PM2.5 contributed to pulmonary epithelial senescence and ferroptosis by regulating USP3-SIRT3-P53 axis

Malondialdehyde (MDA), 4-hydroxy-nonenal (HNE) and the F2-isoprostane 15(S)-8-iso-prostaglandin F2α (15(S)-8-iso-PGF2α) are the best investigated products of lipid peroxidation. MDA, HNE and 15(S)-8-iso-PGF2α are produced from polyunsaturated fatty acids (PUFAs) both by chemical reactions and by reactions catalyzed by enzymes. 15(S)-8-iso-PGF2α and other F2-isoprostanes are derived exclusively from arachidonic acid (AA). The number of PUFAs that may contribute to MDA and HNE is much higher. MDA is the prototype of the so called thiobarbituric acid reactive substances (TBARS). MDA, HNE and 15(S)-8-iso-PGF2α are the most frequently measured biomarkers of oxidative stress, namely of lipid peroxidation. In many diseases, higher concentrations of MDA, HNE and 15(S)-8-iso-PGF2α are measured in biological samples as compared to health. Therefore, elevated oxidative stress is generally regarded as a pathological condition. Decreasing the concentration of biomarkers of oxidative stress by changing life style, by nutritional intake of antioxidants or by means of drugs is generally believed to be beneficial to health. Reliable assessment of oxidative stress by measuring MDA, HNE and 15(S)-8-iso-PGF2α in biological fluids is highly challenging for two important reasons: Because of the duality of oxidative stress, i.e., its origin from chemical and enzymatic reactions, and because of pre-analytical and analytical issues. This article focuses on these key issues. It reviews reported analytical methods and their principles for the quantitative measurement of MDA, HNE and 15(S)-8-iso-PGF2α in biological samples including plasma and urine, and critically discusses their biological and biomedical outcome which is rarely crystal clear and free of artefacts.

To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic cells: the ubiquitin-proteasome system (UPS) and autophagy. The UPS and autophagy form an interconnected quality control network where decision-making is self-organized on the basis of biophysical parameters (binding affinities, local concentrations, and avidity) and compartmentalization (through membranes, liquid-liquid phase separation, or the formation of aggregates). We highlight cellular quality control factors that delineate their differential deployment toward macromolecular complexes, liquid-liquid phase-separated subcellular structures, or membrane-bound organelles. Finally, we emphasize the need for continuous promotion of quantitative and mechanistic research into the roles of the UPS and autophagy in human pathophysiology.

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.