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- Lonnberg, Tapio, et al.
(författare)
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T-cell activation induces selective changes of cellular lipidome
- 2013
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Ingår i: Frontiers in Bioscience (Elite Edition). - : Frontiers in Bioscience. - 1945-0494 .- 1945-0508. ; 5, s. 558-573
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Tidskriftsartikel (refereegranskat)abstract
- Activation of naïve T helper cells by presentation of cognate antigen initiates a complex intracellular signaling process leading to development of functionally active effector cell population. The switch from quiescent naïve state to activated state involves a profound change of cellular metabolism, required for completion of multiple rounds of proliferation. Using ultra performance liquid chromatography mass spectrometry, we analyzed how this change is reflected on the cellular lipid composition in human umbilical cord blood T-cells. We found that considerable concentration changes take place during the first 72 hours after T-cell receptor activation, correlating with first rounds of activation-induced cell division. Most importantly, composition of phosphatidylcholines and phosphatidylethanolamines exhibited consistent trend towards shorter and more saturated molecular species. Together with related transcriptomics data, the results clearly suggested induction of de novofatty acid synthesis and accumulation of endogenously synthesized fatty acids into the cellular membranes, leading to partial remodeling of the cellular lipidome in the newly developed effector cell population.
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- Ludvigsson, Johnny
(författare)
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C-peptide in diabetes diagnosis and therapy
- 2013
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Ingår i: Frontiers in Bioscience (Elite Edition). - : Frontiers in Bioscience. - 1945-0494 .- 1945-0508. ; 5, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- C-peptide is known for several decades. It is released in equimolar amounts together with insulin from the pancreatic beta cells. Still there has been quite remarkable lack of interest in C-peptide. C-peptide is rarely used to classify type of diabetes although it seems self-evident that it is important to estimate the function of those cells which do not function good enough and therefore causes a syndrome which requires life-long treatment and leads to serious complications. Not until recent years C-peptide is accepted as a relevant outcome in trials aiming at preservation of beta cell function, although it is known for decades that some C-peptide is associated with less complications in type 1 diabetes (T1D). Preservation of beta cell function is important to make diabetes milder, and when beta cell function can be preserved before clinical manifestation of T1D, we are on our way to prevent that disease. Residual C-peptide/insulin secretion can be of value in classification of diabetes in different types. C-peptide may give valuable clinical information on why patients are more or less stable/labile in their blood glucose and more or less easy to treat. It explains why patients with T1D have different tendency to develop severe acute complications, both severe hypoglycaemia and diabetic keto-acidosis (DKA). Longstanding C-peptide may decrease risk of developing severe late complications. Finally, although still under debate, C-peptide seems to have several effects on different organs suggesting that it is an important hormone, interesting per se, and not only as a reflection of insulin secretion.
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- Regberg, Jakob, et al.
(författare)
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Cell-penetrating peptides : from cell cultures to in vivo applications
- 2013
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Ingår i: Frontiers in Bioscience (Elite Edition). - 1945-0494 .- 1945-0508. ; 5, s. 509-516
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Forskningsöversikt (refereegranskat)abstract
- The field of gene therapy is starting to move towards clinical applications but is currently limited by the lack of efficient delivery systems. Cell-penetrating peptides provide a means of cellular delivery for gene therapy applications as well as delivery of traditional drugs. Using cell-penetrating peptides a range of different cargos have been successfully delivered into a number of cell types, in vitro as well as in vivo. In this review we discuss uptake mechanisms of different cell-penetrating peptides, with or without cargo. The transition from in vitro to in vivoapplications and strategies to increase the bioavailability of cell-penetrating peptides are also discussed.
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- Yakimova, Rositza, et al.
(författare)
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ZnO materials and surface tailoring for biosensing
- 2012
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Ingår i: Frontiers in bioscience (Elite edition). - Albertson, NY, United States : Frontiers in Bioscience. - 1945-0508 .- 1945-0494. ; 4:1, s. 254-278
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Tidskriftsartikel (refereegranskat)abstract
- ZnO nanostructured materials, such as films and nanoparticles, could provide a suitable platform for development of high performance biosensors due to their unique fundamental material properties. This paper reviews different preparation techniques of ZnO nanocrystals and material issues like wettability, biocompatibility and toxicity, which have an important relevance to biosensor functionality. Efforts are made to summarize and analyze existing results regarding surface modification and molecular attachments for successful biofunctionalization and understanding of the mechanisms involved. A section is devoted to implementations of tailored surfaces in biosensors. We end with conclusions on the feasibility of using ZnO nanocrystals for biosensing.
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- Gonzalez Perez, Alfredo, et al.
(författare)
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Different strategies for controlling DNA conformation: compaction and decompaction.
- 2009
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Ingår i: Frontiers in Bioscience (Elite Edition). - 1945-0508. ; 1, s. 228-241
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Tidskriftsartikel (refereegranskat)abstract
- In the present review we summarize different strategies to induce DNA compaction and decompaction. DNA compaction is achieved using different cationic co-solutes, such as trivalent ions, surfactant, and polycations. In addition, single-chained DNA compaction can also be achieved in solvents with low dielectric constants and by confinement. The decompaction strategies depend, naturally, on the method used for the compaction and can be accomplished by, for example, heparins, cyclodextrins, non-ionic or anionic surfactants.
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- Gram, Magnus, et al.
(författare)
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Increased levels of hemoglobin and alpha1-microglobulin in Huntington's disease.
- 2012
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Ingår i: Frontiers in Bioscience (Elite Edition). - 1945-0508. ; 4, s. 950-957
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin released from damaged erythrocytes is a major pro-oxidant, generator of free radicals and inflammatory mediator. Huntington's disease is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities, in which oxidative stress has been suggested as a possible pathogenic mechanism. In the present work we have investigated levels of hemoglobin and markers of oxidative damage, including the heme- and radical-scavenger alpha1-microglobulin, in plasma and urine samples from two separate sample cohorts, including controls, premanifest gene carriers and subjects at different stages of Huntington's disease. The results show statistically significant increased levels of hemoglobin and alpha1-microglobulin in Huntington's disease urine samples. Interestingly, urine hemoglobin levels correlate with clinical severity. The results suggest that hemolysis may be linked to the pathogenesis of Huntington's disease and that assay of hemoglobin and alpha1-microglobulin may provide biomarkers that are linked to biologically relevant processes.
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- Hedner, Ulla
(författare)
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FVIIa as therapeutic agent in hemophilia and beyond.
- 2012
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Ingår i: Frontiers in Bioscience (Elite Edition). - 1945-0508. ; 4, s. 1210-1223
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Tidskriftsartikel (refereegranskat)abstract
- Around 20percent of the patients with severe hemophilia develop inhibitory antibodies against the factor they lack. In these patients the administration of FVIII/FIX-concentrates are not hemostatically effective. Since FVIIa is not enzymatically active unless complexed with tissue factor (TF) exposed following an injury to the vessel wall, it was considered an attractive candidate for improved treatment of patients with inhibitors. Plasma-derived FVIIa was purified and shown to induce hemostasis in two hemophilia A patients with inhibitors. Later recombinant FVIIa (rFVIIa) was developed and pharmacological doses have an efficacy rate of around 90percent in serious bleedings and permit major orthopaedic surgery. These findings were a breakthrough in understanding the FVII-TF pathway in hemostasis. The initially formed FVIIa-TF complexes provide a limited amount of thrombin, activating FVIII, FV, FXI as well as platelets. On the activated platelet surface the full burst of thrombin necessary for generating a firm fibrin hemostatic plug occurs. In case of impaired thrombin generation, loose fibrin plugs easily dissolved are formed. Extra rFVIIa enhances thrombin generation and generates tight fibrin plugs.
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