Oxygen, Volume 6, Issue 1 (March 2026) – 5 articles

Hypoxic pulmonary vasoconstriction (HPV) is a rapid and reversible constrictor response of the pulmonary vasculature, and especially its small muscular precapillary arteries, which is initiated by episodes of local alveolar hypoxia. Acting as a protective homeostatic vasomotor mechanism, HPV enables maximal gas exchange by diverting blood from poorly ventilated alveoli into those rich in oxygen, thereby optimizing oxygen uptake and the ventilation–perfusion (V/Q) ratio so as to maintain the arterial oxygen partial pressure (P_aO₂) within the physiological range. HPV is an intrinsic mechanism of pulmonary artery smooth muscle cells (PASMCs), and requires an O₂ sensor which acts through mediator(s) to trigger effector mechanisms within these cells to evoke constriction. Whereas HPV effector mechanisms are reasonably well defined, the nature of the O₂ sensor and mediators remains in dispute, and a number of proposals have been developed to account for these. Some (but not all) of these share a focus on the concept that hypoxia activates effector mechanisms by inducing a change in the PASMC cytoplasmic redox state. Of these, the Redox Theory, first proposed by Kenneth Weir and Stephen Archer in 1995, proposes that hypoxia inhibits mitochondrial production of reactive oxygen species (ROS), thereby causing the cytoplasm to become more reduced. This inhibits ongoing vasorelaxation maintained by the opening of voltage-gated K⁺ channels. In contrast, according to the Mitochondrial ROS hypothesis, introduced by Paul Schumacker and Naveen Chandel in 2001, hypoxia increases mitochondrial ROS production, causing an oxidizing shift in the cytoplasmic redox state that activates several vasoconstricting pathways. In a third redox-based scenario, developed by Michael Wolin and Sachin Gupte, hypoxia evokes contraction by causing a fall in H₂O₂ production by NADPH oxidase and by activating the pentose phosphate pathway. These effects inhibit basal vasorelaxation maintained by the guanylate cyclase and protein kinase G and also stimulate vasoconstricting mechanisms. In this comprehensive review, we first provide a detailed summary of the key studies contributing to the development of these proposals and then subject the evidence supporting them to a critical appraisal, based in part on how well they accord with the wider literature and recent developments in our understanding of how cells shape and deploy redox mechanisms in order to regulate cell function. Full article

Oxidative stress seems to be part of many deranged processes in the organism, affecting multiple degenerative conditions at a cellular and tissue level. Coumarins and flavonoids comprise two main categories of naturally derived compounds with multiple effects and applications. Our aim in this paper is the design of compounds with increased antioxidant activity with the conjugation of two moieties with highly antioxidant potency in the frame of one molecule. A series of novel derivatives, comprising fusion of 7-hydroxycoumarin (Umbelliferone) and Quercetin (flavonol) have been synthesized using classical organic chemistry methods. Additionally, one novel flavone derivative was prepared for comparison. The novel compounds were tested for their radical, reactive oxygen and nitrogen species (ROS and RNS) scavenging, their reductive activity, and their labile metal chelating potency, as well as with in silico tools. All of them were more active, in most cases, than reference molecules Trolox and vitamin C. The most active compound 2 reached IC₅₀ of 4.03 and 43.75 μM for ABTS and DPPH, respectively (up to three times lower than that of Trolox). Compound 1 was of equal to vitamin C activity in H₂O₂ scavenging, whilst compound 3 was up to 6.4 times more active than Trolox in NO scavenging. Since our designed compounds seem to exhibit high antioxidant potential, scavenging reactive nitrogen and oxygen species, which are accumulated and promote the progression of inflammatory conditions, and have reductive and metal chelating abilities, they can be considered as potential candidates for protection in cases of oxidative stress derived toxicity. Full article

Salt stress is a major agricultural issue. A promising modern agriculture method is the foliar treatment of zinc oxide nanoparticles (ZnONPs). This approach has shown promise in boosting challenged tomato yields, fruit quality, and leaf extract antibacterial activity against pathogens. A greenhouse experiment was conducted. The previously synthesized and characterized ZnONPs were used to alleviate the harmful effects of NaCl stress. Tomato fruit weight from different treatments was determined, and the gas–liquid chromatography device was used to observe the changes in fatty acid production. The antimicrobial activities of the aqueous and diethyl ether extracts from tomato leaves were determined against six bacterial and six fungal strains. The plants that were salinity-stressed and sprayed with 0.075 and 0.15 g/L ZnONPs showed a better improvement compared to the salinity-stressed plants. Also, the sprayed plants that were not stressed at all showed promising results compared to the control and the other different treatments. Through the process of molecular docking, it was shown that caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, and apigenin-7-glucoside are essential chemicals that possess antibacterial and antifungal effects against the DNA Gyrase inhibitor and the sterol 14-alpha demethylase (CYP51) enzyme, respectively. It is concluded that salt stress can negatively affect the growth, quality, and variant plant features. However, the foliar application of ZnONPs is able to overcome those adverse effects in the stressed plants, and enhance the non-stressed as well. Full article

Age-related macular degeneration (AMD) is an age-associated disease characterized by damage to the central retina and represents a leading cause of acquired blindness, with increasing prevalence in aging populations. However, effective therapeutic options remain limited. The accumulation of dysfunctional mitochondria in retinal pigment epithelial (RPE) cells leads to excessive production of reactive oxygen species (ROS), triggering cellular senescence and cell death that contribute to the pathogenesis of AMD. Therefore, removal of accumulated dysfunctional mitochondria in senescent RPE cells is expected to treat AMD. Herein, we investigated transferrin (Trf)-modified mitophagy-inducing dual-drug nanocarriers (Trf-M-NCs) for the treatment of a senescent RPE cell. To evaluate efficacy, we used sodium iodate-treated ARPE-19 cells. The Trf-M-NCs exhibited significantly higher uptake by ARPE-19 cells than the unmodified M-NCs. Importantly, Trf-M-NC treatment alleviated cellular senescence by restoring the mitochondrial functions. Furthermore, Trf-M-NC treatment not only restored the production of α-ketoglutarate, an essential energy source for photoreceptor cells, but also reduced the secretion of IL-6, a key inflammatory cytokine. These findings suggest that improving mitochondrial quality in RPE cells is a novel and promising therapeutic approach for AMD. Full article