Background: Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Methods: Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10. Results: Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea. Conclusion: We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma.

The purpose of this study was to investigate the effects of Oolong tea drinking on the auditory functions in aged subjects. Retrospective cohort study was conducted on 265 subjects who were older than 55 years old. Tea drinking was determined from responses to a medical and food consumption questionnaires. The effects of Oolong tea drinking on pure tone thresholds (PTAs) for peripheral hearing and pitch pattern sequence (PPS) scores for central hearing were analyzed. Results showed that, before adjusting for other factors, PTas were not significantly different between “non-tea drinkers” and “Oolong tea drinkes”. But, the mean PPS score was higher in the “Oolong tea drinkers” (74.5 ± 12.7 %) than in the “non-tea drinkers” (68.4 ± 13.9 %). after adjusting for age, gender, waist circumference, and other variables, Oolong tea drinking (coefficient (β) ± standard error (se) = 2.60 ± 0.67, P<0.001) was positively associated with PPs score, but not with PTAs, by multivariate linear regression analysis. in subgroup analysis for PPS score by gender, Oolong tea drinking showed a significant positive association with PPS score in males (β ± se=4.75 ± 0.95, P<0.001), but showed association of borderline significance with PPS score in females (β ± se=1.57 ± 0.94, P=0.097), with adjustment of other risk factors. in conclusion, Oolong tea drinking was associated with better central auditory function, but not with peripheral hearing thresholds, especially in male aged subjects.

The effects of transient ischemic attack (TIA) on pure tone average of low frequencies (PTA-low), of middle frequencies (PTA-mid), and of high frequencies (PTA-high), and audiometric configurations, which were classified by cluster analysis, were analyzed in older subjects. TIA showed significant positive association with PTA-high [β coefficient (β) ± standard error (SE) = 8.63 ± 2.81, p = 0.002] after adjusting for age, sex, hypertension, and coronary artery disease. Besides, multinomial logistic regression for audiogram patterns showed that the moderate 8-kHz dip pattern (β ± SE = 1.70 ± 0.78, p = 0.029) was significantly more prevalent in the TIA group after adjusting for age, sex, and mean hearing level at all frequencies. We concluded that TIA without an obvious infarct lesion could contribute to hearing degeneration in older subjects, especially in high frequencies.

Lipocalin-2 (LCN2) exhibits pro- and anti-carcinogenic effects in several cancers, but its role in the progression of glioblastoma multiforme (GBM) remains unclear. This study aims to elucidate the effect of LCN2 in human GBM cell, and the mechanism underlying its effects on GBM malignant progression. We observed that LCN2 expression was significantly lower in GBM than in normal tissues and was associated with poorer GBM patient survival. LCN2-overexpressing GBM cells showed significantly reduced proliferation and migration/invasion abilities. Human protease antibody array analysis showed that the expression of cathepsin D (CTSD) protein and mRNA was lower in LCN2-overexpressing GBM cells than in controls. Higher CTSD expression was observed in GBM tumors than in normal tissues, and higher CTSD expression was associated with poorer overall and disease-free survival. LCN2-overexpressing GBM cells exhibited increased ERK phosphorylation. Treatment of these cells with a MEK inhibitor (U0126) restored CTSD expression, cell migration, and cell invasiveness. In conclusion, LCN2 might be serving as a prognostic marker and promising anti-proliferative and anti-metastatic target for treating GBM.

A 62-year-old woman had progressively developing throbbing right neck pain for 1 year. The pain radiated to the right suboccipital area, sometimes accompanied by breathlessness. To rule out cancer, patient received FDG PET/CT, which showed an intraspinal cord intense FDG-avid calcified mass at the level of the first cervical spine, mimicking malignancy. MRI showed it effacing the medulla; surgery is probably a challenge. She received laminectomy with tumor removal; pathology showed psammomatous meningioma, World Health Organization grade I. This case suggests that benign spinal cord psammomatous meningioma with calcification may show high FDG uptake, mimicking malignancy.