SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes DOI Creative Commons
Shota Okuno, Shuichiro Higo, Takumi Kondo

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 4, 2023

Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism not elucidated. This study investigated the direct effects receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated purified S-RBD demonstrated that was bound to internalized into subcellular space in iPSC-CMs, depending ACE2. combined live cell imaging a recombinant fused superfolder GFP (S-RBD-sfGFP) membrane, co-localized RAB5A, then delivered endosomes lysosomes iPSC-CMs. Quantitative PCR array analysis followed by single RNA sequence clarified S-RBD-sfGFP treatment significantly upregulated NF-kβ pathway-related gene (CXCL1) non-cardiomyocytes, while interferon (IFN)-responsive genes (IFI6, ISG15, IFITM3) matured cardiomyocytes. promoted protein ISGylation, ISG15-mediated post-translational modification ACE2-WT-iPSC-CMs, which suppressed ACE2-KO-iPSC-CMs. Our experimental demonstrates is through endolysosomal pathway, upregulates IFN-responsive promotes ISGylation

Language: Английский

The Controversial Roles of Areca Nut: Medicine or Toxin? DOI Open Access
Pei‐Feng Liu, Yung-Fu Chang

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8996 - 8996

Published: May 19, 2023

Areca nut (AN) is used for traditional herbal medicine and social activities in several countries. It was as early about A.D. 25-220 a remedy. Traditionally, AN applied medicinal functions. However, it also reported to have toxicological effects. In this review article, we updated recent trends of research addition acquire new knowledge AN. First, the history usage from ancient years described. Then, chemical components their biological functions compared; arecoline an especially important compound extract has different effects caused by components. Thus, dual with pharmacological were summarized. Finally, described perspectives, challenges will provide insight removing or modifying toxic compounds extractions enhancing activity treat diseases future applications.

Language: Английский

Citations

17
The Yin and Yang of TLR4 in COVID-19 DOI
Suprabhat Mukherjee, Jagadeesh Bayry

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

5
Exploring the diverse biological activities of Garcinia cowa: Implications for future cancer chemotherapy and beyond DOI
Asad Ur Rahman, Pharkphoom Panichayupakaranant

Food Bioscience, Journal Year: 2024, Volume and Issue: 61, P. 104525 - 104525

Published: June 6, 2024

Language: Английский

Citations

4
Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling DOI Creative Commons

Huynh Van Tin,

Lekha Rethi,

Satoshi Higa

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(16), P. 1331 - 1331

Published: Aug. 11, 2024

Background: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to viral entry and can cause cardiac injuries. Toll-like receptor 4 (TLR4) NOD-, LPR-, pyrin-domain-containing 3 (NLRP3) inflammasome are critical immune system components implicated in fibrosis. activates NLRP3 through TLR4 or angiotensin-converting enzyme (ACE2) receptors, damaging various organs. However, the role fibrosis humans, as well its interactions with inflammasomes TLR4, remain poorly understood. Methods: We utilized scratch assays, Western blotting, immunofluorescence evaluate migration, signaling, mitochondrial calcium levels, reactive oxygen species (ROS) production, cell morphology cultured human fibroblasts (CFs) treated (S1) for 24 h without an anti-ACE2 neutralizing antibody, a blocker, inhibitor. Results: S1 enhanced CFs migration expressions collagen 1, α-smooth muscle actin, transforming growth factor β1 (TGF-β1), phosphorylated SMAD2/3, interleukin 1β (IL-1β), nuclear kappa-light-chain-enhancer activated B cells (NF-κB). increased ROS production but did not affect content morphology. Treatment antibody attenuated effects on 1 TGF-β1 expressions. Moreover, (MCC950) NF-kB inhibitors, inhibitor TAK-242, prevented protein-enhanced overexpression TGF-β1, IL-1β. Conclusion: by priming NF-κB signaling ACE2-dependent manner.

Language: Английский

Citations

2
SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes DOI Creative Commons
Shota Okuno, Shuichiro Higo, Takumi Kondo

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 4, 2023

Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism not elucidated. This study investigated the direct effects receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated purified S-RBD demonstrated that was bound to internalized into subcellular space in iPSC-CMs, depending ACE2. combined live cell imaging a recombinant fused superfolder GFP (S-RBD-sfGFP) membrane, co-localized RAB5A, then delivered endosomes lysosomes iPSC-CMs. Quantitative PCR array analysis followed by single RNA sequence clarified S-RBD-sfGFP treatment significantly upregulated NF-kβ pathway-related gene (CXCL1) non-cardiomyocytes, while interferon (IFN)-responsive genes (IFI6, ISG15, IFITM3) matured cardiomyocytes. promoted protein ISGylation, ISG15-mediated post-translational modification ACE2-WT-iPSC-CMs, which suppressed ACE2-KO-iPSC-CMs. Our experimental demonstrates is through endolysosomal pathway, upregulates IFN-responsive promotes ISGylation

Language: Английский

Citations

2