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S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.
Int J Biol Sci
January 2025
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.
View Article and Find Full Text PDFGinkgo biloba extract mediates HT22 cell proliferation and migration after oxygen-glucose deprivation/reoxygenation via regulating RhoA-ROCK2 signalling pathway.
Metab Brain Dis
January 2025
Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No.42 Wenhua West Road, Jinan, 250011, P.R. China.
Vascular dementia (VD) is a neurocognitive disorder resulting from cerebral vascular disorders, leading to the demise of neurons and cognitive deficits, posing significant health concerns globally. Derived from Ginkgo biloba leaves, EGb761 is a potent bioactive compound widely recognized for its benefits in treating cerebrovascular diseases. Previous studies have demonstrated that the administration of EGb761 to VD rats enhances the proliferation, differentiation, and migration of neurons, effectively alleviating cognitive dysfunction.
View Article and Find Full Text PDFThe cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.
Proc Natl Acad Sci U S A
January 2025
Department of Human Molecular Genetics and Biochemistry, Faculty of Health & Medical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging.
View Article and Find Full Text PDFThymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 Subtype C Reverse Transcriptase to Islatravir.
Viruses
December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
View Article and Find Full Text PDFA Mutation in the Herpes Simplex Virus Type 1 (HSV-1) UL29 Gene is Associated with Anti-Herpesvirus Drugs' Susceptibility.
Viruses
November 2024
Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Herpes simplex virus type 1 (HSV-1) acyclovir (ACV) resistance is acquired by mutations in the viral thymidine kinase (TK) or DNA polymerase (DNApol) genes. We previously obtained an ACV-resistant clone (HSV-1_VZV_TK_clone α) by sequential passages of HSV-1_VZV-TK, a recombinant virus which lacked its endogenous TK activity and instead expressed the varicella-zoster virus (VZV) TK ectopically. HSV-1_VZV_TK_clone α had been generated using an HSV-1_BAC in the presence of increasing concentrations of ACV.
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