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

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 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.

Язык: Английский

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Calycosin mitigates chondrocyte inflammation and apoptosis by inhibiting the PI3K/AKT and NF-κB pathways

Journal of Ethnopharmacology, Год журнала: 2022, Номер 297, С. 115536 - 115536

Опубликована: Июль 14, 2022

Язык: Английский

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Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 14, 2023

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by the damage of alveolar epithelial cells and pulmonary capillary endothelial cells. It mainly manifested non-cardiogenic edema, resulting from intrapulmonary extrapulmonary risk factors. ARDS often accompanied immune system disturbance, both locally in lungs systemically. As a common heterogeneous disease critical care medicine, researchers are faced with failure clinical trials. Latent class analysis had been used to compensate for poor outcomes found that targeted treatment after subgrouping contribute therapy. The subphenotype caused sepsis has garnered attention due its refractory nature detrimental consequences. Sepsis stands as most predominant cause ARDS, accounting approximately 32% cases. Studies indicate sepsis-induced tends be more severe than other factors, leading poorer prognosis higher mortality rate. This comprehensive review delves into immunological mechanisms sepsis-ARDS, heterogeneity existing research on treatments, aiming providing mechanism understanding exploring ideas accurate or sepsis-ARDS.

Язык: Английский

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A review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of the Astragalus memeranaceus

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Авг. 23, 2023

Astragali Radix (Huangqi) is mainly distributed in the Northern Hemisphere, South America, and Africa rarely North America Oceania. It has long been used as an ethnomedicine Russian Federation, Mongolia, Korea, Kazakhstan, China. was first recorded Shennong Ben Cao Jing includes effects of reinforcing healthy qi, dispelling pathogenic factors, promoting diuresis, reducing swelling, activating blood circulation, dredging collaterals. This review systematically summarizes botanical characteristics, phytochemistry, traditional uses, pharmacology, toxicology Astrag alus to explore potential Huangqi expand its applications. Data were obtained from databases such PubMed, CNKI, Wan Fang Data, Baidu Scholar, Google Scholar. The collected material also classic works Chinese herbal medicine, Pharmacopoeia, Medicine Dictionary, PhD Master’s theses. pharmacological isoflavone fraction have studied extensively; are reflected anti-inflammatory, anti-tumor, anti-oxidant, anti-allergic, anti-diabetic properties ability treat several related diseases. Additionally, medicinal chemical composition, activity, toxicology, quality control require further elucidation. Here, we provide a comprehensive botany, Astragalus assist future innovative research identify develop new drugs involving Huangqi.

Язык: Английский

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Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment

Pharmaceuticals, Год журнала: 2024, Номер 17(4), С. 472 - 472

Опубликована: Апрель 8, 2024

Sepsis-induced acute lung injury (ALI), characterized by widespread dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source have demonstrated therapeutic potential against sepsis-induced ALI. These small molecules may provide a promising alternative treatment option for This review aims summarize pathogenesis sepsis targets. It assembles critical updates (from 2014 2024) on ALI, detailing their sources, structures, effects, mechanisms action.

Язык: Английский

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Sterile inflammation of peritoneal membrane caused by peritoneal dialysis: focus on the communication between immune cells and peritoneal stroma

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 8, 2024

Peritoneal dialysis is a widely used method for treating kidney failure. However, over time, the peritoneal structure and function can deteriorate, leading to failure of this therapy. This deterioration primarily caused by infectious sterile inflammation. Sterile inflammation, which inflammation without infection, particularly concerning as it be subtle often goes unnoticed. The onset involves various pathological processes. cells detect signals that promote release substances attract immune from bloodstream. These contribute initiation escalation inflammatory response. existing literature extensively covers involvement different cell types in including mesothelial cells, fibroblasts, endothelial adipocytes, well such macrophages, lymphocytes, mast cells. work together occurrence progression although exact mechanisms are not fully understood. review aims provide comprehensive overview both stromal components system, reciprocal interactions between cellular components, during By understanding molecular underlying we may potentially develop therapeutic interventions counteract membrane damage restore normal function.

Язык: Английский

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High glucose dialysate-induced peritoneal fibrosis: Pathophysiology, underlying mechanisms and potential therapeutic strategies

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115246 - 115246

Опубликована: Июль 29, 2023

Peritoneal dialysis is an efficient renal replacement therapy for patients with end-stage kidney disease. However, continuous exposure of the peritoneal membrane to dialysate frequently leads fibrosis, which alters function and results in withdrawal from patients. Among others, high glucose considered as a predisposing factor fibrosis on dialysis. Glucose-induced inflammation, metabolism disturbance, activation renin-angiotensin-aldosterone system, angiogenesis noninflammation-induced reactive oxygen species are implicated pathogenesis dialysate-induced fibrosis. Specifically, causes chronic inflammation recurrent peritonitis, could cause migration polarization inflammatory cells, well release cytokines High also interferes lipid glycolysis by activating sterol-regulatory element-binding protein-2/cleavage-activating protein pathway increasing hypoxia inducible factor-1α expression, leading Activation system Ras-mitogen activated kinase signaling another contributing Ultimately, transforming growth factor-β1/Smad involved mesothelial-mesenchymal transition or epithelial-mesenchymal transition, development Although possible intervention strategies targeting have occasionally been proposed, lack laboratory evidence renders clinical decision-making difficult. We therefore aim revisit upstream pathways factor-beta1/Smad propose potential therapeutic targets glucose-induced

Язык: Английский

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HMGB1 inhibition blocks ferroptosis and oxidative stress to ameliorate sepsis‐induced acute lung injury by activating the Nrf2 pathway

The Kaohsiung Journal of Medical Sciences, Год журнала: 2024, Номер 40(8), С. 710 - 721

Опубликована: Июнь 5, 2024

Abstract The proinflammatory properties of high‐mobility group box protein 1 (HMGB1) in sepsis have been extensively studied. This study aimed to investigate the impact HMGB1 on ferroptosis and its molecular mechanism sepsis‐induced acute lung injury (ALI). A septic mouse model was established using cecal ligation puncture method. Blocking resulted improved survival rates, reduced injury, decreased levels markers (reactive oxygen species, malondialdehyde, Fe 2+ ), enhanced antioxidant enzyme activities (superoxide dismutase catalase) mice. In addition, knockdown cellular permeability, markers, raised lipopolysaccharide (LPS)‐stimulated MLE‐12 cells. Silencing led elevations expressions core‐regulators LPS‐treated cells, such as solute carrier family 7 member 11 (SLC7A11), 3 A2 (SLC3A2), glutathione peroxidase 4. Furthermore, blocking did not alter ferroptosis, oxidative stress‐related changes, permeability cells that were pretreated with ferrostatin‐1 (a inhibitor). inhibition also elevated nuclear factor erythroid 2‐related 2 (Nrf2) downstream targets, heme oxygenase‐1 (HO‐1) NAD(P)H: quinone oxidoreductase (NQO1) tissues from Nrf2‐specific inhibitor ML385 reversed effects silencing cell Our findings indicated restrains stress, thereby alleviating ALI through activation Nrf2 signaling.

Язык: Английский

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Metformin Mitigates Sepsis-Induced Acute Lung Injury and Inflammation in Young Mice by Suppressing the S100A8/A9-NLRP3-IL-1β Signaling Pathway

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 3785 - 3799

Опубликована: Июнь 1, 2024

Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among vulnerable organs incur sepsis-linked inflammatory storm frequently culminates into ARDS/ALI. metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects sepsis, but underlying mechanisms remain unclear. This study aimed to ascertain metformin's functions a young mouse model of sepsis-induced ALI.

Язык: Английский

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Protective effect and mechanism of Sufentanil on acute lung injury in septic mice

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 16, 2025

This study was designed to investigate the protective effect and mechanism of Sufentanil on acute lung injury in septic mice based network pharmacology animal experiments, provide new ideas for clinical treatment. To this end, a protein-protein interaction (PPI) common targets first constructed with Swiss Target Prediction Database, GeneCards Draw Venn Diagram Software, STRING 11.5 Cytoscape 3.10.0 Software Metascape then key were subject enrichment analysis by Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) obtain treatment pulmonary sepsis, verified experiments. A sepsis model cecal ligation puncture (CLP) study, tissues bronchoalveolar lavage fluid (BALF) taken from each group mice. The morphological changes apoptosis observed HE TUNEL staining, content inflammatory factors detected ELISA, expression proteins, such as p-JAK2 p-STAT3, Western blotting. According results pharmacology, total 40 screened out GO involved 1,483 biological processes (BPs), 84 cellular components (CCs) 125 molecular functions (MFs); KEGG identified 137 signaling pathways p < 0.05 JAK-STAT. compared control group, had severe tissue elevated relevant tissue. Compared CLP + showed reduced pathomorphologic lesions, lower level, well p-STAT3 proteins experiments consistent pharmacology. In summary, may improve inhibiting JAK2-STAT3 pathway, which provides basis research

Язык: Английский

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