Pedunculagin and tellimagrandin-I stimulate inflammation and angiogenesis and upregulate vascular endothelial growth factor and tumor necrosis factor-alpha in vivo.

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Novel sulfonamide-chalcone hybrid stimulates inflammation, angiogenesis and upregulates vascular endothelial growth factor (VEGF) in vivo.

Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.

Pedunculagin isolated from Plinia cauliflora seeds exhibits genotoxic, antigenotoxic and cytotoxic effects in bacteria and human lymphocytes.

Pedunculagin (PD), an ellagitannin found in different plant species, possesses several pharmaceutical properties, including antitumor, antioxidant, gastroprotective, hepatoprotective, and anti-inflammatory properties. However, the effects of PD alone on DNA remain to be determined. The aim of this study was to investigate the potential cytotoxic, genotoxic, and antigenotoxic activities of PD isolated from Plinia cauliflora seeds using in silico and in vitro assays. To elucidate the biological activities of PD, in silico tools indicative of antioxidant, antineoplastic, and chemopreventive activities of PD were used. Subsequently, the mutagenic/antimutagenic effects of PD were later assessed using bacteria with the Ames test, and the cytotoxic, genotoxic, and antigenotoxic effects utilizing human lymphocytes as evidenced by trypan blue exclusion test and CometChip assay. In silico analysis indicated potential antioxidant, chemopreventive, free radical scavenger, and cytostatic activities of PD. In the Ames test, PD was found to be not mutagenic; however, this plant component protected DNA against damage-mediated by mutagens 4-nitroquinoline-1-oxide and sodium azide. Regarding human lymphocytes, PD alone was cytotoxic and genotoxic; however, it also reduced DNA damage induced by doxorubicin at co- and post-treatment. In conclusion, PD showed genotoxic, antigenotoxic and cytotoxic effects in human lymphocytes and antimutagenic effects in bacteria.

Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil.

Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5µg/µL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing.

Dioclea violacea lectin inhibits tumorigenesis and tumor angiogenesis in vivo.

Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster, and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-ß levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects.

Sistemas e serviços de saúde em âmbito mundial: organização da Atenção Primária à Saúde / Health systems and services worldwide: organization of primary health care / Sistemas y servicios de salud en nivel mundial: organización de la atención primaria de salud

Objetivo: Caracterizar, com base na literatura, sistemas e serviços de saúde em âmbito mundial. Método: Trata-se de uma Scoping Review, das bases de dados: Biblioteca Virtual de Saúde, Embase, ProQuest, National Library of Medicine National Institutes of Health e Scientific Electronic Library Online. Utilizou-se os descritores e suas combinações: Health Systems, Health Services, Structure of Services e Primary Health Care, entre 2009 e 2019, disponíveis em espanhol, francês, inglês, português. Foram analisados considerando objetivos dos estudos, tipo de proteção social, prestação de serviços, estrutura e organização da Atenção Primária à Saúde e financiamento. Resultados: Foram incluídos 12 estudos que se aquedaram à proposta da pesquisa. Os sistemas evidenciados estão relacionados aos países Iraque, Equador, Dinamarca, Argentina, Holanda, Canadá, Irlanda, Bélgica, França, Suécia, Reino Unido e Itália. Conclusões: Dentre os sistemas e serviços de saúde dos países analisados, alguns estão orientados pelo modelo de mercado, outros pela oferta pública da atenção à saúde e há aqueles que integram os dois modelos. Os sistemas de saúde devem ofertar serviços que alcancem toda a população, organizados a partir da Atenção Primária à Saúde. Os que adotam o modelo seguridade social são os que mais se aproximam deste cenário. (AU)

Objective: To map, from the literature, health systems and services worldwide, characterizing them as to the type of social protection, service provision, organizational structure of the PHC and origin of financing. Methods: This is a Scoping Review of databases: Virtual Health Library, Embase, ProQuest, National Library of Medicine, National Institutes of Health and Scientific Electronic Library Online. The descriptors and their combinations were used: Health Systems, Health Services, Structure of Services and Primary Health Care, between 2009 and 2019, available in Spanish, French, English, Portuguese. They were analyzed considering study objectives, type of social protection, service provision, structure and organization of Primary Health Care and financing. Results: Twelve studies that followed the research proposal were included. The systems shown are related to the countries: Iraq, Ecuador, Denmark, Argentina, Netherlands, Canada, Ireland, Belgium, France, Sweden, United Kingdom and Italy. Conclusion: Among the health systems and services of the analyzed countries, some are guided by the market model, others by the public offer of health care and there are those that integrate the two models. Health systems must offer services that reach the entire population, organized based on Primary Health Care. Those who adopt the social security model are the closest to this scenario. (AU)

Objetivo: Mapear, con base em la literatura, los sistemas y servicios de salud a nivel mundial, presentandolos em relación a su protección social, prestacion de los servicios de salud, estrutura organizacional y su fuente de financiamento. Caracterizar, con base en la literatura, los sistemas y servicios de salud a nivel mundial. Metodos: Esta es una revisión de alcance de las bases de datos: Biblioteca Virtual de Salud, Embase, ProQuest, Biblioteca Nacional de Medicina, Institutos Nacionales de Salud y Biblioteca Electrónica Científica en Línea. Se utilizaron los descriptores y sus combinaciones: Sistemas de Salud, Servicios de Salud, Estructura de Servicios y Atención Primaria de Salud, entre 2009 y 2019, disponibles en español, francés, inglés, portugués. Fueron analizados considerando: objetivos del estudio, tipo de protección social, prestación de servicios, estructura y organización de la Atención Primaria de Salud y financiamiento. Resultados: Se incluyeron doce estudios que se adhirieron a la propuesta de investigación. Los sistemas mostrados están relacionados con los países: Irak, Ecuador, Dinamarca, Argentina, Países Bajos, Canadá, Irlanda, Bélgica, Francia, Suecia, Reino Unido e Italia. Conclusion: Entre los sistemas y servicios de salud de los países analizados, algunos se guían por el modelo de mercado, otros por la oferta pública de atención en salud y existen los que integran los dos modelos. Los sistemas de salud deben ofrecer servicios que lleguen a toda la población, organizados en base a la Atención Primaria de Salud, quienes adoptan el modelo de seguridad social son los más cercanos a este escenario. (AU)