Legacy and alternative per- and polyfluoroalkyl substances (PFAS) alter the lipid profile of HepaRG cells.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various industrial and consumer products. They have gained attention due to their ubiquitous occurrence in the environment and potential for adverse effects on human health, often linked to immune suppression, hepatotoxicity, and altered cholesterol metabolism. This study aimed to explore the impact of ten individual PFAS, 3 H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP/Adona), ammonium perfluoro-(2-methyl-3-oxahexanoate) (HFPO-DA/GenX), perfluorobutanoic acid (PFBA), perfluorobutanesulfonic acid (PFBS), perfluorodecanoic acid (PFDA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS) on the lipid metabolism in human hepatocyte-like cells (HepaRG).

CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane-induced alopecia.

Taxanes are a leading cause of severe and often permanent chemotherapy-induced alopecia. As the underlying pathobiology of taxane chemotherapy-induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell-rich outer root sheath compartments, including within Keratin 15+ cell populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity and permanence of taxane chemotherapy-induced alopecia.

Quantification of Intracellular Accumulation and Retention of Lysosomotropic Macrocyclic Compounds by High-Throughput Imaging of Lysosomal Changes.

Many marketed pharmaceuticals reach extremely high tissue concentrations due to accumulation in lysosomes (lysosomotropism). Quantitative prediction of intracellular concentrations of accumulating drugs is challenging, especially for macrocyclic compounds that mainly do not fit in current in silico models. We tested a unique library of 47 compounds (containing 39 macrocycles) specifically designed to cover the entire range of accumulation intensities observed with pharmaceuticals so far.

Lysosomotropic cationic amphiphilic drugs inhibit adipocyte differentiation in 3T3-L1K cells via accumulation in cells and phospholipid membranes, and inhibition of autophagy.

Some cationic amphiphilic drugs (CADs) have been individually reported to interfere with the differentiation of immune system cells, such as macrophages and dendritic cells. To investigate the possible generic nature of this process, in this study we aimed to see whether these drugs are capable of interfering with the differentiation of adipocytes. Further, we investigated whether this feature might be connected to the lysosomotropic character of these drugs, and their disturbance of intracellular membrane trafficking rather than to the individual pharmacologic properties of each drug.

Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21, p27 and p57) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis.

A primer for studying cell cycle dynamics of the human hair follicle.

The cell cycle is of major importance to human hair follicle (HF) biology. Not only is continuously active cell cycling required to facilitate healthy hair growth in anagen VI HFs, but perturbations in the cell cycle are likely to be of significance in HF pathology (i.e.