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Toll-like Receptor 4-mediated Apoptotic Cell Death in Primary Isolated Human Cervical Cancers
Jinyoung Won(원진영),Yunkyung Hong(홍윤경),Sookyoung Park(박수경),Joo-Heon Kim(김주헌),Yonggeun Hong(홍용근) 한국생명과학회 2018 생명과학회지 Vol.28 No.6
Toll 유사수용체의 TLR4는 세포자연사(apoptosis)와 관련하여 세포의 생존과 증식에 영향을 미치는 것으로 알려져 있다. 본 연구에서는 TLR4의 활성이 부인과 질환 특이적 종양세포의 세포사멸기작에 어떠한 영향을 미치는지 살펴보았다. TLR4의 활성에 의한 세포자연사를 확인하기 위하여 부인암 조직(자궁경부암, 자궁내막암, 난소암)에서 종양세포를 분리하여 초대배양시스템을 구축하였고, lipopolysaccharide (LPS)에 의한 TLR4의 활성유도 과정에서 종양세포의 형태학적 변화를 살펴보았다. 또한, TLR4 매개성 세포사멸 기작을 확인하기 위하여 역전사 중합효소 연쇄반응(RT-PCR)을 통해 유전자 분석을 진행하였다. 연구 결과, 부인암의 초대배양세포에서 세포접촉저지(contact inhibition)현상이 감소되었고, 세포의 배가시간(doubling time)이 단축되어, 종양세포의 성장률 변화를 확인하였다(p<0.05). 자궁근육층(정상조직)의 초대배양세포에서는 민무늬근육 확인 인자인 ITGA5 (an alpha5 integrin marker)의 유전자 발현이 나타났으나, 자궁경부조직의 초대배양세포에서는 발현변화를 확인할 수 없었다. 종양세포의 유전자분석 결과에서 p53과 같은 종양억제인자의 발현이 유의적으로 증가한 반면(p<0.05), 세포사멸 신호기작과 관련하여 TLR4와 Caspase-3의 발현은 감소하였다(Caspase-3, p<0.05). LPS를 처리한 종양세포에서는 LPS 비처리군과 비교 시, TLR4의 발현증가와 함께 Caspase-3의 발현변화가 동반되었다. 이러한 결과들은 TLR4 매개성 apoptosis 유도가 종양세포의 증식억제에 중요한 영향을 미치는 것을 의미하며, TLR4 신호기작을 이용한 종양세포의 새로운 치료적 접근법을 제시할 것으로 기대한다. Toll-like receptor 4 (TLR4) has been implicated in cell proliferation and apoptosis in several types of cancer. In this study, the impact of TLR4 activation on apoptotic cell death in gynecologic cancers induced by lipopolysaccharide (LPS) was investigated. Cervical cancer cell lines were produced from isolated surgical specimens supplied by Paik Hospital. The primary cultures of normal myometrium and gynecologic cancers, including cervical, endometrial, and ovarian cancers, were used to examine the differences in morphological characteristics between normal and cancerous cells. A reverse transcription polymerase chain reaction analysis was used to determine the relative expression levels of TLR4 gene involved in apoptosis-associated signaling in cervical cancer cells. The cancer cell colonies showed a tendency to reach high levels of confluency compared with normal cells. In addition, an enhanced growth rate and loss of contact inhibition were observed in gynecologic cancer cells compared with normal cells (doubling times of 16.6 hr vs. 26 hr, respectively). The expression level of ITGA5, an alpha-5 integrin marker, was upregulated in normal myometrial cells, but this tendency was not exhibited in cervical cancer cells. Furthermore, p53 tumor suppressor gene expression was upregulated, whereas TLR4 and caspase-3 gene expressions were downregulated in cervical cancer cells. Notably, the expression levels of TLR4 and caspase-3 were increased significantly in LPS-treated cancer cells compared with those in non-LPS-treated cells. These results suggest that the TLR4-mediated caspase-dependent apoptotic signaling pathway could be suggested as a therapeutic target for the treatment of gynecologic cancers, including cervical cancers.
Steam Reforming of Toluene Over Ni/Coal Ash Catalysts: Effect of Coal Ash Composition
( Jinyoung Jang ),( Gunung Oh ),( Ho Won Ra ),( Sung Min Yoon ),( Tae Young Mun ),( Myung Won Seo ),( Jihong Moon ),( Jae-goo Lee ),( Sang Jun Yoon ) 한국화학공학회 2021 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.59 No.2
The development of a low cost catalyst with high performance and small amount of carbon deposition on catalyst from toluene steam reforming were investigated by using coal ash as a support material. Ni-loaded coal ash catalyst showed similar catalytic activity for toluene steam reforming compared with the Ni/Al<sub>2</sub>O<sub>3</sub>. At 800℃, the toluene conversion was 77% for Ni/TAL, 68% for Ni/KPU and 78% for Ni/Al<sub>2</sub>O<sub>3</sub>. Ni/TAL showed similar toluene conversion to Ni/Al<sub>2</sub>O<sub>3</sub>. However, Ni/KPU produced higher hydrogen yield at relatively lower toluene conversion. Ni/KPU catalyst showed a remarkable ability of suppressing the carbon deposition. The difference in coke deposition and hydrogen yield is due to the composition of KPU ash (Ca and Fe) which increase coke resistance and water gas shift reaction. This study suggests that coal ash catalysts have great potential for the application in the steam reforming of biomass tar.
Won, Jinyoung,Jin, Yunho,Choi, Jeonghyun,Park, Sookyoung,Lee, Tae Ho,Lee, Sang-Rae,Chang, Kyu-Tae,Hong, Yonggeun MDPI AG 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.6
<P>Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (<I>fmr</I>) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the <I>fmr</I> gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.</P>
Yang Jinyoung,Hyeon Seokhwan,Baek Jin Yang,Kang Min Seo,Lee Keon Young,Lee Young Ho,Huh Kyungmin,Cho Sun Young,Kang Cheol-In,Chung Doo Ryeon,Peck Kyong Ran,Won Gunho,Lee Hye Won,Kim Kwangwook,Hwang In 대한의학회 2023 Journal of Korean medical science Vol.38 No.27
Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND50 of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND50 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND50 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.
Jinyoung Hong,Joonsang Yu,Hyunjung Gu,Juhee Lee,Woochang Lee,Sail Chun,Won-Ki Min 대한임상검사정도관리협회 2022 Journal of Laboratory Medicine And Quality Assuran Vol.44 No.3
Background: Next-generation sequencing (NGS)-based liquid biopsy testing using peripheral blood is a minimally invasive technique that can identify the characteristics of tumor-derived circulating tumor DNA (ctDNA) in cellfree DNA (cfDNA). External quality assessment (EQA) should be implemented to ensure the reliability of NGS-based liquid biopsy tests. This study aims to establish a method for producing EQA materials for NGS-based liquid biopsy tests. Methods: Eight cell lines harboring clinically important somatic mutations were selected for further analysis. Genomic DNA from the cell lines was extracted and fragmented using an ultrasonicator (Covaris Inc., USA). Two EQA materials were produced by spiking fragmented DNA into fresh frozen plasma and frozen at –70℃. The manufactured EQA materials were evaluated using a cfDNA gene panel (Dxome, Korea) using NextSeq Dx (Illumina, USA). Results: After sonication, the average sizes of the fragmented DNA were 203 and 201 bp, respectively. The results of the cell-free NGS panel showed a combination of different variants between the two EQA materials, and clinically important somatic mutations were detected as intended. Conclusions: In this study, a method for manufacturing materials for an NGS-based liquid biopsy test EQA scheme is presented. EQA materials with conditions similar to ctDNA clinical specimens can be produced at a relatively low cost using cell line-derived DNA and an ultrasonicator. The distribution of adequate EQA materials can improve the reliability of NGS-based liquid biopsy tests.
Jinyoung Oh,Sang Won Han,Sun Yoon Chung 대한신경초음파학회 2023 대한신경초음파학회지 (JNN) Vol.15 No.1
Several cases of cerebral venous thrombosis (CVT) due to spontaneous intracranial hypotension (SIH) have been reported, with an estimated occurrence rate of 1–2% among patients with decreased intracranial pressure. However, the causal relationship between SIH and CVT as a potential risk factor is not well understood. According to the Monro-Kellie principle, this is thought to be caused by compensatory expansion of the cerebral venous system, damage to the intravenous wall due to changes in cerebral buoyancy, or increased venous blood viscosity. Although anticoagulation therapy is typically the first choice of treatment for patients diagnosed with CVT, considering the potential risk of intracerebral hemorrhage in patients with CVT secondary to SIH is important. We report the case of a patient who developed CVT as a complication of SIH and discuss its mechanisms and treatment options. Early identification and appropriate treatment can lead to successful outcomes and the prevention of potential complications.