15 results on '"Bastos, Margarida M.S.M."'
Search Results
2. Comparison of pesticides levels in grape skin and in the whole grape by a new liquid chromatographic multiresidue methodology
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Teixeira, Maria Joana, Aguiar, Ana, Afonso, Carlos M.M, Alves, Arminda, and Bastos, Margarida M.S.M
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- 2004
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3. Glucose and fructose levels on grape skin: interference in Lobesia botrana behaviour
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Varandas, Susana, Teixeira, Maria Joana, Marques, José C, Aguiar, Ana, Alves, Arminda, and Bastos, Margarida M.S.M
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- 2004
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4. Separation of the metallic and non-metallic fractions of waste printed circuit boards – A review focused on the organic swelling.
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Martelo, Liliana M., Bastos, Margarida M.S.M., and Soares, Helena M.V.M.
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PRINTED circuits , *FRACTIONS , *WASTE recycling , *EPOXY resins , *SUPERCRITICAL fluid extraction - Abstract
This paper reviews the procedures to separate the metallic (MF) and non-metallic (NMF) fractions of the waste printed circuit boards (WPCBs) for recycling their most valuable fractions. Firstly, a comprehensive overview of the whole process of recycling WPCBs, starting from the composition and structure of the WPCBs and exploring the currently available and implemented technologies (physical and/or chemical) is presented. In a second stage, the recent progresses made on the development of more environmentally friendly methods (supercritical fluid extraction and organic swelling) to separate particularly metals (the most valuable fraction of WPCBs) is reviewed, focusing particular attention on the organic swelling. This last strategy demonstrated to be an excellent pre-treatment in the recycling of WPCBs as it dissolves the brominated epoxy resin (BER) from the WPCBs and promotes the total delamination of WPCBs, which increases the recovery of the MF and NMF (and, thus, the economic revenue) minimizing the environmental impact of the WPCBs recycling processes comparatively to the traditional technologies. Additionally, two theoretical models (Hildebrand and Hansen), which are useful to predict the solubility between the solvent and the BER, and its mechanistical interpretation are presented. Finally, some challenges and opportunities of the WPCBs recycling processes are highlighted. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Recovery of humic-like susbtances from low quality composts
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Silva, Maria Elisabete F., Lemos, Luís T., Bastos, Margarida M.S.M., Nunes, Olga C., and Cunha-Queda, Ana C.
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HUMIC acid , *PRODUCT quality , *MUNICIPAL solid waste incinerator residues , *PARAMETER estimation , *ELECTRIC conductivity , *LIQUID fertilizers , *PHYTOTOXICITY - Abstract
Abstract: The quality of four commercial composts produced from poultry litter and municipal solid wastes was assessed based on their physic-chemical, stability and maturity parameters. These properties varied among the analysed composts; it was found that electric conductivity, heavy metals content and maturity were the parameters that limited the composts quality. Therefore, the feasibility of using them to obtain liquid fertilisers rich in humic-like substances (HS) was assessed. The HS yield, phytotoxicity, heavy metals co-extraction and chemical characterization were carried out. The linkage of the HS chemical composition with the compost properties was assessed by multivariate analysis. Among the compost properties, germination indices, Cr and Cu contents were the parameters that correlated most with the HS chemical composition. The low levels of metals and absence of phytotoxicity in all the analysed HS extracts indicate that composts with low quality may be used to produce liquid organic fertilisers, substituting those from natural resources. [Copyright &y& Elsevier]
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- 2013
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6. Microwave-assisted organic swelling promotes fast and efficient delamination of waste printed circuit boards.
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Monteiro, Bruno, Martelo, Liliana M., Sousa, Paulo M.S., Bastos, Margarida M.S.M., and Soares, Helena M.V.M.
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PRINTED circuits , *INDUSTRIAL waste management , *EPOXY resins , *DIMETHYLFORMAMIDE , *DIMETHYL sulfoxide - Abstract
• Swelling of epoxy resin from waste printed circuit boards (WPCBs) was performed. • Eight solvents combined with microwave, thermostatic or ultrasonic baths were tested. • From all techniques tested, microwave evidenced to be the most efficient and fast. • N-methylpyrrolidone combined with microwave was the most efficient to swell WPCBs. • Microwave (200 °C, 2 cycles of 10 min) allowed delamination of WPCBs (225 mm2). A large amount of waste printed circuit boards (WPCBs) that contain valuable metals, namely gold and copper, are produced annually. WPCBs are constituted by a multi-layer structure reinforced by a brominated epoxy resin (BER), which is very difficult to separate into the metallic and non-metallic components. The main aim of this work was to evaluate the ability of microwave for assisting in the delamination of WPCBs by organic swelling of the BER. Additionally, its performance was compared with other strategies (thermostatic and ultrasonic baths) previously described in the literature. Firstly, a library of solvents [dimethyl formamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), cyclohexanone (CH), γ-butyrolactone (GBL), tetrahydrofurfuryl alcohol (TFA) and dimethyl malonate (DM)] was selected based on the calculation of Hansen solubility parameters plus others exclusion parameters and their performance to detach all components of WPCBs (25 mm2) was tested by microwave (200 °C for 10 min), thermostatic (153 °C for 10 min) and ultrasonic (60 °C for 25 h) baths. Microwave showed to be the most efficient approach and the delamination order for WPCBs was: NMP > DMSO > DMF > DMAc. Subsequent optimization of key parameters (dimensions of WPCBs and reaction time) were obtained: dimensions of 225 mm2 using NMP (solid/liquid ratio of 300 g/L) at 200 °C with 2 cycles of 10 min. In conclusion, microwave-assisted swelling revealed to be more efficient and faster process to delaminate WPCBs into metallic and non-metallic components, which are important advantages when envisaging a future industrial waste management implementation. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Effect of peroxide oxidation on the expansion of potato starch foam.
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Barbosa, Joana V., Martins, Jorge, Carvalho, Luísa, Bastos, Margarida M.S.M., and Magalhães, Fernão D.
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STARCH , *CHAIN scission , *FOAM , *INTRINSIC viscosity , *OXIDATION , *MOLECULAR weights - Abstract
• Starch was oxidized with hydrogen peroxide. • NMR and FTIR analyses confirmed different degrees of oxidation. • Oxidation causes chain scission that decreases paste viscosity. • Oxidation produces carboxyl groups that counteract chain scission for low oxidation. • Oxidation improves starch foam expansion due to decreased paste viscosity. Starch-based foams are drawing increasing interest as bio-sourced alternatives to petroleum-based products when a low-density or air-filled cell structure combined with reasonable mechanical resistance is required. The chemical modification of starch, mainly via oxidation, can improve its expansion capability and, thus, reduce the density of the resulting foam. This study was done to investigate how the oxidation of potato starch with different concentrations of hydrogen peroxide changes its chemical structure. This work provides new insights into how this impacts the paste foaming performance. The intrinsic viscosity of the starch solutions exhibited a linear decrease as the degree of oxidation increased, indicating that the molecular weight of the starch is reduced by oxidation because of chain scission. FTIR (and second derivative) analysis revealed the decrease in the number of C H and C O bonds caused by the conversion of CH 2 OH-6 into carboxyl groups in the oxidation reaction. In addition, NMR measurements showed a reduction in the signal assigned to the OH-6 hydroxyl groups, confirming their transformation into carboxyl groups. The densities of the foams prepared with the modified starches decreased as the oxidant concentration increased, from 308 kg/m3 for native starch (NS) to 142 kg/m3 for starch oxidized with 25% H 2 O 2 (OS25). However, the starch prepared with the highest peroxide concentration showed a high density of 258 kg/m3 (OS70). The dependence of the starch paste viscosity on the oxidant concentration, which results from a balance between the decrease in molecular weight and the increase in attractive chain interactions, was analyzed and an adequate interpretation for this behavior was provided. The internal bond strength of the foams exhibited the same trend as the density as a function of oxidant concentration (from 0.641 in NS to 0.439 in OS25) as expected because a lower density implies less mechanical cohesion within the foam. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Study on the antineoplastic and toxicological effects of pomegranate (Punica granatum L.) leaf infusion using the K14-HPV16 transgenic mouse model.
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Yu, Manyou, Gouvinhas, Irene, Pires, Maria J., Neuparth, Maria J., Costa, Rui M. Gil da, Medeiros, Rui, Bastos, Margarida M.S.M., Vala, Helena, Félix, Luis, Venâncio, Carlos, Barros, Ana I.R.N.A., and Oliveira, Paula A.
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TRANSGENIC mice , *POMEGRANATE , *LABORATORY mice , *HUMAN papillomavirus , *ORAL drug administration , *ANIMAL disease models - Abstract
Punica granatum L. (pomegranate) has been used in functional foods due to its various health benefits. However, the in vivo biological potential of its leaf remains little known. This study has aimed to characterize the antineoplastic and toxicological properties of using pomegranate leaf infusion (PLI) on transgenic mice carrying human papillomavirus (HPV) type 16 oncogenes. Thirty-eight mice were divided into 3 wild-type (WT) and 3 transgenic (HPV) groups, with exposure to 0.5% PLI, 1.0% PLI, and water. The animals' body weight, drink and food consumption were recorded. Internal organs, skin samples and intracardiac blood were collected to evaluate toxicological parameters, neoplastic lesions and oxidative stress. The results indicated that PLI was safe as no mortality, no behavioural disorders and no significant differences in the levels of microhematocrit, serum biochemical markers, internal organ histology, and oxidative stress was found among the WT groups. Histological analysis revealed that HPV animals that consumed PLI exhibited reduced hepatic, renal and cutaneous lesions compared with the HPV control group. Low-dose PLI consumption significantly diminished renal hydronephrosis lesions and relieved dysplasia and carcinoma lesions in the chest skin. Oxidative stress analysis showed that low-dose PLI consumption may have more benefits than high-dose PLI. These results suggest that oral administration of PLI has the potential to alleviate non-neoplastic and neoplastic lesions against HPV16-induced organ and skin injuries, though this requires further scientific research studies. [Display omitted] • Pomegranate leaf can serve as green functional food due to many healthy potentials. • Pomegranate leaf infusion was non-toxic due to no differences among wild-type groups. • The infusions with two dosages significantly diminished renal hydronephrosis lesions. • The low-dose infusion relieved dysplasia and carcinoma lesions in the chest skins. • The infusion may have antitumoral and curative effects against HPV16-induced lesions. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Dysregulated expression of microRNA-150 in human papillomavirus-induced lesions of K14-HPV16 transgenic mice.
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Santos, Joana M.O., Fernandes, Mara, Araújo, Rita, Sousa, Hugo, Ribeiro, Joana, Bastos, Margarida M.S.M., Oliveira, Paula A., Carmo, Diogo, Casaca, Fátima, Silva, Sandra, Teixeira, Ana L., Gil da Costa, Rui M., and Medeiros, Rui
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MICRORNA , *CARCINOGENICITY , *CARCINOGENICITY testing , *NON-coding RNA , *PAPILLOMAVIRUSES , *SQUAMOUS cell carcinoma - Abstract
Aims High-risk human papillomavirus (HPV) infection is one of the major causes of infection-related cancers worldwide. MicroRNAs (miRNAs) are a family of non-coding RNAs (ncRNAs), whose dysregulated levels may cause an aberrant expression of genes involved in oncogenic pathways and consequently lead to cancer development. This is the case of the miRNA-150 (miR-150), whose expression in HPV-induced lesions remains unclear and the present work aims to clarify it. We employed K14-HPV16 mice, which express the early genes of HPV16 in basal keratinocytes, leading to the development of hyperplastic and dysplastic skin lesions and squamous cell carcinomas, and are a representative model of HPV-induced cancers. Main methods In order to evaluate the expression of miR-150 in HPV-induced lesions, we performed qPCR in wild-type mice (HPV −/− ) and in skin lesions of K14-HPV16 transgenic mice (HPV +/− ). Matched skin samples were analyzed histologically. Key findings 24–26 weeks-old HPV +/− mice showed diffuse epidermal hyperplasia and focal dysplasia in a hyperplastic background (31.8% incidence), but 28–30 weeks-old HPV +/− mice presented higher incidence of dysplasia (100.0%). MiR-150 was upregulated in HPV +/− mice when compared with HPV −/− mice ( p < 0.001). MiR-150 was also overexpressed in diffuse dysplastic lesions when compared with hyperplastic lesions ( p = 0.005). Significance The present results suggest that miR-150 is overexpressed in HPV-induced lesions in this model and its expression seems to increase with lesion progression, along the process of multi-step carcinogenesis. [ABSTRACT FROM AUTHOR]
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- 2017
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10. HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary polyphenols via NF-κB inhibition.
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Gil da Costa, Rui M., Aragão, Sofia, Moutinho, Magda, Alvarado, Antonieta, Carmo, Diogo, Casaca, Fátima, Silva, Sandra, Ribeiro, Joana, Sousa, Hugo, Ferreira, Rita, Nogueira-Ferreira, Rita, Pires, Maria João, Colaço, Bruno, Medeiros, Rui, Venâncio, Carlos, Oliveira, Maria Manuel, Bastos, Margarida M.S.M., Lopes, Carlos, and Oliveira, Paula A.
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PAPILLOMAVIRUSES , *WASTING syndrome , *POLYPHENOLS , *NF-kappa B , *LABORATORY mice - Abstract
Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24 weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-κB were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-κB canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-κB inhibitors may be useful resources for treating this syndrome. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Ptaquiloside from bracken (Pteridium spp.) inhibits tumour-infiltrating CD8+ T cells in HPV-16 transgenic mice.
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Santos, Carlos, Ferreirinha, Pedro, Sousa, Hugo, Ribeiro, Joana, Bastos, Margarida M.S.M., Neto, Tiago, Oliveira, Paula A., Medeiros, Rui, Vilanova, Manuel, and Gil da Costa, Rui M.
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PAPILLOMAVIRUS diseases , *PTAQUILOSIDE , *CD8 antigen , *T cells , *ANTINEOPLASTIC agents , *IMMUNOSUPPRESSIVE agents , *TRANSGENIC mice - Abstract
Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of ptaquiloside on tumour-infiltrating CD8 + T lymphocytes, which are critical players in anti-tumour immunity. HPV16 +/− mice received ptaquiloside (0.5 mg/mouse/week) for 10 weeks. These were then euthanized at 30 weeks of age, along with age-matched untreated controls. Skin samples were enzymatically digested and CD8 + T cells analysed for CD107a and CD44 surface expression. Ptaquiloside-exposed HPV16 +/− mice showed a significantly decreased percentage (P < 0.05) of CD8 + CD107a + and CD8 + CD44 + T cells when compared with untreated HPV16 +/− animals. Histologically, 100% of ptaquilosidetreated mice showed diffuse epidermal dysplasia, compared with 50% of the untreated mice. These findings suggest that ptaquiloside exerts an immunosuppressive role by decreasing CD8 + T cell activation and degranulation in HPV-induced lesions. Given the key role of CD8 + T lymphocytes against HPV-induced lesions, this effect is likely to contribute for viral persistence, tumour progression and increased aggressiveness in patients with HPV-related malignancies. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice.
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Santos, Carlos, Neto, Tiago, Ferreirinha, Pedro, Sousa, Hugo, Ribeiro, Joana, Bastos, Margarida M.S.M., Faustino-Rocha, Ana I., Oliveira, Paula A., Medeiros, Rui, Vilanova, Manuel, and da Costa, Rui M. Gil
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CELECOXIB , *T cells , *PAPILLOMAVIRUSES , *CARCINOGENS , *CYCLOOXYGENASE 2 inhibitors , *LABORATORY mice , *THERAPEUTICS - Abstract
Aims Human papillomavirus (HPV) is a known biologic carcinogen which is commonly transmitted through sexual intercourse. CD8 + T cells are known effectors against tumour cells and an important prognostic marker in HPV-induced cancers. COX-2 inhibitors enhance CD8 + T cell activity against some cancers. In this work, we sought to study the presence and activation of CD8 + T lymphocytes in lesions from K14-HPV16 transgenic mice and the immunomodulatory effect of celecoxib (CXB) over these cells. Main methods Skin samples of CXB-treated and untreated HPV16 −/− and HPV16 +/− mice were enzymatically digested and analysed by flow cytometry to assess CD8 + and CD8 + CD107a + T cell infiltrates. Matched skin samples were classified histologically. Key findings HPV16 +/− mice presented higher CD8 + T cell infiltration than HPV16 −/− animals ( P < 0.001). Older HPV16 +/− animals showed epidermal dysplasia and increased percentages of CD8 + CD107a + T cells compared with younger animals with hyperplasia ( P < 0.001), validating this model for testing the effects of celecoxib on CD8 + T cells. CXB-treated HPV16 +/− mice showed higher percentages of CD8 + CD107a + T cells compared with untreated HPV16 +/− animals ( P < 0.01), but no differences were observed concerning the progression of epidermal lesions. Significance These findings indicate that celecoxib enhances the degranulation of CD8 + T cells on HPV16-induced lesions, suggesting the potential clinical use of COX-2 inhibitors. Additionally, this study demonstrates the usefulness of the K14-HPV16 mouse model for testing therapeutic immunomodulatory approaches. [ABSTRACT FROM AUTHOR]
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- 2016
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13. MicroRNA-21 expression and susceptibility to HPV-induced carcinogenesis — role of microenvironment in K14-HPV16 mice model.
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Paiva, Isabel, Gil da Costa, Rui M., Ribeiro, Joana, Sousa, Hugo, Bastos, Margarida M.S.M., Faustino-Rocha, Ana, Lopes, Carlos, Oliveira, Paula A., and Medeiros, Rui
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PAPILLOMAVIRUSES , *CARCINOGENESIS , *MICRORNA , *DISEASE susceptibility , *NON-coding RNA , *GENETIC regulation , *TRANSGENIC mice - Abstract
Aims Human papillomaviruses (HPVs) are responsible for several types of cancer. K14-HPV16 transgenic mice express the HPV16 early genes, developing multi-step carcinogenesis associated with marked inflammation, as observed in human patients. MicroRNAs (MiRNA) constitute a class of non-coding RNAs that regulate gene expression. In particular, miR-21 has been associated with carcinogenesis. However, little is known about this microRNA in the normal tissue microenvironment and its possible relationship with cancer predisposition. We hypothesized that miR-21 expression influences each tissue's susceptibility to HPV-induced carcinogenesis. Main methods In order to test this hypothesis, we evaluated miR-21 expression by RT-qPCR in ear and chest skin samples from 24–28 weeks old, female K14-HPV16 transgenic and wild-type mice. Key findings In wild-type mice (HPV −/−) miR-21 expression was lower in ear skin compared with that of chest skin (p = 0.036). Under the influence of HPV16 oncogenes, transgenic animals (HPV16 +/−), developed in situ carcinoma in all ear samples and epidermal hyperplasia in chest samples. These results are consistent with the hypothesis that microRNA expression in the microenvironment of normal tissues may influence HPV-associated carcinogenesis. Furthermore, among transgenic animals, miR-21 expression was lower in in situ carcinoma samples compared with hyperplasia (p = 0043). Significance This suggests that, despite the well-known role of miR-21 as an oncogene, its anti-inflammatory and immunomodulatory properties may modulate HPV-induced carcinogenesis in a tissue-dependent manner. Further studies are warranted in order to explore the role of microRNAs in tissue susceptibility to carcinogenesis. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Multiple genotoxic activities of ptaquiloside in human lymphocytes: Aneugenesis, clastogenesis and induction of sister chromatid exchange
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Gil da Costa, Rui M., Coelho, Patrícia, Sousa, Rosa, Bastos, Margarida M.S.M., Porto, Beatriz, Teixeira, João P., Malheiro, Isabel, and Lopes, Carlos
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GENETIC toxicology , *PTAQUILOSIDE , *LYMPHOCYTES , *SISTER chromatid exchange , *GLYCOSIDES , *PTERIDIUM , *CARCINOGENS , *CHROMOSOME abnormalities - Abstract
Abstract: Ptaquiloside, a norsesquiterpene glycoside from bracken (Pteridium aquilinum), is a known carcinogen towards animals. Its genotoxicity is mainly attributed to its DNA-alkylating and clastogenic properties. This study analyses various modes of genotoxic action of ptaquiloside in human mononuclear blood cells. The alkaline comet assay was performed on cells exposed to 5μg/ml ptaquiloside for 5, 10, 20, 30, 40 or 50min. Tail length was used as a DNA-damage parameter. Assays to determine structural and numerical chromosomal aberrations and sister-chromatid exchange were conducted on cells exposed to 5, 10 or 20μg/ml ptaquiloside for 48h. The tail length showed maximum DNA damage at 20–30min, diminishing onwards. Highly significant (p <0.001) dose-dependent increases in structural and numerical chromosomal aberrations and SCE were observed in response to ptaquiloside. These results indicate that ptaquiloside is not only a DNA-alkylating agent, but expresses its genotoxicity through multiple mechanisms including clastogenesis, aneugenesis and the mechanism underlying SCE induction, which is not entirely understood. Recent studies support the role played by aneuploidy in oncogenesis, highlighting the importance of this endpoint for mutagenicity screening. SCE are thought to represent the long-term effects of mutagens and are an important genotoxicity biomarker. The present results also agree with data from epidemiological studies and from animal in vivo studies, further supporting the hypothesis that ptaquiloside may represent a significant threat to human health. [Copyright &y& Elsevier]
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- 2012
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15. Ptaquiloside-induced, B-cell lymphoproliferative and early-stage urothelial lesions in mice
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Gil da Costa, Rui M., Oliveira, Paula A., Vilanova, Manuel, Bastos, Margarida M.S.M., Lopes, Célia C., and Lopes, Carlos
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INDAN , *LYMPHOPROLIFERATIVE disorders , *B cells , *PTERIDIUM , *TRANSITIONAL cell carcinoma , *GLYCOSIDES , *CARCINOGENICITY , *LABORATORY mice - Abstract
Abstract: Bracken (Pteridium aquilinum) has long been known to cause cancer in farm and laboratory animals. Ptaquiloside, a norsesquiterpene glycoside found in bracken, is considered its main carcinogenic toxin and is capable of inducing tumours in a variety of organ systems, but especially in the urinary bladder, depending on the animal species, the administration route employed and the duration of exposure. In the present study, 12 male CD-1 mice were intraperitoneally administered with 0.5 mg ptaquiloside weekly for 15 weeks, followed by 15 weeks without any treatment. Twelve animals used as controls were administered the vehicle solution (phosphate buffered saline). Two exposed animals died during the experimental work. On necropsy, blood and tissue samples (brain, eyes, thymus, heart, lungs, liver, digestive system, spleen, bladder, kidney, adrenal gland, urinary bladder, sexual accessory glands, testes, muscle, skin and femur) were collected for histological analysis. Leukograms were prepared from blood smears and total WBC counts obtained with a Neubauer chamber. Flow cytometry was used to assess blood T-(CD3+) and B-(CD19+)-lymphocytes, medullary granulocytic (CD11b+/Ly-6G−, CD11b+/Ly-6G+) and lymphocytic (CD19+/IgM−, CD19+/IgM+) populations and thymic lymphoid (CD4+, CD8+, CD4+/CD8+) populations. Lymphoproliferative lesions were analysed immunohistochemically using antibodies against CD45R and CD3. All of the 10 surviving mice developed a lymphoproliferative malignancy. Lymphoproliferative disease was characterized by multifocal B-(CD45+/CD3−)-lymphocytic renal (10/10 animals) and hepatic (2/10 animals) invasion, splenic white pulp hyperplasia (10/10) together with a significant increase in circulating B-(CD19+)-lymphocytes and the appearance of circulating dysplastic lymphoid cells. Eight out of 10 ptaquiloside-exposed animals developed urothelial dysplasia (six low-grade dysplasia and two high-grade dysplasia). No lesions were detected in control mice. These results show that ptaquiloside is capable of inducing malignant transformation in mice and provide an in-depth characterisation of lymphoproliferative lesions. Furthermore, the urinary bladder is shown to be a target organ for this toxin in mice as well as in other animal species. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
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