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Blockade of endothelial growth factor, angiopoietin-2, reduces indices of ards and mortality in mice resulting from the dual-insults of hemorrhagic shock and sepsis
In this study we show that Ang-2 in lung tissue and plasma spikes following hemorrhage (priming) and remain elevated at sepsis induction. In addition, that transient inhibition of Ang-2 function immediately following hemorrhage, suppressing priming, but not following sepsis, impacts the development of iARDS in our model. Our data demonstrate that selective temporal blockade of Ang-2 function following hemorrhagic shock priming significantly improved PO2/FIO2, decreased lung protein leak and indices of inflammation, and improved 10-day survival in our murine model for the development iARDS.
Source: Shock - January 21, 2016 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

MiR-155 Alleviates Septic Lung Injury by Inducing Autophagy Via Inhibition of Transforming Growth Factor-β-Activated Binding Protein 2
Conclusion: The current study observed a higher level of miR-155 in the BALF from sepsis patients with acute respiratory distress syndrome and demonstrated that miR-155 alleviated inflammation in septic lung injury in mouse and cell models by inducing autophagy via inhibition of TAB2.
Source: Shock - June 15, 2017 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Matrine Protects Cardiomyocytes From Ischemia/Reperfusion Injury by Regulating HSP70 Expression Via Activation of the JAK2/STAT3 Pathway
In conclusion, matrine attenuates myocardial I/R injury by upregulating HSP70 expression via the activation of the JAK2/STAT3 pathway.
Source: Shock - November 14, 2018 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Crocin Alleviates Myocardial Ischemia/Reperfusion-Induced Endoplasmic Reticulum Stress via Regulation of miR-34a/Sirt1/Nrf2 Pathway
In conclusion, crocin attenuates I/R-induced cardiomyocyte apoptosis via suppressing ER stress, which is regulated by the miR-34a/Sirt1/Nrf2 pathway.
Source: Shock - December 15, 2018 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Total Salvianolic Acid Injection Prevents Ischemia/Reperfusion-Induced Myocardial Injury Via Antioxidant Mechanism Involving Mitochondrial Respiratory Chain Through the Upregulation of Sirtuin1 and Sirtuin3
Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are known to participate in regulating mitochondrial function. However, whether Total Salvianolic Acid Injection (TSI) protects against myocardial ischemia/reperfusion (I/R) injury through regulating Sirt1, Sirt3, and mitochondrial respiratory chain complexes is unclear. The aim of this study was to explore the effects of TSI on I/R-induced myocardial injury and the underlying mechanism. Male Sprague–Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 90 min reperfusion with or without TSI treatment (8 mg/kg/h). The results...
Source: Shock - May 15, 2019 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

LncRNA-Ang362 Promotes Pulmonary Arterial Hypertension by Regulating miR-221 and miR-222
Conclusion: Lnc-Ang362 played an important role in regulating the biological function of HPASMCs by promoting miR-221 and miR-222. Lnc-Ang362 thus may be a novel therapeutic lncRNA candidate for treating PAH.
Source: Shock - May 16, 2020 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Critical Role of Mortalin/GRP75 in Endothelial Cell Dysfunction Associated with Acute Lung Injury
In this study, we sought to determine the role of mortalin/GRP75 in mediating vascular inflammation and permeability linked to the pathogenesis of acute lung injury (ALI). In an aerosolized bacterial lipopolysaccharide inhalation mouse model of ALI, we found that administration of mortalin/GRP75 inhibitor mean kinetic temperature-077, both prophylactically and therapeutically, protected against polymorphonuclear leukocytes influx into alveolar airspaces, microvascular leakage, and expression of pro-inflammatory mediators such as interleukin-1β, E-selectin, and tumor necrosis factor TNFα. Consistent with this, thrombin-in...
Source: Shock - July 30, 2020 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

ERK1/2 Has Divergent Roles in LPS-Induced Microvascular Endothelial Cell Cytokine Production and Permeability
Endothelial cells play a major role in inflammatory responses to infection and sterile injury. Endothelial cells express Toll-like receptor 4 (TLR4) and are activated by LPS to express inflammatory cytokines/chemokines, and to undergo functional changes, including increased permeability. The extracellular signal-regulated kinase 1/2 (ERK1/2) mediates pro-inflammatory signaling in monocytes and macrophages, but the role of ERK1/2 in LPS-induced activation of microvascular endothelial cells has not been defined. We therefore studied the role of ERK1/2 in LPS-induced inflammatory activation and permeability of primary human...
Source: Shock - February 12, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Fibrinogen Activates PAK1/Cofilin Signaling Pathway to Protect Endothelial Barrier Integrity
Conclusion: We have identified a novel pathway by which fibrinogen activates PAK1 signaling to stimulate/dephosphorylate cofilin, leading to disassembly of stress fibers and reduction of endothelial permeability.
Source: Shock - April 21, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

KLF6 Promotes Pyroptosis of Renal Tubular Epithelial Cells in Septic Acute Kidney Injury
Septic acute kidney injury (SAKI) represents a clinical challenge with high morbidity and mortality. The current study aimed to analyze the effects and molecular mechanism of Krüppel-like factor 6 (KLF6) on SAKI. First, SAKI mouse models were established by cecum ligation and puncture, while in vivo cell models were established using lipopolysaccharide (LPS). RT-qPCR assay was subsequently performed to detect the levels of KLF6 mRNA. SAKI mice and LPS-treated TCMK-1 cells were further treated with KLF6 siRNA. Afterward, HE staining, PAS staining, Western blot assay, and ELISA were adopted to ascertain the effects of KLF6 ...
Source: Shock - March 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Exosomal Transfer of DNA Methyl-Transferase mRNA Induces an Immunosuppressive Phenotype in Human Monocytes
Conclusion: These data support a role for exosome-mediated transfer of DNMT mRNA with resultant methylation and gene silencing. Pharmacologic uptake inhibition or targeted siRNA mediated DNMT gene silencing prevented DNMT mRNA transfer and maintained the cell's ability to express TNFα in response to LPS. This highlights the potential therapeutic value of targeting these exosome-mediated epigenetic events to maintain the host immune response during sepsis.
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research

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