The ABCA1 agonist CS6253 shows favorable safety and pharmacokinetics in IND‐enabling toxicology and Phase 1 human studies aimed at the indication of Alzheimer’s disease.

Background: ABCA1‐mediated cholesterol transport is a central feature in many lipid‐ dependent diseases including APOE4‐associated Alzheimer’s disease and atherosclerosis‐CVD. ABCA1 upregulation of RNA transcription by nuclear factors (LXR, RXR) have been associated with liver side‐effects because of the common promotor element for ABCA1 and Fatty Acid Synthase. The ABCA1 agonist CS6253, derived from the C‐terminal of apoE was designed to stabilize and enhance ABCA1 function, thereby providing a safe alternative to transcriptional upregulation.

End-procedural adherence to recommended hemodynamic targets does not improve the outcome of elective tips in cirrhotic patients.

Background Aims: In clinical practice, the reduction of porto-caval pressure gradient (PCPG) following trans-jugular intra-hepatic porto-systemic shunt (TIPS) does not always meet the recommendation of current guidance. We evaluated the impact of different degrees of PCPG reduction, measured at the end of an elective TIPS, on ascites control, recurrence of portal hypertension-related bleeding (PHRB) and survival.

Approach And Results: Cirrhotic patients receiving TIPS for refractory ascites (RA) or for the secondary prophylaxis of PHRB were consecutively enrolled.

Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.

Background & Aims: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes.

Methods: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake.

Background & Aims: Quantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT).

Decreased cardio-respiratory information transfer is associated with deterioration and a poor prognosis in critically ill patients with sepsis.

Assessing illness severity in the ICU is crucial for early prediction of deterioration and prognosis. Traditional prognostic scores often treat organ systems separately, overlooking the body's interconnected nature. Network physiology offers a new approach to understanding these complex interactions.

Prevalence, characteristics and outcomes of patients with metabolic and alcohol related/associated liver disease (MetALD): a systematic review and meta-analysis.

Background: In light of the new nomenclature of steatotic liver disease (SLD), we aimed to enhance the existing knowledge on the epidemiology and clinical outcomes of metabolic and alcohol related/associated liver disease (MetALD).

Methods: A systematic review and meta-analysis were performed in Medline/PubMed, Embase, Scopus and Cochrane databases to evaluate the prevalence and outcomes of MetALD within the SLD population and to compare the characteristics between MetALD patients and those with metabolic dysfunction associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD). Nineteen studies from nine countries that evaluated 4,543,341 adult participants with SLD were included.

Optimized and Simplified Technique for the Production and Culture of Precision-Cut Liver Slices.

This protocol presents a simple system for the creation and culture of Precision-cut Liver Slices (PCLS). PCLS contains all cells in an intact environment and, therefore, resembles a mini model of the whole organ. They enable the study of live tissues while replicating their complex phenotypes.

The effect of haemoglobin and blood transfusion on preterm infant gut perfusion and injury.

Introduction: There is significant uncertainty regarding the role that anaemia or red blood cell transfusion (RBCT) plays in the development of gut injury in preterm infants. This study evaluated Near Infrared Spectroscopy (NIRS) together with a range of known biomarkers of gut inflammation to identify their relationship with anaemia and RBCT.

Method: A prospective observational study of preterm infants born at <30 weeks gestation was conducted from birth until either 36 weeks post conceptional age or discharge home.

Fetal hepatocytes protect the HSPC genome via fetuin-A.

The maintenance of genomic integrity in rapidly proliferating cells is a substantial challenge during embryonic development. Although numerous cell-intrinsic mechanisms have been revealed, little is known about genome-protective effects and influences of developmental tissue microenvironments on tissue-forming cells. Here we show that fetal liver hepatocytes provide protection to haematopoietic stem and progenitor cell (HSPC) genomes.

A Pax3 lineage gives rise to transient haematopoietic progenitors.

During embryonic development, muscle tissues, skin, and a subset of vascular endothelial cells arise from Pax3-expressing embryonic progenitors defined as paraxial mesoderm. By contrast, haemogenic potential is well established for extra-embryonic mesoderm and intra-embryonic lateral plate mesoderm, which do not express Pax3. To date, it is not known whether the haematopoietic system also contains Pax3 lineage cells.

Breakthroughs in nanoparticle-based strategies for pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, mainly due to its high heterogeneity, resistance to therapy and late diagnosis, with a 5-year survival rate of less than 10%. This dismal prognosis has promoted strategies to develop more effective treatments. Nanoparticle-based strategies have emerged, in the last decades, as a great opportunity because they can enhance drug delivery and promote controlled release, presenting lower side effects than conventional therapeutic regimens.

Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease.

In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.

The new digital era in decompensated cirrhosis.

There is a growing global burden of liver disease with the current management for complications of liver cirrhosis being reactive as opposed to proactive, affecting outcomes. Management can often be suboptimal in overburdened health-care systems with considerable socioeconomic and geographical disparity existing, which was exacerbated by the COVID-19 pandemic, highlighting the need for sustainable care pathways to be delivered remotely. To this end, digital health care could be the key and, in this Review, we highlight the principal studies that have explored the use of digital technology in the management of cirrhosis complications.

Overweight and obesity among Israeli adolescents and the risk for serious morbidity in early young adulthood: a nationwide retrospective cohort study.

Background: Morbidities related to obesity are usually associated with its severity and duration. Yet, the onset of serious morbidities in early adulthood among otherwise healthy adolescents with obesity is understudied. We aimed to investigate the association between adolescent BMI and serious morbidities before age 25 years.

: an underestimated pathogen in brain infection?

is an oral commensal organism belonging to the group (SAG). causes periodontitis as well as invasive, pyogenic infection of the central nervous system, pleural space or liver. Compared with other SAG organisms, has a higher mortality as well as a predilection for intracranial infection, suggesting it is likely to possess virulence factors that mediate specific interactions with the host resulting in bacteria reaching the brain.

Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ.

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure.

VPS4A is the selective receptor for lipophagy in mice and humans.

Lipophagy is a ubiquitous mechanism for degradation of lipid droplets (LDs) in lysosomes. Autophagy receptors selectively target organelles for lysosomal degradation. The selective receptor for lipophagy remains elusive.