IntroductionNoise-induced calcium overload in sensory hair cells has been well documented as an early step in the pathogenesis of noise-induced hearing loss (NIHL). Alterations in cellular calcium homeostasis mediate a series of cellular events, including activation of calcium-dependent protein kinases and phosphatases. Using cell-membrane- and blood-brain-barrier-permeable calpain-1 (μ-calpain) and calpain-2 (m-calpain) inhibitor MDL-28170, we tested the involvement of calpains, a family of calcium-dependent cysteine proteases, and the potential of MDL-28170 in preventing NIHL.MethodsCBA/J mice at the age of 12 weeks were exposed to broadband noise with a frequency spectrum from 2–20 kHz for 2 h at 101 dB sound pressure level to induce permanent hearing loss as measured by auditory brainstem response and distortion product otoacoustic emissions. Morphological damage was assessed by quantification of remaining sensory hair cells and inner hair cell synapses 2 weeks after the exposure.ResultsMDL-28170 treatment by intraperitoneal injection significantly attenuated noise-induced functional deficits and cochlear pathologies. MDL-28170 treatment also prevented noise-induced cleavage of alpha-fodrin, a substrate for calpain-1. Furthermore, MDL-28170 treatment prevented reduction of PI3K/Akt signaling after exposure to noise and upregulated p85α and p-Akt (S473) in outer hair cells.DiscussionThese results indicate that noise-induced calpain activation negatively regulates PI3K/Akt downstream signaling, and that prevention of NIHL by treatment with MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathways.

IntroductionTraumatic brain injury (TBI) is a major health concern worldwide. D-dimer levels, commonly used in the diagnosis and treatment of neurological diseases, may be associated with adverse events in patients with TBI. However, the relationship between D-dimer levels, TBI-related in-hospital complications, and long-term mortality in patients with TBI has not been investigated. Here, examined whether elevated D-dimer levels facilitate the prediction of in-hospital complications and mortality in patients with TBI.MethodsOverall, 1,338 patients with TBI admitted to our institute between January 2016 and June 2022 were retrospectively examined. D-dimer levels were assessed within 24 h of admission, and propensity score matching was used to adjust for baseline characteristics.ResultsAmong the in-hospital complications, high D-dimer levels were associated with electrolyte metabolism disorders, pulmonary infections, and intensive care unit admission (p < 0.05). Compared with patients with low (0.00–1.54 mg/L) D-dimer levels, the odds of long-term mortality were significantly higher in all other patients, including those with D-dimer levels between 1.55 mg/L and 6.35 mg/L (adjusted hazard ratio [aHR] 1.655, 95% CI 0.9632.843), 6.36 mg/L and 19.99 mg/L (aHR 2.38, 95% CI 1.416–4.000), and >20 mg/L (aHR 3.635, 95% CI 2.195–6.018; p < 0.001). D-dimer levels were positively correlated with the risk of death when the D-dimer level reached 6.82 mg/L.ConclusionOverall, elevated D-dimer levels at admission were associated with adverse outcomes and may predict poor prognosis in patients with TBI. Our findings will aid in the acute diagnosis, classification, and management of TBI.