Selective genetic inactivation of Caspase 8 in hepatocytes ameliorates progression of MASH following Jnk deficiency.

Background And Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is associated with c-Jun N-terminal kinases (JNK) activation across various cell types, but its hepatocyte-specific function in steatotic liver disease remains unclear. Our study investigates the role of JNK1/JNK2 during MASH progression and dissect its hepatocyte-specific function.

Approach And Results: We showed that UK biobank patients with a predicted-loss-of-function (pLOF) variant of JNK1 presented an increased prevalence of MASLD and liver damage.

Comprehensive transcriptome, miRNA and kinome profiling identifies new treatment options for personalized lung cancer therapy.

Background: Basic research identified oncogenic driver mutations in lung cancer (LC). However, <10% of patients carry driver mutations. Thus, most patients are not recommended for first-line kinase inhibitor (KI)-based therapies.

The role of vascularity and the fibrovascular interface in interstitial lung diseases.

Interstitial lung disease (ILD) is a clinical term that refers to a diverse group of non-neoplastic lung diseases. This group includes idiopathic and secondary pulmonary entities that are often associated with progressive pulmonary fibrosis. Currently, therapeutic approaches based on specific structural targeting of pulmonary fibrosis are limited to nintedanib and pirfenidone, which can only slow down disease progression leading to a lower mortality rate.

'Diagnosis and Treatment of Hypersensitivity Pneumonitis' S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology.

German recommendations for the diagnosis of hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis (EAA), were last published in 2007 [1]. The current S2k Guideline for the Diagnosis and Treatment of Hypersensitivity Pneumonitis (HP) replaces these diagnostic recommendations. They were supplemented by the aspect of chronic, and in particular of the chronic fibrotic phenotype of HP, and also, as first HP guideline, include treatment recommendations.

3D multiscale characterization of the human placenta: Bridging anatomy and histology by X-ray phase-contrast tomography.

The human placenta exhibits a complex three-dimensional (3D) structure with a interpenetrating vascular tree and large internal interfacial area. In a unique and yet insufficiently explored way, this parenchymal structure enables its multiple functions as a respiratory, renal, and gastrointestinal multiorgan. The histopathological states are highly correlated with complications and health issues of mother, and fetus or newborn.

The IBEX Imaging Knowledge-Base: A Community Resource Enabling Adoption and Development of Immunofluoresence Imaging Methods.

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modeled after efforts in the open-source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge-Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non-recommended reagents, e.

Various Hydrogel Types as a Potential In Vitro Angiogenesis Model.

Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine.

Protective effect of interferon type I on barrier function of human airway epithelium during rhinovirus infections in vitro.

The airway epithelium provides a crucial barrier against infection with respiratory pathogens. This barrier can be impaired following viral infection, paving the way for bacterial superinfections. Type I interferons (IFNs) are important antiviral mediators, and inhaled formulations of these glycoproteins are considered a potential approach for the treatment of respiratory viral infections.

GrandQC: A comprehensive solution to quality control problem in digital pathology.

Histological slides contain numerous artifacts that can significantly deteriorate the performance of image analysis algorithms. Here we develop the GrandQC tool for tissue and multi-class artifact segmentation. GrandQC allows for high-precision tissue segmentation (Dice score 0.

Synchrotron-Based Phase-Contrast Micro-CT Combined With Histology to Decipher Differences Between Hereditary and Sporadic Pediatric Pulmonary Veno-Occlusive Disease.

Pulmonary veno-occlusive disease (PVOD) is a lethal variant of pulmonary hypertension. The degree of pulmonary arterial involvement varies. Here, we compare two PVOD patients who were transplanted at 8 years of age, whereof one is a homozygous mutation carrier.

[Neoadjuvant therapy for resectable non-small cell lung cancer].

Treatment perspectives for non-small cell lung cancer (NSCLC) have been significantly expanded by the integration of immune checkpoint inhibitors into multimodal therapy concepts. Currently, combined, immune checkpoint-inhibitor-based therapy concepts are also advancing into early, resectable stages of NSCLC. Neoadjuvant and perioperative chemoimmunotherapy opened up a promising new preoperative treatment approach, but also raises some new questions and challenges.

Line-dropped gelatin multi-element calibration standards in LA-ICP-MS: a statistically verifying comparison with cryosectioned homogenized lung and liver as matrix-matched calibration standards and as corresponding reference materials.

Calibrations in LA-ICP-MS are typically very time-consuming and complex, as they need to be matched to the samples being measured and sectioned on a microtome. Alternatively, gelatin can be in droplet form or as a section, which is a more recent development. In this study, we report on investigations where hot multi-element gelatin solutions are placed in a linear fashion on microscopic slides to conduct comparative statistical observations between doped tissue homogenates from the liver and lung.

Distribution and volume of mitochondria in alveolar epithelial type 1 cells in infant and adult human lungs.

Alveolar epithelial type I (AE1) cells with their wide spatial expansion form approximately 95% of the outer surface area of the air-blood barrier inside the lung. Serial block-face scanning electron microscopy (SBF-SEM) investigations led to the hypothesis that AE1 cell mitochondria are preferentially distributed as aggregates in those parts of AE1 cells that are located above connective tissue pillars between capillaries, thus not increasing the thickness of the diffusion distance for oxygen and carbon dioxide. Furthermore, it was hypothesised that postnatal development requires adapting the amount and distribution of mitochondria in AE1 cells.

Deep learning for 3D vascular segmentation in hierarchical phase contrast tomography: a case study on kidney.

Automated blood vessel segmentation is critical for biomedical image analysis, as vessel morphology changes are associated with numerous pathologies. Still, precise segmentation is difficult due to the complexity of vascular structures, anatomical variations across patients, the scarcity of annotated public datasets, and the quality of images. Our goal is to provide a foundation on the topic and identify a robust baseline model for application to vascular segmentation using a new imaging modality, Hierarchical Phase-Contrast Tomography (HiP-CT).

The IBEX Knowledge-Base: Achieving more together with open science.

Iterative Bleaching Extends multipleXity (IBEX) is a versatile method for highly multiplexed imaging of diverse tissues. Based on open science principles, we created the IBEX Knowledge-Base, a resource for reagents, protocols and more, to empower innovation.

The metalloproteinase ADAM10 sheds angiotensin-converting enzyme (ACE) from the pulmonary endothelium as a soluble, functionally active convertase.

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in the regulation of blood pressure and fluid balance, with angiotensin-converting enzyme (ACE) being a key transmembrane enzyme that converts angiotensin I to angiotensin II. Hence, ACE activity is an important drug target in cardiovascular pathologies such as hypertension. Our study demonstrates that human pulmonary microvascular endothelial cells (HPMECs) are an important source of proteolytically released ACE.

Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.

Background: Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure.

Methods: This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days.

Low-Volume Lung Perfusion System for Single Lung Application in a Small Animal Model Enables Optimal Compliance With "" in 3R Principles of Animal Research.

lung perfusion (ESLP) is used for organ reconditioning, repair, and re-evaluation prior to transplantation. Since valid preclinical animal models are required for translationally relevant studies, we developed a 17 mL low-volume ESLP for double- and single-lung application that enables cost-effective optimal compliance "reduction" of the 3R principles of animal research. In single-lung mode, ten Fischer344 and Lewis rat lungs were subjected to ESLP and static cold storage using STEEN or PerfadexPlus.

Prognostic implications of HIF-1α expression in anal squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT).

Background: Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy.

Methods: We conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022.

Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice.

The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and IL17af mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis.

[Diagnosis and Treatment of Hypersensitivity Pneumonitis - S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology].

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time.