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1.
Mediators Inflamm ; 2022: 8457010, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185385

RESUMO

Glibenclamide displays an anti-inflammatory response in various pulmonary diseases, but its exact role in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) remains unknown. Herein, we aimed to explore the effect of glibenclamide in vivo and in vitro on the development of LPS-induced ALI in a mouse model. LPS stimulation resulted in increases in lung injury score, wet/dry ratio, and capillary permeability in lungs, as well as in total protein concentration, inflammatory cells, and inflammatory cytokines including IL-1ß, IL-18 in bronchoalveolar lavage fluid (BALF), and lung tissues, whereas glibenclamide treatment reduced these changes. Meanwhile, the increased proteins of NLRP3 and Caspase-1/p20 after LPS instillation in lungs were downregulated by glibenclamide. Similarly, in vitro experiments also found that glibenclamide administration inhibited the LPS-induced upregulations in cytokine secretions of IL-1ß and IL-18, as well as in the expression of components in NLRP3 inflammasome in mouse peritoneal macrophages. Of note, glibenclamide had no effect on the secretion of TNF-α in vivo nor in vitro, implicating that its anti-inflammatory effect is relatively specific to NLRP3 inflammasome. In conclusion, glibenclamide alleviates the development of LPS-induced ALI in a mouse model via inhibiting the NLRP3/Caspase-1/IL-1ß signaling pathway, which might provide a new strategy for the treatment of LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Inflamassomos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Glibureto/farmacologia , Glibureto/uso terapêutico , Inflamassomos/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais
2.
J Cardiothorac Vasc Anesth ; 34(6): 1614-1621, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31420312

RESUMO

Perioperative coagulopathy and bleeding are common complications in cardiovascular surgery with cardiopulmonary bypass and result in an increased rate of allogeneic blood transfusion. Both bleeding and transfusion can increase postoperative mortality and morbidity. Patient blood management can significantly reduce allogeneic blood transfusions, improve clinical outcomes, and conserve blood resources; however, measures to protect platelets from destruction by cardiopulmonary bypass still are lacking. As an unusual method of autologous blood transfusion, autologous platelet-rich plasmapheresis can effectively protect platelets from damage and has been used successfully in cardiovascular surgery. This narrative review aims to address some major clinical applications and debates of using autologous platelet-rich plasmapheresis in cardiovascular surgery. In addition, this review summarizes the application of autologous platelet gel, a product developed from autologous platelet-rich plasma, in cardiac surgery.


Assuntos
Plaquetas , Transfusão de Sangue Autóloga , Transfusão de Sangue , Ponte Cardiopulmonar , Humanos , Plasmaferese
3.
Discov Oncol ; 15(1): 256, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955935

RESUMO

Cancer-associated thrombosis is a significant complication in cancer patients, leading to increased morbidity and mortality. The expression of coagulation/fibrinolysis genes, termed the "coagulome", plays a critical role in this process. Using the single-sample gene set enrichment analysis (ssGSEA), we identified seven cancer types with significantly activated coagulation pathways, focusing on lower-grade glioma (LGG) and stomach adenocarcinoma due to their predictive value for overall survival. Through 1000 iterations of the Least Absolute Shrinkage and Selection Operator (LASSO), we selected prognostic genes and constructed effective Cox regression models, particularly for LGG. Incorporating clinical characteristics, we constructed a nomogram for LGG, achieving an impressive area under the curve (AUCs) of 0.79, 0.82, and 0.81 at 1, 3, and 5 years in the test dataset, indicating strong potential for clinical application. Functional enrichment analysis between high-risk and low-risk LGG groups revealed significant enrichment of genes involved in the inflammatory response, interferon-gamma response, and epithelial-mesenchymal transition pathways. Combined with CIBERSORT and single-cell RNA sequencing analysis of LGG, our results demonstrated that the interplay between coagulation and the tumor microenvironment, particularly involving gliomas and myeloid cells, significantly influences tumor progression and patient outcomes.

4.
Cell Rep ; 43(7): 114453, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38985677

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.


Assuntos
Vesículas Extracelulares , Macrófagos Alveolares , Staphylococcus aureus Resistente à Meticilina , MicroRNAs , Necroptose , Animais , Vesículas Extracelulares/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/microbiologia , Camundongos , MicroRNAs/metabolismo , MicroRNAs/genética , Fagocitose , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/metabolismo , Masculino , Humanos
5.
J Extracell Vesicles ; 13(4): e12437, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38594787

RESUMO

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterised by an uncontrolled inflammatory response, and current treatment strategies have limited efficacy. Although the protective effect of M2-like macrophages (M2φ) and their extracellular vesicles (EVs) has been well-documented in other inflammatory diseases, the role of M2φ-derived EVs (M2φ-EVs) in the pathogenesis of ALI/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide-induced ALI to first demonstrate a decrease in endogenous M2-like alveolar macrophage-derived EVs. And then, intratracheal instillation of exogenous M2φ-EVs from the mouse alveolar macrophage cell line (MH-S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2φ-EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL-6, TNF-α and IL-1ß both in vivo and in vitro, which were closely related to NF-κB/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2φ-EVs was partly mediated by miR-709, as evidenced by the inhibition of miR-709 expression in M2φ-EVs mitigated their protective effect against lipopolysaccharide-induced ALI in mice. In addition, we found that the expression of miR-709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a marker for ARDS severity. Altogether, our study revealed that M2φ-EVs played a protective role in the pathogenesis of ALI/ARDS, partly mediated by miR-709, offering a potential strategy for assessing disease severity and treating ALI/ARDS.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , MicroRNAs , Síndrome do Desconforto Respiratório , Humanos , Camundongos , Animais , Lipopolissacarídeos , Vesículas Extracelulares/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Macrófagos/metabolismo , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , MicroRNAs/metabolismo
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