Polycystic ovary syndrome (PCOS) has a series of reproductive and metabolic consequences. Although the link between PCOS, IR, and obesity, their impact on the pathogenesis of PCOS has yet to be det...

The most prevalent endocrine disorder affecting women is PCOS. Programmed death of ovarian cells has yet to be elucidated. Ferroptosis is a kind of iron-dependent necrosis featured by significantly Fe⁺²-dependent lipid peroxidation. The ongoing study aimed to reinforce fertility by combining therapy with AgNPs and (Zileuton) in PCOS rats' model. The study included 75 adult female rats divided into 5 groups; control, PCOS, PCOS treated with AgNPs, PCOS treated with Zileuton, and PCOS group treated with AgNPs and Zileuton. The study investigated the anti-ferroptotic, anti-inflammatory, antioxidant, antiapoptotic, histopathological and immunohistochemical examinations of COX-2 and VEGF. The combination of AgNPs and Zileuton showed significant reduction of inflammatory mediators (IL-6, TNF-α, NFk-B) compared with diseased group (P-value < 0.05), regression of ferroptosis marks (Panx1 and TLR4 expression, Fe⁺² levels) compared with diseased group (P-value < 0.05), depression of apoptotic marker caspase 3 level compared with diseased animals (P-value < 0.05), depression of MDA level, elevation of HO-1, GPx4 activity, and reduction of Cox2 and VEGF as compared with the diseased, AgNPs or zileuton-treated groups (P-value < 0.05). The study showed that the combination of AgNPs and zileuton guards against, inflammation, apoptosis, and ferroptosis in PCO.

Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung disorders associated with high morbidity and mortality. Dysregulation of the renin–angiotensin system (RAS) and proinflammatory pathways play an indispensable role in ALI progression. Aim: This study aimed to investigate the protective potential of nobiletin (NOB) in mitigating ALI and hyperinflammatory lung injury. Material and Methods: The study enrolled 32 male albino rats allocated into four groups: (Control, NOB, lipopolysaccharide [LPS], and NOB + LPS groups). Rats received NOB 20 mg/kg by oral gavage for 1 week; on the seventh day, a single dose of 15 mg/kg LPS was given by intranasal instillation. After 24 h of LPS administration, plasma and lung tissue samples were analyzed for inflammatory cytokines, mitochondrial complex‐I, oxidative stress markers, and molecular signaling pathways. Results: NOB administration significantly downregulated miR‐200 expression, associated with ACE2 activation and attenuated AT1R‐mediated inflammatory responses. It also decreased NF‐κB and p38 MAPK signaling, reducing pulmonary and systemic levels of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), granulocyte monocyte‐colony stimulating factor (GM‐CSF), and interleukin‐17A (IL‐17A). Additionally, NOB improved the high mobility group box 1 (HMGB1)/NF‐κB/mammalian target of rapamycin (mTOR) pathway, and increased mitochondrial complex‐I may be consistent with improved tissue preservation. Conclusion: NOB exerts protective effects against ALI by improving inflammatory cytokine, oxidative stress, miRNA‐200, mitochondrial complex‐I, and ACE2, highlighting its potential as a protective candidate for ALI and hyperinflammatory‐associated lung injury.