Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: a multicenter retrospective cohort study DOI Creative Commons
Yuting Li, Jianjun Zhao,

Jiahui Wei

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 19, 2025

Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat improvement oxygenation among syndrome (ARDS) induced by COVID-19. A large multicentre cohort study ARDS COVID-19 who had been admitted to intensive care units (ICUs). used propensity score matching compare outcomes treated those were not. The differences continuous assessed Wilcoxon signed-rank test. Kaplan–Meier method was show 28-day survival curves matched cohorts. log-rank P-test stratified on pairs test equality estimated curves. Cox proportional hazards model incorporated a robust sandwich-type variance estimator account for nature data estimate hazard ratios (HR). All statistical analyses performed SPSS 26.0 R 4.2.3. two-sided p-value < 0.05 considered statistically significant. total 387 met inclusion criteria, including 259 (66.9%) sivelestat. In 158 treatment, associated improved oxygenation, decreased Murray lung injury score, increased non-mechanical ventilation time within 28 days, alive ICU-free days (HR, 1.85; 95% CI 1.29 2.64; p 0.001), shortened ICU stay ultimately 2.78; 1.32 5.88; = 0.0074). Among induce COVID-19, administration is clinical outcomes.

Language: Английский

Neutrophil extracellular traps in homeostasis and disease DOI Creative Commons

Han Wang,

Susan J. Kim,

Lei Yu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

Citations

29
SARS-CoV-2 immunity in animal models DOI Creative Commons
Chen Zhao,

Yaochang Yuan,

Qing‐Tao Hu

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(2), P. 119 - 133

Published: Jan. 18, 2024

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in illness and can lead significant complications affected individuals. These encompass symptoms such as coughing, distress, fever, infectious shock, distress (ARDS), even multiple-organ failure. Animal models serve crucial tools for investigating pathogenic mechanisms, immune responses, escape antiviral drug development, vaccines against SARS-CoV-2. Currently, various animal infection, nonhuman primates (NHPs), ferrets, hamsters, many different mouse models, have been developed. Each model possesses distinctive features applications. In this review, we elucidate the response elicited patients provide an overview of characteristics mainly used well corresponding responses applications these models. A comparative analysis transcriptomic alterations lungs from revealed that K18-hACE2 mouse-adapted virus exhibited highest similarity with deceased patients. Finally, highlighted current gaps related research between studies clinical investigations, underscoring lingering scientific questions demand further clarification.

Language: Английский

Citations

18
TLRs: Innate Immune Sentries against SARS-CoV-2 Infection DOI Open Access
Stefania Mantovani, Barbara Oliviero, Stefania Varchetta

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8065 - 8065

Published: April 29, 2023

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been responsible for a devastating pandemic since March 2020. Toll-like receptors (TLRs), crucial components in the initiation of innate immune responses to different pathogens, trigger downstream production pro-inflammatory cytokines, interferons, and other mediators. It demonstrated that they contribute dysregulated response observed patients with COVID-19. TLR2, TLR3, TLR4 TLR7 have associated COVID-19 severity. Here, we review role TLRs etiology pathogenesis COVID-19, including TLR3 rare variants, L412F polymorphism negatively regulates anti-SARS-CoV-2 responses, TLR3-related cellular senescence, interaction TLR2 SARS-CoV-2 proteins implication NET formation SARS-CoV-2. The activation contributes viral clearance resolution. However, may represent double-edged sword which elicit signaling, leading proinflammatory mediators, resulting disease. TLR-dependent excessive inflammation antiviral tip balance towards former or latter, altering equilibrium drives severity

Language: Английский

Citations

34
Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease DOI Creative Commons
Janis K. Shute

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(4), P. 584 - 584

Published: April 13, 2023

Unfractionated heparin has multiple pharmacological activities beyond anticoagulation. These anti-inflammatory, anti-microbial, and mucoactive are shared in part by low molecular weight non-anticoagulant derivatives. Anti-inflammatory include inhibition of chemokine activity cytokine synthesis, inhibitory effects on the mechanisms adhesion diapedesis involved neutrophil recruitment, heparanase activity, proteases coagulation complement cascades, elastase neutralisation toxic basic histones, HMGB1 activity. This review considers potential for its derivatives to treat inflammatory lung disease, including COVID-19, ALI, ARDS, cystic fibrosis, asthma, COPD via inhaled route.

Language: Английский

Citations

27
Genetically Engineered Cellular Nanovesicle as Targeted DNase I Delivery System for the Clearance of Neutrophil Extracellular Traps in Acute Lung Injury DOI Creative Commons
Yang Du, Yining Chen, Fangyuan Li

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(32)

Published: Sept. 27, 2023

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are prevalent critical illnesses with a high mortality rate among patients in intensive care units. Neutrophil extracellular traps (NETs) implicated the pathogenesis of ALI/ARDS and represent promising therapeutic target. However, clinical application deoxyribonuclease I (DNase I), only drug currently available to clear NETs, is limited due lack precise efficient delivery strategies. Therefore, targeted DNase inflamed remains issue be addressed. Herein, novel biomimetic system developed (DCNV) that employs genetically bioorthogonally engineered cellular nanovesicles for pulmonary NETs clearance. The CXC motif chemokine receptor 2 overexpressed can mimic inflammatory chemotaxis neutrophils ALI/ARDS, leading enhanced accumulation. Furthermore, immobilized through bioorthogonal chemistry exhibits remarkable enzymatic activity degradation, thus restraining inflammation safeguarding tissue lipopolysaccharide‐induced ALI murine model. Collectively, findings present groundbreaking proof‐of‐concept utilization deliver treating ALI/ARDS. This innovative strategy may usher new era development pharmacological interventions various inflammation‐related diseases.

Language: Английский

Citations

21
What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study DOI Creative Commons
Cristina Diego, Ana Lasierra,

Lucía López-Vergara

et al.

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

Published: Jan. 19, 2024

Abstract Background Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, are scarce data evolution during the disease. We studied circulating NET markers in patients with throughout hospitalization. Methods prospectively included 93 (201 blood samples), evaluating disease 3 evolutionary phases (viral, early, late inflammation). Of these, 72 had 180 samples various phases. also evaluated 55 controls similar age, sex comorbidities. measured 4 serum: cfDNA, CitH3, MPO-DNA NE-DNA complexes; as well neutrophil-related cytokines IL-8 G-CSF. Results The group higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), MPO-DNA, (7.87 2.56 ng/mL; 0.80 0.52 1.04 0.72, respectively, < 0.001 for all) than hospitalisation. cfDNA was only marker clearly severity, it remained non-survivors Only an independent risk factor mortality need intensive care. count, IL-8, G-CSF were significantly severity. showed significant correlations (r: 0.483, 0.001), including all across grades, they days 10–16 of those who died. Correlations among other lower expected. Conclusions biomarkers NETs present associated mortality, but three little or association these outcomes. activity neutrophil count better reflected formation. appeared be more overall tissue damage; previous widespread use this could overestimated relationship between Currently, limitations accurate measurement that make difficult assess its true role pathogenesis.

Language: Английский

Citations

8
The roles of arginases and arginine in immunity DOI
Stefania Canè, Roger Geiger, Vincenzo Bronte

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Language: Английский

Citations

7
A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury DOI Open Access
Xinyu Zhou,

Jiajia Jin,

Tangfeng Lv

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1464 - 1464

Published: Jan. 25, 2024

Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation treatment of ARDS remains major research focus. There are various causes ARDS, among which pneumonia non-pulmonary sepsis most common. Trauma blood transfusion can also cause ARDS. In aggregation infiltration neutrophils in lungs have great influence on development disease. Neutrophils regulate inflammatory responses through pathways, release neutrophil extracellular traps (NETs) is considered to be one important mechanisms. NETs mainly composed DNA, histones, granuloproteins, all mediate downstream signaling pathways that activate responses, generate immune clots, damage surrounding tissues. At same time, components promote formation NETs, thus forming vicious cycle continuously aggravates progression associated with cytokine storms balance. Since DNA main component DNase I viable drug for removing NETs. Other therapeutic methods inhibit worthy further exploration. This review discusses mechanism Understanding association between may help develop new perspectives

Language: Английский

Citations

6
NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins DOI Creative Commons
Ilya Tsukalov, Ildefonso Sánchez‐Cerrillo,

Olga Rajas

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 7, 2024

Abstract Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate activation or differentiation response to different proteins remain poorly characterized. Here, we show that Spike 1 but not nucleoprotein induce into subsets from both peripheral blood bronchoalveolar lavage samples a NFκB-dependent manner, this process does require inflammasome activation. NLRP3 NLRC4 differentially regulated CD86 expression Nucleoprotein, respectively. Moreover, exposed significantly higher proportions Th1 Th17 CD4 + T cells. In contrast, Nucleoprotein reduce degranulation CD8 cells severe patients. Our study provides insights differential impact regulating proteins, which might be useful better understand immunopathology identify therapeutic targets.

Language: Английский

Citations

6
Targeting Macrophage Polarization in Infectious Diseases: M1/M2 Functional Profiles, Immune Signaling and Microbial Virulence Factors DOI
Cláudio Daniel Cerdeira, Maı́sa Ribeiro Pereira Lima Brigagão

Immunological Investigations, Journal Year: 2024, Volume and Issue: 53(7), P. 1030 - 1091

Published: June 24, 2024

An event of increasing interest during host-pathogen interactions is the polarization patrolling/naive monocytes (MOs) into macrophage subsets (MФs). Therapeutic strategies aimed at modulating this are under investigation.

Language: Английский

Citations

6