Morphological variations on vital systems in a conjoined twin.

Conjoined twins (CTs), popularly referred to as Siamese twins, are a rare anomaly due to monochorionic and monoamniotic twin pregnancies. Dicephalus dibrachius dipus, a type of parapagus conjoined twin which is characterized by possessing two arms, two legs, a single trunk and two heads, epidemiologically, is an even rarer occurrence of CTs. In this article, a rare, well-preserved anatomical specimen of a dicephalus dibrachius dipus conjoined twin is presented. This study was conducted in a specimen which is part of the collection of the Embryology Museum of the institution by donation and approved by the Research Ethics Committee (REC). The female conjoined twins were born at full-term by cesarean section in the 1970s and died hours after birth. A thorough anatomical description was made through observational analysis, computed tomography and 3D reconstructed images. Major abnormalities were observed in the cardiovascular, respiratory and digestive systems. The internal anatomy exhibited a heart with three atria, two ventricles, two aortic arches, two pulmonary arteries, one innominate venous trunk and a respiratory system with two tracheas and four lungs. No other report was similar to our three atria heart description. This article provides a thorough anatomical description of all systems, which is valuable information for further studies on CTs.

Bisphenol A disruption promotes mammary tumor microenvironment via phenotypic cell polarization and inflammatory response.

Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-ß1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-ß1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.

Avaliação dos perfis fitoquímicos, antioxidante e citotóxicos do extrato alcoólico de folhas de cajá-manga (spondias dulcis) / Evaluation of phytochemical, antioxidant and cytotoxic profiles of the alcoholic extract of cajamanga leaves (spondias dulcis) / Evaluación de perfiles fitoquímicos, antioxidante y citotóxicos del extracto alcohólico de hojas de cajamanga (spondias dulcis)

Introdução: As espécies de plantas frutíferas, além da importância nutricional, podem ser usadas como fontes de compostos bioativos de interesse para o desenvolvimento de novos medicamentos. Entre as plantas com potencial terapêutico destacamos a Spondias dulcis (cajá-manga) indicada pela medicina tradicional para tratamento de condições médicas dos sistemas tegumentar, respiratório e genitourinário. Objetivos: Realizar a caraterização fitoquímica, antioxidante e citotóxica do extrato alcoólico bruto de folhas de Spondia dulcis. Material e Métodos: O extrato bruto foi obtido por percolação com o uso de 20 g das folhas secas e trituradas de Spondia dulcis e 100 ml de etanol a 70o por 24h. Na padronização do extrato foram utilizadas diferentes reações para análises de identificação de compostos do metabolismo secundário, bem como a determinação da atividade antioxidante pela captura do radical livre do DPPH. Após retirada do álcool por rotaevaporação, foram realizados testes de citotoxidade in vitro (hemólise) em solução glicosilada (5%) de hemácias (4%) nas diferentes concentrações do extrato (0,5%, 1% e 1,5%). Resultados: As análises fitoquímicas qualitativas identificaram a presença de compostos fenólicos, flavonoides, taninos genéricos e cumarinas. A avaliação dos compostos terpenoides mostrou presença de saponinas e ausência de sesquiterpenos e triterpenos. Os alcaloides foram detectados pelas reações de Bouchardat, Dragendorff, Mayer e Sheibler. A análise da atividade antioxidante do extrato indicou alta capacidade antioxidante (71%). No ensaio de hemólise a citotoxidade foi baixa nas concentrações de 0,5% e 1% e relativa na concentração de 1,5%. Conclusão: O extrato alcoólico bruto de Spondia dulciscontém compostos bioativos anti-inflamatórios, alta capacidade antioxidante e baixa citotoxicidade até a concentração de 1,5% com potencial de aplicação farmacológica (AU)

Introduction: Fruit plant species, in addition to their nutritional importance, can be used as sources of bioactive compounds of interest for the development of new drugs. Among the plants with therapeutic potential, we highlight Spondias dulcis (cajá-manga) indicated by traditional medicine for the treatment of medical conditions of the integumentary, respiratory and genitourinary systems. Objectives: To carry out the phytochemical, antioxidant and cytotoxic characterization of the leaves crude alcoholic extract of Spondia dulcis. Material and Methods: The crude extract was obtained by percolation using 20 g of dried and crushed leaves of Spondia dulcis and 100 ml of ethanol at 70° for 24 hours. In the standardization of the extract, different reactions were used to analyze the identification of compounds of secondary metabolism, as well as the determination of the antioxidant activity by capturing the free radical of DPPH. After removing the alcohol by rotary evaporation, in vitro cytotoxicity tests (hemolysis) were performed in a glycosylated solution (5%) of red blood cells (4%) at different concentrations of the extract (0.5%, 1% and 1.5%). Results: Qualitative phytochemical analyzes identified the presence of phenolic compounds, flavonoids, generic tannins and coumarins. The evaluation of terpenoid compounds showed the presence of saponins and the absence of sesquiterpenes and triterpenes. Alkaloids were detected by Bouchardat, Dragendorff, Mayer and Sheibler reactions. The analysis of the antioxidant activity of the extract indicated that the crude extract of Spondia dulcis has a high antioxidant capacity (71%). In the hemolysis assay, cytotoxicity was low at concentrations of 0.5% and 1% and relative at concentrations of 1.5%. Conclusion: The crude alcoholic extract of Spondia dulcis contains anti-inflammatory bioactive compounds, high antioxidant capacity and low cytotoxicity up to a concentration of 1.5% with potentialfor pharmacological application (AU)

Introducción: Las especies de plantas frutales, además de su importancia nutricional, pueden ser utilizadas como fuentes de compuestos bioactivos de interés para el desarrollo de nuevos fármacos. Entre las plantas con potencial terapéutico destacamos Spondias dulcis (cajamanga) indicada por la medicina tradicional para el tratamiento de afecciones médicas de los sistemas tegumentario, respiratorio y genitourinario. Objetivos: Realizar la caracterización fitoquímica, antioxidante y citotóxica del extracto alcohólico crudo de hojas de Spondia dulcis. Material y Métodos: El extracto crudo se obtuvo por percolación utilizando 20 g de hojas secas y trituradas de Spondia dulcis y 100 ml de etanol a 70° durante 24 horas. En la estandarización del extracto se utilizaron diferentes reacciones para analizar la identificación de compuestos de metabolismo secundario, así como la determinación de la actividad antioxidante mediante la captura del radical libre de DPPH. Después de eliminar el alcohol por evaporación rotatoria, se realizaron pruebas de citotoxicidad (hemólisis) in vitro en una solución glicosilada (5%) de glóbulos rojos (4%) a diferentes concentraciones del extracto (0,5%, 1% y 1,5%). Resultados: Los análisis fitoquímicos cualitativos identificaron la presencia de compuestos fenólicos, flavonoides, taninos genéricos y cumarinas. La evaluación de los compuestos terpenoides mostró la presencia de saponinas y la ausencia de sesquiterpenos y triterpenos. Los alcaloides fueron detectados por las reacciones de Bouchardat, Dragendorff, Mayer y Sheibler. Los estudios han demostrado que el extracto crudo de Spondiadulcis tiene una alta capacidad antioxidante (71%). En el ensayo de hemólisis, la citotoxicidad fue baja a concentraciones de 0,5% y 1% y relativa a concentraciones de 1,5%. Conclusión: El extracto alcohólico crudo de Spondia dulcis contiene compuestos bioactivos antiinflamatorios, alta capacidad antioxidante y baja citotoxicidad hasta una concentración de 1,5% conpotencial de aplicación farmacológica (AU)

Estudo comparativo dos perfis fitoquímicos e citotóxicos do extrato alcoólico de folhas de graviola (annona muricata) e fruta do conde (annona squamosa) / Comparative study of the phytochemical and cytotoxic profiles of the alcoholic extract of soursop (annona muricata) and custard apple (annona squamosa) leaves / Estudio comparativo de los perfiles fitoquímicos y citotóxicos del extracto alcohólico de hojas de guanábana (annona muricata) y del conde (annona squamosa)

Introdução: As plantas apresentam potencial medicinal devido aos metabólitos secundários e possuem compostos com alto potencial anti-inflamatório, com possibilidades terapêuticas. Das espécies vegetais de interesse destacamos e comparamos a graviola (Annona muricata) e a fruta do conde (Annona squamosa). Objetivo: Comparar o potencial do extrato alcoólico bruto de folhas da graviola e fruta do conde em ensaios fitoquímicos e citotóxicos. Método: Os extratos de folhas de graviola e fruta do conde foram obtidos por percolação, com o uso de 20g de folhas secas e trituradas com 100 ml de álcool de cereais. Na padronização dos extratos foram utilizadas análises de idenficação de componentes químicos, os taninos, flavonoides, saponinas e alcaloides, por meio de difrentes reações químicas e os antioxidantes foram analisados pela atividade do DPPH. A citotoxicidade das diferentes concentrações dos extratos também foram analisadas por hemólise e pelo teste da membrana corioalantide (CAM). Resultados: As análises fitoquímicas indicaram a presença de alcaloides, taninos, flavonoides e saponinas para ambos os extratos com alta capacidade antioxidante. Os testes de hemólise e CAM mostraram ausência de citotoxicidade na concentração de 2% e 4% para ambos os extratos e elevada citotoxicidade em 10% para o extrato de graviola. Conclusão: O extrato alcoólico das folhas da graviola e fruta do conde mostraram importante perfil antioxidante e com compostos anti-inflamatórios com pouca diferença entre os extratos o que estimula estudos futuros e continuidade para exploração anti-inflamatória.

Introduction: Plants have medicinal potential due to secondary metabolites and have compounds with high antiinflammatory potential, with therapeutic possibilities. Of the plant species of interest we highlight and compare the graviola (Annona Muricata) and the fruit of the count (Annona squamosa). Objective: To compare the potential of crude alcoholic extract of soursop and conde fruit leaves in phytochemical and cytotoxic assays. Method: The leaves extracts of soursop and fruit of the count were obtained by percolation, with the use of 20g of dry leaves and crushed with 100 ml of grain alcohol. In the standardization of the extracts were used idenfication analyzes of chemical components, tannins, flavonoids, saponins and alkaloids, through different chemical reactions and antioxidants were analyzed by the activity of DPPH. The cytotoxicity of the different concentrations of the extracts were also analyzed by hemolysis and by the corioalantide membrane test (CAM). Results: Phytochemical analysis indicated the presence of alkaloids, tannins, flavonoids and saponins for both extracts with high antioxidant capacity. The hemolysis and CAM tests showed absence of cytotoxicity at the concentration of 2% and 4% for both extracts and high cytotoxicity in 10% for graviola extract. Conclusion: The alcoholic extract of the leaves of soursop and fruit of the count showed important antioxidant profile and with anti-inflammatory compounds with little difference between the extracts which stimulates future studies and continuity for anti-inflammatory exploration.

Introducción: Las plantas tienen potencial medicinal debido a los metabolitos secundarios y poseen compuestos con alto potencial antiinflamatorio, además de ser utilizadas en tratamientos terapéuticos. De las especies vegetales de interés, destacamos y comparamos la guanábana (Annona muricata) y la fruta del conde (Annona squamosa). Objetivo: Comparar el potencial del extracto alcohólico crudo de hojas de guanábana y chirimoya en ensayos fitoquímicos y citotóxicos. Método: El extracto de hojas de guanábana y fruta del conde se obtuvo por percolación, utilizando 20g de hojas secas y trituradas con 100 ml de alcohol de grano. En la estandarización de los extractos se utilizaron análisis para identificar componentes químicos, taninos, flavonoides, saponinas y alcaloides, a través de diferentes reacciones químicas y los antioxidantes fueron analizados por la actividad de DPPH. También se analizó la citotoxicidad de diferentes concentraciones de extractos por hemólisis y por la prueba de membrana de corioalantida (CAM). Resultados: Los análisis fitoquímicos indicaron la presencia de alcaloides, taninos y flavonoides y saponinas para ambos extractos con alta capacidad antioxidante. Las pruebas de hemólisis y CAM mostraron ausencia de citotoxicidad a una concentración del 4% y alta citotoxicidad a partir del 10% también para ambos extractos. Conclusión: El extracto alcohólico de hojas de guanábana y chirimoya mostró importantes perfiles antioxidantes y con compuestos antiinflamatorios, lo que estimula futuros estudios y continuidad para la exploración antiinflamatoria.

Exercise Training and Verbena officinalis L. Affect Pre-Clinical and Histological Parameters.

Verbena officinalis L. or vervain is an herbal medicine and dietary supplement used worldwide. It is used for antidepressant and anticonvulsant purposes, as well as to treat inflammatory disorders, skin burns, abrasions, and gastric diseases, among others. Here, we investigated the biochemical, antioxidant, and histopathological effects of vervain against chronic physical stress. Male Wistar rats were submitted to chronic physical training and oral administration of 200 mg/kg of extract for 7 weeks. Control animals were not treated with either stress or vervain. Body weight was monitored during the study. Liver, kidney, spleen, testis, epididymis, heart, skeletal muscle, and brain samples were collected. Blood cholesterol, lactate dehydrogenase (LDH), bilirubin, and creatinine kinase (CREA), among others, were studied. Glutathione peroxidase (GPox) and superoxide dismutase (SOD) antioxidant activity was analyzed in the blood, liver, and kidney. Testosterone measurements were also performed on whole testis extracts. We found significant weight ratios differences in the epididymis, brain, and heart. Animals submitted to training showed hemorrhagic livers. Kidney histology was affected by both stress and vervain. Cell disruption and vacuolization were observed in the testes and epididymis of animals submitted to stress. Hematological and biochemical markers as CREA, LDH, TP, CKI, URCA, γGT, and glucose revealed statistically significantly differences. Additionally, the activity of glutathione peroxide (GPox) and superoxide dismutase (SOD) in the blood was also impacted. Both stress and vervain have significant in vivo effects. Infusions of vervain include phenylpropanoids, iridoids, verbenalin, hastatoside, and flavonoids, amongst others, which interact synergistically to produce the preclinical effects reported here.

Evaluation of the healing properties of Garcinia brasiliensis extracts in a cutaneous wound model.

ETHNOPHARMACOLOGICAL RELEVANCE: Wound healing is a complex process that can leave pathological scars, especially in case of infections from opportunistic microorganisms. In this context, herbal medicines open up great possibilities for investigation. One of the species of interest native to Brazil is Garcinia brasiliensis ("bacupari"). Traditionally known for treating wounds and ulcers, G. brasiliensis presents anti-inflammatory, antioxidant and antimicrobials properties. But, its wound healing profile in experimental models, in order to validate its efficacy, is still litle studied. AIM OF THE STUDY: Thus, the objective of this work was to evaluate, in an infected cutanous wound model, the potential of formulations incorporated with G. brasiliensis leaves extracts. MATERIALS AND METHODS: Crude extract (CE), Ethyl Acetate Fraction (EAF) and Hexanic Fraction (HF) were submitted to phytochemical assays, high performance thin layer chromatography (HTPLC) and cytotoxicity studies. CE and EAF were also tested for microbicidal properties and incorporated in cream and gel formulations at 10% concentration. After stability testing, the gel formulations with CE or EAF at 10% were selected and applied to skin wounds infected or not with Staphylococcus aureus in Wistar rats. The healing potenttial of the extracts was verified by the expression of the protein Annexin A1 (AnxA1), related to the processes of inflammation and antifibrotic function, the cells immunostaining for Gasdermin-D (GSDM-D), a marker of pyroptotic cell death, and the dosage of interleukin-10 (IL-10) and monocyte chemotactic protein (MCP)-1 inflammatory mediators. RESULTS: Phytochemical studies indicated the presence of compounds of pharmacological interest, including Catechin, Quercetin and Berberine in addition to low cytotoxicity of CE and EAF at 10%. After the 6-day topical treatments, CE and EAF gel formulations demonstrated to control the pruritus formation process. The treatments decreased AnxA1 expression and the amount of cells immunostained for GSDM-D, and increased the expression of MCP-1 in infected wounds. CONCLUSIONS: Together, the results show important anti-inflammatory profile and skin healing potential of CE and EAF from G. brasiliensis leaves, even in infected lesions, with therapeutic perspectives.

Administração do extrato de garcinia brasiliensis e modulação do ambiente tumoral em modelo de carcinogênese pulmonar / Administration of garcinia brasiliensis extract and modulation of the tumor environment in a model of pulmonary carcinogenesis / Administración de extracto de garcinia brasiliensis y modulación del ambiente tumoral en un modelo de carcinogénesis pulmonar

Introdução: O benzopireno é um dos principais hidrocarbonetos aromáticos policíclicos presentes no ambiente e com alta capacidade carcinogênica, sendo, portanto, usado em modelos in vivo de carcinogênese pulmonar. Investigações têm mostrado o envolvimento dos mastócitos na modulação do ambiente tumoral e que os fármacos anti-inflamatórios podem reduzir a incidência de câncer de pulmão. Entre as possibilidades terapêuticas estão os fitoterápicos. O extrato de Garcinia brasiliensis, conhecido popularmente como bacupari, mostra propriedades anti-inflamatórias e antitumorais, mas ainda pouco estudado em modelos animais. Objetivos: Avaliar os efeitos da administração do extrato alcoólico de G. brasiliensis em modelo de carcinogênese induzida por benzopireno. Material e Método: O extrato bruto foi obtido por percolação com o uso de 20 g das folhas secas e trituradas de G. brasiliensis e 100 ml de etanol a 70%, por 24h. Ratos Wistar foram divididos em 3 grupos, um controle sem indução ou tratamento, um induzido pelo benzopireno (100 mg/kg, diluído em DMSO e administrado intraperitonealmente, uma única aplicação) e um grupo tratado por gavagem (1 ml) com extrato de bacupari a 4% (3x/semana, por 7 semanas, a partir da 15o semana da indução. Os animais de todos os grupos foram eutanasiados após 21 semanas para coleta dos pulmões que foram processados para análises histopatológicas (HE) e histoquímicas (Azul de Toluidina e Azul de Alcian Safranina) para quantificação dos mastócitos. Resultados: Os resultados das análises histopatológicas mostraram desorganização do parênquima pulmonar, aumento de tecido linfático associado aos brônquios, grande influxo de células inflamatórias e regiões de displasia. Pela coloração de azul de toluidina os mastócitos foram identificados na forma intacta e desgranulada (em processo de ativação). Na coloração conjunta Azul de Alcian e Safranina, os mastócitos corados em azul representam as fases iniciais do processo de maturação, enquanto os corados em vermelho estão maduros. A quantificações evidenciaram maior quantidade de mastócitos desgranulados, azul de Alcian e mistos (corados pelo Azul de Alcian e Safranina) nos grupos tratados com o extrato. Conclusão: Os dados indicam que o ambiente tumoral nos animais tratados mostra maior modulação dos mastócitos, com mais células jovens e ativadas. Mais análises serão realizadas para verificar se a ativação dos mastócitos promovida pelo tratamento com o extrato ocorre para contenção ou promoção do processo tumoral.(AU)

Introduction: Benzopyrene is one of the main polycyclic aromatic hydrocarbons present in the environment and with a high carcinogenic capacity, being, therefore, used in in vivo models of lung carcinogenesis. Investigations have shown the involvement of mast cells in modulating the tumor environment and that anti-inflammatory drugs can reduce the incidence of lung cancer. Among the therapeutic possibilities are herbal medicines. Garcinia brasiliensis extract, popularly known as bacupari, shows anti-inflammatory and antitumor properties, but still little studied in animal models. Objectives: To evaluate the effects of the administration of the alcoholic extract of G. brasiliensis in a model of carcinogenesis induced by benzopyrene. Material and Methods: The crude extract was obtained by percolation using 20 g of dried and crushed leaves of G. brasiliensis and 100 ml of 70% ethanol for 24 hours. Wistar rats were divided into 3 groups, a control without induction or treatment, one induced by benzopyrene (100 mg/kg, diluted in DMSO and administered intraperitoneally, a single application) and a group treated by gavage (1 ml) with bacupari extract. at 4%...(AU)

Introducción: El benzopireno es uno de los principales hidrocarburos aromáticos policíclicos presentes en el ambiente y tiene una elevada capacidad carcinogénica, por lo que se utiliza en modelos in vivo de carcinogénesis pulmonar. Las investigaciones han demostrado la implicación de los mastocitos en la modulación del entorno tumoral y que los fármacos antiinflamatorios pueden reducir la incidencia del cáncer de pulmón. Entre las posibilidades terapéuticas están las fitoterapias. El extracto de Garcinia brasiliensis, conocido popularmente como bacupari, muestra propiedades antiinflamatorias y antitumorales, pero todavía está sido poco estudiado en modelos animales. Objetivos: Evaluar los efectos de la administración del extracto alcohólico de G. brasiliensis en el modelo de carcinogénesis inducido por el benzopireno. Material y métodos: El extracto crudo se obtuvo por percolación utilizando 20 g de hojas de G. brasiliensis secas y trituradas y 100 ml de etanol al 70%, durante 24h. Las ratas Wistar fueran divididas en 3 grupos, uno de control sin inducción ni tratamiento, otro inducido por benzopireno (100 mg/kg, diluido en DMSO y administrado por vía intraperitoneal, una sola aplicación) y un grupo tratado por gavage (1ml) con extracto de bacupari 4% (3x/semana, durante 7 semanas, desde la 15ª semana de inducción). Los animales de todos los grupos fueron eutanasiados después de 21 semanas para recoger los pulmones que se procesaron para los análisis histopatológicos (HE) e histoquímicos (azul de toluidina y azul de safranina) para la cuantificación de los mastocitos. Resultados: Los resultados de los análisis histopatológicos mostraron desorganización del parénquima pulmonar, aumento del tejido linfoide asociado a los bronquios, gran afluencia de células inflamatorias y regiones de displasia. Mediante la tinción con azul de toluidina, los mastocitos se identificaron como intactos y degranulados (en proceso de activación). En la tinción conjunta de azul Alcian y Safranina, los mastocitos teñidos de azul representan las fases iniciales del proceso de maduración, mientras que los teñidos de rojo son maduros. La cuantificación mostró una mayor cantidad de mastocitos degranulados, azul Alcian y mixtos (teñidos con azul Alcian-Safranin) en los grupos tratados con el extracto. Conclusión: Los datos indican que el entorno del tumor en los animales tratados muestra una mayor modulación de los mastocitos, con más células jóvenes y activadas. Se llevarán a cabo más análisis para verificar si la activación de los mastocitos promovida por el tratamiento con el extracto se produce para contener o promover el proceso tumoral.(AU)

Protective effects of piperlongumin in the prevention of inflammatory damage caused by pulmonary exposure to benzopyrene carcinogen.

Benzopyrene is one of the main polycyclic aromatic hydrocarbons with carcinogenic capacity. Research has shown that anti-inflammatory drugs can reduce the incidence of lung cancer. In this scenario, we highlight piperlongumin (PL), an alkaloid from Piper longum with anti-inflammatory properties. Therefore, our aim was to study the effect of PL administration in a model of pulmonary carcinogenesis induced by benzopyrene in Balb/c mice. Animals were divided into 3 groups (n = 10/group): sham (10% DMSO), induced by benzopyrene (100 mg/kg, diluted in DMSO) without treatment (BaP) for 12 weeks and induced by benzopyrene and treated with PL (BaP/PL) (2 mg/kg in 10% DMSO) from the eighth week post-induction. Animals were weighed daily and pletsmography was performed in the 12th week. Genotoxicity and hemoglobin levels were analyzed in blood and quantification of leukocytes in bronchoalveolar lavage (BAL). Lungs were collected for histopathological evaluation, immunohistochemical studies of annexin A1 (AnxA1), cyclooxygenase 2 (COX-2), anti-apoptotic protein Bcl-2 and nuclear transcription factor (NF-kB) and also the measurement of interleukin cytokines (IL)-1ß, IL-17 and tumor necrosis factor (TNF) -α. Treatment with PL reduced the pulmonary parameters (p < 0,001) of frequency, volume and pulmonary ventilation, decreased lymphocytes, monocytes and neutrophils in BAL (p < 0,05) as well as blood hemoglobin levels (p < 0,01). PL administration also reduced DNA damage and preserved the pulmonary architecture compared to the BaP group. Moreover, the anti-inflammatory effect of PL was evidenced by the maintenance of AnxA1 levels, reduction of COX-2 (p < 0,05), Bcl-2 (p < 0,01) and NF-kB (p < 0,001) expressions and decreased IL-1ß, IL-17 (p < 0,01) and TNF-α (p < 0,05) levels. The results show the therapeutic potential of PL in the treatment of pulmonary anti-inflammatory and anti-tumor diseases with promising therapeutic implications.

Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis.

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

Perfis fitoquímicos, microbiológicos, citotóxicos e antiinflamatórios do extrato alcoólico de folhas de atemoia (annona squamosa, l. X annona cherimola) / Phytochemical, microbiological, cytotoxic and anti-inflammatory profiles of the alcoholic extract of atemoy leaves (annona squamosa, l. X annona cheremola) / Perfiles fitoquímico, microbiológico, citotóxico y antiinflamatorio del extracto alcohólico de hojas de atemoy (annona squamosa, l. X annona cheremola)

Introdução: Os extratos alcoólicos de plantas com potencial medicinal possuem compostos com alto potencial antiinflamatório e aplicação terapêutica. Dentre as espécies vegetais de interesse destacamos a atemoia, um hibrido de Annona cherimola, Mill e Annonas quamosa, L. Objetivo: Caracterizar o extrato alcoólico bruto de folhas da atemoia em ensaios fitoquímicos, microbiológicos, citotóxicos e no modelo de peritonite. Método: O extrato de folhas de atemoia foi obtido por percolação, com o uso de 20g de folhas secas e trituradas com 100 ml de álcool de cereais. Na padronização dos extratos foram utilizadas análises de idenficação de componentes químicos, os taninos, flavonoides, saponinas e alcaloides, por meio de difrentes reações químicas e os antioxidantes foram analisados pela atividade do DPPH. Diferentes cepas bacterianas foram avaliadas quanto a sensililidade ao extrato em várias concentrações. A citotoxicidade das diferentes concentrações do extrato também foi analisada por hemólise e pelo teste da membrana corioalantide (CAM). Ainda, a capacidade anti-inflamatória do extrato a 4% foi avaliada na peritonite induzida por endotoxina em ratas. Resultados: As análises fitoquímicas indicaram a presença de alcaloides, taninos e flavonoides e ausência de saponinas além da alta capacidade antioxidante. Na concentração de 100% o extrato inibiu a proliferação de bactérias Gram-positivas e Gram-negativas. Os testes de hemólise e CAM mostraram ausência de citotoxicidade na concentração de 4% e elevada citotoxicidade a partir de 10%. No modelo de peritonite, a administração do extrato na concentração de 4% inibiu a migração de neutrófilos para a cavidade peritoneal. Conclusão: O extrato alcoólico das folhas da atemoia mostra importante perfil anti-inflamatório e antioxidante o que estimula estudos futuros para sua aplicação farmacológica. (AU)

Introduction: The alcohol extracts of plants with medicinal potential have compounds with high anti-inflammatory potential and therapeutic application. Among the plant species of interest, we highlight athemoia, a hybrid of Annona cherimola, Mill and Annonas quamosa, L. Objective: To characterize the raw alcoholic extract of athemoious leaves in phytochemical, microbiological, cytotoxic tests and in the peritonitis model. Method: The extract of atemoia leaves was obtained by percolation, with the use of 20g of dried leaves and crushed with 100 ml of cereal alcohol. In the standardization of the extracts were used idenfication analyses of chemical components, tannins, flavonoids, saponins and alkaloids, by means of diffractive chemical reactions and antioxidants were analyzed by DPPH activity. Different bacterial strains were evaluated regarding the sensitivity to the extract in different concentrations. Cytotoxicity of the different concentrations of the extract were also analyzed by hemolysis and by the corioalantide membrane (CAM) test and the anti-inflammatory capacity of the 4% extract was evaluated in endotoxin-induced peritonitis in rats. Results: Phytochemical analysis indicated the presence of alkaloids, tannins and flavonoids and absence of saponins and high antioxidant capacity. At 100% concentration the extract inhibited the proliferation of gram-positive and gram-negative bacteria. Hemolysis and CAM tests showed no cytotoxicity at 4% concentration and high cytotoxicity at 10% level. In the peritonitis model, administration of the extract at the 4% concentration inhibited the migration of neutrophils to the peritoneal cavity. Conclusion: The alcoholic extract of the leaves of athemoia shows an important anti-inflammatory and antioxidant profile which stimulates future studies for its pharmacological application.(AU)

Introducción: Los extractos alcohólicos de plantas con potencial medicinal presentan compuestos con alto potencial antiinflamatorio y aplicación terapéutica. Entre las especies vegetales de interés destacamos la atemoya, un híbrido de Annona cherimola, Mill y Annonas quamosa L. Objetivo: Caracterizar el extracto alcohólico crudo de hojas de atemoya en ensayos modelo fitoquímicos, microbiológicos, citotóxicos y de peritonitis. Método: El extracto de hojas de atemoya se obtuvo por percolación, utilizando 20g de hojas secas y trituradas con 100 ml de alcohol de grano. En la estandarización de los extractos se utilizaron análisis para identificar componentes químicos, taninos, flavonoides, saponinas y alcaloides, a través de diferentes reacciones químicas y los antioxidantes fueron analizados por la actividad de DPPH. Se evaluó la sensibilidad al extracto de diferentes cepas bacterianas a diferentes concentraciones. También se analizó la citotoxicidad de las diferentes concentraciones del extracto por hemólisis y por el test de membrana de corioalantida (CAM) y se evaluó la capacidad antiinflamatoria del extracto al 4% en peritonitis inducida por endotoxinas en ratas. Resultados: Los análisis fitoquímicos indicaron la presencia de alcaloides, taninos y flavonoides y la ausencia de saponinas y alta capacidad antioxidante. A una concentración del 100%, el extracto inhibió la proliferación de bacterias Gram-positivas y Gram-negativas. Las pruebas de hemólisis y CAM no mostraron citotoxicidad a una concentración del 4% y alta citotoxicidad a partir del 10%. En el modelo de peritonitis, la administración del extracto a una concentración del 4% inhibió la migración de neutrófilos a la cavidad peritoneal. Conclusión: El extracto alcohólico de hojas de atemoya muestra un importante perfil antiinflamatorio y antioxidante, lo que estimula futuros estudios para su aplicación farmacológica.(AU)

Anti-Acanthamoeba synergistic effect of chlorhexidine and Garcinia mangostana extract or α-mangostin against Acanthamoeba triangularis trophozoite and cyst forms.

Acanthamoeba spp. can cause amoebic keratitis (AK). Chlorhexidine is effective for AK treatment as monotherapy, but with a relative failure on drug bioavailability in the deep corneal stroma. The combination of chlorhexidine and propamidine isethionate is recommended in the current AK treatment. However, the effectiveness of treatment depends on the parasite and virulence strains. This study aims to determine the potential of Garcinia mangostana pericarp extract and α-mangostin against Acanthamoeba triangularis, as well as the combination with chlorhexidine in the treatment of Acanthamoeba infection. The minimal inhibitory concentrations (MICs) of the extract and α-mangostin were assessed in trophozoites with 0.25 and 0.5 mg/mL, for cysts with 4 and 1 mg/mL, respectively. The MIC of the extract and α-mangostin inhibited the growth of A. triangularis trophozoites and cysts for up to 72 h. The extract and α-mangostin combined with chlorhexidine demonstrated good synergism, resulting in a reduction of 1/4-1/16 of the MIC. The SEM results showed that Acanthamoeba cells treated with a single drug and its combination caused damage to the cell membrane and irregular cell shapes. A good combination displayed by the extract or α-mangostin and chlorhexidine, described for the first time. Therefore, this approach is promising as an alternative method for the management of Acanthamoeba infection in the future.

VEGFA and NFE2L2 Gene Expression and Regulation by MicroRNAs in Thyroid Papillary Cancer and Colloid Goiter.

Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower VEGFA mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC.

Effect of piperlongumine during exposure to cigarette smoke reduces inflammation and lung injury.

Chronic obstructive pulmonary disease (COPD) is related to smoking and anti-inflammatory therapy is indicated. Among the mediators with anti-inflammatory properties, we highlight piperlongumine (PL), an alkaloid/amide of Piper longum. Here we evaluated the PL administration on an experimental model of respiratory inflammation resulting from exposure to cigarette smoke. Male Balb/c mice were exposed to burning of 10 commercial cigarettes, 2x/day, for five weeks on specific equipment. PL efficacy was evaluated in control, exposed to smoke without treatment and PL treated (2.0 mg/kg, 3x/week) groups. Animals were weighed and plethysmographic analyses performed at the end of the exposure protocol. Inflammatory cells were evaluated in the bronchoalveolar lavage (BAL) and hemoglobin and glucose in the blood. Lung fragments were processed for histopathological studies and AnxA1, COX-2, NF-kB and neutrophil elastase expressions. Plethysmography revealed that PL maintained pulmonary frequency, volume and ventilation parameters similar to controls, with respiratory volume reduction compared to untreated animals. Final weight was reduced in both exposed groups. PL decreased hemoglobin concentration, attenuated the reduction of glucose levels and reduced influx of lymphocytes, neutrophils and macrophages in BAL. Histopathologically occured infiltration of inflammatory cells, increase of the interalveolar septa and intra-alveolar spaces in untreated animals. But, PL administration recovered lung tissues and, immunohistochemically, promoted increased expression of AnxA1 and reduction of COX-2, NF-kB and neutrophil elastase. Together the results indicate that PL attenuates systemic and pulmonary inflammatory changes, partially by modulating the expression the endogenous AnxA1, and may represent a promising therapy in preventing the inflammation induced by cigarette smoke.

Isotretinoína durante a gestação e malformações fetais associadas / Isotretinoin during pregnancy and associated fetal malformations / Isotretinoína durante el embarazo y malformaciones fetales asociadas

Introdução: A isotretinoína (13-cis-ácido retinóico) é a substância ativa do medicamento Roacutan®, retinoide de ação antisseborreica específico para tratamento oral de acne grave. Contudo, o uso indiscriminado deste medicamento para tratamento de acne, sem o conhecimento dos efeitos causados ao feto, contribui para ocorrência de malformações irreversíveis na criança. Objetivo: Relatar os impactos induzidos pelo uso da isotretinoína (Roacutan®) na gestação. Método: Os dados foram coletados, após aprovação pelo CEP/UNIFIPA, por meio de questionários distribuídos on-line para mulheres previamente contatadas via internet em sites sobre o tema gestação e Roacutan® e convidadas a participar do estudo por meio de plataforma específica. Doze mulheres com idades entre 27 e 37 anos responderam o questionário, residentes nos estados de São Paulo, Minas Gerais, Bahia, Rio de Janeiro, Paraná e Rio Grande do Sul, sendo três profissionais da área de saúde, três das áreas de humanas e exatas e seis de outras áreas. Resultados: As participantes relataram o uso do medicamento entre os anos de 2012 e 2018, por questões estéticas, quando estavam com idade entre 22 e 35 anos, por períodos menores que 20 dias (20%), de um mês a três meses (50%), seis meses (20%) e dez meses (10%), na dosagem de 20 mg, com ingestão de um (80%) a dois comprimidos por dia. Todas usaram o medicamento após prescrição médica e foram alertadas para fazerem uso de anticoncepcional. Contudo, duas mulheres engravidaram antes do início do tratamento (20%), oito durante o uso do medicamento (80%), sendo que maioria das mulheres usou o medicamento durante o primeiro mês de gestação (70%), uma até o segundo mês (10%) e duas até o terceiro mês (20%). A maioria informou que foi a primeira gestação (67%) e nenhuma delas teve outro filho depois. Ao saberem da gravidez com o uso concomitante do medicamento todas as mães relataram receio de malformações, especialmente relacionadas a defeitos neurológicos e cardíacos. Após o nascimento, oito bebês (80%) ficaram internados na UTI por períodos de dois a 25 dias e um deles veio a óbito. Com exceção de uma criança que não apresentou malformação, todas as outras apresentaram malformações como microtia e anotia uni ou bilateral, fenda palatina, paralisia facial uni ou bilateral e cardiopatia, na maioria dos casos em associação. Duas das crianças afetadas (20%) passaram por procedimentos cirúrgicos. Atualmente, todas as crianças estão bem de saúde, de forma geral. Nenhuma das participantes fez novo uso da isotretinoína e a maioria (90%) alerta outras mulheres sobre os riscos do medicamento em uma possível gestação. Uma das participantes alerta também os homens que fazem uso de isotretinoína. A única mulher que não informa sobre os efeitos teratogênicos do medicamento, coincidentemente, é de quem a criança não apresentou malformações congênitas. Conclusão: Embora esteja bem estabelecido o caráter teratogênico da isotretinoína na gestação e o medicamento seja usado mediante prescrição médica e com indicação de não engravidar, ainda os casos de gestação durante o tratamento são comuns. Dessa forma, é importante que campanhas de conscientização sobre esse assunto sejam realizadas de maneira continuada.(AU)

Introduction: Isotretinoin (13-cis retinoic acid) is the active substance in Roacutan®, a specific anti-seborrhoic retinoid for oral severe acne treatment. However, the indiscriminate use of this medicine for acne treatment, without knowledge of the effects caused to the fetus, contributes to the occurrence of irreversible malformations in children. Objectives: Report the impacts induced by the use of isotretinoin (Roacutan®) during pregnancy. Method: Data were collected, after approval by CEP/UNIFIPA, through questionnaires distributed online to women previously contacted via the Internet on pregnancy and Roacutan® websites and invited to participate to the study through a specific platform. Twelve women aged between 27 and 37 years old answered the questionnaire, they live in São Paulo, Minas Gerais, Bahia, Rio de Janeiro, Paraná and Rio Grande do Sul states. Three of them are health professionals, three are from the humanities and six from other fields. Results: Participants reported the use of the drug between 2012 and 2018, for aesthetic reasons, when they were aged 22 to 35 years old. The reported periods were shorter than 20 days (20%), from one month to three months (50%), six months (20%) and ten months (10%), at a dosage of 20mg, with the ingestion of one (80%) to two tablets per day. All used the drug after prescription and were warned to use contraceptive. However, two women became pregnant before treatment (20%) and eight during medication use (80%). Most women used the drug during the first month of pregnancy (70%), one until the second month. (10%) and two until the third month (20%). Most reported that it was their first pregnancy (67%) and none of them had another child afterwards. Upon knowing about pregnancy with concomitant use of the drug all mothers reported fear of malformations, especially related to neurological and cardiac defects. After birth, eight babies (80%) were admitted to the ICU (Intensive Care Unit) for periods of two to 25 days and one of them died. Except for one child who had no malformation, all the others presented malformations such as unilateral and bilateral microtia and anotia, cleft palate, unilateral or bilateral facial paralysis and heart disease, in most cases in association. Two of the affected children (20%) underwent surgical procedures. Today all children are in good health overall. None of the participants made new use of isotretinoin and most of them (90%) warn other women about the risks of the drug in a possible pregnancy. One of the participants also warns men who use isotretinoin. Conclusion: The only woman who does not report about the teratogenic effects of the drug, coincidentally, is whose child did not have congenital malformations. Although the teratogenic character of isotretinoin in pregnancy is well established and the drug is used under medical prescription and doctors indicate contraceptive use, pregnancy is still common during treatment. Therefore, it is important that awareness campaigns on this subject be carried out on a continuous basis.(AU)

Introducción: La isotretinoína (ácido 13-cis retinoico) es el principio activo de Roacutan®, un retinoide antiseborreico específico para el tratamiento oral del acné severo. Sin embargo, el uso indiscriminado de este medicamento para el tratamiento del acné, sin conocer los efectos causados al feto, contribuye a la aparición de malformaciones irreversibles en los niños. Objetivo: Informar los impactos inducidos por el uso de isotretinoína (Roacutan®) durante el embarazo. Método: Los datos se recopilaron, después de la aprobación del CEP/UNIFIPA, a través de cuestionarios distribuidos en línea a mujeres previamente contactadas a través de Internet sobre sitios de embarazo y Roacutan® e invitadas a participar en el estudio a través de una plataforma específica. Doce mujeres de 27 a 37 años respondieron el cuestionario, que residen en los estados de São Paulo, Minas Gerais, Bahía, Río de Janeiro, Paraná y Rio Grande do Sul, siendo tres profesionales de la salud, tres de los humanos y y seis de otras áreas. Resultado: Los participantes informaron el uso de la droga entre 2012 y 2018, por razones estéticas, cuando tenían entre 22 y 35 años, por períodos de menos de 20 días (20%), de un mes a tres meses (50%) , seis meses (20%) y diez meses (10%), a una dosis de 20 mg, con la ingestión de una (80%) a dos tabletas por día. Todos usaron el medicamento después de la prescripción y se les advirtió que usaran anticonceptivos. Sin embargo, dos mujeres quedaron embarazadas antes del inicio del tratamiento (20%), ocho durante el uso de medicamentos (80%), y la mayoría de las mujeres usaron el medicamento durante el primer mes de embarazo (70%), una hasta el segundo mes. (10%) y dos hasta el tercer mes (20%). La mayoría informó que era su primer embarazo (67%) y ninguno de ellos tuvo otro hijo después. Al enterarse del embarazo con el uso concomitante de la droga, todas las madres informaron temor a malformaciones, especialmente relacionadas con defectos neurológicos y cardíacos. Después del nacimiento, ocho bebés (80%) fueron ingresados en la UCI por períodos de dos a 25 días y uno de ellos murió. A excepción de un niño que no tenía malformación, todos los demás tenían malformaciones como microthay y anotación unilateral y bilateral, paladar hendido, parálisis facial unilateral o bilateral y enfermedad cardíaca, en la mayoría de los casos en combinación. Dos de los niños afectados (20%) se sometieron a procedimientos quirúrgicos. Hoy todos los niños gozan de buena salud en general. Ninguno de los participantes hizo un nuevo uso de isotretinoína y la mayoría (90%) advierte a otras mujeres sobre los riesgos del medicamento en un posible embarazo. Uno de los participantes también advierte a los hombres que usan isotretinoína. La única mujer que no informa sobre los efectos teratogénicos de la droga, casualmente, es cuyo hijo no tuvo malformaciones congénitas. Conclusión: Aunque el carácter teratogénico de la isotretinoína en el embarazo está bien establecido y el medicamento se usa con receta médica y con una indicación de no quedar embarazada, el embarazo sigue siendo común durante el tratamiento. Por lo tanto, es importante que las campañas de sensibilización sobre este tema se lleven a cabo de manera continua.(AU)

Modulation of the endogenous Annexin A1 in a cigarette smoke cessation model: Potential therapeutic target in reversing the damage caused by smoking?

BACKGROUND: Smoking cessation may help in the reversal of inflammation and damage caused by smoking. The endogenous annexin A1 (AnxA1) protein has anti-inflammatory effects which instigates the understanding of its role in the attenuation of inflammatory processes caused by smoking. MATERIAL AND METHODS: Wistar rats were exposed to cigarette smoke for 8 weeks. After the exposure period, one of the groups remained other 8 weeks in the absence of smoke. Animals not exposed to smoke were used as control. Blood, trachea and lungs were obtained for histopathological, immunohistochemical and biochemical analyses. RESULTS: Loss of cilia of the tracheal lining epithelium was found by smoke exposure, but smoking cessation led to recovery of the tracheal epithelium. Similarly, chronically exposed-to-smoke animals showed increased lymphocytes and macrophages in bronchoalveolar lavage and higher levels of glucose and gamma-GT in their blood. Reduction of lymphocytes, glucose and gamma-GT occurred after smoking cessation. In addition, IL-1ß, IL-6, IL-10, TNF-α and MCP-1 levels were elevated by smoke exposure. Smoking cessation significantly reduced the levels of IL-1ß, IL-6 and MCP-1 but increased the IL-10 concentration. Numerous mast cells and macrophages were observed in the lung of chronically exposed-to-smoke animals with reduction by smoking cigarette abstinence. AnxA1 increased expression and concomitant NF-κB reduction were found in the smoking cessation group. CONCLUSION: Our results showed that cigarette abstinence promoted partial recovery of the inflammatory process. The attenuation of the inflammatory profile may be associated with the overexpression of AnxA1 protein.

Expression of the Annexin A1 and its correlation with matrix metalloproteinases and the receptor for formylated peptide-2 in diffuse astrocytic tumors.

Astrocytomas represent the majority of cerebral gliomas. Studies show that the anti-inflammatory protein Annexin-A1 (ANXA1) is associated with the tumor invasion process and that its actions can be mediated by the receptor for formylated peptides (FPR). Therefore, we evaluated the expression of ANXA1, the receptor FPR2 and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in brain astrocytomas. Detection of proteins was performed in sections of diffuse astrocytomas (grade II), anaplastic astrocytomas (grade III) and glioblastomas (GBM, grade IV) and quantifications were made by densitometry. Our analyses showed increased expression of ANXA1 in astrocytomas of all grades, but especially in GBM. The expression of FPR2 is similar to that found for ANXA1, being higher in GBM. Immunostaining for MMPs is also stronger as the degree of malignancy increases, especially with respect to MMP-9. The positive correlation between ANXA1/FPR2 and ANXA1/MMP-9 was observed in all tumors studied. The data indicate the possible action of ANXA1 and FPR2 on the development and progression of astrocytomas, related to increased expression of MMP-9. Thereby, ANXA1 and FPR2 are involved in the biology and malignancy of diffuse astrocytic tumors.

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD.

Chronic obstructive pulmonary disease (COPD) is related to inflammatory process caused by smoking habit. In this scenario, the anti-inflammatory protein Annexin A1 (AnxA1) may represent a therapeutic alternative. We performed experiments to evaluate the effects of the AnxA1 mimetic peptide Ac2-26 in an initial COPD model by physiological, histopathological, biochemical and immunohistochemical analyses. Weight loss, increased blood pressure, reductions in the pulmonary frequency and ventilation, loss of tracheal cilia, enlargement of the pulmonary intra-alveolar spaces and lymphoid tissue found in untreated smoke-exposed group were attenuated by AnxA1 peptide treatment. The Ac2-26 administration also protected against leukocytes influx in bronchoalveolar lavage (BAL), lung and trachea, and it also led to decreased hemoglobin, glucose, cholesterol, gamma glutamyl transferase and aspartato aminotransferase levels. Similarly, reduction of proinflammatory mediators and higher concentration of anti-inflammatory cytokine were found in macerated lung supernatant, blood plasma and BAL in the treated animals. Besides Ac2-26 group showed reduced tissue expressions of AnxA1, cyclooxygenase-2 and metalloproteinase-9, but formylated peptide receptor 2 (FPR2) overexpression. Our results all together highlighted the protective role of the Ac2-26 mimetic peptide in COPD with promising perspectives.

Salicornia ramosissima J. Woods seeds affected the normal regenerative function on carbon tetrachloride-induced liver and kidney injury.

The growing importance of Salicornia plants as bioactive agents and health promoters associated with the continuous demand for alternative treatments for liver disorders, has stimulated us to evaluate the renal and hepatic effects of S. ramosissima seeds in mice under normal conditions and exposure to toxic products as carbon tetrachloride (CCl4). Thus, histopathological and lipid peroxidation evaluations of the liver and kidneys were performed. Powdered dried seeds of S. ramosissima (SRS) were administered orally for 22 days at a dose of 2000 mg/kg/day to male mice in three different settings: 1) seed effects, 2) protection against CCl4 acute toxicity (0.2 mL/kg) and 3) regeneration after acute exposure to CCl4 (0.2 mL/kg), each study being performed with appropriate control animals. Mice treated with SRS per se had slightly enlarged hepatic sinusoids and noticeable renal inflammation. SRS did not show effective protection against mice exposed to CCl4 and had no positive influence on liver and kidney recovery after CCl4 administration. These results demonstrated that SRS failed to improve hepato- and nephrotoxicity, in addition to the apparent synergism between CCl4 and SRS under these experimental conditions. Although the biological mechanisms of S. ramosissima are not fully understood, the evidence suggests further research to elucidate its adverse biological effects.

Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke.

The effects of four medicinal herbs (Arctium lappa, Plantago major, Mikania glomerata Spreng and Equisetum arvense) with anti-inflammatory properties were evaluated in a chronic obstructive pulmonary disease (COPD) model. Wistar rats were exposed to cigarette smoke during 8 weeks and one of the groups was orally given a solution containing 4% of each alcoholic herbal extracts during the exposure period. Control group was not exposed to smoke or treated. Histopathological, immunohistochemical and biochemical analyzes were performed. Normal blood plasma levels of gamma glutamyl transferase indicated no toxicity of the administered herbal extracts. The treatment reduced leukocytes influx in bronchoalveolar lavage, mast cell and macrophages numbers in lungs, as well as prevented pulmonary congestion and tracheal metaplasia. Herbal mixture also decreased plasma inflammatory mediator levels and pulmonary expression of annexin A1 and nuclear factor-k?. Our data indicate synergistic and protective effects of the used herbal medicines in animals exposed to cigarette smoke as a potential therapeutic strategy.

Avaliação da atividade antimicrobiana e citotoxicidade hemolítica em diferentes extratos vegetais / Evaluation of antimicrobial activity and hemolytic cytotoxicity in different plant extracts

Introdução: A busca por novos agentes terapêuticos tem incentivado as pesquisas com plantas medicinais, pois muitas delas podem apresentar propriedade antimicrobiana e conhecer o potencial citotóxico dos extratos é fundamental para garantir a segurança durante o uso. Objetivo: Avaliar a atividade antimicrobiana e a citotoxicidade hemolítica de Arctium lappa (bardana), Equisetum arvense (cavalinha), Mikania glomerata (guaco), Morus nigra (amora) e Plantago major (tanchagem), amplamente consumidos pela população na forma de chás medicinais. Material e Métodos: Os extratos etanólicos fora preparados a 20% por percolação. Na avaliação antimicrobiana foi utilizada a técnica de difusão em disco, empregando as bactérias Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobactersp, Enterococcus sp e Salmonella sp. O ensaio de citotoxicidade baseou-se na exposição dos extratos a 5%, 25%, 50%, 75% e 100% em suspensão de hemácias a 37ºC por 30 minutos, seguido de centrifugação e visualização do grau de hemólise. Resultados: Todos os extratos apresentaram inibição de crescimento microbiano, principalmente sobre Acinetobacter sp (amora), Enterococcus sp (amora e cavalinha), K. pneumoniae(amora, bardana e guaco), P. aeruginosa (cavalinha, tanchagem, bardana e guaco) e Salmonellasp (amora e bardana). No ensaio de citotoxicidade, o grau de hemólise foi classificado como baixo para tanchagem e bardana (5%) e médio para cavalinha, guaco e amora (25%) nas concentrações testadas. Conclusão: Os resultados mostram o potencial antimicrobiano dos extratos de amora, bardana, cavalinha, guaco e tanchagem contra bactérias Gram negativas e a baixa citotoxicidade hemolítica confirma a segurança no uso dos mesmos como agentes terapêuticos.