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Estrogen catechols detection as biomarkers in schistosomiasis induced cancer and infertility

Publication . Botelho, M.C.; Alves, H.; Richter, J.

Urogenital schistosomiasis is a chronic infection caused by the human blood fluke Schistosoma haematobium. Schistosomiasis haematobium is a known risk factor for cancer leading to squamous cell carcinoma of the urinary bladder (SCC). This is a neglected tropical disease endemic in many countries of Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These molecules are metabolized to active quinones that cause alterations in DNA (leading in other contexts to breast or thyroid cancer). Our group have shown that schistosome egg associated catechol estrogens induce tumor-like phenotypes in urothelial cells, originated from parasite estrogen-host cell chromosomal DNA adducts and mutations. Here we review recent findings on the role of estrogen-DNA adducts and how their shedding in urine may be prognostic of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.

2017-01Journal article

Open access

The effect of cooking methods on the mineral content of quinoa (Chenopodium quinoa), amaranth (Amaranthus sp.) and buckwheat (Fagopyrum esculentum)

Publication . Motta, Carla; Nascimento, Ana; Santos, Mariana; Delgado, Inês; Coelho, Inês; Rêgo, A.; Matos, Ana Sofia; Torres, Duarte; Castanheira, Isabel

In this study, we assessed the impact of two cooking methods, steaming and boiling, through the true retention (%TR) of minerals in pseudocereals and rice (varieties Indica and Japonica). Mineral content was determined by ICP-OES. Cooking methods have an impact on mineral composition of pseudocereals with losses up to 20%. Quinoa’s %TR varied from 100% (manganese, phosphorus and iron) in steaming, to 83% (copper) in boiled. In amaranth, it ranged from 98% (copper) in boiling method, to 80% (magnesium) in steaming. Buckwheat presents a %TR of 100% in iron and 87% in zinc. For boiled rice, the losses were higher in the variety Indica, with a decrease of 34% for manganese. Steamed amaranth is a higher density food in particular for manganese, magnesium and phosphorus, which present a recommended nutrient intake (RNI) contribution of 70%, 65% and 44%, respectively. Rice represents the lowest contribution to mineral RNI. This study demonstrates that estimation of mineral intake should be based on data obtained from cooked food.

2016-06Journal article

Restricted access

Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection

Publication . Cardoso, R.; Lacerda, P.C.; Costa, P.P.; Machado, A.; Carvalho, A.; Bordalo, A.; Fernandes, R.; Soares, R.; Richter, J.; Alves, H.; Botelho, M.C.

Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.

2017-11-28Journal article

Open access

Imbalance of steroid hormones in hamsters infected with Schistosoma mansoni

Publication . Oliveira, K.C.; Cardoso, R.; Santos, A.C.D.; Fernandes, R.; Botelho, M.C.

Objective: Schistosomiasis is a debilitating disease that affects 200 million people worldwide. Schistosoma haematobium and Schistosoma mansoni are the major causative agents of this disease. Cancer-association and infertility-association in Schistosoma haematobium infection have already been described and it is known that the parasite produces a catechol-estrogen molecule that induces a hormonal imbalance in the host. Methods: In order to better understand the relation of hormonal imbalance in experimental Schistosoma mansoni infection, we investigated a serum panel of steroid hormones in Schistosoma mansoni infected hamsters. Results: We found a decrease in the serum levels of Estradiol (E2), Testosterone and Progesterone in infected females and an increase of Testosterone and a decrease in Progesterone in infected males in comparison with controls. Conclusion: These results indicate that S. mansoni alters the levels of steroid hormones in infected males and females and it will increase the repertoire of data about the host-parasite molecular interplay and its relation with the endocrine system.

2019-05-29Journal article

Restricted access

In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes

Publication . Pereira, Isabel; Fraga, Sónia; Maltez, Luís; Requicha, João; Guardão, Luísa; Oliveira, Joana; Prada, Justina; Alves, Helena; Santos, José Domingos; Teixeira, João Paulo; Pereira, José Eduardo; Soares, Raquel; Gama, Francisco Miguel

The worldwide incidence of bone disorders is raising, mainly due to aging population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic-based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels (HGs) to produce injectable/moldable SBSs. Dextrin, a low-molecular-weight carbohydrate, was used to develop a fully resorbable and injectable HG. It was first oxidized with sodium periodate and then cross-linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin-based HG was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction, or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike (250-500 μm) to obtain a moldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling, and molding properties of the formulation, as well as an efficient cohesion of the granules.

2019-04-12Journal article

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