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The endogenous dynorphin/kappa opioid receptor (KOR) system in the brain mediates the dysphoric effects of stress, and KOR antagonists may have therapeutic potential for the treatment of drug addiction, depression, and psychosis. One class of KOR antagonists, the long-acting norBNI-like antagonists, have been suggested to act by causing KOR inactivation through a cJun-kinase mechanism rather than by competitive inhibition. In this study, we screened for other opioid ligands that might produce norBNI-like KOR inactivation and found that nalfurafine (a G-biased KOR agonist) and nalmefene (a KOR partial agonist) also produce long-lasting KOR inactivation.
View Article and Find Full Text PDFFirst-in-human Study of ABY-029, a Novel Fluorescent Peptide that Targets Epidermal Growth Factor Receptor, Applied to Soft-Tissue Sarcomas.
Mol Cancer Ther
December 2024
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies.
View Article and Find Full Text PDFMicro-Doses of DNP Preserve Motor and Muscle Function with a Period of Functional Recovery in Amyotrophic Lateral Sclerosis Mice.
Ann Neurol
November 2024
Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL.
Article Synopsis
- Mitochondrial dysfunction is an early issue in ALS, and this study investigates the potential of 2,4-dinitrophenol (DNP), a mitochondrial uncoupler, as a treatment for ALS in a mouse model.
- Mice were given varying doses of DNP from early stages of the disease, and their motor skills and muscle function were assessed regularly, showing improvements in coordination, muscle performance, and reduced inflammation.
- The findings suggest that DNP can delay disease onset and even lead to recovery in motor abilities for symptomatic mice, indicating its potential as a novel treatment option for ALS if properly timed and dosed.
Framework for Microdosing Odors in Virtual Reality for Psychophysiological Stress Training.
Sensors (Basel)
October 2024
Department of Computer Science, University of the Bundeswehr Munich, 85579 Neubiberg, Germany.
Article Synopsis
- Emergency personnel are using virtual reality (VR) stress training to manage stress during emergencies, but olfactory stimuli (smells) are often overlooked.
- The paper explores how incorporating odors can enhance immersion and perceived stress during VR simulations, aiming to show their potential benefits in civilian stress training.
- Additionally, it describes the creation of a portable fragrance dosing system using micropumps to deliver controlled odors, ensuring a consistent scent experience during VR training.
Construction of an electrochemical aptamer-based sensors for rapid quantification of the anticancer drug imatinib in blood to improve drug bioavailability at microdoses.
Int J Biol Macromol
December 2024
Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350116, China; Department of Anesthesiology, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. Electronic address:
Imatinib (Ima), as a commonly used anticancer drug for the clinical treatment of leukemia and gastrointestinal mesenchymal stromal tumour, requires timely monitoring of patients' blood concentration to ensure efficacy while reducing complications and achieving precision medicine due to its narrow therapeutic window (1-5 μM) and the varying sensitivity and resistance of different patients to Ima. However, traditional assays are slow and cumbersome, so improved and innovative platforms for monitoring Ima in the clinic are necessary. In this work, a nanoporous electrochemical aptamer-based (E-AB) sensor was designed for the detection of Ima and imatinib mesylate (Ima-Mes) in blood.
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