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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).
From fatty liver to fibrosis: the impact of miRNAs on NAFLD and NASH.
Funct Integr Genomics
January 2025
Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.
Non-alcoholic fatty liver disease (NAFLD) is a disease with various levels varying from fatty liver steatosis to acute steatosis which is non-alcoholic steatohepatitis (NASH), which can develop into hepatic failure, as well as in some conditions it can develop into hepatocellular carcinoma (HCC). In the NAFLD and NASH context, aberrant microRNA (miRNA) expression has a thorough contribution to the incidence and development of these liver disorders by influencing key biological actions, involving lipid metabolism, inflammation, and fibrosis. Dysregulated miRNAs can disrupt the balance between lipid accumulation and clearance, exacerbate inflammatory responses, and promote fibrogenesis, thus advancing the severeness of the disorder from simple steatosis to more complex NASH.
View Article and Find Full Text PDFUpregulation 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 PDFEpstein-Barr virus-infected nasopharyngeal carcinoma therapeutics: oncoprotein targets and clinical implications.
Med Oncol
January 2025
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
Nasopharyngeal carcinoma (NPC) is a distinctive epithelial cancer closely associated with Epstein-Barr Virus (EBV) infection, posing significant challenges in diagnosis and treatment due to its resistance to conventional therapies and high recurrence rates. Current therapies, including radiotherapy and chemotherapy, exhibit limited efficacy, particularly in recurrent or metastatic cases, highlighting the urgent need for novel therapeutic strategies. Targeting EBV oncoproteins, such as Epstein-Barr Virus encoded Nuclear Antigen 1 (EBNA1), Latent Membrane Protein 1 (LMP1), and Latent Membrane Protein 2 (LMP2), presents a promising therapeutic avenue in NPC treatment.
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