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Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice
Jung Ah Kim,Sung-Hee Kim,Jung Seon Seo,노현아,Haengdueng Jeong,Jiseon Kim,Donghun Jeon,Jeong Jin Kim,Dain On,윤서연,Sang Gyu Lee,이윤우,Hui Jeong Jang,In Ho Park,Jooyeon Oh,Sang-Hyuk Seok,Yu Jin Lee,홍승민,안세희,Jo 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.
Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah Kim,Sung-Hee Kim,Jeong Jin Kim,Hyuna Noh,Su-bin Lee,Haengdueng Jeong,Jiseon Kim,Donghun Jeon,Jung Seon Seo,Dain On,Suhyeon Yoon,Sang Gyu Lee,Youn Woo Lee,Hui Jeong Jang,In Ho Park,Jooyeon Oh,S The Korean Association of Immunobiologists 2024 Immune Network Vol.24 No.2
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10<sup>5</sup> plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10<sup>2</sup> PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10<sup>2</sup> PFU-virus-infected lungs from 2 dpi, but not in 1×10<sup>5</sup> PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10<sup>5</sup> PFU; however, 1×1<sup>2</sup> PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice
Jung Ah Kim,Sung-Hee Kim,Jung Seon Seo,노현아,Haengdueng Jeong,Jiseon Kim,Donghun Jeon,Jeong Jin Kim,Dain On,윤서연,Sang Gyu Lee,이윤우,Hui Jeong Jang,박인호,Jooyeon Oh,Sang-Hyuk Seok,Yu Jin Lee,홍승민,안세희,Joon-Yong 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.
Park, Jooyeon,Kim, Bokyoung,Han, Jin,Oh, Jaewon,Park, Subeom,Ryu, Seungmi,Jung, Subin,Shin, Jung-Youn,Lee, Beom Seob,Hong, Byung Hee,Choi, Donghoon,Kim, Byung-Soo American Chemical Society 2015 ACS NANO Vol.9 No.5
<P>Mesenchymal stem cell (MSC) implantation has emerged as a potential therapy for myocardial infarction (MI). However, the poor survival of MSCs implanted to treat MI has significantly limited the therapeutic efficacy of this approach. This poor survival is primarily due to reactive oxygen species (ROS) generated in the ischemic myocardium after the restoration of blood flow. ROS primarily causes the death of implanted MSCs by inhibiting the adhesion of the MSCs to extracellular matrices at the lesion site (<I>i.e.</I>, anoikis). In this study, we proposed the use of graphene oxide (GO) flakes to protect the implanted MSCs from ROS-mediated death and thereby improve the therapeutic efficacy of the MSCs. GO can adsorb extracellular matrix (ECM) proteins. The survival of MSCs, which had adhered to ECM protein-adsorbed GO flakes and were subsequently exposed to ROS <I>in vitro</I> or implanted into the ischemia-damaged and reperfused myocardium, significantly exceeded that of unmodified MSCs. Furthermore, the MSC engraftment improved by the adhesion of MSCs to GO flakes prior to implantation enhanced the paracrine secretion from the MSCs following MSC implantation, which in turn promoted cardiac tissue repair and cardiac function restoration. This study demonstrates that GO can effectively improve the engraftment and therapeutic efficacy of MSCs used to repair the injury of ROS-abundant ischemia and reperfusion by protecting implanted cells from anoikis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-5/nn507149w/production/images/medium/nn-2014-07149w_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn507149w'>ACS Electronic Supporting Info</A></P>
하현빈,Jooyeon Lee,박명환,Byunghyuck Jung,김민 대한화학회 2020 Bulletin of the Korean Chemical Society Vol.41 No.6
The synthesis of amine skeletons and catalytic bond formation in aliphatic amines are important synthetic methodologies. Although various metal-catalyzed organic transformations have been successfully used to functionalize and construct amine molecules, there are still many hurdles toward practical application. Moreover, site-selectivity is generally achieved using a traditional directing group (DG) strategy, which requires at least two additional steps for the installation and removal of the DGs. Recently, a transient directing group (TDG) strategy, also known as traceless DG and temporary DG, has been widely studied for a range of selective transition metal-catalyzed C─H bond functionalization. In this account, we have focused on the recent developments of the TDG strategy toward the site-selective C─H bond functionalization of aliphatic amines. The design of the TDGs used for the target reaction and their critical roles in the reaction mechanism will be covered along with their selectivity and synthetic utility.
이주연(Jooyeon Lee),정의철(Eui-Chul Jung) 한국HCI학회 2020 한국HCI학회 학술대회 Vol.2020 No.2
디자인 프로세스는 사용자를 이해하여 컨셉을 제안하는 과정이다. 이 과정에서 다양한 데이터를 수집, 분석, 해석하고 이를 통해 디자인 영감을 얻게 된다. 전통적 디자인 프로세스에서 데이터는 참고자료로 간주가 되었으나, 점차 디자인 프로세스가 데이터를 활용한 지식 창조 활동으로 보는 관점이 형성되면서, 다양한 데이터 수집 기술을 활용하여, 데이터를 디자인 컨셉 창작의 재료로 활용하려는 시도가 많이지고 있다. 즉, 디자인 프로세스에서 데이터는 사용자와 디자인 대상을 이해하고, 컨셉을 설득하기 위한 수단으로 활용되었으나, 데이터의 패턴을 이해하여 문제를 보다 체계적으로 분석하여 풍부한 디자인 영감을 제공하는 방법으로 활용되기 시작하였다. 최근에는, 사물인터넷 기기등을 활용한 데이터 수집이 가능해지면서, 사용자와의 협업을 통해 컨셉을 만들어가는 데이터 기반 기다인(data-enabled design)개념으로 발전하고 있다. 4 차산업혁명 키워드의 하나인 데이터를 디자인 프로세스 관점에서 해석하는 것은 이러한 배경에서 중요하다고 볼 수 있다. 따라서, 본 연구는 디자인 프로세스에서 데이터를 활용하는 다양한 방법을 고찰하는 것을 목표로 한다. 이를 위한 연구 방법은 디자인 프로세스에서 데이터를 활용하는 관점과 접근을 문헌고찰을 통해 정리하였다. 문헌 고찰을 기반으로, 최근 논의가 활발한 데이터 중심 디자인의 방법에 대해 사례를 조사하여, 데이터를 활용한 디자인이 사용자 디자인 관점에서 어떠한 장점이 있는가를 논의하였다. 이 연구를 통하여, 디자인 프로세스를 데이터의 관점으로 재정의하고, 데이터 기반 디자인 방법의 방향성을 논의할 수 있는 토대를 만들 수 있을 것으로 기대한다.