Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Nanoencapsulation of Methylene-Blue for Enhanced Skin Cancer Cell Phototoxicity and Cutaneous Penetration in Association with Sonophoresis.

Photodynamic therapy (PDT) using methylene blue (MB) as a photosensitizer has emerged as an alternative treatment for skin cancers, such as squamous cell carcinoma (SCC). To increase the cutaneous penetration of the drug, some strategies are used, such as the association of nanocarriers and physical methods. Thus, herein we address the development of nanoparticles based on poly-Ɛ-caprolactone (PCL), optimized with the Box-Behnken factorial design, for topical application of MB associated with sonophoresis. The MB-nanoparticles were developed using the double emulsification-solvent evaporation technique and the optimized formulation resulted in an average size of 156.93 ± 8.27 nm, a polydispersion index of 0.11 ± 0.05, encapsulation efficiency of 94.22 ± 2.19% and zeta potential of -10.08 ± 1.12 mV. Morphological evaluation by scanning electron microscopy showed spherical nanoparticles. In vitro release studies show an initial burst compatible with the first-order mathematical model. The nanoparticle showed satisfactory generation of reactive oxygen species. The MTT assay was used to assess cytotoxicity and IC50; values of 79.84; 40.46; 22.37; 9.90 µM were obtained, respectively, for the MB-solution and the MB-nanoparticle without and with light irradiation after 2 h of incubation. Analysis using confocal microscopy showed high cellular uptake for the MB-nanoparticle. With regard to skin penetration, a higher concentration of MB was observed in the epidermis + dermis, corresponding to 9.81, 5.27 µg/cm2 in passive penetration and 24.31 and 23.81 µg/cm2 after sonophoresis, for solution-MB and nanoparticle-MB, respectively. To the best of our knowledge, this is the first report of MB encapsulation in PCL nanoparticles for application in skin cancer using PDT.

Identification of the centrosomal maturation factor SSX2IP as a Wtip-binding partner by targeted proximity biotinylation.

Wilms tumor-1-interacting protein (Wtip) is a LIM-domain-containing adaptor that links cell junctions with actomyosin complexes and modulates actomyosin contractility and ciliogenesis in Xenopus embryos. The Wtip C-terminus with three LIM domains associates with the actin-binding protein Shroom3 and modulates Shroom3-induced apical constriction in ectoderm cells. By contrast, the N-terminal domain localizes to apical junctions in the ectoderm and basal bodies in skin multiciliated cells, but its interacting partners remain largely unknown. Targeted proximity biotinylation (TPB) using anti-GFP antibody fused to the biotin ligase BirA identified SSX2IP as a candidate protein that binds GFP-WtipN. SSX2IP, also known as Msd1 or ADIP, is a component of cell junctions, centriolar satellite protein and a targeting factor for ciliary membrane proteins. WtipN physically associated with SSX2IP and the two proteins readily formed mixed aggregates in overexpressing cells. By contrast, we observed only partial colocalization of full length Wtip and SSX2IP, suggesting that Wtip adopts a 'closed' conformation in the cell. Furthermore, the double depletion of Wtip and SSX2IP in early embryos uncovered the functional interaction of the two proteins during neural tube closure. Our results suggest that the association of SSX2IP and Wtip is essential for cell junction remodeling and morphogenetic processes that accompany neurulation. We propose that TPB can be a general approach that is applicable to other GFP-tagged proteins.

Rspo2 inhibits TCF3 phosphorylation to antagonize Wnt signaling during vertebrate anteroposterior axis specification.

The Wnt pathway activates target genes by controlling the ß-catenin-T-cell factor (TCF) transcriptional complex during embryonic development and cancer. This pathway can be potentiated by R-spondins, a family of proteins that bind RNF43/ZNRF3 E3 ubiquitin ligases and LGR4/5 receptors to prevent Frizzled degradation. Here we demonstrate that, during Xenopus anteroposterior axis specification, Rspo2 functions as a Wnt antagonist, both morphologically and at the level of gene targets and pathway mediators. Unexpectedly, the binding to RNF43/ZNRF3 and LGR4/5 was not required for the Wnt inhibitory activity. Moreover, Rspo2 did not influence Dishevelled phosphorylation in response to Wnt ligands, suggesting that Frizzled activity is not affected. Further analysis indicated that the Wnt antagonism is due to the inhibitory effect of Rspo2 on TCF3/TCF7L1 phosphorylation that normally leads to target gene activation. Consistent with this mechanism, Rspo2 anteriorizing activity has been rescued in TCF3-depleted embryos. These observations suggest that Rspo2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling.

Lipid Rafts from Olfactory Ensheathing Cells: Molecular Composition and Possible Roles.

Olfactory ensheathing cells (OECs) are specialized glial cells of the olfactory system, believed to play a role in the continuous production of olfactory neurons and ensheathment of their axons. Although OECs are used in therapeutic applications, little is known about the cellular mechanisms underlying their migratory behavior. Recently, we showed that OEC migration is sensitive to ganglioside blockage through A2B5 and Jones antibody in OEC culture. Gangliosides are common components of lipid rafts, where they participate in several cellular mechanisms, including cell migration. Here, we characterized OEC lipid rafts, analyzing the presence of specific proteins and gangliosides that are commonly expressed in motile neural cells, such as young neurons, oligodendrocyte progenitors, and glioma cells. Our results showed that lipid rafts isolated from OECs were enriched in cholesterol, sphingolipids, phosphatidylcholine, caveolin-1, flotillin-1, gangliosides GM1 and 9-O-acetyl GD3, A2B5-recognized gangliosides, CNPase, α-actinin, and ß1-integrin. Analysis of the actin cytoskeleton of OECs revealed stress fibers, membrane spikes, ruffled membranes and lamellipodia during cell migration, as well as the distribution of α-actinin in membrane projections. This is the first description of α-actinin and flotillin-1 in lipid rafts isolated from OECs and suggests that, together with ß1-integrin and gangliosides, membrane lipid rafts play a role during OEC migration. This study provides new information on the molecular composition of OEC membrane microdomains that can impact on our understanding of the role of OEC lipid rafts under physiological and pathological conditions of the nervous system, including inflammation, hypoxia, aging, neurodegenerative diseases, head trauma, brain tumor, and infection.

EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles.

The epidermal growth factor receptor (EGFR) belongs to the tyrosine kinase receptors family and is present in the epithelial cell membrane. Its endogenous activation occurs through the binding of different endogenous ligands, including the epidermal growth factor (EGF), leading to signaling cascades able to maintain normal cellular functions. Although involved in the development and maintenance of tissues in normal conditions, when EGFR is overexpressed, it stimulates the growth and progression of tumors, resulting in angiogenesis, invasion and metastasis, through some main cascades such as Ras/Raf/MAPK, PIK-3/AKT, PLC-PKC and STAT. Besides, considering the limitations of conventional chemotherapy that result in high toxicity and low tumor specificity, EGFR is currently considered an important target. As a result, several monoclonal antibodies are currently approved for use in cancer treatment, such as cetuximab (CTX), panitumumab, nimotuzumab, necitumumab and others are in clinical trials. Aiming to combine the chemotherapeutic agent toxicity and specific targeting to EGFR overexpressing tumor tissues, two main strategies will be discussed in this review: antibody-drug conjugates (ADCs) and antibody-nanoparticle conjugates (ANCs). Briefly, ADCs consist of antibodies covalently linked through a spacer to the cytotoxic drug. Upon administration, binding to EGFR and endocytosis, ADCs suffer chemical and enzymatic reactions leading to the release and accumulation of the drug. Instead, ANCs consist of nanotechnology-based formulations, such as lipid, polymeric and inorganic nanoparticles able to protect the drug against inactivation, allowing controlled release and also passive accumulation in tumor tissues by the enhanced permeability and retention effect (EPR). Furthermore, ANCs undergo active targeting through EGFR receptor-mediated endocytosis, leading to the formation of lysosomes and drug release into the cytosol. Herein, we will present and discuss some important aspects regarding EGFR structure, its role on internal signaling pathways and downregulation aspects. Then, considering that EGFR is a potential therapeutic target for cancer therapy, the monoclonal antibodies able to target this receptor will be presented and discussed. Finally, ADCs and ANCs state of the art will be reviewed and recent studies and clinical progresses will be highlighted. To the best of our knowledge, this is the first review paper to address specifically the EGFR target and its application on ADCs and ANCs.

TMEM79/MATTRIN defines a pathway for Frizzled regulation and is required for Xenopus embryogenesis.

Wnt signaling through the Frizzled (FZD) family of serpentine receptors is essential for embryogenesis and homeostasis, and stringent control of the FZD protein level is critical for stem cell regulation. Through CRISPR/Cas9 genome-wide screening in human cells, we identified TMEM79/MATTRIN, an orphan multi-span transmembrane protein, as a specific inhibitor of Wnt/FZD signaling. TMEM79 interacts with FZD during biogenesis and promotes FZD degradation independent of ZNRF3/RNF43 ubiquitin ligases (R-spondin receptors). TMEM79 interacts with ubiquitin-specific protease 8 (USP8), whose activating mutations underlie human tumorigenesis. TMEM79 specifically inhibits USP8 deubiquitination of FZD, thereby governing USP8 substrate specificity and promoting FZD degradation. Tmem79 and Usp8 genes have a pre-bilaterian origin, and Tmem79 inhibition of Usp8 and Wnt signaling is required for anterior neural development and gastrulation in Xenopus embryos. TMEM79 is a predisposition gene for Atopic dermatitis, suggesting deregulation of Wnt/FZD signaling a possible cause for this most common yet enigmatic inflammatory skin disease.

Rspo2 antagonizes FGF signaling during vertebrate mesoderm formation and patterning.

R-spondins are a family of secreted proteins that play important roles in embryonic development and cancer. R-spondins have been shown to modulate the Wnt pathway; however, their involvement in other developmental signaling processes have remained largely unstudied. Here, we describe a novel function of Rspo2 in FGF pathway regulation in vivo Overexpressed Rspo2 inhibited elongation of Xenopus ectoderm explants and Erk1 activation in response to FGF. By contrast, the constitutively active form of Mek1 stimulated Erk1 even in the presence of Rspo2, suggesting that Rspo2 functions upstream of Mek1. The observed inhibition of FGF signaling was accompanied by the downregulation of the FGF target genes tbxt/brachyury and cdx4, which mediate anterioposterior axis specification. Importantly, these target genes were upregulated in Rspo2-depleted explants. The FGF inhibitory activity was mapped to the thrombospondin type 1 region, contrasting the known function of the Furin-like domains in Wnt signaling. Further domain analysis revealed an unexpected intramolecular interaction that might control Rspo2 signaling output. We conclude that, in addition to its role in Wnt signaling, Rspo2 acts as an FGF antagonist during mesoderm formation and patterning.

The Chalcone Lonchocarpin Inhibits Wnt/ß-Catenin Signaling and Suppresses Colorectal Cancer Proliferation.

The deregulation of the Wnt/ß-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/ß-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/ß-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs ß-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/ß-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.

Laboratório Sensorial: uma proposta de ativação do corpo / Sensory laboratory: a proposal for activating the body / Laboratorio Sensorial: una propuesta de activación del cuerpo

Este artigo apresenta um ensaio poético-fotográfico sobre o Laboratório Sensorial, um dispositivo do projeto de extensão universitária Expressão e Transformação, vinculado ao Instituto de Psicologia da Universidade Federal do Rio de Janeiro, Brasil (UFRJ). Inspirado na Fenomenologia e na Arte Contemporânea, o laboratório é uma proposta de sensibilização corporal que busca desnaturalizar a percepção e os modos cotidianos automatizados de estar no mundo. Os participantes são convidados a vendar os olhos e a serem conduzidos por um percurso de estimulações sensoriais no qual experimentam texturas, odores e sonoridades em temporalidades distintas das do cotidiano. Em seguida, registram suas experiências em mapas corporais. Nas diversas edições realizadas, percebemos que a experiência vivida expande a percepção de si e do outro, avivando uma potência poética de expressão e memória do corpo. Originada na Psicologia Clínica, esta proposta dialoga com outras disciplinas e linguagens, articulando as dimensões ética, estética e política da existência.(AU)

This article presents a poetic photo-essay about the Sensory Laboratory, a facility of the extension project Expression and Transformation attached to the Institute of Psychology at the Federal University of Rio de Janeiro, Brazil (UFRJ). Inspired by Phenomenology and Contemporary Art, the laboratory is a proposal for body awareness aimed at denaturalizing perception and automated everyday modes of being in the world. Participants are invited to wear a blindfold and conducted through a series of sensory stimulations where they experience different textures, odors, and sounds in temporalities that are different to those of everyday life. Their experiences are then depicted in body maps. The findings show that the participants' experiences expand self and other-awareness, vivifying a poetic power of expression and body memories. Originating from Clinical Psychology, this proposal converges towards other disciplines and languages, articulating ethical, aesthetic, political, and existential dimensions.(AU)

Este artículo presenta un ensayo poético-fotográfico sobre el Laboratorio Sensorial, un dispositivo del proyecto de extensión universitaria Expresión y Transformación, vinculado al Instituto de Psicología de la de la Universidad Federal de Rio de Janeiro, Brasil (UFRJ). Inspirado en la Fenomenología y en el Arte Contemporáneo, el laboratorio es una propuesta de sensibilización corporal que busca desnaturalizar la percepción y los modos cotidianos automatizados de estar en el mundo. Los participantes son invitados a vendar los ojos y a ser conducidos por un recorrido de estímulos sensoriales en el cual experimentan texturas, olores y sonidos en temporalidades diferentes de las del cotidiano. A continuación, registran sus experiencias en mapas corporales. En las diversas ediciones realizadas, percibimos que la experiencia vivida expande la percepción de sí mismo y del otro, avivando una potencia poética de expresión y memoria del cuerpo. Originada en la Psicología Clínica, esta propuesta dialoga con otras disciplinas y lenguajes, articulando las dimensiones ética, estética y política de la existencia.(AU)

Manejo dos pais frente à expressão de raiva dos filhos / Management of parents for their children expressing anger / Gestión de los padres para sus hijos que expresan la ira

O pai e a mãe têm uma importância fundamental no desenvolvimento psicossocial dos filhos, bem como na regulação das emoções. Na pesquisa objetivou-se investigar o manejo dos pais frente à expressão da emoção raiva dos filhos do sexo masculino e feminino. Participaram 26 casais tendo dois filhos de seis a doze anos. Para coleta dos dados, utilizou-se questionário de dados gerais, Critério de Classificação Econômica Brasil, entrevista estruturada e história-estímulo. Verificou-se que as estratégias mais utilizadas pelos pais e mães frente à raiva dos filhos foram reação centrada no problema e reação punitiva, respectivamente estratégias, adaptativa e desadaptativa. Tanto os pais quanto as mães tenderam a reagir com minimização maior com o filho e reagir com distração maior com a filha. Conclui-se que pais e mães utilizam-se das mesmas estratégias mediante à expressão de raiva dos filhos de ambos os sexos, porém, há diferenças de gênero quanto à prática parental. (AU)

The father and the mother have a fundamental importance in the psychosocial development of children, as well as in the regulation of emotions. The objective of this research was to investigate the management of parents in the face of the expression of anger in male and female children. A total of 26 couples participated in the research, including couples that have two children from six to 12 years old. For data collection we used a general data questionnaire, the Brazilian Economic Classification Criteria, a structured interview, and a story-stimulus. We verified that the strategies most used by parents against their children's anger were problem-centered reactions and punitive reactions, respectively adaptive and maladaptive strategies. Both fathers and mothers tended to react with a greater minimization with the son and more distractedly with the daughter. It is concluded that fathers and mothers use the same strategies for both sexes against their children's anger expressions, but there are some gender differences in parental practice. (AU)

Los padres tienen una importancia fundamental en el desarrollo psicosocial de los hijos, así como en la regulación de las emociones. Se buscó investigar el manejo de los padres frente a la expresión de emoción de rabia de los hijos de ambos sexos. Participaron 26 parejas con dos hijos de seis a doce años. Para recolección de datos, se utilizó un cuestionario de datos generales, Criterio de Clasificación Económica Brasil, entrevista estructurada e historia-estímulo. Se verificó que las estrategias más utilizadas por los padres frente a la rabia de los hijos fueron; reacción centrada en el problema y reacción punitiva del problema; respectivamente, estrategias adaptativas y desadaptativas. Tanto la madre como el padre tienden a reaccionar con minimizacion mayor para el hijo y con más distracción con la hija. Conclusión: los padres utilizan las mismas estrategias mediante la expresión de rabia de los hijos, pero hay diferencias de género en cuanto a la práctica parental. (AU)

Estrangeirismos na cidade: inventando o comum em zonas urbanas fronteiriças / Estrangement in the city: inventing the common in urban fringe zones / Extranjerismos en la ciudad: inventando lo común en zonas urbanas fronterizas

Nossas cidades são fortemente marcadas por processos de segregação socioespacial que as dividem em territórios estrangeiros, cada qual com seu universo cultural próprio. Esses estrangeirismos frequentemente colocam desafios às práticas de extensão universitária, ou outras práticas de pesquisa e trabalho que colocam em contato distintos universos culturais. A partir da experiência de se sentir estrangeira na Favela da Mangueira, que se deu no âmbito de um projeto de extensão universitária vinculado ao Instituto de Psicologia da UFRJ, pretendemos traçar uma reflexão sobre como delimitam-se essas fronteiras urbanas e sobre as possibilidades de invenção do comum em uma cidade dividida, colocando em diálogo nossas experiências no campo com as elaborações de autores da fenomenologia, filosofia política, história, arte e urbanismo. Buscamos colaborar, desta forma, com aqueles que atuam em projetos de pesquisa-intervenção, extensão universitária, movimentos sociais, ONGs e outras formas de organização social que trabalhem em zonas fronteiriças dentro da cidade.

Our cities are keenly characterized by processes of socio-spatial segregation which divide them into estranged territories, each with its own cultural universe. Such estrangements are often challenging to university extension practices, as well as to other work and research practices which foster contact between different cultural universes. Based on our experience of 'feeling like a foreigner' in the Favela da Mangueira during a university extension project associated with the Institute of Psychology of the Federal University of Rio de Janeiro, we offer a reflection on how urban partitions arise and how we can invent the common in a divided city. We look to make our experiences in the field conversant with the works of authors from different areas, such as phenomenology, political philosophy, history, art and urbanism. Thus, we seek to collaborate with other researchers who direct research-intervention projects, university extension, social movements, NGOs and other types of social organizations working in urban fringe zones.

Nuestras ciudades son fuertemente marcadas por los procesos de segregación socio espacial que las dividen en territorios extranjeros, cada cual con su universo cultural propio. Esos extranjerismos frecuentemente generan desafíos para las prácticas de extensión universitaria, u otras prácticas de investigación y trabajo que ponen en contacto distintos universos culturales. A partir de la experiencia de sentirse extranjera en la Favela de Mangueira, que se dio en el ámbito de un proyecto de extensión universitaria vinculado al Instituto de Psicología de la UFRJ, pretendemos trazar una reflexión sobre cómo se delimitan esas fronteras urbanas y sobre las posibilidades de invención de lo común en una ciudad dividida, colocando en dialogo nuestras experiencias en el campo con las elaboraciones de autores de la fenomenología, filosofía, política historia, arte y urbanismo. Buscamos colaborar, de esta forma, con aquellos que actúan en proyectos de investigación-intervención, extensión universitaria, movimientos sociales, ONGs y otras formas de organización social que trabajen en zonas fronterizas dentro de la ciudad.

Congenital cystic adenomatoid malformation type I.

Congenital cystic adenomatoid malformation (CCAM) is an hamartomatous congenital pulmonary airway malformation with incidence ranging between 1:10,000 and 1:35,000 newborns. Currently CCAM is classified into five groups according to clinical and pathological features. The clinical outcome varies depending on the subtype and the extent of involvement. The authors report the case of a premature male newborn with the prenatal diagnosis of CCAM Type 1 associated with cardiac right axis deviation, who died 67 hours after birth due to respiratory failure. In addition to the autopsy report of this rare entity, the authors present its classification and prognosis.

Connective-Tissue Growth Factor (CTGF/CCN2) Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro.

Connective-tissue growth factor (CTGF) is a modular secreted protein implicated in multiple cellular events such as chondrogenesis, skeletogenesis, angiogenesis and wound healing. CTGF contains four different structural modules. This modular organization is characteristic of members of the CCN family. The acronym was derived from the first three members discovered, cysteine-rich 61 (CYR61), CTGF and nephroblastoma overexpressed (NOV). CTGF is implicated as a mediator of important cell processes such as adhesion, migration, proliferation and differentiation. Extensive data have shown that CTGF interacts particularly with the TGFß, WNT and MAPK signaling pathways. The capacity of CTGF to interact with different growth factors lends it an important role during early and late development, especially in the anterior region of the embryo. ctgf knockout mice have several cranio-facial defects, and the skeletal system is also greatly affected due to an impairment of the vascular-system development during chondrogenesis. This study, for the first time, indicated that CTGF is a potent inductor of gliogenesis during development. Our results showed that in vitro addition of recombinant CTGF protein to an embryonic mouse neural precursor cell culture increased the number of GFAP- and GFAP/Nestin-positive cells. Surprisingly, CTGF also increased the number of Sox2-positive cells. Moreover, this induction seemed not to involve cell proliferation. In addition, exogenous CTGF activated p44/42 but not p38 or JNK MAPK signaling, and increased the expression and deposition of the fibronectin extracellular matrix protein. Finally, CTGF was also able to induce GFAP as well as Nestin expression in a human malignant glioma stem cell line, suggesting a possible role in the differentiation process of gliomas. These results implicate ctgf as a key gene for astrogenesis during development, and suggest that its mechanism may involve activation of p44/42 MAPK signaling. Additionally, CTGF-induced differentiation of glioblastoma stem cells into a less-tumorigenic state could increase the chances of successful intervention, since differentiated cells are more vulnerable to cancer treatments.

Derricin and derricidin inhibit Wnt/ß-catenin signaling and suppress colon cancer cell growth in vitro.

Overactivation of the Wnt/ß-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/ß-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/ß-catenin pathway. Both chalcones are able to affect the cell distribution of ß-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/ß-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/ß-catenin pathway and colon cancer cell growth in vitro.

Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/ß-catenin signaling pathway.

Flavonoids are plant-derived polyphenolic molecules that have potential biological effects including anti-oxidative, anti-inflammatory, anti-viral, and anti-tumoral effects. These effects are related to the ability of flavonoids to modulate signaling pathways, such as the canonical Wnt signaling pathway. This pathway controls many aspects of embryonic development and tissue maintenance and has been found to be deregulated in a range of human cancers. We performed several in vivo assays in Xenopus embryos, a functional model of canonical Wnt signaling studies, and also used in vitro models, to investigate whether isoquercitrin affects Wnt/ß-catenin signaling. Our data provide strong support for an inhibitory effect of isoquercitrin on Wnt/ß-catenin, where the flavonoid acts downstream of ß-catenin translocation to the nuclei. Isoquercitrin affects Xenopus axis establishment, reverses double axes and the LiCl hyperdorsalization phenotype, and reduces Xnr3 expression. In addition, this flavonoid shows anti-tumoral effects on colon cancer cells (SW480, DLD-1, and HCT116), whereas exerting no significant effect on non-tumor colon cell (IEC-18), suggesting a specific effect in tumor cells in vitro. Taken together, our data indicate that isoquercitrin is an inhibitor of Wnt/ß-catenin and should be further investigated as a potential novel anti-tumoral agent.

Expression and evolution of the Tiki1 and Tiki2 genes in vertebrates.

Tiki1 is a Wnt protease and antagonist specifically expressed in the Spemann-Mangold Organizer and is required for head formation in Xenopus embryos. Here we report neighbor-joining phylogenetic analysis of vertebrate Tiki genes and their mRNA expression patterns in chick, mouse, and rabbit embryos. Tiki1 and Tiki2 orthologues are highly conserved, and exhibit similar but also different developmental expression patterns among the vertebrate/mammalian species analyzed. The Tiki1 gene is noticeably absent in the rodent lineage, but is present in lagomorphs and all other vertebrate/mammalian species examined. Expression in Hensen's node, the equivalent of the Xenopus Organizer, was observed for Chick Tiki2 and Rabbit Tiki1 and Tiki2. Mouse Tiki2 was detected at low levels at gastrulation and head fold stages, but not in the node. Mouse Tiki2 and chick Tiki1 display similar expression in the dorsal spinal cord. Chick Tiki1 expression was also detected in the surface ectoderm and maxillary bud, while chick Tiki2 was found in the anterior intestinal portal, head mesenchyme and primitive atrium. Our expression analyses provide evidence that Tiki1 and Tiki2 are evolutionarily conserved among vertebrate species and their expression in the Organizer and other regions suggests contributions of these Wnt inhibitors to embryonic patterning, as well as organogenesis. Our analyses further reveal mis-regulation of TIKI1 and TIKI2 in human cancer and diseases.

A arte como dispositivo à recriação de si: uma prática em psicologia social baseada no fazer artístico / Art as a gadget to the recreation of oneself: a practice in social psychology based in artistic making / El arte como dispositivo de recreación de sí: una practica en psicologia social basada en el hacer artístico

O presente trabalho enfoca a arte como instrumento na prática em psicologia social, por meio do relato da experiência com um grupo de arteterapia. A proposta do grupo, desenvolvido em um centro comunitário de Florianópolis - SC, consistia na realização de variadas atividades artísticas - desenho, pintura, colagem, modelagem em argila, escrita - como um meio para o desenvolvimento (inter)pessoal. As intervenções realizadas e a discussão aqui apresentada fundamentam-se nos aportes da psicologia histórico-cultural e especialmente nas ideias de Vigotski e Bakhtin acerca da arte. O trabalho trouxe resultados positivos aos sujeitos, que na atividade criadora encontraram novas formas de objetivação e subjetivação, desenvolvendo um olhar estético e (re)criando nas obras artísticas imagens outras de si e da vida, transformando-se neste processo...

The current work focus on art as an instrument in the practice of social psychology, through the report of experience of an art-therapy group. The proposal of the group, developed in a communitarian center in Florianópolis – SC, Brazil, consisted in the realization of several artistic activities – drawing, painting, collage, clay modeling, writing – as a resource to inter(personal) development. The interventions made and the discussionshown here are well-grounded in the references of historic-cultural psychology and specially in the ideas of Vigotski and Bakhtin concerning art. The work brought positive results to the subjects, which found in the creative activity new ways of objectivism and subjectivism, developing an aesthetic look and (re)creating in the artistic action other images of themselvesand of life, transforming themselves in this process...

El presente trabajo trata del arte como instrumento en la práctica de la psicología social, por medio de relato de la experiencia con un grupo de arte terapia. La propuesta del grupo de un centro comunitario de Florianópolis – SC, consiste en la realización de diversas actividades artísticas: dibujo, pintura, encolamiento, moldeo en barro e escritura para el desarrollo (inter) personal. Las intervenciones realizadas y la discusión se fundamentan en los aportes de la psicología histórico-cultural y especialmente en las ideas de Vygotsky y Bakhtin sobre el arte. El trabajo trajo resultados positivos a los sujetos que en la actividad creadora encontraron nuevas formas de objetivación y subjetivación, desarrollando una mirada estética y (re)creando en las obras artísticas imágenes de la vida y de sí, transformándose en el proceso...

Arteterapia: a arte como instrumento no trabalho do Psicólogo / Art therapy: art as an instrument in the work of the Psychologist / Arte terapia: el arte como instrumento en el trabajo del Psicólogo

A arteterapia é um método baseado no uso de várias formas de expressão artística com uma finalidade terapêutica. O presente artigo aborda a arteterapia tendo como objetivo refletir sobre a arte como instrumento de trabalho no campo específico da Psicologia. Apoiando-se na revisão de literatura sobre a temática, o artigo parte de um olhar histórico, examinando o contexto em que a arteterapia surge e seu desenvolvimento no Brasil. A seguir, são analisados os pressupostos fundamentais que norteiam o psicólogo nessa prática, assim como os aspectos conceituais e metodológicos próprios a cada uma das abordagens principais em arteterapia: psicanalítica, junguiana e gestáltica. A reflexão desenvolvida mostra que, apesar das diferentes molduras teóricas, a arteterapia é perpassada por uma concepção estética do humano, visto como um ser criativo, capaz de se transformar em artista da própria vida. Conclui-se, então, que a arte pode ser uma ferramenta valiosa para a atuação do psicólogo nos mais diferentes contextos, vinculada ao seu compromisso ético de contribuir para que o sujeito se (re)constitua como autor da própria história...

Art therapy is a method based on the use of various forms of artistic expression for therapeutic purposes. This article approaches art therapy aiming to think about art as a working tool specifically in the field of psychology. Based on current literature review of the subject, our starting point was an historical outlook in order to examine the context in which art therapy emerges and evolves in Brazil. Following that, fundamental notions that guide the psychologist in this practice are analyzed, as well as the conceptual and methodological aspects specific to each one of the main approaches in art therapy: psychoanalytical, jungian and Gestalt. This reflection lead us to think, despite the different theoretical frames, that art therapy is pervaded by a conception of human aesthetics, seeing the person as a creative being, and capable of becoming his own life's artist. The conclusion is that art can be a valuable tool for psychologists in many different contexts, in connection to the ethical commitment of contributing to the subject so that he/she can (re)constitute him/herself as the author of his/her own history...

El arte terapia es un método basado en el uso de varias formas de expresión artística con la finalidad terapéutica. El presente artículo aborda el arte terapia con el objetivo de reflexionar sobre el arte como un instrumento de trabajo en el campo específico de la psicología. El estudio se apoya en la revisión de la literatura y una visión histórica sobre la temática, se examina el contexto en que el arte terapia surge y desarrolla en Brasil. A seguir los análisis de los presupuestos fundamentales para el psicólogo en la práctica, también los aspectos conceptuales y metodológicos propios para cada uno de los abordajes principales en arte terapia: psicoanalítica, junguiana y gestáltica. La reflexión sobre el tema muestra que, a pesar de los diferentes marcos teóricos el arte terapia pasa por una concepción estética del humano, visto como un ser creativo, capaz de transformarse en el artista de su propia vida. Se concluye que el arte puede ser una herramienta valiosa en la actuación del psicólogo en los diferentes contextos, vinculado al su compromiso ético de contribuir para que el sujeto se (re)construya como el autor de su propia historia...

Subjetividade e experiência do corpo na Biodança / Subjectivity and body experience in Biodanza

A Biodança é um sistema terapêutico criado pelo psicólogo chileno Rolando Toro, baseada em vivências realizadas em grupo, mediadas pela música e pela dança. O presente trabalho, desenvolvido na área da Psicologia Social, tem como objetivo refletir sobre a experiência do corpo na Biodança e suas relações com a subjetividade, a partir dos sentidos atribuídos a essa atividade entre participantes de um grupo regular de Biodança. A investigação foi pautada na fenomenologia merleau-pontyana, buscando-se apreender os sentidos do vivido mediante a observação participante no grupo e entrevista com cada um dos seus integrantes. Os resultados mostram que a Biodança possibilita uma experiência de metamorfoses do corpo, cujos movimentos o "transformam" em: pássaro, música, flor, barro, escultura, água, onda. Analisa-se que estes aspectos relacionam-se a transformações da subjetividade, uma vez que configuram novos modos de objetivação e subjetivação, possibilitando aos sujeitos a vivência de novos modos de ser e dando abertura ao seu processo de (re)criação existencial...

Biodanza is a therapeutic system created by psychologist Chilean RolandoToro and based on experiences conducted in groups, mediated by music and dance. This work, developed in the field of Social Psychology, aims to reflect on the experience of the body in Biodanza and its relation to subjectivity,from the meanings attributed to this activity by participating in a regulargroup of Biodanza. The research was based on phenomenology merleaupontyana, seeking to understand the meanings of the lived through participant observation and group interviews with each of its members. The results show that Biodanza provides an experience of the body metamorphoses, whose movements the "turn" in: bird, song, flower, clay, sculpture, water, wave. We analyze these aspects relate to transformations of subjectivity, since configure new modes of subjectivity and objectivity, allowing the subjects to experience new ways of being and giving vent to his process of (re)creation existential...