Objective: In this study, a comprehensive and comparative cytotoxic evaluation of morin against verapamil on rat intestinal epithelium as P-gp inhibitors through in-vitro gastrointestinal short-term toxicity assays involving permeability studies for safety evaluation was investigated.
Methods: In this study, the effect of morin (1 mM or 10 mM) or verapamil (1 mM or 10 mM) or sodium deoxycholate (10 mM) was investigated on intestinal epithelium and isolated brush border membrane using biomarker assays. Cytotoxicity was determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The nutrients transport was assessed using everted sacs studies. Paracellular permeability was measured using Lucifer yellow, followed by morphometric analysis of intestinal sacs.
Key Findings: Our results indicated that morin was effective in maintaining cell viability with no significant changes (P > 0.05) in the activity of intestinal brush border markers, membrane integrity and morphometric analysis as compared with control. On the contrary, dramatic (P < 0.01) changes were noticed in the release of membrane markers, cell viability and surface characteristics of intestinal segments when treated with verapamil or sodium deoxycholate as compared with control or morin.
Conclusions: Our findings confirm that morin is non-toxic to rat intestinal epithelium against verapamil demonstrating the potential use of bioflavonoid as safe and novel pharmaceutical adjuvant as P-gp inhibitor.
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http://dx.doi.org/10.1111/jphp.12400 | DOI Listing |
Nat Med
January 2025
BioNTech US, Cambridge, MA, USA.
New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.
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January 2025
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, AvInstituto Politécnico Nacional 2508, Col San Pedro ZacatencoCDMX, C.P. 07360, Mexico City, Mexico.
Fluoride is emitted into the air not only through gas emissions but also from volcanic ash, leading to contact via inhalation. Therefore, the objective of the present study was to evaluate the cellular and biochemical responses in the A549 cell line after exposure to NaF (sodium fluoride) concentrations lower than those previously used in other studies to determine the impact on the lung epithelium. A549 cells were exposed to different concentrations (0.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Stereotactic and Functional Neurosurgery, University Hospital of Bonn, 53127, Bonn, Germany.
Despite the favorable effects of immunotherapies in multiple types of cancers, its complete success in CNS malignancies remains challenging. Recently, a successful clinical trial of cytokine-induced killer (CIK) cell immunotherapy in patients with glioblastoma (GBM) has opened a new avenue for adoptive cellular immunotherapies in CNS malignancies. Prompt from these findings, herein, we investigated whether dendritic cells (DC) in combination with cytokine-induced killer cells (DC-CIK) could also provide an alternative and more effective way to improve the efficacy of GBM treatment.
View Article and Find Full Text PDFSci Rep
January 2025
Obstetrics and Gynaecology Department, Faculty of Medicine, Minia University, Minia, Egypt.
Nanomedical applications have increased significantly. This work aimed to fabricate and characterize cobalt oxide nanoparticles (CoOnps) synthesized biologically via aqueous Alhagi maurorum extract and evaluate their cytotoxic and antimicrobial impacts. Green-synthesized CoOnps were prepared and analyzed using UV-Vis spectrophotometer UV-vis, Scanning electron microscopy (SEM), Transmission electron microscopy TEM, Energy dispersive X-ray analysis EDAX, Fourier transform infrared, FTIR, and X-ray diffraction (XRD).
View Article and Find Full Text PDFJ Nucl Med
January 2025
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;
Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.
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