• 한국발생생물학회지:발생과생식
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• 제25권4호
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• pp.213-223
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• 2021

Controlled ovarian hyperstimulation (COH) is routinely used in the in vitro fertilization and embryo transfer (IVF-ET) cycles to increase the number of retrieved mature oocytes. However, the relationship between repeated COH and ovarian function is still controversial. Therefore, we investigated whether repeated ovarian stimulation affects ovarian aging and function, including follicular development, autophagy, and apoptosis in follicles. Ovarian hyperstimulation in mice was induced by intraperitoneal injection with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Mice subjected to ovarian stimulation once were used as a control group and 10 times as an experimental group. Repeated injections with PMSG and hCG significantly reduced the number of primary follicles compared to a single injection. The number of secondary and antral follicles increased slightly, while the number of corpus luteum increased significantly with repeated injections. On the other hand, repeated injections did not affect apoptosis in follicles associated with follicular atresia. The expression of autophagy-related genes Atg5, Atg12, LC3B, and Beclin1, cell proliferation-related genes mTOR, apoptosis-related genes Fas, and FasL was not significantly different between the two groups. In addition, the expression of the aging-related genes Dnmt1, Dnmt3a, and AMH were also not significantly different. In this study, we demonstrated that repeated ovarian stimulation in mice affects follicular development, but not autophagy, apoptosis, aging in ovary. These results suggest that repetition of COH in the IVF-ET cycle may not result in ovarian aging, such as a decrease in ovarian reserve in adult women.

• 한국지진공학회논문집
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• 제25권3호
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• pp.145-152
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• 2021

KAERI has planned to carry out a series of dynamic tests using a shaking table and time-history analyses for a channel-type concrete shear wall to investigate its seismic performance because of the recently frequent occurrence of earthquakes in the south-eastern parts of Korea. The overall size of a test specimen is b×l×h =2500 mm×3500 mm×4500 mm, and it consists of three stories having slabs and walls with thicknesses of 140 mm and 150 mm, respectively. The system identification, FE model updating, and time-history analysis results for a test shear wall are presented herein. By applying the advanced system identification, so-called pLSCF, the improved modal parameters are extracted in the lower modes. Using three FE in-house packages, such as FEMtools, Ruaumoko, and VecTor4, the eigenanalyses are made for an initial FE model, resulting in consistency in eigenvalues. However, they exhibit relatively stiffer behavior, as much as 30 to 50% compared with those extracted from the test in the 1st and 2nd modes. The FE model updating is carried out to consider the 6-dofs spring stiffnesses at the wall base as major parameters by adopting a Bayesian type automatic updating algorithm to minimize the residuals in modal parameters. The updating results indicate that the highest sensitivity is apparent in the vertical translational springs at few locations ranging from 300 to 500% in variation. However, their changes seem to have no physical meaning because of the numerical values. Finally, using the updated FE model, the time-history responses are predicted by Ruaumoko at each floor where accelerometers are located. The accelerograms between test and analysis show an acceptable match in terms of maximum and minimum values. However, the magnitudes and patterns of floor response spectra seem somewhat different because of the slightly different input accelerograms and damping ratios involved.

• 생약학회지
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• 제49권4호
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• pp.291-297
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• 2018

Coxsackievirus B3 (CVB3) is a very well-known causative agent for viral myocarditis and meningitis in human. However, the effective vaccine and therapeutic drug are not developed yet. CVB3 infection activates host cell AKT signaling. Inhibition of AKT signaling pathway may attenuate CVB3 replication and prevent CVB3-mediate viral myocarditis. In this study, we determined antiviral effect of the selected natural plant extract to develop a therapeutic drug for CVB3 treatment. We screened several chemically extracted natural compounds by using HeLa cell-based cell survival assay. Among them, Linum usitatissimum L. extract was selected for antiviral drug candidate. L. usitatissimum extract significantly decreased CVB3 replication and cell death in CVB3 infected HeLa cells with no cytotoxicity. CVB3 protease 2A induced eIF4G1 cleavage and viral capsid protein VP1 production were dramatically decreased by L. usitatissimum extract treatment. In addition, virus positive and negative strand genome amplification were significantly decreased by 1 mg/ml L. usitatissimum extract treatment. Especially, L. usitatissimum extract was associated with inhibition of AKT signal and maintain mTOR activity. In contrast, Atg12 and LC3 expression were not changed by L. usitatissimum extract treatment. In this study, the potential AKT signal inhibitor, L. usitatissimum extract, was significantly inhibited viral genome replication and protein production by inhibition of AKT signal. These results suggested that L. usitatissimum extract is a novel therapeutic agent for treatment of CVB3-mediated diseases.

• BMB Reports
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• 제52권8호
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Molecules and Cells
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• 제44권1호
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• pp.50-62
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• 2021

Among all cancer types, lung cancer ranks highest worldwide in terms of both incidence and mortality. The crosstalk between lung cancer cells and their tumor microenvironment (TME) has begun to emerge as the "Achilles heel" of the disease and thus constitutes an attractive target for anticancer therapy. We previously revealed that crosstalk between lung cancer cells and endothelial cells (ECs) induces chemoresistance in multicellular tumor spheroids (MCTSs). In this study, we demonstrated that factors secreted in response to crosstalk between ECs and lung cancer cells play pivotal roles in the development of chemoresistance in lung cancer spheroids. We subsequently determined that the expression of hypoxia up-regulated protein 1 (HYOU1) in lung cancer spheroids was increased by factors secreted in response to crosstalk between ECs and lung cancer cells. Direct interaction between lung cancer cells and ECs also caused an elevation in the expression of HYOU1 in MCTSs. Inhibition of HYOU1 expression not only suppressed stemness and malignancy, but also facilitated apoptosis and chemosensitivity in lung cancer MCTSs. Inhibition of HYOU1 expression also significantly increased the expression of interferon signaling components in lung cancer cells. Moreover, the activation of the PI3K/AKT/mTOR pathway was involved in the HYOU1-induced aggression of lung cancer cells. Taken together, our results identify HYOU1, which is induced in response to crosstalk between ECs and lung cancer cells within the TME, as a potential therapeutic target for combating the aggressive behavior of cancer cells.

• BMB Reports
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• 제54권6호
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.

• 한국지형학회지
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• 제19권3호
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• pp.123-134
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• 2012

동천구곡은 자연지형과 인간 심성활동의 결합체이다. 본 논문은 동천구곡의 장소성과 경관 이미지를 구성하는 기본요소인 지형경관의 특성에 대하여 조사 확인한 결과를 정리한 것이다. 우리나라 동천구곡은 주로 태백산맥과 소백산맥의 산지 지역에 주로 입지 분포하며, 이는 인근에 위치한 양반의 계거촌과 관련이 있다. 동천구곡이 자리 잡은 지역의 기반암 특성이 지형경관 특성에 크게 영향을 미치는데, 우리나라에서는 화강암과 퇴적암 경관이 이를 가장 대표한다. 우리나라 동천구곡은 산지 내부를 흐르는 곡류하도에 주로 입지하여, 곡류하도 주변에 나타나는 다양한 지형요소들이 주요 경관을 이루고 있다. 이러한 주요 지형요소로는 봉우리, 소규모 평탄면, 토르, 수직절벽, 폭포, 여울, 소, 포인트바, 그리고 너럭바위, 거력, 암설사력퇴, 마식된 암반하상과 포트홀 등이 있다. 이를 동천구곡에서는 대(臺) 암(巖) 봉(峰) 벽(璧) 벼리(遷) 학(壑) 반석(盤石) 천(泉) 폭(瀑) 담(潭) 연(淵) 추(湫) 소(沼) 천(川) 탄(灘) 등으로 칭한다.

• Journal of Gastric Cancer
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• 제21권4호
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• 한국콘텐츠학회논문지
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• 제22권4호
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• pp.70-82
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• 2022

4단계 이전의 자율주행은 반자율주행 단계로 차량이 주행을 하다가 운전자에게 빠르게 제어권을 넘겨야 하는 상황이 반복적으로 벌어진다. 하지만 지금의 자율주행 차량은 제어권을 넘길 때 일괄적으로 간단한 메시지와 경고음만을 사용해 운전자에게 알림을 주고 있어 개개인의 특성에 대한 고려나 다양한 위급 상황에 대한 설명을 제대로 전달하지 못하고 있다. 본 연구에서는 자율주행 차량의 판단에 대한 시·청각 정보 제공 정도와 운전자의 운전 효능감이 제어권 전환 요청 상황에서 운전자의 판단과 행동에 미치는 영향을 살펴보았다. 연구 결과 제어권 전환 요구 시 제공된 시·청각 정보 조합 방식에 따른 운전자의 인지 부하, 신뢰도, 안전감, 사용성 및 유용성의 설문 항목에서 조건에 따라 유의한 차이가 있는 것을 확인할 수 있었다. 본 연구를 통해 운전자의 운전 효능감에 따라 제어권 전환 상황에서 요청을 전달하는 효율적인 정보 제공 방식이 달라진다는 인사이트를 발견할 수 있었다. 급박한 제어권 전환 상황에서 운전자의 특성을 고려한 요청이 이루어져야 한다는 본 연구의 결과는 보다 안전하고 효율적으로 운전자와 소통할 수 있는 자율주행 차량을 설계하는데 도움을 줄 수 있을 것으로 기대한다.

• BMB Reports
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• 제55권11호
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.