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1.
J Exp Clin Cancer Res ; 41(1): 315, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289544

RESUMO

BACKGROUND: Tumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis; however, the mechanisms by which they acquire metastatic traits are not well understood. METHODS: LAMC2 transcriptional levels were evaluated using publicly available transcriptome data sets, and LAMC2 immunohistochemistry was performed using a tissue microarray composed of PDAC and normal pancreas tissues. Silencing and tracing of LAMC2 was performed using lentiviral shRNA constructs and CRISPR/Cas9-mediated homologous recombination, respectively. The contribution of LAMC2 to PDAC tumorigenicity was explored in vitro by tumor cell invasion, migration, sphere-forming and organoids assays, and in vivo by tumor growth and metastatic assays. mRNA sequencing was performed to identify key cellular pathways upregulated in LAMC2 expressing cells. Metastatic spreading induced by LAMC2- expressing cells was blocked by pharmacological inhibition of transforming growth factor beta (TGF-ß) signaling. RESULTS: We report a LAMC2-expressing cell population, which is endowed with enhanced self-renewal capacity, and is sufficient for tumor initiation and differentiation, and drives metastasis. mRNA profiling of these cells indicates a prominent squamous signature, and differentially activated pathways critical for tumor growth and metastasis, including deregulation of the TGF-ß signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of the TGF-ß type I receptor (activin receptor-like kinase-5, ALK5), completely abrogated lung metastasis, primarily originating from LAMC2-expressing cells. CONCLUSIONS: We have identified a highly metastatic subpopulation of TICs marked by LAMC2. Strategies aimed at targeting the LAMC2 population may be effective in reducing tumor aggressiveness in PDAC patients. Our results prompt further study of this TIC population in pancreatic cancer and exploration as a potential therapeutic target and/or biomarker.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I , RNA Interferente Pequeno , Neoplasias Pancreáticas/patologia , Células-Tronco Neoplásicas/metabolismo , Fator de Crescimento Transformador beta , RNA Mensageiro , Receptores de Ativinas , Movimento Celular/genética , Linhagem Celular Tumoral , Laminina/genética , Laminina/metabolismo , Neoplasias Pancreáticas
2.
J Biochem Mol Toxicol ; 35(10): e22875, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34350654

RESUMO

Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Moléculas de Adesão Celular/urina , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gentamicinas/toxicidade , Túbulos Renais Proximais/lesões , Túbulos Renais Proximais/metabolismo , Compostos Organometálicos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Canais de Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citoplasma/metabolismo , Modelos Animais de Doenças , Histonas/metabolismo , Masculino , Fosforilação , Ratos , Ratos Wistar , Canais de Cátion TRPV/metabolismo
3.
Oncogene ; 39(21): 4271-4285, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32291413

RESUMO

Pancreatic stellate cells (PSCs) secrete high levels of transforming growth factor-ß1 (TGF-ß1) that contributes to the development of pancreatic ductal adenocarcinoma (PDAC). TGF-ß1 modulates the expression of L1 cell adhesion molecule (L1CAM), but its role in tumour progression still remains controversial. To clarify L1 function in PDAC and cellular phenotypes, we performed L1CAM cell sorting, silencing and overexpression in several primary pancreatic cancer cells. PSCs silenced for TGF-ß1 were used for crosstalk experiments. We found that TGF-ß1 secreted by PSCs negatively regulates L1CAM expression, through canonical TGF-ß-Smad2/3 signalling, leading to a more aggressive PDAC phenotype. Cells with reduced expression of L1CAM harboured enhanced stemness potential and tumourigenicity. Inactivation of TGF-ß1 signalling in PSCs strongly reduced the aggressiveness of PDAC cells. Our data provide functional proof and mechanistic insights for the tumour-suppressive function of L1CAM via reducing stemness. Rescuing L1CAM expression in cancer cells through targeting of TGF-ß1 reverses stemness and bears the potential to improve the still miserable prognosis of PDAC patients.


Assuntos
Carcinogênese/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Molécula L1 de Adesão de Célula Nervosa/biossíntese , Neoplasias Pancreáticas/metabolismo , Células Estreladas do Pâncreas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Humanos , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Molécula L1 de Adesão de Célula Nervosa/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Fator de Crescimento Transformador beta1/genética
4.
Int J Mol Sci ; 20(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480481

RESUMO

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.


Assuntos
Anticarcinógenos/uso terapêutico , Bifidobacterium longum , Neoplasias Colorretais/terapia , Licopeno/uso terapêutico , Probióticos/uso terapêutico , Administração Oral , Animais , Anticarcinógenos/administração & dosagem , Bifidobacterium longum/fisiologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Licopeno/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Probióticos/administração & dosagem , Receptor IGF Tipo 1/análise
5.
Int J Pharm ; 532(2): 686-695, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28705622

RESUMO

The ZnGa1.995Cr0.005O4 persistent luminescence nanoparticles offer the promise of revolutionary tools for biological imaging with applications such as cell tracking or tumor detection. They can be re-excited through living tissues by visible photons, allowing observations without any time constraints and avoiding the undesirable auto-fluorescence signals observed when fluorescent probes are used. Despite all these advantages, their uses demand extensive toxicological evaluation and control. With this purpose, mice were injected with a single intravenous administration of hydroxylated or PEGylated persistent luminescence nanoparticles at different concentrations and then a set of standard tests were carried out 1day, 1 month and 6 months after the administration. High concentrations of hydroxylated nanoparticles generate structural alterations at histology level, endoplasmic reticulum damage and oxidative stress in liver, as well as rising in white blood cells counts. A mechanism involving the endoplasmic reticulum damage could be the responsible of the observed injuries in case of ZGO-OH. On the contrary, no toxicological effects related to PEGylated nanoprobes treatment were noted during our in vivo experiments, denoting the protective effect of PEG-functionalization and thereby, their potential as biocompatible in vivo diagnostic probes.


Assuntos
Cromo/toxicidade , Nanopartículas/toxicidade , Óxidos/toxicidade , Zinco/toxicidade , Animais , Contagem de Células Sanguíneas , Ensaio Cometa , Gálio/toxicidade , Hidroxilação , Injeções Intravenosas , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/ultraestrutura , Luminescência , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Polietilenoglicóis/química , Baço/efeitos dos fármacos , Baço/ultraestrutura
6.
J Med Food ; 19(6): 607-14, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27214602

RESUMO

The aim of the present study was to evaluate the synergic effect of lycopene (LYC) treatment with a dietary control in a nonalcoholic fatty liver disease (NAFLD) model induced with a high-fat diet (HFD). Sprague-Dawley rats were fed during 4 weeks with a normal diet (ND·4w) or an HFD (HFD·4w) to produce an NAFLD model. Then, rats from the ND·4w group continued during 4 weeks with the same diet (ND·8w), and rats from HFD were fed during 4 weeks with an ND (HFD·4w+ND·4w) or an ND plus LYC (HFD·4w+ND+LYC·4w). LYC (20 mg/kg) was administered daily by gavage. ND and ND+LYC diets partially reverted the following alterations due to HFD: liver weight, serum low-density lipoproteins (LDL), hepatic total cholesterol (TC), and catalytic activity of hepatic superoxide dismutase, catalase, and glutathione peroxidase, as well as macroscopic and microscopic images of livers. A higher recuperation to reach normality was obtained with ND+LYC in: liver weight, hepatic TC, serum LDL, and, in some instances, macroscopic and microscopic images of livers. Failures to recovery with both NDs were observed for malondialdehyde level and serum aspartate aminotransferase activity. Taken together, the results from this study suggest the potentially protective role of LYC against NAFLD; however, more clinical trials are needed to support this idea.


Assuntos
Carotenoides/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Glutationa Peroxidase/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Licopeno , Masculino , Malondialdeído/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue
7.
Immunity ; 44(2): 406-21, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26885861

RESUMO

Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells.


Assuntos
Ácidos Graxos/metabolismo , Glucose/metabolismo , Glicólise , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Antígenos CD4/metabolismo , Proliferação de Células , Células Cultivadas , Fatores de Transcrição Forkhead/metabolismo , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Oxirredução , Proteômica , Transcriptoma
9.
Cir Cir ; 83(6): 527-31, 2015.
Artigo em Espanhol | MEDLINE | ID: mdl-26164135

RESUMO

BACKGROUND: Testicular germ-cell carcinoma is the most frequent neoplasm in males aged 15 to 35 years old. It is bilateral in 2% to 3%, and synchronous in 20% to 25% of the cases. CLINICAL CASE: The case is presented of a 19 year-old male, with abdominal pain. Physical examination revealed abdominal mass in the umbilical region, and the computed tomography scan showed a retroperitoneal tumour, with α-fetoprotein, lactate dehydrogenase, and human chorionic gonadotropin above limits. Testicular ultrasound showed bilateral lesions. Exploratory laparotomy was performed, identifying an unresectable retroperitoneal tumour. Biopsies were taken, reporting mixed germ cell tumour composed of choriocarcinoma and embryonal carcinoma. Six cycles of chemotherapy were given, based on bleomycin, etoposide and cisplatin, with partial tumour response. Later on, the patient underwent bilateral radical orchiectomy, with pathology reporting a synchronous bilateral testicular teratoma. A second line of chemotherapy was given, based on vincristine, etoposide, ifosfamide and cisplatinum. Nevertheless, the disease progressed, with metastatic dissemination and the patient died. DISCUSSION: Germ cells tumours can present in primary extra-gonadal locations. It is difficult to distinguish a retroperitoneum primary germ cell tumour from metastatic disease of a clinically undetected gonadal tumour or one that has regressed, like the situation described in the case presented. CONCLUSIONS: Ninety percent of patients diagnosed with germ cell tumours can be cured. However, delay in diagnosis correlates with an advanced clinical stage and poor prognosis.


Assuntos
Carcinoma Embrionário/diagnóstico , Coriocarcinoma/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Teratoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Dor Abdominal/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Carcinoma Embrionário/tratamento farmacológico , Carcinoma Embrionário/patologia , Carcinoma Embrionário/cirurgia , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Coriocarcinoma/cirurgia , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Evolução Fatal , Humanos , Ifosfamida/administração & dosagem , Masculino , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Orquiectomia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia , Teratoma/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Vincristina/administração & dosagem , Adulto Jovem
10.
J Bioenerg Biomembr ; 47(4): 337-53, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26060181

RESUMO

Electron transport chain (ETC) dysfunction, excessive ROS generation and lipid peroxidation are hallmarks of mitochondrial injury in the diabetic liver, with these alterations also playing a role in the development of non-alcoholic fatty liver disease (NAFLD). Enhanced mitochondrial sensitivity to lipid peroxidation during diabetes has been also associated to augmented content of C22:6 in membrane phospholipids. Thus, we aimed to test whether avocado oil, a rich source of C18:1 and antioxidants, attenuates the deleterious effects of diabetes on oxidative status of liver mitochondria by decreasing unsaturation of acyl chains of membrane lipids and/or by improving ETC functionality and decreasing ROS generation. Streptozocin-induced diabetes elicited a noticeable increase in the content of C22:6, leading to augmented mitochondrial peroxidizability index and higher levels of lipid peroxidation. Mitochondrial respiration and complex I activity were impaired in diabetic rats with a concomitant increase in ROS generation using a complex I substrate. This was associated to a more oxidized state of glutathione, All these alterations were prevented by avocado oil except by the changes in mitochondrial fatty acid composition. Avocado oil did not prevented hyperglycemia and polyphagia although did normalized hyperlipidemia. Neither diabetes nor avocado oil induced steatosis. These results suggest that avocado oil improves mitochondrial ETC function by attenuating the deleterious effects of oxidative stress in the liver of diabetic rats independently of a hypoglycemic effect or by modifying the fatty acid composition of mitochondrial membranes. These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Mitocôndrias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Diabetes Mellitus Experimental/patologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Masculino , Mitocôndrias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Persea , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
11.
Food Funct ; 6(6): 1865-74, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25940690

RESUMO

Peppermint (Mentha piperita) infusions represent an important source of bioactive compounds with health benefits, which can be enhanced by applying salicylic acid (SA) during plant cultivation. The aim of this study was to evaluate the effect of SA (0, 0.5 and 2 mM) during peppermint cultivation on the chemical profile of saponins and alkaloids, as well as the anti-diabetic properties of the resulting infusions. The results showed that a 2 mM SA treatment significantly improved the chemical profiles of the infusions. Furthermore, the administration of 2 mM SA-treated peppermint infusions for 4 weeks to a high-fat diet/streptozotocin-induced diabetic rats decreased serum glucose levels (up to 25%) and increased serum insulin levels (up to 75%) as compared with the diabetic control. This can be related to the observed protection on pancreatic ß-cells. Furthermore, 0.5 and 2 mM SA-treated peppermint infusions decreased LDL (24 and 47%, respectively) and increased HDL levels (18 and 37%, respectively). In addition, all groups treated with peppermint infusions had lower serum and liver triglyceride contents, where 2 mM SA peppermint infusion showed the highest effect (44% and 56%, respectively). This is probably caused by its higher capacity to inhibit pancreatic lipase activity and lipid absorption. Moreover, SA-treated peppermint infusions improved the steatosis score in diabetic rat liver and decreased serum transaminase levels, probably as a result of the increase in steroidal saponins and alkaloids, such as trigonellin. Therefore, the application of 2 mM SA during cultivation of peppermint could be used to improve the anti-diabetic properties of peppermint infusions.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Suplementos Nutricionais , Fertilizantes , Hipoglicemiantes/uso terapêutico , Mentha piperita/química , Extratos Vegetais/uso terapêutico , Ácido Salicílico/metabolismo , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Suplementos Nutricionais/análise , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/uso terapêutico , Hiperlipidemias/complicações , Hiperlipidemias/prevenção & controle , Hipoglicemiantes/química , Insulina/agonistas , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Lipase/antagonistas & inibidores , Lipase/metabolismo , Fígado/patologia , Masculino , Mentha piperita/crescimento & desenvolvimento , Mentha piperita/metabolismo , México , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/complicações , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Distribuição Aleatória , Ratos Wistar
12.
Food Chem Toxicol ; 80: 144-153, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25795146

RESUMO

Red oak (Quercus spp.) leaves are traditionally used as food in Mexico, and some of their infusions have potential anticarcinogenic and anti-inflammatory effects; however, these properties have not yet been scientifically tested. The aim of this work was to explore the anti-inflammatory activity in HT-29 cells and anticarcinogenic effect in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis of red oak infusions. Quercus infusions were prepared and administered as the sole source of drink to male Sprague-Dawley rats (1% w/v) for the entire 26-week experimental period. On week 4, rats received 8 subcutaneous injections of DMH (21 mg/kg body weight) once a week. The results showed that mean tumor (0.9 ± 0.2 vs. 2.6 ± 0.3) and multiplicity (1.2 ± 0.1 vs. 2.0 ± 0.23), and ß-catenin protein level (2.2-fold) in adenocarcinomas were significantly lower in Quercus sideroxyla-treated group compared with DMH group. By contrast, Quercus durifolia and Quercus eduardii infusions had no protective effect. Additionally, the experiments in HT-29 cells confirmed that Q. sideroxyla infusion effectively decreased the levels of the inflammatory markers COX-2 and IL-8 by modulating the expression of NF-κB. These results highlight some of the molecular mechanisms related to the chemopreventive effect of Q. sideroxyla infusion and its potential value as a source of bioactive compounds.


Assuntos
1,2-Dimetilidrazina/toxicidade , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Neoplasias do Colo/prevenção & controle , Extratos Vegetais/farmacologia , Quercus/química , Animais , Anti-Inflamatórios/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Biomarcadores , Sobrevivência Celular , Neoplasias do Colo/induzido quimicamente , Células HT29 , Humanos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Quercus/classificação , Ratos , Especificidade da Espécie
13.
Plant Foods Hum Nutr ; 70(2): 146-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25680741

RESUMO

Mexico has the highest per capita consumption of corn in the world, which is consumed mainly as tortilla. However, only a few in vivo studies have demonstrated the anticarcinogenic potential of some maize components against colon cancer, but not as a whole food product. Therefore, our objective was to evaluate the protective effect of corn tortillas against the development of colon cancer. First, blue, red, yellow and white corn grains were lime-cooked and processed to elaborate tortillas. Then, tortillas were administered into the diet (27% w/w) to male Sprague-Dawley rats induced with the colon carcinogen 1,2-dimethylhydrazine (DMH). Our results indicated that consumption of tortillas, particularly from white and blue corns, significantly decreased adenocarcinoma incidence (up to 77.5%) and mean number compared to DMH-treated animals. In addition, an inhibition of ß-glucuronidase activity, and induction of detoxifying enzymes in liver and colon, as well as a decrease in the expression of the two most important proliferative proteins (K-ras and ß-catenin) involved in colon carcinogenesis, were also observed. These results highlight some of the molecular mechanisms related to the chemopreventive effect of tortillas, thus indicating that corn products retain their biological properties even after nixtamalization and tortilla processing.


Assuntos
1,2-Dimetilidrazina/toxicidade , Anticarcinógenos/farmacologia , Neoplasias do Colo/prevenção & controle , Manipulação de Alimentos , Zea mays/química , Animais , Colo/efeitos dos fármacos , Colo/enzimologia , Neoplasias do Colo/induzido quimicamente , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos , Ratos Sprague-Dawley , beta Catenina/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-25572857

RESUMO

Millepora complanata is a cnidarian widely distributed in the coral reefs of the Mexican Caribbean. This species is popularly known as "fire coral", since contact with it causes severe pain, skin eruptions and blisters. Intravenous administration of of M. complanata aqueous extract induces violent convulsions and death in mice within 1 min (LD50=4.62µgprotein/g of body weight). Doses less than the LD50 produced histopathological damage in kidneys and lungs. Such histopathological damage was completely eliminated after incubation of the extract in heat denaturing conditions. Unexpectedly, the denatured extract conserved its lethal effect. These findings demonstrated that the extract contained hemolytic and phospholipase activities that might be responsible for the histopathological damage, and additionally it contained other unidentified thermostable toxins with lethal effects in mice. Chromatographic analysis of the extract led to the isolation of a 61 kDa vasoconstrictor protein. Furthermore, several non-peptidic vasoconstrictor fractions were separated. Particularly interesting was the fraction MC1-IIA obtained as a result of three-step chromatography processes (ion exchange, gel filtration and reverse phase). Like the original crude extract, this fraction induced vasoconstriction and delayed hemolysis and lethal effects in mice. A subsequent chromatographic analysis of MC1-IIA showed that this fraction contained at least four non-peptidic compounds. MS and NMR spectroscopic data analyses indicated that these metabolites were poly-oxygenated alkylbenzenes. The present study constitutes the first report of the presence of non-peptidic lethal toxins in an organism of the class Hydrozoa, and evidences the great structural diversity of the toxins produced by the Millepora species.


Assuntos
Antozoários/química , Neurotoxinas/toxicidade , Animais , Eritrócitos , Rim/efeitos dos fármacos , Rim/patologia , Dose Letal Mediana , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Neurotoxinas/química , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/patologia
15.
Toxicol Rep ; 2: 63-69, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28962338

RESUMO

Our previous studies have shown that a lectin rich fraction (TBLF) extracted from Tepary bean seeds differentially inhibits cancer cells proliferation in vitro. Before testing the in vivo anticancer effect, the acute and subchronic toxicological assays in rats were conducted, where an oral dose of 50 mg/body weight kg was determined as the NOAEL. This study evaluated the resistance to digestion and complete blood count (CBC) after 24 h of the orally administered 50 mg/kg TBLF. The digestion resistance test showed lectins activity retention after 72 h and the CBC study showed a high level of eosinophils, suggesting an allergic-like response. Tolerability was assayed after 6 weeks of treatment by dosing with an intragastric cannula every third day per week. It was observed a transient reduction in food intake and body weight in the first weeks, resulting in body weight gain reduction of 10% respect to the control group at the end of the study. Additionally, organs weight, histopathological analysis and blood markers for nutritional status and for liver, pancreas and renal function were not affected. Our results suggest that 50 mg/kg TBLF administered by oral route, exhibit no toxicity in rats and it was well tolerated. Further studies will focus on long-term studies.

16.
J Trace Elem Med Biol ; 27(4): 364-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23992869

RESUMO

Exposure to lead induces oxidative stress and renal damage. Although most forms of oxidative stress are characterized by simultaneous elevation of nitrogen and oxidative species, lead-induced oxidative stress is unusual in that it is associated with a reduction in nitric oxide (NO) levels in the kidney. The role of NO in kidney injury is controversial; some studies suggest that it is associated with renal injury, whereas others show that it exerts protective effects. Concentration-dependent effects have also been proposed, linking low levels with vasodilatation and high levels with toxicity. The aim of this study was to evaluate the effects of melatonin co-exposure on the lead-induced reduction in renal NO levels. We found that sub-acute intraperitoneal administration of 10 mg/kg/day of lead for 15 days induced toxic levels of lead in the blood and caused renal toxicity (pathological and functional). Under our experimental conditions, lead induced an increase in lipid peroxidation and a decrease in NO. Melatonin co-treatment decreased lead-induced oxidative stress (peroxidation level) and toxic effects on kidneys without altering the lead-induced reduction in renal NO. These results suggest that, in our experimental model, the reduction in renal NO levels by lead exposure is not the only responsible factor for lead-induced kidney damage.


Assuntos
Rim/efeitos dos fármacos , Melatonina/farmacologia , Óxido Nítrico/química , Compostos Organometálicos/antagonistas & inibidores , Animais , Peso Corporal/efeitos dos fármacos , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Masculino , Melatonina/administração & dosagem , Óxido Nítrico/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/sangue , Compostos Organometálicos/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Magn Reson Imaging ; 31(3): 408-13, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23102942

RESUMO

OBJECTIVES: The aim of this study is to analyze the chronological development of macroscopic, microscopic and magnetic resonance imaging (MRI) findings in a rat model of Superior Mesenteric Venous (SMV) ligation, and to evaluate the role of MRI in the diagnosis of mesenteric venous thrombosis. METHODS: Thirty adult Sprague-Dawley rats were used and divided in two different groups that underwent a different surgical model and a different monitoring of ischemic damage. Group I underwent macroscopical and histological observation; Group II underwent 7T µMRI evaluation and histological analysis. RESULTS: The first alterations occurred 30 min after SMV ligation and progressively worsened until the eighth hour. The morphological and MRI findings showed the same course. CONCLUSIONS: This study provides a systematic evaluation of early anatomopathological and MRI findings following the SMV ligation. MRI allows to identify the early pathological findings of venous mesenteric ischemia and allows to correlate those to the histopathological features. Our data suggest a relevant role of MRI in the diagnostic management of mesenteric venous thrombosis, allowing to non-invasively identify and characterize the histopathologic findings. So, thanks to these skills, its future application in early diagnosis of human mesenteric venous ischemia is supposable.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Isquemia/patologia , Angiografia por Ressonância Magnética/métodos , Veias Mesentéricas/patologia , Mesentério/irrigação sanguínea , Mesentério/patologia , Trombose Venosa/patologia , Animais , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Rev Med Inst Mex Seguro Soc ; 50(2): 189-92, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-22882988

RESUMO

The abdominal aortic aneurysm (AAA) is defined as increasing the diameter of the aorta in more than 50 % of its original size and the infra-renal location is the most common (90 %). AAA disease mainly affects older men and white smokers, and has a male: female ratio of 4:1, as well the diagnosis is rare in women under age 55. Aneurysm rupture is the most common complication and cause of death in the general population, its etiology is unclear, but is commonly associated with atherosclerosis. The AAA do not exhibit rupture and it is usually asymptomatic diagnosed incidentally, however, as the aneurysm grows, appears symptoms such as back pain, abdominal or groin pain, well as palpation of a pulse mass on umbilical and supra-umbilical region. Imaging study such as ultrasound and CT scan are the mainstay of diagnosis. We present a case of 52 years old patient with no history related to the diagnosis, who presented sudden and severe abdominal pain. She was admitted to the emergency room with a diagnosis of acute cholecystitis vs. acute pancreatitis. After ultrasound and CT studies, the diagnosis was a complicated abdominal aortic aneurysm.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia
19.
Asia Pac J Clin Nutr ; 21(2): 312-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22507620

RESUMO

Some studies, that consider polymorphisms of the apolipoprotein B (APOB) gene as risk factors for coronary artery disease (CAD), have reported discordant results. The aim of the present study was to search for associations between plasma lipid profiles with the DNA Xba I polymorphism of the APOB gene in CAD patients diagnosed by angiography (CAD+). In the present study we compared 114 Mexican patients (80 men and 34 women) with CAD+ and 132 control patients (59 men and 73 women) without evidence of ischemia or arterial damage (CAD-). The frequency of X+/X+ genotype of Xba I polymorphism, in CAD+ group, was 23% (26/114) compared with 8% (11/132) in the CAD- (OR 3.25, p = 0.002). The patients with X+/X+ for the Xba I genotype APOB gene had higher concentration of triglycerides (TG) and VLDL in plasma than CAD- (p< 0.05). The genotype X+/X+ in the CAD had an effect increasing the TG and VLDL plasma levels when compared with individuals with X-/X- and X-/X+ genotypes. The present study indicated that the X+X+ genotype of Xba I polymorphism is associated with CAD+ patients and high plasma levels of TG and VLDL, in the Mexican population.


Assuntos
Apolipoproteínas B/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Lipoproteínas VLDL/sangue , Polimorfismo de Fragmento de Restrição , Triglicerídeos/sangue , Idoso , Alelos , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Estudos de Associação Genética , Homozigoto , Humanos , Hipercolesterolemia/etnologia , Hipercolesterolemia/genética , Hipertrigliceridemia/etnologia , Hipertrigliceridemia/genética , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença
20.
World J Gastroenterol ; 18(13): 1496-501, 2012 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-22509081

RESUMO

AIM: To define the evolution of ischemic lesions with 7T magnetic resonance imaging (7T-MRI) in an animal model of acute colonic ischemia. METHODS: Adult Sprague-Dawley rats were divided into two groups. Group I underwent inferior mesenteric artery (IMA) ligation followed by macroscopic observations and histological analysis. In group II, 7T-MRI was performed before and after IMA ligation and followed by histological analysis. RESULTS: Morphological alterations started to develop 1 h after IMA ligation, when pale areas became evident in the splenic flexure mesentery and progressively worsened up to 8 h thereafter, when the mesentery was less pale, and the splenic flexure loop appeared very dark. The 7T-MRI results reflected these alterations, showing a hyperintense signal in both the intraperitoneal space and the colonic loop wall 1 h after IMA ligation; the latter progressively increased to demonstrate a reduction in the colonic loop lumen at 6 h. Eight hours after IMA ligation, MRI showed a persistent colonic mural hyperintensity associated with a reduction in peritoneal free fluid. The 7T-MRI findings were correlated with histological alterations, varying from an attenuated epithelium with glandular apex lesions at 1 h to coagulative necrosis and loss of the surface epithelium detected 8 h after IMA ligation. CONCLUSION: MRI may be used as a substitute for invasive procedures in diagnosing and grading acute ischemic colitis, allowing for the early identification of pathological findings.


Assuntos
Doença Aguda , Colite Isquêmica/diagnóstico , Imageamento por Ressonância Magnética/métodos , Animais , Colite Isquêmica/patologia , Modelos Animais de Doenças , Humanos , Ligadura , Artéria Mesentérica Inferior/patologia , Artéria Mesentérica Inferior/cirurgia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
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