Kayoung Ko;Seohee Choi;Miri Jo;Chaeyoung Kim;Napissara Boonpraman;Jihyun Youm;Sun Shin Yi
Journal of Veterinary Science
/
v.25
no.4
/
pp.49.1-49.15
/
2024
Importance: Endochondral ossification plays an important role in skeletal development. Recent studies have suggested a link between increased intracellular reactive oxygen species (ROS) and skeletal disorders. Moreover, previous studies have revealed that increasing the levels of myeloperoxidase (MPO) and osteopontin (OPN) while inhibiting NADPH oxidase 4 (NOX4) can enhance bone growth. This investigation provides further evidence by showing a direct link between NOX4 and MPO, OPN in bone function. Objective: This study investigates NOX4, an enzyme producing hydrogen peroxide, in endochondral ossification and bone remodeling. NOX4's role in osteoblast formation and osteogenic signaling pathways is explored. Methods: Using NOX4-deficient (NOX4-/-) and ovariectomized (OVX) mice, we identify NOX4's potential mediators in bone maturation. Results: NOX4-/- mice displayed significant differences in bone mass and structure. Compared to the normal Control and OVX groups. Hematoxylin and eosin staining showed NOX4-/- mice had the highest trabecular bone volume, while OVX had the lowest. Proteomic analysis revealed significantly elevated MPO and OPN levels in bone marrow-derived cells in NOX4-/- mice. Immunohistochemistry confirmed increased MPO, OPN, and collagen II (COLII) near the epiphyseal plate. Collagen and chondrogenesis analysis supported enhanced bone development in NOX4-/- mice. Conclusions and Relevance: Our results emphasize NOX4's significance in bone morphology, mesenchymal stem cell proteomics, immunohistochemistry, collagen levels, and chondrogenesis. NOX4 deficiency enhances bone development and endochondral ossification, potentially through increased MPO, OPN, and COLII expression. These findings suggest therapeutic implications for skeletal disorders.
Sang Hui Yong;Sang-Mi Kim;Gyeong Woon Kong;Seung Hwan Ko;Eun-Hye Lee;Yohan Oh;Chang-Hwan Park
BMB Reports
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v.57
no.8
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pp.363-368
/
2024
Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neurons development.
Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem-leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD. Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay. Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line. Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.
An, Na Young;Kim, Ji-Eun;Hwang, DaeYoun;Ryu, Ho Kyung
Journal of Nutrition and Health
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v.47
no.6
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pp.394-402
/
2014
Purpose: Dendropanax morifera Leveille (DML) exhibits diverse biological and pharmacological activities, including anti-oxidative effect, anti-cancer activity, hepatoprotection, immunological stimulation, and bone regeneration. As part of the identification for novel functions of DML, we investigated the therapeutic effects of DML on diabetes induced by streptozotocine (STZ) treatment. Methods: First, the four extracts including the water extract of leaf (DLW), the ethanol extract of leaf (DLE), the water extract of stem (DSW), and the ethanol extract of stem (DSE) were collected from the leaf and stem of DML using a hot water and ethanol solvent. Alterations in body weight, glucose concentration, insulin level, and pancreatic islet structure were investigated in diabetic mice after treatment with extracts of DML for 2 weeks. Results: Among four extracts, the highest level of total polyphenols and total flavonoids was detected in DLW, while the lowest level of these was measured in DSE. The radical scavenging activity was also higher in DLW than in the other three extracts at the concentration of $25-100{\mu}g/mL$, although this activity was maintained at a constant level in all groups at the concentration of $500{\mu}g/mL$. Based on the results of anti-oxidant activity, DLW and DLE were selected for examination of anti-diabetic effects in a diabetes model. Body weight was gradually decreased in all STZ treated groups compared with the No treated group. However, four STZ/DML treated groups maintained a high level of body weight during 7-14 days, while the STZ/vehicle treated group showed a gradual decrease of body weight during the same period. Also, a significant decrease or increase in the concentration of glucose and insulin in the blood of the diabetes model was detected in a subset of groups, although the highest increase was detected in the STZ/DLE-200 treated group. In addition, the histological structure of pancreatic islet was significantly recovered after treatment with DLW and DLE. Conclusion: These results suggest that DLW and DLE may contribute to attenuation of clinical symptoms of diabetes as well as prevent the destruction of pancreatic ${\beta}$-cells in STZ-induced diabetes mice.
Park, So Hyun;Seong, Joon Seob;Lee, Keon Soo;Park, Young Min;Xuan, Song Hua;Cha, Mi Yeon;Kang, Hee Cheol;Park, Soo Nam
Journal of the Society of Cosmetic Scientists of Korea
/
v.43
no.3
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pp.255-263
/
2017
In this study, the antioxidant activities, cellular protective effects, and inhibitory effects on elastase of non-fermented and fermented extracts of Parthenocissus tricuspidata (P. tricuspidata) stem using Lactobacillus pentosus were investigated. The free radical scavenging activities ($FSC_{50}$) of non-fermented and fermented extracts were 42.3 and $34.5{\mu}g/mL$, respectively, in which the activity after fermentation was approximately 18.4% higher. Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) in $Fe^{3+}-EDTA/H_2O_2$ system of non-fermented and fermented extracts were 2.6 and $2.5{\mu}g/mL$, respectively. The activity after fermentation was approximately 4.2% higher. In the $^1O_2$-induced cellular damage of erythrocytes, the cellular protective effects (${\tau}_{50}$) of non-fermented and fermented extracts were 126.4 and 173.0 min at $50{\mu}g/mL$, respectively. The activity after fermentation was approximately 34.0% higher. The effect of fermented extract was 3.9 times higher than $(+)-{\alpha}$-tocopherol (${\tau}_{50}=43.4min$), known as a lipophilic antioxidant at $50{\mu}g/mL$. The inhibitory effect of elastase was investigated to predict the anti-wrinkle efficacy using Hs68 human fibroblasts cells. The elastase inhibitory activities ($IC_{50}$) of non-fermented and fermented extracts were 873.6 and $687.8{\mu}g/mL$, respectively, and the activity after fermentation was approximately 21.3% higher. These results indicated that fermented extract of P. tricuspidata stem has potentials as natural cosmetic ingredients with antioxidant and anti-wrinkle effect.
The contents of proximate composition, free amino acids and phenolic acids in the Fomitella fraxinea cultivated-Rhus verniciflua stem bark(FRVSB), and its adipogenesis effect were investigated. The proximate composition(%) of FRVSB was as follows: moisture(7.64), ash(6.30), crude fat(3.86), crude protein(3.59) and sugar(not detected); while Rhus verniciflua stem bark(RVSB) contained 1.64, 8.09, 7.28, 6.48 and 5.39, respectively. The total free amino acids concentration was 97.41 mg% in FRVSB and 71.91 mg% in RVSB. Phosphoserine(55.06 mg%), ammonia(17.84mg%) and aspartic acid(6.05mg%) were predominant amino acids. The content of total phenolic acids was 422.89 ppm in ethanol extract and 283.86 ppm in water extract, with syringic and gallic acid as the main component. The FRVSB extracts showed a potent free radical scavenging activity for DPPH(2,2-diphenyl-1-picrylhydrazyl hydrate) with $IC_{50}$ of $28.54\;{\mu}g$(EtOH) and $54.70\;{\mu}g$(water), respectively, whereas $IC_{50}$ value of gallic acid was $1.84\;{\mu}g$. The protective effect of both ethanol and water extract the extracts against UV-induced oxidative stress in NIH3T3 was observed. The water extracts of FRVSB may promote adipogenesis in 3T3-L1 cells.
Ye-Eun Choi;Jung-Mo Yang;Chae-Won Jeong;Hee-Won Yoo;Hyun-Duck Jo;Ju-Hyun Cho
Journal of Food Hygiene and Safety
/
v.39
no.1
/
pp.44-53
/
2024
Global interest in natural functional materials to strengthen human immunity is increasing due to the increase in immune-related diseases associated with COVID-19 and the aging population. In this study, we determined the potential therapeutic effect of Eleutherococcus senticosus stems on immune enhancement according to the cultivation region. The contents of eleutheroside B and E, which are chemical components of E. senticosus stems, were analyzed. We showed that the eleutheroside B content of E. senticosus stems in different cultivation regions ranged from 2.96±0.11 to 6.24±0.05 mg/g and from 1.11±0.05 to 2.11±0.03 mg/g in 70% ethanol and hot water extracts, respectively. The eleutheroside E content ranged from 4.93±0.20 to 10.79±0.03 mg/g and 1.75±0.14 to 3.64±0.05 mg/g in 70% ethanol and hot water extracts, respectively. In addition, the immunomodulatory effect of E. senticosus stems was evaluated using RAW 264.7 macrophages. The 70% ethanol extract of E. senticosus stems showed no cytotoxicity up to 200 ㎍/mL, and the hot water extract showed no cytotoxicity up to 500 ㎍/mL. Additionally, the E. senticosus stem extract significantly increased the production of nitric oxide and cytokines (TNF-α, IL-6, and IL-1β) compared to their production in the control group. These results suggest that E. senticosus stem extracts are a potential functional food material and ingredient to enhance the immune response.
The morphological, anatomical and physiological traits were eximined for Populus alba ${\times}$ glandulosa which is an important planting species in Korea. The results obtained are as follows: 1. External characters in the leaf shape and chaff shape in the catkin were inherited as incomplete dominance but nectar gland was inherited as dominance. 2. Among the 15 selected clones, 9 clones were male, 2 clones female and 2 clones monoecious. 3. There were well-developed cork layers and bast fiber bundles in the bark. 4. Primordial leaves composed of 3 layers of cells and those undifferentiated into palisade and spongy parenchymas differed in its origin. 5. Leaf scare consisted of two kinds of tissues; one is connected to vascular bundle and the other not to vascular bundle. Tissues which had been connected to vascular bundle were isolated with only 2 or 3 layers of cork cells from the outside. 6. There was complicated arrangement in the vascular bundle of petioles. 7. Growth of the hybrid was sensitively influenced by external temperature, day-length and amount of light. In particular, it was apparent in height growth. 8. Flatness, loam soils and a $60{\times}60cm$ spacing might be best factors for the growth of P. alba ${\times}$ glandulosa. 9. The rooting of 15 clones was dependant upon external factors. 10. The growth of P. alba ${\times}$ glandulosa was best at around 80% of soil moisture content on the basis of plot water capacity. 11. Temperature difference between inside and outside stems below 100cm during the winter was the greatest at the south among seasons and among directions. 12. The sap movement was markedly influenced by air temperature, relative humidity in forest stand and moisture content in stem. 13. Total sugars in the cortex changed with season but did not differ in the dircetion of the stem. 14. Isoperoxidase variations in the leaf were different among 15 clones. Thus, it may be useful as a criterium for clonal identification. 15. The rate of soil moisture content decreased at a rapid slope was faster than that at a slow slope. Poor growth of P. alba ${\times}$ glandulosa at the slope was probably due to depletion of soil moisture.
Nana, Andre Wendindonde;Yang, Pei-Ming;Lin, Hung-Yun
Asian Pacific Journal of Cancer Prevention
/
v.16
no.16
/
pp.6813-6823
/
2015
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.
Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy.
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