• Molecules and Cells
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• v.46 no.10
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• pp.573-578
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• 2023

The mammalian skin contains hair follicles, which are epidermal appendages that undergo periodic cycles and exhibit mini-organ features, such as discrete stem cell compartments and different cellular components. Wound-induced hair follicle neogenesis (WIHN) is the remarkable ability to regenerate hair follicles after large-scale wounding and occurs in several adult mammals. WIHN is comparable to embryonic hair follicle development in its processes. Researchers are beginning to identify the stem cells that, in response to wounding, develop into neogenic hair follicles, as well as to understand the functions of immune cells, mesenchymal cells, and several signaling pathways that are essential for this process. WIHN represents a promising therapeutic approach to the reprogramming of cellular states for promoting hair follicle regeneration and preventing scar formation. In the scope of this review, we investigate the contribution of several cell types and molecular mechanisms to WIHN.

• BMB Reports
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• v.43 no.9
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• pp.584-592
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• 2010

Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. Through regulation of NOS activity BH4 plays a pivotal role not only in a variety of normal cellular functions but also in the pathogenesis of cardiovascular and neurodegenerative diseases, which develop under oxidative stress conditions. It appears that a balanced interplay between BH4 and NOS is crucial for cellular fate. If cellular BH4 homeostasis maintained by BH4 synthesis and regeneration fails to cope with increased oxidative stress, NOS is uncoupled to generate superoxide rather than NO and, in turn, exacerbates impaired BH4 homeostasis, thereby leading to cell death. The fundamental biochemical events involved in the BH4-NOS interplay are essentially the same, as revealed in mammalian endothelial, cardiac, and neuronal cells. This review summarizes information on the cellular BH4 homeostasis in mammals, focusing on its regulation under normal and oxidative stress conditions.

• International Journal of Stem Cells
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• v.17 no.3
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• pp.213-223
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• 2024

Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with in vitro organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.

• The Journal of Korean Physical Therapy
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• v.12 no.3
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• pp.415-432
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• 2000

In mammals. axotomy of peripheral nerve leads to a complex. These events include swelling of cell body, disappearance of Nissl substance. Proximal and distal axon undergoes a variable deriable degree of traumatic degeneration and wallerian degeneration, respectively. Nerve injury may result in cell death or regeneration. Molecular changes include proliferation of Schwann cells, upregulation of neurotropism, neural cell adhesion molecules and cytokine. Also growth cone plays an essential role in axon guidance through interaction of cytoskeleton. We review cellular and molecular events after nerve injury and describe nerve regeneration and associated proteins.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• Journal of the Korean Society of Visualization
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• v.20 no.2
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• pp.70-77
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• 2022

Skeletal muscle tissues feature cellular heterogeneity, including differentiated myofibers, myoblasts, and satellite cells. Thanks to the presence of undifferentiated myoblasts and satellite cells, skeletal muscle tissues can self-regenerate after injury. In skeletal muscle regeneration, the collective motions among these cell types must play a significant role, but little is known about the dynamic collective behavior during the regeneration. In this study, we constructed in vitro platform to visualize the migration behavior of skeletal muscle cells in specific conditions that mimic the biochemical environment of injured skeletal muscles. We then visualized the spatiotemporal distribution of stresses arising from the differential collectiveness in the cellular clusters under different conditions. From these analyses, we identified that the heterogeneous population of muscle cells exhibited distinct collective migration patterns in the injury-mimicking condition, suggesting selective activation of a specific cell type by the biochemical cues from the injured skeletal muscles.

• BMB Reports
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• v.53 no.3
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• pp.148-153
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• 2020

Erythropoietin and iron have individually shown beneficial effects on early-phase liver regeneration following partial hepatectomy (PHx); however, there are limited data on the combined effect on late-phase liver regeneration after PHx. Here we examined combined effects of recombinant human erythropoietin (rhEPO, 3,000 IU/kg) and iron isomaltoside (IIM, 40 mg/kg) on late-phase liver regeneration following PHx and investigated the possible underlying mechanism. Rats administrated with rhEPO showed significantly higher liver mass restoration, interleukin-6 (IL-6, a hepatocyte mitogen) levels, and Ki-67-positive hepatocytes on day 7 after PHx than saline-treated controls. These beneficial effects were further enhanced on days 7 and 14 by co-treatment with IIM. This combination also significantly improved liver function indices, such as increased albumin production and decreased bilirubin levels, but did not alter serum levels of toxic parameters, such as aspartate transaminase and alanine transaminase. This study demonstrates that the combination of rhEPO and IIM synergistically improves late-phase liver regeneration and function after PHx, probably by promoting IL-6-mediated hepatocyte proliferation without adverse effects. Thus, this combination treatment can be a potential therapeutic strategy for patients undergoing resection for hepatic malignancies.

• Journal of Periodontal and Implant Science
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• v.40 no.1
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• pp.3-10
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• 2010

Purpose: Periodontal regenerative therapies for defects created by severe periodontitis are mainly focused on bone regeneration. Although cementum regeneration needs to be better understood, it is believed to play an important role in periodontal regeneration. The first step toward a full understanding of cementum regeneration is to compare repaired cementum to pristine cementum. This study, which used histological techniques, was designed to focus on cementum regeneration and to compare pristine cementum to repaired cementum after surgical procedures with 8 and 24 week healing periods in a canine model. Methods: Buccal and lingual mucoperiosteal flaps of 10 beagle dogs were surgically reflected to create critical-sized defects. Intrabony one-wall defects, of which dimension is 4 mm width and 5 mm depth, were made at the distal aspect of mandibular second premolars and the mesial aspect of mandibular fourth premolars in the right and left jaw quadrants. Animals were sacrificed after 8 and 24 weeks post-surgery for histological specimen preparation and histometric analysis. Results: The repaired cementum was composed mostly of acellular cementum and cellular mixed fiber cementum and was thicker in the apical area than in the coronal area. The acellular cementum of the supracrestal area appeared to be amorphous. The newly formed cellular cementum was partially detached from the underlying circumpulpal dentin, which implied a weak attachment between new cementum and dentin, and this split was observed to a lesser extent in the 24 week group than in the 8 week group. The vertical height of the repaired cementum was greater in the 24 week group than in the 8 week group. Conclusions: Within the limitations of this study, we can conclude that repaired cementum after root planing was mainly acellular cementum and cementum tissue that matured to a shape similar to pristine cementum as the healing progressed from 8 to 24 weeks.

• Journal of Haehwa Medicine
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• v.25 no.1
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• pp.37-44
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• 2016

Objectives : This study was designed to investigate the effect of Gamishinchubogun-tang (JiaweiShenzhuibujian-tang; GSB) on regeneration of PC12 cells. Methods : PC12 cells have been used extensively as a model for studying the cellular and molecular effects of neuronal cells. In order to check the effect of GSB on the regeneration of PC12 cells, the morphological change of PC12 cells were observed comparatively in GSB group and control group. Results : The significant changes in neurite length of PC12 cells have been observed on GSB group. In proportion to the concentration of GSB it was observed an increase in neurite outgrowth. Conclusions : This study confirmed that GSB made a significant influence on regeneration of PC12 cells.

• Molecules and Cells
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• v.40 no.1
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• pp.10-16
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• 2017

When peripheral axons are damaged, neuronal injury signaling pathways induce transcriptional changes that support axon regeneration and consequent functional recovery. The recent development of bioinformatics techniques has allowed for the identification of many of the regeneration-associated genes that are regulated by neural injury, yet it remains unclear how global changes in transcriptome are coordinated. In this article, we review recent studies on the epigenetic mechanisms orchestrating changes in gene expression in response to nerve injury. We highlight the importance of epigenetic mechanisms in discriminating efficient axon regeneration in the peripheral nervous system and very limited axon regrowth in the central nervous system and discuss the therapeutic potential of targeting epigenetic regulators to improve neural recovery.