A redundant system of thioredoxin and glutathione is essential for pancreatic acinar integrity.

Background & Aims: Oxidative stress and antioxidant defense mechanisms have long been implicated in the pathogenesis of acute pancreatitis (AP). However, there is a notable lack of in vivo experimental evidence clarifying their precise role.

Methods: We generated and analyzed mice with a pancreas-specific deletion of Txnrd1 (Txnrd1).

Novel Coating Approaches for Polyethylene Biliary Stents to Reduce Microbial Adhesion, Prevent Biofilm Formation, and Prolong Stent Patency.

: Occlusion of plastic biliary stents is a common complication in biliary drainage, often requiring exchange procedures every 2-4 months due to microbial colonization and sludge formation. This study aimed to evaluate diamond-like carbon (DLC) coatings, with and without silver nanoparticle additives, for preventing stent occlusion. : Polyethylene (PE) stents were coated with DLC using PlasmaImpax for DLC-1 and pulsed laser deposition for DLC-2.

Polyunsaturated fatty acid-induced metabolic exhaustion and ferroptosis impair the anti-tumour function of MAIT cells in MASLD.

Background & Aims: Mucosal-associated invariant T (MAIT) cells constitute a highly abundant innate-like T-cell population in the human liver that is critical for immune surveillance of hepatic cancers. However, MAIT cells are often dysfunctional in human hepatocellular carcinoma (HCC), for reasons that remain unclear. Here, we aimed to identify the mechanisms driving MAIT cell dysfunction in metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic liver condition that predisposes patients to HCC.

Risk factors for vancomycin resistance in patients with bloodstream infections: an analysis of the Munich Multicentric Enterococci Cohort.

Unlabelled: is difficult to treat owing to its intrinsic and acquired resistance to antibiotics, particularly vancomycin. Vancomycin-resistant is an important cause of bloodstream infections in healthcare settings with limited treatment options. This study aimed to analyze the risk factors for vancomycin-resistant bloodstream infection.

Label-free single-cell phenotyping to determine tumor cell heterogeneity in pancreatic cancer in real time.

Resistance to chemotherapy of pancreatic ductal adenocarcinoma (PDAC) is largely driven by intratumoral heterogeneity (ITH) due to tumor cell plasticity and clonal diversity. To develop alternative strategies to overcome this defined mechanism of resistance, tools to monitor and quantify ITH in a rapid and scalable fashion are needed urgently. Here, we employed label-free digital holographic microscopy (DHM) to characterize ITH in PDAC.

Approximation of EVLWI in severe COVID-19 pneumonia using quantitative imaging techniques: an observational study.

Background: This study aimed to approximate the level of extravascular lung water (EVLW) in patients with severe COVID-19 pneumonia using quantitative imaging techniques. The elevation of EVLW is known to correlate with the degree of diffuse alveolar damage and linked with the mortality of critically ill patients. Transpulmonary thermodilution (TPTD) is the gold standard technique to estimate the total amount of EVLW, but it is invasive and requires specialized equipment and trained personnel.

Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma.

Locally advanced esophageal adenocarcinoma remains difficult to treat and the ecological and evolutionary dynamics responsible for resistance and recurrence are incompletely understood. Here, we performed longitudinal multiomic analysis of patients with esophageal adenocarcinoma in the MEMORI trial. Multi-region multi-timepoint whole-exome and paired transcriptome sequencing was performed on 27 patients before, during and after neoadjuvant treatment.

Activation of RAS/MEK/ERK signalling drives biliary differentiation in primary liver cancer.

Background: mutations are frequently observed in human cholangiocarcinoma (CCA), while they are relatively rare in hepatocellular carcinoma (HCC). The role of RAS-dependent signalling pathways in CCA development is currently not well understood.

Objective: The objective of this study was to investigate RAS-dependent signalling pathways in CCA and their role in tumour development and differentiation.

Loss of FXR or Bile Acid-dependent Inhibition Accelerate Carcinogenesis of Gastroesophageal Adenocarcinoma.

Background & Aims: The incidence of Barrett esophagus (BE) and gastroesophageal adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BAs) support fat digestion and undergo microbial metabolism in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis.

Epithelial genetic muscarinic receptor 3 ablation induces sex-specific modulation of colonic intestinal progenitor cells and response to intestinal injury.

Background & Aims: Epithelial muscarinic acetylcholine receptor subtype 3 (M3R) signaling modulates intestinal stem and progenitor cell function, yet its impact on colonic homeostasis remains unclear. Hence, this study explores the sex-specific effects of epithelial genetic M3R ablation and muscarinic receptor agonism on murine colonic Lgr5-EGFP+ progenitor cells and epithelial homeostasis.

Methods: Genetic ablation of M3R was achieved using Vil-Cre × M3R fl/fl mice.

A decision point between transdifferentiation and programmed cell death priming controls KRAS-dependent pancreatic cancer development.

KRAS-dependent acinar-to-ductal metaplasia (ADM) is a fundamental step in the development of pancreatic ductal adenocarcinoma (PDAC), but the involvement of cell death pathways remains unclear. Here, we show that key regulators of programmed cell death (PCD) become upregulated during KRAS-driven ADM, thereby priming transdifferentiated cells to death. Using transgenic mice and primary cell and organoid cultures, we show that transforming growth factor (TGF)-β-activated kinase 1 (TAK1), a kinase regulating cell survival and inflammatory pathways, prevents the elimination of transdifferentiated cells through receptor-interacting protein kinase 1 (RIPK1)-mediated apoptosis and necroptosis, enabling PDAC development.

Decreased overall survival in patients with hepatocellular carcinoma during the COVID-19 pandemic.

Background: The coronavirus disease-2019 (COVID-19) pandemic had a profound influence on screening, diagnosis and treatment of cancer patients worldwide. Due to overloaded health care facilities, screening and surveillance visits for early cancer detection were postponed or completely omitted. This included surveillance of patients with liver cirrhosis who are at risk for development of hepatocellular carcinoma (HCC) and resulted in a decrease in HCC diagnoses.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

HBV-related HCC development in mice is STAT3 dependent and indicates an oncogenic effect of HBx.

Background & Aims: Although most hepatocellular carcinoma (HCC) cases are driven by hepatitis and cirrhosis, a subset of patients with chronic hepatitis B develop HCC in the absence of advanced liver disease, indicating the oncogenic potential of hepatitis B virus (HBV). We investigated the role of HBV transcripts and proteins on HCC development in the absence of inflammation in HBV-transgenic mice.

Methods: HBV-transgenic mice replicating HBV and expressing all HBV proteins from a single integrated 1.

[Infections and liver cirrhosis].

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H.

Metabolic Reprogramming Is an Initial Step in Pancreatic Carcinogenesis That Can Be Targeted to Inhibit Acinar-to-Ductal Metaplasia.

Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis.

Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition.

Background: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolization in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis.

Herpes Simplex Virus Bronchopneumonitis in Critically Ill Patients with Acute on Chronic Liver Failure: A Retrospective Analysis.

(1) Background: Critically ill patients are frequently diagnosed with pulmonary Herpes simplex virus-1 (HSV) reactivation, which then can lead to HSV bronchopneumonitis and is associated with higher mortality and longer mechanical ventilation. For the particular subgroup of critically ill patients with acute on chronic liver failure (ACLF), however, the impact of HSV reactivation is unknown. We investigated the impact of HSV reactivation in these patients.