| 1. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 2. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 3. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 4. |
- Biffi, Stefania, et al.
(författare)
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Cubosomes for in vivo fluorescence lifetime imaging
- 2017
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Ingår i: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 28:5
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Tidskriftsartikel (refereegranskat)abstract
- Herein we provided the first proof of principle for in vivo fluorescence optical imaging application using monoolein-based cubosomes in a healthy mouse animal model. This formulation, administered at a non-cytotoxic concentration, was capable of providing both exogenous contrast for NIR fluorescence imaging with very high efficiency and chemospecific information upon lifetime analysis. Time-resolved measurements of fluorescence after the intravenous injection of cubosomes revealed that the dye rapidly accumulated mainly in the liver, while lifetimes profiles obtained in vivo allowed for discriminating between free dye or dye embedded within the cubosome nanostructure after injection.
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| 5. |
- Caltagirone, Claudia, et al.
(författare)
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Solvatochromic fluorescent BODIPY derivative as imaging agent in camptothecin loaded hexosomes for possible theranostic applications
- 2015
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:30, s. 23443-23449
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Tidskriftsartikel (refereegranskat)abstract
- We here discuss the potential theranostic nanomedicine application of an innovative formulation consisting of monoolein-based nanoparticles with a two-dimensional hexagonal inner structure stabilized in water using a mixture of PEO132-PPO50-PEO132 block copolymers with and without conjugated folate for targeting. The proposed tumor-cell targeted formulation was shown to be able to simultaneously host the model anticancer drug camptothecin and a pyrene-modified BODIPY fluorophore, based on dynamic light scattering, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The photophysical properties of the fluorophore were studied in solution in various solvents. A marked fluorescent solvatochromism, whose origin was explained by time-dependent density functional theory theoretical calculations, was observed. Fluorescence microscopy showed that HeLa cells readily internalize these nanoparticles, and that the fluorophore localizes within the lipid droplets. In addition, cytotoxicity test revealed that these nanoparticles are not toxic at the concentration used for the imaging analysis.
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| 6. |
- Meli, Valeria, et al.
(författare)
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Docetaxel-Loaded Fluorescent Liquid-Crystalline Nanoparticles for Cancer Theranostics.
- 2015
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 31:35, s. 9566-9575
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe a novel monoolein-based cubosome formulation engineered for possible theranostic applications in oncology. The Docetaxel-loaded nanoparticles were stabilized in water by a mixture of commercial Pluronic (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer) F108 (PF108) and rhodamine- and folate-conjugated PF108 so that the nanoparticles possess targeting, therapeutic, and imaging properties. Nanoparticles were investigated by DLS, cryo-TEM, and SAXS to confirm their structural features. The fluorescent emission characterization of the proposed formulation indicated that the rhodamine conjugated to the PF108 experiences an environment less polar than water (similar to chloroform), suggesting that the fluorescent fragment is buried within the poly(ethylene oxide) corona surrounding the nanoparticle. Furthermore, these nanoparticles were successfully used to image living HeLa cells and demonstrated a significant short-term (4 h incubation) cytotoxicity effect against these cancer cells. Furthermore, given their analogy as nanocarriers for molecules of pharmaceutical interest and to better stress the singularities of these bicontinuous cubic nanoparticles, we also quantitatively evaluated the differences between cubosomes and multilamellar liposomes in terms of surface area and hydrophobic volume.
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| 7. |
- Meli, Valeri, et al.
(författare)
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Theranostic hexosomes for cancer treatments : an in vitro study
- 2017
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Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1144-0546 .- 1369-9261. ; 41:4, s. 1558-1565
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Tidskriftsartikel (refereegranskat)abstract
- We have formulated and investigated innovative lipid-based nanoparticles characterized by a reverse hexagonal liquid crystalline inner structure (hexosomes). These nanoparticles were doped with a potent, highly water insoluble anticancer drug, namely docetaxel, and stabilized by a mixture of commercial and folate- and rhodamine-conjugated Pluronic F108. Thus, they simultaneously possess therapeutic, imaging, and targeting properties toward cancer cells. The morphological and structural aspects of the hexosomes were investigated at different temperatures (10, 25, 37, and 50 °C), and our results demonstrate good performance in terms of stability of these nanoparticles. The latter was furthermore confirmed by the very slow and continuous release profile of docetaxel observed in drug release experiments. Although it was not possible to assess a specific compartmentalization of the dye, this formulation allowed the successful visualization of HeLa cells. Finally, cytotoxic assays showed a 20-fold higher toxic effect of the drug-doped hexosomes against HeLa cells with respect to the free (not loaded in hexosomes) anticancer drug. On the whole, these results indicate that this formulation is a potential theranostic tool in oncology.
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| 8. |
- Murgia, Sergio, et al.
(författare)
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Nanoparticles from Lipid-Based Liquid Crystals: Emulsifier Influence on Morphology and Cytotoxicity.
- 2010
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 114:10, s. 3518-3525
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Tidskriftsartikel (refereegranskat)abstract
- Here, monoolein-based nanoparticles (NPs), obtained through fragmentation of bulk liquid crystalline phases, and stabilized by two different emulsifiers, namely, Pluronic F127 (PF127) and lauroylcholine chloride (LCh), are investigated for structural features and for short-term in vitro cytotoxicity. Depending on the emulsifiers, different morphologies of the lipid NPs (cubosomes and liposomes) are obtained, as demonstrated by cryo-TEM images. Although NPs offer many advantages in medical applications and various chemicals used for their preparation are under investigation, so far there are no standardized procedures to evaluate cell biocompatibility. Two different protocols to evaluate the impact of these lipid NPs on biological systems are presented. Results show that nanoparticles stabilized by PF127 (cubosomes) display a relevant toxicity toward different cell lines, whereas those stabilized by LCh (liposomes) affect cell viability at a much lesser extent.
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