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Influence of REST Deficiency on Obesity-Related Endometrial cancer and Chromogranin A Expression in Mice
No full textObesity increases the risk of endometrial cancer (EC). It was previously demonstrated that the transcription regulator, REST, may be a putative tumor suppressor in EC. Chromogranin A (CHGA) is elevated in various cancers, including neuroendocrine tumors. Interestingly, REST knockdown has been shown to upregulate CHGA in breast cancer and may play a role in carcinogenesis. The objective of this study was to determine if Rest deficiency augments obesity related EC in mice and if Chga is altered in this pathway. To determine the impact of diet-induced obesity and uterine Rest deficiency on the development of uterine cancer, uterine Rest deficient mice (Restd/d) and control mice (Restfl/fl) were placed on high-fat/high-sucrose (HFHS) or control diets (n=6 mice/diet/genotype). After 24 weeks, total body weight and body fat were measured, and glucose tolerance tests were performed. Endometrial histology was evaluated by H&E staining while immunohistochemistry (IHC) for Chga was quantified using H-Scores. Chga expression was quantitated by qRT-PCR and data is represented as fold change (FC). Data were analyzed by unpaired t-test or ANOVA (or the non-parametric equivalent) where applicable with significance defined as p<0.05. After 24 weeks, total body weight and body fat content were significantly higher in mice on HFHS diet compared to control diet regardless of genotype. Uterine weight was higher in Restd/d mice compared to Restfl/fl mice, regardless of diet. Glucose levels were significantly higher after 30 min in Restd/d/HFHS diet (521mg/dL vs 366mg/dL, p=0.03) and Restfl/fl/HFHS diet (509mg/dL vs 366mg/dL, p=0.04) compared to Restfl/fl/control diet mice. Histologically, all Restfl/fl uterine sections had small glands with gland to stroma ratio <2:1 and no overcrowding of glands. Restd/d mice demonstrated large/dilated glands with some degree of overcrowding and gland to stroma ratio >2:1 in n=3/6 on the control diet and n=6/6 on the HFHS diet. No myoinvasion was seen in any of the groups. Stromal cell Chga expression by IHC was higher in Restd/d/HFHS diet compared to Restfl/fl/control diet mice (H-score: 0.29 vs 0.0, p<0.01), Restfl/fl/HFHS diet (H-score: 0.29 vs 0.04, p<0.01), and Restd/d/control diet (H-score: 0.29 vs 0.08, p<0.01). Chga mRNA expression was higher in Restd/d/control diet (FC:392,4X, p<0.05) and Restd/d/HFHS diet (FC:525,6X, p<0.01) compared to Restfl/fl/control diet mice.
In conclusion, Restd/d mice on HFHS diet exhibited elevated Chga expression as well as uterine pathology with large/dilated glands and gland to stroma ratio >2:1, without myoinvasion, mimicking endometrial hyperplasia. In previous work high levels of CgA may cause vascular abnormalities leading to cancer cell multiplication; it can inhibit capillary tube formation and angiogenesis. These data support the notion that REST deficiency may have an influence on obesity related uterine pathology potentially by upregulation of CHGA. Interestingly, carcinoma was not detected in Restd/d mice. It is possible that an extended observation period or additional mutational factors may be necessary for the development of EC
La giustificazione della guerra e le prospettive di pace nel pensiero di Luigi Taparelli D'Azeglio
No full textTra i pionieri della rinascita tomistica nell’Italia, il gesuita piemontese Luigi Taparelli d’Azeglio fu una delle penne più prestigiose ed influenti dello schieramento intransigente del cattolicesimo italiano ottocentesco. Attraverso le pagine del Saggio teoretico e di alcuni suoi interventi pubblicati sulla Civiltà Cattolica, di cui fu uno dei fondatori, il presente contributo si propone di esaminare le riflessioni taparelliane su un tema poco frequentato dagli studiosi, quello della guerra – e di riflesso della pace – che ispireranno la linea editoriale della rivista e il pensiero dei pontefici ancora nel corso del Novecento.A pioneer of the Thomistic revival in Italy, the Piedmontese Jesuit Luigi Taparelli d’Azeglio was one of the most prominent and influential figures within the intransi-gent front of 19th-century Italian Catholicism. Through his Saggio teoretico and vari-ous writings in La Civiltà Cattolica, of which he was a founding member, this paper seeks to explore Taparelli’s reflections on a topic rarely studied by scholars: war and, by extension, peace. These reflections would later shape the journal’s editorial stance and influence papal thought well into the 20th century
La nominazione nel Novellino di Masuccio
No full textStudio complessivo sulle strategie di nominazione nel Novellino di Masuccio Salernitan
Policies for Full Employment in the Context of Capitalism’s Crises: Historical Development and the Italian Debate in the 1990s
No full text
Genetic and Molecular Analysis of Micro- and Nanomaterials of Biomedical Interest
No full textThe synthesis of plastic polymers, started in the 19th century, helped industries to increase their
production with cheap and malleable materials. Today, this massive usage brought to a consolidate
environmental emergency: plastic residues are defined as the most spread pollutants in the world
and they are found bioaccumulated in most organisms, humans included. The aim of my PhD thesis
is to contribute to determine the impact of plastic residues on health and disease. I used Drosophila
melanogaster as an in vivo model to test polystyrene nanoparticles as major representant of risk
associated with oral exposure and murine macrophages as an in vitro model to test tire wears
microparticles to assess respiratory exposure.
I used the model organism Drosophila melanogaster to ascertain whether polystyrene nanoparticles
(PSNPs) harm DNA, increase the incidence of cancer and worsen the course of genetic diseases
associated with polycystic kidney and neurodevelopment. Orally administered fluorescent PSNPs
were absorbed by intestinal cells and deposited in the fat body of wild-type flies. The weight of
PSNPs-fed flies was significantly lower than negative controls, and they developed more slowly and
showed reduced resilience to heat shock and starvation. When PSNPs were given to DNAlig4
mutants—which are known to be susceptible to dietary stresses—climbing performance was
decreased. All of these findings imply that PSNPs have an effect on fly metabolism and development.
Through qPCR analysis, I observed that the intestines of wild type larvae fed with PSNPs showed an
upregulation of genes related to the cell damage response. PSNPs-fed heterozygous warts mutants,
which are known to favor epithelial tumors even in humans, showed a larger number of aberrant
masses than untreated flies, demonstrating the PSNPs carcinogenic potential. To assess the
potential influence of PSNPs on further pathologies, I used Drosophila models of Polycystic Kidney
Disease (PKD) and TANGO2 Deficiency Disorder (TDD) and detected aggravated diseased
phenotypes in both cases. Specifically, PSNPs consumption increased cyst numbers in PKD flies and
impaired climbing assay performance of TDD flies compared to wild-type controls.
For the in vitro assessment on murine macrophages, I started with the chemical characterization of
the materials using electron microscopy to confirm their composition. Then, the morphological
assessment of the treated cells by transmission electron microscopy showed mitochondria and
endoplasmic reticulum alterations. A qPCR was used for gene expression analysis and confirmed
with western blotting. They showed the overexpression of cellular stress biomarkers. According to
the findings, there was first evidence of an apoptotic process induction, although Bcl2 later reversed
the trigger and treated cells did show some modest cellular anomalies
Il dentro e il fuori. Lavoratrici domestiche capoverdiane, eritree, etiopi e filippine a Roma (1970-1989)
No full textQuesta ricerca riguarda l'esperienza di lavoratrici domestiche capoverdiane, eritree, etiopi e filippine immigrate a Roma tra anni Settanta e Novanta. Queste donne sono protagoniste dei primi flussi verso l'Italia, allora pensata come paese di sola emigrazione. Le loro voci rivelano una fitta trama di pratiche coercitive che si diramano tra spazio privato, pubblico e nella reciproca interazione tra i due
