Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 19, 2025

Abstract Nucleic acids from both self- and non-self-sources act as vital danger signals that trigger immune responses. Critical illnesses such acute respiratory distress syndrome, sepsis, trauma ischemia lead to the aberrant cytosolic accumulation massive release of nucleic are detected by antiviral innate receptors in endosome or cytosol. Activation for deoxyribonucleic ribonucleic triggers inflammation, a major contributor morbidity mortality critically ill patients. In past decade, there has been growing recognition therapeutic potential targeting acid sensing critical care. This review summarizes current knowledge ischemia. Given extensive research on common pathological conditions like cancer, autoimmune disorders, metabolic disorders aging, we provide comprehensive summary beyond illness offer insights may inform its role conditions. Additionally, discuss strategies specifically target sensing. By examining sources, sensor activation function, well impact regulating these pathways across various diseases, highlight driving illness.

Language: Английский

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Anti-inflammatory sesquiterpenoids from Ligularia fischeriTurcz

Fitoterapia, Journal Year: 2024, Volume and Issue: 177, P. 106088 - 106088

Published: June 17, 2024

Language: Английский

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Association of IL-6-572 polymorphism with sepsis: An updated meta-analysis

Cytokine, Journal Year: 2024, Volume and Issue: 179, P. 156597 - 156597

Published: April 20, 2024

Language: Английский

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Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells

Cellular Signalling, Journal Year: 2024, Volume and Issue: 121, P. 111285 - 111285

Published: July 3, 2024

Language: Английский

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Thiostrepton Modulates TLR4 Expression and Induces Apoptosis in MDA MB 231 cells: An In Vitro and In Silico Analysis

Meandros Medical And Dental Journal, Journal Year: 2024, Volume and Issue: 25(3), P. 209 - 221

Published: Sept. 24, 2024

Objective: Toll-like receptors (TLRs) are key pattern recognition involved in tumorigenesis, apoptosis, and metastasis. Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis. Although the role of TLRs remains underexplored, recent studies suggest targeting TNBC could be beneficial. In this study Thiostrepton, an antibiotic novel inhibitor TLR7-9 psoriatic inflammation, was investigated for its effects on TLR3, TLR4, TLR9 expression cells (MDA-MB-231). Materials Methods: The cytotoxicity thiostrepton assessed using MTT assay. RT-PCR used to measure gene levels TLR9, Bax, Bcl-2, Nf-κB, E-cadherin. Cell morphology changes were analyzed Acridine Orange/Ethidium Bromide (AO/EtBr) staining. Molecular docking dynamics simulations examined interactions between TLR4-MD-2 complex. Results: Thiostrepton led concentration- time-dependent decrease cell viability. It significantly inhibited Bcl-2 increased Nf-κB levels. Bax expression, along alterations morphology, demonstrated that promoted apoptosis MDA-MB-231 cells. While reduction not significant, notably TLR3 decreased TLR4 expression. three independent molecular binds stably TLR4-MD2 domain, exhibiting high binding affinity as indicated by free energy calculations. Conclusion: effectively induces reduces viability silico analysis modulate highlighting potential candidate further research therapeutic development.

Language: Английский

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Thiostrepton: multifaceted biological activities and its applications in treatment of inflammatory diseases

Inflammopharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 2, 2024

Language: Английский

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