Wenting Xu

Bio: Wenting Xu is an academic researcher from Anhui Medical University. The author has contributed to research in topics: Lung injury. The author has an hindex of 1, co-authored 1 publications receiving 3 citations.

Role of Ferroptosis in Lung Diseases

Abstract: Ferroptosis is a new type of programmed cell death characterized by intracellular iron accumulation and lipid peroxidation that leads to oxidative stress and cell death. The metabolism of iron, lipids, and amino acids and multiple signalling pathways precisely regulate the process of ferroptosis. Emerging evidence has demonstrated that ferroptosis participates in the occurrence and progression of various pathological conditions and diseases, such as infections, neurodegeneration, tissue ischaemia-reperfusion injury and immune diseases. Recent studies have also indicated that ferroptosis plays a critical role in the pathogenesis of acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection and asthma. Herein, we summarize the latest knowledge on the regulatory mechanism of ferroptosis and its association with iron, lipid and amino acid metabolism as well as several signalling pathways. Furthermore, we review the contribution of ferroptosis to the pathogenesis of lung diseases and discuss ferroptosis as a novel therapeutic target for various lung diseases.

Is the Macrophage Phenotype Determinant for Fibrosis Development

Abstract: Fibrosis is a pathophysiological process of wound repair that leads to the deposit of connective tissue in the extracellular matrix. This complication is mainly associated with different pathologies affecting several organs such as lung, liver, heart, kidney, and intestine. In this fibrotic process, macrophages play an important role since they can modulate fibrosis due to their high plasticity, being able to adopt different phenotypes depending on the microenvironment in which they are found. In this review, we will try to discuss whether the macrophage phenotype exerts a pivotal role in the fibrosis development in the most important fibrotic scenarios.

The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities

Abstract: The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

Postconditioning with Irisin Attenuates Lung Ischemia/Reperfusion Injury by Suppressing Ferroptosis via Induction of the Nrf2/HO-1 Signal Axis

Abstract: Iron-dependent lipid peroxidation causes ferroptosis. This study was aimed at verifying that irisin postconditioning can inhibit ferroptosis and minimize lung ischemia/reperfusion (I/R) damage via activating the Nrf2/HO-1 signal axis. We constructed a murine model of I/R lung damage. At the onset of reperfusion, irisin, ferroptosis inhibitor ferrostatin-1, and ferroptosis inducer Fe-citrate were all administered. We discovered that irisin could reduce lung I/R injury, consistent with ferrostatin-1's action. Furthermore, irisin suppressed ferroptosis in lung I/R damage, as evidenced by lower ROS, MDA, and Fe2+, as well as alterations in critical protein expression (GPX4 and ACSL4). However, Fe-citrate abolished the protective effects of irisin. Transcriptome research found that irisin increased the mRNA levels of Nrf2 and HO-1. Thus, we used siRNA to investigate the role of the Nrf2/HO-1 axis in irisin-mediated protection against hypoxia/reoxygenation (H/R) damage in MLE-12 cells. Irisin consistently reduced ferroptosis and improved mitochondrial dysfunction caused by H/R. Irisin's cytoprotective function was eliminated when Nrf2 was silenced. As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis.

Targeting Ferroptosis for Lung Diseases: Exploring Novel Strategies in Ferroptosis-Associated Mechanisms.

Abstract: Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.

Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis

Abstract: Abstract Context Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis. Objective To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms. Materials and methods The caecal ligation and puncture (CLP) manoeuvre was applied to establish a murine model of sepsis-induced ALI, and female BALB/c mice (6 mice per group) were subjected to 100 mg/kg FA or 0.8 mg/kg ferrostatin-1 (Fer-1, ferroptosis inhibitor) treatment to clarify the role of FA in preserving alveolar epithelial barrier function and inhibiting ferroptosis. Lipopolysaccharide (LPS; 500 ng/mL)-induced cell models were prepared and subjected to FA (0.1 μM), sh-Nrf2, and Fe (Fe-citrate, ferroptosis inducer; 5 M) treatment to study the in vitro effect of FA on LPS-induced alveolar epithelial cell injury and the role of the Nrf2/HO-1 pathway. Results We found that FA decreased the lung injury score (48% reduction), lung wet/dry weight ratio (33% reduction), and myeloperoxidase activity (58% reduction) in sepsis-induced ALI. Moreover, FA inhibited ferroptosis of alveolar epithelial cells and improved alveolar epithelial barrier dysfunction. The protective role of FA against alveolar epithelial barrier dysfunction could be reversed by the ferroptosis inducer Fe-citrate, suggesting that FA alleviates alveolar epithelial barrier dysfunction by inhibiting ferroptosis. Mechanistically, we found that FA inhibited ferroptosis of alveolar epithelial cells by activating the Nrf2/HO-1 pathway. Conclusion Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.