Innate immune evasion strategies of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 11, 2023

Language: Английский

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Ferulic Acid: A Review of Pharmacology, Toxicology, and Therapeutic Effects on Pulmonary Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8011 - 8011

Published: April 28, 2023

Ferulic acid (FA), a prevalent dietary phytochemical, has many pharmacological effects, including anti-oxidation and anti-inflammation been widely used in the pharmaceutical, food, cosmetics industries. Many studies have shown that FA can significantly downregulate expression of reactive oxygen species activate nuclear factor erythroid-2-related factor-2/heme oxygenase-1 signaling, exerting anti-oxidative effects. The anti-inflammatory effect is mainly related to p38 mitogen-activated protein kinase factor-kappaB signaling pathways. demonstrated potential clinical applications treatment pulmonary diseases. transforming growth factor-β1/small mothers against decapentaplegic 3 pathway be blocked by FA, thereby alleviating fibrosis. Moreover, context asthma, T helper cell 1/2 imbalance restored FA. Furthermore, ameliorates acute lung injury inhibiting pathways via toll-like receptor 4, consequently decreasing downstream inflammatory mediators. Additionally, there moderate neuraminidase inhibitory activity showing tendency reduce interleukin-8 level response influenza virus infections. Although application broad prospects, more preclinical mechanism-based research should carried out test these settings. This review not only covers literature on effects mechanisms but also discusses therapeutic role toxicology several

Language: Английский

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Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 2, 2023

Abstract The incorporation of machine learning methods into proteomics workflows improves the identification disease-relevant biomarkers and biological pathways. However, models, such as deep neural networks, typically suffer from lack interpretability. Here, we present a approach to combine pathway analysis biomarker increase interpretability experiments. Our integrates priori knowledge relationships between proteins pathways processes sparse networks create biologically informed networks. We employ these differentiate clinical subphenotypes septic acute kidney injury COVID-19, well respiratory distress syndrome different aetiologies. To gain insight complex syndromes, utilize feature attribution-methods introspect for important distinguishing subtypes. algorithms are implemented in freely available open source Python-package ( https://github.com/InfectionMedicineProteomics/BINN ).

Language: Английский

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Necroptosis does not drive disease pathogenesis in a mouse infective model of SARS-CoV-2 in vivo

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 30, 2024

Abstract Necroptosis, a type of lytic cell death executed by the pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) has been implicated in detrimental inflammation caused SARS-CoV-2 infection. We minimally and extensively passaged single clinical isolate to create models mild severe disease mice allowing us dissect role necroptosis pathogenesis. infected wild-type MLKL-deficient found no significant differences viral loads or lung pathology. In our model COVID-19, MLKL-deficiency did not alter host response, ameliorate weight loss, diminish systemic pro-inflammatory cytokines levels, prevent lethality aged animals. Our vivo indicate that is dispensable pathogenesis COVID-19.

Language: Английский

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PathIntegrate: Multivariate modelling approaches for pathway-based multi-omics data integration

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(3), P. e1011814 - e1011814

Published: March 25, 2024

As terabytes of multi-omics data are being generated, there is an ever-increasing need for methods facilitating the integration and interpretation such data. Current typically output lists, clusters, or subnetworks molecules related to outcome. Even with expert domain knowledge, discerning biological processes involved a time-consuming activity. Here we propose PathIntegrate, method integrating datasets based on pathways, designed exploit knowledge systems thus provide interpretable models studies. PathIntegrate employs single-sample pathway analysis transform from molecular pathway-level, applies predictive single-view multi-view model integrate Model outputs include pathways ranked by their contribution outcome prediction, each omics layer, importance molecule in pathway. Using semi-synthetic demonstrate benefit grouping into detect signals low signal-to-noise scenarios, as well ability precisely identify important at effect sizes. Finally, using COPD COVID-19 showcase how enables convenient complex high-dimensional datasets. available open-source Python package.

Language: Английский

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Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(5), P. 104668 - 104668

Published: April 1, 2023

Language: Английский

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Delta (B1.617.2) variant of SARS-CoV-2 induces severe neurotropic patterns in K18-hACE2 mice

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

Published: Feb. 27, 2023

A highly contagious virus, severe acute respiratory syndrome coronavirus 2, caused the disease 19 (COVID-19) pandemic (SARS-CoV-2). SARS-CoV-2 genetic variants have been reported to circulate throughout COVID-19 pandemic. symptoms include symptoms, fever, muscle pain, and breathing difficulty. In addition, up 30% of patients experience neurological complications such as headaches, nausea, stroke, anosmia. However, neurotropism infection remains largely unknown. This study investigated neurotropic patterns between B1.617.2 (Delta) Hu-1 (Wuhan, early strain) in K18-hACE2 mice. Despite both inducing similar pathogenic various organs, B1.617.2-infected mice demonstrated a higher range phenotypes weight loss, lethality, conjunctivitis when compared those Hu-1-infected histopathological analysis revealed that infects brain more rapidly effectively than Hu-1. Finally, we discovered that, mice, activation signature genes involved innate cytokines necrosis-related response was most pronounced The present findings indicate neuroinvasive properties link them fatal neuro-dissemination during onset.

Language: Английский

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Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines

Genome Medicine, Journal Year: 2022, Volume and Issue: 14(1)

Published: Nov. 29, 2022

COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe critical. Severe critical patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about epigenetic alterations that occur these cells during hyperinflammatory responses patients. In this study, we obtained DNA methylome transcriptome peripheral blood monocytes samples extracted CD14 + CD15- 48 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. parallel, single-cell transcriptomics 10 generated. CellPhoneDB was used infer crosstalk between other immune cell types. We observed methylation CpG sites associated interferon-related genes antigen presentation, concordant gene expression changes. These significantly overlapped those occurring bacterial sepsis, although specific viral infection also identified. found comprise some differentiation under influence inflammatory cytokines. A progression relation Sequential Organ Failure Assessment (SOFA) score be related T-helper 1 cytokine production. analysis transcriptomes types suggested existence altered like NK regulatory T cells. Our findings show occurrence an transcriptional reprogramming monocytes, which could release aberrant immature increased systemic levels pro-inflammatory cytokines,

Language: Английский

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TNFAIP3‐interacting protein 1 (ABIN‐1) negatively regulates caspase‐8/FADD‐dependent pyroptosis

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

TNFAIP3‐interacting protein 1 (TNIP1; also known as ABIN‐1) is a ubiquitin‐binding that suppresses death‐receptor‐ or Toll‐like receptor‐mediated apoptosis and necroptosis; however, it remains unclear whether ABIN‐1 capable of regulating pyroptosis. In the present study, we found that, in mouse embryonic fibroblasts macrophages, deficiency sensitized cells to poly(I:C) + TAK1 inhibitor 5Z‐7‐oxozeaenol‐induced pyroptosis besides necroptosis. The sensitizing effect on depended caspase‐8 its adaptor molecule FAS‐associated death domain protein. model polymicrobial sepsis, myeloid‐specific deletion Abin‐1 rendered mice more sensitive pyroptosis, necroptosis, exacerbated disease severity. Interestingly, triggered gasdermin‐E‐mediated fibroblasts, but induced gasdermin‐D‐mediated both caspase‐8‐dependent manner. Furthermore, demonstrated upon 5Z‐7‐oxozeaenol stimulation, facilitates recruitment caspase‐8; thus, mechanism by which downregulates activity conserved tumor necrosis factor receptor type 3 signaling‐induced cell death. Together, our work identifies previously unrecognized role for negative regulator addition suggesting represents promising halt reverse progression refractory inflammatory disorders whose pathogenesis involves multiple forms programmed

Language: Английский

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The Interplay Between Viral Infection and Cell Death: A Ping‐Pong Effect

Advances in Virology, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Programmed cell death (PCD) is a well‐studied cellular mechanism that plays critical role in immune responses, developmental processes, and the maintenance of tissue homeostasis. However, viruses have developed diverse strategies to bypass or manipulate host apoptotic machinery enhance their replication survival. As result, interaction between PCD pathways has garnered increased interest, leading many studies being published recent years. This study aims provide an overview current understanding significance viral infections. We will discuss various forms pathways, including apoptosis, autophagy, necroptosis, pyroptosis, as well corresponding molecular mechanisms. In addition, we show how prevent delay facilitate replication. emphasizes importance investigating mechanisms by which control host’s gain insight into evolutionary dynamics host‐pathogen interactions develop new approaches for predicting managing threats. Overall, aimed highlight research areas viruses, introduction targets development antiviral drugs modulate novel inhibitors pathways.

Language: Английский

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