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Tissue nanotransfection-based endothelial PLCγ2-targeted epigenetic gene editing in vivo rescues perfusion and diabetic ischemic wound healing.
Mol Ther
January 2025
Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, United States; Department of Surgery, Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address:
Diabetic wounds are complicated by underlying peripheral vasculopathy. Reliance on vascular endothelial growth factor (VEGF) therapy to improve perfusion makes logical sense, yet clinical study outcomes on rescuing diabetic wound vascularization have yielded disappointing results. Our previous work has identified that low endothelial phospholipase Cγ2 (PLCγ2) expression hinders the therapeutic effect of VEGF on the diabetic ischemic limb.
View Article and Find Full Text PDFGITRL enhances cytotoxicity and persistence of CAR-T cells in cancer therapy.
Mol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFAdhesion-driven vesicle translocation through membrane-covered pores.
Biophys J
January 2025
Theoretical Physics of Living Matter, Institute of Biological Information Processing and Institute for Advanced Simulation, Forschungszentrum Jülich, 52425 Jülich, Germany. Electronic address:
Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii.
View Article and Find Full Text PDFRepression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFEndogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis.
J Transl Med
January 2025
Medical School of Nanjing University, Nanjing, 210093, China.
Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC and its potential anti-cancer properties were examined.
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