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Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.
NPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFThe 2023 Dengue Outbreak in Lombardy, Italy: A One-Health Perspective.
Travel Med Infect Dis
January 2025
General Directorate of Welfare, Regione Lombardia, Milano, Italy.
Introduction: Here we reported the virological, entomological and epidemiological characteristics of the large autochthonous outbreak of dengue (DENV) occurred in a small village of the Lombardy region (Northern Italy) during summer 2023.
Methods: After the diagnosis of the first autochthonous case on 18 August 2023, public health measures, including epidemiological investigation and vector control measures, were carried out. A serological screening for DENV antibodies detection was offered to the population.
Magnetic field-oriented conductive decellularized extracellular matrix hydrogel synergizes with electrical stimulation to promote spinal cord injury repair and electrophysiological function restoration.
Biomater Adv
December 2024
Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center of Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address:
Spinal cord injury (SCI) results in electrophysiological and behavioral dysfunction. Electrical stimulation (ES) is considered to be an effective treatment for mild SCI; however, ES is not applicable to severe SCI due to the disruption of electrical conduction caused by tissue defects. Therefore, the use of conductive materials to fill the defects and restore electrical conduction in the spinal cord is a promising therapeutic strategy.
View Article and Find Full Text PDFDual-Enzyme-Instructed Peptide Self-Assembly to Boost Immunogenic Cell Death by Coordinating Intracellular Calcium Overload and Chemotherapy.
ACS Nano
January 2025
Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, Zhejiang, P. R. China.
The concept of immunogenic cell death (ICD) induced by chemotherapy as a potential synergistic modality for cancer immunotherapy has been widely discussed. Unfortunately, most chemotherapeutic agents failed to dictate effective ICD responses due to their defects in inducing potent ICD signaling. Here, we report a dual-enzyme-instructed peptide self-assembly platform of (CPT-GFFpY-PLGVRK-Caps) that cooperatively utilizes camptothecin (CPT) and capsaicin (Caps) to promote ICD and engage systemic adaptive immunity for tumor rejection.
View Article and Find Full Text PDFLanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis.
J Med Chem
January 2025
The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism.
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