Infection with carcinogenic helminth parasites and its production of metabolites induces the formation of DNA-adducts

Background: Infections classified as group 1 biological carcinogens include the helminthiases caused by Schistosoma haematobium and Opisthorchis viverrini. The molecular mediators underlying the infection with these parasites and cancer remain unclear. Although carcinogenesis is a multistep process, we have postulated that these parasites release metabolites including oxysterols and estrogen-like metabolites that interact with host cell DNA. How and why the parasite produce/excrete these metabolites remain unclear. A gene encoding a CYP enzyme was identified in schistosomes and opisthorchiids. Therefore, it is reasonable hypothesized that CYP 450 might play a role in generation of pro-inflammatory and potentially carcinogenic compounds produced by helminth parasites such as oxysterols and catechol estrogens. Here, we performed enzymatic assays using several isoforms of CYP 450 as CYP1A1, 2E1 and 3A4 which are involved in the metabolism of chemical carcinogens that have been associated with several cancer. The main aim was the analysis of the role of these enzymes in production of helminth-associated metabolites and DNA-adducts. Method: The effect of cytochrome P450 enzymes CYP 1A1, 2E1 and 3A4 during the interaction between DNA, glycocholic acid and taurochenodeoxycholate sodium on the formation of DNA-adducts and metabolites associated with urogenital schistosomiasis (UGS) and opisthorchiasis was investigated in vitro. Liquid chromatography/mass spectrometry was used to detect and identify metabolites. Main findings: Through the enzymatic assays we provide a deeper understanding of how metabolites derived from helminths are formed and the influence of CYP 450. The assays using compounds similar to those previously observed in helminths as glycocholic acid and taurochenodeoxycholate sodium, allowed the detection of metabolites in their oxidized form and their with DNA. Remarkably, these metabolites were previously associated with schistosomiaisis and opisthorchiasis. Thus, in the future, it may be possible to synthesize this type of metabolites through this methodology and use them in cell lines to clarify the carcinogenesis process associated with these diseases. Principal conclusions: Metabolites similar to those detected in helminths are able to interact with DNA in vitro leading to the formation of DNA adducts. These evidences supported the previous postulate that imply helminth-like metabolites as initiators of helminthiases-associated carcinogenesis. Nonetheless, studies including these kinds of metabolites and cell lines in order to evaluate its potential carcinogenic are required.This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia, in the framework of the project, Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). The FCT and FEDER (European Union) also supported these studies through project number IF/00092/2014/CP1255/CT0004info:eu-repo/semantics/publishedVersio

Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium

Background Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens. Methodology/Principal Findings A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed) to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn) to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32–4.84; P≤0.001). In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13–16.70; P≤0.05). Conclusions/Significance Estrogen metabolites occur widely in diverse metabolic pathways. In view of the statistically significant association between catechol-estrogens/ DNA adducts and self-reported infertility, we propose that an estrogen-DNA adduct mediated pathway in S. haematobium-induced ovarian hormonal deregulation could be involved. In addition, the catechol-estrogens/ DNA adducts described here represent potential biomarkers for schistosomiasis haematobia

Nutritional and phytochemical composition of Vaccinium padifolium Sm wild berries and radical scavenging activity

Blueberries have a well-deserved reputation as a potential functional food, supported by studies which have identified and quantified various nutrients and bioactive phytochemicals with known benefits for human diet and health. Wild blueberries have attracted particular attention due to the levels and concentrations of those phytonutrients. This study aims to evaluate for the first time the chemical composition of Madeira Island's endemic Vaccinium padifolium Sm wild berry. Results show that this fruit contains high values of total soluble phenolic content (around 4 g GAE kg-1 FW), as well as significant values of total monomeric anthocyanin content (around 3 g eq. cyanidin kg-1 FW) and DPPH scavenging activity (around 86.72%). Additionally, results reveal that this fruit has water content of about 88% as well as low sugar content (17.98 and 29.73 g kg-1 for glucose and fructose, respectively). Results also confirm that this wild blueberry is a good source of dietary fiber, fat and minerals. The high level of terpenoid compounds stands out in the aroma profile analysis.Ana C. Pereira acknowledges Agencia Regional para o Desenvolvimento da Investigação Tecnologia e Inovação (ARDITI) for financial support through her grant, M1420-09-5369-FSE- 000001.info:eu-repo/semantics/publishedVersio

The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these metabolites emphasizing their potential effects on the dysregulation of the tumor suppressor gene p53 expression during urogenital schistosomiasis. Enhanced understanding of these potential carcinogens may not only shed light on urogenital schistosomiasis-induced neoplasia of the bladder, but would also facilitate development of interventions and biomarkers for this and other infection-associated cancers at large

Effects of residues on the degradation of PHA produced from mixed microbial cultures and processed in extrusion

Thermal degradation upon melting is one of the major drawbacks reported for polyhydroxyalkanoates (PHA). However, the role of residues originating from the fermentation and the extraction steps on the thermal stability of this class of biopolymers still needs to be clarified. In the particular case of PHA produced from mixed microbial cultures (MMC), this topic is even less documented in the literature. Here, two polyhydroxy(butyrate-co-valerate) (PHBV) produced from MMC enriched in PHA accumulating organisms and fed with cheese whey were studied. A micro extrusion line is used to produce filaments and assess the processability and the degradation of processed PHBV. The prototype micro extrusion line allows for studying grams of materials. The two PHBV contain 18 mol% HV. PHBV was recovered with 11 wt% residues, and further submitted to a purification procedure resulting in a second biopolyester containing less than 2 wt% impurities. The thermorheological characterization of the two PHBV is first presented, together with their semicrystalline properties. Then the processing windows of the two biopolyesters are presented. Finally, the properties of extruded filaments are reported and the thermomechanical degradation of PHBV is extensively studied. The structure was assessed by wide angle X-ray diffraction, mechanical and rheological properties are reported, thermal properties are studied with differential scanning calorimetry and thermogravimetric analysis, whereas Fourier Transform Infrared spectroscopy was used to assess the impact of the extrusion on PHBV chemical structure. All results obtained with the two PHBV are compared to assess the effects of residues on both PHBV processability and degradation

Valores como predictores de satisfacción con la vida en los jóvenes

Numa perspectiva funcionalista, os valores são uma expressão cognitiva das necessidades humanas, princípios que orientam o comportamento para metas mais pessoais, sociais ou gerais de vida, cujo impacto psicossocial merece mais investigação. Neste estudo, analisou-se em que medida o tipo de orientação dos valores prediz a satisfação com a vida de 562 jovens portugueses (n = 303, 53,9% mulheres), com idades entre 14 e 22 anos (M = 16,9, DP = 1,71), que frequentam o ensino médio: via profissionalizante (63,7%) e regular (36,3%). Os jovens completaram o Questionário de Valores Básicos e a Escala de Satisfação com a Vida. Os resultados da análise de regressão linear indicam que a orientação dos valores explica menos de um quarto da variabilidade da satisfação com a vida, o que suscita a necessidade de se analisar o seu poder explicativo em conjunto com outras variáveis, por exemplo, de personalidade e sociocognitivas.In a functionalist perspective, values are a cognitive expression of human needs as well as principles that guide behaviors to personal, social or general life goals, whose psychosocial impact deserves more investigation. This study aimed to analyze whether the type of values orientation predicts life satisfaction in 562 Portuguese youths (n = 303, 53.9% women) aged 14 to 22 years (M = 16.9; SD = 1.71), attending high school studies, being 63.7% technical and (36.3%) regular high school.Students completed the Basic Values Survey and the Satisfaction With Life Scale. The results of the linear regression analyzes indicate that the values orientation explains less than a quarter of life satisfaction variability, which indicated the need to further analyze its explanatory power together with other variables, such as, personality and socio-cognitive.Desde el punto de vista funcional, los valores son una expresión cognitiva de las necesidades humanas, principios que orientan el comportamiento hacia metas más personales, sociales o generales de vida, cuyo impacto psicosocial necesita más investigación. En este estudio se analizó en qué medida el tipo de orientación de los valores predice la satisfacción con la vida de 562 jóvenes portugueses (n = 303, 53.9% mujeres), con edades entre 14 y 22 años ( = 16.9, P = 1.71) que frecuentan Enseñanza Secundaria: profesional (63.7%) y normal (36.3%). Los jóvenes completaron el Cuestionario de Valores Básicos y la Escala de Satisfacción con la Vida. Los resultados del análisis de regresión lineal indican que la orientación de los valores explica menos de una cuarta parte de la variabilidad de satisfacción con la vida, lo que plantea la necesidad de analizar su poder explicativo, junto con otras variables, por ejemplo, de personalidad y socio-cognitivas.(undefined)info:eu-repo/semantics/publishedVersio

Características analíticas de los aceites de oliva producidos por diversas técnicas de extracción con la variedad portuguesa ‘Galega Vulgar’

A metal hammer-decanter (HD) olive processing line was compared to a traditional metal hammer-press (HP) line, a discontinuous method which, when properly used, yields high-quality virgin olive oils. Galega olives (traditional Portuguese variety) were used. Olives were picked at a predetermined maturation stage and plagues and oil content were evaluated before processing. Years, extraction technology, data replicates, and years*extraction, were taken into account and compared using statistical treatment. In spite of significant differences among the results obtained, only acidity was statistically significant and sufficient for classifying the produced olive oil into a lampante category.Se han comparado dos líneas de procesamiento de aceite, utilizando un sistema de prensas (SP) o un decantador centrífugo (DC). El procesamiento que recurre al sistema de prensas es un sistema discontinuo que, sin embargo permite obtener aceites vírgenes de gran calidad. Para este estudio se ha utilizado la variedad Portuguesa Galega común. Las aceitunas fueron tratadas contra el ataque de plagas, y recogidas en un punto de maduración predeterminado. Del mismo modo, se evaluó el porcentaje de aceite obtenido de la cosecha. Se han considerado los resultados analíticos teniendo en cuenta la determinación de la influencia de la extracción en el producto final. Este punto ha sido evaluado por medio de un tratamiento estadístico. Aunque se han observado diferencias significativas entre los resultados de algunos de los parámetros analizados, sólo las diferencias verificadas en el grado de acidez son susceptibles de modificar la clasificación final del aceite, situándolo en la categoría lampante

Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture

Adult diagnosis of Swyer-James-MacLeod syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Swyer-James-MacLeod syndrome or unilateral hyperlucent lung syndrome is a rare entity associated with postinfectious bronchiolitis obliterans occurring in childhood. It is characterized by hypoplasia and/or agenesis of the pulmonary arteries resulting in pulmonary parenchyma hypoperfusion.</p> <p>Case presentation</p> <p>Here we report the case of a 53-year-old Caucasian woman with Swyer-James-MacLeod syndrome found in the differential diagnosis workup for a new onset of heart failure, secondary to pulmonary arterial hypertension complicated by a patent ductus arteriosus.</p> <p>Conclusion</p> <p>Typically, this disorder is diagnosed in childhood after evaluation for recurrent respiratory infections, but sometimes an indolent course means diagnosis is not made until adulthood.</p