Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their ...Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity.These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.展开更多
Although compliance with the European limit values for air pollutants has been achieved over large parts in Spain, some challenges remain for O3 on the maximum daily 8-hour mean and information limit values, for parti...Although compliance with the European limit values for air pollutants has been achieved over large parts in Spain, some challenges remain for O3 on the maximum daily 8-hour mean and information limit values, for particulate matter on the PM10 annual and daily limit values and for NO2 on annual and hourly limit values. Transboundary transport of air pollutants has started to be recognized as a mechanism affecting air quality. Nevertheless, as a consequence of the complexity of atmospheric chemistry it is not easy to determine the importance of this effect. Photochemical models constitute an adequate tool to address this challenge, allowing the identification of pollutant pathways and the quantifi- cation of the influence of long-range transport of air pollutants. In this paper we evaluate the influence of out-of-Spain emissions on this non-compliance picture by using the CHIMERE photochemical model. For this purpose the model was run at a 0.2?-horizontal resolution for a European domain. Although at this resolution not all the local effects can be captured, transboundary transport of air pollutants can be examined. Several simulations were performed considering different emission scenarios. To see all out-of-Spain emissions influence, all the emissions were set to zero, excepting those in Spain. This includes examining European and ships effects on air quality in Spain. A second simulation was performed setting to zero just European-countries emissions, to see the effect of Europe. The third and fourth simulations were carried out by setting to zero France and Portugal emissions respectively. Ozone has been found to be the pollutant more affected by this transboundary transport, in particular in the summer period. The model indicates that the incoming air masses contributed in 2009 to the non-compliance with the European normative regulating the maximum daily 8-hour mean.展开更多
In this work, a method for quantification of heavy metals Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS) in soil samples of El Bierzo district (Spain) has been optimized and validated. Optimizati...In this work, a method for quantification of heavy metals Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS) in soil samples of El Bierzo district (Spain) has been optimized and validated. Optimization was carried out for elements: Cr, Mn, Co, Ni, Cu, Zn, Se, As, Cd, Hg, Pb and U. Validation of the method was performed with Certified and Standard Reference Materials (CRMs and SRMs);SRM2709, CRM020-051 and CRM050-051. Results obtained under optimized conditions can be summarized as follows: a) the Limits of Detection (LODs) were in the order of sub fg·g-1 for Cr, Mn, Cu, Co, As, Cd, Hg, Pb and U, and few fg·g-1for Ni, Zn and Se;b) precision measurement, in terms of relative standard deviation (RSD), was been below 5%;c) the average recovery of CRM was between 81.3% and 98%. In conclusion, the method offers several advantages: fast, good accuracy, very low values of Limits of Quantification (LOQs) and high sensitivity on measurement of heavy metal.展开更多
基金This work was funded by project PI17/00578,from the“Instituto de Salud Carlos III”(Ministry of Science,Innovation and Universities)and co-funded by the European Regional Development Fund,and approved by the Ethics Committee of our Institution.It has been founded also by projects CB16/12/00228,PI16/00161,RD16/0011/0011,RD12/0019/0023 and SAF2017–84248-PWe would like to thank Rebeca Sánchez-Domínguez and Omaira Alberquilla for their help with the flow cytometry studies+3 种基金Federico Sánchez-Sierra and Pilar Hernández for their excellent histological processing of the samplesthe personnel of the CIEMAT Animal Unit for mouse careWe also thank Manuel Serrano(Institute for Research in Biomedicine,Barcelona,Spain)for his generous gift of Ink4a/Arf KO miceThanks also go to Anton Berns(Netherlands Cancer Institute,NKI,The Netherlands)for supplying the p53EKO mice.
文摘Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity.These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.
文摘Although compliance with the European limit values for air pollutants has been achieved over large parts in Spain, some challenges remain for O3 on the maximum daily 8-hour mean and information limit values, for particulate matter on the PM10 annual and daily limit values and for NO2 on annual and hourly limit values. Transboundary transport of air pollutants has started to be recognized as a mechanism affecting air quality. Nevertheless, as a consequence of the complexity of atmospheric chemistry it is not easy to determine the importance of this effect. Photochemical models constitute an adequate tool to address this challenge, allowing the identification of pollutant pathways and the quantifi- cation of the influence of long-range transport of air pollutants. In this paper we evaluate the influence of out-of-Spain emissions on this non-compliance picture by using the CHIMERE photochemical model. For this purpose the model was run at a 0.2?-horizontal resolution for a European domain. Although at this resolution not all the local effects can be captured, transboundary transport of air pollutants can be examined. Several simulations were performed considering different emission scenarios. To see all out-of-Spain emissions influence, all the emissions were set to zero, excepting those in Spain. This includes examining European and ships effects on air quality in Spain. A second simulation was performed setting to zero just European-countries emissions, to see the effect of Europe. The third and fourth simulations were carried out by setting to zero France and Portugal emissions respectively. Ozone has been found to be the pollutant more affected by this transboundary transport, in particular in the summer period. The model indicates that the incoming air masses contributed in 2009 to the non-compliance with the European normative regulating the maximum daily 8-hour mean.
文摘In this work, a method for quantification of heavy metals Inductively Coupled Plasma Sector Field Mass Spectrometry (ICP-SFMS) in soil samples of El Bierzo district (Spain) has been optimized and validated. Optimization was carried out for elements: Cr, Mn, Co, Ni, Cu, Zn, Se, As, Cd, Hg, Pb and U. Validation of the method was performed with Certified and Standard Reference Materials (CRMs and SRMs);SRM2709, CRM020-051 and CRM050-051. Results obtained under optimized conditions can be summarized as follows: a) the Limits of Detection (LODs) were in the order of sub fg·g-1 for Cr, Mn, Cu, Co, As, Cd, Hg, Pb and U, and few fg·g-1for Ni, Zn and Se;b) precision measurement, in terms of relative standard deviation (RSD), was been below 5%;c) the average recovery of CRM was between 81.3% and 98%. In conclusion, the method offers several advantages: fast, good accuracy, very low values of Limits of Quantification (LOQs) and high sensitivity on measurement of heavy metal.
