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Este trabajo busca contribuir a explicar el desequilibrio de género en la judicatura española. Aunque las mujeres constituyen el 54% de los integrantes de la carrera judicial, su presencia se concentra en los órganos unipersonales y es escasa en la cúpula del poder judicial. El trabajo se articula a partir de las explicaciones de las propias magistradas sobre este desequilibrio, extraídas de una investigación basada en entrevistas biográficas a 20 magistradas, con un mínimo de 20 años de experiencia como jueces profesionales. Las explicaciones son tratadas como hipótesis explicativas que se contrastan con otros datos publicados por el Consejo General del Poder Judicial (CGPJ). Las explicaciones examinadas son tres: la reciente incorporación de las mujeres a la carrera judicial; la autoexclusión de las mujeres de puestos de libre designación por parte del CGPJ y puestos gubernativos; la exclusión de las mujeres de los puestos discrecionales a través de los mecanismos selectivos. La revisión de las estadísticas y el análisis de las trayectorias profesionales de las magistradas permiten descartar el argumento de que el acceso tardío de las mujeres a la carrera judicial explica su escasa presencia en la alta magistratura y los puestos discrecionales. Parece más prometedor, sin embargo, profundizar en las hipótesis basadas en la autoexclusión y la existencia de sesgos de género en los procesos selectivos, así como en su relación.

Autophagy is a crucial mechanism for the functioning and survival of pancreatic beta cells. Its dysregulation has been associated with obesity, insulin resistance, and glucose intolerance. Furthermore, decreased autophagy in insulin-secret ing beta cells has been reported to contribute to the devel opment of type 2 diabetes mellitus (T2DM), which constitutes about 95% of all diabetes cases and is a chronic metabolic disease that it currently affects millions of people around the world. In different models of rodents, whether diabetic or obese, it has been observed that treatment with autophagy enhancers lowers glucose levels, increases insulin sensitivity, and protects beta cells from apoptosis. As stated above, it has recently been proposed to carry out an early intervention in patients with T2DM, using drugs that promote autophagy, which could help preserve the mass of beta cells and prevent the progression of the disease. This review provides an over view of the importance of the physiological process of auto phagy and its imminent role in the development of T2DM. Keywords: Pancreatic beta cells; autophagy; cell death; diabetes mellitus type 2

Here we describe the preparation, characterisation, liquid crystal properties and photophysical studies of new potassium salts of tetrakis(β-diketonate)europium(III) complexes based on long-chained symmetrical and unsymmetrically substituted 1,3-dialkyloxyphenyl-β-diketones ligands, K[Eu(OOR(n)R(m))4] (R(n) = OC6H4OCnH2n+1; R(m) = OC6H4OCmH2m+1; n = m = 8, 10, 12, 14, 16; n = 4, 8, m = 12, 16; n = 12, m = 16). All compounds exhibit mesomorphic and luminescence behaviour, regardless the presence of symmetrical or unsymmetrical ligands. It has been shown that the shortest molecular lengths, established by the summation of the two alkyl chains at the substituents of the β-diketonate ligand, give rise to more effective mesophase transition temperatures, while the asymmetry favours higher clearing temperatures. Related to the ionic salts based on long-chained pirazolium cations [H2pzR(n)]+ (R(n) = OC6H4OCnH2n+1; n = 4, 6, 8, 10, 12, 14, 16, 18) and tetrakis(1,3-bis(methoxyphenyl)propane-1,3-dionate)europium(III) as anion, they have also been studied and proved to be luminescent materials. By contrast, none of them was found to be mesomorphic. Therefore, the strategically increased chain length at the cation did not show to be effective for achieving liquid crystal properties. Integration of one of these luminescent europium complexes onto a polymeric PMMA matrix was positively evaluated towards its use as a temperature sensor and fluoride or cyanide ion sensor.

The repression of anti-austerity protests in Spain from 2011 to 2014 constitutes an example of how neoliberal developments are facilitated by the penal system as it limits political resistances to the imposition of precarious working conditions and social cuts. The limits imposed on contentious politics are both material (consisting of banning acts that are prominent in social movement’s repertoire of contention, fining demonstrators, etc.) and symbolic (consisting of transforming the meaning of legitimate politics by imposing new legal and political definitions). This case study is used to illustrate the interconnection between labor markets, social policies and the repression of social protest, and to elaborate on Wacquant’s approach to the relationship between punishment and other social institutions. It is at such times of political and economic crisis when institutional interconnections seem particularly exposed, arguably enabling more profound analyses.

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer, however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5.

Ethnopharmacological relevance The use of medicinal plants in Mexico has been documented since pre-Hispanic times. Nevertheless, the level of use of medicinal plants by health professionals in Mexico remains to be explored. Aim of the study To evaluate the use, acceptance and prescription of medicinal plants by health professionals in 9 of the states of Mexico. Materials and methods Direct and indirect interviews, regarding the use and acceptance of medicinal plants, with health professionals (n=1614), including nurses, physicians, pharmacists, and odontologists from nine states in Mexico were performed from January 2015 to July 2016. The interviews were analyzed with the factor the informant consensus (FIC). Results The information obtained indicated that 46% of those interviewed feel patients should not use medicinal plants as an alternative therapy. Moreover, 54% of health professionals, and 49% of the physicians have used medicinal plants as an alternative therapy for several diseases. Twenty eight percent of health professionals, and 26% of the physicians, have recommended or prescribed medicinal plants to their patients, whereas 73% of health professionals were in agreement with receiving academic information regarding the use and prescription of medicinal plants. A total of 77 plant species used for medicinal purposes, belonging to 40 botanical families were reported by the interviewed. The results of the FIC showed that the categories of diseases of the digestive system (FIC=0.901) and diseases of the respiratory system (FIC=0.898) had the greatest agreement. Conclusions This study shows that medicinal plants are used for primary health care in Mexico by health professionals.

Este texto pertenece a una mesa redonda que ofrece un debate con James B. Jacobs, autor del clásico de la sociología de las prisiones Stateville: The penitentiary in mass society, sobre la vigencia de su obra cuarenta años después. Este comentario destaca dos contribuciones importantes de la obra y las relaciona con cambios acaecidos en la sociedad y en la articulación del castigo desde entonces. En primer lugar, y a partir de este ejemplar estudio de las relaciones entre la cárcel y la sociedad, se plantea si esta ha variado sustancialmente con la existencia de mayores canales de comunicación y con el incremento de personas encarceladas. En segundo lugar, reconociendo su excelente uso de Weber para entender el castigo, se plantean dinámicas contradictorias que empujan a la vez hacia un ejercicio de la autoridad más legal-racional y más carismático. This text belongs to a round table which offers a discussion with James B. Jacobs, author of the classic in sociology of prisons Stateville: The penitentiary in mass society, on the importance of his work 40 years later. This commentary stresses two important contributions of his work and relates them to changes in society and the configuration of punishment since then. First, this outstanding study of the relations between prison and society is used as a springboard from which to pose the question of whether this relationship has varied substantially with the existence of more channels of communication and the increase of people being imprisoned. Second, acknowledging his excellent use of Weber for understanding punishment, the issue of contradictory dynamics pushing for a more legal-rational and more charismatic exercises of authority is raised. Aquest text pertany a una taula rodona que ofereix un debat amb James B. Jacobs, autor del clàssic de la sociologia de les presons Stateville: The penitentiary in mass society, sobre la vigència de la seva obra quaranta anys després. Aquest comentari destaca dues contribucions importants de l'obra i les relaciona amb canvis esdevinguts en la societat i en l'articulació del càstig des de llavors. En primer lloc, i a partir d'aquest estudi exemplar de les relacions entre la presó i la societat, es planteja si aquesta ha variat substancialment amb l'existència de més canals de comunicació i amb l'increment de persones empresonades. En segon lloc, reconeixent el seu excel·lent ús de Weber per entendre el càstig, es plantegen dinàmiques contradictòries que empenyen alhora cap a un exercici de l'autoritat més legal-racional i més carismàtic.

9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone γH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway. Using two-dimensional gel electrophoresis and mass spectrometry, the upregulation of the protein GRP78, the cleavage of Cytokeratin 18, and the downregulation of prothymosine, calumenin, and the α chain of the nascent polypeptide associated complex were observed in HeLa cells treated with D3ClP. An increase in GRP78 has been related with the onset and progression of the unfolded protein response (UPR), a process aimed to reduce endoplasmic reticulum (ER) stress and protein misfolding. The IRE1-α dependent splicing of mRNA encoding X-box binding protein 1 was detected. Microtubule-associated Proteins 1A/1B, Light Chain 3-II (LC3b-II) accumulation was observed, and suggest some involvement of autophagy. The production of the pro-apoptotic protein DNA-damage-inducible protein 153 (GADD-153) was also detected. These results, are consistent with the induction of the UPR and the DNA-Damage Response in D3ClP-treated HeLa cells, and are also consistent with a concurrent apoptotic cell death. J. Cell. Biochem. 118: 1164-1173, 2017. © 2016 Wiley Periodicals, Inc.

Novel alkyloxyphenyl-substituted β,δ-triketonate difluoroboron complexes have been efficiently synthesised and thoroughly characterised. Significant features such as liquid crystal behaviour and solid and solution fluorescence are observed in all cases. The mesomorphism was determined by the presence of one, two or three alkyl chains in each substituent aromatic group of the triketonate ligand. So, smectic C mesophases were found for compounds carrying two lateral chains, each of them located at one of each phenyl substituent, while the presence of four or six chains at the whole molecule gave rise to smectic A or discotic lamellar and hexagonal columnar mesophases, respectively. Fluorescence in the solid state and in solution is again proved to be dependent on the ligand substitution as well as to be maintained in the mesophase. These multifunctional materials also present luminescent sensor activity towards Hg2+ and Cu2+.

En el presente artículo se analizan los procesos punitivos que afectan de una manera notable a las personas extranjeras en España. Tras una breve contextualización del proceso migratorio, y de su problematización en términos relacionados con la inseguridad y la delincuencia, se presta atención a dos formas de penalización: la administrativa, vinculada a las leyes de extranjería, y la penal, reforzada por la situación precaria de estos colectivos. Posteriormente se analizan sus efectos materiales –relacionados con el mercado laboral-, simbólicos –en las categorizaciones sociales- y disciplinarios –en la conformación de subjetividades-. Se defiende la pertinencia de estudiar los procesos de penalización para vislumbrar dinámicas sociales más amplias y la pertinencia de dar mayor importancia a estos procesos en los estudios sobre las personas migrantes.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential.

El siguiente trabajo tiene como objetivo hacer algunas propuestas con el ánimo de intentar superar algunas de las limitaciones de la economía política del castigo. Para ello, se señalarán algunas de las principales aportaciones de esta corriente, a fin de reconocerles su valor e intentar mantenerlas en futuros trabajos. A continuación se repasarán algunas de las críticas más recurrentes. En la tercera parte se propondrán algunas soluciones a partir del trabajo del sociólogo Pierre Bourdieu, quien en su propia obra se planteó superar algunas limitaciones de los enfoques marxistas. This chapter offers up proposals in the hope of overcoming some of the limitations of the political economy of punishment. To that end, some of the main contributions this trend makes will be highlighted; their value acknowledged and recovered for future works. Next, the most recent criticisms will be reviewed. The third part will be devoted to proposing some solutions departing from the work of sociologist Pierre Bourdieu, who considered some of the limitations of Marxist approaches in his own work.

El debate sobre la eficiencia de las instituciones de castigo en tanto espacios de rehabilitación y reinserción ha sido abordado desde diferentes disciplinas, entre las que se incluye la sociología. Sin embargo, pocas personas han podido integrar la perspectiva sociológica en el trabajo en prisiones. María Jesús Miranda ha sido pionera en nuestro país en el estudio sociológico del delito, el conflicto y la desviación y, sobre todo, ha podido analizar a través de su trabajo en instituciones penitenciarias las modificaciones del sistema jurídico y penal español de los últimos cuarenta años y la repercusión que ello ha tenido en la estructura y los procesos de las cárceles.

Desde Encrucijadas hemos entendido imprescindible dedicar un número monográfico a las cuestiones relacionadas con la delincuencia, pero también con la constitución de grupos, con la moralidad y su expresión, con las formas de ejercer autoridad y poder y con un sistema que tiende a proteger más a los grupos dominantes, contribuyendo así, y no sólo garantizando, a la dominación social. Se trata de ámbitos relacionados con el castigo, el control, las instituciones y las políticas penales, así como las representaciones que las acompañan. Para tratar estas cuestiones e intentar conseguir una reflexión fundamentada sobre un tema que trasciende lo coyuntural, consideramos interesante abordarlos desde las ciencias sociales y, en concreto, desde la sociología.

The influence of economic crises on crime and penality is one of the fundamental issues in economic analysis of the punitive field, and the topic has been explored from various perspectives in a wide range of criminology theories. From a criminal-motivation viewpoint, economic crises are seen to favor crime-rate growth because of their serious effects of increasing unemployment, increasing in poverty, and generating inequality. Similarly, diverse economic approaches to penality (though not all of them, for example, law- and economics-based theses) hold that economic crises usually produce a rise in punitiveness and a consequent rise in incarceration rates. However, specialized academic literature has highlighted that the generally accepted view is far from accurate in all cases. Economic crises do not necessarily produce an increase in crime (at least not in all types of crime), nor do they always lead to an increase in punitiveness. Indeed, empirical studies about the effect of diverse economic crises (the Great Depression, the oil crisis of the 1970s, and the recent Great Recession) reveal an ambiguous panorama of the evolution in crime and penality. The impact of economic turmoil on crime and punishment should be examined in all its complexity. Crime rates and incarceration rates are hardly correlated, and the latter are far more influenced by a variegated set of political, social, cultural, and economic forces than by changes in crime patterns themselves. To scrutinize the effect of economic determinants on the penal field, the analysis of economic crises and crime should therefore be separated from the analysis of economic crises and penality. Unfortunately, there is a shortage of academic literature and empirical data on the implications of pre-21st-century financial crises for crime and punishment. The recent Great Recession thus has great utility for delving into the consequences of periods of economic chaos on crime and punitiveness.

Ionic liquid crystals (ILCs) are a class of materials that combine the properties of liquid crystals (LCs) and ionic liquids (ILs). This type of materials is directed towards properties such as conductivity in ordered systems at different temperatures. In this work, we synthesize five new families of ILCs containing symmetrical and unsymmetrical substituted pyrazolium cations, with different alkyl long-chains, and anions such as Cl−, BF4−, ReO4−, p-CH3-6H4SO3− (PTS) and CF3SO3− (OTf). We study their thermal behavior by polarized light optical microscopy (POM) and differential scanning calorimetry (DSC). All of them, except those with OTf as counteranion, show thermotropic mesomorphism. The observations by POM reveal textures of lamellar mesophases. Those agree with the arrangement observed in the X-ray crystal structure of [H2pzR(4),R(4)][ReO4]. The nature of the mesophases is also confirmed by variable temperature powder X-ray diffraction. On the other hand, the study of the dielectric properties at variable temperature in mesomorphic (Cl− and BF4−) and non-mesomorphic (OTf) salts indicates that the supramolecular arrangement of the mesophase favors a greater ionic mobility and therefore ionic conductivity.

Tropical trees of Calophyllum genus (Calophyllaceae) have chemical and biological importance as potential source of secondary active metabolites which can lead to the development of new drugs. Research on this species has been rising since 1992 due to the discovering of anti-HIV properties of Calanolide A found in Calophyllum inophyllum leaves. This compound is the most important natural product for potential development of new anti-HIV drugs and phytomedicines. The scientometric analysis (1953---2014) here performed revealed that the most studied species of Calophyllum genus are: C. inophyllum and C. brasiliense, distributed in the Asian, and American continents, respectively. Current research on these species is carried out mainly in India and Brazil, respectively, where these species grow. Research on C. brasiliense is focused mainly on ecological, antiparasitic, cytotoxic properties, and isolation of new compounds. Chemical studies and biodiesel development are the main topics in the case of C. inophyllum. Text mining analysis revealed that coumarins, and xanthones are the main secondary active metabolites responsible for most of the reported pharmacological properties, and are potential compounds for the treatment of leukemia and against intracellular parasites causing American Trypanosomiasis and Leshmaniasis. On the other hand, C. inophyllum represents an important source for the development of 2nd generation biodiesel. Medicinal and industrial applications of these species may impulse sustainable forest plantations. To our knowledge this is the first scientometric and text mining analysis of chemical and biomedical research on Calophyllum genus, C. brasiliense and C. inophyllum.

In order to contribute to the knowledge of the chemical constituents and bioactivity of lichens from Colombian páramo region, methanolic extracts of Lobariella pallida and Stereocaulon strictum var. compressum were submitted to phytochemical and cytotoxic studies. Lobariellin (methyl 3-formyl-2,4-dihydroxy-5,6-dimethylbenzoate) (1), along with methyl orsellinate (2) were isolated from the Lobariella pallida. The active constituents namely porphyrilic acid (3), methyl haematommate (4), methyl β-orcinolcaboxylate (5) and atranorin (6) were isolated from the Stereocaulon strictum. The structures of 1-6 were determined by analysis of their spectroscopic (NMR, IR, UV) and spectrometric data. In addition, the structures of 1, 2 and 3 were unequivocally corroborated by single-crystal X-ray diffraction studies. Neither methanol extracts nor compounds 1, 3, 4 and 6 were cytotoxic to the normal (HaCaT) and transformed (MCF-7, HeLa, K562, PC3) mammalian cell tested, which could be indicative of a possible innocuousness and be helpful in other biomedical usefulness.

The páramo ecosystem is situated in northwest of South America, and it is well known for distribution of lichens. It is documented that lichens produce antioxidant activity, and protect cells from oxidative stress by scavenging free radical. Hence we checked the antioxidant and protective abilities to prevent cell and DNA damage by oxidative stress of Lobariella pallida and Stereocaulon strictum var. compressum extracts. Additionally, the active constituents namely lobariellin (1), methyl orsellinate (2), stereocaullin (3), methyl haematommate (4), methyl β-orcinol carboxylate (5), porphyrilic acid (6) and atranorin (7), were isolated from both extracts and their antioxidant activity was evaluated. The DPPH·, ferric reducing power and inhibition of lipid peroxidation model were used to determined the antioxidant activity of extracts and isolated compounds. The cell and DNA protective effects of extracts and isolated compounds were investigated by exposing keratinocytes, neurons and pUC18 plasmid to hydroxyl radicals, and examined cell viability or DNA cleavage of sample. The findings exhibits that the compounds 1, 4 and 6 scavenged free radicals, inhibited lipid peroxidation and reduced ferric ions at maximum level compared to other isolated compound and extracts. Additionally, 1 and 4 protected cells from oxidative damage and 1 also preserved DNA. These results suggest that 1 and 4 imparts antioxidant activity to prevent oxidative skin and neurodegenerative damage.

Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle. Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis. Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways.

The political economy of punishment is a branch of the study of punitive forms, of their articulation, functioning and functionality, which has a long and intermittent tradition. It is mainly based on Karl Marx’s analysis of capitalism and of the relations and dynamics it generates and Pashukanis’ analysis of Law. Bourdieu’s work is testimony to a constant struggle to overcome limitations found in Marx, Weber, and Durkheim when applied to empirical research. Societies work through symbolic systems. These systems, following Durkheim, are forms of classification that fulfil a function in social order integration. These forms of classification are social and historical, that is to say, they are variable, become dated, and have their origin in relations. The state is of central importance for punishment. It is important to take the danger of over-simplification seriously where the state is mainly understood as a tool at the service of the ruling class.

Three families of polycatenar 1,3-alkyloxyphenyl β-diketonate boron difluoride complexes with three (I) four (II) or five (III) peripheral chains unsymmetrically distributed, have been prepared and characterised. The thermal behaviour was analysed in light of their molecular characteristics, allowing us to establish that the complexes of III are liquid crystal materials in contrast to the absence of mesomorphism for the related derivatives I and II. Compounds III were found to be discotic liquid crystals exhibiting hexagonal columnar (Colh) mesophases. In addition, when the complexes presented a higher asymmetry degree related to the presence of flexible chains with different lengths at both substituents, the mesophases were raised at room temperature. The photophysical characterisation of the boron derivatives was also carried out, and in all cases it showed a high fluorescent emission in the green region for solution and for the solid state. All these features make these bifunctional luminescent mesogens good candidates to be potentially applied in technological fields, which require soft emissive compounds.

Objectives The aim of this study was to determine the cellular and molecular mechanisms of cell death induced by mammea A/BA and A/BB (3 : 1) on K562 cells. Methods These compounds were isolated from Calophyllum brasiliense and its cytotoxicity was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell death was evaluated by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunocytofluorescence of active caspase-3. Genotoxicity was tested using comet assay. Lastly, a chemoinformatic analysis was performed with Osiris-Molinspiration software. Key findings The mixture of mammea A/BA and A/BB (3 : 1) showed cytotoxic activity against K562 cells (IC50 = 43.5 μm). TUNEL positive cells and active caspase-3 were detected after treatment. Genotoxicity of mammea A/BA and A/BB on K562 was detected since first hour of treatment. Additionally, mammea A/BA and A/BB were found to be in compliance with Lipinski ‘rule of 5’ suggesting that they possess strong potential of druglikeness. Conclusions The overall results confirm and extend the knowledge about coumarins as an important resource of antitumor drugs, and indicate that these compounds could be used in further preclinical studies against leukaemia.

Cancer prevention remains a high priority for the scientific world. Magnolia dealbata Zucc (Magnoliaceae), a Mexican endemic species, is used for the empirical treatment of cancer.To evaluate the cytotoxic and cancer chemopreventive effects of an ethanol extract of Magnolia dealbata seeds (MDE).The cytotoxic effect of MDE, at concentrations ranging from 1 to 200 µg/ml, on human cancer cells and human nontumorigenic cells was evaluated using the MTT assay for 48 h. The apoptotic activities of MDE 25 μg/ml on MDA-MB231 breast cancer cells were evaluated using the TUNEL assay and the detection of caspase 3 using immunofluorescence analysis for 48 h, each. The chemopreventive effect was evaluated by administrating different doses of MDE, between 1 and 50 mg/kg, injected intraperitoneally daily into athymic mice which were implanted with MDA-MB231 cells during 28 days. The growth and weight of tumors were measured.MDE showed cytotoxic effects on MDA-MB231 cells (IC₅₀ = 25 µg/ml) and exerted pro-apoptotic activities as determined by DNA fragmentation in MDA-MB231 cells. MDE 25 µg/ml also induces the activation of caspase 3 in MDA-MB231 cells. These results suggest that Magnolia dealbata may be an optimal source of the bioactive compounds: honokiol (HK) and magnolol (MG). MDE 50 mg/kg i.p. exerted chemopreventive effects by inhibiting the growth of MDA-MB231 tumor by 75% in athymic mice, compared to the control group.MDE exerts cytotoxic, apoptotic and chemopreventive activities on MDA-MB231 human cancer cells.

Monocytes and their cell derivatives can participate in drug metabolism. These cells express different Phase-I or -II drug metabolizing enzymes and can be differentiated into neo-hepatocytes (NeoHep) and represent a promising alternative strategy to test drug metabolism. This is particularly useful as primary human hepatocytes (PHH), are difficult to obtain and maintain in culture.The authors analyze the use of blood monocytes and their derivatives for the study of drug metabolism. They also compare them to the in vitro ability of cells from different sources including: PHH, immortalized hepatocytes, tumor cell lines and NeoHep.The use of monocytes, macrophages, dendritic or Kupffer cells, to test drug metabolism, has serious limitations because these cells express lower levels of cytochrome P450 enzymes than PHH. The best available option, to replace PHH, have been tumor cell lines such as HepaRG, as well as immortalized hepatocytes from adult or fetal sources. Monocyte-derived NeoHep cells are novel and easily accessible cells, which express many drug metabolizing enzymes at levels comparable to PHH. These cells allow drug evaluation under a diverse genetic background. While these cells are in the early stages of evaluation and do need to be examined more thoroughly, they constitute a promising new tool for in vitro drug testing.

9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinolone (D3ClP) is a bioisostere of N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide (m-AMSA) a DNA topoisomerase II inhibitor with proven cytotoxic activity and known to induce DNA damage and apoptotic cell death in K562 cells. However, recent evidence is not consistent with DNA topoisomerase II (DNA TOP2) as the primary target of D3ClP, in contrast to m-AMSA. We provide evidence of histone γH2AX phosphorylation at Ser135 in HeLa cells treated with D3ClP, a marker of DNA double strand repair through Mre11-Rad50-Nbs1 (MRN) pathway. Using two-dimensional gel electrophoresis and mass spectrometry, the upregulation of the protein GRP78, the cleavage of Cytokeratin 18, and the downregulation of prothymosine, calumenin, and the α chain of the nascent polypeptide associated complex were observed in HeLa cells treated with D3ClP. An increase in GRP78 has been related with the onset and progression of the unfolded protein response (UPR), a process aimed to reduce endoplasmic reticulum (ER) stress and protein misfolding. The IRE1-α dependent splicing of mRNA encoding X-box binding protein 1 was detected. Microtubule-associated Proteins 1A/1B, Light Chain 3-II (LC3b-II) accumulation was observed, and suggest some involvement of autophagy. The production of the pro-apoptotic protein DNA-damage-inducible protein 153 (GADD-153) was also detected. These results, are consistent with the induction of the UPR and the DNA-Damage Response in D3ClP-treated HeLa cells, and are also consistent with a concurrent apoptotic cell death. J. Cell. Biochem. 118: 1164-1173, 2017. © 2016 Wiley Periodicals, Inc.

Highly luminescent and liquid crystal materials were successfully prepared by the strategic introduction of unsymmetrically alkyloxyphenyl substituted β-diketones, as ligands towards the BF2 group. So, four families of ligands and their boron derivatives were prepared, each of them containing invariable the alkyl chain at one of the substituents in the 1(3) position, with 12, 14, 16 or 18 carbon atoms, while for the other substituent at the 3(1) position, the number of alkyl carbon atoms was increased from 4 to 18. In this way, the influence of factors as asymmetry or molecular length was evaluated towards the liquid crystal behavior of the compounds. The photophysical characterization of the boron derivatives was also carried out, showing in all cases a high fluorescent emission in the blue–violet region in solution and in the green region in the solid state, with quantum yields near the unity. In addition, thermal studies by DSC, as well as the analysis by POM and XRD were determinant to characterize the compounds as liquid crystal materials, exhibiting B1 mesophases, in agreement with the banana molecular shape. In contrast the corresponding β-diketone precursors behave again as liquid crystals showing SmC and N mesophases.

Thiazolo[5,4-b]quinolines are compounds structurally related to m-Amsacrine (m-Amsa), a potent antileukemic drug that intercalates to DNA and inhibits topoisomerase II in vitro inducing cell death. The clinical use of m-Amsa and other neoplastic drugs is limited due to side effects and drug resistance. In the present study we evaluated one thiazolo[5,4-b]quinoline derivate, 9-[(3-chloro)phenylamine]-2-[3-(diethylamine)propylamine]thiazolo[5,4-b]quinoline (D3CLP), considered isosteric with 9-anilinoacridines, in order to determine its relative cytotoxic activity in tumoral versus non-tumoral cells, as well as the cell death mechanism induced by D3CLP on K-562 human leukemia cells. D3CLP was found to be four times more cytotoxic to tumor cells than Peripheral Blood Monocyte Cells (PBMCs). On the other hand, D3CLP induces cell death without previous cell cycle arrest at any phase, as shown by flow cytometry after 12 h of exposure to this compound. Interestingly, we detected a subdiploid peak 24 h after treatment. Signs of apoptosis were evident, as detected by TUNEL positive cells, chromatin condensation and nuclear fragmentation. Effector caspases activation were assessed with peak activity at 24 h after treatment (as detected by fluorometry assays), at which time a subdiploid peak was found in flow cytometry histograms. All data are consistent with the induction of apoptotic cell death in K-562 cells via effector caspases activation. In conclusion, the significant cytotoxicity of D3CLP together with the cell death type it produces, justifies further experimental and preclinical evaluation of this compound in the effort to find new and highly specific anti-tumor agents against leukemia cells.

Some novel 9-anilinothiazolo[5,4-b]quinoline derivatives were synthesized and their cytotoxic activities were examined. The inhibition of some of the most active compounds over human topoisomerase II (Topo II) activity was assessed with the kDNA decatenation assay. The novel compounds differ in the substituents attached to the anilino ring, a dialkylamino alkylamino group, a saturated heterocyclic moiety, a methylthio group at position 2 and a fluorine atom present or absent at 7-position. According to the data, compounds with a diethylaminopropylamino group and a chlorine atom at 4'-position of the anilino ring were the most cytotoxic. The molecular models of all compounds indicated a correlation between hydrophobicity and cytotoxic activity although the direction and magnitude of the dipole moment also had a significant influence on its cytotoxicity. The 2-dialkylaminoalkylamino substituent is flexible and is known to facilitate the crossing of cell membranes; thus, this last barrier may be a limiting step in the mechanisms mediating the cytotoxicity. On the other hand, the activity of 2-methylthio derivatives seems to rely more on the electronic effects brought about by the substitution of the aniline ring. The synthesis, cytotoxicity against cancer cell lines, in vitro inhibition of human topoisomerase II, molecular modeling and the preliminary analysis of structure-activity relationships are presented.

En este artículo se trata la relación positiva que algunos estudios han venido recogiendo entre la aplicación de políticas neoliberales y la expansión del sistema penal. Comienza mostrando algunos de los cambios más significativos de la penalidad en España, y señala la escasa atención que le ha prestado la Sociología española. Tras defender la pertinencia de estudiar el castigo como una institución social, presenta la evidencia empírica internacional que apunta a fuertes correlaciones entre estas dos variables, mucho más predecibles que las que mantiene el sistema penal con las tasas de delincuencia. Tras señalar las limitaciones de estos estudios, se propone pensar el neoliberalismo como un paradigma de políticas que debería reflejarse en la configuración institucional, y se anima a otra tipo de estudios más cualitativos (o, preferiblemente, estudios de caso) para poder aclarar algunos de los múltiples problemas existentes para poder sugerir relaciones causales más allá de estas correlaciones.

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

Pachyrhizus erosus (Fabaceae) is a herb commonly known as ‘yam bean’, which has been cultivated in México since pre-Columbian times for its edible tubers. The seeds are also known for their acaricidal and insecticidal properties due to rotenone and other isoflavonoid contents. Rotenone has exhibited cytotoxic activity against several human tumour cell lines; however, its mechanism of action is still not fully understood. In this study, we determined the cytotoxicity of rotenone isolated from P. erosus seeds on K562 human leukaemia cells. Rotenone exhibited significant cytotoxic activity (IC50 = 13.05 μM), as determined by the MTT assay. Three other isolated isoflavonoids were not cytotoxic. Rotenone genotoxicity was detected using the comet assay. Rotenone induced cell death, and caspase-3 activation as indicated by TUNEL assay, and immunocytofluorescence. Plasmid nicking assay indicated that rotenone does not interact directly with DNA.

Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree, mainly distributed in South and Central America. It is an important source of bioactive natural products like, for instance soulatrolide, and mammea type coumarins. Soulatrolide is a tetracyclic dipyranocoumarins and a potent inhibitor of HIV-1 reverse transcriptase and Mycobacterium tuberculosis. Mammea A/BA and A/BB coumarins, pure or as a mixture, are highly active against several leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. In the present work, a toxicogenomic analysis of Soulatrolide and Mammea A/BA+A/BB (3:1) mixture was performed in order to validate the toxicological potential of this type of compounds. Soulatrolide or mixture of mammea A/BA + A/BB (3:1) was administered orally to male mice (CD-1) at dose of 100mg/kg/daily, for 1week. After this time, mice were sacrificed, and RNA extracted from the liver of treated animals. Transcriptomic analysis was performed using Affymetrix Mouse Gene 1.0 ST Array. Robust microarray analysis (RMA) and two way ANOVA test revealed for mammea mixture treatment 46 genes upregulated and 72 downregulated genes; meanwhile, for soulatrolide 665 were upregulated and 1077 downregulated genes. Enrichment analysis for such genes revealed that in both type of treatments genetic expression were mainly involved in drug metabolism. Overall results indicate a safety profile. The microarray data complies with MIAME guidelines and are deposited in GEO under accession number GSE72755.