Damage-activated stem/progenitor cells play important roles in regenerating lost cells and in tissue repair. Previous studies reported that the mouse utricle has limited hair cell regeneration ability after hair cell ablation. However, the potential progenitor cell population regenerating new hair cells remains undiscovered. In this study, we first found that Lgr5, a Wnt target gene that is not usually expressed in the neonatal mouse utricle, can be activated by 24 h neomycin treatment in a sub-population of supporting cells in the striolar region of the neonatal mouse utricle. Lineage tracing demonstrated that these Lgr5-positive supporting cells could regenerate new hair cells in explant culture. We isolated the damage-activated Lgr5-positive cells with flow cytometry and found that these Lgr5-positive supporting cells could regenerate hair cells in vitro, and self-renew to form spheres, which maintained the capacity to differentiate into hair cells over seven generations of passages. Our results suggest that damage-activated Lgr5-positive supporting cells act as hair cell progenitors in the neonatal mouse utricle, which may help to uncover a potential route to regenerate hair cell in mammals.
Although the connection between heat shock protein 70 (HSP70) and vestibular migraine is not clear, HSP70 is neuroprotective in other scenarios. This study aimed to investigate the potential of exogenous HSP70 for treating migraine-like symptoms in a mouse model of nitroglycerin (NTG) induced migraine. HSP70 levels were assessed in patients with vestibular migraine and healthy individuals by ELISA. Migraine was induced in mice by NTG and HSP70 expression was examined in the trigeminal nucleus caudalis (TNC) tissue of mice treated with NTG and NTG together with exogenous HSP70. The effects of exogenous HSP70 on migraine-like symptoms were assessed through behavioral assays. Finally, the impact of HSP70 on oxidative stress and NF-κB signaling in migraine mice was investigated. Serum HSP70 in patients with vestibular migraine was significantly lower than that of healthy individuals. NTG administration significantly suppressed HSP70 expression in mouse TNC tissue which were reversed by exogenous HSP70. HSP70 alleviated NTG-induced mechanical hypersensitivity, light aversion and anxiety-like behavior. Finally, exogenous HSP70 suppressed NTG-induced oxidative stress and NF-κB signaling. Our study suggests that exogenous HSP70 may be a potential therapy for alleviating migraine symptoms and our promising finding warrants further investigation of HSP70 for clinical application.
The rapid development of personalized medicine places high demands on the control of drug dose and cellular drug response to provide patients with better curative effects and low side effects. To solve the problem of low detection accuracies of the cell-counting kit-8 (CCK8) method, a detection method based on surface-enhanced Raman spectroscopy (SERS) of cell-secreted proteins was adopted to evaluate the concentration of the anticancer drug cisplatin and the cellular drug response of nasopharyngeal carcinoma. CNE1 and NP69 cell lines were used to evaluate cisplatin response. The results showed that the combination of the SERS spectrum with principal component analysis–linear discriminant analysis could detect the difference in the response of cisplatin with a concentration difference of 1 μg/mL, which considerably exceeded that of CCK8. In addition, the SERS spectral peak intensity of the cell-secreted proteins strongly correlated with the cisplatin concentration. Furthermore, the mass spectrum of the secreted proteins of the nasopharyngeal carcinoma cells was analyzed to verify the results obtained using the SERS spectrum. The results demonstrated that SERS of secreted proteins has great potential for high-precision detection of chemotherapeutic drug response.
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