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Inhibition of Retinal Neovascularization by BEZ235: Targeting the Akt/4EBP1/Cyclin D1 Pathway in Endothelial Cells.
Invest Ophthalmol Vis Sci
January 2025
Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China.
Purpose: To investigate the therapeutic efficacy of BEZ235, a dual PI3K/mTOR inhibitor, in suppressing pathological neovascularization in an oxygen-induced retinopathy (OIR) mouse model and explore the role of cyclin D1 in endothelial cell cycle regulation.
Methods: Single-cell RNA sequencing was performed to analyze gene expression and cell-cycle alterations in retinal endothelial cells under normoxic and OIR conditions. The effects of BEZ235 on human umbilical vein endothelial cells (HUVECs) and human retinal microvascular endothelial cells (HRMECs) were evaluated by assessing cell viability, cell-cycle progression, proliferation, migration, and tube formation.
Survival Among Patients With ERBB2-Positive Metastatic Breast Cancer and Central Nervous System Disease.
JAMA Netw Open
January 2025
Department of Neurosurgery and Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York.
Importance: Approximately one-third of patients with ERBB2 (formerly HER2 or HER2/neu)-positive (ERBB2+) metastatic breast cancer (MBC) develop brain metastasis. It is unclear whether patients with disease limited to the central nervous system (CNS) have different outcomes and causes of death compared with those with concomitant extracranial metastasis.
Objective: To assess overall survival (OS) and CNS-related mortality among patients with ERBB2+ breast cancer and a diagnosis of CNS disease by disease distribution (CNS only vs CNS plus extracranial metastasis).
Upregulation of the MAP2K4 gene triggers endothelial-mesenchymal transition in COVID-19.
Mol Biol Rep
January 2025
Department of Molecular Biology and Genetics, Faculty of Art and Science, Tokat Gaziosmanpasa University, Tokat, 60200, Türkiye.
Background: SARS-CoV-2 infection is marked by an excessive inflammatory response, leading to elevated production of pro-inflammatory cytokines through activation of intracellular pathways like mitogen-activated protein kinase (MAPK). Viruses can use the MAPK signaling pathway to their advantage, but the relationship of this pathway to the severe SARS-CoV-2 period has not been fully elucidated. MAP2K4 is involved in the MAPK signaling pathway and affects cellular processes such as cell-cell junction, cell proliferation, differentiation and apoptosis.
View Article and Find Full Text PDFEbastine-mediated destabilization of E3 ligase MKRN1 protects against metabolic dysfunction-associated steatohepatitis.
Cell Mol Life Sci
January 2025
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer.
View Article and Find Full Text PDFFerroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.
J Gastroenterol
January 2025
Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham (UAB), Birmingham, Alabama, 35294, USA.
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and exhibits a limited response to apoptosis-dependent chemotherapeutic drugs (e.g., gemcitabine, Gem).
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