Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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Alle origini della sussidiarietà
No full textScheda breve che traccia un profilo storico-giuridico della genesi del principio di sussidiarieta
Fecal biomarker discovery by mass spectrometry-based proteomics: a perspective towards non-invasive colorectal cancer screening methods
No full textColorectal cancer (CRC) represents the second-leading cause of cancer death worldwide. 1 Up to now,
screening programs involve the detection of occult blood in stools - characterized by high false-positive rate
and, in case of positivity, subsequent colonoscopy, whose invasiveness causes reluctance to perform it.
Consequently, non-invasive diagnostic screening tests are strongly required to increase patient engagement,
and to improve the prognosis and the efficacy of the pharmacological therapy. Mass spectrometry (MS)-
based proteomics could serve as a powerful tool for discovering new disease biomarkers, to further develop
reliable diagnostic tests for early and accurate diagnosis. 2,3 Investigation of non-invasive stool samples is
crucial to boost population engagement in preventive care screening.
Hence, the present work aims to combine the discovery of faecal CRC biomarkers by MS-based proteomics,
with the perspective of implementation of immunochemical point-of-care assays based on smart
electrochemical sensing devices. Stool samples were collected from patients who underwent colonoscopy
and had at least one adenomatous polyp or cancer, stratified according to histology in low-grade dysplasia,
high-grade dysplasia, and adenocarcinoma; the study included also healthy controls. Untargeted MS-based
shotgun proteomics was performed using a nano-LC coupled to an Orbitrap Exploris 480 with a High-Field
Asymmetric Waveform Ion Mobility Spectrometry System. The applied sample preparation procedure
involved the use of a lysis buffer combined with sonication and protein precipitation, and permitted to extract
an average of 100 proteins per sample. A total of 513 distinct proteins were identified and semi-quantified
across all the samples. Statistical analysis highlighted the presence of some enriched human proteins in
patients with low-grade dysplasia, high-grade dysplasia and adenocarcinoma with respect to healthy
subjects: two most promising CRC biomarkers were shortlisted, here generically named as PROT1 and
PROT2 (Figure 1). The upregulation of these proteins throughout cancer progression found confirmation in
the literature.
The next step of the project will be the development of electrochemical immunosensors for the non-invasive
determination of Prot1 and Prot2 in stool samples, through proper optimization of experimental conditions,
among which a fast and non-denaturant extraction procedure
Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study
No full textBackground: Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis. Methods: We utilized genome-wide association studies (GWAS) summary statistics to explore these associations. GWAS data on DTC were derived from a meta-analysis of six studies including 7705 cases and 963,612 controls of European ancestry. GWAS summary statistics on sex hormones, reproductive factors, and gynecological conditions were retrieved from publicly available sources. We used the inverse-variance weighted (IVW) method to estimate odds ratio (OR), with additional sensitivity analyses and conducted multivariable MR (MVMR) to account for potential confounding by body mass index (BMI) and thyrotropin (TSH). Results: We identified a positive association between sex hormone binding globulin (SHBG) and DTC (ORivw = 1.13, p = 0.046). After controlling for TSH and BMI in a MVMR analysis, the strength of this association remained similar but lost statistical significance. Bioavailable testosterone also showed a positive but marginally significant association with DTC after adjustment for BMI in the MVMR (ORivw = 1.13, p = 0.07). Putative causal association was observed with uterine fibroids in females under 50 years old (ORivw = 1.52, p = 0.017). Endometrial cancer was associated with DTC (ORivw = 1.15, p = 9.0 × 10−3); however, a genetic correlation of r2 = 13% suggested potential pleiotropy. No significant associations were observed for other investigated factors. Conclusions: Our study does not provide strong evidence for a causal role of reproductive and hormonal factors in DTC risk, despite the observed sex disparity in incidence rates. The associations observed with SHBG, bioavailable testosterone, uterine fibroids, and endometrial cancer indicate potential risk factors, but further investigation is required
Proteome-Based Biomarkers for Alzheimer’s Disease: Old Acquisitions and Innovative Proposals
Get PDFAlzheimer’s disease (AD) is one of the most widespread neurodegenerative disorders, primarily affecting individuals over the age of 65. It is characterized by severe cognitive impairment, memory loss, difficulties in performing daily activities, ventricular enlargement, and ultimately, dementia. AD is associated with the accumulation of amyloid (Formula presented.) protein plaques, intracellular neurofibrillary tangles (NFTs), progressive inflammation, and impairment of both synaptic transmission and mitochondrial function. Due to the limited diagnostic tools available for detecting the disease in its early stages, proteomic biomarkers have gained paramount importance, as they can monitor prodromal molecular alterations linked to AD. Furthermore, proteomic biomarkers can facilitate the longitudinal assessment of disease progression and contribute to the development of personalized therapeutic strategies before the devastating onset of dementia. Research has primarily focused on identifying proteomic biomarkers in cerebrospinal fluid (CSF) and plasma, as discussed in this review, but also in alternative matrices such as saliva and urine. These studies highlight both the high potential of proteomic approaches and the ongoing challenge of identifying clinically available, sensitive, and specific biomarkers for the various stages of the disease
Nell’età di Berengario I: il mondo monastico italiano e le sue trasformazioni
No full textIl saggio prende in considerazione il mondo monastico italiano al tempo di Berengario I, seguendo la parabola politica di questi, prima ancora della conquista del potere regio prima e imperiale poi. Il contesto familiare e l'esperienza giovanile del futuro re mostrano stretti intrecci con il monachesimo, intrecci che, mutatis mutandis, si manterranno nei successivi, travagliati decenni. Vengono presi in considerazione i monasteri del tempo di Berengario sotto diversi punti di vista: come centri patrimoniali ed economici, come "punti forti" nel territorio (anche in rapporto alla crescente militarizzazione di questo), come oggetto di conflitto istituzionale e giuridico, come spazi di devozione e di memoria. Viene altresì esaminata la realtà materiale di alcuni contesti oggetto di scavo o di studi sugli elevati, che restituiscono interessanti spaccati dell'organizzazione o delle scelte topografico-architettoniche operate all'interno dei centri monastici di questo momento
Holy Week in Piedmont
No full textThis article examines the theatrical aspects of the celebration of Holy Week in Piedmont, Italy, focusing on the so-called “Procession of Machines” in the city of Vercelli. This is a parade featuring statues depicting various moments of the Passion as well as saints. Special attention is focused on the problem of preserving (and reviving) traditions that were considered doomed to extinction and their functions in new conditions