Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder with limited clinical treatments. The occurrence of PD includes both genetic and environmental toxins, such as the pesticides paraquat (PQ), as major contributors to PD pathology in both invertebrate and mammalian models. Calycosin, an isoflavone phytoestrogen, has multiple pharmacological properties, including neuroprotective activity. However, the paucity of information regarding the neuroprotective potential of calycosin on PQ-induced neurodegeneration led us to explore whether calycosin can mitigate PD-like phenotypes and the underlying molecular mechanisms. We used a PQ-induced PD model in Drosophila as a cost-effective in vivo screening platform to investigate the neuroprotective efficacy of natural compounds on PD. We reported that calycosin shows a protective role in preventing dopaminergic (DA) neuronal cell death in PQ-exposed Canton S flies. Calycosin-fed PQ-exposed flies exhibit significant resistance against PQ-induced mortality and locomotor deficits in terms of reduced oxidative stress, loss of DA neurons, the depletion of dopamine content, and phosphorylated JNK-caspase-3 levels. Additionally, mechanistic studies show that calycosin administration improves PQ-induced mitochondrial dysfunction and stimulates mitophagy and general autophagy with reduced pS6K and p4EBP1 levels, suggestive of a maintained energy balance between anabolic and catabolic processes, resulting in the inhibition of neuronal cell death. Collectively, this study substantiates the protective effect of calycosin against PQ-induced neurodegeneration by improving DA neurons’ survival and reducing apoptosis, likely via autophagy induction, and it is implicated as a novel therapeutic application against toxin-induced PD pathogenesis.

Imperatorin (IMP) could downregulate several inflammatory transcription factor signaling pathways. Some studies have pointed out that IMP could interfere with toll-like receptor 4 (TLR4) signaling. This study evaluates how IMP interferes with the TLR4 co-receptors signaling through the protein-ligand docking model, Western blotting, immunofluorescence (IF), and atomic force microscopy (AFM) assays in lipopolysaccharide (LPS) stimulated macrophage-like RAW264.7 cells in vitro. The results of the protein-ligand docking demonstrate that IMP interferes with LPS binding to the LPS-binding protein (LBP), the cluster of differentiation 14 (CD14), and the toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) co-receptors in LPS-stimulated RAW264.7 cells. Compared with TLR4 antagonist CLI-095 or dexamethasone, IMP could suppress the protein expressions of LBP, CD14, and TLR4/MD-2 in LPS-stimulated cells. Furthermore, the three-dimensional (3D) image assay of the AFM showed IMP could prevent the LPS-induced morphological change in RAW264.7 cells. Additionally, IMP could activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and it increased the antioxidative protein expression of heme oxygenase-1 (HO-1), superoxidase dismutase (SOD), and catalase (CAT). Our results are the first to reveal that the anti-inflammatory effect of IMP interferes with LPS binding to TLR4 co-receptor signaling and activates the antioxidative Nrf2 signaling pathway.

We addressed the underrepresentation of non-European populations in genome-wide association studies (GWASs) by building HiGenome, a large-scale genetic resource for the Taiwanese Han population. Using a custom genotyping array, we integrated deidentified electronic medical records (2003 to 2021) with genomic data to enable GWASs, phenome-wide association studies, and polygenic risk score (PRS) analysis. Among 413,000 participants, 323,397 passed ancestry and quality control filtering. GWASs covered 1085 traits, focusing on diseases prevalent in Taiwan such as type 2 diabetes, chronic kidney disease, gout, and alcoholic liver damage. PRSs were calculated for 238 traits, with the strongest associations observed in musculoskeletal disorders. Incorporating PRS into clinical practice supports early risk prediction and personalized prevention. To further expand translational value, we also conducted pharmacogenomic analysis and human leukocyte antigen typing. HiGenome offers a large-scale genetic and clinical dataset from the Taiwanese Han population, supporting population-specific analyses and precision medicine development in East Asia. The hospital-based design enables continuous follow-up and longitudinal data expansion.