Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes

The Lancet, Journal Year: 2022, Volume and Issue: 400(10358), P. 1145 - 1156

Published: Sept. 4, 2022

Language: Английский

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Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management

The Lancet, Journal Year: 2022, Volume and Issue: 400(10358), P. 1157 - 1170

Published: Sept. 4, 2022

Language: Английский

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Ribosome biogenesis in disease: new players and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 9, 2023

Abstract The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis the process generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, transformation. mTORC1, Myc, noncoding RNA signaling pathways are primary mediators work jointly with polymerases proteins to control protein synthesis. Activation of mTORC1 required for normal fetal growth development tissue regeneration after birth. Myc implicated cancer by enhancing Pol II activity, leading uncontrolled growth. deregulation RNAs such as microRNAs, long RNAs, circular involved developing blood, neurodegenerative diseases, atherosclerosis. We review similarities differences between eukaryotic bacterial molecular mechanism ribosome-targeting antibiotics resistance. also most recent findings dysfunction COVID-19 other conditions discuss consequences frameshifting, ribosome-stalling, ribosome-collision. summarize various diseases. Furthermore, we current clinical trials, prospective vaccines COVID-19, therapies targeting cancer, cardiovascular disease, aging, disease.

Language: Английский

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STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(6)

Published: June 6, 2022

Abstract Compelling evidences have revealed the emerging role of ferroptosis in pathophysiological process acute lung injury (ALI), but its modulation is not clear. Here, we identified that STAT6 acted as a critical regulator epithelium during ALI. Firstly, expression and activity were increased ALI mice models caused by crystalline silica (CS), LPS X-ray exposure. Followed confirming contribution above with ferrostatin-1 deferoxamine intervention, bioinformatic analyses was negatively correlated ferroptosis. Consistently, epithelium-specific depletion or knockdown cultured epithelial cells exacerbated While overexpression attenuated Mechanistically, SLC7A11 typical ferroptosis-related gene regulated P53. CREB-binding protein (CBP) acetyltransferase P53 acetylation, showing valuable regulation on targets’ transcription. Herein, found regulates through competitively binding CBP, which inhibits acetylation transcriptionally restores expression. Finally, pulmonary-specific decreased CS induced injury. Our findings pivotal ferroptosis, may be potential therapeutic target for treatment

Language: Английский

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Obacunone alleviates ferroptosis during lipopolysaccharide-induced acute lung injury by upregulating Nrf2-dependent antioxidant responses

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: March 19, 2022

Acute lung injury (ALI) has received considerable attention in the field of intensive care as it is associated with a high mortality rate. Obacunone (OB), widely found citrus fruits, natural bioactive compound anti-inflammatory and antioxidant activities. However, not clear whether OB protects against lipopolysaccharide (LPS)-induced ALI. Therefore, this study, we aimed to evaluate protective effects potential mechanisms LPS-induced ALI BEAS-2B cell injury.We established model mouse by treating LPS. Samples vitro were subjected death, Cell Counting Kit-8, lactate dehydrogenase (LDH) release assays. The total number cells neutrophils, protein content, levels IL-6, TNF-α, IL-1β determined bronchoalveolar lavage fluid (BALF). Glutathione, reactive oxygen species, malondialdehyde tissue. Additionally, immunohistochemical analysis, immunofluorescence, western blot, quantitative real-time PCR, enzyme-linked immunosorbent assay conducted examine OB. Furthermore, mice treated an Nrf2 inhibitor (ML385) verify its role ferroptosis. Data analyzed using one-way analysis variance or paired t-tests.Compared LPS group, effectively alleviated decreasing wet/dry weight ratio, species production, superoxide dismutase glutathione consumption vivo. In addition, significantly histopathological injury, reduced inflammatory cytokine secretion Fe2+ 4-HNE levels, upregulated GPX4, SLC7A11, expression. Mechanistically, activated inhibiting ubiquitinated proteasome degradation. ML385 reversed ALI.Overall, alleviates ALI, making novel agent

Language: Английский

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From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(2), P. 155 - 166

Published: April 30, 2024

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach required integrated biologic physiologic data identify reproducible subpopulations may respond differently treatment. This article reviews the current state of field considers how successfully transition precision medicine approach. To impact care, identification must do more than differentiate prognosis. It response treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). are now multiple examples sepsis, acute respiratory distress syndrome, kidney brain injury described using clinical, physiological, and/or biological data. Many these have demonstrated potential define differential treatment response, largely in retrospective studies, same treatment-responsive cross syndromes (treatable traits). bring about change practice, be evaluated prospective studies requiring novel adaptive trial designs. Several such underway, but there challenges tackled. Such readily identifiable applicable all critically ill populations around world. Subdividing into will require large numbers. Global collaboration investigators, clinicians, industry, patients over many years therefore ultimately realize advances seen other medical fields.

Language: Английский

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S100A9-/- alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116233 - 116233

Published: Feb. 2, 2024

Acute lung injury (ALI) is characterized by pulmonary diffusion abnormalities that may progress to multiple-organ failure in severe cases. There are limited effective treatments for ALI, which makes the search new therapeutic avenues critically important. Macrophages play a pivotal role pathogenesis of ALI. The degree macrophage polarization closely related severity and prognosis S100A9 promotes M1 macrophages. present study assessed effects S100A9-gene deficiency on acute injury. Our cohort showed plasma S100A8/A9 levels had significant diagnostic value pediatric pneumonia primarily correlated with monocyte-macrophages neutrophils. We established lipopolysaccharide (LPS)-induced mouse model demonstrated knockout gene mitigated inflammation suppressing secretion pro-inflammatory cytokines, reducing number inflammatory cells bronchoalveolar lavage fluid, inhibiting cell apoptosis, ameliorated mice. vitro vivo mechanistic studies inhibited reduced chemotactic factors cytokines TLR4/MyD88/NF-κB signaling pathway reversing expression NLRP3 pyroptosis pathway, death. In conclusion, alleviated LPS-induced via TLR4/MyD88/NFκB suggests potential strategy treatment

Language: Английский

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Towards a biological definition of ARDS: are treatable traits the solution?

Intensive Care Medicine Experimental, Journal Year: 2022, Volume and Issue: 10(1)

Published: March 11, 2022

Abstract The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation protein-rich pulmonary edema in air spaces and interstitial areas lung, variable degrees epithelial injury, endothelial barrier disruption, transmigration leukocytes, alongside impaired fluid ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range pharmacological interventions targeting these processes have failed improve patient outcomes. manuscript, our goal provide narrative summary potential methods capture underlying heterogeneity ARDS discuss how information could inform future redefinitions. We what tests available identify with any following predominant patterns: (1) and/or (2) protein rich (3) systemic or within lung inflammatory responses.

Language: Английский

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Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 9, 2023

Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) pomegranate intestinal flora metabolite anti-inflammatory, antioxidant, anti-aging properties. Ferroptosis critical factor in lipopolysaccharide (LPS)-induced acute (ALI). However, the link between UA ferroptosis unknown. The purpose of this research was to look into role regulating LPS-induced ALI. current study used LPS injure two models, one BEAS-2B cell model ALI mouse model. effectively alleviated compared group by lowering vivo wet/dry weight ratio, reactive oxygen species, malondialdehyde production, as well superoxide dismutase, catalase, glutathione depletion. Furthermore, increasing GPX4 SLC7A11 expression decreasing Fe2+ levels, histopathological damage, inflammatory cytokine secretion, levels can be significantly reduced. Keap1-Nrf2/HO-1 pathway upregulated UA, which inhibited ferroptosis. ML385 UA's protective effect against These findings suggested that could novel potential therapeutic target for

Language: Английский

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Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 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.

Language: Английский

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