Aminoglycoside-induced ototoxicity can have a major impact on patients' quality of life and social development problems. Oxidative stress affects normal physiologic functions and has been implicated in aminoglycoside-induced inner ear injury. Excessive accumulation of reactive oxygen species (ROS) damages DNA, lipids, and proteins in cells and induces their apoptosis. Dihydromyricetin (DHM) is a natural flavonol with a wide range of health benefits including anti-inflammatory, antitumor, and antioxidant effects; however, its effects and mechanism of action in auditory hair cells are not well understood. The present study investigated the antioxidant mechanism and antiototoxic potential of DHM using House Ear Institute-Organ of Corti (HEI-OC)1 auditory cells and cochlear explant cultures prepared from Kunming mice. We used gentamicin to establish aminoglycoside-induced ototoxicity models. Histological and physiological analyses were carried out to determine DHM's pharmacological effects on gentamicininduced ototoxicity. Results showed DHM contributes to protecting cells from apoptotic cell death by inhibiting ROS accumulation. Western blotting and quantitative RT-PCR analyses revealed that DHM exerted its otoprotective effects by up-regulating levels of peroxisome proliferator activated receptor γ-coactivator (PGC)-1α and Sirtuin (SIRT)3. And the role of PGC-1α and SIRT3 in the protective effects of DHM was evaluated by pharmacologic inhibition of these factors using SR-18292 and 3-(1H-1,2,3-triazol-4-yl) pyridine, respectively, which indicated DHM's protective effect was dependent on activation of the PGC-1α/SIRT3 signaling. Our study is the first report to identify DHM as a potential otoprotective drug and provides a basis for the prevention and treatment of hearing loss caused by aminoglycoside antibiotic-induced oxidative damage to auditory hair cells.

Competing endogenous RNA (ceRNA) pathways play pivotal roles in the formation and progression of gastric cancer (GC). Employing multi-omics analysis, we sought to identify a ceRNA network associated with GC progression. We analyzed3Gene Expression Omnibus datasets as well as data from The Cancer Genome Atlas to identify genes that were differentially expressed in GC tissues. A total of 84 upregulated genes and 106 downregulated genes were found. Enrichment analysis indicated that some pathways were strongly linked with tumor formation and progression. We also screened hub genes to establish a lncRNA-miRNA-mRNA network. We ultimately identified 8 hub genes, 6 key miRNAs and 4 key lncRNAs that interact within a common ceRNA network. Correlation analysis and in vitro experiments were conducted to verify the regulatory effect of the ceRNA network in GC. A knockdown assay confirmed that the DLGAP1-AS1/miR-203a-3p/THBS2 axis is a ceRNA network involved in GC progression. In this study, we elucidated the role of the DLGAP1-AS1/miR-203a-3p/THBS2 ceRNA network in the progression of GC. These molecules maybe evaluated as therapeutic targets and prognostic biomarkers for GC.

Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways. The results of ototoxicity models indicate the importance of this process in the etiology of ototoxicity. A number of recent investigations of the control of cell fate by mitophagy have enhanced our understanding of the mechanisms by which mitophagy regulates ototoxicity and other hearing-related diseases, providing opportunities for targeting mitochondria to treat ototoxicity.

Tinnitus is perception of sound in the absence of an apparent external acoustic stimulus. The condition is prevalent in adults, especially the elderly (≥65 years), and may be associated with cognitive function decline and significantly impacts on the quality of life, heralding difficulties in managing this challenging disorder. Interventions for tinnitus have been varied. However, drugs have not yet been approved for the treatment of tinnitus and there is no pharmacotherapy recommended by existing guidelines. Still, herbal medicines are used for the treatment of tinnitus in many countries, especially Gingko (G.) biloba. In the current updated literature review, we evaluated the efficacy of herbal medicines in the treatment of tinnitus by reviewing the evidence of relevant randomized controlled trials. The authors also highlight some of the issues in clinical trials of herbal medicines given that currently available evidence on herbal medicines for tinnitus is overall of insufficient quality and the conclusions from existing trials are conflicting. Nevertheless, there is a clear and urgent need for safe and effective pharmacotherapy of tinnitus.