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1.
Environ Sci Pollut Res Int ; 30(17): 49685-49702, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36780079

RESUMO

Even if Archaea deliver important ecosystem services and are major players in global biogeochemical cycles, they remain poorly understood in freshwater ecosystems. To our knowledge, no studies specifically address the direct impact of xenobiotics on the riverine archaeome. Using environmental DNA metabarcoding of the 16S ribosomal gene, we previously demonstrated bacterial communities significant shifts linked to pollutant mixtures during an extreme flood in a typical Mediterranean coastal watercourse. Here, using the same methodology, we sought to determine whether archaeal community shifts coincided with the delivery of environmental stressors during the same flood. Further, we wanted to determine how archaea taxa compared at different seasons. In contrast to the bacteriome, the archaeome showed a specific community in summer compared to winter and autumn. We also identified a significant relationship between in situ archaeome shifts and changes in physicochemical parameters along the flood, but a less marked link to those parameters correlated to river hydrodynamics than bacteria. New urban-specific archaeal taxa significantly related to multiple stressors were identified. Through statistical modeling of both domains, our results demonstrate that Archaea, seldom considered as bioindicators of water quality, have the potential to improve monitoring methods of watersheds.


Assuntos
Archaea , Ecossistema , Archaea/genética , Estações do Ano , RNA Ribossômico 16S/genética , Bactérias/genética , Rios/microbiologia
2.
Front Vet Sci ; 9: 919454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353254

RESUMO

Large animal models of acute myocardial infarction (AMI) play a crucial role in translating novel therapeutic approaches to patients as denoted by their use in the right-before-human testing platform. At present, the porcine model of AMI is used most frequently as it mimics the human condition and its anatomopathological features accurately. We want to describe to, and share with, the translational research community our experience of how different anaesthetic protocols (sevoflurane, midazolam, ketamine+xylazine+midazolam, and propofol) and pig breeds [Large White and Landrace x Large White (LLW)] can dramatically modify the outcomes of a well-established porcine model of closed-chest AMI. Our group has extensive experience with the porcine model of reperfused AMI and, over time, we reduced the time of ischaemia used to induce the disease from 90 to 50 min to increase the salvageable myocardium for cardioprotection studies. For logistical reasons, we changed both the anaesthetic protocol and the pig breed used, but these resulted in a dramatic reduction in the size of the myocardial infarct, to almost zero in some cases (sevoflurane, 50-min ischaemia, LLW, 2.4 ± 3.9% infarct size), and the cardiac function was preserved. Therefore, we had to re-validate the model by returning to 90 min of ischaemia. Here, we report the differences in infarct size and cardiac function, measured by different modalities, for each combination of anaesthetic protocol and pig breed we have used. Furthermore, we discuss these combinations and the limited literature pertaining to how these two factors influence cardiac function and infarct size in the porcine model of AMI.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36232192

RESUMO

This paper examines horizontally differentiated duopolies à la Hotelling with environmentally conscious consumers and a planner promoting a sustainable good with costly awareness campaigns (ACs). The objective is to find the planner's optimal strategies and their effects on the firms' behaviour. The analysis is carried out with two approaches, considering a private and a public duopoly. In both, it is shown that the planner chooses the average characteristic supported by a higher intensity campaign. However, with the private one, such an outcome is possible if the planner has minimal resources. Consumer consciousness and ACs have opposite effects on the firms and the planner. It is proven that consumer awareness favours the interests of the duopolies and reduces those of the planner, while the contrary is true for ACs. Finally, it is shown that a public duopoly is the best scenario for sustainability. This study provides an environmental policy to replace or complement traditional instruments and a more suitable business framework to achieve efficient results.


Assuntos
Comércio , Estado de Consciência , Política Ambiental
4.
Cell Death Dis ; 13(10): 906, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302756

RESUMO

Oncogenic transformation leads to changes in glutamine metabolism that make transformed cells highly dependent on glutamine for anabolic growth and survival. Herein, we investigated the cell death mechanism activated in glutamine-addicted tumor cells in response to the limitation of glutamine metabolism. We show that glutamine starvation triggers a FADD and caspase-8-dependent and mitochondria-operated apoptotic program in tumor cells that involves the pro-apoptotic TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), but is independent of its cognate ligand TRAIL. In glutamine-depleted tumor cells, activation of the amino acid-sensing general control nonderepressible-2 kinase (GCN2) is responsible for TRAIL-R2 upregulation, caspase-8 activation, and apoptotic cell death. Interestingly, GCN2-dependent ISR signaling induced by methionine starvation also leads to TRAIL-R2 upregulation and apoptosis. Moreover, pharmacological inhibition of transaminases activates a GCN2 and TRAIL-R2-dependent apoptotic mechanism that is inhibited by non-essential amino acids (NEAA). In addition, metabolic stress upon glutamine deprivation also results in GCN2-independent FLICE-inhibitory protein (FLIP) downregulation facilitating caspase-8 activation and apoptosis. Importantly, downregulation of the long FLIP splice form (FLIPL) and apoptosis upon glutamine deprivation are inhibited in the presence of a membrane-permeable α-ketoglutarate. Collectively, our data support a model in which limiting glutamine utilization in glutamine-addicted tumor cells triggers a previously unknown cell death mechanism regulated by GCN2 that involves the TRAIL-R2-mediated activation of the extrinsic apoptotic pathway.


Assuntos
Glutamina , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Caspase 8/metabolismo , Glutamina/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases/metabolismo
7.
Food Chem ; 337: 127970, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919270

RESUMO

High tannin content in sorghum grains is an undesirable characteristic for poultry and pig feeding and represents a challenge for breeding programs. On the other hand, moderate content of tannins in sorghum may be beneficial in human diets because they exert anti-cancer, anti-inflammatory and reduced carbohydrate uptake effects, among others. The aim of this study was to compare tannin contents of twenty sorghum cultivars available in Brazil, as well as to compare results obtained with four methods of tannin quantification: butanol/HCl, vanillin/HCl, BSA/FeCl3 and PVPP/Folin-Ciocalteu. The results obtained with butanol/HCl and vanillin/HCl were higher than with BSA/FeCl3 and PVPP/Folin-Ciocalteu. A known amount of purified quebracho tannin was used to test the validation of methods of tannin quantification and vanillin/HCl stood out for its high accuracy degree. The sampling used reveals wide genetic diversity regarding tannin contents. The expectation of predicting tannin contents on basis of grain color seems unfeasible.


Assuntos
Sorghum/química , Taninos/análise , Técnicas de Química Analítica/métodos , Grão Comestível/química
8.
Sci Total Environ ; 732: 139047, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32473395

RESUMO

Rivers are representative of the overall contamination found in their catchment area. Contaminant concentrations in watercourses depend on numerous factors including land use and rainfall events. Globally, in Mediterranean regions, rainstorms are at the origin of fluvial multipollution phenomena as a result of Combined Sewer Overflows (CSOs) and floods. Large loads of urban-associated microorganisms, including faecal bacteria, are released from CSOs which place public health - as well as ecosystems - at risk. The impacts of freshwater contamination on river ecosystems have not yet been adequately addressed, as is the case for the release of pollutant mixtures linked to extreme weather events. In this context, microbial communities provide critical ecosystem services as they are the only biological compartment capable of degrading or transforming pollutants. Through the use of 16S rRNA gene metabarcoding of environmental DNA at different seasons and during a flood event in a typical Mediterranean coastal river, we show that the impacts of multipollution phenomena on structural shifts in the particle-attached riverine bacteriome were greater than those of seasonality. Key players were identified via multivariate statistical modelling combined with network module eigengene analysis. These included species highly resistant to pollutants as well as pathogens. Their rapid response to contaminant mixtures makes them ideal candidates as potential early biosignatures of multipollution stress. Multiple resistance gene transfer is likely enhanced with drastic consequences for the environment and human-health, particularly in a scenario of intensification of extreme hydrological events.


Assuntos
Ecossistema , Monitoramento Ambiental , Poluentes Ambientais , Região do Mediterrâneo , RNA Ribossômico 16S , Rios
9.
Artigo em Inglês | MEDLINE | ID: mdl-31357381

RESUMO

Skipping breakfast might have an impact on cognitive functions, such as interference, which is a basic capacity of executive functions that denotes the possibility of controlling an automated response. This study aimed to analyze the association between nutritional quality of breakfast and cognitive interference in a sample of university students. A cross-sectional study was conducted, a total of 422 students between 18 and 25 years participated. Cognitive interference was assessed with the Stroop Test. Breakfast was assessed with a questionnaire assigning a score for each serving of each food group that was consumed. Logistic regression models were performed. The performance in cognitive tasks was slower in those who had a poor breakfast (32.9 ± 6 vs 29.3 ± 6 s, p < 0.050). Poor cognitive interference was greater in students with poor breakfast (53% versus 23%, p = 0.001). A slower word reading was associated with skipping vegetables (OR: 2.78, 95% CI: 0.09-2.13), and cereals (OR: 1.70, 95% CI: 1.03-2.81). Wrong color identification was associated with skipping fruits (OR: 1.55, 95% CI: 1.43-1.99) and animal protein sources (OR: 1.63, 95% CI: 1.07-2.49). Skipping fat-rich cereals was a protector factor (OR: 0.55, 95% CI: 0.36-0.85). Difficulty in the ability to inhibit interference was associated with skipping vegetables (OR: 2.72, 95% CI: 1.25-4.80) and cereals (OR: 2.65, 95% CI: 1.28-4.68). The nutritional quality of breakfast was associated with the time spent answering the Stroop test, but not with cognitive interference.


Assuntos
Desjejum/psicologia , Cognição , Função Executiva , Comportamento Alimentar/psicologia , Valor Nutritivo , Estudantes/psicologia , Adolescente , Adulto , Estudos Transversais , Inquéritos sobre Dietas , Grão Comestível , Feminino , Frutas , Humanos , Modelos Logísticos , Masculino , México , Universidades , Saúde da População Urbana , Verduras , Adulto Jovem
10.
Cell Death Dis ; 10(2): 51, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30718520

RESUMO

Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM kinases are serine/threonine kinases that promote cell survival and proliferation and are highly expressed in different tumors. In this work, we studied the role of PIM kinases as regulators of TRAIL sensitivity in GBM cells. Remarkably, PIM inhibition or knockdown facilitated activation by TRAIL of a TRAIL-R2/DR5-mediated and mitochondria-operated apoptotic pathway in TRAIL-resistant GBM cells. The sensitizing effect of PIM knockdown on TRAIL-induced apoptosis was mediated by enhanced caspase-8 recruitment to and activation at the death-inducing signaling complex (DISC). Interestingly, TRAIL-induced internalization of TRAIL-R2/DR5 was significantly reduced in PIM knockdown cells. Phospho-proteome profiling revealed a decreased phosphorylation of p62/SQSTM1 after PIM knockdown. Our results also showed an interaction between p62/SQSTM1 and the DISC that was reverted after PIM knockdown. In line with this, p62/SQSTM1 ablation increased TRAIL-R2/DR5 levels and facilitated TRAIL-induced caspase-8 activation, revealing an inhibitory role of p62/SQSTM1 in TRAIL-mediated apoptosis in GBM. Conversely, upregulation of TRAIL-R2/DR5 upon PIM inhibition and apoptosis induced by the combination of PIM inhibitor and TRAIL were abrogated by a constitutively phosphorylated p62/SQSTM1S332E mutant. Globally, our data represent the first evidence that PIM kinases regulate TRAIL-induced apoptosis in GBM and identify a specific role of p62/SQSTM1Ser332 phosphorylation in the regulation of the extrinsic apoptosis pathway activated by TRAIL.


Assuntos
Glioblastoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteína Sequestossoma-1/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Transfecção
11.
Clin Optom (Auckl) ; 10: 103-108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319301

RESUMO

PURPOSE: The aim of this study was to show the potential applicability of optical coherence tomography angiography (OCTA) for the evaluation of the peripheral fitting of fully scleral contact lenses. METHODS: A pilot study was proposed fitting three different scleral contact lenses (Irregular Corneal Design [ICD]) with different sagittal heights (4200, 4800, and 5600 mm) in a healthy volunteer of 27 years old. We evaluated by means of optical coherence tomography (OCT, DRI Triton) the apical clearance achieved with each of the three lenses fitted. The impact over scleral flow was assessed with the OCTA module of the same device. RESULTS: The apical clearance was 310, 901, and 1680 µm with the scleral lenses of sagittal heights 4200, 4800, and 5600 µm, respectively. With OCTA, we evaluated the impact of the lens bearing on the conjunctival vascular flow, observing an area of vascular interruption of 0, 25, and 75% with the lenses of 4200, 4800, and 5600 µm of sagittal heights, respectively. The vascular interruption was induced in the perilimbar area, suggesting the need of readjusting the limbal clearance zone of the lens. CONCLUSION: Fully scleral contact lens fitting may be optimized with the use of OCTA, allowing the practitioner to perform the fitting with better control of the peripheral bearing of the lens on the conjunctival tissue, assessing the impact on vascular structures. This potential use of OCTA must be investigated further in future studies including large samples of eyes.

12.
Environ Sci Pollut Res Int ; 25(7): 6107-6121, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29285698

RESUMO

Concentrations of pharmaceutically active compounds (PACs) in freshwater systems depend on numerous factors such as land use and hydrometeorological conditions. In the Mediterranean, heavy rain events are of particular importance as they highly influence the concentration of micropollutants found in freshwater and are a source of recurrent first foul flushes due to combined sewer overflows (CSOs). In this study, we seek to assess the dynamics of pharmaceuticals during storm events in coastal Mediterranean rivers at a fine scale and to determine their contribution to multicontamination phenomena owing to CSOs. Our results showed that, while dissolved PACs followed the same trend as other contaminants, i.e., they increased significantly during CSOs, PACs in the total fraction did not peak yet maintained their already high concentrations for slightly longer due to their release via CSOs. Pharmaceutical concentrations for both the dissolved and the total fraction were dramatically diluted during the peak river flow. A fine-scale follow-up of PACs dynamics in the total fraction, including the differentiation of sewer overflows from both the right and left river banks, as well as the analyses of a large amount of PACs molecules, allowed us to clearly identify their major sources. While domestic inputs were dominated by nicotine and caffeine, the use of gadolinium (an MRI contrast agent) as a marker, attributed the main source of medical drugs such as tramadol, ibuprofen, and diclofenac to the major public hospital of the region. Thus, identifying major sources of PACs and implementing adapted water treatments directly at those sources would be the most cost-efficient alternative to cope with pharmaceutical drugs in coastal Mediterranean aquatic environments. Moreover, PACs behavior differed depending on the molecules considered and the source of these molecules, but we could not establish a direct link between their behavior and their chemical or physical properties. Our study highlights the importance of monitoring at strategic locations and with a high frequency sampling in order to better understand fate, sources, and behavior of pharmaceuticals in aquatic environments.


Assuntos
Monitoramento Ambiental/métodos , Preparações Farmacêuticas/análise , Chuva/química , Rios/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Clima , França , Região do Mediterrâneo , Estações do Ano
13.
Oncotarget ; 8(55): 93688-93703, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212182

RESUMO

Oncogenic transformation triggers reprogramming of cell metabolism, as part of the tumorigenic process. However, metabolic reprogramming may also increase the sensitivity of transformed cells to microenvironmental stress, at the early stages of tumor development. Herein, we show that transformation of human breast epithelial cells by the p95HER2/611CTF oncogene markedly sensitizes these cells to metabolic stress induced by the simultaneous inhibition of glucose and glutamine metabolism. In p95HER2/611CTF-transformed cells, metabolic stress activates a TNF related apoptosis-inducing ligand (TRAIL)-R and caspase-8-dependent apoptotic process that requires prior down-regulation of cellular FLICE-like inhibitor protein (c-FLIP) levels. Importantly, sustained mTOR activation is involved in FLIP down-regulation and apoptosis induced by metabolic stress. In vivo experiments in immunodeficient mice demonstrate a requirement for caspase-8 in restraining primary tumor growth of xenografts with p95HER2/611CTF-transformed cells. Collectively, these data define a critical role of the extrinsic pathway of apoptosis in the control of tumor initiation by microenvironmental cues.

14.
J Dev Behav Pediatr ; 38 Suppl 1: S82-S83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28141731

RESUMO

CASE: Pedro is a 2-year 7-month-old boy who was presented for the first time after a visit to a local emergency room (ER) for diarrhea. At the time of his birth, his undocumented mother, Clara, was 20 years old, uninsured, and with limited English proficiency living approximately 400 miles south of our practice in a different state. Although she had been brought to the United States as a child, she had never finished high school. Pedro was born what mother thought was full-term at his parent's home, where a lay midwife assisted during the delivery. Pedro was not brought to a medical facility at birth; therefore, neither medical nor legal documentation of his birth in the United States, or elsewhere, existed.After enduring 4 years of ongoing verbal and physical abuse, Clara fled to her maternal aunt in our community. The child's initial exposure to medical care was during the emergency visit, which ended up in referral to us. The ED physician suggested that the child visit a primary care physician, but establishment of pediatric care was not made until months later. The child received his first vaccines and immediately was referred to the Growth and Nutrition clinic due to mild wasting and stunting based on Waterlow criteria.Pedro speaks both English and Spanish and has no 2-word combinations and a 50-word combined vocabulary in English and Spanish. In addition, a complete blood count was consistent with iron deficiency anemia, but both sickle cell and G6PD screening are negative.The nutritionist from the specialty clinic obtained a detailed history including overall appetite, feeding skills, meal plans, and eating environment noting that the child was a competent finger feeder. The family's meals were distributed throughout the day as a meal at home and a shared fast food meal while accompanying mother, as she worked as a hair stylist 6 days per week. In addition, the diet is supplemented by ricewater mixed with sugar and ground carrots throughout the day.Where would you head next?REFERENCE1. Waterlow JC. Classification and definition of protein-calorie malnutrition. Br Med J. 1972;3:566-569.


Assuntos
Insuficiência de Crescimento/diagnóstico , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Imigrantes Indocumentados/legislação & jurisprudência , Pré-Escolar , Insuficiência de Crescimento/terapia , Humanos , Transtornos do Desenvolvimento da Linguagem/terapia , Masculino
15.
Sci Total Environ ; 579: 10-21, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27871755

RESUMO

Contaminants found in watercourses are not only the result of anthropogenic activities but also depend on river's seasonal hydrodynamics. This is particularly true in Mediterranean climate regions where long dry periods are interrupted by strong rainfalls. Storm events remobilize particles from soils and sediments and, as a consequence, the load of particulate matter in rivers can be quite considerable, severely affecting water quality. Nevertheless, an absence of fieldwork studies exists concerning the simultaneous dynamics of mixtures of pollutants in river waters, particularly during strong rainfalls and floods. Our study assessed the concentrations of six families of pollutants, including pesticides, at these events, and compared them to those observed at drought sampling periods. We have used as model a typical Mediterranean coastal river from Southeast France, the Têt River, whose hydrodynamics and major elements fluxes have been fairly investigated. As expected, our results show that chemical mixtures due to human activities occur and that they are particularly relevant during storm events. But the results of our study argue that exceptional multicontamination phenomena actually happen more often than expected because they are linked to recurrent sudden intense rainfall events in the Mediterranean. In particular, combined sewer overflows are responsible for this major issue in urbanized areas, whereas runoff and leaching will be the most important sources of pollutant mixtures occurring at flood flow peak. After an overview of the sources responsible for chronic multiple stressors events in regions under a Mediterranean climate regime worldwide, we revisit best management measures to reduce risks from the presence of chemical mixtures in the environment.

16.
Cir Esp ; 93(8): 530-5, 2015 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25659535

RESUMO

INTRODUCTION: Dynamic endoanal ultrasound has emerged in recent years as a test that could replace the now existing tests in the diagnosis of pelvic floor disorders. The aim of this paper is to determine the usefulness of echodefecography in the diagnosis and evaluation of patients with symptoms of anorrectal obstruction, and show the results obtained after its implementation in a pelvic floor unit, as a complementary tool that could replace conventional defecography. METHODS: In this retrospective study we analyzed 66 patients with a mean age of 55 years (19-83), 61 women (92%). All dynamic ultrasound was performed in 3 dimensions and was correlated with symptoms and physical findings in the consultation. A descriptive and inferential study was performed to find a kappa correlation between physical examination and echodefecography. RESULTS: The reasons for consultation were: Anorrectal obstruction syndrome 36 patients (54.5%), pelvic organ prolapse 27 patients (40.9%), and anorrectal obstruction syndrome along with pelvic organ prolapse 3 patients (4.5%). The correlation of the 2 groups indicated that echodefecography diagnosed more patients with grade III rectocele, enteroceles, and anismus than the combination of scan-ultrasound-manometry-proctoscopy (Kappa 0.26, 0.38 and 0.21, 95% CI: from 0,07 to 1.00, 0.15 to 1.00 and from 0.12 to 1.00, respectively) (P<.001). Conversely, echodefecography diagnosed less perineal descense (Kappa 0.28, 95% CI: 0.12 to 1.00). CONCLUSIONS: Dynamic anal ultrasonography may have a role as a complementary test in patients with pelvic floor disorders, achieving diagnoses that would go undetected by inspection, physical examination and manometry.


Assuntos
Imageamento Tridimensional , Distúrbios do Assoalho Pélvico/diagnóstico por imagem , Diafragma da Pelve/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Defecografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Cancer Res ; 74(6): 1766-77, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24453000

RESUMO

HER2/Neu/ERBB2 is a receptor tyrosine kinase overexpressed in approximately 20% of human breast tumors. Truncated or mutant isoforms that show increased oncogenicity compared with the wild-type receptor are found in many breast tumors. Here, we report that constitutively active ERBB2 sensitizes human breast epithelial cells to agents that induce endoplasmic reticulum stress, altering the unfolded protein response (UPR) of these cells. Deregulation of the ERK, AKT, and mTOR activities elicited by mutant ERBB2 was involved in mediating this differential UPR response, elevating the response to endoplasmic reticulum stress, and apoptotic cell death. Mechanistic investigations revealed that the increased sensitivity of mutant ERBB2-expressing cells to endoplasmic reticulum stress relied upon a UPR effector signaling involving the PERK-ATF4-CHOP pathway, upregulation of the proapoptotic cell surface receptor TRAIL-R2, and activation of proapoptotic caspase-8. Collectively, our results offer a rationale for the therapeutic exploration of treatments inducing endoplasmic reticulum stress against mutant ERBB2-expressing breast tumor cells.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Sistema de Sinalização das MAP Quinases , Receptor ErbB-2/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Linhagem Celular Tumoral , Humanos , Receptor Cross-Talk , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Tapsigargina/farmacologia , Fator de Transcrição CHOP/metabolismo , Resposta a Proteínas não Dobradas
18.
Curr Pharm Des ; 20(17): 2819-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23944369

RESUMO

Activation of cell surface death receptors of the tumor necrosis factor (TNF) receptor superfamily by the appropriate ligands represents an attractive therapeutic strategy to induce cell death by apoptosis in cancer cells. However, the toxic effects of TNF-alpha and CD95/Fas ligand (FasL) in normal tissues have significantly hampered the clinical application of these ligands in cancer treatment. TNF-related apoptosis-inducing ligand (TRAIL/APO-2L), another member of the TNF family, has been shown to induce apoptosis selectively in many tumor cell lines. Interestingly, TRAIL treatment also results in significant growth suppression of TRAIL-sensitive human cancer xenografts in mice and nonhuman primates. At the same time, recombinant TRAIL and agonistic TRAIL receptor antibodies show no significant cytotoxicity in these studies. Despite some adverse effects of certain TRAIL preparations, activation of proapoptotic TRAIL receptors represents a promising approach in cancer therapy. Herein we review what is known about proapoptotic TRAIL signaling, the role of intracellular survival pathways in the regulation of resistance to TRAIL and the activation of non-apoptotic signaling by TRAIL. We also discuss the role of the TRAIL system in tumorigenesis and the results of clinical trials with recombinant TRAIL and various TRAIL receptor agonistic antibodies, either as monotherapy or in combination with targeted or conventional chemotherapy.


Assuntos
Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Transformação Celular Neoplásica/metabolismo , Humanos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/agonistas , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
19.
J Dev Behav Pediatr ; 33(7): 590-1, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22947886

RESUMO

REFERENCE: Pedro is a 2-year 7-month-old boy who was presented for the first time after a visit to a local emergency room (ER) for diarrhea. At the time of his birth, his undocumented mother, Clara, was 20 years old, uninsured, and with limited English proficiency living approximately 400 miles south of our practice in a different state. Although she had been brought to the United States as a child, she had never finished high school. Pedro was born what mother thought was full-term at his parent's home, where a lay midwife assisted during the delivery. Pedro was not brought to a medical facility at birth; therefore, neither medical nor legal documentation of his birth in the United States, or elsewhere, existed.After enduring 4 years of ongoing verbal and physical abuse, Clara fled to her maternal aunt in our community. The child's initial exposure to medical care was during the emergency visit, which ended up in referral to us. The ED physician suggested that the child visit a primary care physician, but establishment of pediatric care was not made until months later. The child received his first vaccines and immediately was referred to the Growth and Nutrition clinic due to mild wasting and stunting based on Waterlow criteria.Pedro speaks both English and Spanish and has no 2-word combinations and a 50-word combined vocabulary in English and Spanish. In addition, a complete blood count was consistent with iron deficiency anemia, but both sickle cell and G6PD screening are negative.The nutritionist from the specialty clinic obtained a detailed history including overall appetite, feeding skills, meal plans, and eating environment noting that the child was a competent finger feeder. The family's meals were distributed throughout the day as a meal at home and a shared fast food meal while accompanying mother, as she worked as a hair stylist 6 days per week. In addition, the diet is supplemented by rice water mixed with sugar and ground carrots throughout the day.Where would you head next?


Assuntos
Serviços de Saúde da Criança/normas , Transtornos da Nutrição Infantil/terapia , Insuficiência de Crescimento/terapia , Adulto , Pré-Escolar , Insuficiência de Crescimento/diagnóstico , Feminino , Humanos , Masculino , Maus-Tratos Conjugais/psicologia , Estados Unidos , Adulto Jovem
20.
FEMS Microbiol Ecol ; 82(3): 616-28, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22703298

RESUMO

Marine waterlogged woods on the ocean floor provide the foundation for an ecosystem resulting in high biomass and potentially high macrofaunal diversity, similarly to other large organic falls. However, the microorganisms forming the base of wood fall ecosystems remain poorly known. To study the microbial diversity and community structure of sunken woods, we analyzed over 2800 cloned archaeal and bacterial 16S rRNA gene sequences from samples with different geographic locations, depths, and immersion times. The microbial communities from different wood falls were diverse, suggesting that sunken woods provide wide-ranging niches for microorganisms. Microorganisms dwelling at sunken woods change with time of immersion most likely due to a change in chemistry of the wood. We demonstrate, for the first time in sunken woods, the co-occurrence of free-living sulfate-reducing bacteria and methanogens and the presence of sulfide oxidizers. These microorganisms were similar to those of other anaerobic chemoautotrophic environments suggesting that large organic falls can provide similar reduced habitats. Furthermore, quantification of phylogenetic patterns of microbial community assembly indicated that environmental forces (habitat filtering) determined sunken wood microbial community structure at all degradation phases of marine woodfalls. We also include a detailed discussion on novel archaeal and bacterial phylotypes in this newly explored biohabitat.


Assuntos
Archaea/classificação , Archaea/isolamento & purificação , Bactérias/classificação , Bactérias/isolamento & purificação , Ecossistema , Água do Mar/microbiologia , Archaea/genética , Bactérias/genética , Biomassa , Euryarchaeota/genética , Oceanos e Mares , Filogenia , RNA Ribossômico 16S/genética
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