TRIM3 facilitates ferroptosis in non-small cell lung cancer through promoting SLC7A11/xCT K11-linked ubiquitination and degradation.

Ferroptosis, a unique form of regulated necrotic cell death, is caused by excessive iron-dependent lipid peroxidation. However, the underlying mechanisms driving ferroptosis in human cancers remain elusive. In this study, we identified TRIM3, an E3 ubiquitin-protein ligase, as a key regulator of ferroptosis. TRIM3 is downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two major types of non-small cell lung cancer (NSCLC). Forced expression of TRIM3 promotes cell death by enhancing the cellular level of ROS and lipid peroxidation. Moreover, our in vivo study determined that TRIM3 overexpression diminishes the tumorigenicity of NSCLC cells, indicating that TRIM3 functions as a tumor suppressor in NSCLC. Mechanistically, TRIM3 directly interacts with SLC7A11/xCT through its NHL domain, leading to SCL7A11 K11-linked ubiquitination at K37, which promotes SLC7A11 proteasome-mediated degradation. Importantly, TRIM3 expression exhibits a negative correlation with SCL7A11 expression in clinical NSCLC samples, and low TRIM3 expression is associated with a worse prognosis. This study reveals that TRIM3 functions as a tumor suppressor that can impede the tumorigenesis of NSCLC by degrading SLC7A11, suggesting a novel therapeutic strategy against NSCLC.

Treatment of syphilitic aortitis with coronary artery bypass grafting and "open" stent placement.

Cardiovascular syphilis manifests many years after primary infection. Here, we report the successful treatment of a patient who developed syphilitic aortitis with bilateral coronary ostial stenosis and aortic insufficiency. The patient underwent right coronary artery bypass grafting, left main coronary ostial "open" stent placement, and mechanical aortic valve placement during open-heart surgery.

Mitral valve repair in patients with mirror-image dextrocardia and situs inversus: two cases and a review of the literature.

Dextrocardia is a rare cardiac malposition that was first described in 1606. Mirror-image dextrocardia is characterized by a mirror-image change of the normal position of the heart. Most cases are accompanied by situs inversus viscerum, whereas only 3% to 10% of cases are associated with intracardiac anomalies. Valve surgery for acquired valvular lesions in patients with mirror-image dextrocardia with situs inversus is rare. Diagnosing situs anomalies in adults is important to prevent errors during surgical operations, emergency procedures, or interventional operations. In this report, we present two cases of mitral regurgitation in patients with mirror-image dextrocardia. One patient had mirror-image dextrocardia with subacute infective endocarditis and mitral regurgitation, and the other patient had mirror-image dextrocardia with mitral Carpentier type I regurgitation. In both patients, mitral valve repair was successfully performed using a transseptal approach.

Management of chronic Stanford type A aortic dissection combined with Neri type C coronary occlusion: a case report and literature review.

While there are many reports on partial aortic root remodelling, it is rarely performed for chronic aortic dissection of the coronary artery. This case report describes a 71-year-old male patient with chronic aortic dissection who was admitted to hospital due to repeated palpitations and chest distress. He had a long-term occlusion of the right coronary artery and an abnormal origin of the left vertebral artery. A carefully planned surgical strategy was arranged for this patient, and the surgical experience is described and discussed herein. Briefly, the patient was treated by aortic root repair plus ascending aorta replacement plus Sun's procedure plus left vertebral artery graft implantation plus coronary artery bypass graft (right coronary artery to saphenous vein to innominate artery). At approximately 6 months following surgery, the patient had returned to normal living conditions without any reports of discomfort.

Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation.

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment of restenosis by the paracrine function of extracellular vesicles (EVs). However, the risk of tumorigenicity and poor cell survival limits its clinical applications. In this study, we for the first time applied a highly efficient and robust three-dimensional (3D) protocol for hiPSC differentiation into endothelial cells (ECs) with subsequent isolation of EVs from the derived hiPSC-EC (ECs differentiated from hiPSCs), and validated their therapeutic effect in intimal hyperplasia (IH) models. We found that intravenously (iv) injected EVs could accumulate on the carotid artery endothelium and significantly alleviate the intimal thickening induced by the carotid artery ligation. To elucidate the mechanism of this endothelial protection, we performed miRNA expression profiling and found out that among the most conserved endothelial miRNAs, miR-126 was the most abundant in hiPSC-EC-produced EVs (hiPSC-EC-EV). MiR-126 depletion from hiPSC-EC-EV can hinder its protective effect on human umbilical vein endothelial cells (HUVECs) in an inflammatory process. A variety of functional in vitro studies revealed that miR-126 was able to prevent endothelial apoptosis after inflammatory stimulation, as well as promote EC migration and tube formation through autophagy upregulation. The latter was supported by in vivo studies demonstrating that treatment with hiPSC-EC-EV can upregulate autophagy in mouse carotid artery ECs, thereby preventing IH and modulating vascular homeostasis via remodeling of the vascular intima. Our findings suggest a regulatory mechanism for the therapeutic effect on arterial restenosis by autophagy regulation, and provide a potential strategy for clinical treatment of the disease.

LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear. METHODS: PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1. RESULTS: PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells. CONCLUSION: PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.

Artificial Intelligent Multi-Modal Point-of-Care System for Predicting Response of Transarterial Chemoembolization in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks the second most lethal tumor globally and is the fourth leading cause of cancer-related death worldwide. Unfortunately, HCC is commonly at intermediate tumor stage or advanced tumor stage, in which only some palliative treatment can be used to offer a limited overall survival. Due to the high heterogeneity of the genetic, molecular, and histological levels, HCC makes the prediction of preoperative transarterial chemoembolization (TACE) efficacy and the development of personalized regimens challenging. In this study, a new multi-modal point-of-care system is employed to predict the response of TACE in HCC by a concept of integrating multi-modal large-scale data of clinical index and computed tomography (CT) images. This multi-modal point-of-care predicting system opens new possibilities for predicting the response of TACE treatment and can help clinicians select the optimal patients with HCC who can benefit from the interventional therapy.