| 1. |
- Bölükbas, D. A., et al.
(författare)
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Fine-tuning lung cancer nanotherapy using closed cardiopulmonary circulation
- 2019
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Ingår i: Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium : 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence - 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence. - 9781510883901 ; 40
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Konferensbidrag (refereegranskat)abstract
- Statement of Purpose: Lung cancer is the leading cause of cancer-related deaths and efficient therapies remain elusive. One emerging approach is to use nanoparticles (NPs) that are designed to specifically target malignant cells (1). Such targeting increases on-site drug doses and reduces systemic side effects. A common target in lung tumors is epidermal growth factor receptor (EGFR). Here, we explored the targeting efficacy of EGFR-targeted mesoporous silica nanoparticles (MSN GE11 ) for lung cancer treatment. Though specifically taken up by cancer cells in vitro, when administered intravenously or intratracheally in lung cancer mouse models, the NPs could not reach the depths of solid tumors and often strayed away from their target. This raises concerns whether NPs are suitable for therapeutically targeting lung tumors and challenges translational value of current approaches. To circumvent physiological barriers of solid lung tumors and consequent systemic clearance of NPs, we extended our analysis to a treatment strategy where the NPs are administered intravenously in a closed cardiopulmonary (CP) circulation loop. This approach not only makes the therapy more local, but also eliminates confounding factors for NP delivery such as liver/spleen deposition of NPs in vivo.
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| 2. |
- Mancina, Rosellina Margherita, et al.
(författare)
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PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes
- 2016
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 22:1, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. Methods: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. Results: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). Conclusions: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
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| 3. |
- Montalcini, T., et al.
(författare)
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Nutrients Utilization in Obese Individuals with and without Hypertriglyceridemia
- 2014
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 6:2, s. 790-798
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low fat utilization is linked to weight gain and to the presence of certain atherosclerosis markers. It is not clear whether the presence of hyperlipidemia can further affect nutrients utilization. The main objective of this study was to investigate the fasting fuel utilization of obese subjects suffering from hypertriglyceridemia, and to compare it with that of individuals that are solely obese. Method: We recruited 20 obese individuals with hypertriglyceridemia and 20 matched individuals not affected by hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by respiratory gas exchange, by Indirect Calorimetry. Results: There was a significant difference in fuel utilization and HDL-cholesterol between cases and controls (respiratory quotient 0.89 +/- 0.07 vs. 0.84 +/- 0.06; p = 0.020 respectively). The univariate and multivariate linear regression analysis confirmed that hypertrygliceridemia was positively correlated to the respiratory quotient (p = 0.035). Conclusion: obese subjects with hypertriglyceridemia had a higher respiratory quotient in comparison to unaffected subjects. This could suggest a limitation in the beta-oxidation mechanisms; this could actually imply that fatty acids may be redirected from oxidation to reesterification into triglycerides. The study could suggest the presence of different mechanisms unrelated to obesity and also a potential new therapeutic target for hypertriglyceridemia management.
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| 4. |
- Giri, R., et al.
(författare)
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Folding pathways of proteins with increasing degree of sequence identities but different structure and function
- 2012
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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. ; 109:44, s. 17772-17776
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Tidskriftsartikel (refereegranskat)abstract
- Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed.
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| 5. |
- Rovera, C., et al.
(författare)
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Mechanical behavior of biopolymer composite coatings on plastic films by depth-sensing indentation – A nanoscale study
- 2018
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Ingår i: Journal of Colloid and Interface Science. - : Academic Press. - 0021-9797 .- 1095-7103. ; 512, s. 638-646
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Tidskriftsartikel (refereegranskat)abstract
- Fundamental physical behaviors of materials at the nanoscale level are crucial when local aspects govern the macroscale performance of nanocomposites, e.g., interface and surface phenomena. Because of the increasing interest in biopolymer nanocomposite coatings for many different applications (e.g., optical devices, displays/screens, and packaging), this work investigates the potential of nanoindentation as a method for clarifying the interplay between distinct phases (i.e., organic and inorganic) at local level in thin biopolymer films loaded with nanoparticles. The nanomechanical features of pullulan nanocomposite coatings laid on polyethylene terephthalate (PET) were quantified in terms of elastic modulus (E), hardness (H), and creep (C) through an instrumented indentation test composed of a loading-holding-unloading cycle. Colloidal silica (CS) and cellulose nanocrystals (CNCs) were used as spherical and rod-like nanoparticles, respectively. An overall reinforcing effect was shown for all nanocomposite coatings over the pristine (unfilled) pullulan coating. A size effect was also disclosed for the CS-loaded surfaces, with the highest E value recorded for the largest particles (8.19 ± 0.35 GPa) and the highest H value belonging to the smallest ones (395.41 ± 25.22 MPa). Comparing CS and CNCs, the addition of spherical nanoparticles had a greater effect on the surface hardness than cellulose nanowhiskers (353.50 ± 83.52 MPa and 321.36 ± 43.26 MPa, respectively). As for the elastic modulus, the addition of CS did not provide any improvement over both the bare and CNC-loaded pullulan coatings, whereas the coating including CNCs exhibited higher E values (p <. 05). Finally, CS-loaded pullulan coatings were the best performing in terms of C properties, with an average indentation depth of 16.5 ± 1.85 nm under a load of ∼190 μN. These results are discussed in terms of local distribution gradients, surface chemistry of nanoparticles, and how nanoparticle aggregation occurred in the dry nanocomposite coatings.
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| 6. |
- Sacchetto, Daniela, et al.
(författare)
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Mammographic density : Comparison of visual assessment with fully automatic calculation on a multivendor dataset
- 2016
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Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 26:1, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset. Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (kappa) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification. While the agreement of individual radiologists with the PMR ranged from kappa = 0.483 to kappa = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (kappa = 0.620, standard deviation [SD] = 0.140), individual versus PMR (kappa = 0.736, SD = 0.117), and individual versus ABDE (kappa = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (kappa = 0.831). The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation. aEuro cent Individual BD assessment differs from PMR with kappa as low as 0.483. aEuro cent An ABDE correctly classified 92 % of mammograms with almost perfect agreement (kappa = 0.831). aEuro cent An ABDE can be a valid alternative to subjective BD assessment.
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| 7. |
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