Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells

Epidemiological data indicate that the daily consumption of extra‑virgin olive oil (EVOO), a common dietary habit of the Mediterranean area, lowers the incidence of certain types of cancer, in particular bladder neoplasm. The aim of the present study was to evaluate the antiproliferative activity of polyphenols extracted from EVOO on bladder cancer (BCa), and to clarify the biological mechanisms that trigger cell death. Furthermore, we also evaluated the ability of low doses of extra‑virgin olive oil extract (EVOOE) to modulate the in vitro activity of paclitaxel or mitomycin, two antineoplastic drugs used in the management of different types of cancer. Our results showed that EVOOE significantly inhibited the proliferation and clonogenic ability of T24 and 5637 BCa cells in a dose‑dependent manner. Furthermore, cell cycle analysis after EVOOE treatment showed a marked growth arrest prior to mitosis in the G2/M phase for both cell lines, with the subsequent induction of apoptosis only in the T24 cells. Notably, simultaneous treatment of mitomycin C and EVOOE reduced the drug cytotoxicity due to inhibition of ROS production. Conversely, the co‑treatment of T24 cells with paclitaxel and the polyphenol extract strongly increased the apoptotic cell death at each tested concentration compared to paclitaxel alone. Our results support the epidemiological evidence indicating that olive oil consumption exerts health benefits and may represent a starting point for the development of new anticancer strategies

Conservative surgical treatment in cervical dysplastic lesions associated with cystorectocele

The treatment of cervical intraepithelial neoplasia aims at removing the squamocolumnar junction area, including abnormal tissues, up to the healthy tissue. Old postpartum perineal tears associated with cystorectocele, hypertrophic cervical elongation, and first and second degree uterine prolapse are pelvic static disorders. Particular aspects of pelvic-genital static disorder are related to the vulnerability of the pelvic-perineal floor during birth. On the occasion of birth, especially when there are different forms of dystocia during labor, the degradation of soft pelvic, genital, and vaginal-perineal tissues can occur. The objective of this study was to re-evaluate the conservative treatment of cervical dysplasia, depending on the degree of cervical lesions, the surface extension, the age of the patients, and the pathology associated with cervical lesions – colpocele, cystorectocele, and urinary incontinence in the old postpartum perineal tears. In order to solve the three types of concomitant lesions, we used the Manchester operation: the anterior colporrhaphy with the recalibration of the urethra and the suspension of the cystocele, the minimal colpectomy, the lesional cervical amputation with the anterior fixation of the parameters, and the posterior colpoperineorrhaphy with high myorrhaphy of the levator ani muscles. The decision on the management of cervical dysplasia has taken into account the degree of cervical lesions, the extension on the surface, the patients’ age and the pregnancy planning, and the pathology associated with cervical lesions. The Manchester operation is a conservative surgical procedure, effective in women under 45 years old, multiparous, with present genital activity, with dysplastic cervical lesions and cystorectocele. It also solves cystorectocele, cervical dysplasia, hypertrophic cervical elongation, and first and second degree uterine prolapse

Linear and nonlinear post-processing of numerically forecasted surface temperature

International audienceIn this paper we test different approaches to the statistical post-processing of gridded numerical surface air temperatures (provided by the European Centre for Medium-Range Weather Forecasts) onto the temperature measured at surface weather stations located in the Italian region of Puglia. We consider simple post-processing techniques, like correction for altitude, linear regression from different input parameters and Kalman filtering, as well as a neural network training procedure, stabilised (i.e. driven into the absolute minimum of the error function over the learning set) by means of a Simulated Annealing method. A comparative analysis of the results shows that the performance with neural networks is the best. It is encouraging for systematic use in meteorological forecast-analysis service operations

Peribiliary glands as a niche of extra-pancreatic precursors yielding insulin-producing cells in experimental and human diabetes

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, towards pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) towards insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N=12) or 120 mg/kg (N=12) of streptozotocin. Liver, pancreas and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepato-pancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with up-regulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepato-pancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures towards pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the patho-physiology and complications of this disease. This article is protected by copyright. All rights reserved

Reinitiation of protein synthesis in Escherichia coli can be induced by mRNA cis-elements unrelated to canonical translation initiation signals

AbstractIn Eubacteria, de novo translation of some internal cistrons may be inefficient or impossible unless the 5′ neighboring cistron is also translated (translational coupling). Translation reinitiation is an extreme case of translational coupling in which translation of a message depends entirely on the presence of a nearby terminating ribosome. In this work, the characteristics of mRNA cis-elements inducing the reinitiation process in Escherichia coli have been investigated using a combinatorial approach. A number of novel translational reinitiation sequences (TRSs) were thus identified, which show a wide range of reinitiation activities fully dependent on a translational coupling event and unrelated to the presence/absence of secondary structure or mRNA stability. Moreover, some of the isolated TRSs are similar to intercistronic sequences present in the E. coli genome

Importancia en el sistema de salud de la infección por Treponema pallidum, la enfermedad de Chagas y el virus de la inmunodeficiencia humana 1 en amerindios de Argentina: un estudio observacional

El objetivo de este trabajo fue estimar la prevalencia de Treponema pallidum, Trypanosoma cruzi y virus de la inmunodeficiencia humana (HIV-1) en 5 comunidades originarias de Argentina. Para ello, se realizó un estudio retrospectivo en 857 individuos (112 kollas, 298 mbyá-guaraníes, 79 sagua huarpes, 368 wichis) desde el 2007 hasta el 2010. Se realizó el diagnóstico completo para T. pallidum, T. cruzi y HIV-1. En todas las comunidades se confirmaron infecciones por T. pallidum y T. cruzi con una prevalencia total del 4,2 y del 16,8%, respectivamente. Aunque no se detectó HIV-1, sífilis y Chagas, representan un desafío para el sistema de salud, teniendo que reforzarse las estrategias de salud pública teniendo en cuenta el aislamiento socio-económico que sufren estas poblaciones.The objective of this study was to estimate the prevalence of Treponema pallidum, Trypanosoma cruzi and Human immunodeficiency virus 1 (HIV-1) in five Amerindian populations of Argentina. A retrospective study was conducted among 857 Amerindian populations (112 Kollas, 298 Mbyá-guaraníes, 79 Sagua Huarpes, 368 Wichis) from 2007 to 2010. Screening and confirmation of T. pallidum, T. cruzi and HIV-1 were performed. T. pallidum and T. cruzi infections were detected in all communities with an overall prevalence rate of 4.2% and 16.8%, respectively. Although HIV was not detected, syphilis and Chagas’ disease represent a challenge for the health care system and the reinforcement of public health strategies is necessary considering the socioeconomic isolation of these populations.Fil: Eirin, Maria Emilia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Delfino, Cecilia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Pedrozo, Williams René. Provincia de Misiones. Banco de Sangre Central; ArgentinaFil: Malan, Richard. Provincia de Misiones. Banco de Sangre Central; ArgentinaFil: Puca, Alberto. Laboratorio de Bioquímica "A. A. Puca"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Espejo, Rogelio. Provincia de San Juan. Ministerio de Salud. Hospital Público "Dr. Guillermo Rawson". Laboratorio Central; ArgentinaFil: Gallo Vaulet, Maria Lucia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Rodríguez Fermepin, Marcelo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Biglione, Mirna Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Berini, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Adult human biliary tree stem cells differentiate to β-pancreatic islet cells by treatment with a recombinant human Pdx1 peptide

Generation of β-pancreatic cells represents a major goal in research. The aim of this study was to explore a protein-based strategy to induce differentiation of human biliary tree stem cells (hBTSCs) towards β-pancreatic cells. A plasmid containing the sequence of the human pancreatic and duodenal homeobox 1 (PDX1) has been expressed in E. coli. Epithelial-Cell-Adhesion-Molecule positive hBTSCs or mature human hepatocyte cell line, HepG2, were grown in medium to which Pdx1 peptide was added. Differentiation toward pancreatic islet cells were evaluated by the expression of the β-cell transcription factors, Pdx1 and musculoapo-neurotic fibrosarcoma oncogene homolog A, and of the pancreatic hormones, insulin, glucagon, and somatostatin, investigated by real time polymerase chain reaction, western blot, light microscopy and immunofluorescence. C-peptide secretion in response to high glucose was also measured. Results indicated how purified Pdx1 protein corresponding to the primary structure of the human Pdx1 by mass spectroscopy was efficiently produced in bacteria, and transduced into hBTSCs. Pdx1 exposure triggered the expression of both intermediate and mature stage β-cell differentiation markers only in hBTSCs but not in HepG2 cell line. Furthermore, hBTSCs exposed to Pdx1 showed up-regulation of insulin, glucagon and somatostatin genes and formation of 3-dimensional islet-like structures intensely positive for insulin and glucagon. Finally, Pdx1-induced islet-like structures exhibited glucose-regulated C-peptide secretion. In conclusion, the human Pdx1 is highly effective in triggering hBTSC differentiation toward functional β-pancreatic cells