The Pyruvate Dehydrogenase Complex Mitigates LPS-Induced Endothelial Barrier Dysfunction by Metabolic Regulation
Sepsis is a fatal health issue induced by an aberrant host response to infection, and it correlates with organ damage and a high mortality rate. Endothelial barrier dysfunction and subsequent capillary leakage play major roles in sepsis-induced multiorgan dysfunction. Anaerobic glycolysis is the primary metabolic mode in sepsis and the pyruvate dehydrogenase complex (PDHC) serves as a critical hub in energy regulation. Therefore, it is important to understand the role of PDHC in metabolic regulation during the development of sepsis-induced endothelial barrier dysfunction.
In present study, human umbilical vein endotheli...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Inhibition of Nitrosative Stress Attenuates Myocardial Injury and Improves Outcomes after Cardiac Arrest and Resuscitation
Conclusions:
Inhibition of nitrosative stress is a novel molecular target to alleviate myocardial injury and improve outcomes in a rat model of CA/CPR. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Defining Endotheliopathy in Murine Polytrauma Models
Conclusions:
A murine model of polytrauma including TBI, hemorrhagic shock, and laparotomy abdominal crush is a reliable method for evaluation of endotheliopathy secondary to trauma as indicated by differential changes in serum biomarkers. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Redox Potential Correlates with Changes in Metabolite Concentrations Attributable to Pathways Active in Oxidative Stress Response in Swine Traumatic Shock
Conclusions:
Real-time RP measures demonstrate significant relationships with metabolites attributable to metabolic pathways involved in systemic responses to oxidative stress, as well as those involved in these processes. These data support RP measures as a feasible, biologically relevant marker of oxidative stress. As a direct measure of redox state, RP may be a useful biomarker and clinical tool in guiding diagnosis and therapy in states of increased oxidative stress and may offer value as a marker for organ injury in these states as well. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Hepcidin Alleviates LPS-Induced ARDS by Regulating the Ferritin-Mediated Suppression of Ferroptosis
The effects of ferroptosis, an iron-dependent cell death, on acute respiratory distress syndrome (ARDS) remain largely elusive. Hepcidin, encoded by the HAMP gene, affects inflammation, and iron homeostasis. The present study aimed to investigate whether hepcidin protects against ferroptosis in lipopolysaccharide (LPS)-induced ARDS. Our results confirmed that ferroptosis aggravated lung inflammation and damage in LPS-induced ARDS. Hepcidin defended against ferroptosis, with results similar to those of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Moreover, hepcidin decreased iron uptake, as determined by Transferrin Rec...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Defining Sepsis Phenotypes—Two Murine Models of Sepsis and Machine Learning
Introduction:
The immunobiology defining the clinically apparent differences in response to sepsis remains unclear. We hypothesize that in murine models of sepsis we can identify phenotypes of sepsis using non-invasive physiologic parameters (NIPP) early after infection to distinguish between different inflammatory states.
Methods:
Two murine models of sepsis were used: gram-negative pneumonia (PNA) and cecal ligation and puncture (CLP). All mice were treated with broad spectrum antibiotics and fluid resuscitation. High-risk sepsis responders (pDie) were defined as those predicted to die within 72 h following ...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
A Limited Role for AMD3100 Induced Stem Cell Mobilization for Modulation of Thoracic Trauma Outcome
Thoracic trauma is a major cause of mortality due to the associated inflammatory acute respiratory distress syndrome and morbidity due to impaired tissue regeneration. Trauma-induced lung inflammation is characterized by the early recruitment of cells with pro- or anti-inflammatory activity to the lung. Therapeutic interventions reducing the level of tissue inflammation may result in decreased tissue damage and improved healing and recovery. Stem cells might be able to improve trauma outcome via immunomodulation or by enhancing tissue regeneration.
Here, we describe the migratory dynamics of murine mesenchymal, hematopo...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury
Background:
Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process. However, no study has specifically addressed whether fecal microbiota transfer (FMT) attenuates neurologic deficits after TBI.
Hypothesis:
We hypothesized that fecal microbiota transfer would attenuate neurocognitive, anatomic, and pathologic deficits after TBI.
Methods:
C57Bl/6 mice were subjected to severe TBI (n = 20...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Whole Blood Selective Aortic Arch Perfusion for Exsanguination Cardiac Arrest: Assessing Myocardial Tolerance to the Duration of Cardiac Arrest
Conclusion:
Whole blood SAAP can accomplish ROSC at high rates even after 10 min of unsupported cardiac arrest secondary to hemorrhage, with some viability beyond to 15 min. This is promising as a tool for ECA, but requires additional optimization and clinical trials.
Animal Use Protocol, IACUC: 0919015. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Basic Science Aspects (Animal Subjects) Source Type: research
Burn Injury-Induced Extracellular Vesicle Production and Characteristics
Extracellular vesicles (EVs) are nano-sized membrane-bound particles containing biologically active cargo molecules. The production and molecular composition of EVs reflect the physiological state of parent cells, and once released into the circulation, they exert pleiotropic functions via transferring cargo contents. Thus, circulating EVs not only serve as biomarkers, but also mediators in disease processes or injury responses. In the present study, we performed a comprehensive analysis of plasma EVs from burn patients and healthy subjects, characterizing their size distribution, concentration, temporal changes, cell orig...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) 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)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research
Growth Differentiation Factor-15 Correlates with Mortality and Severity in Severe Burns
Conclusions:
In the acute phase of severe burn, GDF-15 levels were associated with mortality and SOFA scores. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research
Circular RNA UBAP2 (hsa_circ_0007367) Correlates with Microcirculatory Perfusion and Predicts Outcomes of Cardiogenic Shock Patients Undergoing Extracorporeal Membrane Oxygenation Support
Conclusion:
The expression of circUBAP2 correlates with microcirculatory perfusion and has the potential in predicting outcomes for on-ECMO patients with cardiogenic shock. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research
Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation
Background:
Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use.
Objective:
To determine the association between longitudinal cytometric, proteomic, bioenergetic, and metabolomic markers of immunometabolic dysregulation and pathogen type in pediatric sepsis.
Methods:
Serial peripheral blood mononuclear cell (PBMC) samples were obtained from 14 sepsis patients (34 total samples) and 7 control patients for this observational study. Flow cytometry was used to define imm...
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research
Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance in Early Human Sepsis
Conclusions:
An attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome. (Source: Shock)
Source: Shock - June 1, 2022 Category: Emergency Medicine Tags: Clinical Aspects (Human Subjects) Source Type: research
