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GSK-LSD1,an LSD1 inhibitor,quashes SARS-CoV-2-triggered cytokine release syndrome in-vitro

Signal Transduction and Targeted Therapy 2020年第1期5卷 255-257页

作者： Kyung Soo Hong June Hong Ahn Jong Geol Jang Jong Ho lee Hong Nam Kim Dongha Kim wonhwa lee Division of Pulmonology and Allergy Department of Internal MedicineCollege of MedicineYeungnam University and Regional Center for Respiratory DiseasesYeungnam University Medical CenterDaegu 42415Republic of Korea Department of Laboratory Medicine College of MedicineYeungnam UniversityYeungnam University Medical CenterDaegu 42415Republic of Korea Brain Science Institute Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolKorea University of Science and Technology(UST)Seoul 02792Republic of Korea Department of Anatomy College of MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea Aging Research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 34141Republic of Korea

Dear Editor,Since the COVID-19 demonstrated a remarkable transmission speed and a high mortality risk,COVID-19 is currently declared as a pandemic by the World Health *** is the first time that the WHO has declared a pandemic since H1N1 in *** of 6 September 2020,the total number of COVID-19 patients is 26,763,217(876,616 deaths),and it continues to rise(https://***/).In spite of the urgent demand for the vaccines and therapeutics,global efforts are primarily focused on the utilization of the existing anti-viral drugs,such as remdesivir,hydroxychloroquine,and dexamethasone,to relieve the symptoms due to the limited development of renovative therapeutics.

关键词： drugs mortality cytokine

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COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm

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Signal Transduction and Targeted Therapy 2020年第1期5卷 910-920页

作者： wonhwa lee June Hong Ahn Hee Ho Park Hong Nam Kim Hyelim Kim Youngbum Yoo Hyosoo Shin Kyung Soo Hong Jong Geol Jang Chun Gwon Park Eun Young Choi Jong-Sup Bae Young-Kyo Seo Aging Research Center Korea Research Institute of Bioscience and BiotechnologyDaejeon 34141Republic of Korea Division of Pulmonology and Allergy Department of Internal MedicineCollege of MedicineYeungnam University and Regional Center for Respiratory DiseasesYeungnam University Medical CenterDaegu 42415Republic of Korea Department of Biotechnology and Bioengineering Kangwon National UniversityChuncheonGangwon-do 24341Republic of Korea Center for BioMicrosystems Brain Science InstituteKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Division of Bio-Medical Science and Technology KIST SchoolKorea University of Science and TechnologySeoul 02792Republic of Korea College of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Department of Biomedical Engineering SKKU Institute for ConvergenceSungkyunkwan University(SKKU)SuwonRepublic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University2066 Seobu-roJangan-guSuwon 16419Republic of Korea College of Pharmacy CMRIResearch Institute of Pharmaceutical SciencesBK21 Plus KNU Multi-Omics based Creative Drug Research TeamKyungpook National UniversityDaegu 41566Republic of Korea

Sterol regulatory element binding protein-2(SREBP-2)is activated by cytokines or pathogen,such as virus or bacteria,but its association with diminished cholesterol levels in COVID-19 patients is ***,we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in ***,we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’blood and propose SREBP-2 C-terminal fragment as an indicator for determining *** confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression,while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU *** an infectious disease mouse model,inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary *** results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

关键词： cytokine diagnosis damage

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