A pilot observational exposure study was performed to evaluate methods for collecting multimedia measurements (air, dust, food, urine) and activity patterns to assess potential exposures of young children to pesticides in their homes. Nine children (mean age ¼ 5 years) and their caregivers participated in this study, performed in the Duval County, Florida, in collaboration with the Centers for Disease Control and Prevention and the Duval County Health Department. For all nine children, the total time reported for sleeping and napping ranged from 9.5 to 14 h per day, indoor quiet time from 0 to 5.5 h per day, indoor active time from 0.75 to 5.5 h per day, outdoor quiet time from 0 to 1.5 h per day, and outdoor active time from 0.5 to 6.5 h per day. Each home had one to three pesticide products present, with aerosols being most common. Pesticide inventories, however, were not useful for predicting pesticide levels in the home. Synthetic pyrethroids were the most frequently identified active ingredients in the products present in each home. Fifteen pesticide active ingredients were measured in the application area wipes (not detected (ND) to 580 ng/cm 2 ), 13 in the play area wipes (ND-117 ng/cm 2 ), and 14 in the indoor air samples (ND-378 ng/m 3 ) and the socks (ND-1000 ng/cm 2 ). Cis-permethrin, trans-permethrin, and cypermethrin were measured in all nine homes. Chlorpyrifos was measured in all nine homes even though it was not reported used by the participants. All urine samples contained measurable concentrations of 3-phenoxybenzoic acid (3-PBA). The median 3-PBA urinary concentration for the nine children was 2.2 mg/l. A wide variety of pesticide active ingredients were measured in these nine homes at median concentrations that were often higher than reported previously in similar studies. These data highlight the need for additional observational studies in regions where pesticides are used in order to understand the factors that affect young children's exposures and the education/mitigation strategies that can be used to reduce children's exposures.
Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.
Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2’s role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.
Ganoderma lucidum
extract (GLE) is a potent ancient Asian remedy for the treatment of various diseases. This study investigated GLE preventive effects on LPS-stimulated inflammation of BV-2 microglial cells. The results show that pre-treatment with GLE decreased expression of pro-inflammatory cytokines: G-CSF, IL1-α, MCP-5, MIP3α, and, with a higher effect in MIP3α. In RT-PCR assays, pre-treatment with GLE decreased mRNA expression of
CHUK
,
NFκB1/p150
, and
IKBKE
(NFƙB signaling), which may be associated with the neuropathology of Alzheimer’s disease. The data show GLE inhibiting ability on pro-inflammatory mediators’ release and suggest a potential role of GLE in neurodegenerative disease prevention.
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