Influence of inner ear impedance on middle ear sound transfer functions.

Introduction: For experimental studies on sound transfer in the middle ear, it may be advantageous to perform the measurements without the inner ear. In this case, it is important to know the influence of inner ear impedance on the middle ear transfer function (METF). Previous studies provide contradictory results in this regard. With the current study, we investigate the influence of inner ear impedance in more detail and find possible reasons for deviations in the previous studies. Methods: 11 fresh frozen temporal bones were prepared in our study. The factors related to inner ear impedance, including round window membrane stiffness, cochleostomy, cochlea fluid and cochlea destruction were involved in the experimental design. After measuring in the intact specimen as a reference (step 1), the round window membrane was punctured (step 2), then completely removed (step 3). The cochleostomy was performed (step 4) before the cochlear fluid was carefully suctioned through scala tympani (step 5) and scala vestibuli (step 6). Finally, cochlea was destroyed by drilling (step 7). Translational and rotational movement of the stapes footplate were measured and calculated at each step. The results of the steps were compared to quantify the effect of inner ear impedance changing related to the process of cochlear drainage. Results: As the inner ear impedance decreases from step 1 to 7, the amplitudes of the METF curves at each frequency gradually increase in general. From step 6 on, the measured METF are significantly different with respect to the intact group at high frequencies above 3 kHz. The differences are frequency dependent. However, the significant decrement of rotational motion appears at the frequencies above 4.5 kHz from the step 5. Conclusion: This study confirms the influence of inner ear impedance on METF only at higher frequencies (≥3 kHz). The rotational motions are more sensitive to the drainage of fluid at the higher frequency. Study results that found no influence of cochlea impedance may be due to incomplete drainage of the cochlea.

Gene Expression, Network Analysis, and Drug Discovery of Neurofibromatosis Type 2-Associated Vestibular Schwannomas Based on Bioinformatics Analysis.

Neurofibromatosis Type 2- (NF2-) associated vestibular schwannomas (VSs) are histologically benign tumors. This study aimed to determine disease-related genes, pathways, and potential therapeutic drugs associated with NF2-VSs using the bioinformatics method. Microarray data of GSE108524 were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened using GEO2R. The functional enrichment and pathway enrichment of DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG). Furthermore, the STRING and Cytoscape were used to analyze the protein-protein interaction (PPI) network of all differentially expressed genes and identify hub genes. Finally, the enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in NF2-associated VSs. A total of 542 DEGs were identified, including 13 upregulated and 329 downregulated genes, which were mainly enriched in terms of focal adhesion, PI3K-Akt signaling pathway, ECM-receptor interaction, Toll-like receptor signaling pathway, Rap1 signaling pathway, and regulation of actin cytoskeleton. 28 hub genes were identified based on the subset of PPI network, and 31 drugs were selected based on the Drug-Gene Interaction database. Drug discovery using bioinformatics methods facilitates the identification of existing or potential therapeutic drugs to improve NF2 treatment.

Study on the Drug Targets and Molecular Mechanisms of Rhizoma Curcumae in the Treatment of Nasopharyngeal Carcinoma Based on Network Pharmacology.

AIM: To analyse the target of Rhizoma Curcumae in nasopharyngeal carcinoma by using network pharmacological techniques and to explore the associated molecular mechanism. METHODS: The targets of nasopharyngeal carcinoma were retrieved from the GeneCards database. At the same time, the drug therapeutic targets of Rhizoma Curcumae were obtained from the TCMSP and SymMap databases. The data were imported into the STRING database and Cytoscape 3.7.1 to construct a network of "Chinese medicine component-target-disease" interactions; then, the intersection was screened as the core Rhizoma Curcumae antinasopharyngeal cancer targets. Through GO target function and KEGG pathway enrichment analyses of the core targets, we predicted the biological processes and key signalling pathways involved in the Rhizoma Curcumae treatment of nasopharyngeal carcinoma. RESULTS: Twenty-five core targets of Rhizoma Curcumae in nasopharyngeal carcinoma were mined: TP53, BCL2 ICAM1 RXRA, TLR3 and TLR9, TNF, PTGS2, IL-6, CTSD, MMP2, MMP9, MMP14, TIMP2, ABCC1, ABCB1, ABCG2, and so on. The results of visual analysis showed that the Rhizoma Curcumae treatment of nasopharyngeal carcinoma mainly involves leukocyte adhesion to vascular endothelial cells, positive regulation of NF-κB import into the nucleus, regulation of the reactive oxygen species biosynthetic and metabolic process, regulation of the chemokine biosynthetic and metabolic process, various cancer-related signalling pathways, and a variety of cytokine signal transduction pathways, such as the NF-κB, TLR, IL-17, and TNF signalling pathways. CONCLUSION: The core targets predicted by our research can be used as molecular markers for the treatment and prediction of nasopharyngeal carcinoma. The mechanism of Rhizoma Curcumae treatment in NPC may be related to immune regulatory pathways, the inhibition of cancer cell proliferation, metastasis, and angiogenesis, as well as the regulation of tumour microenvironment. Combined with the prediction of its associated mechanism of action, the core targets can provide targeted reference value for subsequent drug development related to Curcuma.