There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion in vitro, together with tumour growth and metastasis in vivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics.
The cochlear basilar membrane (CBM) contains inner hair cells and outer hair cells that convert sound waves into electrical signals and transmit them to the central auditory system. Cochlear aging, the primary reason of age-related hearing loss, can reduce the signal transmission capacity. There is no ideal in vitro aging model of the CBM. In this study, we cultured the CBM, which was dissected from the cochlea of the C57BL/6 mice 5 days after birth, in a medium containing 20 mg/mL, 40 mg/mL, or 60 mg/ mL D-galactose (D-gal). Compared with the control group, the levels of senescence-associated b-galactosidase were increased in a concentration-dependent manner in the CBM of the D-gal groups. In addition, levels of the mitochondrial superoxide and patterns of an age-related mitochondrial DNA3860-bp deletion were significantly increased. The ATP levels and the membrane potential of the mitochondrial were significantly decreased in the CBM of the D-gal groups compared with the control group. Furthermore, in comparison with the control group, damaged hair cell stereocilia and a loss of inner hair cell ribbon synapses were observed in the CBM of the D-gal groups. A loss of hair cells and activation of caspase-3-mediated outer hair cell apoptosis were also observed in the CBM of the high-dose D-gal group. These insults induced by D-gal in the CBM in vitro were similar to the ones that occur in cochlear natural aging in vivo. Thus, we believe that this is a successful in vitro aging model using cultured CBM. These results demonstrate
Importance Cochlear implantation (CI) is an effective therapy for patients with severe to profound sensorineural hearing loss. It remains controversial whether children younger than 12 months of age should undergo CI. Objective To evaluate the safety and effectiveness of CI in children younger than 12 months of age. Methods We performed a retrospective study of clinical data of pediatric patients younger than 12 months of age who underwent CI and were followed up for 1 to 2 years. Patients’ developmental levels were evaluated by the Gesell score before CI. Intraoperative and postoperative complications were recorded to evaluate the safety of CI. Auditory and speech abilities were scored by the LittlEARS® auditory questionnaire (LEAQ), categories of auditory performance (CAP), speech intelligibility rating (SIR), infant‐toddler meaningful auditory integration scale (IT‐MAIS), and meaningful use of speech scale (MUSS) at 1, 2, 3, 6, 9, and 12 months after CI. The associations between clinical characteristics before CI and postoperative scores at 1 year after CI were analyzed by the linear mixed‐effects model. Results Eighty‐nine children (47 boys and 42 girls) were included in this study (mean age at CI, 9.2 ± 1.6 months). Sixteen patients were diagnosed with cochlear malformation and 16 underwent bilateral CI. No severe complications occurred in any patients. The mean developmental quotient of the Gesell score was 78.00 ± 10.03. The median LEAQ scores were 0, 5, 10, 16, 22, 26 and 30 before and at 1, 2, 3, 6, 9, and 12 months after CI, respectively. These findings implied that the LEAQ score greatly improved in the first year after CI. The overall CAP, SIR, IT‐MAIS, and MUSS scores also increased with increasing duration after CI. No significant associations were detected between clinical characteristics (age, sex, implant number, pre‐CI Gesell score, and inner ear malformation) and LEAQ outcomes at 12 months after CI. Interpretation With increasing duration after CI, auditory and speech behavior dramatically improve in young children. Our findings indicate that CI is feasible for children younger than 12 months of age.
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