Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
J Sch Health ; 93(12): 1061-1069, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37867403

RESUMEN

BACKGROUND: COVID-19 screening testing (ST) can detect asymptomatic or pre-symptomatic cases, allowing for prompt identification of cases and close contacts. This study examined parents' and school staffs' knowledge and attitudes toward to a pilot school-based ST program in a school district in southern Arizona. METHODS: In May 2021, online surveys to parents and school staff were administered to examine attitudes toward ST and impacts of the COVID-19 pandemic. Unweighted percent estimates were calculated, and bivariate differences were examined by demographics. Associations were assessed using chi-square tests and logistic regression. RESULTS: The survey had response rates of 10% (606/6085) and 22% (187/849) among parents and staff, respectively. Approximately one-third of responding parents (35%) would or already allow their child to participate in school-based ST, 37% would not participate; 28% were unsure. Among responding staff, 46% would or already participate in ST, 33% would not; 21% were unsure. The top concern (38%) among responding staff was taking job-related leave if testing positive. CONCLUSION: Schools work to balance the needs of students, families, and staff by implementing supportive and flexible policies and practices founded on buy-in and acceptance from their communities.


Asunto(s)
COVID-19 , Niño , Humanos , Estados Unidos , COVID-19/diagnóstico , COVID-19/epidemiología , Pandemias , Instituciones Académicas , Prueba de COVID-19 , Padres
2.
Foods ; 11(17)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36076774

RESUMEN

Aqueous and ethanolic pomegranate peel extracts (PPE) were studied as a source of phenolic compounds with antimicrobial, anti-quorum sensing, and antioxidant properties. The aqueous extract showed higher total phenolic and flavonoid content (153.43 mg GAE/g and 45.74, respectively) and antioxidant capacity (DPPH radical inhibition: 86.12%, ABTS radical scavenging capacity: 958.21 mg TE/dw) compared to the ethanolic extract. The main phenolic compounds identified by UPLC-DAD were chlorogenic and gallic acids. The aqueous PPE extract showed antimicrobial activity against Listeria monocytogenes, Salmonella Typhimurium, Candida tropicalis (MICs 19-30 mg/mL), and anti-quorum sensing activity expressed as inhibition of Chromobacterium violaceum violacein production (%). The aqueous PPE extracts at 25 mg/mL applied on alfalfa sprouts reduced psychrophilic bacteria (1.12 Log CFU/100 g) and total coliforms (1.23 Log CFU/100 g) and increased the antioxidant capacity of the treated sprouts (55.13 µmol TE/100 g (DPPH) and 126.56 µmol TE/100 g (ABTS)) compared to untreated alfalfa. This study emphasizes PPE's antioxidant and antimicrobial activities in alfalfa sprouts preservation.

3.
Insects ; 13(8)2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-36005367

RESUMEN

Chili pepper is a vegetable of worldwide economic and gastronomic importance. The psyllid, Bactericera cockerelli, is an economically important pest in this crop, causing considerable losses in its production. Currently, the application of insecticides is the main way to control B. cockerelli. However, the use of varieties resistant to this insect is a viable alternative for its control and management. In this work, the oviposition rate, development, and survival of B. cockerelli in two native varieties of chili were evaluated. Choice and non-choice trials showed that the B. cockerelli oviposition was reduced on CJ-2018 by 92.17 and 80.18%, respectively, compared to the control. In CM-334, the insect showed a behavior similar to the control in the non-choice test, while in the choice test it laid more eggs on CM-334 compared to the control. The development and survival assay showed that only 1.33% of the eggs managed to reach the adult stage on CJ-2018. In contrast, on CM-334 the survival of B. cockerelli was similar to the control. These results suggest that CJ-2018 presented a resistance based on antixenosis and antibiosis against B. cockerelli.

4.
Braz J Microbiol ; 53(3): 1187-1197, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35380361

RESUMEN

Phellinus Quél is one of the largest genera of Hymenochaetaceae; it comprises about 220 species widely distributed on Earth. Most Phellinus species are lignicolous mushrooms that accumulate bioactive compounds. This research studied the phenolic composition of Phellinus spp. and their relationship with antibacterial and antiviral capacity. Phenolics were extracted from Phellinus badius, P. fastuosus, and P. grenadensis; their antiviral and antibacterial activities were evaluated against Listeria monocytogenes, Staphylococcus aureus, Salmonella enterica, and Escherichia coli O157: H7; and the bacteriophages MS2 and Φ- × 174. Gallic acid, chlorogenic acid, caffeic acid, epicatechin, ferulic acid, catechin, 1,3-dicaffeoylquinic acid, p-coumaric acid, and rutin were found in different proportions among Phellinus spp. Total phenolic content ranged from 96 to 209 mg GAE/g, and total flavonoids from 10 to 27 QE/g. The minimum inhibitory concentrations of P. badius, P. grenadensis, and P. fastuosus against E. coli O157: H7 were 13, 20, and 27 mg/mL, against S. enterica were 20, 30, and 15 mg/mL, and against L. monocytogenes were 10, 15, and 25 mg/mL, respectively. The phenolic content was better correlated with the antibacterial effect against E. coli O157: H7 and L. monocytogenes (r = 0.8-0.9), but not against S. enterica (r = 0.05). The antiviral activity of the extracts (0.9 mg/mL) was 29 to 41% against MS2 and 27 to 38% for Φ-X174 virus (r = 0.8-0.9). In silico analysis showed binding energy values of - 7.9 and - 4.8 kcal/mol between the identified phenolic compounds and the M and G proteins of each virus. The antibacterial and antiviral properties of Phellinus species were correlated with the phenolic content.


Asunto(s)
Escherichia coli O157 , Listeria monocytogenes , Antibacterianos/farmacología , Antivirales/análisis , Antivirales/farmacología , Microbiología de Alimentos , Phellinus , Fenoles/análisis , Fenoles/farmacología
5.
Biomedicines ; 9(11)2021 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-34829898

RESUMEN

Bacterial diseases and reactive oxygen species can cause dental caries and oral cancer. Therefore, the present review analyzes and discusses the antibacterial and antioxidant properties of synthetic and plant-derived substances and their current and future patents to formulate dental products. The reviewed evidence indicates that chlorhexidine, fluorides, and hydrogen peroxide have adverse effects on the sensory acceptability of oral care products. As an alternative, plant-derived substances have antimicrobial and antioxidant properties that can be used in their formulation. Also, adding plant metabolites favors the sensory acceptability of dental products compared with synthetic compounds. Therefore, plant-derived substances have antibacterial, antioxidant, and flavoring activity with the potential to be used in the formulation of toothpaste, mouth rinses, dentures cleansers-fixatives, and saliva substitutes.

6.
Molecules ; 26(1)2020 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-33375633

RESUMEN

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.


Asunto(s)
Antineoplásicos Fitogénicos/química , Asteraceae/química , Neoplasias/tratamiento farmacológico , Extractos Vegetales/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Flavonoides/química , Flores/química , Células HEK293 , Humanos , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/farmacología
7.
Molecules ; 23(9)2018 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-30213053

RESUMEN

Six new cyclodiprenyl phenols were synthesized by direct coupling of perillyl alcohol and the appropriate phenol. Their structures were established by IR, HRMS and mainly NMR. Three human cancer cell lines-breast (MCF-7), prostate (PC-3) and colon (HT-29)-were used in antiproliferative assays, with daunorubicin and dunnione as positive controls. Results described in the article suggest that dihydroxylated compounds 2⁻4 and monohydroxylated compound 5 display selectivity against cancer cell lines, cytotoxicity, apoptosis induction, and mitochondrial membrane impairment capacity. Compound 2 was identified as the most effective of the series by displaying against all cancer cell lines a cytotoxicity close to dunnione antineoplastic agent, suggesting that the cyclodiprenyl phenols from perillyl alcohol deserve more extensive investigation of their potential medicinal applications.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Fenoles/síntesis química , Fenoles/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HT29 , Humanos , Células MCF-7 , Membranas Mitocondriales/efectos de los fármacos , Estructura Molecular , Fenoles/química , Relación Estructura-Actividad
8.
Foods ; 7(8)2018 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-30061481

RESUMEN

Plant extracts have the potential to be used as food additives; however, their use have been limited by causing undesirable changes in the sensory attributes of foods. We characterized the mango seed extract as a preserving agent for fresh-cut mangoes. We established the maximum concentration of extract that, while increasing the antioxidant activity, and limiting microbial contamination of the fruit, did not negatively affect fruit sensory acceptability. The extract contained 277.4 g gallic acid equivalent (GAE)/kg dw (dry weight) of polyphenols and 143.7 g quercetin equivalent (QE)/kg dw of flavonoids. Antioxidant capacity values were 2034.1 and 4205.7 µmol Trolox equivalent (TE)/g against 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, respectively. Chromatographic analysis revealed the presence of gallic and chlorogenic acids. The extract (16 g/L) inhibited the growth of Escherichia coli, Salmonella Typhimurium, Staphylococcus aureus and Listeria monocytogenes. The highest concentration with sensory acceptability was 6.25 g/L. At such concentration, the extract preserved fresh-cut fruits, increasing polyphenols (0.427 g GAE/kg fw (fresh weight)), flavonoid content (0.234 g QE/kg fw) and antioxidant activity (DPPH = 2.814 and ABTS = 0.551 mol TE/kg fw). It also reduced inoculated bacteria (range: 5.50 × 10³ to 1.44 × 105 colony forming units (CFU)/g). These results showed the importance of considering consumer acceptability to determine the effective concentration of plant extracts as additives.

9.
World J Gastroenterol ; 24(28): 3071-3089, 2018 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-30065554

RESUMEN

Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.


Asunto(s)
Microbioma Gastrointestinal/fisiología , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori/fisiología , Interacciones Huésped-Patógeno/fisiología , Inflamación/fisiopatología , Coevolución Biológica/fisiología , Mucosa Gástrica/microbiología , Mucosa Gástrica/fisiopatología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Humanos , Inflamación/microbiología
10.
Artículo en Inglés | MEDLINE | ID: mdl-29552079

RESUMEN

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells.

11.
Artículo en Inglés | MEDLINE | ID: mdl-28401064

RESUMEN

Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.


Asunto(s)
Ciclina D1/metabolismo , Mucosa Gástrica/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Hipoxia de la Célula , Línea Celular , Ciclina D1/farmacología , Mucosa Gástrica/microbiología , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Transportador de Glucosa de Tipo 1/efectos de los fármacos , Transportador de Glucosa de Tipo 1/metabolismo , Interacciones Huésped-Patógeno , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/farmacología , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , ARN Mensajero/análisis , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas , Serina-Treonina Quinasas TOR/efectos de los fármacos , Factores de Transcripción/metabolismo , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Cancer Lett ; 372(1): 10-23, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26718258

RESUMEN

Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells. Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells. To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data. Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Lactonas/farmacología , Melanoma Experimental/tratamiento farmacológico , Sesquiterpenos/farmacología , Carga Tumoral/efectos de los fármacos , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina B1/metabolismo , Ciclina D1/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Proteínas Inhibidoras de la Apoptosis/metabolismo , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Proteínas Represoras/metabolismo , Transducción de Señal/efectos de los fármacos , Survivin , Factores de Tiempo
13.
World J Gastroenterol ; 21(45): 12742-56, 2015 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-26668499

RESUMEN

The sequence of events associated with the development of gastric cancer has been described as "the gastric precancerous cascade". This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.


Asunto(s)
Epigénesis Genética , Mucosa Gástrica/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Lesiones Precancerosas/microbiología , Neoplasias Gástricas/metabolismo , Animales , Proteínas Bacterianas/metabolismo , Proteínas de Ciclo Celular/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Daño del ADN , Metilación de ADN , Mucosa Gástrica/patología , Gastritis/diagnóstico , Gastritis/genética , Regulación Neoplásica de la Expresión Génica , Glicoproteínas/genética , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/genética , Helicobacter pylori/enzimología , Interacciones Huésped-Patógeno , Humanos , MicroARNs/genética , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Virulencia , gamma-Glutamilciclotransferasa/metabolismo
14.
Genes (Basel) ; 6(2): 436-50, 2015 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-26110319

RESUMEN

The initiation step of DNA replication is the crucial determinant of proliferation in all organisms. This step depends on the specific interaction of DNA sequences present at origins of DNA replication and their cognate activators. We wished to explore the hypothesis that the presence of ectopic origin copies may interfere with proper genome duplication. Bacteriophage λ was used as a model system. To this end, the outcome of an infection of an E. coli strain harboring ectopic copies of the λ origin region was analyzed. By measuring the effect on the host growth, viral production, and electro-microscopic visualization of the resulting λ replicative intermediates, we concluded that the ectopic copies had prevented the normal initiation step of λ DNA replication. These results suggest that DNA decoys encoding viral origins could constitute effective tools to specifically arrest viral proliferation.

15.
Biochim Biophys Acta ; 1852(5): 693-708, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25572853

RESUMEN

A considerable body of evidence exists implicating high levels of free saturated fatty acids in beta pancreatic cell death, although the molecular mechanisms and the signaling pathways involved have not been clearly defined. The membrane protein caveolin-1 has long been implicated in cell death, either by sensitizing to or directly inducing apoptosis and it is normally expressed in beta cells. Here, we tested whether the presence of caveolin-1 modulates free fatty acid-induced beta cell death by reexpressing this protein in MIN6 murine beta cells lacking caveolin-1. Incubation of MIN6 with palmitate, but not oleate, induced apoptotic cell death that was enhanced by the presence of caveolin-1. Moreover, palmitate induced de novo ceramide synthesis, loss of mitochondrial transmembrane potential and reactive oxygen species (ROS) formation in MIN6 cells. ROS generation promoted caveolin-1 phosphorylation on tyrosine-14 that was abrogated by the anti-oxidant N-acetylcysteine or the incubation with the Src-family kinase inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7(dimethylethyl)pyrazolo[3,4-d]pyrimidine). The expression of a non-phosphorylatable caveolin-1 tyrosine-14 to phenylalanine mutant failed to enhance palmitate-induced apoptosis while for MIN6 cells expressing the phospho-mimetic tyrosine-14 to glutamic acid mutant caveolin-1 palmitate sensitivity was comparable to that observed for MIN6 cells expressing wild type caveolin-1. Thus, caveolin-1 expression promotes palmitate-induced ROS-dependent apoptosis in MIN6 cells in a manner requiring Src family kinase mediated tyrosine-14 phosphorylation.


Asunto(s)
Apoptosis/efectos de los fármacos , Caveolina 1/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Palmitatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/farmacología , Animales , Western Blotting , Caveolina 1/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/farmacología , Peróxido de Hidrógeno/farmacología , Células Secretoras de Insulina/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos C57BL , Microscopía Confocal , Oxidantes/farmacología , Fosforilación/efectos de los fármacos , Pirimidinas/farmacología , Esfingosina/análogos & derivados , Esfingosina/farmacología , Tirosina/metabolismo , Familia-src Quinasas/antagonistas & inhibidores , Familia-src Quinasas/metabolismo
16.
Mol Cancer ; 13: 209, 2014 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-25204429

RESUMEN

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and ß-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-ß-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased ß-catenin protein levels, ß-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced ß-catenin protein levels and ß-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced ß-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.


Asunto(s)
Proteínas Inhibidoras de la Apoptosis/metabolismo , Melanoma Experimental/irrigación sanguínea , Neovascularización Patológica/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Represoras/metabolismo , Transcripción Genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , beta Catenina/metabolismo , Animales , Pollos , Membrana Corioalantoides/metabolismo , Regulación hacia Abajo , Femenino , Células HEK293 , Humanos , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Neovascularización Patológica/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Survivin , Factor A de Crecimiento Endotelial Vascular/genética
17.
Biochem Pharmacol ; 91(2): 168-80, 2014 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-25058527

RESUMEN

Hepatocellular carcinoma is one of the most frequent tumor types worldwide and oxidative stress represents a major risk factor in pathogenesis of liver diseases leading to HCC. Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor activated by oxidative stress that governs the expression of many genes which constitute the antioxidant defenses of the cell. In addition, oxidative stress activates AMP-activated protein kinase (AMPK), which has emerged in recent years as a kinase that controls the redox-state of the cell. Since both AMPK and Nrf2 are involved in redox homeostasis, we investigated whether there was a crosstalk between the both signaling systems in hepatocarcinoma cells. Here, we demonstrated that AMPK activator AICAR, in contrary to the A769662 allosteric activator, induces Nrf2 activation and concomitantly modulates the basal redox state of the hepatocarcinoma cells. When the expression of Nrf2 is knocked down, AICAR failed to induce its effect on redox state. These data highlight a major role of Nrf2 signaling pathway in mediating the AICAR effect on basal oxidative state. Furthermore, we demonstrated that AICAR metabolization by the cell is required to induce Nrf2 activation while, the silencing of AMPK does not have any effect on Nrf2 activation. This suggests that AICAR-induced Nrf2 activation is independent of AMPK activity. In conclusion, we identified AICAR as a potent modulator of the redox state of human hepatocarcinoma cells, via the Nrf2 signaling pathway and in an AMPK-independent mechanism.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ribonucleósidos/farmacología , Proteínas Quinasas Activadas por AMP/genética , Transporte Activo de Núcleo Celular/fisiología , Aminoimidazol Carboxamida/farmacología , Compuestos de Bifenilo , Carcinoma Hepatocelular/etiología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/fisiología , Silenciador del Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch , Neoplasias Hepáticas/etiología , Factor 2 Relacionado con NF-E2/genética , Fosforilación , Pironas/farmacología , Tiofenos/farmacología
18.
Mol Syst Biol ; 10: 722, 2014 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-24682507

RESUMEN

The metazoan genome is replicated in precise cell lineage-specific temporal order. However, the mechanism controlling this orchestrated process is poorly understood as no molecular mechanisms have been identified that actively regulate the firing sequence of genome replication. Here, we develop a mechanistic model of genome replication capable of predicting, with accuracy rivaling experimental repeats, observed empirical replication timing program in humans. In our model, replication is initiated in an uncoordinated (time-stochastic) manner at well-defined sites. The model contains, in addition to the choice of the genomic landmark that localizes initiation, only a single adjustable parameter of direct biological relevance: the number of replication forks. We find that DNase-hypersensitive sites are optimal and independent determinants of DNA replication initiation. We demonstrate that the DNA replication timing program in human cells is a robust emergent phenomenon that, by its very nature, does not require a regulatory mechanism determining a proper replication initiation firing sequence.


Asunto(s)
Cromatina/ultraestructura , Momento de Replicación del ADN/genética , Replicación del ADN/genética , Cromatina/genética , Genoma Humano , Humanos , Modelos Genéticos , Origen de Réplica/genética
19.
Helicobacter ; 19(3): 182-93, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24628778

RESUMEN

BACKGROUND: Helicobacter pylori is a motile microaerophilic bacterium that colonizes the human stomach. H. pylori infection triggers gastric diseases, such as gastritis, peptic ulcer and gastric cancer. Stomach represents a barrier for microorganism colonization, particularly because of its high hydrochloric acid concentration. The main mechanism developed by H. pylori to maintain intracellular pH homeostasis in this environment is the urease activity. However, urease negative strains can be also isolated from clinical samples, suggesting that H. pylori presents other components involved in acid resistance. OBJECTIVE: Here, we present some evidence that the arginine decarboxylase gene (speA) in H. pylori could be involved in an acid adaptation mechanism similar to the one in Enterobacteriaceae, which is dependent on the presence of arginine. METHODS: Indeed, speA mRNA and protein expression are acutely induced by acid stress. RESULTS: Moreover, we showed that H. pylori uses arginine in an acid response mechanism required for its growth in acid conditions. CONCLUSION: Altogether, these results provide novel information regarding the H. pylori physiology and acid response mechanism.


Asunto(s)
Ácidos/toxicidad , Carboxiliasas/metabolismo , Tolerancia a Medicamentos , Helicobacter pylori/enzimología , Helicobacter pylori/fisiología , Carboxiliasas/genética , Perfilación de la Expresión Génica , Helicobacter pylori/genética , Homeostasis , Humanos , Concentración de Iones de Hidrógeno
20.
J Food Sci ; 79(2): R129-37, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24446991

RESUMEN

Many food preservation strategies can be used for the control of microbial spoilage and oxidation; however, these quality problems are not yet controlled adequately. Although synthetic antimicrobial and antioxidant agents are approved in many countries, the use of natural safe and effective preservatives is a demand of food consumers and producers. This paper proposes medicinal plants, traditionally used to treat health disorders and prevent diseases, as a source of bioactive compounds having food additive properties. Medicinal plants are rich in terpenes and phenolic compounds that present antimicrobial and antioxidant properties; in addition, the literature revealed that these bioactive compounds extracted from other plants have been effective in food systems. In this context, the present hypothesis paper states that bioactive molecules extracted from medicinal plants can be used as antimicrobial and antioxidant additives in the food industry.


Asunto(s)
Antiinfecciosos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Conservantes de Alimentos/aislamiento & purificación , Modelos Biológicos , Plantas Medicinales/química , Antiinfecciosos/efectos adversos , Antiinfecciosos/química , Antioxidantes/efectos adversos , Antioxidantes/química , Comportamiento del Consumidor , Etnofarmacología , Conservantes de Alimentos/efectos adversos , Conservantes de Alimentos/química , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...