Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3/SLC7A11 pathway.

Ferroptosis is a novel form of programmed cell death triggered by iron-dependent lipid peroxidation and has been associated with various diseases, including cancer. Erastin, an inhibitor of system Xc-, which plays a critical role in regulating ferroptosis, has been identified as an inducer of ferroptosis in cancer cells. In this study, we investigated the impact of butyrate, a short-chain fatty acid produced by gut microbiota, on erastin-induced ferroptosis in lung cancer cells. Our results demonstrated that butyrate significantly enhanced erastin-induced ferroptosis in lung cancer cells, as evidenced by increased lipid peroxidation and reduced expression of glutathione peroxidase 4 (GPX4). Mechanistically, we found that butyrate modulated the pathway involving activating transcription factor 3 (ATF3) and solute carrier family 7 member 11 (SLC7A11), leading to enhanced erastin-induced ferroptosis. Furthermore, partial reversal of the effect of butyrate on ferroptosis was observed upon knockdown of ATF3 or SLC7A11. Collectively, our findings indicate that butyrate enhances erastin-induced ferroptosis in lung cancer cells by modulating the ATF3/SLC7A11 pathway, suggesting its potential as a therapeutic agent for cancer treatment.

Development of neuromodulation for atrial fibrillation: a narrative review.

Background and Objective: Atrial fibrillation (AF) is a prevalent clinical arrhythmia with a high incidence of disability and mortality. Autonomic nervous system (ANS) plays a crucial role in the onset and persistence of AF, and can lead to electrophysiological changes and alterations in atrial structure. Both animal models and clinical findings suggest that parasympathetic and sympathetic activity within the cardiac ANS could induce atrial remodeling and AF. Remodeling of the cardiac autonomic nerves is a significant structural basis for promoting AF. Given the challenges faced by conventional pharmacological and atrial ablation techniques in the treatment of AF, increasing attention has been paid to autonomic intervention strategies for AF. Current research has demonstrated that the frequency and severity of AF episodes can be significantly reduced by modulating the activity of ANS. ANS neuromodulation is expected to lead more effective and personalized treatment options for patients with AF. The objective of this review is to provide a broader perspective for future related studies by reviewing preclinical and clinical studies of neuromodulation methods for the treatment of AF, searching for relevant approaches to treat AF, as well as identifying the strengths and weaknesses demonstrated by current relevant studies, and providing researchers with a broader overview of the latest neurological treatments for AF. Methods: A narrative review was conducted on the literature on PubMed, WanFang data, and Google Scholar, including all relevant studies published until November 2023. Key Content and Findings: In this review, we delve into the innervation of cardiac autonomic nerves, the role of the ANS in the development and maintenance of AF, and the current neuromodulation methods for AF treatment. These methods include stellate ganglion (SG) resection or ablation, vagus nerve stimulation (VNS), thoracic subcutaneous nerve stimulation (ScNS), renal denervation (RDN) therapy, ganglionated plexus (GP) ablation, and epicardial botulinum toxin or CaCl2 injection. More and more research suggests that neuromodulation methods for the treatment of AF have broad prospects. Conclusions: ANS plays a crucial role in AF development and maintenance through cardiac autonomic nerve remodeling. Modulating ANS activity can significantly reduce AF frequency and severity, offering more personalized treatment options. Current research on autonomic interventions for AF shows promise for more effective and personalized treatments.

Butyrate attenuates the stemness of lung cancer cells through lysosome Fe2+- and SLC7A11-mediated ferroptosis.

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of in vitro experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and in vivo tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both in vitro and in vivo experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe2+ in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe2+- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe2+ in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.

Solanum nigrum Polyphenol Extracts Inhibit Hepatic Inflammation, Oxidative Stress, and Lipogenesis in High-Fat-Diet-Treated Mice.

Patients with diabetes, obesity, and hyperlipidemia are all high-risk groups for fatty liver; however, the mechanism of fatty liver formation is not completely understood. Studies have indicated that abnormal fat metabolism, oxidative stress, and insulin resistance are positively correlated with peroxidation and abnormal cytokine production. Recent studies have revealed that Solanum nigrum extracts (SNE) possess anti-inflammatory, antioxidation, antihyperlipidemia, and liver protection abilities. Therefore, the present study investigated the in vivo and in vitro effects of an SNE on nonalcoholic fatty liver (NAFL)-induced hepatitis. In vivo data demonstrated that the SNE reduced blood triglyceride, sugar, and cholesterol levels, as well as fat accumulation, oxidative stress, and lipid peroxidation in high-fat-diet-treated mice. The results indicated that the SNE downregulated the expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and sterol regulatory element-binding proteins (SREBPs) through the AMP-activated protein kinase (AMPK) pathway and upregulated the expression of carnitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-activated receptor alpha. Furthermore, we prepared a Solanum nigrum polyphenol extract (SNPE) from the SNE; the SNPE reduced hepatic lipid (oleic acid) accumulation. Therefore, SNE have the potential to alleviate NAFL-induced hepatitis, and polyphenolic compounds are the main components of SNE. Moreover, SNE can be used to develop health-food products for preventing NAFL disease.