Epithelial homeostasis is essential for sensory transduction in the auditory and vestibular organs of the inner ear, but how it is maintained during trauma is poorly understood. To examine potential repair mechanisms, we expressed β-actin-enhanced green fluorescent protein (EGFP) in the chick inner ear and used live-cell imaging to study how sensory epithelia responded during aminoglycoside-induced hair cell trauma. We found that glial-like supporting cells used two independent mechanisms to rapidly eliminate dying hair cells. Supporting cells assembled an actin cable at the luminal surface that extended around the pericuticular junction and constricted to excise the stereocilia bundle and cuticular plate from the hair cell soma. Hair bundle excision could occur within 3 min of actin-cable formation. After bundle excision, typically with a delay of up to 2-3 h, supporting cells engulfed and phagocytosed the remaining bundle-less hair cell. Dual-channel recordings with β-actin-EGFP and vital dyes revealed phagocytosis was concurrent with loss of hair cell integrity. We conclude that supporting cells repaired the epithelial barrier before hair cell plasmalemmal integrity was lost and that supporting cell activity was closely linked to hair cell death. Treatment with the Rho-kinase inhibitor Y-27632 did not prevent bundle excision but prolonged phagocytic engulfment and resulted in hair cell corpses accumulating within the epithelium. Our data show that supporting cells not only maintain epithelial integrity during trauma but suggest they may also be an integral part of the hair cell death process itself.
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http://dx.doi.org/10.1523/JNEUROSCI.3042-10.2010 | DOI Listing |
Int J Biol Macromol
December 2024
Nano Drug Delivery Systems (NDDS), Cancer Biology Division, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Poojappura, Thiruvananthapuram, Kerala 695014, India. Electronic address:
Severe burns pose significant threats to patient well-being, characterized by pain, inflammation, bacterial infection, and extended recovery periods. While exosome-loaded hydrogels have demonstrated considerable promise in wound healing, current formulations often fall short of achieving optimal therapeutic efficacy for burn wounds due to challenges related to their adaptability to wound shape and limited anti-bacterial capabilities. In this study a novel exosome laden sprayable thermosensitive polysaccharide-based hydrogel (ADA-aPF127@LL18/Exo) comprising alginate dialdehyde (ADA) and aminated Pluronic F127 (aPF127) was fabricated via Schiff base reaction.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA; Center for Clinical Pharmacology, Washington University School of Medicine and University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA; Department of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy, St. Louis, Missouri, 63110, USA. Electronic address:
Inhibition of mitochondrial pyruvate transport via the mitochondrial pyruvate carrier (MPC) has shown beneficial effects in treating metabolic diseases, certain cancers, various forms of neurodegeneration, and hair loss. These benefits arise either from the direct inhibition of mitochondrial pyruvate metabolism or from the metabolic rewiring when pyruvate entry is inhibited. However, current MPC inhibitors are either nonspecific or possess poor pharmacokinetic properties.
View Article and Find Full Text PDFHear Res
December 2024
Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United States; Department of Otolaryngology-Head & Neck Surgery, Harvard Medical School, Boston, MA, United States. Electronic address:
Auditory-nerve fibers (ANFs) from a given cochlear region can vary in threshold sensitivity by up to 60 dB, corresponding to a 1000-fold difference in stimulus level, although each fiber innervates a single inner hair cell (IHC) via a single synapse. ANFs with high-thresholds also have low spontaneous rates (SRs) and synapse on the side of the IHC closer to the modiolus, whereas the low-threshold, high-SR fibers synapse on the side closer to the pillar cells. Prior biophysical work has identified modiolar-pillar differences in both pre- and post-synaptic properties, but a comprehensive explanation for the wide range of sensitivities remains elusive.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Department of Oncology, The Second People's Hospital of Banan District, Chongqing 400054, China.
Objective: To explore the impact of neoadjuvant immunotherapy on the clinical efficacy of stage IIIA-N2 non-small cell lung cancer (NSCLC) patients.
Methods: The retrospective study was conducted on 120 patients with stage IIIA-N2 NSCLC admitted to our hospital during April 2020 to April 2022. The control group received local chemotherapy, while the combination group received neoadjuvant immunotherapy on the basis of chemotherapy.
Mol Plant Pathol
December 2024
Shanghai Center for Plant Stress Biology, Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai, China.
Microbial pathogens and other parasites can modify the development of their hosts, either as a target or a side effect of their virulence activities. The plant-pathogenic bacterium Ralstonia solanacearum, causal agent of the devastating bacterial wilt disease, is a soilborne microbe that invades host plants through their roots and later proliferates in xylem vessels. In this work, we studied the early stages of R.
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