Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 765 - 765

Published: July 1, 2021

Host pattern recognition receptors (PRRs) sense pathogen-associated molecular patterns (PAMPs), which are signatures shared by different pathogens. Recognition of PAMPs PRRs initiate innate immune responses via diverse signaling pathways. Over recent decades, advances in our knowledge sensing have enhanced understanding the host response to poxviruses. Multiple PRR families been implicated poxvirus detection, mediating initiation cascades, activation transcription factors, and, ultimately, expression antiviral effectors. To counteract defense, poxviruses evolved a variety immunomodulators that strategies disrupt or circumvent triggered PRRs. These interactions influence outcomes infections. This review focuses on current roles poxviruses, their elicited effector functions, and how poxviral antagonize PRR-mediated responses.

Language: Английский

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Proposed Mechanisms of Targeting COVID-19 by Delivering Mesenchymal Stem Cells and Their Exosomes to Damaged Organs

Stem Cell Reviews and Reports, Journal Year: 2021, Volume and Issue: 17(1), P. 176 - 192

Published: Jan. 11, 2021

With the outbreak of coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome 2 (SARS-CoV-2), world has been facing an unprecedented challenge. Considering lack appropriate therapy for COVID-19, it is crucial to develop effective treatments instead supportive approaches. Mesenchymal stem cells (MSCs) as multipotent stromal have shown possess treating potency through inhibiting or modulating pathological events in COVID-19. MSCs and their exosomes participate immunomodulation controlling cell-mediated immunity cytokine release. Furthermore, they repair renin-angiotensin-aldosterone system (RAAS) malfunction, increase alveolar fluid clearance, reduce chance hypercoagulation. Besides lung, which primary target SARS-CoV-2, heart, kidney, nervous system, gastrointestinal tract are also affected Thus, efficacy targeting these organs via different delivery routes should be evaluated ensure safe administration This review focuses on proposed therapeutic mechanisms damaged organs. It discusses possible application primed genetically modified a promising drug Moreover, recent advances clinical trials MSCs-derived one approaches COVID-19 reviewed.

Language: Английский

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Cytokines on the way to secretion

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 79, P. 52 - 65

Published: Aug. 25, 2024

The activation of immune cells by pro-inflammatory or immunosuppressive stimuli is followed the secretion immunoregulatory cytokines which serve as messengers to activate response in target cells. Although mechanisms that control are not yet fully understood, several key aspects this process have recently emerged. This review focuses on cytokine release via exocytosis and highlights routes trafficking leading constitutive regulated well impact sorting receptors process. We discuss involvement cytoskeletal rearrangements vesicular transport, secretion, formation immunological synapses. Finally, we describe non-classical pathways independent ER-Golgi transport. Instead, these based processing inflammasome autophagic mechanisms. Ultimately, understanding molecular behind may help identify potential therapeutic targets diseases associated with altered responses.

Language: Английский

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Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: May 5, 2021

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) showed promising clinical efficacy toward COVID-19 (Coronavirus disease 2019) patients as potent painkillers and agents. However, the prospective anti-COVID-19 mechanisms of NSAIDs are not evidently exposed. Therefore, we intended to decipher most influential candidate(s) its novel mechanism(s) against by network pharmacology. FDA (U.S. Food & Drug Administration) approved (19 active one prodrug) were used for this study. Target proteins related selected target identified Similarity Ensemble Approach, Swiss Prediction, PubChem databases, respectively. Venn diagram overlapping between proteins. The interactive networking was analyzed STRING. RStudio plotted bubble chart KEGG (Kyoto Encyclopedia Genes Genomes) pathway enrichment analysis Finally, binding affinity determined through molecular docking test (MDT). Geneset exhibited 26 signaling pathways COVID-19. Inhibition proinflammatory stimuli tissues and/or cells inactivating RAS key mechanism NSAIDs. Besides, MAPK8, MAPK10, BAD explored associated RAS. Among twenty NSAIDs, 6MNA, Rofecoxib, Indomethacin revealed with highest score three proteins, Overall, our proposed (6MNA, Indomethacin) might block thus may alleviate excessive inflammation induced SARS-CoV-2.

Language: Английский

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Therapeutic Targeting of Inflammation and Virus Simultaneously Ameliorates Influenza Pneumonia and Protects from Morbidity and Mortality

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 318 - 318

Published: Jan. 23, 2023

Influenza pneumonia is a severe complication caused by inflammation of the lungs following infection with seasonal and pandemic strains influenza A virus (IAV), that can result in lung pathology, respiratory failure, death. There currently no treatment for disease IAV. Antivirals are available but only effective if initiated within 48 h onset symptoms. complications mortality often associated high viral load an excessive inflammatory cytokine response. Therefore, we simultaneously targeted inflammation. We used antiviral oseltamivir anti-inflammatory drug etanercept to dampen TNF signaling after clinical signs treat mouse model IAV infection. The combined down-regulated cytokines TNF, IL-1β, IL-6, IL-12p40, chemokines CCL2, CCL5, CXCL10. Consequently, signal transducer activator transcription 3 (STAT3) inhibitor effectively reduced pathology. Combined using or STAT3 dampened overlapping set cytokines. Thus, therapy targeting specific pathway provide strategy ameliorating pneumonia. This approach might apply treating acute syndrome coronavirus 2 (SARS-CoV-2).

Language: Английский

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Targeting tumour necrosis factor to ameliorate viral pneumonia

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(4), P. 883 - 900

Published: Feb. 24, 2021

Pneumonia is a serious complication associated with inflammation of the lungs due to infection viral pathogens. Seasonal and pandemic influenza viruses, variola virus (agent smallpox) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; agent COVID-19) are some leading examples. Viral pneumonia triggered by excessive dysregulated cytokine production, termed 'cytokine storm'. Several cytokines have been implicated but tumour necrosis factor (TNF) plays critical role in driving lung inflammation, pathology death. Despite this, exact TNF aetiology pathogenesis infection-induced complications not well understood. In this review, we discuss pathological immunomodulatory roles contributing immunopathology resolution respectively, mouse models influenza- smallpox (mousepox)-induced pneumonia. We review studies that investigated dampening on outcome orthopoxvirus infections. Most model evaluated efficacy treatment anti-inflammatory drugs, including anti-TNF agents, animal day infection. question merits those as they transferable clinic given individuals generally present at hospital only after onset disease symptoms propose research should be directed determining whether will reduce morbidity mortality. Such strategy more relevant clinically.

Language: Английский

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Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy

Acta Pharmacologica Sinica, Journal Year: 2021, Volume and Issue: 43(3), P. 659 - 671

Published: June 8, 2021

Language: Английский

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Expression of Concern: The pathophysiological and immunological background of the monkeypox virus infection: An update

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Oct. 11, 2022

Abstract In addition to the COVID‐19 waves, globe is facing global monkeypox (MPX) outbreak. MPX an uncommon zoonotic infection characterized by symptoms similar smallpox. It caused virus (MPXV), a double‐stranded DNA that belongs genus Orthopoxvirus (OPXV). MPXV, which causes human disease, has been confined Africa for many years, with only few isolated cases in other areas. Outside of Africa, continuing MPXV outbreak multiple countries 2022 greatest recorded history. The current outbreak, over 10 000 confirmed 50 between May and July 2022, demonstrates may travel rapidly among humans pose danger health worldwide. rapid spread such outbreaks recent times elevated status rising disease significant epidemic potential. While not as deadly or contagious variola smallpox, it poses threat because could evolve into more potent pathogen. This review assesses potential population provides brief overview what currently known about this reemerging virus. By analyzing biological effects on health, its shifting epidemiological footprint, available therapeutic options, presented most insights biology study also clarifies key be blame present draw attention major research questions promising new avenues combating epidemic.

Language: Английский

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Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(8)

Published: Feb. 17, 2022

Significance Antivirals are ineffective in treating viral pneumonia if administered after 48 h post onset of disease symptoms. Lung pathology during respiratory infections is triggered by the host inflammatory response and tissue damage caused replicating virus. Therefore, targeting both virus inflammation would be more effective pneumonia. Simultaneous treatment with an anti-inflammatory drug TNF or STAT3 combined antiviral significantly improved clinical disease, reduced lung load protected mice from severe ectromelia infection. The suppressed multiple proinflammatory cytokines cytokine-signaling pathways, including NF-κB STAT3. Late symptoms, alone cannot ameliorate pneumonia, as it reduce effectively.

Language: Английский

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Markers of the ageing macrophage: a systematic review and meta-analysis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 13, 2023

Introduction Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations, a plethora of data exist the power scientific conclusions can vary substantially. This meta-analysis by information content (MAIC) systematic literature review (SLR) aims determine overall changes in macrophage gene protein expression, well function, with age. Methods PubMed was utilized collate peer-reviewed relating ageing. Primary studies comparing at least two age groups were included. Data pertaining or expression alongside method used extracted for MAIC analysis. For SLR analysis, included all macrophage-specific age, species, ontogeny assessed. Results A total 240 included; 122 which qualified MAIC. The majority papers focussed on count/infiltration function followed expression. found iNOS TNF be most commonly investigated entities, 328 genes 175 proteins showing consistent dysregulation across literature. Overall findings indicate cytokine secretion phagocytosis are reduced reactive oxygen production increased ageing macrophage. Discussion Collectively, our analysis identifies critical consistently dysregulated, highlighting targets further investigation. Consistent here confirm an phenotype specific experimental models.

Language: Английский

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