Functionalization of Ruthenium(II) terpyridine complexes with cyclic RGD peptides to target integrin receptors in cancer cells

The lack of selectivity for cancer cells and the resulting negative impact on healthy tissue is a severe drawback of actual cancer chemotherapy. Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible strategy to overcome such a problem. The pentapeptide cyc(RGDfK) targets the integrin receptor αvβ3, important for tumor growth and metastasis formation. In this work, two terpyridine based Ru(II) complexes were prepared and for the first time conjugated to cyc(RGDfK) via amide bond formation resulting in a monomeric and a dimeric bioconjugate. Both Ru(II) complexes bind strongly and selectively to integrin αvβ3, with the dimeric molecule displaying a 20-fold higher affinity to the receptor than the monomeric one. However, the cytotoxicity of the complexes and related bioconjugates against human A549 and SKOV-3 cell lines is still not sufficient for application as anticancer agents. Nevertheless, considering the high selectivity for integrin receptor αvβ3, the synthesis of Ru-based bioconjugates with cyc(RGDfK) paves a promising way towards the design of effective targeted anticancer agents

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116wt cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC50 value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116-p53 and HTC116-Bax cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the proapoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/ M in HCT116wt without cytotoxicity in HTC116-p21 cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma.The authors thank Dr. Larsen (Institut National de la Santé et de la Recherche Médicale) for the gift of HCT116-Bax, HCT116-p21 and HCT116-p53 cells. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2013) and L. Barros contract. T.C. Finimundy thanks CAPES Foundation, Ministry of Education of Brazil (CAPES fellow, process number 88881.134581/ 2016–01). This work is supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundaçãoinfo:eu-repo/semantics/publishedVersio

Polarization and Interference Effects in Ionization of Li by Ion Impact

We present initial-state selective fully differential cross sections for ionization of lithium by 24 MeV O8+ impact. The data for ionization from the 2s and 2p states look qualitatively different from each other and from 1s ionization of He. For ionization from the 2p state, to which in our study the mL=-1 substate predominantly contributes, we observe orientational dichroism and for 2s ionization pronounced interference which we trace back to the nodal structure of the initial-state wave function

Postcollision Effects in Target Ionization by Ion Impact at Large Momentum Transfer

We have measured and calculated fully differential cross sections for target ionization in 16-MeV O7++He and 24-MeV O8++Li collisions. As in previous studies, in the case of the He target we observe a pronounced forward shift in the angular distribution of the electrons relative to the direction of the momentum transfer q at small q (q \u3c 1 a.u.). An unexpected result is that we also find a strong forward shift at large q (q \u3e 2 a.u.), while at intermediate q this shift becomes very weak or even turns into a backward shift. For the Li target, in contrast, the forward shift monotonically increases with increasing q. These observations are qualitatively reproduced by our calculations. The comparison to theory suggests that at large q the forward shift is due to the postcollision interaction between the outgoing projectile and the ejected electron, but at small q it is mostly due to an interplay between the projectile-target core interaction and the electron-target core interaction

Prejuízos cognitivos em Diabetes Mellitus: revisão da literatura

O Diabetes Mellitus consiste em uma doença crônica que ocorre quando o pâncreas não produz insulina o suficiente, ou o organismo não é capaz de utilizar efetivamente a insulina produzida, o Diabetes Mellitus esta sendo considerado um problema de saúde pública com forte influência no ponto de vista social e econômico em vários países do mundo. Esta doença esta associada a déficits cognitivos, alterações estruturais e neurofisiológicas no cérebro. As alterações cognitivas têm como importante preocupação as possíveis dificuldades dos pacientes na adesão para um bom controle glicêmico. Foi realizada uma pesquisa bibliográfica na base de dados PubMed no período de 10 anos, entre 2003 a fevereiro de 2013. Percebeu-se a necessidade de um maior conhecimento sobre quais são os mecanismos e quais sã

Prejuízos cognitivos em Diabetes Mellitus: revisão da literatura

O Diabetes Mellitus consiste em uma doença crônica que ocorre quando o pâncreas não produz insulina o suficiente, ou o organismo não é capaz de utilizar efetivamente a insulina produzida, o Diabetes Mellitus esta sendo considerado um problema de saúde pública com forte influência no ponto de vista social e econômico em vários países do mundo. Esta doença esta associada a déficits cognitivos, alterações estruturais e neurofisiológicas no cérebro. As alterações cognitivas têm como importante preocupação as possíveis dificuldades dos pacientes na adesão para um bom controle glicêmico. Foi realizada uma pesquisa bibliográfica na base de dados PubMed no período de 10 anos, entre 2003 a fevereiro de 2013. Percebeu-se a necessidade de um maior conhecimento sobre quais são os mecanismos e quais sã

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Congenital Zika syndrome is associated with maternal protein malnutrition

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.Fil: Barbeito Andrés, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Pezzuto, Paula. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza. Universidade Federal do Rio de Janeiro; BrasilFil: Dias, André Alves. Universidade Federal do Rio de Janeiro; BrasilFil: Vasconcelos, Janaina. Universidade Federal do Pará; BrasilFil: Santos, T. M. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Ferreira, Jéssica. Universidade Federal do Rio de Janeiro; BrasilFil: Ferreira, R. O.. Universidade Federal do Rio de Janeiro; BrasilFil: Dutra, F. F.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, A. D.. Universidade Federal do Rio de Janeiro; BrasilFil: Barbosa, R. V.. Universidade Federal Do Rio de Janeiro. Centro Nacional de Biologia Estrutural E Bioimagem.; BrasilFil: Amorim, C. K. N.. Evandro Chagas Institute; BrasilFil: de Souza, M. P. C.. Evandro Chagas Institute; BrasilFil: Chimelli, L.. Instituto Estadual do Cérebro Paulo Niemeyer ; BrasilFil: Aguiar, R. S.. Universidade Federal do Rio de Janeiro; BrasilFil: Gonzalez, Paula Natalia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Lara, F. A.. Oswaldo Cruz Institute; BrasilFil: Castro, M.C.. Harvard University. Harvard School of Public Health; Estados UnidosFil: Molnár, Z.. University of Oxford; Reino UnidoFil: Lopes, R. T.. Universidade Federal do Rio de Janeiro; BrasilFil: Bozza, M. T.. Universidade Federal do Rio de Janeiro; BrasilFil: Vianez, J. L. S. G.. Evandro Chagas Institute; BrasilFil: Barbeito, Claudio Gustavo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Cuervo, P.. Oswaldo Cruz Institute; BrasilFil: Bellio, M.. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, P. P.. Universidade Federal do Rio de Janeiro; Brasi