3篇
您的检索式：作者名="Changlei Bao"
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| 1 | SARS-CoV-2 spike protein receptor-binding domain perturbates intracellular calcium homeostasis and impairs pulmonary vascular endothelial cells显示文摘Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy.In this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium.Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated apoptosis.These effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,BAPTA-AM.Blockade of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]i.Comparing to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell apoptosis.Transcriptomic analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda S-RBD.In summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and Orai1.Targeted inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases. | Kai Yang Shiyun Liu Han Yan Wenju Lu Xiaoqian Shan Haixia Chen Changlei Bao Huazhuo Feng Jing Liao Shuxin Liang Lei Xu Haiyang Tang Jason X-J.Yuan Nanshan Zhong Jian Wang | 2023 | Signal Transduction and Targeted Therapy2023，8，8： | 2 |
| 2 | Au(Ⅰ)-Catalyzed Annulation of Benzofurazan N-oxides with Ynamides: From Predicting the Chemo-Selectivity to the Synthesis of 7-Nitroindole Derivatives显示文摘Summaryof main observation and conclusion It could be proposed that gold(I)-catalyzed reactions of ynamides with benzofurazan N-oxidesmightproceed through eitherO-attack or N-attack to affordα-oxo orα-imino Au(I)-carbenoidintermediates.Computational studies were performed to predict that benzofurazan N-oxides are ready to undergo the chemoselective N-attack tothe Au(I)-activatedynamides to generate theα-imino Au(I)-carbenoid intermediate.Experimental studies were carried out to confirm the computational results and the 7-nitroindole derivatives were synthesized in a concise and efficient manner.The unfavored O-attack for benzofurazan N-oxides,which is in contrast to nitrones and pyridine/quinoline N-oxides,in the Au(I)-catalyzed reactions with ynamides is rationalized. | Changlei Zhu Luyao Kou Xiaoguang Bao | 2020 | Chinese Journal of Chemistry2020，38，1： | 1 |
| 3 | SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy显示文摘Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets. | Shuxin Liang Changlei Bao Zi Yang Shiyun Liu Yanan Sun Weitao Cao Ting Wang Tae-Hwi Schwantes-An John S.Choy Samisubbu Naidu Ang Luo Wenguang Yin Stephen M.Black Jian Wang Pixin Ran Ankit A.Desai Haiyang Tang | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 0 |
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