Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common causes of hereditary hearing loss in humans, and previous studies showed postnatal development arrest of the organ of Corti in different Cx26-null mouse models. To explore the pathological changes and the mechanism behind the cochlear abnormalities in these mice further, we established transgenic mouse models by conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory brainstem responses were recorded and the morphological features in the organ of Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group displayed severe hearing loss at all frequencies, whereas mice in the P8 knockdown group showed nearly normal hearing. In the P8 knockdown group, the organ of Corti displayed normal architecture, and no ultrastructural changes were observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells did not develop into finger-like structures, and the formation of microtubules in the pillar cells was significantly reduced; moreover, the amount of acetylated α-tubulin was reduced in pillar cells. Our results indicate that Gjb2 participates in postnatal development of the cytoskeleton in pillar cells during structural maturation of the organ of Corti. In P0 knockdown mice, the reduction in microtubules in pillar cells might be responsible for the failure of the tunnel of Corti to open, and the malformed phalangeal processes might negatively affect the supporting framework of the organ of Corti, which would be a new mechanism of Gjb2-related hearing loss.

Connexin26 (Cx26, encoded by GJB2) mutations are the most common cause of non-syndromic deafness. GJB2 is thought to be involved in noise-induced hearing loss (NIHL). However, the role of Cx26 in NIHL is still obscure. To explore the association between Cx26 and NIHL, we established a Cx26 knockdown (KD) mouse model by conditional knockdown of Cx26 at postnatal day 18 (P18), and then we observed the auditory threshold and morphologic changes in these mice with or without noise exposure. The Cx26 KD mice did not exhibit substantial hearing loss and hair cell degeneration, while the Cx26 KD mice with acoustic trauma experienced higher hearing loss than simple noise exposure siblings and nearly had no recovery. Additionally, extensive outer hair cell loss and more severe destruction of the basal organ of Corti were observed in Cx26 KD mice after noise exposure. These data indicate that reduced Cx26 expression in the mature mouse cochlea may increase susceptibility to noise-induced hearing loss and facilitate the cell degeneration in the organ of Corti.

Human glioma is the most common type of primary brain tumor and one of the most invasive and aggressive tumors, which, even with treatments including surgery, radiotherapy and chemotherapy, often relapses and exhibits resistance to conventional treatment methods. Developing novel strategies to control human glioma is, therefore, an important research focus. The present study investigated the mechanism of apoptosis induction in U251 human glioma cells by capsaicin (Cap) and dihydrocapsaicin (DHC), the major pungent ingredients of red chili pepper, using the Cell Counting Kit-8 assay, transmission electron microscopy analysis, flow cytometry analysis, laser scanning confocal microscope analysis and immunohistochemical staining. Treatment of U251 glioma cells with Cap and DHC resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells. The apoptosis-inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase-9 and −3. These effects were further confirmed by observations of the anti-tumor effects of Cap and DHC in vivo in a U251 cell murine tumor xenograft model. These results demonstrate that Cap and DHC are effective inhibitors of in vitro and in vivo survival of human glioma cells, and provide the rationale for further clinical investigation of Cap and DHC as treatments for human glioma.