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2.
Breast Cancer Res ; 25(1): 84, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461077

RESUMO

The receptor for advanced glycation end products (RAGE) is implicated in diabetes and obesity complications, as well as in breast cancer (BC). Herein, we evaluated whether RAGE contributes to the oncogenic actions of Insulin, which plays a key role in BC progression particularly in obese and diabetic patients. Analysis of the publicly available METABRIC study, which collects gene expression and clinical data from a large cohort (n = 1904) of BC patients, revealed that RAGE and the Insulin Receptor (IR) are co-expressed and associated with negative prognostic parameters. In MCF-7, ZR75 and 4T1 BC cells, as well as in patient-derived Cancer-Associated Fibroblasts, the pharmacological inhibition of RAGE as well as its genetic depletion interfered with Insulin-induced activation of the oncogenic pathway IR/IRS1/AKT/CD1. Mechanistically, IR and RAGE directly interacted upon Insulin stimulation, as shown by in situ proximity ligation assays and coimmunoprecipitation studies. Of note, RAGE inhibition halted the activation of both IR and insulin like growth factor 1 receptor (IGF-1R), as demonstrated in MCF-7 cells KO for the IR and the IGF-1R gene via CRISPR-cas9 technology. An unbiased label-free proteomic analysis uncovered proteins and predicted pathways affected by RAGE inhibition in Insulin-stimulated BC cells. Biologically, RAGE inhibition reduced cell proliferation, migration, and patient-derived mammosphere formation triggered by Insulin. In vivo, the pharmacological inhibition of RAGE halted Insulin-induced tumor growth, without affecting blood glucose homeostasis. Together, our findings suggest that targeting RAGE may represent an appealing opportunity to blunt Insulin-induced oncogenic signaling in BC.


Assuntos
Neoplasias da Mama , Insulina , Receptor para Produtos Finais de Glicação Avançada , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteômica , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/fisiologia
3.
Food Chem ; 383: 132364, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35193091

RESUMO

Food product nutritional and sensory characteristics are often deeply linked to its territory of origin; therefore, its authentication by means of elemental composition becomes crucial for traceability and fighting food fraud. This study aims to establish a fast and reproducible procedure for origin and quality assessment of Sicilian tomato fruits, including PGI "Pomodoro di Pachino", by using the X-ray fluorescence (XRF) technique. Measurements were performed on different parts of PGI Pachino tomatoes belonging to the same production lot. Principal Component and Cluster Analyses show that the samples cluster accordingly with the production lot, disentangling the different parts of the fruit. This procedure, which uses XRF yield elemental pattern and statistical analysis, establishes a solid basis for characterizing elemental profiles by a fast XRF in-situ campaign, supporting the traceability system. The reliability of XRF results was confirmed by comparing elemental concentrations with ICP-MS measurements, performed for comparison, and tomato literature values.


Assuntos
Frutas , Solanum lycopersicum , Estudos de Viabilidade , Reprodutibilidade dos Testes
4.
Pancreatology ; 21(5): 950-956, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33795194

RESUMO

BACKGROUND: Ampullary carcinoma (AC) is histologically classified as intestinal (In-AC), pancreaticobiliary (Pb-AC) or mixed-AC. The prognostic role of AC subtypes has been debated and remains unclear. The aims of this study were to evaluate outcomes after pancreatoduodenectomy (PD) for each subtype of AC and to compare these with pancreatic ductal adenocarcinoma [PDAC] and distal cholangiocarcinoma [DCC]. METHODS: PDs performed for AC between 2010 and 2018 were retrospectively evaluated. Histological subtype was obtained for all patients. One-year, 3-year and 5-year disease-free-survival (DFS) and overall survival (OS) rates were calculated. Kaplan-Meier survival analysis was performed to compare Pb-AC, In-AC and mixed-AC. Comparison with PDs performed for PDAC and DCC during the same period was also performed. RESULTS: A total of 97 patients undergoing PD for AC were evaluated: 34 (35.1%) In-AC, 54 (55.7%) Pb-AC and 9 mixed-AC (9.3%). DFS and OS rates for Pb-AC were significantly lower compared to In-AC (p < 0.05 and p < 0.01), but similar to mixed-AC (p = 0.3 and p = 0.4). Adjuvant therapy was not associated with increased survival, regardless of the histological subtype (p > 0.05). During the same period, 337 and 53 PDs for PDAC and DCC, respectively, were performed. In-AC was associated with significantly better outcomes compared to PDAC and DCC (p < 0.001); DFS and OS rates for Pb-AC and mixed AC were significantly higher compared to PDAC (p < 0.001), but similar to DCC (p > 0.05). CONCLUSIONS: Pb-AC has significantly worse survival compared to In-AC. Moreover, mixed-AC should be considered as Pb-AC. Pb-AC and mixed-AC seem to have better prognosis compared to PDAC, but similar to DCC.


Assuntos
Ampola Hepatopancreática , Neoplasias dos Ductos Biliares , Carcinoma Ductal Pancreático , Colangiocarcinoma , Neoplasias do Ducto Colédoco , Neoplasias Pancreáticas , Ampola Hepatopancreática/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Ductal Pancreático/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Humanos , Chumbo , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Prognóstico , Estudos Retrospectivos , Neoplasias Pancreáticas
5.
J Transl Med ; 18(1): 340, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883314

RESUMO

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables. METHODS: Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected. RESULTS: In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4-63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036). CONCLUSIONS: Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.


Assuntos
Linfócitos do Interstício Tumoral , Recidiva Local de Neoplasia , Biomarcadores , Humanos , Antígenos Comuns de Leucócito , Prognóstico
6.
Sci Rep ; 10(1): 453, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949213

RESUMO

Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISC ribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs can exist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emerging that in addition to sequence even the structure adopted by mature miRNAs might play an important role to reach the target. Indeed, we analysed by several spectroscopic techniques the secondary structures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates to silence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having the same seed region, but different biological activity. Our results demonstrate that both endogenous and artificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity toward the targets.


Assuntos
MicroRNAs/química , MicroRNAs/genética , Sequência de Bases , Receptores ErbB/deficiência , Receptores ErbB/genética , Inativação Gênica , Conformação de Ácido Nucleico , Proteínas Proto-Oncogênicas c-met/deficiência , Proteínas Proto-Oncogênicas c-met/genética , Análise de Sequência de RNA
7.
Br J Surg ; 106(13): 1819-1828, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31282569

RESUMO

BACKGROUND: Total pancreatectomy is required to treat diseases involving the entire pancreas, and is characterized by high morbidity rates and impaired long-term quality of life (QoL). To date, risk factors associated with perioperative and long-term outcomes have not been determined fully. METHODS: Data from patients undergoing total pancreatectomy between 2000 and 2014 at two high-volume centres were analysed retrospectively to assess risk factors for major surgical complications. Short Form (SF) 36, European Organisation for Research and Treatment of Cancer QLQ-PAN26 and Audit of Diabetes Dependent questionnaires, as well as an original survey were used to investigate factors influencing QoL. RESULTS: A total of 329 consecutive patients underwent total pancreatectomy in the two centres. Overall, total pancreatectomy was associated with a morbidity rate of 59·3 per cent and a 30-day mortality rate of 2·1 per cent. Age over 65 years and long duration of surgery (more than 420 min) were independently associated with major complications (at least Clavien-Dindo grade III). QoL analysis was available for 94 patients (28·6 per cent) with a median follow-up of 63 (i.q.r. 20-109) months; the most common indication for total pancreatectomy in these patients was intraductal papillary mucinous neoplasms (46 per cent). Both physical (PCS) and mental (MCS) component summary scores of SF-36® were lower after total pancreatectomy compared with scores for a normative population (P = 0·020 and P < 0·001 respectively). Linear regression analysis showed that young age, abdominal pain and worse perception of body image were negatively associated with the PCS, whereas diabetes, sexual satisfaction and perception of body image affected MCS. CONCLUSION: Total pancreatectomy can be performed with acceptable morbidity and mortality rates. Older patients had a higher risk of postoperative complications but reported better QoL than younger patients.


ANTECEDENTES: La pancreatectomía total es una cirugía necesaria para tratar enfermedades que afectan a la totalidad el páncreas y se caracteriza por una alta morbilidad y una disminución de la calidad de vida (QoL) a largo plazo. Hasta la fecha, los factores de riesgo asociados a los resultados perioperatorios y a largo plazo no han sido completamente determinados. MÉTODOS: Los datos de los pacientes que se sometieron a una pancreatectomía total desde el año 2000 al 2015 en dos centros de alto volumen se analizaron retrospectivamente para evaluar los factores de riesgo de las complicaciones quirúrgicas mayores. Se utilizaron el SF-36, el EORTC-PAN-26, los cuestionarios ADD-QoL y una encuesta original para investigar los factores que afectan la QoL. RESULTADOS: Un total de 329 pacientes consecutivos se sometieron a una pancreatectomía total en los dos centros. En general, la pancreatectomía total se asoció a un 59,3% de morbilidad y un 2,1% de mortalidad a los 30 días. La edad > 65 años y el tiempo operatorio prolongado (> 420 minutos) se asociaron de forma independiente a las complicaciones Clavien-Dindo ≥ III. El análisis de QoL estuvo disponible en 94 (28,6%) de los pacientes con una mediana de seguimiento de 63 meses (rango intercuartílico 20-109) y la indicación más común fue una neoplasia papilar mucinosa intraductal (IPMN) (45,7%). Las puntuaciones del SF-36 fueron más bajas en ambos componentes sumatorios físico (PCS) y mental (MCS) (P = 0,002; P < 0,001) en comparación con una población normal. El modelo de regresión lineal mostró que la edad joven, el dolor abdominal y la peor percepción de la imagen corporal se asociaron negativamente con el PCS; mientras que la diabetes, la satisfacción sexual y la percepción de la imagen corporal afectaron al MCS. CONCLUSIÓN: Se puede realizar una pancreatectomía total con morbilidad y mortalidad aceptables. Los pacientes de mayor edad tienen un riesgo más elevado de complicaciones postoperatorias, pero presentaron mejor QoL que los pacientes más jóvenes.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Neoplasias Pancreáticas/psicologia , Período Perioperatório , Complicações Pós-Operatórias/psicologia , Prognóstico , Estudos Retrospectivos , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
8.
Nutr Metab Cardiovasc Dis ; 28(6): 636-642, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29625779

RESUMO

BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.


Assuntos
Insuficiência Cardíaca/diagnóstico , Desnutrição/sangue , Peptídeo Natriurético Encefálico/sangue , Admissão do Paciente , Insuficiência Renal Crônica/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Comorbidade , Feminino , Avaliação Geriátrica/métodos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Itália , Contagem de Leucócitos , Masculino , Desnutrição/diagnóstico , Desnutrição/mortalidade , Desnutrição/terapia , Avaliação Nutricional , Estado Nutricional , Readmissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Fatores de Risco , Fatores de Tempo
9.
Nutr Metab Cardiovasc Dis ; 28(1): 23-27, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29241668

RESUMO

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported to be associated with subclinical atherosclerosis, but its predictive role of the presence of carotid atherosclerotic plaques remains undefined. This study aims to assess this association which gives additional value to this biomarker, with respect to the main risk factors, in the prediction of carotid atherosclerosis in older adults. METHODS AND RESULTS: We recruited 324 patients, aged ≥65 years, without hematopoietic disorders, and/or history of malignancies, evidence of acute infections, chronic inflammatory status, and history of glucocorticoid therapy within the past three months, hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy from January 2014 to December 2016. All patients underwent blood sampling for white blood cell, neutrophil, lymphocyte and platelet counts, and for measurements of inflammatory markers, NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients also underwent carotid scan by ultrasonography (US) to evaluate abnormalities of carotid wall. NLR resulted a strong predictor of the presence of carotid plaques. NLR > 2.4 predicted with 80% probability carotid plaques (p < 0.01), while NLR > 3.68 gave 97% probability (p = 0.013). Furthermore, NLR > 2.4 was associated with an average presence of 2.86 carotid plaques (p < 0.001). Fibrinogen and CRP performed well, but with lesser significance, as predictors of the presence of carotid plaques (p = 0.002). CONCLUSION: NLR is a strong predictor of the presence and the number of carotid atherosclerotic plaques. Its use could be useful to identify the risk of harboring carotid plaques.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Linfócitos , Neutrófilos , Placa Aterosclerótica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Contagem de Linfócitos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
10.
Nutr Metab Cardiovasc Dis ; 26(12): 1129-1139, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27756518

RESUMO

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers. METHODS AND RESULTS: We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation. CONCLUSIONS: These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo.


Assuntos
Hepatócitos/metabolismo , Fígado/metabolismo , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Antígenos CD36/genética , Antígenos CD36/metabolismo , Sobrevivência Celular , Ceramidas/metabolismo , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Biologia Computacional , Diglicerídeos/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Marcadores Genéticos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ácido Oleico/toxicidade , Análise de Sequência com Séries de Oligonucleotídeos , Ácido Palmítico/toxicidade , Fosforilação , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de Tempo
11.
Cell Death Dis ; 7: e2206, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-27124580

RESUMO

Glycogen synthase kinase-3ß (GSK-3ß) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3ß expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3ß were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3ß mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3ß-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3ß-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3ß in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3ß in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3ß as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.


Assuntos
Apoptose , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/metabolismo , Doença de Huntington/patologia , Proteínas tau/metabolismo , Adulto , Idoso , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Caspase 3/metabolismo , Células Cultivadas , Citocinas/metabolismo , Giro Denteado/metabolismo , Modelos Animais de Doenças , Feminino , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Glicogênio Sintase Quinase 3 beta/genética , Hipocampo/citologia , Hipocampo/patologia , Humanos , Doença de Huntington/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Neurônios/metabolismo , Estresse Oxidativo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Índice de Gravidade de Doença
12.
Biomed Res Int ; 2014: 529519, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24783210

RESUMO

This paper presents different applications, in various foodstuffs, by a novel electronic nose (EN) based on a mixed metal oxide sensors array composed of thin films as well as nanowires. The electronic nose used for this work has been done, starting from the commercial model EOS835 produced by SACMI Scarl. The SENSOR Lab (CNR-INO, Brescia) has produced both typologies of sensors, classical MOX and the new technologies with nanowire. The aim of this work was to test and to illustrate the broad spectrum of potential uses of the EN technique in food quality control and microbial contamination diagnosis. The EN technique was coupled with classical microbiological and chemical techniques, like gas chromatography with mass spectroscopy (GC-MS) with SPME technique. Three different scenarios are presented: (a) detection of indigenous mould in green coffee beans, (b) selection of microbiological spoilage of Lactic Acid Bacteria (LAB), and (c) monitoring of potable water. In each case, the novel EN was able to identify the spoiled product by means of the alterations in the pattern of volatile organic compounds (VOCs), reconstructed by principal component analysis (PCA) of the sensor responses. The achieved results strongly encourage the use of EN in industrial laboratories. Finally, recent trends and future directions are illustrated.


Assuntos
Nariz Eletrônico , Análise de Alimentos , Microbiologia de Alimentos , Membranas Artificiais , Nanofios/química , Compostos Orgânicos Voláteis/análise , Análise de Alimentos/instrumentação , Análise de Alimentos/métodos , Microbiologia de Alimentos/instrumentação , Microbiologia de Alimentos/métodos
13.
Neuropediatrics ; 41(6): 246-55, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21445814

RESUMO

BACKGROUND: There are only a few series in the literature on acute disseminated encephalomyelitis (ADEM) in children. OBJECTIVES AND METHODS: the aims of this study were to perform (i) a prospective clinical/imaging study (1992-2009) on ADEM in children consecutively referred to our institution in Catania, Italy, and (ii) to undertake a systematic review and meta-analysis of published ADEM pediatric cohorts (>10 cases). RESULTS: We identified 17 patients with ADEM (incidence <10 years of age=1.1 per 100 000 person-years). 15 previously published cohorts were compared with our cohort: (i) systematically reviewed (750 cases); and (ii) meta-analyzed (492/750 cases). The 17 patients had the following characteristics: (a) male-to-female ratio, 1.4 (vs. 1.2-1.3 in previous cohorts); (b) mean age at presentation, 3.6 years (vs. 7.1 years in previous cohorts); (c) specific preceding triggering factor, 88% (vs. 69-79% in previous cohorts); (d) the most common initial signs were ataxia, seizures, headache, and thalamic syndrome; (e) brain imaging revealed >3 lesions in 100% (vs. 92% in previous cohorts); (f) the outcome was good in 94% (vs. 70-75% in previous cohorts); and (g) 12% relapsed once (vs. 18% in previous cohorts). CONCLUSIONS: ADEM is generally a benign condition that mosly affects boys more than girls and rarely recurs.


Assuntos
Encéfalo/patologia , Encefalomielite Aguda Disseminada/diagnóstico , Corticosteroides/uso terapêutico , Idade de Início , Encéfalo/fisiopatologia , Criança , Eletroencefalografia , Encefalomielite Aguda Disseminada/tratamento farmacológico , Encefalomielite Aguda Disseminada/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
14.
Database (Oxford) ; 2009: bap008, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20157481

RESUMO

miRò is a web-based knowledge base that provides users with miRNA-phenotype associations in humans. It integrates data from various online sources, such as databases of miRNAs, ontologies, diseases and targets, into a unified database equipped with an intuitive and flexible query interface and data mining facilities. The main goal of miRò is the establishment of a knowledge base which allows non-trivial analysis through sophisticated mining techniques and the introduction of a new layer of associations between genes and phenotypes inferred based on miRNAs annotations. Furthermore, a specificity function applied to validated data highlights the most significant associations. The miRò web site is available at: http://ferrolab.dmi.unict.it/miro.Database URL:http://ferrolab.dmi.unict.it/miro.

15.
Bioinformatics ; 23(7): 910-2, 2007 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-17277332

RESUMO

UNLABELLED: NetMatch is a Cytoscape plugin which allows searching biological networks for subcomponents matching a given query. Queries may be approximate in the sense that certain parts of the subgraph-query may be left unspecified. To make the query creation process easy, a drawing tool is provided. Cytoscape is a bioinformatics software platform for the visualization and analysis of biological networks. AVAILABILITY: The full package, a tutorial and associated examples are available at the following web sites: http://alpha.dmi.unict.it/~ctnyu/netmatch.html, http://baderlab.org/Software/NetMatch.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Armazenamento e Recuperação da Informação/métodos , Modelos Biológicos , Transdução de Sinais/fisiologia , Software , Interface Usuário-Computador , Algoritmos , Gráficos por Computador , Simulação por Computador
16.
Apoptosis ; 11(1): 57-66, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16374542

RESUMO

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.


Assuntos
Apoptose/efeitos da radiação , Neoplasias/radioterapia , Terapia com Prótons , Apoptose/genética , Sequência de Bases , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Dano ao DNA , Primers do DNA/genética , Espectroscopia de Ressonância de Spin Eletrônica , Feminino , Citometria de Fluxo , Humanos , Masculino , Necrose , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fótons/uso terapêutico , RNA Mensageiro/genética , RNA Neoplásico/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Methods Inf Med ; 44(2): 215-20, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15924179

RESUMO

OBJECTIVE: The development of computational Grids is making huge amounts of computing power and data storage available for a lot of scientific applications. At this stage of development, the use of the Grid is mainly based on Command Line Interface (CLI) tools that are not very friendly and can be considered an obstacle to the use of these powerful tools. The objective of this paper is to present a solution to this problem. METHODS: To ease the access of new users to the grid the GENIUS (Grid Enabled web eNvironment for site Independent User job Submission) grid portal has been jointly developed by INFN and NICE within the context of both the Italian INFN Grid and the European DataGrid Projects. Here we devote particular care to the description of job creation and submission and the services for transparent access to user's data and applications. RESULTS: Using GENIUS, the obstacle of complicated CLI can be overtaken and simple web interfaces can be built for specific user communities and applications. Here we show examples in the field of bio-medical applications. CONCLUSIONS: The use of Grid can be made easy with the use of Grid portals such as GENIUS.


Assuntos
Armazenamento e Recuperação da Informação/métodos , Internet/instrumentação , Aplicações da Informática Médica , Sistemas Computadorizados de Registros Médicos/instrumentação , Biologia de Sistemas/instrumentação , Integração de Sistemas , Algoritmos , Sistemas de Gerenciamento de Base de Dados , Bases de Dados Factuais , Europa (Continente) , Humanos , Internacionalidade , Itália , Desenvolvimento de Programas
18.
Suppl Tumori ; 4(3): S74-5, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16437913

RESUMO

In this article, we describe a successfully performed total esophagogastrectomy for esophageal carcinoma in young man. The esophagus was mobilized via the right thoracotomy. Intestinal continuity, installed isoperistaltically was restituted in the same operation using an ileo-colic segment transferred to the left lateral cervical aspect by way of the posterior mediastinum. The procedure was used in one patient and mortality and complications were nil.


Assuntos
Colo/cirurgia , Esofagectomia/métodos , Esôfago/cirurgia , Gastrectomia/métodos , Íleo/cirurgia , Jejuno/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
19.
Suppl Tumori ; 4(3): S106-7, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16437936

RESUMO

Gastrointestinal stromal tumors (GIST) comprise a rare group of neoplasms of unpredictable malignant. The stomach is the most common site of occurrence in the gastrointestinal tract. A combination of prognostic factors (patient age, histologic grade, mitotic rate, tumor size, and DNA analysis) have been utilized to predict their biologic behavior. Lymphatic spread of gastrointestinal stromal tumors is uncommon therefore a formal lymph node dissection is not standard surgical management. Consequently, complete surgical resection of the primary tumor is the most definitive treatment. Although numerous operative approaches have been utilized for gastric submucosal tumors, laparoscopic wedge resection has been regarded as the treatment of choice in recent years. As widespread use of diagnostic endoscopy has exposed a number of gastric submucosal tumors, the laparoscopic wedge resections are being performed with increased frequency. In this article, we describe a successfully performed laparoscopic sleeve gastrectomy for a bleeding GIST.


Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia , Idoso , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/complicações , Humanos
20.
Suppl Tumori ; 4(3): S128, 2005.
Artigo em Italiano | MEDLINE | ID: mdl-16437947

RESUMO

Although hemangiopericytoma (HPT) may arise in any anatomic site, it rarely develops in the greater omentum. To our knowledge, only twelve cases have been reported to date in the English language literature. In this report, we describe the case of a patient with sudden severe lower abdominal pain caused by primary HPT in the greater omentum treated with laparoscopic approach and a review of the reported cases is made.


Assuntos
Hemangiopericitoma/cirurgia , Laparoscopia , Omento , Neoplasias Peritoneais/cirurgia , Cirurgia Vídeoassistida , Humanos
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