Search

Purpose Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck. This study aimed to investigate the crucial genes and regulatory networks involved in the carcinogenesis of NPC using a bioinformatics approach. Methods Five mRNA and two miRNA expression datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and miRNAs (DEMs) between NPC and normal samples were analyzed using R software. The WebGestalt tool was used for functional enrichment analysis, and protein-protein interaction (PPI) network analysis of DEGs was performed using STRING database. Transcription factors (TFs) were predicted using TRRUST and Transcriptional Regulatory Element Database (TRED). Kinases were identified using X2Kgui. The miRNAs of DEGs were predicted using miRWalk database. A kinase-TF-mRNA-miRNA integrated network was constructed, and hub nodes were selected. The hub genes were validated using NPC datasets from the GEO and Oncomine databases. Finally, candidate small-molecule agents were predicted using CMap. Results A total of 122 DEGs and 44 DEMs were identified. DEGs were associated with the immune response, leukocyte activation, endoplasmic reticulum stress in GO analysis, and the NF-κB signaling pathway in KEGG analysis. Four significant modules were identified using PPI network analysis. Subsequently, 26 TFs, 73 kinases, and 2499 miRNAs were predicted. The predicted miRNAs were cross-referenced with DEMs, and seven overlapping miRNAs were selected. In the kinase-TF-mRNA-miRNA integrated network, eight genes (PTGS2, FN1, MMP1, PLAU, MMP3, CD19, BMP2, and PIGR) were identified as hub genes. Hub genes were validated with consistent results, indicating the reliability of our findings. Finally, six candidate small-molecule agents (phenoxybenzamine, luteolin, thioguanosine, reserpine, blebbistatin, and camptothecin) were predicted. Conclusion We identified DEGs and an NPC regulatory network involving kinases, TFs, mRNAs, and miRNAs, which might provide promising insight into the pathogenesis, treatment, and prognosis of NPC.

Stimulating the round window membrane via an active actuator of the middle ear implant, named the reverse stimulation, has become an option to help patients with ossicular chain deformity (OCD) to restore hearing. However, there is still no concise description of how OCD affects reverse stimulation considering the overflow characteristics of third windows. In the present study, an impedance model considering the vestibular and cochlear aqueducts was used to investigate the dynamic response of the cochlea to reverse stimulation under OCD. First, a finite-element (FE) model of the middle ear and the ear canal was used to estimate the changes in reverse middle-ear impedance caused by ossicular chain fixation and ossicular chain interruption. Then, the impedance model was used to predict the reverse transfer function, which characterizes the effect of OCD on the dynamic response of the cochlea. The results show that ossicular chain fixation reduces the reverse stimulation's performance. Moreover, the existence of the third windows complicates the effect of ossicular chain fixation on the reverse stimulation and boosts obviously the reverse stimulation's performance at low frequencies. In contrast, regardless of the existence of third windows, ossicular chain interruption enhances the effect of reverse stimulation.

Emerging evidence of significant hearing loss occurring shortly after cisplatin administration in cancer patients has stimulated research into the causes and treatment of this side effect. Although the aetiology of cisplatin-induced hearing loss (CIHL) remains unknown, an increasing body of research suggests that it is associated with excessive generation of intracellular reactive oxygen species (ROS) in the cochlea. Astaxanthin, a xanthophyll carotenoid, has powerful anti-oxidant, anti-inflammatory, and anti-apoptotic properties based on its unique cell membrane function, diverse biological activities, and ability to permeate the blood-brain barrier. In this review, we summarize the role of ROS in CIHL and the effect of astaxanthin on inhibiting ROS production. We focus on investigating the mechanism of action of astaxanthin in suppressing excessive production of ROS.

Osteoporosis (OP) is common with advancing age. Several studies have shown a strong correlation between OP and otosclerosis. However, no studies have investigated OP of the malleus, incus or stapes in the human middle ear, its effect on middle ear transfer function. Here, we investigate whether these three ossicles develop OP, and how this affects middle ear transfer function. The effect of OP on middle ear transfer function was investigated in simulations based on a finite element (FE) method. First, the FE model used in our previous study was refined, and optimized by introducing viscoelastic properties to selected soft tissues of the middle ear. Then, the FE model was used to simulate OP of the three ossicles and assess its influence on middle ear transfer function. Other possible age-related changes, such as stiffness of the joints or ligaments in the middle ear, were also investigated. The results indicated that OP of the ossicles could increase the high frequency displacement of both the umbo and stapes footplate (FP). However, the stiffness of the middle ear soft tissue can lead to the decrease of middle ear gain at lower frequencies. Furthermore, loosening of these joints or ligaments could increase displacement of the umbo and stapes FP. In conclusion, although age-related hearing loss is most commonly conceived of as sensorineural hearing loss (SNHL), we found that age-related changes may also include OP and changes in joint stiffness, but these will have little effect on middle ear transfer function in elderly people.

Down-regulating human telomerase reverse transcriptase (hTERT) expression will significantly suppress the cell viability of laryngeal squamous cell carcinoma Hep-2, which was mainly due to the inhibition of cyclin D1 and thus G1/S phase transition.Small-interfering RNA (siRNA) targeting hTERT can arrest the cell cycle of cancer cells, as well as inhibit telomerase activity and cell viability. However, the precise mechanisms still remain unclear. Here, we investigate the regulatory role of hTERT in cyclin D1 in laryngeal squamous carcinoma.Short hairpin RNAs (shRNAs) specifically targeting hTERT were constructed and expressed in Hep-2 cells. Cell proliferation was measured by CCK-8 assay. Expression of hTERT, cyclin D1, cyclin E, c-myc, and GAPDH was detected by RT-PCR and Western blot; cyclin D1 and hTERT proteins in laryngeal squamous carcinoma tissue microarray were analyzed by quantum dots immunofluorescence.hTERT silence by shRNAs decreased the proliferation of Hep-2 cells by 76.8% at day 4 (96 h). Furthermore, transfection with hTERT shRNA for 48 h also significantly reduced expression of hTERT, cyclin D1, and c-Myc, but not cyclin E. Quantum dots immunofluorescence analysis of 36 laryngeal squamous carcinoma tissue samples found that hTERT expression was highly correlated with cyclin D1 expression.

It was found that an atomic-scale graded structure was formed, and a phase change occurred, in an In–Pb alloy by the sedimentation of substitutional solute atoms under an ultrastrong gravitational field (820 000 g (maximum); 150°C; 100 h). Continuous gradients in the concentration of Pb (from about 6 to 45 at.%) and In (from about 94 to 55 at.%) and resulting changes in the lattice constant were observed. Fcc (Pb-rich) and tetragonal (In-rich) phases appeared in the strong- and weak-gravity regions respectively from a single starting fct α phase. It is suggested that sedimentation of substitutional atoms can be used to control the compositions and structure of bulk materials and also thin films or layer interfaces.

The sedimentation of isotope atoms has been realized in monoatomic liquid and solid Se. It was observed that the concentration ratio 82Se/76Se increased by % level in the specimen ultracentrifuged at 0.7–0.9 million G under liquid and solid states. The present result is evidence of sedimentation of substitutional atoms in condensed matter via self-diffusion, and suggests its possible application to isotope separation by condensed matter centrifugation.