Percorrer por autor "Fernandes, R."
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- Angiogenesis in Schistosoma haematobium-associated urinary bladder cancerPublication . Dematei, A.; Fernandes, R.; Soares, R.; Alves, H.; Richter, J.; Botelho, M.C.Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. During infection, eggs are deposited in the bladder causing an intense inflammatory reaction. Angiogenesis is defined as the formation of new blood vessels from preexisting ones and is recognized as a key event in cell proliferation and carcinogenesis and spread of malignant lesions. A growing amount of evidence points to angiogenesis playing a key role in schistosomiasis-associated bladder cancer. Thus, identifying biomarkers of this process plays an important role in the study of cancer. Here, we review recent findings on the role of angiogenesis in bladder cancer and the growth factors that induce and assist in their development, particularly SCC of the bladder associated to urogenital schistosomiasis.
- Anti-cancer potential of Fasciola hepatica extractsPublication . Ferreira, S.; Fernandes, R.; Alves, H.; Richter, J.; Botelho, M.C.Fascioliasis is a food borne disease caused by infection with a liver fluke termed Fasciola (F.) hepatica. Fascioliasis, as a neglected tropical disease, commonly affects poor people from developing countries. It has been estimated that at least 2.6 million people are infected with fascioliasis worldwide. According to the International Agency for Research on Cancer, two other liver flukes Opistorchis viverrini and Clonorchis sinensis) have been recognized as definitive causes of cancer (IARC, 2012). On the other hand even long-lasting and/ or repeated F. hepatica infections have not been associated with cancer, so far. There are any known causative associations between this parasite and cholangiocarcinoma or liver cancer.
- Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium InfectionPublication . 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.
- Expression of angiogenic and inflammation markers in murine schistosomiasis mansoniPublication . Dematei, A.; Fernandes, R.; Soares, R.; Alves, H.; Richter, J.; Botelho, M.C.Aim: to study angiogenesis in the livers of mice infected with S. mansoni.
- Imbalance of steroid hormones in hamsters infected with Schistosoma mansoniPublication . 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.
- Interstitial deletion on chromosome 14q in prenatal diagnosisPublication . Simão, L.; Alves, C.; Marques, B.; Pedro, S.; Ferreira, C.; Viegas, M.; Ventura, C.; Furtado, J.; Cruz, J.; Martins, A.; Cohen, A.; Fernandes, R.; Freixo, J.; Correia, J.; Correia, H.A limited number of prenatal diagnosis (PND) cases have reported interstitial deletions of the long arm of chromosome 14 involving the 14q31-32 region. Those cases presented cardiac anomalies, urogenital anomalies, congenital diaphragmatic hernia, and mild pyelectasis. We report the PND of a 33-year-old pregnant woman, who underwent chorionic villus sampling at 12 weeks of gestation after a positive combined 1st trimester screen. The karyotype revealed a 14q interstitial deletion. Amniocentesis was performed at 18 weeks of gestation to confirm the deletion and to exclude a confined placental mosaicism and a microarray analysis was performed in order to accurately define the deletion breakpoints. Cytogenetics analysis revealed a karyotype 46,XY,del(14)(q31q32.2)dn. Microarray analysis allowed to redefined the breakpoints accurate localization and the identification of a ~21Mb deletion (arr[hg19] 14q31.1q32.31(79917376_101568230)x1). At 18 weeks of gestation the fetus presented abnormal fetal biometric parameters (occipitofrontal diameter, cephalic perimeter and abdominal circumference) on ultrasound. After counseling the couple opted for pregnancy termination. The postmorten analysis presented decreased biometry, low weight and low fetal size, facial dysmorphism, clinodactyly, club foot, overlapping fingers and short penis. In internal habitus he presented thymus hypoplasia, bladder hypoplasia, and horseshoe kidneys. The genotype-phenotype correlation in PND pure del(14q) cases is not well established. Furthermore, to our knowledge, del(14q) had not been reported so early in the gestation yet. In this case the positive 1st trimester screen was related to the inverted ductus venosus and low PAPP-A value. The urogenital anomalies (as horseshoe kidneys) and biometry anomalies are described in the literature. However, to our knowledge, some features of the present case were not seen in other reported cases, for instance clinodactyly, club foot, overlapping fingers, thymus hypoplasia and bladder hypoplasia. Other reports described cardiac and cerebral anomalies, diaphragmatic hernia, and also UPD(14)like phenotypes, which are possibly liked to the 14q32 imprinted region. The establishment of a phenotype-genotype correlation is difficult given the size of the deletion, which includes a large number of genes in distinct regions. Nevertheless, this work contributes to a better identification of additional features associated to del(14q) that can be present in PND.
- Mouse model of Schistosomiasis: infection with Schistosoma mansoni in CD-1 micePublication . Luis, C.; Soares, R.; Fernandes, R.; Botelho, M.Schistosomiasis is a parasitic disease that affects almost 240 million worldwide. CD1 mice were infected with cercariae of S. mansoni, after which infection developed for 8 weeks. Tissues were processed to immuno-histological techniques. It was performed H&E staining for overall analyses, Sirius Red for fibrosis and immunohistochemistry for inflammation biomarkers. The most infected organ was the liver, fibrosis decreased with egg development and Galectin-3 (Gal3) and Interleukin 6 (IL-6) were expressed inside granulomas
- Regulatory Variants In LDLR And PCSK9 Promoters And 5'UTRs: Investigating The impact In Familial HypercholesterolaemiaPublication . Graça, R.; Menezes, J.; Fernandes, R.; Alves, A.C.; Romão, L.; Bourbon, M.Background and Aims: Familial Hypercholesterolaemia (FH) is a genetic disorder of lipid metabolism caused by pathogenic variants in LDLR, APOB, and PCSK9. While diagnostic efforts traditionally focus on coding variants, non-coding regions, such as promoters and 5'UTRs, remain understudied despite their importance. This work aims to characterise 100 variants in the promotor/5'UTR of LDLR and PCSK9. Methods: The promotor/5'UTR sequences of LDLR and PCSK9 were cloned by SOEing PCR upstream of the Firefly luciferase coding region in the pGL4.10. For LDLR, sequence from c.-319 to the initiation codon was retrieved from literature, while for PCSK9, sequence from c.-650 to the initiation codon was confirmed using a 5'-RACE strategy. The resulting constructs (LDLR_pGL4-WT and PCSK9_pGL4-WT) were subsequently modified through site-directed mutagenesis. LDLR and PCSK9 variants were transfected into CHO-ldlA7 and Huh7 cells, respectively. Cells were cultured in different cholesterol depletion states, and luciferase activity measured using a Dual-Luciferase Reporter Assay System. Results: Compared to their respective wild-type constructs, LDLR and PCSK9 variants displayed a diverse range of phenotypic effects, with statistically significant increases or decreases in promoter activity. These variations can differently impact the FH phenotype and hold significant implications for disease management and therapeutic strategies, as increases or decreases in promoter activity in the two genes have distinctly opposing effects on LDL-C levels. Moreover, as far as we know, this is the first experimental work defining the PCSK9 5’ UTR region. Conclusions: This study provides novel insights into the functional impact of LDLR and PCSK9 promoter/5'UTR variants on gene expression and their potential contributions to the FH phenotype. Importantly, these findings underscore the critical role of functional studies in variant classification, particularly for non-coding regions, which remain underrepresented in genetic diagnostics. By elucidating how these variants influence LDL-C levels through altered promoter activity, this work highlights their relevance in refining FH diagnosis and tailoring patient management strategies.
- The spread of Aedes albopictus in Portugal: an update of its geographic and seasonal distributionPublication . Costa Osório, Hugo; Soares, Patricia; Freitas, R.; Fernandes, R.; Zé-Zé, Líbia; Amaro, Fátima; Alves, Maria JoãoOver the last two decades, the invasive mosquito Aedes albopictus has spread across Europe. Portugal was the last country in southern Europe to report this species, which was first detected in 2017 under the National Vector Surveillance Network—REVIVE. Despite all the measures taken, its distribution has increased rapidly and in 2023, it was introduced in Lisbon, a major urban centre. As Ae. albopictus is a competent vector for dengue, Zika and chikungunya viruses, monitoring its geographic distribution and seasonal dynamics is crucial for public health risk assessment.
- The use of helminths as anti-cancer agentsPublication . Botelho, M.C.; Fernandes, R.Recently, the hygiene hypothesis has been revisited to accommodate the connection between microorganisms and cancer. In a further pathogen-based observation, parasites and their extracts have been studied as antitumor inducers to substantiate the cancer hygiene hypothesis. Indeed, researchers observed the direct effect of molecules released by Echinococcus granulosus whose activity directly inhibits both cancer cell growth and migration. Recently, we have also found that Fasciola hepatica extracts induced death of Chinese Hamster Ovary (CHO) cells suggesting that some molecules produced by F. hepatica extracts could potentially be explored as a preventive or even medicinal anti-cancer innovative strategy.