| 1. |
- Sentinelli, Federica, et al.
(författare)
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Association of FTO polymorphisms with early age of obesity in obese Italian subjects
- 2012
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Ingår i: Experimental Diabetes Research. - : Hindawi Limited. - 1687-5214 .- 1687-5303. ; 2012
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n=752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P<0.043) and rs9930506 (P<0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4kg/m2per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population. Copyright © 2012 Federica Sentinelli et al.
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| 2. |
- Barchetta, Ilaria, et al.
(författare)
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Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children
- 2021
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Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:3, s. 902-910
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. Methods and results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24–28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = −0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
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| 3. |
- Caffaro, Federica, et al.
(författare)
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Falls from Tractors in Older Age : Risky Behaviors in a Group of Swedish and Italian Farmers Over 65
- 2019
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Ingår i: Proceedings of the 20th Congress of the International Ergonomics Association (IEA 2018). : Aging, Gender and Work, Anthropometry, Ergonomics for Children and Educational Environments - Aging, Gender and Work, Anthropometry, Ergonomics for Children and Educational Environments. - Cham : Springer International Publishing. - 9783319960654 - 9783319960647 ; , s. 78-86, s. 78-86
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Konferensbidrag (refereegranskat)abstract
- The frequent mounting and dismounting the tractor required by many farming operations increases the risk of falls, particularly for older farmers. The present study explored the risk factors related to tractor ingress and egress in older farmers from two countries with a different tradition in terms of safety culture: Sweden and Italy. Eighteen male farmers aged 65 + (8 from Skåne region, southern Sweden, and 10 from Piedmont region, northwestern Italy) were observed while mounting and dismounting their most used tractor, to investigate the routine behaviors adopted and to identify possible sources of risk of fall. The presence of three critical behaviors was recorded: the maintenance of three-point contact with the machine when entering and exiting the cab; facing the cab and the use of the last step when exiting. Farmers were also interviewed about their health status, attitudes toward safety, and perceived risks while performing the task. The results showed that similar unsafe behaviors were adopted by most of both Swedish and Italian participants; in particular, none of the farmers got off the tractor by facing the cab. Older farmers from both countries referred to age and previous experience as the major protective factors against falls, without acknowledging that new risks can rise from the age-related changes in their motor skills. The results raised some considerations about the need to develop targeted elderly-centered solutions to support the correct mounting/dismounting behaviors, both in the design of the machines and in information campaigns and training courses, which may have a cross-cultural validity.
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| 4. |
- Grasso, Silvia, et al.
(författare)
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The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.
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| 5. |
- Sentinelli, Federica, et al.
(författare)
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Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:7
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Tidskriftsartikel (refereegranskat)abstract
- Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels of its precursor, pro-NT, predicts the presence and development of metabolic and cardiovascular diseases. Despite the extensive knowledge on the dynamic changes that occur to pro-NT = after fat load, the determinants of fasting pro-NT are unknown. The aim of this study was to determine the possible genetic regulation of plasma pro-NT. The NT gene (NTS) was sequenced for potential functional variants, evaluating its entire genomic and potentially regulatory regions, in DNA from 28 individuals, stratified by low and high pro-NT levels. The identified variant differently distributed in the two pro-NT subgroups was genotyped in a cohort of nine hundred and thirty-two overweight/obese children and adolescents. A total of seven sequence variations across the NTS gene, none of them located in coding regions, were identified. The rs2234762 polymorphism, sited in the NTS gene promoter, was statistically more frequent in the lowest pro-NTS level group. Carriers of the rs2234762 variant showed lower pro-NT levels, after adjusting for sex, age, BMI, triglycerides and the Tanner stage. Having NTS rs2234762 predicted less pronounced insulin resistance at the 6.5-year follow-up with OR: 0.46 (0.216–0.983), at the logistic regression analysis adjusted for age, sex and BMI. In conclusion, the NTS rs2234762 gene variant is a determinant of reduced circulating pro-NT levels in overweight and obese children, which predisposes this group to a more favorable metabolic profile and a reduced insulin resistance later in life, independently from metabolic confounders.
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| 6. |
- Triulzi, Chiara, et al.
(författare)
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Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity Engendered by a Kinase-Inactive Human HER2 Adenovirus-Based Vaccination Mediates Resistance to Breast Tumors
- 2010
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 70:19, s. 7431-7441
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Tidskriftsartikel (refereegranskat)abstract
- Cancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report contributions by antibody responses and natural killer (NK) cells in tumor protection in this model. One i. p. vaccination protected WT mice from the HER2-expressing mouse carcinoma D2F2/E2. Half of the HER2 transgenic mice were protected fully and long term after preventive vaccination. Tumor growth in mice that eventually developed neoplastic lesions was delayed. Protection in WT and HER2 transgenic mice was associated with high or low levels of IgG2a antibodies, respectively, whereas CTLs were observed in WT but not in HER2 transgenic mice. Depleting CD4(+) or CD8(+) cells in vaccinated WT mice had limited effects, suggesting that protection was largely independent of CD4(+) or CD8(+) T cells. In contrast, antibody-mediated tumor rejection seemed to contribute significantly based on a loss of protection in mice deficient for Fc-gamma RI/III or B cells. Further, a role for antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells was indicated by evidence that vaccine protection could be abolished by in vivo depletion of NK cells. Lastly, NK cells and immune sera purified from WT or HER2 transgenic mice exhibited efficient ADCC of HER2-expressing tumor cells in vitro. Our findings define a critical requirement for NK cells in vaccine-induced protection against HER2-expressing tumors.
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