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Sökning: hsv:(MEDICAL AND HEALTH SCIENCES) hsv:(Basic Medicine) hsv:(Physiology) > Chalmers tekniska högskola

  • Resultat 1-10 av 231
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1.
  • Bauzá-Thorbrügge, Marco, et al. (författare)
  • NRF2 is essential for adaptative browning of white adipocytes.
  • 2023
  • Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
  • Tidskriftsartikel (refereegranskat)abstract
    • White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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2.
  • Hallvig, D., et al. (författare)
  • Sleepy driving on the real road and in the simulator - A comparison
  • 2013
  • Ingår i: Accident Analysis and Prevention. - : Elsevier BV. - 0001-4575 .- 1879-2057. ; 50, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Sleepiness has been identified as one of the most important factors contributing to road crashes. However, almost all work on the detailed changes in behavior and physiology leading up to sleep related crashes has been carried out in driving simulators. It is not clear, however, to what extent simulator results can be generalized to real driving. This study compared real driving with driving in a high fidelity, moving base, driving simulator with respect to driving performance, sleep related physiology (using electroencephalography and electrooculography) and subjective sleepiness during night and day driving for 10 participants. The real road was emulated in the simulator. The results show that the simulator was associated with higher levels of subjective and physiological sleepiness than real driving. However, both for real and simulated driving, the response to night driving appears to be rather similar for subjective sleepiness and sleep physiology. Lateral variability was more responsive to night driving in the simulator, while real driving at night involved a movement to the left in the lane and a reduction of speed, both of which effects were absent in the simulator. It was concluded that the relative validity of simulators is acceptable for many variables, but that in absolute terms simulators cause higher sleepiness levels than real driving. Thus, generalizations from simulators to real driving must be made with great caution.
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3.
  • Turanli, Beste, et al. (författare)
  • Drug Repositioning for Effective Prostate Cancer Treatment
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
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6.
  • Venkatakrishnan, Vignesh, 1987, et al. (författare)
  • Novel inhibitory effect of galectin-3 on the respiratory burst induced by Staphylococcus aureus in human neutrophils
  • 2023
  • Ingår i: Glycobiology. - : OXFORD UNIV PRESS INC. - 1460-2423 .- 0959-6658. ; 33:6, s. 503-511
  • Tidskriftsartikel (refereegranskat)abstract
    • Among the responders to microbial invasion, neutrophils represent the earliest and perhaps the most important immune cells that contribute to host defense with the primary role to kill invading microbes using a plethora of stored anti-microbial molecules. One such process is the production of reactive oxygen species (ROS) by the neutrophil enzyme complex NADPH-oxidase, which can be assembled and active either extracellularly or intracellularly in phagosomes (during phagocytosis) and/or granules (in the absence of phagocytosis). One soluble factor modulating the interplay between immune cells and microbes is galectin-3 (gal-3), a carbohydrate-binding protein that regulates a wide variety of neutrophil functions. Gal-3 has been shown to potentiate neutrophil interaction with bacteria, including Staphylococcus aureus, and is also a potent activator of the neutrophil respiratory burst, inducing large amounts of granule-localized ROS in primed cells. Herein, the role of gal-3 in regulating S. aureus phagocytosis and S. aureus-induced intracellular ROS was analyzed by imaging flow cytometry and luminol-based chemiluminescence, respectively. Although gal-3 did not interfere with S. aureus phagocytosis per se, it potently inhibited phagocytosis-induced intracellular ROS production. Using the gal-3 inhibitor GB0139 (TD139) and carbohydrate recognition domain of gal-3 (gal-3C), we found that the gal-3-induced inhibitory effect on ROS production was dependent on the carbohydrate recognition domain of the lectin. In summary, this is the first report of an inhibitory role of gal-3 in regulating phagocytosis-induced ROS production.
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7.
  • Nguyen, Tho D. K., et al. (författare)
  • Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells
  • 2022
  • Ingår i: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:3
  • Tidskriftsartikel (refereegranskat)abstract
    • For decades, "all-or-none"and "kiss-and-run"were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically. © 2022 The Authors. Published by American Chemical Society.
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8.
  • Gennemark, Peter, 1974, et al. (författare)
  • Modeling energy intake by adding homeostatic feedback and drug intervention
  • 2015
  • Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 42:1, s. 79-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Energy intake (EI) is a pivotal biomarker used in quantification approaches to metabolic disease processes such as obesity, diabetes, and growth disorders. Eating behavior is however under both short-term and long-term control. This control system manifests itself as tolerance and rebound phenomena in EI, when challenged by drug treatment or diet restriction. The paper describes a model with the capability to capture physiological counter-regulatory feedback actions triggered by energy imbalances. This feedback is general as it handles tolerance to both increases and decreases in EI, and works in both acute and chronic settings. A drug mechanism function inhibits (or stimulates) EI. The deviation of EI relative to a reference level (set-point) serves as input to a non-linear appetite control signal which in turn impacts EI in parallel to the drug intervention. Three examples demonstrate the potential usefulness of the model in both acute and chronic dosing situations. The model shifts the predicted concentration-response relationship rightwardly at lower concentrations, in contrast to models that do not handle functional adaptation. A fourth example further shows that the model may qualitatively explain differences in rate and extent of adaptation in observed EI and its concomitants in both rodents and humans.
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9.
  • Ghirmai, Semhar, 1993, et al. (författare)
  • Improving the Stability of Red Blood Cells in Rainbow Trout (Oncorhynchus mykiss) and Herring (Clupea harengus): Potential Solutions for Post-mortem Fish Handling to Minimize Lipid Oxidation
  • 2020
  • Ingår i: Food and Bioprocess Technology. - : Springer Science and Business Media LLC. - 1935-5130 .- 1935-5149. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed at limiting hemolysis of fish red blood cells (RBCs) as a strategy to limit hemoglobin (Hb)-induced lipid oxidation duringpost-mortemhandling and processing. Effects of varying temperature, salinity, and mechanical impact were studied using washed resuspended RBCs (wr-RBCs) and whole blood (WB) from rainbow trout (Oncorhynchus mykiss) and herring (Clupea harengus). The wr-RBCs were most stable avoiding mechanical stress, keeping isotonic conditions (0.9-1.3% NaCl) and low temperature 0-6 degrees C, with predicted minimum at 2.5 degrees C. When compared at the same salinity, it was found that hemolysis was more pronounced in herring than trout wr-RBCs. Furthermore, WB was more stable than wr-RBCs, showing protecting the effects of blood plasma. Studying individual plasma components, stabilizing effects were found from glucose, proteins, and ascorbic acid. This study indicates that small adjustments in the early handling and processing of fish such as changing salinity of storage and rinsing solutions could minimize Hb contamination of the fish muscle and thereby improve quality.
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10.
  • Martinez-Tomas, Rebeca, et al. (författare)
  • Daily intake of fruit and vegetable soups processed in different ways increases human serum beta-carotene and lycopene concentrations and reduces levels of several oxidative stress markers in healthy subjects
  • 2012
  • Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 134:1, s. 127-133
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of daily intakes of two differently processed fruit and vegetable soups on beta-carotene and lycopene bioavailability, oxidative stress and cardiovascular risk biomarkers was investigated. An optimised soup produced using heat treatments and high pressure homogenisation for high nutrient retention, and a traditionally produced reference soup were tested. Serum beta-carotene concentration was significantly higher with the optimised than with the reference soup after the supplementation (0.41 +/- 0.05 vs. 0.24 +/- 0.03 mu M, respectively), whereas the serum lycopene concentration was higher in subjects consuming the reference (0.06 +/- 0.02 vs. 0.16 +/- 0.02 mu M). The change in serum homocysteine levels tended to be greater in the optimised group (-1.67 +/- 0.63 vs. 0.02 +/- 0.17 mu M, p = 0.06). Serum antioxidant enzyme activity decreased significantly with consumption of both soups, but to a greater extent with the optimised soup. The consumption of the fruit and vegetable soups increased serum beta-carotene and lycopene concentrations and reduced the levels of several oxidative stress makers, particularly in subjects consuming the optimised soup.
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