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1.
Nat Commun ; 13(1): 450, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35064110

RESUMO

The mevalonate pathway plays a critical role in multiple cellular processes in both animals and plants. In plants, the products of this pathway impact growth and development, as well as the response to environmental stress. A forward genetic screen of Arabidopsis thaliana using Ca2+-imaging identified mevalonate kinase (MVK) as a critical component of plant purinergic signaling. MVK interacts directly with the plant extracellular ATP (eATP) receptor P2K1 and is phosphorylated by P2K1 in response to eATP. Mutation of P2K1-mediated phosphorylation sites in MVK eliminates the ATP-induced cytoplasmic calcium response, MVK enzymatic activity, and suppresses pathogen defense. The data demonstrate that the plasma membrane associated P2K1 directly impacts plant cellular metabolism by phosphorylation of MVK, a key enzyme in the mevalonate pathway. The results underline the importance of purinergic signaling in plants and the ability of eATP to influence the activity of a key metabolite pathway with global effects on plant metabolism.


Assuntos
Trifosfato de Adenosina/farmacologia , Arabidopsis/metabolismo , Espaço Extracelular/química , Redes e Vias Metabólicas , Ácido Mevalônico/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cálcio/metabolismo , Citosol/metabolismo , Imunidade Inata/efeitos dos fármacos , Cinética , Redes e Vias Metabólicas/efeitos dos fármacos , Metaboloma/genética , Mutação/genética , Fenótipo , Fosforilação/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Imunidade Vegetal/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais
2.
Indoor Air ; 31(4): 977-988, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33586827

RESUMO

Children are particularly vulnerable to many classes of the volatile organic compounds (VOCs) detected in indoor environments. The negative health impacts associated with chronic and acute exposures of the VOCs might lead to health issues such as genetic damage, cancer, and disorder of nervous systems. In this study, 40 VOCs including aldehydes and ketones, aliphatic hydrocarbons, esters, aromatic hydrocarbons, cyclic terpenes, alcohols, and glycol ethers were identified and qualified in different locations at the University of Missouri (MU) Child Development Laboratory (CDL) in Columbia, Missouri. Our results suggested that the concentrations of the VOCs varied significantly among classrooms, hallways, and playground. The VOCs emitted from personal care and cleaning products had the highest indoor levels (2-ethylhexanol-1, 3-carene, homomenthyl salicylate with mean concentration of 5.15 µg/m3 , 1.57 µg/m3 , and 1.47 µg/m3 , respectively). A cancer risk assessment was conducted, and none of the 95th percentile dose estimates exceeded the age-specific no significant risk levels (NSRL) in all classrooms. Dimensionless toxicity index scores were calculated for all VOCs using a novel web-based framework called Toxicological Prioritization Index (ToxPi), which integrates multiple sources of toxicity data. According to the method, homomenthyl salicylate, benzothiazole, 2-ethylhexyl salicylate, hexadecane, and tridecane exhibited diverse toxicity profiles and ranked as the five most toxic indoor VOCs. The findings of this study provide critical information for policy makers and early education professionals to mitigate the potentially negative health impacts of indoor VOCs in the childcare facilities.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Criança , Monitoramento Ambiental , Humanos , Medição de Risco , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/toxicidade
3.
Molecules ; 25(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023106

RESUMO

Our recent studies have demonstrated multiple health-promoting benefits from black walnut kernels. These biological functions of black walnuts are likely associated with their bioactive constituents. Characterization of phenolic compounds found in black walnut could point out underexplored bioactive activities of black walnut extracts and promote the development of novel applications of black walnut and its by-products. In the present study, we assessed bioactivity profiles of phenolic compounds identified in the kernels of black walnuts using a high-throughput screening (HTS) approach. Black walnut phenolic compounds were evaluated in terms of their total antioxidant capacity, antioxidant response element (ARE) induction, and anticancer activities. The anticancer activities were identified by evaluating the effects of the phenolic compounds on the growth of the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). Out of 16 phenolic compounds tested, several compounds (penta-O-galloyl-ß-d-glucose, epicatechin gallate, quercetin, (-)-epicatechin, rutin, quercetin 3-ß-d-glucoside, gallic acid, (+)-catechin, ferulic acid, syringic acid) exerted antioxidant activities that were significantly higher compared to Trolox, which was used as a control. Two phenolic compounds, penta-O-galloyl-ß-d-glucose and quercetin 3-ß-d-glucoside, exhibited antiproliferative activities against both the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). The antioxidant activity of black walnut is likely driven not only by penta-O-galloyl-ß-d-glucose but also by a combination of multiple phenolic compounds. Our findings suggested that black walnut extracts possibly possess anticancer activities and supported that penta-O-galloyl-ß-d-glucose could be a potential bioactive agent for the cosmetic and pharmaceutical industries.


Assuntos
Antineoplásicos/análise , Antineoplásicos/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Juglans/química , Fenóis/farmacologia , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Elementos de Resposta/genética
4.
Sci Total Environ ; 748: 142236, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33039138

RESUMO

The rise of hydraulic fracturing and unconventional oil and gas (UOG) exploration in the United States has increased public concerns for water contamination induced from hydraulic fracturing fluids and associated wastewater spills. Herein, we collected surface and groundwater samples across Garfield County, Colorado, a drilling-dense region, and measured endocrine bioactivities, geochemical tracers of UOG wastewater, UOG-related organic contaminants in surface water, and evaluated UOG drilling production (weighted well scores, nearby well count, reported spills) surrounding sites. Elevated antagonist activities for the estrogen, androgen, progesterone, and glucocorticoid receptors were detected in surface water and associated with nearby shale gas well counts and density. The elevated endocrine activities were observed in surface water associated with medium and high UOG production (weighted UOG well score-based groups). These bioactivities were generally not associated with reported spills nearby, and often did not exhibit geochemical profiles associated with UOG wastewater from this region. Our results suggest the potential for releases of low-saline hydraulic fracturing fluids or chemicals used in other aspects of UOG production, similar to the chemistry of the local water, and dissimilar from defined spills of post-injection wastewater. Notably, water collected from certain medium and high UOG production sites exhibited bioactivities well above the levels known to impact the health of aquatic organisms, suggesting that further research to assess potential endocrine activities of UOG operations is warranted.


Assuntos
Água Subterrânea , Fraturamento Hidráulico , Poluentes Químicos da Água , Colorado , Gás Natural , Campos de Petróleo e Gás , Estados Unidos , Águas Residuárias , Poluentes Químicos da Água/análise , Recursos Hídricos
5.
Rev Environ Health ; 34(1): 35-56, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30844763

RESUMO

Background Understanding the role of environmental toxicant exposure on children's development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children's exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited. Objectives The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children's cognitive, socioemotional, and behavioral development among young children. Methods This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children's development across multiple domains. Results The results highlight the potential risk of exposure to multiple environmental toxicants for young children's cognitive and socioemotional development. Discussion Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.


Assuntos
Sucesso Acadêmico , Comportamento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Substâncias Perigosas/efeitos adversos , Criança , Pré-Escolar , Emoções , Exposição Ambiental/classificação , Feminino , Substâncias Perigosas/classificação , Humanos , Lactente , Recém-Nascido , Masculino , Comportamento Social
6.
Arch Environ Contam Toxicol ; 75(2): 247-258, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29623359

RESUMO

Unconventional oil and natural gas (UOG) operations couple horizontal drilling with hydraulic fracturing to access previously inaccessible fossil fuel deposits. Hydraulic fracturing, a common form of stimulation, involves the high-pressure injection of water, chemicals, and sand to fracture the target layer and release trapped natural gas and/or oil. Spills and/or discharges of wastewater have been shown to impact surface, ground, and drinking water. The goals of this study were to characterize the endocrine activities and measure select organic contaminants in groundwater from conventional oil and gas (COG) and UOG production regions of Wyoming. Groundwater samples were collected from each region, solid-phase extracted, and assessed for endocrine activities (estrogen, androgen, progesterone, glucocorticoid, and thyroid receptor agonism and antagonism), using reporter gene assays in human endometrial cells. Water samples from UOG and conventional oil areas exhibited greater ER antagonist activities than water samples from conventional gas areas. Samples from UOG areas tended to exhibit progesterone receptor antagonism more often, suggesting there may be a UOG-related impact on these endocrine activities. We also report UOG-specific contaminants in Pavillion groundwater extracts, and these same chemicals at high concentrations in a local UOG wastewater sample. A unique suite of contaminants was observed in groundwater from a permitted drinking water well at a COG well pad and not at any UOG sites; high levels of endocrine activities (most notably, maximal estrogenic activity) were noted there, suggesting putative impacts on endocrine bioactivities by COG. As such, we report two levels of evidence for groundwater contamination by both UOG and COG operations in Wyoming.


Assuntos
Disruptores Endócrinos/análise , Água Subterrânea/análise , Campos de Petróleo e Gás , Poluentes Químicos da Água/análise , Linhagem Celular , Disruptores Endócrinos/toxicidade , Endométrio/citologia , Monitoramento Ambiental , Feminino , Água Subterrânea/química , Humanos , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Progesterona/antagonistas & inibidores , Testes de Toxicidade/métodos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/toxicidade , Águas Residuárias/química , Poluentes Químicos da Água/toxicidade , Wyoming
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