1.Educational case series of electrocardiographs during the COVID-19 pandemic and the implications for therapy.
Ching-Hui SIA ; Jinghao Nicholas NGIAM ; Nicholas CHEW ; Darius Lian Lian BEH ; Kian Keong POH
Singapore medical journal 2020;61(8):406-412
Adenosine Monophosphate
;
analogs & derivatives
;
therapeutic use
;
Adult
;
Aged
;
Alanine
;
analogs & derivatives
;
therapeutic use
;
Anti-Arrhythmia Agents
;
therapeutic use
;
Arrhythmias, Cardiac
;
diagnosis
;
epidemiology
;
Coronavirus Infections
;
diagnosis
;
drug therapy
;
epidemiology
;
Echocardiography
;
Electrocardiography
;
methods
;
statistics & numerical data
;
Female
;
Follow-Up Studies
;
Humans
;
Male
;
Pandemics
;
statistics & numerical data
;
Pneumonia, Viral
;
diagnosis
;
drug therapy
;
epidemiology
;
Sampling Studies
;
Severe Acute Respiratory Syndrome
;
diagnosis
;
epidemiology
;
Singapore
;
Treatment Outcome
2.Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection.
Rongjuan PEI ; Jianqi FENG ; Yecheng ZHANG ; Hao SUN ; Lian LI ; Xuejie YANG ; Jiangping HE ; Shuqi XIAO ; Jin XIONG ; Ying LIN ; Kun WEN ; Hongwei ZHOU ; Jiekai CHEN ; Zhili RONG ; Xinwen CHEN
Protein & Cell 2021;12(9):717-733
The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.
Adenosine Monophosphate/therapeutic use*
;
Alanine/therapeutic use*
;
Alveolar Epithelial Cells/virology*
;
Antibodies, Neutralizing/therapeutic use*
;
COVID-19/virology*
;
Down-Regulation
;
Drug Discovery
;
Human Embryonic Stem Cells/metabolism*
;
Humans
;
Immunity
;
Lipid Metabolism
;
Lung/virology*
;
RNA, Viral/metabolism*
;
SARS-CoV-2/physiology*
;
Virus Replication/drug effects*
3.Mouse-adapted SARS-CoV-2 replicates efficiently in the upper and lower respiratory tract of BALB/c and C57BL/6J mice.
Jinliang WANG ; Lei SHUAI ; Chong WANG ; Renqiang LIU ; Xijun HE ; Xianfeng ZHANG ; Ziruo SUN ; Dan SHAN ; Jinying GE ; Xijun WANG ; Ronghong HUA ; Gongxun ZHONG ; Zhiyuan WEN ; Zhigao BU
Protein & Cell 2020;11(10):776-782
Adaptation, Physiological
;
Adenosine Monophosphate
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
therapeutic use
;
Administration, Intranasal
;
Alanine
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
therapeutic use
;
Animals
;
Betacoronavirus
;
genetics
;
physiology
;
Chlorocebus aethiops
;
Coronavirus Infections
;
drug therapy
;
virology
;
Disease Models, Animal
;
Female
;
Host Specificity
;
genetics
;
Lung
;
pathology
;
virology
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mutation, Missense
;
Nasal Mucosa
;
virology
;
Pandemics
;
Pneumonia, Viral
;
drug therapy
;
virology
;
RNA, Viral
;
administration & dosage
;
genetics
;
Turbinates
;
virology
;
Vero Cells
;
Viral Load
;
Virus Replication
4.Modified Si-Miao-San inhibits inflammation and promotes glucose disposal in adipocytes through regulation of AMP-kinase.
Jiang-Lin YANG ; Jun-Lian WANG ; Fang HUANG ; Kang LIU ; Bao-Lin LIU
Chinese Journal of Natural Medicines (English Ed.) 2014;12(12):911-919
Modified Si-Miao-San (mSMS) is composed of Rhizoma Coptidis, Cortex Phellodendri, Rhizoma Coptidis Semen Coicis and Atractylodes Rhizome. The prescription is used for the management of diabetes and insulin resistance in the clinic. This study aims to investigate its regulation of glucose disposal in adipocytes. Differentiated 3T3-L1 adipocytes were stimulated with conditioned medium derived from activated macrophages to induce insulin resistance and observed the effects of Mac-CM on insulin-mediated glucose uptake along the insulin receptor substrate-1/PI3K/Akt signaling pathway. Moreover, its regulation of AMPK phosphorylation was also investigated. mSMS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mSMS inhibited NF-κB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. These beneficial effects were diminished in the presence of the AMPK inhibitor compound C. mSMS positively regulated AMPK activity, and this action contributed to improving insulin PI3K signaling by the beneficial regulation of IRS-1 function through inhibition of inflammation in adipocytes.
3T3-L1 Cells
;
Adenosine Monophosphate
;
metabolism
;
Adenylate Kinase
;
metabolism
;
Adipocytes
;
drug effects
;
metabolism
;
Animals
;
Atractylodes
;
Coix
;
Coptis
;
Diabetes Mellitus
;
drug therapy
;
metabolism
;
Drugs, Chinese Herbal
;
pharmacology
;
therapeutic use
;
Glucose
;
metabolism
;
Glucose Transporter Type 4
;
metabolism
;
Inflammation
;
metabolism
;
prevention & control
;
Insulin
;
metabolism
;
Insulin Receptor Substrate Proteins
;
metabolism
;
Insulin Resistance
;
Mice
;
NF-kappa B
;
metabolism
;
Phellodendron
;
Phosphatidylinositol 3-Kinases
;
metabolism
;
Phosphorylation
;
Phytotherapy
;
Proto-Oncogene Proteins c-akt
;
metabolism
;
Signal Transduction