Downregulation of Cav3.1 T-type Calcium Channel Expression in Age-related Hearing Loss Model.

OBJECTIVE: Age-related hearing loss (AHL), characterized by degeneration of cochlea structures, is the most common sensory disorder among the elderly worldwide. The calcium channel is considered to contribute to normal hearing. However, the role of the T-type voltage-activated calcium channel, Cav3.1, remains unclear in AHL. Here, we investigate the age-related change of Cav3.1 expression in the cochlea and D-gal-induced senescent HEI-OC1 cells. METHODS: Cochleae from C57BL/6 mice at 2 months and 12 months of age were assessed. Senescence in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells was induced by D-gal treatment. The immunofluorescence technique was employed to investigate the distribution of Cav3.1 in vivo and in vitro. Quantitative assessment was achieved by Western blotting and real-time PCR. RESULTS: In comparison with 2-month-old animals, 12-month old C57BL/6 mice exhibited great loss of hair cells and elevated auditory brainstem threshold. The Cav3.1 was located in hair cells, spiral ganglion cells, lateral walls, and the expression of Cav3.1 protein and mRNA decreased in the aged cochleae. D-gal-induced senescence assay confirmed the down-regulation of Cav3.1 expression in senescent HEI-OC1 cells. CONCLUSION: Our results show that age-related down-regulated expression of Cav3.1 in the cochleae is associated with AHL and may contribute to the pathogenesis of AHL.

Expression of α2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss.

K+ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K+ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K+ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19.

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Expression Patterns and Implications of LaminB1 in Rat Cochleae.

LaminB1, a major component of the nuclear lamina, is a potent regulator of cellular proliferation and senescence and also known to be essential for neuronal migration and brain development. However, the expression patterns of LaminB1 in the rat cochleae are still not fully revealed. Utilizing immunofluorescence, Western blotting, and quantitative real-time PCR, we identified the distribution and expression of LaminB1 in the rat cochleae. Immunofluorescence staining indicated that LaminB1 was mainly localized in the auditory hair cells (HCs), spiral ganglion cells (SGC), stria vascularis (STV, including spiral ligament), Reissner's membrane (RM), and limbus laminae spiralis (LLS). Western blotting analysis illustrated that the distribution of LaminB1 in rat cochleae was characterized by tissue specificity. The LaminB1 protein was expressed more in SGC and basilar membrane (BM) than in STV. Meanwhile, the mRNA expression of LaminB1 displayed difference in cochlear tissues. These observations preliminarily revealed the expression patterns of LaminB1, providing a theoretical basis for further study on the role of LaminB1 in auditory function.

Downregulation of inwardly rectifying potassium channel 5.1 expression in C57BL/6J cochlear lateral wall.

Age-related hearing loss (AHL) is one of the most common sensory disorders among elderly persons. The inwardly rectifying potassium channel 5.1 (Kir5.1) plays a vital role in regulating cochlear K(+) circulation which is necessary for normal hearing. The distribution of Kir5.1 in C57BL/6J mice cochleae, and the relationship between the expression of Kir5.1 and the etiology of AHL were investigated. Forty C57BL/6J mice were randomly divided into four groups at 4, 12, 24 and 52 weeks of age respectively. The location of Kir5.1 was detected by immunofluorescence technique. The mRNA and protein expression of Kir5.1 was evaluated in mice cochleae using real-time polymerase-chain reactions (RT-PCR) and Western blotting respectively. Kir5.1 was detected in the type II and IV fibrocytes of the spiral ligament in the cochlear lateral wall of C57BL/6J mice. The expression levels of Kir5.1 mRNA and protein in the cochleae of aging C57BL/6J mice were down-regulated. It was suggested that the age-related decreased expression of Kir5.1 in the lateral wall of C57BL/6J mice was associated with hearing loss. Our results indicated that Kir5.1 may play an important role in the pathogenesis of AHL.

Value of High-frequency Ultrasound in the Diagnosis of Peripheral Nerve Compression in Rheumatoid Arthritis Patients.

Objective To evaluate the value of high-frequency ultrasound (HFUS) in diagnosing peripheral nerve compression in patients with rheumatoid arthritis (RA). Methods The upper limb nerves were evaluated by HFUS in 80 RA patients (RA group) and 60 non-RA patients (control group),then the incidence of peripheral nerve compression was recorded respectively. RA patients with/without neurological symptoms were compared in terms of age,disease course,Health Assessment Questionnaire Disability Index (HAQ-DI) score,and clinical disease activity index (CDAI). Results The incidence of upper limb nerve compression in RA group was significantly higher than that in control group(15.0% vs. 3.3%,P=0.046).The patients with nerve compression was older [(60.2±11.4)y vs.(49.2±7.9)y;t=2.343,P=0.039] and had longer disease course [(9.50±5.99) y vs. (5.88±3.87)y;t=2.639,P=0.023] and higher HAQ-DI score (1.58±0.75 vs.0.85±0.67;t=2.490,P=0.030). These two groups had no statistical differences in CDAI (14.50±11.68 vs.16.62±9.24;t=1.141,P=0.278).Conclusions Peripheral neuropathies are common extra-articular manifestations in RA patients. HFUS can be valuable in patients suspected of RA.