Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 335 - 352
Опубликована: Янв. 1, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Сен. 20, 2024
Язык: Английский
Процитировано
43
Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(2), С. 119 - 133
Опубликована: Янв. 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.
Язык: Английский
Процитировано
18
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8065 - 8065
Опубликована: Апрель 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
Язык: Английский
Процитировано
35
Pharmaceuticals, Год журнала: 2023, Номер 16(4), С. 584 - 584
Опубликована: Апрель 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.
Язык: Английский
Процитировано
29
Nature reviews. Immunology, Год журнала: 2024, Номер unknown
Опубликована: Окт. 17, 2024
Язык: Английский
Процитировано
12
Advanced Science, Год журнала: 2023, Номер 10(32)
Опубликована: Сен. 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.
Язык: Английский
Процитировано
23
Respiratory Research, Год журнала: 2024, Номер 25(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
8
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1464 - 1464
Опубликована: Янв. 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
Язык: Английский
Процитировано
7
Journal of Clinical Medicine, Год журнала: 2023, Номер 12(23), С. 7245 - 7245
Опубликована: Ноя. 23, 2023
COVID-19, caused by the SARS-CoV-2 virus, has revealed a complex interplay between inflammation and coagulation, leading to emergence of concept thrombo-inflammation. This recognizes that COVID-19 is not solely respiratory illness, but systemic disease with significant vascular hematological components. associated an unusual prothrombotic state, intense endothelial activation vasculopathy, cytokine storm, complement system hypercoagulability state (the platelets coagulation cascade, impaired fibrinolysis). The aim this review discuss different pathological pathways described in lead thromboembolic events. Widespread vaccination post-COVID-19 immunization allows control over severity pandemic. A better understanding pathophysiology can improve management frail patients who are hospitalized intensive care units.
Язык: Английский
Процитировано
14
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Март 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.
Язык: Английский
Процитировано
6