms and Anastomosing Hemangiomas as a Unique Capillary Liver Neoplasm: A 25-Case Series With Pathomolecular Correlations.

Hepatic small vessel neoplasm (HSVN) and anastomosing hemangioma (AH) are 2 capillary liver neoplasms that are challenging to differentiate in clinical practice. This study aimed to refine their classification through integrated histopathologic and molecular analyses. We conducted a bicentric retrospective study of 25 cases (15 resections and 10 biopsies).

Kupffer Cells Regulate iNKT Cells Through Il-12 to Mitigate the Extent of APAP-Induced Damage in the Liver.

To explore the innate immune response in the occurrence and development of APAP-induced drug-induced liver injury and the biological effect caused by the interaction between immune cells through real-time, in vivo analysis. We used conventional molecular biology technology and multi-photon confocal live imaging to explore the effect of the interactive dialogue between iNKT and Kupffer cells on neutrophil recruitment in the occurrence and development of APAP-induced liver injury. iNKT cell deficient mice were more prone to liver injury induced by excessive APAP, and the degree of liver injury was more severe.