Mild-to-moderate psoriasis is associated with subclinical inflammation in the duodenum and a tendency of disturbed intestinal barrier.

Psoriasis is a chronic skin disease occasionally associated with abdominal symptoms and IBD. We aimed to characterize intestinal immune cells and the integrity of the intestinal barrier in psoriasis. Biopsies from the duodenum and colon were analyzed by flow cytometry and immunohistochemistry for the presence and activation status of different immune cell populations.

Loss of heterozygosity of CYP2D6 enhances the sensitivity of hepatocellular carcinomas to talazoparib.

Background: Loss of heterozygosity (LOH) diminishes genetic diversity within cancer genomes. A tumour arising in an individual heterozygous for a functional and a loss-of-function (LoF) allele of a gene occasionally retain only the LoF allele. This can result in deficiency of specific protein activities in cancer cells, creating unique differences between tumour cells and normal cells of the individual.

Global C tracing and metabolic flux analysis of intact human liver tissue ex vivo.

Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global C tracing, non-targeted mass spectrometry and model-based metabolic flux analysis.

In silico and biological analyses of missense variants of the human biliary efflux transporter ABCC2: effects of novel rare missense variants.

Background And Purpose: The ATP-dependent biliary efflux transporter ABCC2, also known as multidrug resistance protein 2 (MRP2), is essential for the cellular disposition and detoxification of various xenobiotics including drugs as well as endogenous metabolites. Common functionally relevant ABCC2 genetic variants significantly alter drug responses and contribute to side effects. The aim of this study was to determine functional consequences of rare variants identified in subjects with European ancestry using in silico tools and in vitro analyses.

Proteomic Profiling Reveals Age-Related Changes in Transporter Proteins in the Human Blood-Brain Barrier.

The Blood-Brain Barrier (BBB) is a crucial, selective barrier that regulates the entry of molecules including nutrients, environmental toxins, and therapeutic medications into the brain. This function relies heavily on brain endothelial cell proteins, particularly transporters and tight junction proteins. The BBB continues to develop postnatally, adapting its selective barrier function across different developmental phases, and alters with aging and disease.