Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia. Electronic address:
Published: February 2024
AI Article Synopsis
Article Abstract
Transforming growth factor-β (TGF-β) is a pleiotropic cytokine essential for multiple biological processes, including the regulation of inflammatory and immune responses. One of the important functions of TGF-β is the suppression of the proinflammatory cytokine interleukin-12 (IL-12), which is crucial for mounting an anti-tumorigenic response. Although the regulation of the IL-12p40 subunit (encoded by the IL-12B gene) of IL-12 has been extensively investigated, the knowledge of IL-12p35 (encoded by IL-12A gene) subunit regulation is relatively limited. This study investigates the molecular regulation of IL-12A by TGF-β-activated signaling pathways in THP-1 monocytes. Our study identifies a complex regulation of IL-12A gene expression by TGF-β, which involves multiple cellular signaling pathways, such as Smad2/3, NF-κB, p38 and JNK1/2. Pharmacological inhibition of NF-κB signaling decreased IL-12A expression, while blocking the Smad2/3 signaling pathway by overexpression of Smad7 and inhibiting JNK1/2 signaling with a pharmacological inhibitor, SP600125, increased its expression. The elucidated signaling pathways that regulate IL-12A gene expression potentially provide new therapeutic targets to increase IL-12 levels in the tumor microenvironment.
Pulmonary hypertension (PH) is a progressive disease characterized by vascular reHypoxiaing, endothelial cell dysfunction, and inflammation. Liver Kinase B1 (LKB1, also known as STK11) is a central regulator of cell polarity and energy homeostasis. However, its specific role and mechanism of action in PH remain unclear.
Background: Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases.
Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Objective: Endometrial cancer (EC) is the ninth most common malignancy among women. While mutations in JAK2 are frequently observed in EC, the specific biological functions of JAK2 in endometrial cancer are poorly understood.
Methods: The genetic alterations of JAK2 in different cancer types were explored using sequencing dataset deposited at TCGA database.
Pulmonary fibrosis (PF) is a progressive, fatal lung disease lacking effective treatments. Autotaxin (ATX) plays a crucial role in exacerbating inflammation and fibrosis, making it a promising target for fibrosis therapies. Herein, starting from PAT-409 (Cudetaxestat), a series of novel ATX inhibitors bearing 1-indole-3-carboxamide, 4,5,6,7-tetrahydro-7-pyrazolo[3,4-]pyridin-7-one, or 4,5,6,7-tetrahydro-1-pyrazolo[4,3-]pyridine cores were designed based on the structure of ATX hydrophobic tunnel.
Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Aortic dissection (AD) represents a critical condition characterised by a tear in the inner lining of the aorta, leading to the leakage of blood into the layers of the aortic wall, posing a significant risk to life. However, the pathogenesis is unclear. In this study, scRNA-seq was applied to cells derived from aortas of both AD and non-AD donors (control) to unveil the cellular landscape.
