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Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction.
Nat Commun
January 2025
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China.
Chronic allodynia stemming from peripheral stump neuromas can persist for extended periods, significantly compromising patients' quality of life. Conventional managements for nerve stumps have demonstrated limited effectiveness in ensuring their orderly termination. In this study, we present a spatially confined conduit strategy, designed to enhance the self-organization of regenerating nerves after truncation.
View Article and Find Full Text PDFOptimization and Calibration of 384-well Kinetic Ca Mobilization Assays for the Human Transient Receptor Potential Cation Channels TRPM8, TRPV1, and TRPA1.
SLAS Discov
December 2024
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; University of Pittsburgh Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address:
Development, optimization, and calibration of human transient receptor potential (TRP) channel Ca mobilization assays for TRPM8, TRPV1, and TRPA1 are described. Heterologous expression of hTRPM8 in HEK293T cells was required for anti-TRPM8 antibody staining and TRPM8 agonist induced Ca mobilization signals which were both used to optimize transfection efficiency. FLIPR Calcium 6 dye concentration, loading time, and TRPM8 transfected cell seeding density were optimized and a DMSO tolerance of ≤0.
View Article and Find Full Text PDFSea Anemone Kunitz Peptide HCIQ2c1: Structure, Modulation of TRPA1 Channel, and Suppression of Nociceptive Reaction In Vivo.
Mar Drugs
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.
TRPA1 is a homotetrameric non-selective calcium-permeable channel. It contributes to chemical and temperature sensitivity, acute pain sensation, and development of inflammation. HCIQ2c1 is a peptide from the sea anemone that inhibits serine proteases.
View Article and Find Full Text PDFDiscovery of novel oxindole derivatives as TRPA1 antagonists with potent analgesic activity for pain treatment.
Bioorg Chem
December 2024
Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China. Electronic address:
Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in detecting harmful stimuli and endogenous ligands, primarily expressed in sensory neurons. Due to its role in pain and itch, TRPA1 is a potential drug target. We identified an oxindole core structure via high-throughput screening, modified it, and tested the modified compounds in vitro and in vivo.
View Article and Find Full Text PDFIon Channels as Potential Drug Targets in Dry Eye Disease and Their Clinical Relevance: A Review.
Cells
December 2024
Center for Research on Harmful Effects of Biological and Chemical Hazards, Departments of Genetics, Microbiology and Immunology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia.
Dry eye disease (DED) is a common multifactorial disorder characterized by a deficiency in the quality and/or quantity of tear fluid. Tear hyperosmolarity, the dysfunction of ion channel proteins, and eye inflammation are primarily responsible for the development and progression of DED. Alterations in the structure and/or function of ion channel receptors (transient receptor potential ankyrin 1 (TRPA1), transient receptor potential melastatin 8 (TRPM8), transient receptor potential vanilloid 1 and 4 (TRPV1 and TRPV4)), and consequent hyperosmolarity of the tears represent the initial step in the development and progression of DED.
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