PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis.

Neuroblastoma (NB) is a paediatric cancer with noteworthy heterogeneity ranging from spontaneous regression to high-risk forms that are characterised by cancer relapse and the acquisition of drug resistance. The most-used anticancer drugs exert their cytotoxic effect by inducing oxidative stress, and long-term therapy has been demonstrated to cause chemoresistance by enhancing the antioxidant response of NB cells. Taking advantage of an in vitro model of multidrug-resistant (MDR) NB cells, characterised by high levels of glutathione (GSH), the overexpression of the oncoprotein BMI-1, and the presence of a mutant P53 protein, we investigated a new potential strategy to fight chemoresistance.

The Anti-Inflammatory Effect of Lactose-Modified Hyaluronic Acid Molecules on Primary Bronchial Fibroblasts of Smokers.

The progression of smoking-related diseases is characterized by macrophage-mediated inflammation, which is responsible for an increased expression of proinflammatory cytokines and galectins, molecules that bind specifically to β-galactoside sugars. This study aimed to assess the anti-inflammatory and antioxidant effects of a broad selection of differently lactose-modified hyaluronic acids (HA) named HYLACH, which are able to bind proinflammatory galectins. The best HYLACH ligands for Gal-3 were selected in silico and their activities were tested in vitro on primary human bronchial fibroblasts obtained from smokers and inflamed with the conditioned medium of activated U937 monocytes.

Anti-Inflammatory and Pro-Regenerative Effects of Hyaluronan-Chitlac Mixture in Human Dermal Fibroblasts: A Skin Ageing Perspective.

Inflammation and the accumulation of reactive oxygen species (ROS) play an important role in the structural and functional modifications leading to skin ageing. The reduction of inflammation, cellular oxidation and dermal extracellular matrix (ECM) alterations may prevent the ageing process. The aim of this study is to investigate the expression of pro-inflammatory markers and ECM molecules in human dermal fibroblasts derived from young and middle-aged women and the effects of lactose-modified chitosan (Chitlac, CTL), alone or in combination with mid-MW hyaluronan (HA), using an in vitro model of inflammation.

In Vitro Effects of Low Doses of β-Caryophyllene, Ascorbic Acid and d-Glucosamine on Human Chondrocyte Viability and Inflammation.

β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary human chondrocytes. Changes in cell viability, intracellular ROS generation, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan were analyzed in primary human chondrocytes exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN.

Aerobic pyruvate metabolism sensitizes cells to ferroptosis primed by GSH depletion.

Ferroptosis is a non-accidental, regulated form of cell death operated by lipid peroxidation under strict control of GPx4 activity. This is consistent with the notion that lipid peroxidation is initiated by radicals produced from decomposition of traces of pre-existing lipid hydroperoxides. The question, therefore, emerges about the formation of these traces of lipid hydroperoxides interacting with Fe.