PANoptosis: Mechanisms, biology, and role in disease

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

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IFN-γ promotes PANoptosis in Pasteurella multocida toxin-induced pneumonia in mice

Veterinary Microbiology, Journal Year: 2023, Volume and Issue: 285, P. 109848 - 109848

Published: Sept. 7, 2023

Language: Английский

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The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1942 - 1942

Published: Oct. 31, 2023

Zinc is a structural component of proteins, functions as catalytic co-factor in DNA synthesis and transcription hundreds enzymes, has regulatory role protein-DNA interactions zinc-finger proteins. For many years, zinc been acknowledged for its anti-oxidative anti-inflammatory functions. Furthermore, potent inhibitor caspases-3, -7, -8, modulating the caspase-controlled apoptosis necroptosis. In recent immunomodulatory sepsis COVID-19 investigated. Both are related to various regulated cell death (RCD) pathways, including Lack may have negative effect on immune functions, such oxidative burst, cytokine production, chemotaxis, degranulation, phagocytosis, RCD. While plasma concentrations decline swiftly during both COVID-19, this reduction primarily attributed redistribution process associated with inflammatory response. response, hepatic metallothionein production increases reaction release, which linked inflammation, protein effectively captures stores liver. Multiple mechanisms come into play, influencing uptake zinc, binding blood albumin red cells, well buffering modulation cytosolic levels. Decreased levels increasing severity organ dysfunction, prolonged hospital stay increased mortality septic patients. Results studies focusing these topics summarized discussed narrative review. Existing evidence currently does not support pharmacological supplementation patients or COVID-19. Complementation repletion should follow current guidelines micronutrients critically ill Further research investigating mechanism programmed caused by invasive infections therapeutic potential could be worthwhile.

Language: Английский

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PANoptosis, an indicator of COVID-19 severity and outcomes

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(3)

Published: March 27, 2024

Abstract Coronavirus disease 2019 (COVID-19) has been wreaking havoc for 3 years. PANoptosis, a distinct and physiologically relevant inflammatory programmed cell death, perpetuates cytokine storm multi-organ injuries in COVID-19. Although PANoptosis performs indispensable roles host defense, further investigation is needed to elucidate the exact processes through which modulates immunological responses prognosis This study conducted bioinformatics analysis of online single-cell RNA sequence (scRNA-seq) bulk RNA-seq datasets explore potential as an indicator COVID-19 severity. The degree bronchoalveolar lavage fluid (BALF) peripheral blood mononuclear cells (PBMC) indicated severity Single-cell transcriptomics identified pro-inflammatory monocytes one primary sites subsequently demonstrated immune metabolic characteristics this group monocytes. In addition, illustrated that dexamethasone was likely alleviate inflammation by mitigating PANoptosis. Finally, showed PANoptosis-related genes could predict intensive care unit admission (ICU) outcomes patients who are hospitalized.

Language: Английский

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TNF/IFN-γ Co-Signaling Induces Differential Cellular Activation in COVID-19 Patients: Implications for Patient Outcomes

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1139 - 1139

Published: Jan. 28, 2025

TNF and IFN-γ are key proinflammatory cytokines implicated in the pathophysiology of COVID-19. Toll-like receptor (TLR)7 TLR8 known to recognize SARS-CoV-2 induce production. However, it is unclear whether levels altered through TLR-dependent pathways these mediate disease severity during This study aimed investigate association between TNF/IFN-γ immune cell activation understand their role better. We enrolled 150 COVID-19 patients, who were classified by systemic (high (H) or normal–low (N-L)) as TNFHIFNγH, TNFHIFNγN-L, TNFN-LIFNγH, TNFN-LIFNγN-L. Compared patients with TNFN-LIFNγN-L, TNFHIFNγH had high pro- anti-inflammatory cytotoxic molecules, T cells monocytes expressed 1 (TNFR1). Patients presented SNP rs3853839 TLR7 increased MYD88, NFκB, IRF7 (TLR signaling), FADD, TRADD (TNFR1 signaling). Moreover, critical observed four groups, but TNFHIFNγN-L most required invasive mechanical ventilation. concluded that associated hyperactive cells, whereas normal/low hypoactivity, suggesting a model explain may be mediated different depending on levels. These findings highlight potential for exploring modulation therapeutic strategy severe

Language: Английский

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OPG and BAFF as predictive biomarkers of the severity of SARS‐CoV‐2 infection

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(3)

Published: Jan. 31, 2025

Abstract Molecules of the tumour necrosis factor superfamily (TNFSF) are key players in immune regulation; an increase some TNFSF molecules has been reported during severe COVID‐19. In this study, we profiled and evaluated members serum COVID‐19 vaccine‐naïve patients to identify potential biomarkers associated with disease severity. Our data show that TRAIL levels lower severely affected than those mildly by (AUC 0.8, p = 0.0003). On contrary, OPG BAFF higher compared mild cases 0.0001; AUC 0.7, 0.0012; respectively) moderate (OPG < 0.01), ( 0.05). At transcriptional level, TRAIL, elevated cases, also patients. Additionally, found APRIL, LIGHT, CD30L CD40L protein‐levels healthy donors but not significantly different between various clinical statuses. Finally, TNF‐α, TNF‐β, RANKL TWEAK protein were work identifies as therapeutic targets for preventing Due opposite contradictory (protein/transcriptional level), its role should be elucidated clarified more in‐depth studies.

Language: Английский

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PANoptosis: a potential target of atherosclerotic cardiovascular disease

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

Published: April 26, 2025

PANoptosis is a newly discovered cell death pathway triggered by the innate immunizer, which in turn promotes assembly of PANoptosome and activates downstream effectors. As special mode, it characterized apoptosis, pyroptosis, necroptosis at same time; therefore, not feasible to inhibit suppressing single pathway. However, active ingredients targeting can effectively PANoptosis.Given importance disease, would be an important therapeutic tool. Previous studies have focused more on infectious diseases cancer, role cardiovascular field has been comprehensively addressed. While ASCVD number one killer diseases, explore new targets determine future research directions. Therefore, this review focuses PANoptosome, molecular mechanism PANoptosis, related mechanisms leading such as myocardial infarction, ischemic cardiomyopathy stroke, order provide perspective for prevention treatment ASCVD.

Language: Английский

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IRF1 Mediates Growth Arrest and the Induction of a Secretory Phenotype in Alveolar Epithelial Cells in Response to Inflammatory Cytokines IFNγ/TNFα

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3463 - 3463

Published: March 19, 2024

In COVID-19, cytokine release syndrome can cause severe lung tissue damage leading to acute respiratory distress (ARDS). Here, we address the effects of IFNγ, TNFα, IL-1β and IL-6 on growth arrest alveolar A549 cells, focusing role IFN regulatory factor 1 (IRF1) transcription factor. The efficacy JAK1/2 inhibitor baricitinib has also been tested. WT IRF1 KO cells were exposed cytokines for up 72 h. Cell proliferation death evaluated with resazurin assay, analysis cell cycle cycle-regulator proteins, LDH Annexin-V positivity; induction senescence senescence-associated secretory phenotype (SASP) was through β-galactosidase staining quantitation secreted inflammatory mediators. While IL-1 proved ineffective, IFNγ plus TNFα caused a proliferative in alterations morphology, along acquisition phenotype. These STAT IRF1-dependent since they prevented by much less evident than cells. STATs/IRF1 axis is required cytokine-induced Hence, baricitininb promising therapeutic strategy attenuation inflammation.

Language: Английский

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The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9635 - 9635

Published: Sept. 5, 2024

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors discovered. Their functioning provide an explanation for some the events observed COVID-19 cannot be directly explained by model which ACE2 constitutes central point infection. Diabetes mellitus type (T2D) can induce development. Although mechanisms associated with lead increased SARS-CoV-2 virulence diabetes, such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster differentiation 4 (CD4), transferrin (TfR), integrins α5β1/αvβ3, or co-receptors neuropilin (NRP2), vimentin, and even syalilated gangliosides also responsible worsening course. On hand, others play protective roles. Understanding how diabetes-associated via modification needs further extensive studies.

Language: Английский

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Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy

Cell Proliferation, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

ABSTRACT Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, has become one of most common diseases worldwide. In OA various forms cell death have been identified, including apoptosis, necroptosis autophagic death. Ever‐growing observations indicate that ferroptosis, newly‐discovered iron‐dependent form regulated death, detrimental occurrence progression. this review, we first analyse pathogenetic mechanisms which iron overload, inflammatory response mechanical stress contribute ferroptosis. We then discuss how ferroptosis exacerbates progression, focusing on its impact chondrocyte viability, synoviocyte populations extracellular matrix integrity. Finally, highlight several potential therapeutic strategies targeting could be explored for treatment OA.

Language: Английский

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