Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
Tohoku J Exp Med ; 256(4): 309-319, 2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1817583

ABSTRACT

This research investigated the histopathological changes in the tissue of the lung, heart and liver, hepatocyte cell death, autophagy, and the apoptosis inductions in the postmortem cases. Since December 2019, coronavirus disease 2019 (COVID-19) has become a significant global health concern. In order to clarify the changes in tissues of the lung, heart and liver by COVID-19, samples were taken from five patients who died of COVID-19 and five control cases, and the pathological changes in the lung, liver, and heart tissue were studied by X-ray, computed tomography, histological studies, and stereological analysis. The formation of hyaline membranes, alveolar wall edema, and fibrin exudate was seen on histological analysis of the lungs in the COVID-19 group. Stereological analysis illustrated the number of hepatocytes, volume of the sinusoid, and volume of the liver have been decreased, however the pathological changes in the heart tissue were not observed. Serum levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and angiotensin-converting enzyme significantly increased. Real-time PCR results showed that the Bcl2, Caspase3, ATG5, and LC3 decreased while the Bax increased. COVID-19 causes fibrotic changes in the lung tissue and hepatocyte mortality in the liver tissue. Besides, it elevates the level of apoptosis and autophagy markers.


Subject(s)
COVID-19 , Caspase 3/metabolism , SARS-CoV-2 , Apoptosis/genetics , Autophagosomes , Hepatocytes , Humans , Up-Regulation
2.
Stem Cell Reports ; 17(3): 522-537, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1692862

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9cOE) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9cOE. Orf9cOE significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9cOE hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.


Subject(s)
COVID-19/pathology , Coronavirus Nucleocapsid Proteins/genetics , Genome-Wide Association Study/methods , SARS-CoV-2/genetics , Action Potentials/drug effects , Adenosine Triphosphate/metabolism , Apoptosis/drug effects , Apoptosis/genetics , COVID-19/virology , Down-Regulation , Humans , Ivermectin/pharmacology , Meclizine/pharmacology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Phosphoproteins/genetics , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/metabolism , Protein Interaction Maps/genetics , RNA, Messenger/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction/genetics , Transcriptome/drug effects , Up-Regulation
3.
Front Immunol ; 12: 727861, 2021.
Article in English | MEDLINE | ID: covidwho-1477822

ABSTRACT

Inflammatory response is a host-protective mechanism against tissue injury or infections, but also has the potential to cause extensive immunopathology and tissue damage, as seen in many diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic syndrome and many other infectious diseases with public health concerns, such as Coronavirus Disease 2019 (COVID-19), if failure to resolve in a timely manner. Recent studies have uncovered a superfamily of endogenous chemical molecules that tend to resolve inflammatory responses and re-establish homeostasis without causing excessive damage to healthy cells and tissues. Among these, the monocyte chemoattractant protein-induced protein (MCPIP) family consisting of four members (MCPIP-1, -2, -3, and -4) has emerged as a group of evolutionarily conserved molecules participating in the resolution of inflammation. The focus of this review highlights the biological functions of MCPIP-1 (also known as Regnase-1), the best-studied member of this family, in the resolution of inflammatory response. As outlined in this review, MCPIP-1 acts on specific signaling pathways, in particular NFκB, to blunt production of inflammatory mediators, while also acts as an endonuclease controlling the stability of mRNA and microRNA (miRNA), leading to the resolution of inflammation, clearance of virus and dead cells, and promotion of tissue regeneration via its pleiotropic effects. Evidence from transgenic and knock-out mouse models revealed an involvement of MCPIP-1 expression in immune functions and in the physiology of the cardiovascular system, indicating that MCPIP-1 is a key endogenous molecule that governs normal resolution of acute inflammation and infection. In this review, we also discuss the current evidence underlying the roles of other members of the MCPIP family in the regulation of inflammatory processes. Further understanding of the proteins from this family will provide new insights into the identification of novel targets for both host effectors and microbial factors and will lead to new therapeutic treatments for infections and other inflammatory diseases.


Subject(s)
Gene Expression Regulation/genetics , Inflammation Mediators/metabolism , Inflammation/immunology , Ribonucleases/immunology , SARS-CoV-2/immunology , Transcription Factors/immunology , Animals , Apoptosis/genetics , COVID-19/immunology , Humans , Inflammation/pathology , Mice , NF-kappa B/metabolism , RNA Processing, Post-Transcriptional/genetics , Transcriptional Activation/immunology , Ubiquitination
5.
Sci Adv ; 7(34)2021 08.
Article in English | MEDLINE | ID: covidwho-1365115

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Apoptosis/genetics , COVID-19/genetics , Gene Expression Profiling/methods , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/metabolism , COVID-19/virology , Cells, Cultured , Chlorocebus aethiops , Female , Humans , Infant , Lung/cytology , Lung/metabolism , Lung/virology , Male , Mice, Inbred C57BL , Middle Aged , SARS-CoV-2/physiology , Severity of Illness Index , Vero Cells , Virus Internalization
SELECTION OF CITATIONS
SEARCH DETAIL