From MASLD to HCC: What's in the middle?

Metabolic dysfunction associated steatotic liver disease (MASLD) is a progressive pathological condition characterized by the accumulation of triglycerides within hepatocytes that causes histological changes, which, in the long run, might compromise liver functional capacities. MASLD predisposes to metabolic dysfunction-associated steatohepatitis (MASH), in which the persistence of inflammatory reactions perpetuates tissue injury and induces alterations of the extracellular matrix, leading to liver fibrosis and cirrhosis. Furthermore, these processes are also fertile ground for the development of hepatocellular carcinoma (HCC).

Engineering Cell Instructive Microenvironments for In Vitro Replication of Functional Barrier Organs.

Multicellular organisms exhibit synergistic effects among their components, giving rise to emergent properties crucial for their genesis and overall functionality and survival. Morphogenesis involves and relies upon intricate and biunivocal interactions among cells and their environment, that is, the extracellular matrix (ECM). Cells secrete their own ECM, which in turn, regulates their morphogenetic program by controlling time and space presentation of matricellular signals.

Histidine-rich glycoprotein in metabolic dysfunction-associated steatohepatitis-related disease progression and liver carcinogenesis.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide. In 20%-30% of MASLD patients, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) which can lead to fibrosis/cirrhosis, liver failure as well as hepatocellular carcinoma (HCC). Here we investigated the role of histidine-rich glycoprotein (HRG), a plasma protein produced by hepatocytes, in MASLD/MASH progression and HCC development.

Role of the co-stimulatory molecule inducible T-cell co-stimulator ligand (ICOSL) in the progression of experimental metabolic dysfunction-associated steatohepatitis.

Background And Aims: Inducible T-cell Co-Stimulator (ICOS) present on T-lymphocytes and its ligand ICOSL expressed by myeloid cells play multiple roles in regulating T-cell functions. However, recent evidence indicates that reverse signalling involving ICOSL is also important in directing the differentiation of monocyte-derived cells. In this study, we investigated the involvement of ICOS/ICOSL dyad in modulating macrophage functions during the evolution of metabolic dysfunction-associated steatohepatitis (MASH).

Quantitative saccharide release of hydrothermally treated flours by validated salivary/pancreatic on-surface amylolysis (nanoGIT) and high-performance thin-layer chromatography.

The susceptibility of hydrothermally treated flour products to amylolysis was studied. The human salivary α-amylase and porcine pancreatin enzyme mixture containing α-amylase were used on-surface to investigate the release of glucose, maltose, and maltotriose. On the same adsorbent surface (all-in-one), their high-performance thin-layer chromatography separation and detection via selective chemical derivatization was performed.

Metabolic profiling of bacterial co-cultures reveals intermicrobiome interactions and dominant species.

In animal production, the use of probiotic microorganisms has increased since the ban on antibiotic growth promoters in 2006. The added microorganisms interact with the microbiome of the animals, whereby the probiotic activity is not fully understood. Several microorganisms of the genus Bacillus are already known for their probiotic activity and are applied as feed supplements to increase the health status of the animals.

Inflammatory processes involved in NASH-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. In the recent years nonalcoholic fatty liver disease (NAFLD) is becoming a growing cause of HCCs and the incidence of NAFLD-related HCCs is expected to further dramatically increase by the next decade. Chronic inflammation is regarded as the driving force of NAFLD progression and a key factor in hepatic carcinogenesis.

Capturing the spatial and temporal dynamics of tumor stroma for on-chip optimization of microenvironmental targeting nanomedicine.

Malignant cells grow in a complex microenvironment that plays a key role in cancer progression. The "dynamic reciprocity" existing between cancer cells and their microenvironment is involved in cancer differentiation, proliferation, invasion, metastasis, and drug response. Therefore, understanding the molecular mechanisms underlying the crosstalk between cancer cells and their surrounding tissue (, tumor stroma) and how this interplay affects the disease progression is fundamental to design and validate novel nanotherapeutic approaches.

Strain-specific quantification of probiotic Bacillus subtilis in feed by imaging high-performance thin-layer chromatography.

The European Union has banned the use of antibiotic growth promoters in animal production, which has led to increased use of probiotic microorganisms. These feed additives result in higher costs for farmers, which is why the demand for a quality control system to quantify probiotics in feeds has increased in recent years. Imaging high-performance thin-layer chromatography (HPTLC) was proven to be a robust method for determining the probiotic Bacillus subtilis DSM 29784 strain based on the production of selective bacterial metabolites and thus characteristic metabolite pattern.

Bacillus subtilis spores in probiotic feed quantified via bacterial metabolite using planar chromatography.

Interest in probiotics in animal production has increased due to the European ban on antibiotic growth promoters in 2006. Bacillus subtilis DSM 29784 (B. s.

Potential of simple, rapid, and non-target planar bioassay screening of veterinary drug residues.

Veterinary drug residues in food samples of animal origin are currently analyzed by target analysis using high-performance liquid chromatography combined with sophisticated mass spectrometers. Since the results are only partially consistent with the microbiological results and positive findings occur rarely (in the per mil range in Germany), the potential of a simple planar bioassay screening was studied in the field of veterinary drug residue analysis. Using only a simple dilution of the milk for sample preparation, it was challenging to meet the maximum residue limits for antibiotic drug residues, exemplarily shown for the screening of two fluoroquinolones.

Annexin A1 treatment prevents the evolution to fibrosis of experimental nonalcoholic steatohepatitis.

Annexin A1 (AnxA1) is an important effector in the resolution of inflammation which is involved in modulating hepatic inflammation in nonalcoholic steatohepatitis (NASH). In the present study, we have investigated the possible effects of treatment with AnxA1 for counteracting the progression of experimental NASH. NASH was induced in C57BL/6 mice by feeding methionine-choline deficient (MCD) or Western diets (WDs) and the animals were treated for 4-6 weeks with human recombinant AnxA1 (hrAnxA1; 1 µg, daily IP) or saline once NASH was established.

Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair.

The liver capacity to recover from acute liver injury is a critical factor in the development of acute liver failure (ALF) caused by viral infections, ischemia/reperfusion or drug toxicity. Liver healing requires the switching of pro-inflammatory monocyte-derived macrophages(MoMFs) to a reparative phenotype. However, the mechanisms involved are still incompletely characterized.

Hepatocyte-Specific Deletion of HIF2α Prevents NASH-Related Liver Carcinogenesis by Decreasing Cancer Cell Proliferation.

Background & Aims: Hypoxia and hypoxia-inducible factors (HIFs) are involved in chronic liver disease progression. We previously showed that hepatocyte HIF-2α activation contributed significantly to nonalcoholic fatty liver disease progression in experimental animals and human patients. In this study, using an appropriate genetic murine model, we mechanistically investigated the involvement of hepatocyte HIF-2α in experimental nonalcoholic steatohepatitis (NASH)-related carcinogenesis.

Effects of the Probiotic Activity of DSM 29784 in Cultures and Feeding Stuff.

The European Union banned the usage of antibiotic growth promoters in animal production. The probiotic microorganism of the genus appeared to be an attractive candidate to replace antibiotics. The DSM 29784 is one of these strains.

Imaging high-performance thin-layer chromatography as powerful tool to visualize metabolite profiles of eight Bacillus candidates upon cultivation and growth behavior.

Imaging high-performance thin-layer chromatography (HPTLC) was explored with regard to its ability to visualize changes in the metabolite profile of bacteria. Bacillus subtilis has become a model organism in many fields. The increasing interest in these bacteria is driven by their attributed probiotic activity.

Decellularized matrices for tumor cell modeling.

Collagen is the main component of the extracellular matrix and it plays a key role in tumor progression. Commercial collagen solutions are derived from animals, such as rat-tail and bovine or porcine skin. Their cost is quite high and the product is stable only at low temperature, with the disadvantage of a short expiring date.

CD4+ versus CD8+ T-lymphocyte identification in an integrated microfluidic chip using light scattering and machine learning.

T lymphocytes are a group of cells representing the main effectors of human adaptive immunity. Characterization of the most representative T-lymphocyte subclasses, CD4+ and CD8+, is challenging, but has a significant impact on clinical decisions. Up to now, T lymphocytes have been identified by quite complex cytometric assays, which are based on antibody labeling.

Adaptive immunity: an emerging player in the progression of NAFLD.

In the past decade, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease and cirrhosis, as well as an important risk factor for hepatocellular carcinoma (HCC). NAFLD encompasses a spectrum of liver lesions, including simple steatosis, steatohepatitis and fibrosis. Although steatosis is often harmless, the lobular inflammation that characterizes nonalcoholic steatohepatitis (NASH) is considered a driving force in the progression of NAFLD.

CXCR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation.

Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CXCR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation.

One-step scalable fluorescent microgel bioassay for the ultrasensitive detection of endogenous viral miR-US4-5p.

Human cytomegalovirus (hCMV) infection is the leading cause of birth defects in newborns and death in immunosuppressed people. Traditional techniques require time-consuming and costly analyses, and sometimes result in false positive results; thus, a rapid and accurate detection for hCMV infection is necessary. Recently, hcmv-miR-US4-5p was selected as the biomarker for cytomegalovirus diagnosis and follow-up.