Purpose: Ferroptosis is associated with oxidative stress (OS) and is caused by iron-dependent lipid-peroxidative damage, but its role in PE is unclear. The aim of this study is to determine whether pannexin 1 (Panx1) and toll-like receptor 4 (TLR4) are key regulators of ferroptosis in PE. Methods: The study included 65 patients with PE and 25 healthy pregnant women. In normal and PE placental tissues, OS and ferroptosis markers, including Fe²⁺, malondialdehyde (MDA), reduced glutathione (GSH) levels, heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (Gpx4) activity, were estimated. Panx1 and solute carrier family 7 member 11 (SLC7A11) mRNA expression levels were relatively quantified in placental tissues using real‐time polymerase chain reaction (RT‐PCR), while serum Panx1, serum TLR4, and placental activating transcription factor 3 (ATF3) levels were measured by ELISA. Results: In placental tissues, Panx1 and TLR4 expression levels were significantly increased in patients with PE compared to controls and were positively correlated with pro-ferroptosis mediators such as placental Fe²⁺ and MDA levels and negatively correlated with anti-ferroptosis regulators such as placental GSH level, HO-1, and Gpx4 activity. Additionally, Panx1 and TLR4 had a positive correlation with ATF3 and a negative correlation with SLC7A11. Serum Panx1 and TLR4 levels were positively correlated with their placental tissue expression and showed good diagnostic capabilities for ferroptosis in PE. Conclusion: Therefore, Panx1 and TLR4 are suggested to induce ferroptosis in PE via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for PE.

Necroptosis is a tightly adjusted inflammatory necrotizing cell death signaling pathway that participates in pathogenesis of discrete diseases as rheumatoid arthritis (RA). Irisin is a myokine with...

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: As hepatocellular carcinoma (HCC) arising from chronic hepatitis C virus (HCV) infection in liver cirrhosis is a major problem in public health, early and rapid prediction of HCC is urgent. We hypothesized that a single nucleotide polymorphism in the Apa1 SNP in the vitamin D receptor may help diagnosis. Methods: We recruited 3 groups: 80 HCC patients with HCV cirrhosis, 80 HCV cirrhotic patients free of HCC and 80 healthy controls. Apa1 rs7975232 SNP was detected by PCR- RFLP technique. Routine laboratory markers were determined by standard methods. Results: The Apa1 CC genotype was more frequent (75%) in HCC than in the cirrhosis (35%) and control (20%) groups (P<0.0001). CC patients were more likely to have a more severe Child-Pugh score (P=0.027) and MELD score (P<0.05). In multivariate analysis, the CC genotype out-performed AFP is determining HCC. Conclusion: Apa1 CC genotype is linked to HCC in HCV C cirrhotic patients, and so has the potential to be an independent biomarker predictor for HCC occurrence in HCV cirrhosis.