764 research outputs found
Bibliometric Analysis Biodiversity
No full textThis data base was used for the analyses described in the publication "Spatial and Topical Imbalances in Biodiversity Research" by Tydecks, Laura, Jeschke, Jonathan, Wolf, Max, Singer, Gabriel, Tockner, Klement.
The data were derived from Web of Science (WoS). These terms were used to set up the data base: biodiversity, biological diversity, species richness, species evenness, genetic diversity, species diversity, ecosystem diversity, alpha diversity, beta diversity, gamma diversity, taxonomic diversity, phylogenetic diversity, behavio(u)ral diversity, functional diversity.
All articles in English from 1945 to 2014 are included (download date: May 12, 2015).
pid = publication ID
py = publication year
ti = title
ab = abstract
auid = author ID
an = author name
cc = country
tc = times cite
Insulin Decreases Inflammatory Signal Transcription Factor Expression in Primary Human Liver Cells after LPS Challenge
No full textHepatic homeostasis is essential for survival in critically ill and burned patients. Insulin administration improves survival and decreases infections in these patients. To determine the molecular mechanisms, the aim of the present study was to establish a stress model using primary human hepatocytes (PHHs) and to study the effects of insulin on the hepatic inflammatory signaling cascade. Liver tissue was obtained from general surgical patients, and PHHs were isolated and maintained in culture. Primary hepatocyte cultures were challenged with various doses of lipopolysaccharide (LPS), and the inflammatory signal transcription cascade was determined by real-time PCR, In subsequent experiments, primary hepatocyte cultures were challenged with LPS and insulin was added in various doses. Glucose was determined by colorimetric assays. PHHs treated with 100 mu g/mL LPS showed a profound inflammatory reaction with increased expression of interleukin (IL)-6, IL-10, IL-1 beta, tumor necrosis factor (TNF), and signal transducer and activator of transcription 5 (STAT-5), Insulin at 10 IU/mL significantly decreased IL-6, TNF and IL-1 beta at pretranslational levels, an effect associated with decreased STAT-5 mRNA expression (P < 0.05), Glucose concentration and cellular metabolic activity were not different between controls and insulin-treated cells. Based on our results, we suggest that primary hepatocyte cultures can be used to study the effect of LPS on the inflammatory cascade. Insulin decreases hepatic cytokine expression, which is associated with decreased STAT-5 expression
Characterization of White Adipose Tissue Depots After Burn
No full textBurn injury results in a vast and prolonged hypermetabolic state that is characterized by hyperglycemia, cachexia, organ dysfunction, and death. Recently, the adipose has been identified as a major mediator in the activation of the hypermetabolic response. However, the fat, and in particular, the visceral fat, has been largely ignored within this context. Here, we aimed to characterize and compare some of the hallmark responses of burn injury by examining the largest visceral (eWAT) and subcutaneous (iWAT) depots in our murine model. After a 30% burn, we observed the activation of ER stress, lipolysis and browning in different depots. Administration of propranolol (10 mg/kg) for 5 days attenuated these responses. We conclude that burn studies that examine the fat should be mindful of the depot they survey and be careful not to generalize results. Our findings also highlight the use of propranolol as an adjunct treatment for burn injury.M.Sc
Characterization of White Adipose Tissue Depots After Burn
No full textBurn injury results in a vast and prolonged hypermetabolic state that is characterized by hyperglycemia, cachexia, organ dysfunction, and death. Recently, the adipose has been identified as a major mediator in the activation of the hypermetabolic response. However, the fat, and in particular, the visceral fat, has been largely ignored within this context. Here, we aimed to characterize and compare some of the hallmark responses of burn injury by examining the largest visceral (eWAT) and subcutaneous (iWAT) depots in our murine model. After a 30% burn, we observed the activation of ER stress, lipolysis and browning in different depots. Administration of propranolol (10 mg/kg) for 5 days attenuated these responses. We conclude that burn studies that examine the fat should be mindful of the depot they survey and be careful not to generalize results. Our findings also highlight the use of propranolol as an adjunct treatment for burn injury.M.Sc
Burn-Derived Stem Cells - A Promising New Cell Source For Skin Regeneration
No full textIntroduction: Burns affect millions of people worldwide. Available wound coverage materials are insufficient due to a lack of cells. Mesenchymal stem cells (MSCs) promote wound healing but are limited by lack of availability. We hypothesise that burned skin contains functioning MSCs (burn derived MSCs; BD-MSCs) that promote wound healing.
Methods: BD-MSCs were compared to umbilical cord MSCs in terms of key biological characteristics. Then, skin-scaffolds were cellularized with BD-MSCs, applied onto excisional porcine wounds and observed over 30d.
Results: We found no difference between BD- and UC-MSCs in mitochondrial function, proliferation, colony formation, cell cycle stage distribution, reactive oxygen species, and MHC I/II expression. BD-MSCs are safe and improved wound healing in mice and pigs.
Conclusion: Burned skin contains healthy MSCs that promote wound healing. Key biological functions are not altered by burn trauma. Further studies are needed to evaluate the role of BD-MSCs in wound healing.M.Sc
Persistent Hypermetabolism after Severe Burn Injury: Effects of Hepatic Stress and Regeneration
No full textBurn injury represents one of the most severe forms of trauma. Persistent hypermetabolism and inflammatory response are common in major burned patients, contributing to morbidity and mortality. The underlying mechanisms are largely unknown and therefore novel and effective treatments are lacking. Liver is the fundamental mediator of post-burn immunologic and metabolic derangement and significant hepatomegaly is universally present and associated with the persistent hypermetabolism and inflammatory response in severely burned patients. We sought to understand if such a hepatomegaly is the consequence of 1) increased hepatic fat infiltration due to intensified lipolysis in white adipose tissue (WAT) and inter-organ cross-talk between liver and WAT, or 2)aberrant liver regeneration induced by stress response and liver damage which carries on hypermetabolic and pro-inflammatory signaling, contributing to persistent hypermetabolism and inflammatory response after major burn injury.
Rodent models of burn plus LPS administration, high fat diet (HFD) plus burn, and 30% TBSA burn of Sox9-cre/ERT2:ROSA26-EYFP mice were used for the studies.
In the rat model of burn plus LPS, we demonstrated 1) increased ER stress, inflammasome activation, apoptosis and lipolysis in WAT,contributing to liver steatosis (Chapter 2);2) hepatic ER stress and inflammasome activation, contributing to liver damage and organ dysfunction(Chapter 3). In the mouse model of HFD plus burn, we showed that hepatic fat infiltration and meta-flammation augment the liver damage and metabolic dysfunction post-burn(Chapter 4). We lineage-traced the facultative liver progenitor cells after burn injury and demonstrated that liver regeneration by this group of cells peaked around 2 weeks post-burn. Significant activation of multiple inflammatory and metabolic signaling pathways was indicated by transcriptomic analysis and verified by further analysis in the liver stem cells and their progeny post-burn as compared with both sham and self-renewal mature hepatocytes. Concomitant down-regulation of LXR signaling in the liver stem cells post-burn implicated the therapeutic potential of LXR agonist in ameliorating pro-inflammatory response and restoring lipid homeostasis after major burn injury (Chapter 5).
In conclusion, severe burn injury leads to hepatic stress response, liver damage and steatosis, stimulating liver regeneration from facultative stem cells which contributes to persistent hypermetabolism and pro-inflammatory response.Ph.D
The Role of NLPR3 Inflammasome in Response to Thermal Injury and Sepsis
No full textAlthough the induction of acute-phase inflammation after burn injury is essential, if prolonged it can induce increased risk of infection and sepsis. The NLRP3 inflammasome has established itself as an integral mediator of the acute phase response, however there is a current lack of understanding how it is involved in the inflammatory response after burn injury.
In this study we investigated the role of the NLRP3 inflammasome in burn and septic patients and further aimed to determine if its components can be used to predict sepsis. In Chapter 2 we established the hyperinflammatory response in adult burn and septic burn patients. We also showed that there is increased NLRP3 inflammasome activation and expression in white adipose tissue (WAT) of burn patients and that its pro-inflammatory by-products increase with increasing injury severity.
In Chapter 3, we studied the effect that NLRP3 knockout would have on survival and the immune response in rodents. Interestingly, knocking out NLRP3 inflammasome resulted in increased bacterial clearance and survival in rodents. However, it also induced greater acute responsiveness at the site of injury and WAT characterized by greater macrophage and
neutrophil infiltration, ER stress, apoptosis/pyroptosis, and increased systemic inflammation.
Differential effects were found in other organs with an overall faster return to baseline in inflammatory mediators. In septic burn patients, we found peaks in WAT NLRP3 gene expression occurring later than non-septic’s.
Extending these findings in Chapter 4, we used the major source of NLRP3 inflammasome (macrophages) and its by-product (IL-1β) to generate the Septic Predictor Index to identify burn patients susceptible to sepsis. Patients with Index ratios greater than 0.5 had reduced macrophages proportions in WAT that were producing excess amounts of pro-inflammatory IL- 1β, and subsequently developed sepsis. Collectively, these results suggest that the NLRP3 inflammasome is a critical acute-phase mediator in septic burn patients and despite its utility to identify patient susceptible to sepsis, its mechanism is complex yet protective of sepsis development.Ph.D
The Role of NLPR3 Inflammasome in Response to Thermal Injury and Sepsis
No full textAlthough the induction of acute-phase inflammation after burn injury is essential, if prolonged it can induce increased risk of infection and sepsis. The NLRP3 inflammasome has established itself as an integral mediator of the acute phase response, however there is a current lack of understanding how it is involved in the inflammatory response after burn injury.
In this study we investigated the role of the NLRP3 inflammasome in burn and septic patients and further aimed to determine if its components can be used to predict sepsis. In Chapter 2 we established the hyperinflammatory response in adult burn and septic burn patients. We also showed that there is increased NLRP3 inflammasome activation and expression in white adipose tissue (WAT) of burn patients and that its pro-inflammatory by-products increase with increasing injury severity.
In Chapter 3, we studied the effect that NLRP3 knockout would have on survival and the immune response in rodents. Interestingly, knocking out NLRP3 inflammasome resulted in increased bacterial clearance and survival in rodents. However, it also induced greater acute responsiveness at the site of injury and WAT characterized by greater macrophage and
neutrophil infiltration, ER stress, apoptosis/pyroptosis, and increased systemic inflammation.
Differential effects were found in other organs with an overall faster return to baseline in inflammatory mediators. In septic burn patients, we found peaks in WAT NLRP3 gene expression occurring later than non-septic’s.
Extending these findings in Chapter 4, we used the major source of NLRP3 inflammasome (macrophages) and its by-product (IL-1β) to generate the Septic Predictor Index to identify burn patients susceptible to sepsis. Patients with Index ratios greater than 0.5 had reduced macrophages proportions in WAT that were producing excess amounts of pro-inflammatory IL- 1β, and subsequently developed sepsis. Collectively, these results suggest that the NLRP3 inflammasome is a critical acute-phase mediator in septic burn patients and despite its utility to identify patient susceptible to sepsis, its mechanism is complex yet protective of sepsis development.Ph.D
The Reprogramming of White Adipose Tissue to Brown Adipose Tissue Mediates Adverse Metabolic Dysfunction After A Burn Injury
No full textA burn injury represents one of the most severe forms of trauma and affects more than two million people in North America annually. Of all cases, nearly 4000 people die of complications related to the injury. A hallmark of severely burned patients is the activation of a hypermetabolic stress response, which is characterized by hyperglycemia, lipolysis, and protein catabolism. Perhaps the most serious gap in our understanding of the hypermetabolic response in burns is the role of the adipose tissue. Humans harbour two distinct adipose depots, white adipose tissue (WAT) and brown adipose tissue (BAT) that carry out essentially opposite functions. WAT is primarily involved in storing excess energy, whereas BAT burns excess energy in the form heat. This fat burning aspect of BAT has emerged as a powerful tool in combating the metabolic syndrome (hyperglycemia, excess body fat, hypertension). Additionally, it has been discovered that our WAT can be reprogrammed to become BAT, however, whether or not such reprogramming (white to brown fat) occurs after a burn injury is unknown. We therefore investigated the adipose tissue, and its role in post-burn hypermetabolism, by using an animal model of burn injury and tissue from clinical burn patients. In our first study, we report the reprogramming of WAT to BAT in both burn patients and post-burn mice indicated by increased expression of the brown adipocyte marker, uncoupling protein 1 (UCP-1). This reprogramming of WAT post-burn injury required both IL-6 and catecholamine secretion from alternatively activated macrophages. In our second study, we demonstrated that WAT browning with its associated lipolysis increased plasma levels of free fatty acids, leading to the accelerated development of hepatic steatosis and dysfunction after a burn injury. The last study of this thesis was geared towards clinical applications, and centered on the inhibition of the WAT to BAT switch via the use of an IL-6R blocker and propranolol to improve post-burn hypermetabolism and organ steatosis. In summary, our findings highlight an essential role of the adipose tissue in contributing to post-burn hypermetabolism and pathology.Ph.D
Metformin Attenuates Hepatic Mitochondrial Dysfunction and Oxidative Stress in a Model of Burn Injury
No full textElderly burn patients are a high-risk group with poor survival rates. The incidence of organ failure for elderly burns is particularly high, and the organs typically affected, such as the liver, are mitochondria rich. This suggests that mitochondria underly the vulnerability of the elderly to burns, and thus treatments directly targeting mitochondria, such as metformin, may improve their outcome. Thus, we hypothesize that the elderly have a worse outcome due to faulty hepatic mitochondria and that metformin intervention would enable recovery. Our data shows that while adult murine mitochondria rebound from the initial insult, older animals display delayed recovery of mitochondrial bioenergetics. Moreover, metformin treatment suppresses the hypermetabolic mitochondria of the younger cohort while significantly increasing respiration in the aged group. These findings suggest that aging leads to a failure to normalize hepatic mitochondria after trauma and that metformin is a possible agent that can restore mitochondrial responses to burns.M.Sc
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