The mechanism of HMGB1 secretion and release

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(2), P. 91 - 102

Published: Feb. 1, 2022

Abstract High mobility group box 1 (HMGB1) is a nonhistone nuclear protein that has multiple functions according to its subcellular location. In the nucleus, HMGB1 DNA chaperone maintains structure and function of chromosomes. cytoplasm, can promote autophagy by binding BECN1 protein. After active secretion or passive release, extracellular usually acts as damage-associated molecular pattern (DAMP) molecule, regulating inflammation immune responses through different receptors direct uptake. The release fine-tuned variety factors, including posttranslational modification (e.g., acetylation, ADP-ribosylation, phosphorylation, methylation) machinery cell death apoptosis, pyroptosis, necroptosis, alkaliptosis, ferroptosis). this minireview, we introduce basic focus on regulatory mechanism release. Understanding these topics may help us develop new HMGB1-targeted drugs for various conditions, especially inflammatory diseases tissue damage.

Language: Английский

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Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Language: Английский

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Pyroptosis-Induced Inflammation and Tissue Damage

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 434(4), P. 167301 - 167301

Published: Oct. 13, 2021

Language: Английский

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Buformin alleviates sepsis-induced acute lung injury via inhibiting NLRP3-mediated pyroptosis through an AMPK-dependent pathway

Clinical Science, Journal Year: 2022, Volume and Issue: 136(4), P. 273 - 289

Published: Feb. 1, 2022

Abstract Background: NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated macrophage pyroptosis plays an important role in sepsis-induced acute lung injury (ALI). Inhibition of may be a way to alleviate inflammation as well tissue damage triggered after lipopolysaccharide (LPS) stimulation. The aim the present study was explore whether buformin (BF), hypoglycemic agent, could ALI by inhibiting pyroptosis. Methods: Wildtype C57BL/6 mice were randomly divided into control group, BF LPS group and LPS+BF group. pretreated with at dose 25 mg/kg, changes observed. In addition, used interfere THP-1 cells. therapeutic effect has been verified intraperitoneal injection vivo Results: Inflammation significantly reduced mice, indexes related suppressed. phosphorylation AMP-activated protein kinase (AMPK) tissues groups higher. cells, AMPK inhibitor, Compound C added demonstrate that worked via inhibit NLRP3 inflammasome. It further demonstrated up-regulated autophagy, which turn promoted inflammasome degradation. On other hand, decreased mRNA level increasing nuclear factor-erythroid 2 factor (Nrf2). And showed challenge. Conclusion: Our confirmed inhibited NLRP3-mediated up-regulating autophagy Nrf2 through AMPK-dependent pathway. This provides new strategy for clinical mitigation ALI.

Language: Английский

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Crossed Pathways for Radiation-Induced and Immunotherapy-Related Lung Injury

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 1, 2021

Radiation-induced lung injury (RILI) is a form of radiation damage to normal tissue caused by radiotherapy (RT) for thoracic cancers, which most commonly comprised pneumonitis (RP) and pulmonary fibrosis (RPF). Moreover, with the widespread utilization immunotherapies such as immune checkpoint inhibitors first- second-line treatments various incidence immunotherapy-related (IRLI), severe immune-related adverse event (irAE), has rapidly increased. To date, we know relatively little about underlying mechanisms signaling pathways these complications. A better understanding may facilitate prevention exploration potential therapeutic targets. Therefore, this review provides an overview RILI IRLI focuses on their crosstalk in diverse well possible events resulting from combined immunotherapy. Furthermore, proposes targets avenues further research based pathways. Many new studies pyroptosis have renewed appreciation value importance injury. authors posit that be common downstream pathway IRLI; discussion also conducted regarding perspectives crucial treatment.

Language: Английский

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Pyroptosis and respiratory diseases: A review of current knowledge

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 30, 2022

Pyroptosis is a relatively newly discovered programmed cell death accompanied by an inflammatory response. In the classical view, pyroptosis mediated caspases-1,-4,-5,-11 and executed GSDMD, however, recently it was demonstrated that caspase-3 and-8 also participate in process of pyroptosis, cleaving GSDMD/E GSDMD respectively. Different from autophagy apoptosis, many pores are formed on membrane during which makes lose its integrity, eventually leading to release cytokines interleukin(IL)-1β IL-18. When body infected with pathogens or exposed some stimulations, could play immune defense role. It found exists widely infectious respiratory diseases such as acute lung injury, bronchial dysplasia, chronic obstructive pulmonary disease, asthma. Excessive may accompany airway inflammation, tissue damage, induce reaction, more serious damage poor prognosis diseases. This review summarizes relationship between related

Language: Английский

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Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(11), P. 2077 - 2091

Published: Nov. 28, 2022

Abstract Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation mitochondrial citrate (citrate mt ) lipopolysaccharide (LPS)-treated AECs because downregulation Idh3α and carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition Slc25a1 induced necroptosis vitro. Mice with AEC-specific deficiency exhibited exacerbated AEC Interestingly, overexpression decreased levels rescued from Mechanistically, fission excessive mitophagy AECs. Furthermore, directly interacted FUN14 domain-containing protein 1 (FUNDC1) promoted interaction FUNDC1 dynamin-related (DRP1), leading to mitophagy-mediated thereby initiating promoting ALI. Importantly, by was inhibited FUNDC1-knockout show that novel target protection against ALI involving

Language: Английский

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Engineered Magnetic Polymer Nanoparticles Can Ameliorate Breast Cancer Treatment Inducing Pyroptosis–Starvation along with Chemotherapy

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(37), P. 42541 - 42557

Published: Sept. 12, 2022

Nanotechnology has shown a revolution in cancer treatments, including breast cancers. However, there remain some challenges and translational hurdles. Surgery, radiotherapy, chemotherapy are the primary treatment methods for cancer, although drug combinations showed promising results preclinical studies. Herein we report development of smart delivery system (DDS) to efficiently treat by pyroptosis-starvation-chemotherapeutic combination. Cancer-starvation agent glucose oxidase was chemically attached synthesized iron oxide nanoparticles which were entrapped inside poly(lactic-co-glycolic acid) along with apoptosis-associated speck-like protein containing caspase recruitment domain plasmid paclitaxel (PTX). An emulsion solvent evaporation method used prepare DDS. The surface DDS modified chitosan aptamer achieve site-specific targeting. Hence, prepared could be targeted tumor site both external magnet obtain an enhanced accumulation drugs at site. final size aptamer-decorated less than 200 nm, encapsulation efficiency PTX 76.5 ± 2.5%. Drug release from developed much higher pH 5.5 7.4, ensuring sensitivity Due efficient dual targeting DDS, vitro viability 4T1 cells reduced 12.1 1.6%, whereas nontargeted group free reduce 29.2 2.4 46.2 respectively. Our synergistic effect no severe side effects vivo. This strong potential various

Language: Английский

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Isoliquiritin apioside relieves intestinal ischemia/reperfusion-induced acute lung injury by blocking Hif-1α-mediated ferroptosis

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 108, P. 108852 - 108852

Published: May 18, 2022

Language: Английский

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Targeting immunometabolism against acute lung injury

Clinical Immunology, Journal Year: 2023, Volume and Issue: 249, P. 109289 - 109289

Published: March 12, 2023

Language: Английский

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