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Oxidative stress is one of the important mechanisms of inner ear cell damage, which can lead to age-related hearing loss (ARHL). LncRNA H19 is significantly downregulated in the cochlea of old mouse, however, the role of H19 in the development of ARHL remains unclear. In this study, we aim to investigate the expression and function of H19 in oxidative stress injury of cochlear hair cells induced by H2O2. RT-qPCR and western blot analysis confirms that HEI-OC1 cells stimulated with H2O2 decreases the expressions of H19 and SIRT1, but increases the expression of miR-653-5p. Overexpression of H19 could increase cell viability, ATP level and mitochondrial membrane potential, but reduce mitochondrial ROS generation and cell apoptosis ratio in H2O2-stimulated HEI-OC1 cells. MiR-653-5p is a target of H19, which can bind to the 3′-UTR of SIRT1. H19 is found to regulate the expression of SIRT1 through miR-653-5p. Further experiments demonstrates that H19 regulates HEI-OC1 cell viability, ATP level, mitochondrial membrane potential, mitochondrial ROS generation, and cell apoptosis ratio via the miR-653-5p/SIRT1 axis. In conclusion, lncRNA H19 inhibits oxidative stress injury of cochlear hair cells via the miR-653-5p/SIRT1 axis.

Laryngocarcinoma is one of the most frequent malignancies occurring in the head and neck. The roles of spindle- and kinetochore-associated complex 1 (SKA1) in the malignant progression of several cancers have already been discussed. However, the precise significance and action's mechanism of SKA1 in laryngocarcinoma remain largely unknown. In this study, SKA1 was shown to be strongly expressed in laryngocarcinoma tissues and cells, and higher expression of SKA1 was associated with more severe tumor infiltration, larger tumor diameter, higher risk of lymphatic metastasis and later pathological stage. Additionally, loss-of-function assays in vitro suggested that SKA1 depletion caused a reduction in cell proliferation, migration, and colony formation as well as an increase in apoptosis. In animal experiments, tumors generated from AMC-HN-8 cells with SKA1 depletion exhibited declined tumor volume and weight. Similarly, the detection of Ki67 protein in xenograft tumor tissues reflected that knocking down SKA1 curbed tumor growth in vivo. Further exploration on downstream mechanism revealed that after treatment with Pifithrin-α, the suppression in proliferation level caused by SKA1 knockdown was reversed, while the increase of cell apoptosis was withdrawn; at the molecular level, Pifithrin-α treatment caused p-P53 and Bax diminished, while Bcl-2 ameliorated. In short, SKA1 promotes the development of laryngocarcinoma via activating the P53 signaling pathway. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of C-C chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3−/− BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3−/−CG) and iv) AR model with CCR3 knockout (CCR3−/−AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae. Peripheral blood smear and nasal-washing smears were evaluated by Wright's staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood, and nasal washings of the various groups were ranked in the order: AR>CCR3−/−AR>CG>CCR3−/−. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal washings were detected by reverse transcription-polymerase chain reaction. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, and immunoglobulin E (IgE) protein levels in the peripheral serum and nasal washings were investigated by ELISA. CCR3 mRNA expression was not detected in the CCR3−/− and CCR3−/−AR groups, whereas expression levels in the AR group were markedly higher compared with expression in the CG group. Compared with the CG-associated groups (i.e., the CG and CCR3−/−CG groups), the levels of EPO, ECP, MBP, IL-4, and IgE were significantly increased in the AR-associated groups (that is, R and CCR3−/−AR). In addition, the CCR3−/−AR group mice produced significantly lower levels of EPO, ECP, MBP, IL-4 and IgE compared with the AR group, whereas the expression levels of IFN-γ and IL-10 were increased. CCR3 gene knockout may alleviate EOS invasion and the inflammatory response in AR model mice by reducing the expression levels of EPO, ECP, MBP, IL-4, and IgE, and increasing the expression of IL-10 and IFN-γ. [ABSTRACT FROM AUTHOR]