Inhibition of the lymphocyte metabolic switch by the oxidative burst of human neutrophils
Activation of the phagocytic NADPH oxidase (NOX-2) in neutrophils is a critical process in the innate immune system and is associated with elevated local concentrations of superoxide, hydrogen peroxide and hypochlorous acid. Under pathological conditions, NOX-2 activity has been implicated in the development of autoimmunity, indicating a role in modulating lymphocyte effector function. Notably, T cell clonal expansion and subsequent cytokine production requires a metabolic switch from mitochondrial respiration to aerobic glycolysis. Previous studies demonstrate that hydrogen peroxide generated from activated neutrophils suppresses lymphocyte activation but the mechanism is unknown. We hypothesized that activated neutrophils would prevent the metabolic switch and suppress the effector functions of T cells through a hydrogen peroxide-dependent mechanism. To test this, we developed a model co-culture system using freshly isolated neutrophils and lymphocytes from healthy human donors. Extracellular flux analysis was used to assess mitochondrial and glycolytic activity and FACS analysis to assess immune function. The neutrophil oxidative burst significantly inhibited the induction of lymphocyte aerobic glycolysis, caused inhibition of oxidative phosphorylation, and suppressed lymphocyte activation through a hydrogen peroxide-dependent mechanism. The impact of hydrogen peroxide on bioenergetics in the lymphocytes was confirmed using authentic reagent and a redox cycling agent. In s...
Authors: Stange EF, Schroeder BO Abstract Introduction: Inflammatory bowel diseases (IBD) are on the rise worldwide. This review covers the current concepts of the etiology of Crohn´s disease and ulcerative colitis by focusing on an unbalanced interaction between the intestinal microbiota and the mucosal barrier. Understanding these issues is of paramount importance for the development of targeted therapies aiming at the disease cause. Area covered: Gut microbiota alterations and a dysfunctional intestinal mucosa are associated with IBD. Here we focus on specific defense structures of the mucosal barrier, nam...
ConclusionsOromotor exercises are more effective than incentive spirometry training in improving both pulmonary and oromotor functions in children with Down's syndrome.
Publication date: Available online 11 October 2019Source: Journal of Taibah University Medical SciencesAuthor(s): Beuy Joob, Viroj Wiwanitkit
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Publication date: Available online 11 October 2019Source: The SurgeonAuthor(s): Gregory L. Falk
ConclusionsPatients receiving perioperative gabapentin, acetaminophen, and NSAIDs under an ERAS protocol required significantly fewer narcotics and shorter length of stay. This protocol may merit consideration for use at other centers.
ConclusionsMore than half (51%) of women who underwent genetic counseling and received an uninformative negative genetic test result had a significantly elevated risk for the development of breast cancer. It is, therefore, imperative that women do not conclude that a negative genetic test result represents a lack of risk.
Publication date: Available online 11 October 2019Source: The American Journal of SurgeryAuthor(s): Dhruv J. Patel, Waseem Lutfi, Patrick Sweigert, Emanuel Eguia, Gerard Abood, Lawrence Knab, Paul C. Kuo, Marshall S. BakerAbstractBackgroundPrior studies of adjuvant systemic therapy in pancreatic acinar cell carcinoma have been underpowered.MethodsWe queried the National Cancer Data Base to identify patients presenting with resectable (clinical stage I and II) acinar cell carcinoma between 2004 and 2015. Multivariable Cox Regression was used to evaluate the association between overall survival and systemic therapy.Results29...
ConclusionOur pilot curriculum addresses a gap in resident education about surgical cost. Residents generally regard equipment standardization as either improving or not changing hospital metrics.