Glutathione-sensitive nanogels for drug release

Nanogels (NGs) synthesized by pulsed electron-beam irradiation of semi-dilute poly (N-vinyl pyrrolidone) (PVP) aqueous solutions, at relatively low energy per pulse and doses within the sterilization dose range, represent a very interesting family of polymeric nanocarriers. Ionizing irradiation-induced crosslinking of PVP allows to control particle size, and surface chemistry of the polymer nanoparticles without making use of catalysts, organic solvents or surfactants, and with beneficial effects onto the purity and hence biocompatibility of the final products obtained. Furthermore, the availability of reactive functional groups, either generated by the radiation or purposely grafted via copolymerisation with suitable functional monomers enables the conjugation of therapeutics drug, that make them suitable nanocarriers for biomedical applications. In particular, we have developed a carboxyl-functionalized nanogel variant for glutathione-mediated delivery of a chemotherapeutic agent, Doxorubicin. The drug is linked to the nanoparticles through a linker containing a cleavable disulphide bridge, aminoethyldithiopropionic acid (AEDP). In vitro drug release experiments have shown that glutathione can induce the release of Doxorubicin, through the reduction of the disulfide bridge. These results suggest that such redox-responsive nanoparticles can deliver doxorubicin into the nuclei of tumor cells, thus inducing inhibition of cell proliferation, and provide a favourable platform to construct nanoscalar drug delivery systems for cancer therapy

Clinical Network for Big Data and Personalized Health: Study Protocol and Preliminary Results

The use of secondary hospital-based clinical data and electronical health records (EHR) represent a cost-efficient alternative to investigate chronic conditions. We present the Clinical Network Big Data and Personalised Health project, which collects EHRs for patients accessing hospitals in Central-Southern Italy, through an integrated digital platform to create a digital hub for the collection, management and analysis of personal, clinical and environmental information for patients, associated with a biobank to perform multi-omic analyses. A total of 12,864 participants (61.7% women, mean age 52.6 ± 17.6 years) signed a written informed consent to allow access to their EHRs. The majority of hospital access was in obstetrics and gynaecology (36.3%), while the main reason for hospitalization was represented by diseases of the circulatory system (21.2%). Participants had a secondary education (63.5%), were mostly retired (25.45%), reported low levels of physical activity (59.6%), had low adherence to the Mediterranean diet and were smokers (30.2%). A large percentage (35.8%) were overweight and the prevalence of hypertension, diabetes and hyperlipidemia was 36.4%, 11.1% and 19.6%, respectively. Blood samples were retrieved for 8686 patients (67.5%). This project is aimed at creating a digital hub for the collection, management and analysis of personal, clinical, diagnostic and environmental information for patients, and is associated with a biobank to perform multi-omic analyses

Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine

New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and 119Sn Mössbauer in the solid state and by 1H and 13C NMR spectroscopy, in so- lution. Moreover, the crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 are reported. The complexes contain hexacoordinated tin atoms: in Et2SnCl2(dbtp)2 two 5,7-ditertbutyl-1,2,4- triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordina- tion around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph2SnCl2(EtOH)2 (dptp)2 two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo [1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N (3), to the \OH group of the ethanol moieties; Ph2SnCl2(EtOH)2(dptp)2 has an all-trans structure and the C–Sn–C fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et2SnCl2(dbtp)2, while Me2SnCl2(dptp)2 to have a regular all-trans octahedral structure. A distorted cis-R2 trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5 μg/mL, most of all against staphylococcal strains, which shows their inhibitory effect

Verifying the reliability of historical sources through an archaeometric study

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La pianificazione della sicurezza nei progetti di bonifica dei siti contaminati

Gli interventi di bonifica o di messa in sicurezza dei siti contaminati comportano quasi sempre lavori di ingegneria civile; in tale ambito i rischi per la salute e la sicurezza dei lavoratori devono essere gestiti secondo le disposizioni del Titolo IV del D.Lgs. 81/2008 (“Cantieri temporanei e mobili”). Ad oggi sono state riscontrate criticità nella redazione dei documenti richiesti ex lege in fase progettuale per identificare, valutare e gestire i suddetti rischi. Quindi, nella presente memoria sono, dapprima, individuate le corrispondenze tra i livelli progettuali definiti nella normativa ambientale e nel codice dei contratti pubblici; sulla base degli esiti di tale confronto, sono indicati i documenti finalizzati alla tutela della salute e sicurezza dei lavoratori nella progettazione relativa al procedimento di bonifica/messa in sicurezza e, infine, sono specificati i relativi contenuti, con particolare riferimento ai rischi connessi all’esposizione a sostanze pericolose

Management of BRCA mutation carriers

Pathogenic mutations in two autosomal dominant genes, BRCA1 and BRCA2 , with high penetrance are supposed to be the cause for an approximated 5–7% risk of all breast cancer (BC) and ovarian cancer (OC). Compared to sporadic BC, BRCA mutated ( BRCAmut ) BC differs for lifetime risk of onset and sensitivity to systemic therapies. A hereditary BC syndrome should be taken into account when there are numerous relatives with BC early-onset (typically before menopause). Moreover, BRCAmut carriers showed a lifetime possibility of manifesting OC. When a BC diagnosis is made in young patients or in suspicious personal relatives' anamnesis, be aware of being carriers of a BRCA mutation may influence the decision making-process about surgical procedure and prevention strategies. In this review, we examined surgical treatment choice for BRCAmut BC, risk of ipsilateral breast recurrence (IBR) and contralateral breast cancer (CBC). We examined the role of breast-conserving therapy (BCT), risk-reducing mastectomy (RRM) and preventive risk-reducing salpingo-oophorectomy (RRSO) with a special consideration about advantage in terms of mortality reduction for both conservative and prophylactic measures. We also reviewed the sensitivity of mutated BC to platinum-based antineoplastic drugs and poly (ADP-ribose) polymerase inhibitors (PARPi) by emphasizing the results of clinical trials recently published

Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort

Background: High dietary glycaemic index (GI) and load (GL) have been associated with increased risk of various cardiometabolic conditions. Among the molecular potential mechanisms underlying this relationship, DNA methylation has been studied, but a direct link between high GI and/or GL of diet and global DNA methylation levels has not been proved yet. We analyzed the associations between GI and GL and global DNA methylation patterns within an Italian population. Results: Genomic DNA methylation (5mC) and hydroxymethylation (5hmC) levels were measured in 1080 buffy coat samples from participants of the Moli-sani study (mean(SD) = 54.9(11.5) years; 52% women) via ELISA. A 188-item Food Frequency Questionnaire was used to assess food intake and dietary GI and GL for each participant were calculated. Multiple linear regressions were used to investigate the associations between dietary GI and GL and global 5mC and 5hmC levels, as well as the proportion of effect explained by metabolic and inflammatory markers. We found negative associations of GI with both 5mC (β (SE) = - 0.073 (0.027), p = 0.007) and 5hmC (- 0.084 (0.030), p = 0.006), and of GL with 5mC (- 0.14 (0.060), p = 0.014). Circulating biomarkers did not explain the above-mentioned associations. Gender interaction analyses revealed a significant association of the gender-x-GL interaction with 5mC levels, with men showing an inverse association three times as negative as in women (interaction β (SE) = - 0.16 (0.06), p = 0.005). Conclusions: Our findings suggest that global DNA methylation and hydroxymethylation patterns represent a biomarker of carbohydrate intake. Based on the differential association of GL with 5mC between men and women, further gender-based separate approaches are warranted

Organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine and their cytotoxic activities: the importance of being conformers.

The organotin(IV) compounds Me2SnCl2(dbtp)(1), Me2SnCl2(dbtp)2 (2), Et2SnCl2(dbtp) (3), Et2SnCl2(dbtp)2 (4), Et2SnCl2(dptp) (5), nBu2SnCl2(dbtp)2 (6), nBu2SnCl2(dptp) (7), Ph2SnCl2(dbtp) (8), Ph2SnCl2(dptp)2 (9), where dbtp = 5,7-di-tert-butyl-1,2,4-triazolo[1,5-a]pyrimidine and dptp = 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine, have been tested towards their cytotoxic activity by MTT test on three tumor cell lines, HepG2 (human hepatocellular carcinoma), HeLa (human cervix adenocarcinoma) and MCF-7 (human breast cancer). Except for 1 and 2, which were ineffective, all compounds significantly showed a dose-dependent anti-proliferative effect toward the three cell lines. By calculated IC50 values, cytotoxicity of the complexes followed the order nBu > Ph > Et > Me for all the selected tumor cells. Organotin(IV) compounds (6-9)-induced cell death of HepG2 was considered to be apoptotic by measuring the exposure of phosphadytilserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange/ethidium bromide staining. Flow cytometric analysis of propidium iodide-stained cells also demonstrated that organotin(IV) complexes caused apoptosis of HepG2 cells through cell arrest at G0-G1 phase. The crystal structure of 7 was investigated by X-ray diffraction analysis, exhibiting a distorted trigonal bipyramidal geometry with N, Cl as axial atoms and Cl and butyl groups in the equatorial plane. The triazolopyrimidine unit coordinates to the Sn atom through N(3) in a monodentate mode. Two conformational isomers (molecule A and B in the crystallographic independent unit) are cocrystallized in the solid state, a phenomenon that has been observed only occasionally. Conformational mobility of the cytotoxic complex 7 can sum up to the ligands ability to form Hbonds and π···π stacking, facilitating its intracellular uptake

Neuro-Oncology Multidisciplinary Tumor Board: The Point of View of the Neuroradiologist

Background: The multi-disciplinary tumor board (MTB) is essential to quality cancer care and currently recommended to offer the best personalized clinical approach, but little has been published regarding MTBs in neuro-oncology (nMTBs). The aim of the present paper is to describe our nMTB, to evaluate its impact on clinical management decisions, and to assess the role of neuroradiologists. Methods: The retrospective evaluation of the cases discussed at our nMTB from March 2017 to March 2020. From the electronic records, we extracted epidemiological, clinical and other specific data of nMTB. From the radiological records, we calculated data relating to the number, time for revision, and other specifications of MRI re-evaluation. Statistical analysis was performed. Results: a total of 447 discussions were analyzed, representing 342 patients. The requests for case evaluations came from radiation oncologists (58.8%) and neurosurgeons (40.5%), and were mainly addressed to the neuroradiologist (73.8%). The most frequent questions were about the treatment's changes (64.4%). The change in patient treatment was reported in 40.5% of cases, 76.8% of these were based on the neuroradiologic assessment. A total of 1514 MRI examinations were re-evaluated, employing approximately 67 h overall. The median of the MRI exams reviewed per patient was 3 (min-max 1-12). Conclusions: Our study supported that the multidisciplinary approach to patient care can be particularly effective in managing brain tumors. A review by an expert neuroradiologist impacts patient management in the context of nMTBs, but has costs in terms of the time and effort spent preparing for it