Youngbuhm Huh

Ki-Hoon Park, Youngbuhm Huh, Hyung-Joo Chung, Hiroyuki Konishi, Junyang Jung, Na Young Jeong. Anat Cell Biol -0001;0:. https://doi.org/10.5115/acb.24.290

Khan MA, et al. Anat Biol Anthropol. 2023 Sep;36(3):103-110. https://doi.org/10.11637/aba.2023.36.3.103

EduTech (Education and Technology) has drawn great attention in improving education efficiency for non-face-to-face learning and practice. This paper introduced a blended gross anatomy class using both virtual reality (VR) devices and traditional programs alongside a practice-based cadaver dissection and in-class observation. The class allowed the students to get hands-on experience with both practical practice and VR operations to identify the biochemical aspects of the disease-induced internal organ damage as well as to view the three-dimensional (3D) aspect of human structures that cannot be practiced during the gross anatomy practice. Student surveys indicated an overall positive experience using VR education (satisfaction score over 4 out of 5, Likert scale question). There remains room for improvement, and it was discussed with the results of the essay-based question survey. Formative evaluation results showed that the students who trained in blended anatomy classes with VR set-ups received higher scores (85.28 out of 100, average score) than only cadaver-based anatomy class (79.06 out of 100, average score), and this result represents that the hybrid method could improve the academic efficiency and support the understanding of the 3D structure of the body. At present, VR cannot totally replace actual cadaver dissection practice, but it will play a significant role in the future of medical education if both students and practitioners have more VR devices, practice time, and a more intuitive user-friendly VR program. We believe that our paper will greatly benefit the development of EduTech and a potential new curriculum item for future medical education.

Peripheral nerve degeneration (PND) is a preparative process for peripheral nerve regeneration and is regulated by Schwann cells, a unique glial cell in the peripheral nervous system. Dysregulated PND induces irreversible peripheral neurodegenerative diseases (e.g., diabetic peripheral neuropathy). To develop novel synthetic drugs for these diseases, we synthesized a set of new cinnamaldehyde (CAH) derivatives and evaluated their activities in vitro, ex vivo, and in vivo. The 12 CAH derivatives had phenyl or naphthyl groups with different substitution patterns on either side of the α,β-unsaturated ketone. Among them, 3f, which had a naphthaldehyde group, was the most potent at inhibiting PND in vitro, ex vivo, and in vivo. To assess their interactions with transient receptor potential cation channel subfamily A member 1 (TRPA1) as a target of CAH, molecular docking studies were performed. Hydrophobic interactions had the highest binding affinity. To evaluate the underlying pharmacological mechanism, we performed bioinformatics analysis of the effect of 3f on PND based on coding genes and miRNAs regulated by CAH, suggesting that 3f affects oxidative stress in Schwann cells. The results show 3f to be a potential lead compound for the development of novel synthetic drugs for the treatment of peripheral neurodegenerative diseases.

N-ethylmaleimide (NEM) inhibits peripheral nerve degeneration (PND) by targeting Schwann cells in a hydrogen sulfide (H₂S)-pathway-dependent manner, but the underlying molecular and pharmacological mechanisms are unclear. We investigated the effect of NEM, an α,β-unsaturated carboxyl compound, on H₂S signaling in in vitro- and ex vivo-dedifferentiated Schwann cells using global proteomics (LC-MS) and transcriptomics (whole-genome and small RNA-sequencing (RNA-seq)) methods. The multi-omics analyses identified several genes and proteins related to oxidative stress, such as Sod1, Gnao1, Stx4, Hmox2, Srxn1, and Edn1. The responses to oxidative stress were transcriptionally regulated by several transcription factors, such as Atf3, Fos, Rela, and Smad2. In a functional enrichment analysis, cell cycle, oxidative stress, and lipid/cholesterol metabolism were enriched, implicating H₂S signaling in Schwann cell dedifferentiation, proliferation, and myelination. NEM-induced changes in the H₂S signaling pathway affect oxidative stress, lipid metabolism, and the cell cycle in Schwann cells. Therefore, regulation of the H₂S signaling pathway by NEM during PND could prevent Schwann cell demyelination, dedifferentiation, and proliferation.

Irreversible peripheral neurodegenerative diseases such as diabetic peripheral neuropathy are becoming increasingly common due to rising rates of diabetes mellitus; however, no effective therapeutic treatments have been developed. One of main causes of irreversible peripheral neurodegenerative diseases is dysfunction in Schwann cells, which are neuroglia unique to the peripheral nervous system (PNS). Because homeostasis of calcium (Ca²⁺) and magnesium (Mg²⁺) is essential for Schwann cell dynamics, the regulation of these cations is important for controlling peripheral nerve degeneration and regeneration. Transient receptor potential melastatin 7 (TRPM7) is a non-selective ion (Ca²⁺ and Mg²⁺) channel that is expressed in Schwann cells. In the present study, we demonstrated in an ex vivo culture system that inhibition of TRPM7 during peripheral nerve degeneration (Wallerian degeneration) suppressed dedifferentiable or degenerative features (trans-dedifferentiation and proliferation) and conserved a differentiable feature of Schwann cells. Our results indicate that TRPM7 could be very useful as a molecular target for irreversible peripheral neurodegenerative diseases, facilitating discovery of new therapeutic methods for improving human health.

Peripheral neurodegenerative processes are essential for regenerating damaged peripheral nerves mechanically or genetically. Abnormal neurodegenerative processes induce peripheral neurodegenerative diseases via irreversible nerve damage. Carvacrol, a major component in Origanum vulgare, possesses various effects on organisms, such as antibiotic, anti-inflammatory and cytoprotective effects; although transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP canonical 1 (TRPC1), TRP melastatin M7 (TRPM7), and TRP vanilloid 3 (TRPV3) are carvacrol-regulated TRPs, however, effect of carvacrol on the peripheral neurodegenerative process, and its underlying mechanism, remain unclear. Here, we investigated the specificity of carvacrol for TRPM7 in Schwann cells and the regulatory effect of carvacrol on TRPM7-dependent neurodegenerative processes. To construct peripheral nerve degeneration model, we used with a sciatic explant culture and sciatic nerve axotomy. Ex vivo, in vivo sciatic nerves were treated with carvacrol following an assessment of demyelination (ovoid fragmentation) and axonal degradation using morphometric indices. In these models, carvacrol effectively suppressed the morphometric indices, such as stripe, ovoid, myelin, and neurofilament indices during peripheral nerve degeneration. We found that carvacrol significantly inhibited upregulation of TRPM7 in Schwann cells. In this study, our results suggest that carvacrol effectively protects against the peripheral neurodegenerative process via TRPM7-dependent regulation in Schwann cells. Thus, pharmacological use of carvacrol could be helpful to protect against neurodegeneration that occurs with aging and peripheral neurodegenerative diseases, prophylactically.

Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs) are auxiliary factors involved in protein synthesis related to aminoacyl-tRNA synthetases (ARSs). AIMPs, which are well known as nonenzymatic factors, include AIMP1/p43, AIMP2/p38, and AIMP3/p18. The canonical functions of AIMPs include not only protein synthesis via multisynthetase complexes but also maintenance of the structural stability of these complexes. Several recent studies have demonstrated nontypical (noncanonical) functions of AIMPs, such as roles in apoptosis, inflammatory processes, DNA repair, and so on. However, these noncanonical functions of AIMPs have not been studied in peripheral nerves related to motor and sensory functions. Peripheral nerves include two types of structures: peripheral axons and Schwann cells. The myelin sheath formed by Schwann cells produces saltatory conduction, and these rapid electrical signals control motor and sensory functioning in the service of survival in mammals. Schwann cells play roles not only in myelin sheath formation but also as modulators of nerve degeneration and regeneration. Therefore, it is important to identify the main functions of Schwann cells in peripheral nerves. Here, using immunofluorescence technique, we demonstrated that AIMPs are essential morphological indicators of peripheral nerve degeneration, and their actions are limited to peripheral nerves and not the dorsal root ganglion and the ventral horn of the spinal cord.

Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.