Thèse Ecole polytechnique fédérale de Lausanne EPFL, no 4350 (2009), Faculté des sciences et techniques de l'ingénieur STI, Programme doctoral Sciences et Génie des matériaux, Institut des ...matériaux IMX (Laboratoire de métallurgie chimique LMCH). Dir.: Stefano Mischler, Johann Michler.
In recent years, there has been considerable interest in using microalgal lipids in the food, chemical, pharmaceutical, and cosmetic industries. Several microalgal species can accumulate appreciable ...lipid quantities and therefore are characterized as oleaginous. In cosmetic formulations, lipids and their derivatives are one of the main ingredients. Different lipid classes are great moisturizing, emollient, and softening agents, work as surfactants and emulsifiers, give consistence to products, are color and fragrance carriers, act as preservatives to maintain products integrity, and can be part of the molecules delivery system. In the past, chemicals have been widely used but today’s market and customers’ demands are oriented towards natural products. Microalgae are an extraordinary source of lipids and other many bioactive molecules. Scientists’ attention to microalgae cultivation for their industrial application is increasing. For the high costs associated, commercialization of microalgae and their products is still not very widespread. The possibility to use biomass for various industrial purposes could make microalgae more economically competitive.
To evaluate the association between radiomic features (RFs) extracted from
F-FDG PET/CT (
F-FDG-PET) with progression-free survival (PFS) and overall survival (OS) in diffuse large-B-cell lymphoma ...(DLBCL) patients eligible to first-line chemotherapy. DLBCL patients who underwent
F-FDG-PET prior to first-line chemotherapy were retrospectively analyzed. RFs were extracted from the lesion showing the highest uptake. A radiomic score to predict PFS and OS was obtained by multivariable Elastic Net Cox model. Radiomic univariate model, clinical and combined clinical-radiomic multivariable models to predict PFS and OS were obtained. 112 patients were analyzed. Median follow-up was 34.7 months (Inter-Quartile Range (IQR) 11.3-66.3 months) for PFS and 41.1 (IQR 18.4-68.9) for OS. Radiomic score resulted associated with PFS and OS (p < 0.001), outperforming conventional PET parameters. C-index (95% CI) for PFS prediction were 0.67 (0.58-0.76), 0.81 (0.75-0.88) and 0.84 (0.77-0.91) for clinical, radiomic and combined clinical-radiomic model, respectively. C-index for OS were 0.77 (0.66-0.89), 0.84 (0.76-0.91) and 0.90 (0.81-0.98). In the Kaplan-Meier analysis (low-IPI vs. high-IPI), the radiomic score was significant predictor of PFS (p < 0.001). The radiomic score was an independent prognostic biomarker of survival in DLBCL patients. The extraction of RFs from baseline
F-FDG-PET might be proposed in DLBCL to stratify high-risk versus low-risk patients of relapse after first-line therapy, especially in low-IPI patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed ...countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recently, microalgae are arousing considerable interest as a source of countless molecules with potential impacts in the nutraceutical and pharmaceutical fields. Haematococcus pluvialis, also named ...Haematococcus lacustris, is the largest producer of astaxanthin, a carotenoid exhibiting powerful health effects, including anti-lipogenic and anti-diabetic activities. This study was carried out to investigate the properties of two selected strains of H. pluvialis (FBR1 and FBR2) on lipid metabolism, lipolysis and adipogenesis using an in vitro obesity model. FBR1 and FBR2 showed no antiproliferative effect at the lowest concentration in 3T3-L1 adipocytes. Treatment with FBR2 extract reduced lipid deposition, detected via Oil Red O staining and the immunocontent of the adipogenic proteins PPARγ, ACLY and AMPK was revealed using Western blot analysis. Extracts from both strains induced lipolysis in vitro and reduced the secretion of interleukin-6 and tumor necrosis factor-α. Moreover, the FBR1 and FBR2 extracts improved mitochondrial function, reducing the levels of mitochondrial superoxide anion radical and increasing mitochondrial mass compared to untreated adipocytes. These findings suggest that FBR2 extract, more so than FBR1, may represent a promising strategy in overweight and obesity prevention and treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Several studies have demonstrated the effectiveness of plant extracts against various diseases, especially skin disorders; namely, they exhibit overall protective effects. The Pistachio (
L.) is ...known for having bioactive compounds that can effectively contribute to a person's healthy status. However, these benefits may be limited by the toxicity and low bioavailability often inherent in bioactive compounds. To overcome these problems, delivery systems, such as phospholipid vesicles, can be employed. In this study, an essential oil and a hydrolate were produced from
stalks, which are usually discarded as waste. The extracts were characterized by liquid and gas chromatography coupled with mass spectrometry and formulated in phospholipid vesicles intended for skin application. Liposomes and transfersomes showed small size (<100 nm), negative charge (approximately -15 mV), and a longer storage stability for the latter. The entrapment efficiency was determined via the quantification of the major compounds identified in the extracts and was >80%. The immune-modulating activity of the extracts was assayed in macrophage cell cultures. Most interestingly, the formulation in transfersomes abolished the cytotoxicity of the essential oil while increasing its ability to inhibit inflammatory mediators via the immunometabolic citrate pathway.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose: The issue of whether colon and rectal cancer should be considered as a single entity or two distinct entities is still debated,
and there is a need to improve studies addressing the ...heterogeneity of the pathogenetic pathway leading to sporadic colorectal
cancers (SCRCs) as well as to identify biological and/or molecular differences between colon and rectal cancers.
Experimental Design: Specimens of SCRCs were analyzed for somatic mutations in APC , K-ras , and TP53 genes and loss-of-heterozygosity of chromosome 18.
Results: Eleven SCRCs showed microsatellite instability. APC mutation frequency was significantly lower in microsatellite instability (MIN+) than in MIN− SCRCs. All MIN− SCRCs showed
β-catenin overexpression. A combined analysis of the biomarkers revealed two pathways mainly represented by MIN− SCRCs and
differently followed on the basis of tumor location, APC-K-ras-TP53-Ch18q and APC-TP53-Ch18q .
Conclusions: The APC-β-catenin pathway is inactivated in MIN− SCRCs and represents the first hit of SCRC development. Two preferential
pathways followed by SCRCs occur, one K-ras dependent, in agreement with the Fearon and Vogelstein model, and the other K-ras
independent. Significant differences between colon and rectal tumors occur in our series of MIN− SCRCs. The different pathways
observed and their distribution can be summarized as follows: ( a ) K-ras mutations were more commonly detected in colon than in rectum; ( b ) the number of mutations detected was significantly higher in colon than in rectal tumors; and ( c ) a mutational pattern restricted to the APC gene was more common in rectal than in colon tumors. This molecular characterization can be translated into a clinical setting
to improve diagnosis and to direct a rationale pharmacological treatment.
Radiomic analysis of 18FFDG PET/CT images might identify predictive imaging biomarkers, however, the reproducibility of this quantitative approach might depend on the methodology adopted for image ...analysis. This retrospective study investigates the impact of PET segmentation method and the selection of different target lesions on the radiomic analysis of baseline 18FFDG PET/CT images in a population of newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients. The whole tumor burden was segmented on PET images applying six methods: (1) 2.5 standardized uptake value (SUV) threshold; (2) 25% maximum SUV (SUVmax) threshold; (3) 42% SUVmax threshold; (4) 1.3∙liver uptake threshold; (5) intersection among 1, 2, 4; and (6) intersection among 1, 3, 4. For each method, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG) were assessed, and their association with survival outcomes (progression-free survival PFS and overall survival OS) was investigated. Methods 1 and 2 provided stronger associations and were selected for the next steps. Radiomic analysis was then performed on two target lesions for each patient: the one with the highest SUV and the largest one. Fifty-three radiomic features were extracted, and radiomic scores to predict PFS and OS were obtained. Two proportional-hazard regression Cox models for PFS and OS were developed: (1) univariate radiomic models based on radiomic score; and (2) multivariable clinical–radiomic model including radiomic score and clinical/diagnostic parameters (IPI score, SUVmax, TMTV, WTLG, lesion volume). The models were created in the four scenarios obtained by varying the segmentation method and/or the target lesion; the models’ performances were compared (C-index). In all scenarios, the radiomic score was significantly associated with PFS and OS both at univariate and multivariable analysis (p < 0.001), in the latter case in association with the IPI score. When comparing the models’ performances in the four scenarios, the C-indexes agreed within the confidence interval. C-index ranges were 0.79–0.81 and 0.80–0.83 for PFS radiomic and clinical–radiomic models; 0.82–0.87 and 0.83–0.90 for OS radiomic and clinical–radiomic models. In conclusion, the selection of either between two PET segmentation methods and two target lesions for radiomic analysis did not significantly affect the performance of the prognostic models built on radiomic and clinical data of DLBCL patients. These results prompt further investigation of the proposed methodology on a validation dataset.
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