Oxygen-Dependent Changes in the N-Glycome of Murine Pulmonary Endothelial Cells.

Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.

Bariatric Surgery-How Much Malabsorption Do We Need?-A Review of Various Limb Lengths in Different Gastric Bypass Procedures.

The number of obese individuals worldwide continues to increase every year, thus, the number of bariatric/metabolic operations performed is on a constant rise as well. Beside exclusively restrictive procedures, most of the bariatric operations have a more or less malabsorptive component. Several different bypass procedures exist alongside each other today and each type of bypass is performed using a distinct technique. Furthermore, the length of the bypassed intestine may differ as well. One might add that the operations are performed differently in different parts of the world and have been changing and evolving over time. This review evaluates the most frequently performed bariatric bypass procedures (and their variations) worldwide: Roux-en-Y Gastric Bypass, One-Anastomosis Gastric Bypass, Single-Anastomosis Duodeno-Ileal Bypass + Sleeve Gastrectomy, Biliopancreatic Diversion + Duodenal Switch and operations due to weight regain. The evaluation of the procedures and different limb lengths focusses on weight loss, remission of comorbidities and the risk of malnutrition and deficiencies. This narrative review does not aim at synthesizing quantitative data. Rather, it provides a summary of carefully selected, high-quality studies to serve as examples and to draw tentative conclusions on the effects of the bypass procedures mentioned above. In conclusion, it is important to carefully choose the procedure and small bowel length excluded from the food passage suited best to each individual patient. A balance has to be achieved between sufficient weight loss and remission of comorbidities, as well as a low risk of deficiencies and malnutrition. In any case, at least 300 cm of small bowel should always remain in the food stream to prevent the development of deficiencies and malnutrition.

Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine.

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term "oxidative stress" is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

Investigating Disturbances of Oxygen Homeostasis: From Cellular Mechanisms to the Clinical Practice.

Soon after its discovery in the 18th century, oxygen was applied as a therapeutic agent to treat severely ill patients. Lack of oxygen, commonly termed as hypoxia, is frequently encountered in different disease states and is detrimental to human life. However, at the end of the 19th century, Paul Bert and James Lorrain Smith identified what is known as oxygen toxicity. The molecular basis of this phenomenon is oxygen's readiness to accept electrons and to form different variants of aggressive radicals that interfere with normal cell functions. The human body has evolved to maintain oxygen homeostasis by different molecular systems that are either activated in the case of oxygen under-supply, or to scavenge and to transform oxygen radicals when excess amounts are encountered. Research has provided insights into cellular mechanisms of oxygen homeostasis and is still called upon in order to better understand related diseases. Oxygen therapy is one of the prime clinical interventions, as it is life saving, readily available, easy to apply and economically affordable. However, the current state of research also implicates a reconsidering of the liberal application of oxygen causing hyperoxia. Increasing evidence from preclinical and clinical studies suggest detrimental outcomes as a consequence of liberal oxygen therapy. In this review, we summarize concepts of cellular mechanisms regarding different forms of disturbed cellular oxygen homeostasis that may help to better define safe clinical application of oxygen therapy.