Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice.

OBJECTIVE: Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism. METHODS: Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot. RESULTS: The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1ß, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae. CONCLUSIONS: Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.

Low expression of BEX1 predicts poor prognosis in patients with esophageal squamous cell cancer.

The brain expressed x­linked gene 1 (BEX1) is a member of the BEX family and is aberrantly expressed in many cancers. However, the clinical significance of BEX1 expression level and its role in the pathology of esophageal squamous cell cancer (ESCC) remain unknown. In the present study, we determined BEX1 expression in the tumor and adjacent normal tissues from 118 ESCC patients by immunohistochemistry and determined the proliferation and growth of ESCC cells following ectopic overexpression of BEX1 in cultured cells and in mouse­ESCC xenografts. We observed that BEX1 was downregulated in ESCC tissues compared to adjacent normal tissues, and low BEX1 expression was significantly associated with larger ESCC tumor volume (P<0.001), advanced T stage (P=0.011) and advanced clinical stage (P=0.039). Additionally, survival analysis revealed that low expression of BEX1 significantly predicted poor prognosis in patients with ESCC (P<0.001). Multivariate analysis revealed that low BEX1 expression was an independent prognostic factor of poor survival (P=0.039). In vitro analysis revealed that overexpression of BEX1 inhibited ESCC cell proliferation and colony formation. Furthermore, in vivo tumorigenesis assays revealed that ectopic overexpression of BEX1 suppressed ESCC tumor growth in mice. Further immunoblotting analysis demonstrated that BEX1 upregulation led to reduced expression and phosphorylation of NF­κB p65, indicating inhibition of the NF­κB signaling pathway by BEX1. Our findings indicated that low BEX1 expression may be an independent prognostic marker for poor survival and may serve as a potential target for ESCC therapy.

Overexpression of Hepatocyte Cell Adhesion Molecule (hepaCAM) Inhibits the Proliferation, Migration, and Invasion in Colorectal Cancer Cells.

Hepatocyte cell adhesion molecule (hepaCAM), a new type of CAM, belongs to the immunoglobulin superfamily. Recently, hepaCAM was reported to be implicated in cancer development, and many researchers investigated its biological function in the tumorigenesis of various cancers. However, what kind of role hepaCAM plays in colorectal cancer (CRC) remains unknown. In this study, we found that hepaCAM was downregulated in CRC tissues and cell lines. Overexpression of hepaCAM inhibited CRC cell proliferation, migration, and invasion in vitro. Furthermore, the tumorigenesis assay showed that increased expression of hepaCAM suppressed CRC tumor growth and metastasis in vivo. We also demonstrated that overexpression of hepaCAM reduced the protein expression levels of ß-catenin, cyclin D1, and c-Myc, indicating its inhibitory effect on the Wnt/ß-catenin signaling pathway. In conclusion, our study results suggest hepaCAM as a promising therapeutic target for CRC and provide a better understanding for the molecular basis of CRC progression.

[Correlation of osteopontin expression and laryngeal squamous cell carcinoma infiltration and metastasis].

OBJECTIVE: To investigate osteopontin (OPN) expression in plasma and tissue of patients with layngeal squamous cell carcinoma and analyze its role in invasion, metastasis, and clinical significance in laryngeal quamous cell carcinoma. METHOD: Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect expression of OPN in plasma and tissue of 60 cases of laryngeal squamous cell carcinoma, 20 cases of adjacent normal laryngeal tissue and 20 cases of plasma from healthy subjects. RESULT: The expression of plasma OPN was closely correlated with clinical stage and cervical lymphatic metastasis in laryngeal squamous cell carcinoma (P < 0.05), but no significant correlation with the tumor location, pathological grade, gender and age (P > 0.05). The expression of OPN increased in plasma during cancer development: laryngeal squamous cell carcinoma (38.089 ± 9.225) ng/ml, healthy subjects (18.563 ± 9.308) ng/ml. There was a significant difference between the groups (P < 0.05). The expression of OPN in tissue was closely correlated with clinical stage (P < 0.05), pathological grade (P < 0.05) and cervical lymphatic metastasis (P < 0.05) in laryngeal squamous cell carcinoma adjacent atypical hyperplastic epithelium and carcinoma. The expression of OPN increased in tissue during cancer development: laryngeal squamous cell carcinoma (56.67%), adjacent normal laryngeal tissue (15.00%). There was a significant difference between the groups (P < 0.05). Elevated expression of plasma OPN is positively correlated with the expression of OPN in tissue in laryngeal squamous cell carcinoma patients (r = 0. 871, P < 0.05). CONCLUSION: OPN plays an important role in the infiltration, metastasis and carcinogenesis in laryngeal squamous cell carcinoma. Combination of serum OPN, tissue OPN detection can be used as diagnostic and surveillance indicators for laryngeal squamous cell carcinoma infiltration and metastasis.

Polysaccharide biosynthesis protein CapD is a novel pathogenicity-associated determinant of Haemophilus parasuis involved in serum-resistance ability.

The capD gene, encoding a polysaccharide biosynthesis protein, was identified previously as a differential gene between Haemophilus parasuis virulent strain Nagasaki and avirulent strain SW114; however, the characteristics of this gene associating with the pathogenicity of H. parasuis remain unclear. Here, the capD deletion mutant (ΔcapD) and its complement strain (C-capD) were generated in H. parasuis virulent strain SH0165. The deletion of capD gene significantly attenuated the pathogenicity of the SH0165 strain, while the complementation of this gene largely recovered the pathogenicity to piglets. Additionally, the ΔcapD strain could not be recovered from piglets after challenge, while both SH0165 and C-capD strains were recovered from most systemic sites. Moreover, the ΔcapD strain exhibited an extreme sensitivity to the complement-mediated killing compared with SH0165 strain, while its serum-resistance ability largely restored with the capD gene complementation. These data present the evidence that the capD gene is a novel pathogenicity-associated determinant and involved in serum-resistance ability of H. parasuis.

[Analysis of symptoms and quality of life in children with allergic rhinitis].

OBJECTIVE: To evaluate symptoms and quality of life in children with allergic rhinitis, and to evaluate the correlations among the skin prick tests results, symptoms and quality of life. METHOD: Visual analog scale (VAS) was used to assess the symptoms severity, rhinoconjunctivitis quality of life questionnaire (RQLQ) was used to assess quality of life, the skin prick tests results were recorded, and statistics analysis was carried out among them. RESULT: (1) There were significant differences among the five aspects of RQLQ (F = 32.03, P < 0.01), nasal symptoms aspect was the most affected aspect of quality of life, moreover, there were significant differences among all the items of RQLQ (F = 7.35, P < 0.01), the scores of nasal blockage, sneezing and rhinorrhea were the highest, there were no significant differences among them. (2) VAS was significantly correlated with RQLQ, moreover, the scores of unable to get to sleep and embarrassed by symptoms were significantly correlated with rhinorrhea VAS scores (r = 0.230, P < 0.05; r = 0.325, P < 0.01), the score of wake up during the night was significantly correlated with nasal itching and sneezing VAS scores (r = 0.385, P < 0.01; r = 0.231, P < 0.05), the score of can't concentrate was significantly correlated with the scores of unable to get to sleep and wake up during the night (r = 0.316, P < 0.01; r = 0.525, P < 0.01), the score of irritable was significantly correlated with the scores of unable to get to sleep (r = 0.243, P < 0.05). (3) The results of the skin prick tests were related with VAS and RQLQ. CONCLUSION: Nasal symptoms severity may significantly correlated with the quality of life. Rhinorrhea, nasal itching and sneezing may be the main factors affecting the quality of sleep, while the quality of sleep may affect non-hay-fever symptoms and emotions, rhinorrhea may be the main factor affecting embarrassed by symptoms. The allergen level was related with the symptoms severity and quality of life.