• 한국해양생명과학회지
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• 제8권1호
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• pp.32-42
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• 2023

어류의 번식은 뇌에서 분비되는 다양한 신경호르몬과 뇌하수체에서 분비되는 생식소 자극 호르몬에 의해 조절된다. 극동산 뱀장어(Anguilla japonica)의 번식도 이 호르몬들의 작용에 의해 조절되지만 성 성숙 시 신경호르몬이 뇌하수체 호르몬을 조절하는 방법은 완전히 밝혀지지 않았다. 이전 연구에 의하면 progesterone (P4), melatonin 및 serotonin (5-HT) 등과 같은 신경호르몬이 일부 어류의 번식 과정 조절에 관여하는 것으로 밝혀졌다. 본 연구에서는 뱀장어의 뇌하수체를 초대 배양하였고, 안정화된 뇌하수체 세포에 P4, 17β-estradiol (E2), melatonin 및 5-HT를 처리하였다. 이후 처리된 호르몬의 작용이 뇌하수체 세포에서 번식 관련 호르몬인 FSHβ, LHβ, GH 및 SL mRNA 발현에 어떤 영향을 미치는지 조사하였다. 본 연구를 수행한 결과, P4는 뇌하수체 세포에서 FSHβ와 LHβ 발현을 증가시켰고, melatonin은 FSHβ와 LHβ 뿐만 아니라 GH와 SL의 발현을 증가시켰다. 하지만 5-HT는 이 유전자의 mRNA 발현에 유의한 영향을 미치지 않았다. 이상의 결과는 P4 또는 melatonin이 뱀장어의 초기 성 성숙에 중요한 역할을 할 수 있음을 의미한다.

• Journal of Ginseng Research
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• 제42권3호
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• pp.389-399
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• 2018

Background: The antioxidant effects of Panax ginseng have been reported in several articles; however, little is known about the antimelanogenesis effect, skin-protective effect, and cellular mechanism of Panax ginseng, especially of P. ginseng calyx. To understand how an ethanol extract of P. ginseng berry calyx (Pg-C-EE) exerts skin-protective effects, we studied its activities in activated melanocytes and reactive oxygen species (ROS)-induced keratinocytes. Methods: To confirm the antimelanogenesis effect of Pg-C-EE, we analyzed melanin synthesis and secretion and messenger RNA and protein expression levels of related genes. Ultraviolet B (UVB) and hydrogen peroxide ($H_2O_2$) were used to induce cell damage by ROS generation. To examine whether this damage is inhibited by Pg-C-EE, we performed cell viability assays and gene expression and transcriptional activation analyses. Results: Pg-C-EE inhibited melanin synthesis and secretion by blocking activator protein 1 regulatory enzymes such as p38, extracellular signal-regulated kinases (ERKs), and cyclic adenosine mono-phosphate response element-binding protein. Pg-C-EE also suppressed ROS generation induced by $H_2O_2$ and UVB. Treatment with Pg-C-EE decreased the expression of matrix metalloproteinases, mitogen-activated protein kinases, and hyaluronidases and increased the cell survival rate. Conclusion: These results suggest that Pg-C-EE may have antimelanogenesis properties and skin-protective properties through regulation of activator protein 1 and cyclic adenosine monophosphate response element-binding protein signaling. Pg-C-EE may be used as a skin-improving agent, with moisture retention and whitening effects.

• Clinical and Experimental Pediatrics
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• 제63권3호
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• pp.79-87
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• 2020

Inherited platelet disorders (IPDs), which manifest as primary hemostasis defects, often underlie abnormal bleeding and a family history of thrombocytopenia, bone marrow failure, hematologic malignancies, undefined mucocutaneous bleeding disorder, or congenital bony defects. Wide heterogeneity in IPD types with regard to the presence or absence of thrombocytopenia, platelet dysfunction, bone marrow failure, and dysmegakaryopoiesis is observed in patients. The individual processes involved in platelet production and hemostasis are genetically controlled; to date, mutations of more than 50 genes involved in various platelet biogenesis steps have been implicated in IPDs. Representative IPDs resulting from defects in specific pathways, such as thrombopoietin/MPL signaling; transcriptional regulation; granule formation, trafficking, and secretion; proplatelet formation; cytoskeleton regulation; and transmembrane glycoprotein signaling are reviewed, and the underlying gene mutations are discussed based on the National Center for Biotechnology Information database and Online Mendelian Inheritance in Man accession number. Further, the status and prevalence of genetically confirmed IPDs in Korea are explored based on searches of the PubMed and KoreaMed databases. IPDs are congenital bleeding disorders that can be dangerous due to unexpected bleeding and require genetic counseling for family members and descendants. Therefore, the pediatrician should be suspicious and aware of IPDs and perform the appropriate tests if the patient has unexpected bleeding. However, all IPDs are extremely rare; thus, the domestic incidences of IPDs are unclear and their diagnosis is difficult. Diagnostic confirmation or differential diagnoses of IPDs are challenging, time-consuming, and expensive, and patients are frequently misdiagnosed. Comprehensive molecular characterization and classification of these disorders should enable accurate and precise diagnosis and facilitate improved patient management.

• The Plant Pathology Journal
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• 제36권5호
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• pp.428-439
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• 2020

Erwinia pyrifoliae is a Gram-negative bacterial plant pathogen that causes black shoot blight in apple and pear. Although earlier studies reported the genome comparison of Erwinia species, E. pyrifoliae strains for such analysis were isolated in 1996. In 2014, the strain E. pyrifoliae EpK1/15 was newly isolated in the apple tree showing black shoot blight in South Korea. This study aimed to better understand the similarities and differences caused by natural variations at the genomic level between newly isolated E. pyrifoliae EpK1/15 and the strain Ep1/96, which were isolated almost 20 years apart. Several comparative genomic analyses were conducted, and Clusters of Orthologous Groups of proteins (COG) database was used to classify functional annotation for each strain. E. pyrifoliae EpK1/15 had similarities with the Ep1/96 strain in stress-related genes, Tn3 transposase of insertion sequences, type III secretion systems, and small RNAs. The most remarkable difference to emerge from this comparison was that although the draft genome of E. pyrifoliae EpK1/15 was almost conserved, Epk1/15 strain had at least three sorts of structural variations in functional annotation according to COG database; chromosome inversion, translocation, and duplication. These results indicate that E. pyrifoliae species has gone natural variations within almost 20 years at the genomic level, and we can trace their similarities and differences with comparative genomic analysis.

• The Korean Journal of Physiology and Pharmacology
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• 제24권2호
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• pp.149-156
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• 2020

Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.

• 동아시아식생활학회지
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• 제24권3호
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• pp.335-350
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• 2014

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

• Journal of Nutrition and Health
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• 제51권1호
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• pp.23-30
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• 2018

Purpose: Runx2 (runt-related transcription factor 2), a bone-specific transcription factor, is a key regulator of osteoblast differentiation and its expression is induced by the activation of BMP-2 signaling. This study examined whether zinc modulates BMP-2 signaling and therefore stimulates Runx2 and osteoblast differentiation gene expression. Methods: Two osteoblastic MC3T3-E1 cell lines (subclones 4 as a high osteoblast differentiation and subclone 24 as a low osteoblastic differentiation) were cultured in an osteogenic medium (OSM) as the normal control, Zn-($1{\mu}M$ Zn) or Zn+($15{\mu}M$ Zn) for 24 h. The genes and proteins for BMP-2 signaling (BMP-2, Smad-1/p-Smad-1), transcription factors (Runx2, osterix), and osteoblast differentiation marker proteins were assessed. Results: In both cell lines, BMP-2 mRAN and protein expression and extracellular BMP-2 secretion all decreased in Zn-. The expression of Smad-1 (downstream regulator of BMP-2 signaling) and p-Smad-1 (phosphorylated Smad-1) also downregulated in Zn-. Furthermore, the expression of the bone-specific transcription factors, Runx2 and osterix, decreased in Zn-, which might be due to the decreased BMP-2 expression and Smad-1 activation (p-Smad-1) by Zn-, because Runx2 and osterix both are downstream in BMP-2 signaling. Bone marker gene expression, such as alkaline phosphatase (ALP), collagen type I (COLI), osteocalcin, and osteopontin were also downregulated in Zn-. Conclusion: The results suggest that a zinc deficiency in osteoblasts suppresses the BMP-2 signaling pathway via the suppression of Smad-1 activation, and this suppressed BMP-2 signaling can cause poor osteoblast differentiation.

• 미생물학회지
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• 제53권4호
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• pp.351-353
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• 2017

토마토 뿌리에서 분리한 Chryseobacterium sp. T16E-39 균주는 식물생육촉진과 역병, 시들음병에 대한 억제효과가 있었다. 이 균주의 유전체 염기서열은 4,873,888 염기쌍이었으며 G + C 함량은 35.22%이었다. 이 유전체는 4,289개 단백질 유전자, 15개 rRNA 유전자, 71개 tRNA 유전자를 포함하였다. T16E-39 균주의 유전체에서 인산가용화, 식물호르몬 조절, 항산화 활성, 키틴 분해, 제9형 분비시스템에 관여하는 유전자를 확인하였으며, 이들 유전자는 식물의 생육을 촉진하고 병발생을 억제하는 기작과 관련되어 있을 것으로 판단된다.

• IMMUNE NETWORK
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• 제16권1호
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• International Journal of Stem Cells
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• 제15권2호
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• pp.173-182
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• 2022

Background and Objectives: Bone marrow mesenchymal stem cells (BMSCs) show considerable promise in regenerative medicine. Many studies demonstrated that BMSCs cultured in vitro were highly heterogeneous and composed of diverse cell subpopulations, which may be the basis of their multiple biological characteristics. However, the exact cell subpopulations that make up BMSCs are still unknown. Methods and Results: In this study, we used single-cell RNA sequencing (scRNA-Seq) to divide 6,514 BMSCs into three clusters. The number and corresponding proportion of cells in clusters 1 to 3 were 3,766 (57.81%), 1,720 (26.40%), and 1,028 (15.78%). The gene expression profile and function of the cells in the same cluster were similar. The vast majority of cells expressed the markers defining BMSCs by flow cytometry and gene expression analysis. Each cluster had at least 20 differentially expressed genes (DEGs). We conducted Gene Ontology enrichment analysis on the top 20 DEGs of each cluster and found that the three clusters had different functions, which were related to self-renewal, multilineage differentiation and cytokine secretion, respectively. In addition, the function of the top 20 DEGs of each cluster was checked by the National Center for Biotechnology Information gene database to further verify our hypothesis. Conclusions: This study indicated that scRNA-Seq can be used to divide BMSCs into different subpopulations, demonstrating the heterogeneity of BMSCs.