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| 3. |
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| 4. |
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| 5. |
- Gullfot, Fredrika, 1967-
(författare)
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Synthesis of xyloglucan oligo- and polysaccharides with glycosynthase technology
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Xyloglucans are polysaccharides found as storage polymers in seeds and tubers, and as cross-linking glycans in the cell wall of plants. Their structure is complex with intricate branching patterns, which contribute to the physical properties of the polysaccharide including its binding to and interaction with other glycans such as cellulose. Xyloglucan is widely used in bulk quantities in the food, textile and paper making industries. With an increasing interest in technically more advanced applications of xyloglucan, such as novel biocomposites, there is a need to understand and control the properties and interactions of xyloglucan with other compounds, to decipher the relationship between xyloglucan structure and function, and in particular the effect of different branching patterns. However, due to the structural heterogeneity of the polysaccharide as obtained from natural sources, relevant studies have not been possible to perform in practise. This fact has stimulated an interest in synthetic methods to obtain xyloglucan mimics and analogs with well-defined structure and decoration patterns. Glycosynthases are hydrolytically inactive mutant glycosidases that catalyse the formation of glycosidic linkages between glycosyl fluoride donors and glycoside acceptors. Since its first conception in 1998, the technology is emerging as a useful tool in the synthesis of large, complex polysaccharides. This thesis presents the generation and characterisation of glycosynthases based on xyloglucanase scaffolds for the synthesis of well-defined homogenous xyloglucan oligo- and polysaccharides with regular substitution patterns.
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| 6. |
- Cutas, Daniela, 1978, et al.
(författare)
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Legal imperialism in the regulation of stem cell research and therapy: the problem of extraterritorial jurisdiction
- 2010
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Ingår i: Capps BJ & Campbell AV (eds.). CONTESTED CELLS: Global Perspectives on the Stem Cell Debate. - London : Imperial College Press. - 9781848164376 ; , s. 95-119
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Countries worldwide have very different national regulations on human embryonic stem (ES) cell research, informed by a range of ethical values. Some countries find reason to extend the applicability of their regulations on such research to its citizens when they visit other countries. Extraterritorial jurisdiction has recently been identified as a potential challenge towards global regulation of ES cell research. This chapter explores the implications and impact of extraterritorial jurisdiction and global regulation of ES cell research on researchers, clinicians and national health systems, and how this may affect patients. The authors argue that it would make ethical sense for ES cell restrictive countries to extend its regulations on ES cell research beyond its borders, because, if these countries really consider embryo destruction to be objectionable on the basis on the status of the embryo, then they ought to count it morally on par with murder (and thus have a moral imperative to protect embryos from the actions of its own citizens). However, doing so could lead to a legal situation that would result in substantial harm to central values in areas besides research, such as health care, the job market, basic freedom of movement, and strategic international finance and politics. Thus, it seems that restrictive extraterritorial jurisdiction in respect to ES cell research would be deeply problematic, given that the ethical permissibility of ES cell research is characterised by deep and wide disagreement.
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| 7. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.
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| 8. |
- Munthe, Christian, 1962
(författare)
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The Price of Precaution and the Ethics of Risk
- 2011
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Since a couple of decades, the notion of a precautionary principle plays a central and increasingly influential role in international as well as national policy and regulation regarding the environment and the use of technology. Urging society to take action in the face of potential risks of human activities in these areas, the recent focus on climate change has further sharpened the importance of this idea. However, the idea of a precautionary principle has also been problematised and criticised by scientists, scholars and policy activists, and been accused of almost every intellectual sin imaginable: unclarity, impracticality, arbitrariness and moral as well as political unsoundness. In that light, the very idea of precaution as an ideal for policy making rather comes out as a dead end. On the basis of these contrasting starting points, Christian Munthe undertakes an innovative, in-depth philosophical analysis of what the idea of a precautionary principle is and should be about. A novel theory of the ethics of imposing risks is developed and used as a foundation for defending the idea of precaution in environmental and technological policy making against its critics, while at the same time avoiding a number of identified flaws. The theory is shown to have far-reaching consequences for areas such as bio-, information- and nuclear technology, and global environmental policy in areas such as climate change. The author argues that, while the price we pay for precaution must not be too high, we have to be prepared to pay it in order to act ethically defensible. A number of practical suggestions for precautionary regulation and policy making are made on the basis of this, and some challenges to basic ethical theory as well as consumerist societies, the global political order and liberal democracy are identified
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| 9. |
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| 10. |
- Enoksson, Peter, 1957, et al.
(författare)
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Micro- and Nanosystems for Sensing in Medicine
- 2008
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Ingår i: Proceedings of Medicinteknikdagarna 2008, 14-15 October, Göteborg, Sweden. ; , s. 117-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 11. |
- Bergman, Alexandra Linda, 1985, et al.
(författare)
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Heterologous phosphoketolase expression redirects flux towards acetate, perturbs sugar phosphate pools and increases respiratory demand in Saccharomyces cerevisiae
- 2019
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Phosphoketolases (Xfpk) are a non-native group of enzymes in yeast, which can be expressed in combination with other metabolic enzymes to positively influence the yield of acetyl-CoA derived products by reducing carbon losses in the form of CO2. In this study, a yeast strain expressing Xfpk from Bifidobacterium breve, which was previously found to have a growth defect and to increase acetate production, was characterized. Results: Xfpk-expression was found to increase respiration and reduce biomass yield during glucose consumption in batch and chemostat cultivations. By cultivating yeast with or without Xfpk in bioreactors at different pHs, we show that certain aspects of the negative growth effects coupled with Xfpk-expression are likely to be explained by proton decoupling. At low pH, this manifests as a reduction in biomass yield and growth rate in the ethanol phase. Secondly, we show that intracellular sugar phosphate pools are significantly altered in the Xfpk-expressing strain. In particular a decrease of the substrates xylulose-5-phosphate and fructose-6-phosphate was detected (26% and 74% of control levels) together with an increase of the products glyceraldehyde-3-phosphate and erythrose-4-phosphate (208% and 542% of control levels), clearly verifying in vivo Xfpk enzymatic activity. Lastly, RNAseq analysis shows that Xfpk expression increases transcription of genes related to the glyoxylate cycle, the TCA cycle and respiration, while expression of genes related to ethanol and acetate formation is reduced. The physiological and transcriptional changes clearly demonstrate that a heterologous phosphoketolase flux in combination with endogenous hydrolysis of acetyl-phosphate to acetate increases the cellular demand for acetate assimilation and respiratory ATP-generation, leading to carbon losses. Conclusion: Our study shows that expression of Xfpk in yeast diverts a relatively small part of its glycolytic flux towards acetate formation, which has a significant impact on intracellular sugar phosphate levels and on cell energetics. The elevated acetate flux increases the ATP-requirement for ion homeostasis and need for respiratory assimilation, which leads to an increased production of CO2. A majority of the negative growth effects coupled to Xfpk expression could likely be counteracted by preventing acetate accumulation via direct channeling of acetyl-phosphate towards acetyl-CoA.
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| 12. |
- Rems, Lea, et al.
(författare)
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Cell electrofusion using nanosecond electric pulses
- 2013
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Ingår i: Scientific Reports. - : Macmillan Publishers Ltd.. - 2045-2322. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Electrofusion is an efficient method for fusing cells using short-duration high-voltage electric pulses. However, electrofusion yields are very low when fusion partner cells differ considerably in their size, since the extent of electroporation (consequently membrane fusogenic state) with conventionally used microsecond pulses depends proportionally on the cell radius. We here propose a new and innovative approach to fuse cells with shorter, nanosecond (ns) pulses. Using numerical calculations we demonstrate that ns pulses can induce selective electroporation of the contact areas between cells (i.e. the target areas), regardless of the cell size. We then confirm experimentally on B16-F1 and CHO cell lines that electrofusion of cells with either equal or different size by using ns pulses is indeed feasible. Based on our results we expect that ns pulses can improve fusion yields in electrofusion of cells with different size, such as myeloma cells and B lymphocytes in hybridoma technology.
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| 13. |
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| 14. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 15. |
- Apelgren, Peter, et al.
(författare)
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Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.
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| 16. |
- Wang, Guokun, 1988, et al.
(författare)
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RNAi expression tuning, microfluidic screening, and genome recombineering for improved protein production in Saccharomyces cerevisiae
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:19, s. 9324-9332
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Tidskriftsartikel (refereegranskat)abstract
- The cellular machinery that supports protein synthesis and secretion lies at the foundation of cell factory-centered protein production. Due to the complexity of such cellular machinery, the challenge in generating a superior cell factory is to fully exploit the production potential by finding beneficial targets for optimized strains, which ideally could be used for improved secretion of other proteins. We focused on an approach in the yeast Saccharomyces cerevisiae that allows for attenuation of gene expression, using RNAi combined with high-throughput microfluidic single-cell screening for cells with improved protein secretion. Using direct experimental validation or enrichment analysis-assisted characterization of systematically introduced RNAi perturbations, we could identify targets that improve protein secretion. We found that genes with functions in cellular metabolism (YDC1, AAD4, ADE8, and SDH1), protein modification and degradation (VPS73, KTR2, CNL1, and SSA1), and cell cycle (CDC39), can all impact recombinant protein production when expressed at differentially down-regulated levels. By establishing a workflow that incorporates Cas9-mediated recombineering, we demonstrated how we could tune the expression of the identified gene targets for further improved protein production for specific proteins. Our findings offer a high throughput and semirational platform design, which will improve not only the production of a desired protein but even more importantly, shed additional light on connections between protein production and other cellular processes.
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| 17. |
- Kanagarajan, Selvaraju, et al.
(författare)
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Production of functional human fetal hemoglobin in Nicotiana benthamiana for development of hemoglobin-based oxygen carriers
- 2021
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 184, s. 955-966
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin-based oxygen carriers have long been pursued to meet clinical needs by using native hemoglobin (Hb) from human or animal blood, or recombinantly produced Hb, but the development has been impeded by safety and toxicity issues. Herewith we report the successful production of human fetal hemoglobin (HbF) in Nicotiana benthamiana through Agrobacterium tumefaciens-mediated transient expression. HbF is a heterotetrameric protein composed of two identical α- and two identical γ-subunits, held together by hydrophobic interactions, hydrogen bonds, and salt bridges. In our study, the α- and γ-subunits of HbF were fused in order to stabilize the α-subunits and facilitate balanced expression of α- and γ-subunits in N. benthamiana. Efficient extraction and purification methods enabled production of the recombinantly fused endotoxin-free HbF (rfHbF) in high quantity and quality. The transiently expressed rfHbF protein was identified by SDS-PAGE, Western blot and liquid chromatography-tandem mass spectrometry analyses. The purified rfHbF possessed structural and functional properties similar to native HbF, which were confirmed by biophysical, biochemical, and in vivo animal studies. The results demonstrate a high potential of plant expression systems in producing Hb products for use as blood substitutes.
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| 18. |
- Iseri, Emre
(författare)
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Microfluidic Compartmentalization for Smart Materials, Medical Diagnostics and Cell Therapy
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The organisation of fluids in small compartments is ubiquitous in nature, such as in the cellular composition of all life. This work explores several engineering avenues where microscale fluid compartmentalization can bring novel material properties or novel functionality in life sciences or medicine. Here, we introduce four unique compartmentalization methods: 1) 3D fluid self-organisation in microscaffolds (FLUID3EAMS), 2) 2D microcapillary arrays on a dipstick (Digital Dipstick), 3) a sliding microfluidic platform with cross-flow (Slip-X-Chip), and 4) compartmentalization by cutting of soft solid matter (Solidify & Cut). These methods were used in a wide range of applications. Within the area of smart materials, we applied FLUID3EAMS to synthesize materials with temperature-tuneable permeability and surface energy and to establish, in a well-controlled fashion, tissue-like materials in the form of 3D droplet interface bilayer networks. Solidify & Cut was used to form soft composites with a new type of magnetic behaviour, rotation-induced ferromagnetism, that allows easy reprogramming of the magnetization of magnetopolymers. Within the area of medical diagnostics, we applied Digital Dipstick to perform rapid digital bacterial culture in a dipstick format and obtained clinically relevant diagnostic results on samples from patients with a urinary tract infection. Furthermore, Slip-X-Chip enables particle concentration and washing as new functions in sliding microfluidic platforms, which significantly expands their potential application area. Finally, within the area of cell therapy, we explored the microencapsulation of high concentrations of therapeutic cells and presented a novel technique to fabricate core-shell microcapsules by exploiting the superior material properties of spider silk membranes.
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| 19. |
- Böhler, Christian, et al.
(författare)
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Multilayer Arrays for Neurotechnology Applications (MANTA): Chronically Stable Thin-Film Intracortical Implants
- 2023
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 10:14
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Tidskriftsartikel (refereegranskat)abstract
- Flexible implantable neurointerfaces show great promise in addressing one of the major challenges of implantable neurotechnology, namely the loss of signal connected to unfavorable probe tissue interaction. The authors here show how multilayer polyimide probes allow high-density intracortical recordings to be combined with a reliable long-term stable tissue interface, thereby progressing toward chronic stability of implantable neurotechnology. The probes could record 10–60 single units over 5 months with a consistent peak-to-peak voltage at dimensions that ensure robust handling and insulation longevity. Probes that remain in intimate contact with the signaling tissue over months to years are a game changer for neuroscience and, importantly, open up for broader clinical translation of systems relying on neurotechnology to interface the human brain.
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| 20. |
- Ohlson, Sten, et al.
(författare)
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Weak affinity chromatography
- 1993. - 1
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Ingår i: Handbook of affinity chromatography. - New York : Marcel Dekker. - 0824789393 ; , s. 299-314
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 21. |
- Sepehri, Sobhan, 1986, et al.
(författare)
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Volume-amplified magnetic bioassay integrated with microfluidic sample handling and high-Tc SQUID magnetic readout
- 2018
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Ingår i: APL Bioengineering. - : AIP Publishing. - 2473-2877. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- A bioassay based on a high-Tc superconducting quantum interference device (SQUID) reading out functionalized magnetic nanoparticles (fMNPs) in a prototype microfluidic platform is presented. The target molecule recognition is based on volume amplification using padlock-probe-ligation followed by rolling circle amplification (RCA). The MNPs are functionalized with single-stranded oligonucleotides, which give a specific binding of the MNPs to the large RCA coil product, resulting in a large change in the amplitude of the imaginary part of the ac magnetic susceptibility. The RCA products from amplification of synthetic Vibrio cholera target DNA were investigated using our SQUID ac susceptibility system in microfluidic channel with an equivalent sample volume of 3 μl. From extrapolation of the linear dependence of the SQUID signal versus concentration of the RCA coils, it is found that the projected limit of detection for our system is about 1.0 e5 RCA coils (0.2e−18 mol), which is equivalent to 66 fM in the 3 μl sample volume. This ultra-high magnetic sensitivity and integration with microfluidic sample handling are critical steps towards magnetic bioassays for rapid detection of DNA and RNA targets at the point of care.
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| 22. |
- Ušaj, Marko, et al.
(författare)
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Electrofusion of B16-F1 and CHO cells: the comparison of the pulse first and contact first protocols
- 2013
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Ingår i: Bioelectrochemistry. - : Elsevier BV. - 1567-5394 .- 1878-562X. ; 89, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- High voltage electric pulses induce permeabilisation (i.e. electroporation) of cell membranes. Electric pulses also induce fusion of cells which are in contact. Contacts between cells can be established before electroporation, in so-called contact first or after electroporation in pulse first protocol. The lowest fusion yield was obtained by pulse first protocol (0.8%±0.3%) and it was only detected by phase contrast microscopy. Higher fusion yield detected by fluorescence microscopy was obtained by contact first protocol. The highest fusion yield (15%) was obtained by modified adherence method whereas fusion yield obtained by dielectrophoresis was lower (4%). The results are in agreement with current understanding of electrofusion process and with existing electrochemical models. Our data indicate that probability of stalk formation leading to fusion pores and cytoplasmic mixing is higher in contact first protocol where cells in contact are exposed to electric pulses. Another contribution of present study is the comparison of two detection methods. Although fusion yield can be more precisely determined with fluorescence microscopy we should note that by using this detection method single coloured fused cells cannot be detected. Therefore low fusion yields are more reliably detected by phase contrast microscopy.
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| 23. |
- Björn, Niclas, et al.
(författare)
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Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia
- 2020
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Ingår i: The Pharmacogenomics Journal. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 20:2, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.
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| 24. |
- Apelgren, Peter, et al.
(författare)
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Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation
- 2021
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
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| 25. |
- Gillman, Anna, et al.
(författare)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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Ingår i: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Tidskriftsartikel (refereegranskat)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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| 26. |
- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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| 27. |
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| 28. |
- Munthe, Christian, 1962
(författare)
-
Pure Selection. The Ethics of Preimplantation Genetic Diagnosis and Choosing Children without Abortion
- 1999
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Preimplantation ge¬netic diagnosis (PGD) is taken to mark the starting-point of a new phase in human reproduction, where the possibility of choosing children on genetic grounds without having to resort to ethi¬cally controversial procedures (such as abortion) will grad¬ually increase. Ethical and political issues actu¬alised by this develop¬ment are addressed. The discussion touches upon issues regarding the moral status of em¬bryos and gametes, the moral import of respecting individual auton¬omy and its implications for the requirement of informed consent in health-care, the connec¬tion between sickness, dis¬ability and the value of life, the moral status of possible future people, and the connection between choosing children and eugenic policies of the past. Practical policy issues are adressed on the basis of this, as well as an empirical case-study of the intro¬duction of PGD in Sweden. The book ends up in a set of recommendations regarding the management of re¬search on, introduction and routine use of procedures for pure se¬lection, both within health care and from the point of view of society as a whole. It is argued that research on such procedures should be allowed and supported by society. However, tight restrictions regarding the clinical introduction of new procedures in this area is highly desirable. A rough model for implementing such re¬strictions is also pre¬sented. It is further asserted that, although reasons of economy and safety should limit the access to pure se¬lection, society should not apply any explicit restrictions based on ideasregarding how different traits affect a person’s quality of life. It is stressed that, in order to to avoid a re¬sur¬rection of eugenic policies of the past, the development in this field un¬der¬lines the need for continued and strengthen public support to the sick, dis¬abled and mentally retarded.
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| 29. |
- Cámara, Elena, 1985, et al.
(författare)
-
Data mining of Saccharomyces cerevisiae mutants engineered for increased tolerance towards inhibitors in lignocellulosic hydrolysates
- 2022
-
Ingår i: Biotechnology Advances. - : Elsevier BV. - 0734-9750. ; 57
-
Forskningsöversikt (refereegranskat)abstract
- The use of renewable plant biomass, lignocellulose, to produce biofuels and biochemicals using microbial cell factories plays a fundamental role in the future bioeconomy. The development of cell factories capable of efficiently fermenting complex biomass streams will improve the cost-effectiveness of microbial conversion processes. At present, inhibitory compounds found in hydrolysates of lignocellulosic biomass substantially influence the performance of a cell factory and the economic feasibility of lignocellulosic biofuels and chemicals. Here, we present and statistically analyze data on Saccharomyces cerevisiae mutants engineered for altered tolerance towards the most common inhibitors found in lignocellulosic hydrolysates: acetic acid, formic acid, furans, and phenolic compounds. We collected data from 7971 experiments including single overexpression or deletion of 3955 unique genes. The mutants included in the analysis had been shown to display increased or decreased tolerance to individual inhibitors or combinations of inhibitors found in lignocellulosic hydrolysates. Moreover, the data included mutants grown on synthetic hydrolysates, in which inhibitors were added at concentrations that mimicked those of lignocellulosic hydrolysates. Genetic engineering aimed at improving inhibitor or hydrolysate tolerance was shown to alter the specific growth rate or length of the lag phase, cell viability, and vitality, block fermentation, and decrease product yield. Different aspects of strain engineering aimed at improving hydrolysate tolerance, such as choice of strain and experimental set-up are discussed and put in relation to their biological relevance. While successful genetic engineering is often strain and condition dependent, we highlight the conserved role of regulators, transporters, and detoxifying enzymes in inhibitor tolerance. The compiled meta-analysis can guide future engineering attempts and aid the development of more efficient cell factories for the conversion of lignocellulosic biomass.
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| 30. |
- Säljö, Karin, 1981, et al.
(författare)
-
Successful engraftment, vascularization, and In vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue
- 2020
-
Ingår i: Bioprinting. - : Elsevier BV. - 2405-8866. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Autologous fat grafting is commonly used for correction of soft-tissue deformities, despite a high rate of graft resorption and nutrition-supply challenges. Three-dimensional (3D)-bioprinting techniques enable tailor-made architecture of grafts and promote vascularization. In recent years, the importance of adipose tissue-derived stromal/stem cells (ASCs) for graft survival has become evident. This study investigated the printability of mechanically processed lipoaspirate containing ASCs, as well as in vivo survival and neovascularisation of the 3D-bioprinted grafts. Human lipoaspirate-derived adipose tissue was 3D bioprinted in alginate/nanocellulose bioink, implanted into nude mice, and harvested at days 3, 7, and 30, respectively. The processed lipoaspirate showed high viability and good printability when combined with alginate/nanocellulose, and the 3D-bioprinted grafts contained intact vascular structures and a high density of mature adipocytes before and after engraftment. After 30 days in vivo, novel blood vessels were present on the graft surface, showing signs of angiogenesis into the graft, as well as vascularization in the centre of the tissue. Moreover, histologic and immunohistochemical characterisation confirmed the presence of potential ASCs during the first week in vivo. These results demonstrated that human lipoaspirate-derived adipose tissue showed high printability, survived 3D bioprinting and engraftment in vivo, and displayed macroscopic and microscopic evidence of vascularization.
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| 31. |
- Shaner, Sebastian, et al.
(författare)
-
Bioelectronic microfluidic wound healing: a platform for investigating direct current stimulation of injured cell collectives
- 2023
-
Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 23:6, s. 1531-1546
-
Tidskriftsartikel (refereegranskat)abstract
- Upon cutaneous injury, the human body naturally forms an electric field (EF) that acts as a guidance cue for relevant cellular and tissue repair and reorganization. However, the direct current (DC) flow imparted by this EF can be impacted by a variety of diseases. This work delves into the impact of DC stimulation on both healthy and diabetic in vitro wound healing models of human keratinocytes, the most prevalent cell type of the skin. The culmination of non-metal electrode materials and prudent microfluidic design allowed us to create a compact bioelectronic platform to study the effects of different sustained (12 hours galvanostatic DC) EF configurations on wound closure dynamics. Specifically, we compared if electrotactically closing a wound's gap from one wound edge (i.e., uni-directional EF) is as effective as compared to alternatingly polarizing both the wound's edges (i.e., pseudo-converging EF) as both of these spatial stimulation strategies are fundamental to the eventual translational electrode design and strategy. We found that uni-directional electric guidance cues were superior in group keratinocyte healing dynamics by enhancing the wound closure rate nearly three-fold for both healthy and diabetic-like keratinocyte collectives, compared to their non-stimulated respective controls. The motility-inhibited and diabetic-like keratinocytes regained wound closure rates with uni-directional electrical stimulation (increase from 1.0 to 2.8% h−1) comparable to their healthy non-stimulated keratinocyte counterparts (3.5% h−1). Our results bring hope that electrical stimulation delivered in a controlled manner can be a viable pathway to accelerate wound repair, and also by providing a baseline for other researchers trying to find an optimal electrode blueprint for in vivo DC stimulation.
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| 32. |
- Fu, Ying, 1964-, et al.
(författare)
-
Endocytic pathway of vascular cell adhesion molecule 1 in human umbilical vein endothelial cell identified in vitro by using functionalized nontoxic fluorescent quantum dots
- 2019
-
Ingår i: Sensors and actuators. B, Chemical. - : Elsevier B.V.. - 0925-4005 .- 1873-3077. ; 297
-
Tidskriftsartikel (refereegranskat)abstract
- Studies about vascular cell adhesion molecule 1 (VCAM1) in tumor growth, metastasis, and angiogenesis suggest that targeting VCAM1 expression is an attractive strategy for diagnosis and anti-tumor therapy. However, the endocytic pathway of VCAM1 in vascular cells has not been well characterized. In this study we visualize the endocytic pathway of tumor necrosis factor α (TNFα) induced VCAM1 in human umbilical vein endothelial cell (HUVEC) in vitro using 5-carboxyfluorescein labeled VCAM1 binding peptides and fluorescent water-dispersible 3-mercaptopropionic acid (3MPA)-coated CdSe-CdS/Cd0.5Zn0.5S/ZnS core–multishell nontoxic quantum dots (3MPA-QDs) functionalized with VCAM1 binding peptides. Clear key in vitro observations are as follows: (a) 3MPA-QDs functionalized with VCAM1 binding peptides, denoted as VQDs, adhered and aggregated cumulatively to cell membrane around 2 h after VQD deposition to cell culture medium and were found in lysosomes in TNFα-treated HUVECs approximately 24 h after VQD deposition; (b) VQDs remained in TNFα-treated HUVECs for the whole 16 days of the experimental observation period; (c) quite differently, 3MPA-QDs were endocytosed then exocytosed by HUVECs via endosomes in about 24–48 h after 3MPA-QD deposition. Our study suggests that VCAM1 molecules, initially expressed on cell membrane induced by TNFα treatment, are internalized into lysosomes. This provides a novel means to deliver materials to lysosomes such as enzyme replacement therapy. Moreover, our meticulous sensing methodology of devising fluorescent nontoxic QDs advances biosensing technique for studying cellular activities in vitro and in vivo. © 2019 The Authors
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| 33. |
- Huang, Mingtao, 1984, et al.
(författare)
-
Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production
- 2018
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:47, s. E11025-E11032
-
Tidskriftsartikel (refereegranskat)abstract
- Baker’s yeast Saccharomyces cerevisiae is one of the most important and widely used cell factories for recombinant protein production. Many strategies have been applied to engineer this yeast for improving its protein production capacity, but productivity is still relatively low, and with increasing market demand, it is important to identify new gene targets, especially targets that have synergistic effects with previously identified targets. Despite improved protein production, previous studies rarely focused on processes associated with intracellular protein retention. Here we identified genetic modifications involved in the secretory and trafficking pathways, the histone deacetylase complex, and carbohydrate metabolic processes as targets for improving protein secretion in yeast. Especially modifications on the endosome-to-Golgi trafficking was found to effectively reduce protein retention besides increasing protein secretion. Through combinatorial genetic manipulations of several of the newly identified gene targets, we enhanced the protein production capacity of yeast by more than fivefold, and the best engineered strains could produce 2.5 g/L of a fungal α-amylase with less than 10% of the recombinant protein retained within the cells, using fed-batch cultivation.
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| 34. |
- Pettersen, Emily, 1996, et al.
(författare)
-
Electrical stimulation to promote osseointegration of bone anchoring implants: a topical review
- 2022
-
Ingår i: Journal of Neuroengineering and Rehabilitation. - : Springer Science and Business Media LLC. - 1743-0003. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Electrical stimulation has shown to be a promising approach for promoting osseointegration in bone anchoring implants, where osseointegration defines the biological bonding between the implant surface and bone tissue. Bone-anchored implants are used in the rehabilitation of hearing and limb loss, and extensively in edentulous patients. Inadequate osseointegration is one of the major factors of implant failure that could be prevented by accelerating or enhancing the osseointegration process by artificial means. In this article, we reviewed the efforts to enhance the biofunctionality at the bone-implant interface with electrical stimulation using the implant as an electrode. We reviewed articles describing different electrode configurations, power sources, and waveform-dependent stimulation parameters tested in various in vitro and in vivo models. In total 55 English-language and peer-reviewed publications were identified until April 2020 using PubMed, Google Scholar, and the Chalmers University of Technology Library discovery system using the keywords: osseointegration, electrical stimulation, direct current and titanium implant. Thirteen of those publications were within the scope of this review. We reviewed and compared studies from the last 45 years and found nonuniform protocols with disparities in cell type and animal model, implant location, experimental timeline, implant material, evaluation assays, and type of electrical stimulation. The reporting of stimulation parameters was also found to be inconsistent and incomplete throughout the literature. Studies using in vitro models showed that osteoblasts were sensitive to the magnitude of the electric field and duration of exposure, and such variables similarly affected bone quantity around implants in in vivo investigations. Most studies showed benefits of electrical stimulation in the underlying processes leading to osseointegration, and therefore we found the idea of promoting osseointegration by using electric fields to be supported by the available evidence. However, such an effect has not been demonstrated conclusively nor optimally in humans. We found that optimal stimulation parameters have not been thoroughly investigated and this remains an important step towards the clinical translation of this concept. In addition, there is a need for reporting standards to enable meta-analysis for evidence-based treatments.
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| 35. |
- von Mentzer, Ula, 1995, et al.
(författare)
-
Biomaterial Integration in the Joint: Pathological Considerations, Immunomodulation, and the Extracellular Matrix
- 2022
-
Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5195 .- 1616-5187. ; 22:7
-
Forskningsöversikt (refereegranskat)abstract
- Defects of articular joints are becoming an increasing societal burden due to a persistent increase in obesity and aging. For some patients suffering from cartilage erosion, joint replacement is the final option to regain proper motion and limit pain. Extensive research has been undertaken to identify novel strategies enabling earlier intervention to promote regeneration and cartilage healing. With the introduction of decellularized extracellular matrix (dECM), researchers have tapped into the potential for increased tissue regeneration by designing biomaterials with inherent biochemical and immunomodulatory signals. Compared to conventional and synthetic materials, dECM-based materials invoke a reduced foreign body response. It is therefore highly beneficial to understand the interplay of how these native tissue-based materials initiate a favorable remodeling process by the immune system. Yet, such an understanding also demands increasing considerations of the pathological environment and remodeling processes, especially for materials designed for early disease intervention. This knowledge will avoid rejection and help predict complications in conditions with inflammatory components such as arthritides. This review outlines general issues facing biomaterial integration and emphasizes the importance of tissue-derived macromolecular components in regulating essential homeostatic, immunological, and pathological processes to increase biomaterial integration for patients suffering from joint degenerative diseases.
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| 36. |
- Martinez Avila, Hector, 1985, et al.
(författare)
-
Biocompatibility evaluation of densified bacterial nanocellulose hydrogel as an implant material for auricular cartilage regeneration
- 2014
-
Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 98:17, s. 7423-7435
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC), synthesized by the bacterium Gluconacetobacter xylinus, is composed of highly hydrated fibrils (99 % water) with high mechanical strength. These exceptional material properties make BNC a novel biomaterial for many potential medical and tissue engineering applications. Recently, BNC with cellulose content of 15 % has been proposed as an implant material for auricular cartilage replacement, since it matches the mechanical requirements of human auricular cartilage. This study investigates the biocompatibility of BNC with increased cellulose content (17 %) to evaluate its response in vitro and in vivo. Cylindrical BNC structures (48 Au 20 mm) were produced, purified in a built-in house perfusion system, and compressed to increase the cellulose content in BNC hydrogels. The reduction of endotoxicity of the material was quantified by bacterial endotoxin analysis throughout the purification process. Afterward, the biocompatibility of the purified BNC hydrogels with cellulose content of 17 % was assessed in vitro and in vivo, according to standards set forth in ISO 10993. The endotoxin content in non-purified BNC (2,390 endotoxin units (EU)/ml) was reduced to 0.10 EU/ml after the purification process, level well below the endotoxin threshold set for medical devices. Furthermore, the biocompatibility tests demonstrated that densified BNC hydrogels are non-cytotoxic and cause a minimal foreign body response. In support with our previous findings, this study concludes that BNC with increased cellulose content of 17 % is a promising non-resorbable biomaterial for auricular cartilage tissue engineering, due to its similarity with auricular cartilage in terms of mechanical strength and host tissue response.
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| 37. |
- Martinez Avila, Hector, 1985
(författare)
-
Biofabrication, Biomechanics and Biocompatibility of Nanocellulose-based Scaffolds for Auricular Cartilage Regeneration
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In about 2:10,000 births the external part of the ear, the auricle, is severely malformed or absent. Furthermore, tumors and trauma can cause defects to the auricle. For patients with dysplasia of the auricle, and especially for children, an inconspicuous outer appearance with life-like auricles is important for their psychological and emotional well being as well as their psycho-social development. Auricular reconstruction remains a great challenge due to the complexity of surgical reconstruction using rib cartilage. Despite the advances in stem cell technology and biomaterials, auricular cartilage tissue engineering (TE) is still in an early stage of development due to critical requirements demanding appropriate mechanical properties and shape stability of the tissue-engineered construct. This thesis has focused on developing patient-specific tissue-engineered auricles for one-step surgery using a novel biomaterial, bacterial nanocellulose (BNC), seeded with human nasoseptal chondrocytes (hNC) and bone marrow mononuclear cells (MNC).Biomechanical properties of human auricle cartilage were measured and used as a benchmark for tuning BNC properties. In order to meet the biomechanical requirements, a scaffold with bilayer architecture composed of a dense BNC support layer and a macroporous structure was designed. Firstly, the biocompatibility of the dense BNC layer was investigated, demonstrating a minimal foreign body response according to standards set forth in ISO 10993. Secondly, different methods to create macroporous BNC scaffolds were studied and the redifferentiation capacity of hNCs was evaluated in vitro; revealing that macroporous BNC scaffolds support cell ingrowth, proliferation and neocartilage formation. The bilayer BNC scaffold was biofabricated and tested for endotoxins and cytotoxicity before evaluating in long-term 3D culture, and subsequently in vivo for eight weeks—in an immunocompromised animal model. The results demonstrated that the non-pyrogenic and non- cytotoxic bilayer BNC scaffold offers a good mechanical stability and maintains a structural integrity, while providing a porous 3D environment that is suitable for hNCs and MNCs to produce neocartilage, in vitro and in vivo. Furthermore, patient-specific auricular BNC scaffolds with bilayer architecture were biofabricated and seeded with autologous rabbit auricular chondrocytes (rAC) for implantation in an immunocompetent rabbit model for six weeks. The results demonstrated the shape stability of the rAC-seeded scaffolds and neocartilage depositions in the immunocompetent autologous grafts. 3D bioprinting was also evaluated for biofabrication of patient-specific, chondrocyte-laden auricular constructs using a bioink composed of nanofibrillated cellulose and alginate. Bioprinted auricular constructs showed an excellent shape and size stability after in vitro culture. Moreover, this bioink supports redifferentiation of hNCs while offering excellent printability, making this a promising approach for auricular cartilage TE. Furthermore, the use of bioreactors is essential for the development of tissue-engineered cartilage in vitro. Thus, a compression bioreactor was utilized to apply dynamic mechanical stimulation to cell-seeded constructs as a means to enhance production of extracellular matrix in vitro.In this work, a potential clinical therapy for auricular reconstruction using tissue-engineered auricles is demonstrated; where BNC is proposed as a promising non-degradable biomaterial with good chemical and mechanical stability for auricular cartilage TE. Although the primary focus of this thesis is on auricular reconstruction, the methods developed are also applicable in the regeneration of other cartilage tissues such as those found in the nose, trachea, spine and articular joints.
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| 38. |
- Ortiz Catalan, Max Jair, 1982, et al.
(författare)
-
Self-Contained Neuromusculoskeletal Arm Prostheses
- 2020
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:18, s. 1732-1738
-
Tidskriftsartikel (refereegranskat)abstract
- After transhumeral amputation, four patients had implantation of a self-contained, osseointegrated prosthesis with a neuromusculoskeletal interface that allowed intuitive control of the prosthetic hand and arm over 3 to 7 years. A video shows use of the prostheses in daily life. We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.)
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| 39. |
- Skiöld, Sara, et al.
(författare)
-
Radiation-induced stress response in peripheral blood of breast cancer patients differs between patients with severe acute skin reactions and patients with no side effects to radiotherapy
- 2013
-
Ingår i: Mutation research. Genetic toxicology and environmental mutagenesis. - : Elsevier BV. - 1383-5718 .- 1879-3592. ; 756:1-2, s. 152-157
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to compare the radiation-induced oxidative stress response in blood samples from breast cancer patients that developed severe acute skin reactions during the radiotherapy, with the response in blood samples from patients with no side effects. Peripheral blood was collected from 12 breast cancer patients showing no early skin reactions after radiotherapy (RTOG grade 0) and from 14 breast cancer patients who developed acute severe skin reactions (RTOG grade 3-4). Whole blood was irradiated with 0, 5 and 2000 mGy gamma-radiation and serum was isolated. The biomarker for oxidative stress, 8-oxo-dG, was analyzed in the serum by a modified ELISA. While a significant radiation-induced increase of serum 8-oxo-dG levels was observed in serum of the RTOG 0 patients, no increase was seen in serum of the RTOG 3-4 patients. The radiation induced increase in serum 8-oxo-dG levels after 5 mGy did not differ significantly from the increase observed for 2000 mGy in the RTOG 3-4 cohort, thus no dose response relation was observed. A receiver operating characteristic (ROC) value of 0.97 was obtained from the radiation-induced increase in 8-oxo-dG indicating that the assay could be used to identify patients with severe acute adverse reactions to radiotherapy. The results show that samples of whole blood from patients, classified as highly radiosensitive (RTOG 3-4) based on their skin reactions to radiotherapy, differ significantly in their oxidative stress response to ionizing radiation compared to samples of whole blood from patients with no skin reactions (RTOG 0). Extracellular 8-oxo-dG is primarily a biomarker of nucleotide damage and the results indicate that the patients with severe acute skin reactions differ in their cellular response to ionizing radiation at the level of induction of oxidative stress or at the level of repair or both.
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| 40. |
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| 41. |
- Apelgren, Peter, et al.
(författare)
-
In Vivo Human Cartilage Formation in Three-Dimensional Bioprinted Constructs with a Novel Bacterial Nanocellulose Bioink
- 2019
-
Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 5:5, s. 2482-2490
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC) is a 3D network of nanofibrils exhibiting excellent biocompatibility. Here, we present the aqueous counter collision (ACC) method of BNC disassembly to create bioink with suitable properties for cartilage-specific 3D-bioprinting. BNC was disentangled by ACC, and fibril characteristics were analyzed. Bioink printing fidelity and shear-thinning properties were evaluated. Cell-laden bioprinted grid constructs (5 X 5 X 1 mm(3)) containing human nasal chondrocytes (10 M mL(-1)) were implanted in nude mice and explanted after 30 and 60 days. Both ACC and hydrolysis resulted in significantly reduced fiber lengths, with ACC resulting in longer fibrils and fewer negative charges relative to hydrolysis. Moreover, ACC-BNC bioink showed outstanding printability, postprinting mechanical stability, and structural integrity. In vivo, cell-laden structures were rapidly integrated, maintained structural integrity, and showed chondrocyte proliferation, with 32.8 +/- 13.8 cells per mm(2) observed after 30 days and 85.6 +/- 30.0 cells per mm(2) at day 60 (p = 0.002). Furthermore, a full-thickness skin graft was attached and integrated completely on top of the 3D-bioprinted construct. The novel ACC disentanglement technique makes BNC biomaterial highly suitable for 3D-bioprinting and clinical translation, suggesting cell-laden 3D-bioprinted ACC-BNC as a promising solution for cartilage repair.
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| 42. |
- Cutas, Daniela, 1978
(författare)
-
GenEtica Reproducerii : The GenEthics of Reproduction
- 2007
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- The book comprises three parts: (1) a general presentation and analysis of the main relevant concepts: bioethics, human genetic engineering, eugenics, disability and, particularly, of the relations between these; (2) the analysis of two documents of the Council of Europe (the so called “Bioethics Convention” and its first protocol), and the reconstruction of the debates surrounding their primary concerns: human dignity and rights in relation to the prospect of human genetic engineering; and (3) the analysis of a Romanian draft law on human assisted reproduction and of the Romanian legislative endeavours and debates regarding human genetic engineering.
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| 43. |
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| 44. |
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| 45. |
- Nilsson, Björn, et al.
(författare)
-
An improved method for detecting and delineating genomic regions with altered gene expression in cancer
- 2008
-
Ingår i: GENOME BIOL. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 9:1, s. R13-
-
Tidskriftsartikel (refereegranskat)abstract
- Genomic regions with altered gene expression are a characteristic feature of cancer cells. We present a novel method for identifying such regions in gene expression maps. This method is based on total variation minimization, a classical signal restoration technique. In systematic evaluations, we show that our method combines top-notch detection performance with an ability to delineate relevant regions without excessive over-segmentation, making it a significant advance over existing methods. Software (Rendersome) is provided.
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| 46. |
- Walladbegi, Java, et al.
(författare)
-
Three-dimensional bioprinting using a coaxial needle with viscous inks in bone tissue engineering - An in vitro study
- 2020
-
Ingår i: Annals of Maxillofacial Surgery. - : Medknow. - 2249-3816 .- 2231-0746. ; 10:2, s. 370-376
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Vascularized autologous tissue grafts are considered 'gold standard' for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells. Materials and Methods: In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay. Results: Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours. Discussion: Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.
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| 47. |
- Larsson, Karl-Johan, 1985, et al.
(författare)
-
Influences of human thorax variability on population rib fracture risk prediction using human body models
- 2023
-
Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Rib fractures remain a common injury for vehicle occupants in crashes. The risk of a human sustaining rib fractures from thorax loading is highly variable, potentially due to a variability in individual factors such as material properties and geometry of the ribs and ribcage. Human body models (HBMs) with a detailed ribcage can be used as occupant substitutes to aid in the prediction of rib injury risk at the tissue level in crash analysis. To improve this capability, model parametrization can be used to represent human variability in simulation studies. The aim of this study was to identify the variations in the physical properties of the human thorax that have the most influence on rib fracture risk for the population of vehicle occupants. A total of 15 different geometrical and material factors, sourced from published literature, were varied in a parametrized SAFER HBM. Parametric sensitivity analyses were conducted for two crash configurations, frontal and near-side impacts. The results show that variability in rib cortical bone thickness, rib cortical bone material properties, and rib cross-sectional width had the greatest influence on the risk for an occupant to sustain two or more fractured ribs in both impacts. Therefore, it is recommended that these three parameters be included in rib fracture risk analysis with HBMs for the population of vehicle occupants.
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| 48. |
- Dietrich, Franciele, et al.
(författare)
-
Effect of storage and preconditioning of healing rat Achilles tendon on structural and mechanical properties
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Tendon tissue storage and preconditioning are often used in biomechanical experiments and whether this generates alterations in tissue properties is essential to know. The effect of storage and preconditioning on dense connective tissues, like tendons, is fairly understood. However, healing tendons are unlike and contain a loose connective tissue. Therefore, we investigated if storage of healing tendons in the fridge or freezer changed the mechanical properties compared to fresh tendons, using a pull-to-failure or a creep test. Tissue morphology and cell viability were also evaluated. Additionally, two preconditioning levels were tested. Rats underwent Achilles tendon transection and were euthanized 12 days postoperatively. Statistical analyzes were done with one-way ANOVA or Student’s t-test. Tissue force and stress were unaltered by storage and preconditioning compared to fresh samples, while high preconditioning increased the stiffness and modulus (p ≤ 0.007). Furthermore, both storage conditions did not modify the viscoelastic properties of the healing tendon, but altered transverse area, gap length, and water content. Cell viability was reduced after freezing. In conclusion, preconditioning on healing tissues can introduce mechanical data bias when having extensive tissue strength diversity. Storage can be used before biomechanical testing if structural properties are measured on the day of testing.
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| 49. |
- Herring, Matthew, et al.
(författare)
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Exposing kinetic disparities between inflammasome readouts using time-resolved analysis
- 2024
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1β and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others. In this study, we apply time-resolved analysis of a human macrophage model (differentiated THP-1-ASC-GFP cells) to commonly accessible methods. This approach yields the additional quantifiable metrics time-resolved absolute change and acceleration, allowing comparisons between readouts. Using this methodological approach, we reveal (potential) discrepancies between inflammasome-related readouts that otherwise might go undiscovered. The study highlights the importance of time-resolved data in general and may be further extended as well as incorporated into other areas of research.
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| 50. |
- Peris, Eduard, et al.
(författare)
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Antioxidant treatment induces reductive stress associated with mitochondrial dysfunction in adipocytes
- 2019
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 294:7, s. 2340-2352
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Tidskriftsartikel (refereegranskat)abstract
- beta-Adrenergic stimulation of adipose tissue increases mitochondrial density and activity (browning) that are associated with improved whole-body metabolism. Whereas chronically elevated levels of reactive oxygen species (ROS) in adipose tissue contribute to insulin resistance, transient ROS elevation stimulates physiological processes such as adipogenesis. Here, using a combination of biochemical and cell and molecular biology-based approaches, we studied whether ROS or antioxidant treatment affects beta 3-adrenergic receptor (beta 3-AR) stimulation-induced adipose tissue browning. We found that beta 3-AR stimulation increases ROS levels in cultured adipocytes, but, unexpectedly, pretreatment with different antioxidants (N-acetylcysteine, vitamin E, or GSH ethyl ester) did not prevent this ROS increase. Using fluorescent probes, we discovered that the antioxidant treatments instead enhanced beta 3-AR stimulation-induced mitochondrial ROS production. This pro-oxidant effect of antioxidants was, even in the absence of beta 3-AR stimulation, associated with decreased oxygen consumption and increased lactate production in adipocytes. We observed similar antioxidant effects in WT mice: N-acetylcysteine blunted beta 3-AR stimulation-induced browning of white adipose tissue and reduced mitochondrial activity in brown adipose tissue even in the absence of beta 3-AR stimulation. Furthermore, N-acetylcysteine increased the levels of peroxiredoxin 3 and superoxide dismutase 2 in adipose tissue, indicating increased mitochondrial oxidative stress. We interpret this negative impact of antioxidants on oxygen consumption in vitro and adipose tissue browning in vivo as essential adaptations that prevent a further increase in mitochondrial ROS production. In summary, these results suggest that chronic antioxidant supplementation can produce a paradoxical increase in oxidative stress associated with mitochondrial dysfunction in adipocytes.
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