Neuroblastoma (NB) is a common pediatric extracranial solid tumor. Dimethylaminomicheliolide (DMAMCL), a prodrug of Micheliolide (MCL), shows antitumor activity against NB, but its mechanisms remain unclear. This study investigated the antitumor mechanisms of DMAMCL in NB.

Oxidative protein modifications have been linked to several diseases, but the variety and diversity of modifications are less studied.

Due to the proliferative nature of cancer cells, they utilize more dietary extracellular nutrients via one-carbon metabolism for the various metabolic processes, including the synthesis of antioxidants such as glutathione (GSH) and hydrogen sulfide (H2S). Indeed, several studies have found that specific cancer types produce significantly higher levels of GSH and H2S than normal healthy cells, which may serve as a protective mechanism, allowing them to resist stress, survive, and grow. This metabolic heterogeneity, driven by intrinsic and extrinsic factors, contributes to the distinct metabolic characteristics and vulnerabilities of tumor subtypes, which can be exploited to develop anticancer strategies. In this review, we summarize the fundamental roles and regulation of GSH and H2S in normal physiological systems and in the genesis and progression of cancer, their effects on the tumor microenvironment (TME), and their contribution to drug resistance. We also discuss the influences of diet and the gut microbiome on GSH and H2S production, and how cancer cells reprogram their metabolism to grow and survive in a stressful environment by overproducing GSH and H2S.

Collagen is a long-lived protein present in the extracellular matrix of force-bearing tissues. It has a unique amino acid composition of predominantly glycine, proline and hydroxyproline that repeats throughout its characteristic triple helical structure. In the extracellular space, collagen interact first by a non-enzymatic, entropy-driven process given their high hydrophobicity. Then, enzymes, such as lysyl oxidase (LOX), create covalent bonds (i.e. crosslinks) between triple helices, generating reactive oxygen species (ROS) as a byproduct. Moreover, it was recently discovered that collagen itself generates ROS upon stretching. Therefore, given the close proximity of ROS-generating sources, it seems plausible that collagen undergoes non-enzymatic oxidation.

Human serum albumin (HSA) is the most abundant circulating protein and a central mediator of extracellular redox homeostasis. Its antioxidant function has been attributed primarily to the free thiol at cysteine residue 34 (Cys34), whose progressive oxidation-yielding nonmercaptoalbumin isoforms HNA1 and HNA2-serves as a sensitive biomarker of systemic oxidative stress. Advances in electrospray ionisation time-of-flight mass spectrometry have enabled precise quantification of Cys34 modifications, establishing cysteinylated albumin as a clinically applicable marker in chronic kidney disease, chronic liver disease, diabetes, and ageing-related functional decline. Beyond its role as a biomarker, oxidized albumin is now recognized as an active pathogenic mediator in preclinical models, with emerging evidence implicating ferroptosis as a potential mechanism of renal tubular cell injury, and contributing to cardiovascular risk and sarcopenia. A previously unrecognized dimension of albumin redox biology has also emerged: the presence of endogenous oxidized polysulfide bonds (Ox-PSS; RSSn-R', n > 1) across multiple intramolecular cysteine bridges. Quantified using the newly developed Elimination Method for Sulfide from Polysulfide, albumin polysulfides are dynamically regulated by oxidative stress and are significantly depleted in chronic kidney disease and early hepatitis, even when conventional Cys34-based markers remain unchanged. Polysulfide depletion impairs both Site II drug-binding capacity and reactive oxygen species scavenging activity, with direct implications for pharmacokinetics and therapeutic efficacy. These findings collectively reframe HSA as a dynamic polysulfide reservoir and extracellular redox regulator, highlighting albumin polysulfide modulation as a compelling emerging therapeutic strategy.

Alzheimer's disease (AD) is a major global neurodegenerative disorder associated with high morbidity and mortality, yet current treatments remain largely symptomatic and ineffective in halting neurodegeneration. Growing evidence links oxidative stress potentially being an early event in AD progression. Consequently, therapeutic strategies targeting oxidative stress-mediated cellular damage are increasingly attractive. This review summarizes clinical evidence of oxidative stress biomarkers in AD and examines the neuroprotective mechanisms of flavonoids against oxidative stress in vivo, together with current clinical findings. Despite inconsistencies among studies due to variations in detection methods, a consistent trend of elevated oxidative stress in AD is evident, correlating with disease severity. Although in vivo studies have demonstrated that flavonoids restore antioxidant defences and suppress neuroinflammation, convincing clinical evidence of their efficacy in AD patients remains limited. Overall, these findings emphasize oxidative stress as a therapeutic target requiring further validation efforts.