HMGB1

high mobility group box 1

Gene Context Sentence


Table 2. Analysis of context sentence of HMGB1 gene in 14 abstracts.

PMID Gene Context Sentence
32380958 The endogenous damage-associated molecular pattern (DAMP) molecule HMGB1 initiates inflammation via two separate pathways. […] Disulfide-HMGB1 triggers TLR4 receptors generating pro-inflammatory cytokine release. […] Extracellular HMGB1, released from dying cells or secreted by activated innate immunity cells, forms complexes with extracellular DNA, RNA and other DAMP or pathogen-associated molecular (DAMP) molecules released after lytic cell death. […] These complexes are endocytosed via RAGE, constitutively expressed at high levels in the lungs only, and transported to the endolysosomal system, which is disrupted by HMGB1 at high concentrations. […] It is conceivable that extracellular SARS-CoV-2 RNA may reach the cellular cytosol via HMGB1-assisted transfer combined with lysosome leakage. […] Extracellular HMGB1 generally exists in vivo bound to other molecules, including PAMPs and DAMPs. […] It is plausible that these complexes are specifically removed in the lungs revealed by a 40% reduction of HMGB1 plasma levels in arterial versus venous blood. […] Abundant pulmonary RAGE expression enables endocytosis of danger molecules to be destroyed in the lysosomes at physiological HMGB1 levels, but causing detrimental inflammasome activation at high levels. […] Based on these observations we propose extracellular HMGB1 to be considered as a therapeutic target for COVID-19.
32592716 At the intracellular and circulating levels, GLR can trap the high mobility group box 1 protein and thus blocks the alarmin functions of HMGB1.
32600316 The ubiquiotous nuclear protein HMGB1 is extracellularly released by dying cells or activated innate immunity cells to promote inflammation. […] Extracellular HMGB1 plays a prominent role in the pathogenesis of acute lung injury of infectious as well as sterile origin including hyperoxia. […] Excessive amounts of systemic HMGB1 and HMGB1-partner molecule complexes can be retained in the pulmonary circulation indicated by a substantial reduction of HMGB1 plasma levels in arterial versus venous blood. […] The cholinergic antiinflammatory mechanism ameliorates pulmonary inflammation by inhibiting HMGB1 release and HMGB1 receptor expression. […] This comprehension was recently reinforced by results reported in Molecular Medicine by Sitapara and coworkers demonstrating that administration of an α7 nicotinic acetylcholine receptor agonist attenuated hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation.
32629817 The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). […] This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. […] They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells.
32723229 Since the high mobility group box-1 (HMGB1) molecule had been recognized as a pro-inflammatory cytokine, which mediates endotoxin lethality of mice; there have been lots of papers about targeting the HMGB1 within the contexts of infection, inflammation, and cancer. […] The pathogenic impact of HMGB1 to the severe acute respiratory syndrome (SARS) and disease management with herbal formulations targeting this unique protein have already been proposed. […] However, the failure of the numerous current anti-viral therapies on the ongoing viral infections casts reappraisal of the possible interrelationships regarding the HMGB1 and SARS-CoV-2. […] In this paper, we focused on the potential usage of external and/or inhalation preparation of antiviral/antibacterial herbal products capable of targeting HMGB1 for the clinical management candidates of the ongoing COVID-19 infection.
32724296 Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). […] The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection.
32739471 The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.
33086122 The pharmacological activities essentially derive from the capacity of DMC to interact with the protein targets HMGB1 and AMPK. […] Upon binding to HMGB1, DMC inhibits the nucleocytoplasmic transfer of the protein and its extracellular secretion, thereby blocking its alarmin function. […] AMPK activation by DMC reinforces inhibition of HMGB1, to further reduce the release of the alarmin protein, likely contributing to the anticancer effects. […] The characterization of a tight control of DMC over the AMPK-HMGB1 axis not only helps to explain the known activities of DMC but also suggests opportunities to use this chalcone to treat other pathological conditions such as the acute respiratory distress syndrome (which affects patients with COVID-19).
33108622 Analysis of additional endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble-RAGE, D-dimer), will be performed to further define the effect of DSTAT in patients with COVID-19 infection.
33126860 Previously, we have shown that the exposure of mice to hyperoxia induces the release of the nuclear protein high mobility group box-1 (HMGB1) into the pulmonary airways. […] Furthermore, extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). […] The aim of this study was to determine whether GTS-21 (3-(2,4-dimethoxybenzylidene) anabaseine), an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could (1) inhibit hyperoxia-induced HMGB1 release into the airways; (2) enhance macrophage phagocytosis and (3) increase bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. ) and subsequently challenged with PA. . […] In addition, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from RAW 264.7 cells and attenuated hyperoxia-induced NF-κB activation in macrophages and mouse lungs exposed to hyperoxia and infected with PA. […] Our results indicate that GTS-21 is efficacious in improving bacterial clearance and reducing acute lung injury via enhancing macrophage function by inhibiting the release of nuclear HMGB1.
33147444 We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. […] We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63.
33236418 High-mobility group box 1 (HMGB1) is a nuclear protein involved in DNA replication, transcription, recombination, and repair. […] In the extracellular space, the HMGB1 plays an essential role in the onset and perpetuation of inflammation, belonging to the group of damage-associated molecular pattern (DAMP) molecules, also called alarmins. […] For this, HMGB1 has been studied in several acute and chronic inflammatory diseases as an early biomarker of inflammation. […] An increased concentration of HMGB1 has been detected in serum, as the expression of systemic inflammation, and in specific samples (such as stool, synovial fluid, nasal lavage fluid, sputum, and cerebrospinal fluid), as the expression of local production, in several infectious and/or inflammatory diseases.
33313438 Here, we report that high mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) and a central mediator of lethal inflammation, could be a potential target for innovative therapeutic strategies for COVID-19. […] Serum HMGB1 in severe COVID-19 patients is elevated (189.40 ± 140.88 ng/ml). […] Exogenous HMGB1 induces the expression of SARS-CoV-2 entry receptor ACE2 in alveolar epithelial cells in an AGER-dependent manner. […] Importantly, genetic (using AGER siRNA) or pharmacological (using glycyrrhizin, chloroquine, hydroxychloroquine, and FPS-ZM1) inhibition of the HMGB1-AGER pathway blocks ACE2 expression. […] Thus, HMGB1 inhibitors are likewise promising drug candidates for the treatment of patients suffering from COVID-19.
33583045 Furthermore, IL1β, IL6, TNF, JUN, and STAT were mapped to ten pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL1, and IL6 signaling pathways.