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Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog.
Nat Aging
December 2024
Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
The emerging field of senolytics is centered on eliminating senescent cells to block their contribution to the progression of age-related diseases, including cancer, and to facilitate healthy aging. Enhancing the selectivity of senolytic treatments toward senescent cells stands to reduce the adverse effects associated with existing senolytic interventions. Taking advantage of lipofuscin accumulation in senescent cells, we describe here the development of a highly efficient senolytic platform consisting of a lipofuscin-binding domain scaffold, which can be conjugated with a senolytic drug via an ester bond.
View Article and Find Full Text PDFMitochondria-targeted antioxidant MitoQ radiosensitizes tumors by decreasing mitochondrial oxygen consumption.
Cell Death Discov
December 2024
Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Hypoxic tumors are radioresistant stemming from the fact that oxygen promotes reactive oxygen species (ROS) propagation after water radiolysis and stabilizes irradiation-induced DNA damage. Therefore, an attractive strategy to radiosensitize solid tumors is to increase tumor oxygenation at the time of irradiation, ideally above a partial pressure of 10 mm-Hg at which full radiosensitization can be reached. Historically, the many attempts to increase vascular O delivery have had limited efficacy, but mathematical models predicted that inhibiting cancer cell respiration would be more effective.
View Article and Find Full Text PDFA conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.
Nat Commun
December 2024
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.
View Article and Find Full Text PDFA high-throughput micro-scale workflow to quantify molecularly dissolved drug concentrations under solubilizing conditions.
J Pharm Sci
December 2024
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark. Electronic address:
Physiological and artificial solubilizing agents usually enhance apparent solubility of poorly soluble drugs, and in many cases also oral drug exposure. However, exposure may decrease in cases where micellization reduces the molecularly dissolved drug fraction, overriding the solubility advantage. While this information is critical to accurately anticipate the effect of drug micellization on oral absorption, the experimental determination of molecularly dissolved drug concentrations is complex and time consuming.
View Article and Find Full Text PDFChemically defined and growth factor-free system for highly efficient endoderm induction of human pluripotent stem cells.
Stem Cell Reports
December 2024
School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Shandong 266071, China; Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, China; Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangdong 510080, China. Electronic address:
Definitive endoderm (DE) derived from human pluripotent stem cells (hPSCs) holds great promise for cell-based therapies and drug discovery. However, current DE differentiation methods required undefined components and/or expensive recombinant proteins, limiting their scalable manufacture and clinical use. Homogeneous DE differentiation in defined and recombinant protein-free conditions remains a major challenge.
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