Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Sept. 20, 2024
Language: Английский
Citations
37
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Jan. 9, 2024
Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression organ degeneration, but the mechanism regulation of crosstalk network remain unclear. Main body abstract Cellular stress disrupts mitochondrial homeostasis, facilitates opening permeability transition pore leakage DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, subsequently induces activation onset pyroptosis. Meanwhile, inflammasome-associated protein caspase-1, Gasdermin D, CARD domain ASC potassium channel are involved in regulating pathway. Importantly, this has a cascade amplification effect that exacerbates immuno-inflammatory response, worsening pathological process autoimmune diseases. Given importance innate immunity, it is emerging new avenue explore mechanisms multiple disease pathogenesis. Therefore, efforts define strategies selectively modulate different settings have been or ongoing. In review, we will describe how mechanistic understanding driving possible therapeutics targeting network, focusing on interacting regulatory proteins, pathways, hub between inflammasomes, Short conclusion This review aims provide insight into roles pyroptosis, highlight some promising directions future research intervention.
Language: Английский
Citations
28
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Feb. 4, 2025
Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.
Language: Английский
Citations
3
Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 185, P. 106253 - 106253
Published: Aug. 2, 2023
N6-methyladenosine (m6A) plays a crucial role in ischemic stroke, whereas the of methyltransferase-like 14 (METTL14) stroke remains unknown. A model middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cells were used to simulate vivo vitro. We found that METTL14 level was upregulated microglia/macrophage after MCAO OGD/R. enhanced expression KAT3B by promoting m6A modification mRNA. STING has been identified as target for increased enhancing H3K27ac promoter. promoted M1 polarization NLRP3 inflammasome/pyroptosis axis KAT3B-STING signaling depletion relieved brain injury inhibiting M1-like rats. These findings indicate relieves MCAO-induced injury, probably via switching from towards M2 restraining microglia/macrophage.
Language: Английский
Citations
33
Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)
Published: April 27, 2024
Abstract Background Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate cellular immune suppression during process SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) plays an important role. However, function mechanism cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods Lipopolysaccharide (LPS) was combined with caerulein-induced SAP wild type, cGAS −/− sting mice . Primary macrophages were extracted via bronchoalveolar lavage peritoneal lavage. Ana-1 cells pretreated LPS stimulated nigericin sodium salt induce pyroptosis vitro. Results triggered NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated alveolar mouse model. Knockout / STING could ameliorate NLRP3 pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria induced a cGAS- dose-dependent manner. Upregulated signal promote inflammasome-mediated increase serum interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α levels thus, SAP-associated LI (SAP-ALI). Downstream molecules STING, IRF7, IRF3 connect mtDNA–cGAS–STING axis NLRP3–pyroptosis axis. Conclusions Negative regulation any molecule mtDNA–cGAS–STING–IRF7/IRF3 pathway affect inflammasomes, thereby reducing improving SAP-ALI
Language: Английский
Citations
15
Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107063 - 107063
Published: Jan. 11, 2024
Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating signaling pathways to defend the host. Recent studies have revealed additional regulatory functions STING beyond its immune-related activities, including regulation cellular metabolism, DNA repair, senescence, autophagy various cell deaths. These findings highlight broader implications in physiology role immunity. Currently, approximately 10 agonists entered clinical stage. Unlike inhibitors, which maximum inhibition limit, potential infinite amplification. complex process that requires precise ensure balanced responses prevent detrimental autoinflammation. research on structural mechanism autoinhibition negative by adaptor protein 1 (AP-1) provides valuable insights into different effects under physiological pathological conditions, offering new perspective developing drugs. Herein, we present comprehensive overview molecular mechanisms regulation, along with updated details mechanisms. We discuss these regulations diseases, emphasizing importance feasibility targeting immunity-dependent or immunity-independent STING. Moreover, current trend drug development key points research, basic translational related
Language: Английский
Citations
14
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116894 - 116894
Published: June 15, 2024
To explore the neuroprotective mechanism of artemisinin against ischemic stroke from perspective NLRP3-mediated pyroptosis.
Language: Английский
Citations
13
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 128, P. 111474 - 111474
Published: Jan. 6, 2024
Language: Английский
Citations
10
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: Nov. 30, 2024
In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.
Language: Английский
Citations
9
Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
1