Precision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production.

Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors of metabolism (IEM). Precision-cut liver slices (PCLS) represent a promising model for studying glucose production ex vivo. This study quantified the net glucose production of human and murine PCLS in the presence of different gluconeogenic precursors.

Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision-cut liver slices.

Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision-cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking.

Real-Time Monitoring of Oxygen-Consumption Rate in Mouse Liver Slices Incubated in Organ-on-a-Chip Devices.

We developed an organ-on-a-chip (OOC) based on precision-cut liver slices to assess liver function in real-time, both in health and disease, in a controlled and noninvasive manner. We achieved this by integrating fiber-optic-based oxygen sensors before and after the microchamber in which a liver slice was incubated under flow, to measure oxygen concentrations in the medium in real time. We first demonstrated that the basal oxygen consumption rate (OCR) of liver slices is a reliable indicator of liver slice viability.

Effect of hepatitis B vaccination on HBV-infection among school children in Yaounde; ten years after the introduction of HBV vaccine into routine Immunization Program in Cameroon.

Introduction: since the introduction of the anti-HBV vaccine into the Expanded Program on Immunization (EPI) in 2005 in Cameroon, vaccination coverage has reached 99.0%. This coverage would indicate an increase in the number of children immune to Hepatitis B Virus (HBV) and a decrease in susceptibility to HBV-infection.

Fibrogenesis in Human Mucosa and Muscularis Precision-Cut Intestinal Slices.

In Crohn's Disease (CD), intestinal fibrosis is a prevalent yet unresolved complication arising from chronic and transmural inflammation. The histological assessment of CD intestines shows changes in tissue morphology in all the layers, including the mucosa and muscularis. This study aimed to determine the differences in fibrogenesis between mucosa and muscularis.

Osteoprotegerin is an Early Marker of the Fibrotic Process and of Antifibrotic Treatment Responses in Ex Vivo Lung Fibrosis.

Background: Lung fibrosis is a chronic lung disease with a high mortality rate with only two approved drugs (pirfenidone and nintedanib) to attenuate its progression. To date, there are no reliable biomarkers to assess fibrosis development and/or treatment effects for these two drugs. Osteoprotegerin (OPG) is used as a serum marker to diagnose liver fibrosis and we have previously shown it associates with lung fibrosis as well.

Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review.

The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups.

Metabolic Dysfunction-Associated Steatotic Liver Disease in a Dish: Human Precision-Cut Liver Slices as a Platform for Drug Screening and Interventions.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing healthcare problem with limited therapeutic options. Progress in this field depends on the availability of reliable preclinical models. Human precision-cut liver slices (PCLSs) have been employed to replicate the initiation of MASLD, but a comprehensive investigation into MASLD progression is still missing.

Single cell-resolved study of advanced murine MASH reveals a homeostatic pericyte signaling module.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is linked to insulin resistance and type 2 diabetes and marked by hepatic inflammation, microvascular dysfunction, and fibrosis, impairing liver function and aggravating metabolic derangements. The liver homeostatic interactions disrupted in MASH are still poorly understood. We aimed to elucidate the plasticity and changing interactions of non-parenchymal cells associated with advanced MASH.

Matrix metalloproteinases in intestinal fibrosis.

Intestinal fibrosis is a common complication in patients with inflammatory bowel disease [IBD], in particular Crohn's disease [CD]. Unfortunately, at present intestinal fibrosis is not yet preventable, and cannot be treated by interventions other than surgical removal. Intestinal fibrosis is characterized by excessive accumulation of extracellular matrix [ECM], which is caused by activated fibroblasts and smooth muscle cells.

Fluorescent Nanodiamonds for Tracking Single Polymer Particles in Cells and Tissues.

Polymer nanoparticles are widely used in drug delivery and are also a potential concern due to the increased burden of nano- or microplastics in the environment. In order to use polymer nanoparticles safely and understand their mechanism of action, it is useful to know where within cells and tissues they end up. To this end, we labeled polymer nanoparticles with nanodiamond particles.

Targeted delivery of galunisertib using machine perfusion reduces fibrogenesis in an integrated ex vivo renal transplant and fibrogenesis model.

Background And Purpose: Fibrosis in kidney allografts is a major post-transplant complication that contributes to graft failure. Lately, multiple potent inhibitors of fibrosis-related pathways have been developed such as galunisertib, an inhibitor of the transforming growth factor-beta (TGF-β/TGFβ1) signalling pathway. This drug, however, poses risks for adverse effects when administered systemically.

Targeting collagen homeostasis for the treatment of liver fibrosis: Opportunities and challenges.

Liver fibrosis is an excessive production, aberrant deposition, and deficit degradation of extracellular matrix (ECM). Patients with unresolved fibrosis ultimately undergo end-stage liver diseases. To date, the effective and safe strategy to cease fibrosis progression remains an unmet clinical need.

Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles.

Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one-directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications.

Human precision-cut cystic duct and gallbladder slices: a novel method for studying cholangiopathies.

Background And Aims: Precision-cut tissue slices (PCTS) are widely used as an culture tissue culture technique to study pathogeneses of diseases and drug activities in organs . A novel application of the PCTS model may be in the field of translational research into cholangiopathies such as biliary atresia. Therefore, the aim of this study was to apply the precision-cut slice technique to human bile duct and gallbladder tissue.

Placenta-on-a-Chip as an In Vitro Approach to Evaluate the Physiological and Structural Characteristics of the Human Placental Barrier upon Drug Exposure: A Systematic Review.

Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g.

Standardized Protocol for the Preparation of Precision-Cut Kidney Slices: A Translational Model of Renal Fibrosis.

Renal fibrosis is a hallmark of progressive renal diseases. To date, there is a lack of effective therapeutics for the treatment of renal fibrosis, in part due to the scarcity of clinically relevant translational disease models. Since the early 1920s, hand-cut tissue slices have been used as a means to better understand organ (patho)physiology in a variety of scientific fields.

Transcriptomic profiling of induced steatosis in human and mouse precision-cut liver slices.

There is a high need for predictive human ex vivo models for non-alcoholic fatty liver disease (NAFLD). About a decade ago, precision-cut liver slices (PCLSs) have been established as an ex vivo assay for humans and other organisms. In the present study, we use transcriptomics by RNASeq to profile a new human and mouse PCLSs based assay for steatosis in NAFLD.

Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment.

The application of cannabis products in oncology receives interest, especially from patients. Despite the plethora of research data available, the added value in curative or palliative cancer care and the possible risks involved are insufficiently proven and therefore a matter of debate. We aim to give a recommendation on the position of cannabis products in clinical oncology by assessing recent literature.

Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion.

Background: End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.

Methods: Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial.

Hepatoprotective Efficacy of Cycloastragenol Alleviated the Progression of Liver Fibrosis in Carbon-Tetrachloride-Treated Mice.

The continuous death of hepatocytes induced by various etiologies leads to an aberrant tissue healing process and promotes the progression of liver fibrosis and ultimately chronic liver diseases. To date, effective treatments to delay this harmful process remain an unmet clinical need. Cycloastragenol is an active phytochemical substance isolated from , a plant used in traditional Chinese medicine to protect the liver.

Differential effects of oleate on vascular endothelial and liver sinusoidal endothelial cells reveal its toxic features in vitro.

Several fatty acids, in particular saturated fatty acids like palmitic acid, cause lipotoxicity in the context of non-alcoholic fatty liver disease . Unsaturated fatty acids (e.g.

RANKL confers protection against cell death in precision-cut lung slices.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and constitutes a major health problem. The disease is characterized by airflow obstructions due to chronic bronchitis and/or emphysema. Emerging evidence suggests that COPD is the result of impaired epithelial repair.

Verteporfin ameliorates fibrotic aspects of Dupuytren's disease nodular fibroblasts irrespective the activation state of the cells.

Dupuytren's disease is a chronic, progressive fibroproliferative condition of the hand fascia which results in digital contraction. So far, treatments do not directly interfere with the (myo)fibroblasts that are responsible for the formation of the collagen-rich cords and its contraction. Here we investigated whether verteporfin (VP) is able to inhibit the activation and subsequent differentiation of DD nodular fibroblasts into myofibroblasts.