Growth Differentiation Factor 15 as a Biomarker for Risk Stratification in the Cardiothoracic Surgery Intensive Care Unit.

Growth Differentiation Factor 15 (GDF15) is an emerging biomarker that significantly increases during acute stress responses, such as infections, and is moderately elevated in chronic and inflammation-driven conditions. While evidence suggests that high levels of GDF15 in cardiac surgery are associated with worse outcomes, its utility as an evaluator of early postoperative complications remains unclear. This study aims to characterize the postoperative profile of GDF15 in patients undergoing isolated surgical aortic valve replacement, evaluating its association with short-term outcomes.

Immunomodulatory Effects and Protection in Sepsis by the Antibiotic Moxifloxacin.

Sepsis is a leading cause of death in Intensive Care Units. Despite its prevalence, sepsis remains insufficiently understood, with no substantial qualitative improvements in its treatment in the past decades. Immunomodulatory agents may hold promise, given the significance of TNF-α and IL-1β as sepsis mediators.

The impact of cardiopulmonary bypass time on the Sequential Organ Failure Assessment score after cardiac surgery.

Objectives: Postoperative organ dysfunction is common after cardiac surgery, particularly when cardiopulmonary bypass (CPB) is used. The Sequential Organ Failure Assessment (SOFA) score is validated to predict morbidity and mortality in cardiac surgery. However, the impact of CPB duration on postoperative SOFA remains unclear.

DNA damage independent inhibition of NF-κB transcription by anthracyclines.

Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes in primary mouse () macrophages.

Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk.

Unlabelled: Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired.

Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection.

Several classes of antibiotics have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here, we report that tetracycline antibiotics, which target the mitoribosome, protected against sepsis without affecting the pathogen load. Mechanistically, we found that mitochondrial inhibition of protein synthesis perturbed the electron transport chain (ETC) decreasing tissue damage in the lung and increasing fatty acid oxidation and glucocorticoid sensitivity in the liver.

Crosstalk between metabolism and immunity: the 3rd Annual Research Symposium of Instituto Gulbenkian de Ciência.

The 'Crosstalks of immunity and metabolism' Symposium was focused on how the intercommunication between different organs and the immune system affects organismal health. At this meeting, experts in immunology and metabolic research provided novel insights into the growing field of immunometabolism. This report attempts to review and integrate views, ideas, propositions, and conclusions that emanated from the symposium.

CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of -deficient mice protects against abdominal sepsis.

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and that -deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control.

Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis.

Objective: Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome.

A Th2 Cytokine Profile in Appendicular Lavage Fluid Suggests Allergy as a Possible Etiology for Acute Appendicitis.

Acute appendicitis is the most frequent surgical abdominal emergency, but its etiology remains poorly understood. Histological examination of the appendix, following its removal due to acute appendicitis, consistently shows features in common with bronchial asthma, suggesting an allergic reaction as a candidate etiologic factor. Here, we propose the concept of appendicular lavage and use it to study the levels of the Th2 cytokines IL-4, IL-5, and IL-9 in patients with a clinical diagnosis of acute appendicitis.

Changes in Expression of the Gene in Obstructive Sleep Apnea Syndrome Patients Are Not Reverted by Continuous Positive Airway Pressure Treatment.

Purpose: Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment.

Methods: Peripheral blood was collected from male patients diagnosed with severe OSAS (apnea-hypopnea index ≥ 30/h) before and after treatment initiation.

Anthracyclines induce DNA damage response-mediated protection against severe sepsis.

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ.

VEGF-functionalized dextran has longer intracellular bioactivity than VEGF in endothelial cells.

Herein, we report that VEGF-functionalized dextran (dexOx-VEGF) is comparatively superior to free VEGF in prolonging the phosphorylation of VEGF receptor 2 (VEGFR-2). Both dexOx-VEGF and free VEGF activate VEGFR-2, and the complexes are internalized into early endosomes (EEA1(+) vesicles) and then transported to lysosomes (Rab7(+) vesicles). However, after cell activation, dexOx-VEGF is preferentially colocalized in early endosomes where VEGF signaling is still active while free VEGF is preferentially transported to late endosomes or lysosomes.

Improved survival, vascular differentiation and wound healing potential of stem cells co-cultured with endothelial cells.

In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34(+) cells), by co-culturing the stem cells in a 3D fibrin gel with CD34(+)-derived endothelial cells (ECs). ECs differentiated from CD34(+) cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34(+)-derived ECs on CD34(+) cells is mediated, at least in part, by bioactive factors released from ECs.