• Biomolecules & Therapeutics
• /
• 제27권2호
• /
• pp.231-239
• /
• 2019

Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing $G_1$ cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120-172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.

• Journal of Ginseng Research
• /
• 제40권3호
• /
• pp.285-291
• /
• 2016

Background: Ginsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism. Methods: MCT-intoxicated rats were treated with gradient doses of TG, with or without $N^G$-nitro-$\small{L}$-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined. Results: TG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2. Conclusion: TG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways.

• Clinical and Experimental Reproductive Medicine
• /
• 제43권2호
• /
• pp.59-81
• /
• 2016

It is well established that there is a heritable element of susceptibility to chronic human ailments, yet there is compelling evidence that some components of such heritability are transmitted through non-genetic factors. Due to the complexity of reproductive processes, identifying the inheritance patterns of these factors is not easy. But little doubt exists that besides the genomic backbone, a range of epigenetic cues affect our genetic programme. The inter-generational transmission of epigenetic marks is believed to operate via four principal means that dramatically differ in their information content: DNA methylation, histone modifications, microRNAs and nucleosome positioning. These epigenetic signatures influence the cellular machinery through positive and negative feedback mechanisms either alone or interactively. Understanding how these mechanisms work to activate or deactivate parts of our genetic programme not only on a day-to-day basis but also over generations is an important area of reproductive health research.

• IMMUNE NETWORK
• /
• 제13권4호
• /
• pp.133-140
• /
• 2013

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and $IFN-{\gamma}$ production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.

• Clinical and Experimental Reproductive Medicine
• /
• 제40권1호
• /
• pp.33-37
• /
• 2013

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy.

• Journal of Microbiology and Biotechnology
• /
• 제29권8호
• /
• pp.1212-1220
• /
• 2019

The study of metabolomics in natural products using the diverse analytical instruments including GC-MS, LC-MS, and NMR is useful for the exploration of physiological and biological effects and the investigation of drug discovery and health functional foods. Cordyceps militaris has been very attractive to natural medicine as a traditional Chinese medicine, due to its various bioactive properties including anti-cancer and anti-oxidant effects. In this study, we analyzed the metabolite profile in 50% ethanol extracts of C. militaris fruit bodies from three development periods (growth period, matured period, and aging period) using $^1H-NMR$, and identified 44 metabolites, which are classified as 16 amino acids, 10 organic acids, 5 carbohydrates, 3 nucleotide derivatives, and 10 other compounds. Among the three development periods of the C. militaris fruit body, the aging period showed significantly higher levels of metabolites including cordycepin, mannitol (cordycepic acid), and ${\beta}-glucan$. Interestingly, these bioactive metabolites are positively correlated with antitumor growth effect; the extract of the aging period showed significant inhibition of HepG2 hepatic cancer cell proliferation. These results showed that the aging period during the development of C. militaris fruit bodies was more highly enriched with bioactive metabolites that are associated with cancer cell growth inhibition.

• IMMUNE NETWORK
• /
• 제23권4호
• /
• pp.34.1-34.15
• /
• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• 대한치과보철학회지
• /
• 제57권2호
• /
• pp.134-141
• /
• 2019

목적: 본 연구에서는 리튬 디실리케이트-지르코니아 이중도재관과 단일구조 지르코니아로 제작된 구치부 고정성 임플란트 지지 보철물의 2년간의 임상적 결과를 비교하고자 하였다. 대상 및 방법: 2015년에서 2018년 사이 부산대학교 치과병원에 내원하여 치료받은 총 17명의 환자(남성: 12, 여성: 5)를 대상으로 60개의 구치부 고정성 임플란트 지지 보철물을 제작하였다(LP. Lithium disilicate pressed zirconia prostheses: n = 30, MZ. Monolithic zirconia prostheses: n = 30) 보철물 제작 후 2년간의 추적 관찰을 통해 임플란트 생존율, 변연골 흡수량, 치주낭 깊이, 치태지수, 출혈지수, 치석지수 및 합병증을 평가하였다. 결과: 모든 임플란트가 기능적 문제와 동요도 없이 100%의 생존율을 보였다. 변연골 흡수량은 관찰 12개월에 LP군이 MZ군 보다 더 적었으며 (P < .05), 임상 검사시 관찰 12개월의 치주낭 깊이 및 치석 지수는 LP군에서 더 높았다 (P < .05). 주된 합병증으로 MZ군에서 7개에서 1.5 mm 이상의 골흡수가 관찰되었으며, LP군에서 2개의 chipping이 관찰되었다. 결론: 본 연구의 한계 내에서, 구치부 임플란트 지지 보철물에서 리튬 디실리케이트가 프레스된 지르코니아 보철물은 단일구조 지르코니아 보철물과 함께 예지성 있는 치료방법으로 판단된다.

• 한방재활의학과학회지
• /
• 제26권4호
• /
• pp.85-96
• /
• 2016

Objectives The purpose of this study was to investigate the relationship between the effects of acupuncture treatment and heart rate variability (HRV) in pre-menopausal obese women. Methods Thirty-seven obese women who met the inclusion criteria were recruited. To estimate the effects of acupuncture, obesity indices, such as body weight (BW), waist circumference (WC), hip circumference (HC), and the waist-hip ratio (WHR), were measured before and after the treatment. The HRV test was conducted before treatment and analyzed using the frequency domain method. Results The lnLF/HF ratio (natural logarithm of low frequency power/high frequency power ratio of the HRV value) before treatments was negatively correlated with differences in WC, HC, and WHR during treatment. The correlation coefficients between the lnLF/HF ratio and the differences in WC, HC, and WHR were r=-0.459 (p<0.01), r=-0.327 (p<0.05), and r=-0.339 (p<0.05) respectively. Conclusions As the baseline ratio of sympathetic activity to parasympathetic activity decreases, WC, HC, and WHR reduction significantly increased during treatment. Further study is needed to uncover the relationship between obesity-related variables and the autonomic nervous system to predict the effect of acupuncture.

• 한국유전체학회:학술대회논문집
• /
• 한국유전체학회 2005년도 The 14th Korea Genome Conference
• /
• pp.52-52
• /
• 2005