Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy . However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors P-gp inhibition. Moreover, Western blot experiments revealed that inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying of multiple mechanisms to reverse MDR in lung cancer.
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http://dx.doi.org/10.1016/j.apsb.2019.07.007 | DOI Listing |
Open Forum Infect Dis
January 2025
Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Background: Antimicrobial resistance is a global public health emergency. Patients undergoing hematopoietic stem cell transplantation (HCT) are at increased risk for severe infections with multidrug-resistant (MDR) organisms, although more data are needed on the relative burden of MDR Enterobacterales (MDR-E) in immunocompromised populations. In this study, we compare the prevalence of Enterobacterales resistance in cultures from patients undergoing HCT with that of non-HCT patients seeking care at a large healthcare system in North Carolina, USA.
View Article and Find Full Text PDFBioorg Chem
January 2025
CSIR- Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
The expanding prevalence of microbial resistance to conventional treatments has triggered a race to develop alternative/improved strategies to combat drug-resistant microorganisms in an efficient manner. Here, the lethal impact of the biosynthesized gold nanoparticles (AuNPs) against multi-drug resistant (MDR) bacteria has been elucidated. AuNPs, synthesized from the extracts of the fruit, leaf and peel of the Citrus maxima plant, were physicochemically characterized by UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), electron microscopy and spectroscopic techniques not only confirmed the production of AuNPs of size below 100 nm but also identified the phytochemicals adsorbed onto the surface of NPs.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
Multidrug resistant bacteria are causing health problems and economic burden worldwide; alternative treatment options such as natural products and nanoparticles have attained great attention recently. Therefore, we aimed to determine the phytochemicals, antibacterial potential, and anticancer activity of W. unigemmata.
View Article and Find Full Text PDFThromb Haemost
January 2025
Hemostasis and Erythropathology Laboratory, Hematopathology, Pathology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Background: V617F-mutated myeloproliferative neoplasms (MPN) exhibit abnormal proliferation of bone marrow progenitors and increased risk of thrombosis, specifically in splanchnic veins (SVT). The contribution of the endothelium to the development of the prothrombotic phenotype was explored.
Material And Methods: Plasma and serum samples from V617F MPN patients with (n=26) or without (n=7) thrombotic debut and different treatments, were obtained (n=33).
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
Chemotherapy remains the cornerstone of cancer treatment; however, its efficacy is frequently compromised by the development of chemoresistance. Multidrug resistance (MDR), characterized by the refractoriness of cancer cells to a wide array of chemotherapeutic agents, presents a significant barrier to achieving successful and sustained cancer remission. One critical factor contributing to this chemoresistance is the overexpression of ATP-binding cassette (ABC) transporters.
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