In the age of antimicrobial resistance, the urgency by which novel therapeutic approaches need to be introduced into the clinical pipeline has reached critical levels. Antimicrobial blue light (aBL), as an alternative approach, has demonstrated promise as a stand-alone therapeutic method, albeit with a limited window of antimicrobial activity. Work by others indicates that treatment with antibiotics increases the production of reactive oxygen species (ROS) which may, in part, contribute to the bactericidal effects of antibiotics. These findings suggest that there may be potential for synergistic interactions with aBL, that similarly generates ROS. Therefore, in this study, the mechanism of aBL is investigated, and the potential for aBL to synergistically promote antibiotic activity is similarly evaluated. Furthermore, the translatability of using aBL and chloramphenicol in combination within a mouse model of Acinetobacter baumanii burn infection is assessed. It is concluded that porphyrins and hydroxyl radicals driven by "free iron" are paramount to the effectiveness of aBL; and aBL is effective at promoting multiple antibiotics in different multidrug-resistant bacteria. Moreover, rROS up-regulation, and promoted antibiotic uptake are observed during aBL+antibiotic exposure. Lastly, aBL combined with chloramphenicol appears to be both effective and safe for the treatment of A. baumannii burn infection. In conclusion, aBL may be a useful adjunct therapy to antibiotics to potentiate their action.
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http://dx.doi.org/10.1002/advs.202303731 | DOI Listing |
Bioorg Med Chem Lett
December 2024
Carna Biosciences, Inc., 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
In a previous study, we reported that nilotinib, a BCR-ABL tyrosine kinase inhibitor, possesses moderate antimalarial activity against PfK1 and PfFCR3. As a part of our efforts to develop novel antimalarial agents, a series of novel triazine analogs was identified as potent antimalarial agents via structure modification of nilotinib. Compound 15a showed strong antimalarial activities against PfK1 and PfFCR3 with IC values of 0.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
BioLab, Instituto Universitario de Bio-Orgánica "Antonio González", University of La Laguna, La Laguna, Spain.
Glycosylation patterns represent an important signature of cancer cells that can be decoded by glycan-binding proteins, i.e., lectins.
View Article and Find Full Text PDFMalays J Pathol
December 2024
National Institutes of Health, Institute for Medical Research, Cancer Research Centre, Haematology Unit, 40170 Shah Alam, Selangor, Malaysia.
Introduction: The emergence of mutations in the BCR::ABL1 kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contributing to IM resistance. Identification of these mutations is important for treatment decisions and precision medicine in chronic myeloid leukaemia (CML) patients. Our study aims to determine the frequency of BCR::ABL1 KD mutations in CML patients with IM resistance.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei, 10507, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address:
Multidrug resistance (MDR) remains a significant obstacle in cancer treatment, primarily attributable to the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2 within cancer cells. These transporters actively diminish the effectiveness of cytotoxic drugs by facilitating ATP hydrolysis-dependent drug efflux, thereby reducing intracellular drug accumulation. Given the absence of approved treatments for multidrug-resistant cancers and the established benefits of combining tyrosine kinase inhibitors (TKIs) with conventional anticancer drugs, we investigate the potential of vodobatinib, a potent c-Abl TKI presently in clinical trials, to restore sensitivity to chemotherapeutic agents in multidrug-resistant cancer cells overexpressing ABCB1 and ABCG2.
View Article and Find Full Text PDFBr J Surg
December 2024
Bristol Surgical and Perioperative Care Complex Intervention Collaboration, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, UK.
Background: Oncoplastic breast-conserving surgery may be a better option than mastectomy, but high-quality comparative evidence is lacking. The aim of the ANTHEM study (ISRCTN18238549) was to explore clinical and patient-reported outcomes in a multicentre cohort of women offered oncoplastic breast-conserving surgery as an alternative to mastectomy with or without immediate breast reconstruction.
Methods: Women with invasive/pre-invasive breast cancer who were offered oncoplastic breast-conserving surgery with volume replacement or displacement techniques to avoid mastectomy were recruited prospectively.
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