• BMB Reports
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• v.52 no.1
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• pp.24-34
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• 2019

Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide.

• Herbal Formula Science
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• v.13 no.2
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• pp.71-91
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• 2005

A/J mice injected with urethane(1mg/ g of body weight) develop tumors with distinct histological patterns, which are classified as solid and papillary. I divided the mice into 3 groups; control group treatment with saline, BYA group treatment with herbal formula, Bopheyangyoungjeon 0.3g/kg and BYB groups treatment with herbal formula 1.5g/kg. The administration of herbal medicine was done every day for 56 days. The experimental results from herbal medicine treatment were compared to those from a saline-treated control group. Serial sections of the whole lung(150 to 200 sections per mouse) showed solid and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. The number of tumor, in the 8-weeks groups, are decreased in the experimental groups compared to control group. COX-2 protein and IGF- I protein expression was more increased in lung tumors of the control group compared to BYA and BYB groups. These results suggest that Bopheyangyoungjeon extract suppress the carcinogenesis of lung in the A/J mouse.

• Fisheries and Aquatic Sciences
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• v.22 no.10
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• pp.23.1-23.10
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• 2019

Background: Taurine is a conditional essential amino acid for fish. A study was conducted to investigate the compensating effect of supplemental taurine in diets for red seabream (Pagrus major) on impaired growth performance by fish meal (FM) replacement with soybean meal (SM) at low water temperature (14.15 ± 1.95 ℃). Methods: A FM-based diet was considered as a high FM diet and three other experimental diets were formulated to replace FM with SM by 20, 35, or 50% (HFM, SM20, SM35, or SM50, respectively) without taurine and other four diets were formulated by adding 1% taurine to the diets (HFM-T, SM20-T, SM35-T, or SM50-T, respectively). Triplicate groups of fish (108.9 ± 1.58 g/fish) were distributed into 24 polyvinyl circular tanks (215 L) with 20 fish per tank and fed one of the diets to satiation for 20 weeks. Results: Growth performance and feed utilization of red seabream were significantly improved by the dietary taurine supplementation. SM20-T and SM35-T diets increased fish growth that are comparable to HFM diet. Feed intake, feed conversion ratio, and protein efficiency ratio of fish fed SM20-T and SM35-T diets were not significantly different from those of HFM group. Dietary taurine supplementation in each FM replaced group numerically increased innate immunity of the fish. Lysozyme and superoxide dismutase activities were significantly decreased in fish fed SM35, SM50, and SM50-T diets compared to those of fish fed HFM diet while they were not significantly lower in SM20, SM20-T, SM35, and SM35-T groups. Glutathione peroxidase activity was significantly lower in fish group fed SM50 diet while SM50-T group did not significantly lower compared to that of HFM group. The relative expression level of hepatic IGF-1 mRNA was improved in fish fed taurine-supplemented diets compared to their respective SM diets. Conclusions: Growth performance and feed utilization of red seabream can be accelerated or restored by 1% taurine supplementation when they are fed high level of SM up to 35% in diets during low water temperature season.

• Herbal Formula Science
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• v.13 no.2
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• pp.17-40
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• 2005

A/J mice injected with urethane(1mg/ g of body weight) develop tumors with distinct histological patterns, which are classified as solid and papillary. I divided the mice into 3 groups; control group treatment with saline, BA group treatment with herbal formula, Soeuminbojungikgitang 0.4g/kg and BA group treatment with herbal formula 2.0g/kg. The administration of herbal medicine was done every day for 8 weeks. The experimental results from herbal medicine treatment were compared to those from a saline-treated control group. Serial sections of the whole lung(150 to 200 sections per mouse) showed solid and papillary tumors arose from the pulmonary acinus, invading the bronchioles only as the tumors grew. The number of tumor, in the 8 weeks group, are decreased in the experimental groups compared to control group. COX-2 protein and IGF- I protein expression was more increased in lung tumors of the control group compared to BA and BB groups. These results suggest that Soeuminbojungikgitang extract suppress the carcinogenesis of lung in the A/J mouse.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.6
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• pp.879-887
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• 2020

Objective: Numerous studies have indicated that the apoptosis and proliferation of granulosa cells (GCs) are closely related to the normal growth and development of follicles and ovaries. Previous evidence has suggested that miR-126-3p might get involved in the apoptosis and proliferation of GCs, and phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2) gene has been predicted as one target of miR-126-3p. However, the molecular regulation of miR-126-3p on PIK3R2 and the effects of PIK3R2 on porcine GCs apoptosis and proliferation remain virtually unexplored. Methods: In this study, using porcine GCs as a cellular model, luciferase report assay, mutation and deletion were applied to verify the targeting relationship between miR-126-3p and PIK3R2. Annexin-V/PI staining and 5-ethynyl-2'-deoxyuridine assay were applied to explore the effect of PIK3R2 on GCs apoptosis and proliferation, respectively. Real-time quantitative polymerase chain reaction and Western Blot were applied to explore the regulation of miR-126-3p on PIK3R2 expression. Results: We found that miR-126-3p targeted at PIK3R2 and inhibited its mRNA and protein expression. Knockdown of PIK3R2 significantly inhibited the apoptosis and promoted the proliferation of porcine GCs, and significantly down-regulated the mRNA expression of several key genes of PI3K pathway such as insulin-like growth factor 1 receptor (IGF1R), insulin receptor (INSR), pyruvate dehydrogenase kinase 1 (PDK1), and serine/threonine kinase 1 (AKT1). Conclusion: MiR-126-3p might target and inhibit the mRNA and protein expressions of PIK3R2, thereby inhibiting GC apoptosis and promoting GC proliferation by down-regulating several key genes of the PI3K pathway, IGF1R, INSR, PDK1, and AKT1. These findings would provide great insight into further exploring the molecular regulation of miR-126-3p and PIK3R2 on the functions of GCs during the folliculogenesis in female mammals.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.53-79
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• 2002

To screen the effective materials for hair loss treatment, several natural extracts were tested using in vivo and in vitro test models. Firstly, all test materials were applicated onto the back skin of C57BL／6 mouse and then hair growth promoting effect was measured using hair growth index. As a result, Prunus mume, black bean, Brassica campestris subsp. black sesame and Rubi Fructus showed potent hair growth promoting effect, ranking as 1.5-2.0 of hair growth index. However, there were no plant extracts, which have remarkable potential of growth promotion of human hair dermal papilla cells cultured in vitro. In the experiments of 5${\alpha}$-reductase type Ⅱ inhibition assay, Prunus mume, Eriobotryae Folium showed effective potential to inhibit the activity of 5${\alpha}$-reductase type Ⅱ. To investigate the possible involvement of the effect of several plant extracts on the gene expression of growth factors in human hair dermal papilla cells, RT - PCR analyses were performed. However, there were no plant extracts, which have profound effect on the gene expression of several growth factors such as IGF-I, KGF, HGF and VEGF in the dermal papilla cells. Another tests for inhibition of microbial such as P. acne were also carried out to find whether these plant extracts have anti -microbial activities. Rubi Fructus showed anti -microbial effects on Propionibacterium acnes, which is believed as a pathogen of acne. Together, these results showed several plant extracts can be used for hair growth promotion.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.80-103
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• 2002

To screen the effective materials for hair loss treatment, several natural extracts were tested using in vivo and in vitro test models. Firstly, all test materials were applicated onto the back skin of C57BL／6 mouse and then hair growth pormoting effect were measured using hair growth index As a result, Polygonum muitifiorum Thunb and Terrninalia chebula Retz. showed potent hair growth promoting effect, ranking as 1.5-2.0 of hair growth index. However, there were no plant extracts, which have remarkable potential of growth promotion of human hair dermal papilla cells cultured in vitro. In the experiments of 5${\alpha}$-reductase type Ⅱ inhibition assay, Morus alba L., Chaenomelis Fructus, Saussureae Radix, Angelicae Gigantis Radix, Polygonum multifiorum Thunb, and Angelica dahurica (Fischer) Bentham et Hooker f. showed effective potential to inhibit the activity of 5${\alpha}$-reductase type Ⅱ. To investigate the possible involvement of effects of several plant extracts on the gene expression of growth factors in human hair dermal papilla cells, RT-PCR analyses were performed. As a consequences, Mentha haplocalyx Briq., Cimicifuga foetida L., Eclipta prostrata (L.) L., Pinus densiflora S. et. Z, and Polygonum muitifiorum Thunb revealed the regulatory roles on the expression of growth factors such as IGF-I, KGF, HGF and VEGF in the dermal papilla cells. Another test for inhibition of microbial such as P. acne and P. ovale were also carried out to find whether these plant extracts have anti-microbial activities. Morus alba L. and Chaenomelis Fructus showed anti-microbial effects on Propionibacterium acnes, which is believed as a pathogen of acne. Together, these results showed several plant extracts can be used for hair growth promotion.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.3
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• pp.250-265
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• 2008

Distraction osteogenesis is a well-established clinical treatment for limb length discrepancy and skeletal deformities. Appropriate mechanical tension-stress is believed not to break the callus but rather to stimulate osteogenesis. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. Although the biomechanical, histological, and ultrastructural changes associated with distraction osteogenesis have been widely described, the basic biology of the process is still not well known. Moreover, the molecular mechanisms in distraction osteogenesis remain largely unclear. Recent studies have implicated the growth factor cascade is likely to play an important role in distraction. And current reserch suggested that mechanical tension-stress modulates cell shape and phenotype, and stimulates the expression of the mRNA for bone matrix proteins. The purpose of this study is to examine the pattern of expression of growth factors($TGF-{\beta}1$, IGF-I, bFGF) and extracellular matrix proteins(osteoclacin, osteonectin) related to osteogenesis by osteodistraction of the mandible in rabbits. 24 rabbits is used for this experiment. Experimental group are gradual distraction(0.7mm, twice/day), acute distraction(1.4mm, twice/day) and control group is only osteotomized. After 5 days latency, osteotomic site is distracted for each 7 days and 3.5 days. Consolidation period is 28 days. The animal is sacrificed at the 3th, 7th, 14th, 28th. The distracted bone is examined by immunohistochemical analysis and RT-PCR analysis. The results obtained from this study were as follow : No significant difference was found on clinical examination according to distraction rate, but gradual distraction was shown to improve regenerate bone formation on radiographic and histologic examination. Growth factors and extracelluar matrix proteins expression increased in distraction group than control group. From these results, it could be stated that graudal distraction is shown to improve and accelerate bone formation and mechanical stress like distraction has considerable effects on osteogenesis related factors. And rabbit is the most appropriate animal model for further reseach on the molecular mechanisms that mediate osteodistraction. It is believed that understanding the biomolecular mechanisms that mediate distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone healing.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1133-1140
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• 2006

Human HtrA1 (High temperature requirement protein A1) is a homologue of the E. coli periplasmic serine protease HtrA. A recent study has demonstrated that HtrA1 is a serine protease involved in processing of insulin like growth factor binding protein (ICFBP), indicating that it serves as an important regulator of IGF activity. Additionally, several lines of evidence suggest a striking correlation between proteolytic activity of HtrA1 serine protease and the pathogenesis of several diseases; however, physiological roles of HtrA1 remain to be elucidated. We used the pGEX bacterial expression system to develop a simple and rapid method for purifying HtrA1, and the recombinant HtrA1 protein was utilized to investigate the optimal conditions in executing its proteolytic activity. The proteolytically active HtrA1 was purified to approximately 85% purity, although the yield of the recombinant HtrA1 protein was slightly low $460{\mu}g$ for 1 liter E. coli culture). Using in vitro endoproteolytic cleavage assay, we identified that the HtrA1 serine protease activity was dependent on the enzyme concentration and the incubation time and that the best reaction temperature was $42^{\circ}C$ instead of $37^{\circ}C$. We arbitrary defined one unit of proteolytic activity of the HtrA1 serine protease as 200nM of HtrA1 that cleaves half of $5{\mu}M\;of\;{\beta}-casein$ during 3 hr incubation at $37^{\circ}C$. Our study provides a method for generating useful reagents to investigate the molecular mechanisms by which HtrA1 serine protease activity contributes in regulating its physiological function and to identify natural substrates of HtrA1.

• BMB Reports
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• v.54 no.5
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• pp.278-283
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• 2021

Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4⁺ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.