Oxygen, Volume 6, Issue 2 (June 2026) – 5 articles

The yak (Bos grunniens), a unique bovine species that is endemic to the Qinghai–Tibet Plateau and adjacent mountainous regions, exhibits remarkable adaptations to chronic high-altitude hypoxia. However, the molecular mechanisms underlying yaks’ adaptation to this extreme environment remain poorly understood. This study aimed to elucidate the spatiotemporal expression dynamics of hypoxia-inducible factor 1α (HIF-1α) and 2α (HIF-2α) in major tissues of yaks across developmental stages (0.5, 1.5, 2.5, and 4.5 years; n = 3 per group). The tissues (heart, liver, spleen, lungs, kidneys, blood vessels and skeletal muscles) were analyzed using hematoxylin and eosin (H&E) staining and immunohistochemistry. The results revealed significant differences in the expression levels of HIF-1α and HIF-2α between tissues and at different ages. In cardiac tissue, both HIF-1α and HIF-2α are localized to the myocardial interstitium, with HIF-1α expression peaking at 1.5–2.5 years and HIF-2α expression reaching its maximum at 2.5 years. Hepatic HIF-1α showed perivenous hepatocytes enrichment and peaked at 2.5 years (p < 0.01 vs. other ages), while HIF-2α was uniformly distributed across lobules without age-related changes. Splenic HIF-1α and HIF-2α levels increased progressively with age, both peaking at 4.5 years (p < 0.01), and age was strongly correlated with expression levels (HIF-1α: r = 0.430; HIF-2α: r = 0.493). In pulmonary tissues, HIF-1α in bronchial smooth muscle peaked at 2.5 years, whereas alveolar septal HIF-2α peaked at 1.5 years (p < 0.05). In the kidney, HIF-1α was primarily localized to tubular epithelial cells and HIF-2α was diffusely distributed in the glomerular interstitium; neither factor showed significant variation across ages. In vascular tissues, HIF-1α expression remained stable across all ages and was predominantly observed in the smooth muscle layer, while HIF-2α exhibited a significant peak in endothelial cells at 2.5 years (p < 0.01). These findings suggest that HIF-1α predominates during early development stages, while HIF-2α becomes dominant as yaks approach maturity. Full article

Uterine fibroids (leiomyomas) are common benign smooth muscle tumors that impose substantial symptom burden and healthcare costs worldwide. Although uterine fibroid (leiomyoma) pathogenesis is multifactorial, hypoxia has emerged as a key feature of the uterine fibroid (leiomyoma) microenvironment, particularly within poorly perfused tumor cores. Hypoxia-inducible factor-1α (HIF-1α) is a central transcriptional regulator of cellular adaptation to low oxygen and coordinates downstream programs that support angiogenesis, metabolic reprogramming, cell survival, and extracellular matrix (ECM) remodeling. In uterine fibroids (leiomyomas), these HIF-1α–dependent processes intersect with steroid hormone signaling, growth factor pathways, inflammatory mediators, and redox imbalance, together promoting tumor persistence and progressive fibrosis. This review synthesizes the molecular regulation of HIF-1α, highlights major HIF-linked effector pathways relevant to uterine fibroid (leiomyoma) biology, and emphasizes mechanistic crosstalk with estrogen- and progesterone-responsive signaling, TGF-β/SMAD-driven fibrosis, NF-κB-mediated inflammation, and metabolic checkpoint pathways including mTOR and AMPK. Finally, we evaluate emerging therapeutic strategies that target HIF-1α directly or indirectly through upstream regulators. Full article

Pneumonia, an acute inflammatory condition of the lung tissue, imposes a significant burden on global health and is characterized by a high rate of illness and death. The pathogenesis of the disease extends beyond infection to breakdown of redox hemostasis, where the excessive reactive oxygen species produced during the immune response inflict damage on the alveolar tissues and hence promote varying complications. This dual role of oxygen and oxidative mechanisms makes the management of pneumonia challenging, as the very oxygen that is vital for host defense, when not regulated, imposes severe lung damage. Antioxidant administration and oxygen therapy offer limited efficacy, mostly due to their non-specific action and iatrogenic harm from oxygen oversupply. These limitations are overcome by the use of emerging therapeutic strategies, which primarily focus on precision-targeted approaches. These include inhalable antioxidants, nanoparticle-based systems and biomaterials that are engineered to respond to local ROS concentrations, which aim to deliver the therapeutic agent directly to the inflamed regions of the lung. Calcium peroxide- and manganese dioxide-incorporating materials are being designed to modulate the oxygen levels, either by releasing it in hypoxic zones or scavenging it in hyperoxic microenvironments. This approach simultaneously addresses hypoxia and oxidative stress. Despite showing promising results in experimental and preclinical studies, complications related to product stability, regulatory compliance, and manufacturing scalability need to be addressed. Personalized treatment protocols, guided by biomarkers, involve the future generation of treatments, aiming to achieve a delicate recalibration of the lung’s oxidative environment for improved patient outcomes. Full article

Background: Severe lung compromise from COVID-19, ARDS, and recently AH3N2 can progress to life-threatening hypoxia. Past experience led to standardized protocols that assumed similarity to SARS-CoV. Methods: COVID-19 pathophysiology and histopathological lung biopsy photomicrographs are analyzed. Results: Pneumolysis is defined as progressive alveolar–capillary destruction resulting from SARS-CoV-2 attack on pneumocytes. In the final stages preceding pneumolysis, molecular mechanisms in the lungs include apoptosis in alveolar epithelial type I and II cells, compromising alveolar regeneration, and necrosis, resulting in leakage of intracellular contents and amplifying inflammation. Pyroptosis, driven by inflammasome activity, further disrupts alveolar integrity in ARDS. Histopathological findings include Masson bodies, alveolar-coating cells with nuclear atypia, reactive pneumocytes and reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates and abscesses, microthrombi, hyaline membrane remnants, and emphysema. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are shown. Conclusions: Silent hypoxemia rapidly progresses to critical hypoxemia. This progression results from progressive pneumolysis, inflammation, immune overexpression, autoimmunity, and HAPE-type edema, leading to acute pulmonary insufficiency. Long-lasting COVID-19 can result in fibrosis and, as a compensatory mechanism, polierythrocythemia. The proposed treatment (based on tolerance to hypoxia and the hemoglobin factor) includes prompt oxygen administration, control of inflammatory and immune responses, antibiotics, rehydration, erythropoietin and platelet aggregation inhibitors. Full article

Systemic inflammation leading to neuroinflammation is a matter of concern in recent years because of its implication with neurological disorders. Selective peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists have shown promising anti-inflammatory effects in various neurodegenerative diseases. With pioglitazone being one such PPAR-γ agonist, our study was aimed at investigating the role of pioglitazone on oxidative stress and cognitive changes against LPS-induced neuroinflammation in rats. In-house-bred male Wistar rats, about six weeks old, were utilized for the present study. They were categorized as A (preventive) and B (curative) groups, each with five subgroups: control (1A and 1B), neuro-inflammatory (2A and 2B), and three different dosages of pioglitazone treatment (3A, 3B, 4A, 4B, and 5A, 5B). After the experimental period, cognitive changes were examined by behavioral tests. Brain homogenate was used for biochemical parameters. Deteriorated memory, superoxide dismutase activity and increase in lipid peroxidation in the brain tissue induced by LPS exposure were substantially alleviated (p < 0.001) by pioglitazone treatment. These results suggest that pioglitazone may be neuroprotective against LPS-induced neuroinflammation. Full article