A short story of 3AB-OS cancer stem cells, a possible model for studying cancer stemness

Cancer Stem Cells (CSCs) are thought to be the cause of cancer initiation, growth and development. Thus, a challenge in cancer research is their identification and eradication. In our laboratory, by chemical treatment of the human osteosarcoma (OS) MG63 cell line, we have isolated and characterized 3AB-OS cells, a human OS CSC line. 3AB-OS cells transdifferentiate in vitro into cells of the three derivatives germ layers and, when xenografted in athymic mice they are highly tumorigenic and recapitulate in vivo crucial features of human OS. They even express a reprogrammed energy metabolism, with a dependence on glycolytic metabolism more strong than parental MG63 cells. 3AB-OS cells have chromosomes showing a great number of abnormalities which are very similar to abnormalities found in both pediatric and adult osteosarcomas. In comparison with parental MG63 cells (where TP53 gene is hypermethylated, rearranged and in single copy), 3AB-OS cells have TP53 gene unmethylated, rearranged and in multiple copies. Moreover, the mutp53 (p53-R248W/P72R) is post-translationally stabilized, has nuclear localization and a gain of function. A great number of results obtained in our laboratories suggested that p53 mutation could be the “driver mutation” at the origin of the transformation of MG63 cells into 3AB-OS CSCs

Benzo[b]tiophen-3-ol derivatives as effective inhibitors of human monoamine oxidase: design, synthesis, and biological activity

A series of benzo[b]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors in vitro as well as ex vivo in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed

Knowledge and attitudes of healthcare workers towards gender based violence

OBJETIVOS: Várias são as políticas públicas no Brasil para o enfrentamento da violência contra a mulher. Registra-se na literatura que os profissionais de saúde acham o tema de difícil abordagem. Para melhorar o atendimento no SUS em Ribeirão Preto, realizou-se um estudo para avaliar o conhecimento e a atitude dos profissionais de saúde em relação à violência de gênero. MÉTODOS: Contataram-se 278 profissionais de saúde, dos quais 221 foram entrevistados utilizando-se um questionário estruturado. RESULTADOS: 51 (23,0%) eram enfermeiras e 170 (77,0%) médicos; 119 (53,8%) homens e 102 (46,2%) mulheres, com idade média de 38,6 anos; 200 (90,5%) consideravam-se brancos ou asiáticos e 21 (9,5%) pretos e pardos. Tinham em média 12,5 anos de vida profissional e 158 (68,8%) eram oriundos de universidade pública. Apenas pouco mais da metade (58,7%) mostrou conhecimento geral adequado (bom e alto) sobre a violência de gênero, o que indica a necessidade de capacitar os profissionais para este atendimento. Em relação às barreiras para averiguar a violência, os profissionais citaram a falta de uma política institucional e o silêncio da mulher que não revela a violência. Os entrevistados, em particular as mulheres jovens, apresentaram atitudes mais favoráveis para o acolhimento da mulher em situação de violência. CONCLUSÕES: A maioria dos entrevistados demonstrou atitudes positivas e podemos inferir que há bom potencial para o manejo adequado dos casos, se receberem capacitação.OBJECTIVES: There are several public policies to deal with violence against women in Brazil. The literature has reported that healthcare workers find this subject difficult to approach. To improve care in the public health system (SUS) of Ribeirão Preto, a study was conducted aiming to assess knowledge and attitudes of healthcare workers regarding gender violence. METHODS: A total 278 healthcare workers were contacted and 221 were interviewed using a structured questionnaire. RESULTS: 51 (23.0%) were nurses and 170 (77.0%) physicians, 119 (53.8%) males and 102 (46.2%) females, with a mean age of 38.6 years; 200 (90.5%) considered themselves to be white or Asian and 21 (9.5%) black or mulattos. They had an average of 12.5 years of professional practice and 158 (68.8%) had graduated from a public university. About 58.7% had an adequate general knowledge (good and high) about gender violence, which indicates the need to train healthcare workers. Regarding the barriers to identify violence, healthcare workers mentioned the lack of an institutional policy and the silence of women who do not reveal violence. Respondents, especially young women, presented more favorable attitudes towards women living in violence situation. CONCLUSIONS: Therefore, most of them show positive attitudes toward women living in violence and we infer that they present good potential for appropriate case management if they receive training.CNP

Parthenolide prevents resistance of MDA-MB231 cells to doxorubicin and mitoxantrone: the role of Nrf2

Triple-negative breast cancer is a group of aggressive cancers with poor prognosis owing to chemoresistance, recurrence and metastasis. New strategies are required that could reduce chemoresistance and increases the effectiveness of chemotherapy. The results presented in this paper, showing that parthenolide (PN) prevents drug resistance in MDA-MB231 cells, represent a contribution to one of these possible strategies. MDA-MB231 cells, the most studied line of TNBC cells, were submitted to selection treatment with mitoxantrone (Mitox) and doxorubicin (DOX). The presence of resistant cells was confirmed through the measurement of the resistance index. Cells submitted to this treatment exhibited a remarkable increment of NF-E2-related factor 2 (Nrf2) level, which was accompanied by upregulation of catalase, MnSOD, HSP70, Bcl-2 and P-glycoprotein. Moreover, as a consequence of overexpression of Nrf2 and correlated proteins, drug-treated cells exhibited a much lower ability than parental cells to generate ROS in response to a suitable stimulation. The addition of PN (2.0 μM) to Mitox and DOX, over the total selection time, prevented both the induction of resistance and the overexpression of Nrf2 and correlated proteins, whereas the cells showed a good ability to generate ROS in response to adequate stimulation. To demonstrate that Nrf2 exerted a crucial role in the induction of resistance, the cells were transiently transfected with a specific small interfering RNA for Nrf2. Similarly to the effects induced by PN, downregulation of Nrf2 was accompanied by reductions in the levels of catalase, MnSOD, HSP70 and Bcl-2, prevention of chemoresistance and increased ability to generate ROS under stimulation. In conclusion, our results show that PN inhibited the development of the resistance toward Mitox and DOX, and suggest that these effects were correlated with the prevention of the overexpression of Nrf2 and its target proteins, which occurred in the cells submitted to drug treatment

Road traffic pollution and childhood leukemia: a nationwide case-control study in Italy

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Results We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03–3.01 for ALL and 6.35; 95% CI 2.59–15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. Conclusions Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete

Distribución del agua en el suelo y su relación con la estructura radical y producción de biomasa de tres tipos funcionales, en un pastizal de la estepa magallánica seca, Santa Cruz

Uno de los principales aspectos del funcionamiento de los ecosistemas áridos es la dinámica del agua, que determina aspectos estructurales y funcionales, como la dominancia de tipos funcionales (Tf), fenología y productividad. Los objetivos de esta tesis fueron identificar para un pastizal xérico del sur patagónico, las principales variables ambientales que controlan la dinámica del agua en el suelo, los factores que determinan sus variaciones en el perfil (asociados a topografía y parches de vegetación)y evaluar la respuesta de los tres Tf presentes de la vegetación: gramíneas cortas (GC), gramíneas medianas (coirones)y subarbustos frente a esta variaciones temporales y espaciales. En exposiciones norte, sur y plano se midió: potencial hídrico de suelo (10, 25 y 60 cm de profundidad), potencial hídrico foliar y producción de biomasa aérea mensual de los tres Tf. Se determinó la distribución de raíces en cada Tf. y el contenido hídrico del suelo asociado a parches vegetados y de suelo desnudo. Las lluvias se distribuyeron a lo largo del año con dominancia de eventos menor a 5mm (90 por ciento)y ausencia de tormentas. Los tres Tf presentaron más del 60 por de la biomasa de raíces entre 0-10cm del suelo, siguiendo un perfil similar al del frente de mojado de las lluvias más frecuentes, mientras que capas más profundas fueron escasamente exploradas. Los parches de suelo desnudo constituyen una reserva de agua superficial durante el verano, que podría ser utilizada sólo por el subarbusto a través de raíces que se extienden lateralmente. El suelo estuvo húmedo en invierno-primavera, seco en verano y el otoño fue variable de acuerdo al año. La exposición generó un gradiente de humedad en el suelo; la exposición norte fue el extremo más xérico. Este gradiente afectó los potenciales hídricos foliares de los 3 Tf, pero sólo en GC modificó la producción de biomasa. La producción de GC constituye el principal forraje para los ovinos, y probablemente las variaciones temporales y en el paisaje se reflejen en el consumo animal y en la producción secundaria

Method for selecting ornamental species for different shading intensity in urban green spaces

In urban areas, ornamental plants face different constraints, such as the shading of buildings and trees. Therefore, the selection of suitable species and their integration or combination with pre-existing plants is very important. Trees, shrubs, and herbaceous plant species must be distributed according to plant light requirements and shading intensity. Ornamental plants are classified into two groups based on their light intensity or shade tolerance: sun and shade species. To properly position the plants, especially in the immediate vicinity of buildings, it is necessary to study the projection of shadows during the year and the most critical periods, such as July and August. The position of ornamental species with different shading tolerances can be obtained by characterizing the leaf gas exchange for each species. Among the physiological parameters, the most important is the light compensation point, which is the light intensity corresponding to a net photosynthesis equal to zero. This means that the assimilation of carbon dioxide through photosynthesis is equal to the carbon dioxide emitted by respiration. This steady state represents the most critical condition for plants to endure the summer. The distribution of species inside a green area should be determined by considering the minimum light intensity that allows sufficient photosynthesis to compensate for the respiration rate. In this context, non-destructive leaf gas exchange, chlorophyll a fluorescence, and chlorophyll content can be useful tools for selecting suitable ornamental plants under diverse shading conditions