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This review addresses the issues of low consumer engagement and market development difficulties in intangible cultural heritage (ICH) products. Dietary ICH products are selected as research materials to discover contemporary commercial survival paths for ICH through the psychological effects of advertising. Firstly, this study examines the respective advantages of rational and emotional ICH advertisement in terms of emotional responses, cognitive responses, attitudes, recall, and recognition. Then, it explores the effects of different ICH advertisement types (rational advertisement, emotional advertisement) and different degrees of situational involvement (purchasing for oneself, purchasing gifts for others) on the advertising effectiveness, aiming to identify factors influencing the psychological effects of ICH advertisement. Through statistical analysis, the main conclusions are as follows: (1) Rational ICH advertisement prompts consumers to consider the actual attributes of ICH products, leading to a more positive purchasing attitude. (2) Emotional ICH advertisement is more effective in eliciting positive emotions from consumers and enhancing brand memory. (3) Under the scenario of purchasing a gift for others, emotional ICH advertisement has a more positive impact on consumers' attitudes towards advertising. (4) Under different degrees of situational involvement, rational ICH advertisement has a more positive impact on consumers' purchasing attitudes. This study not only provides guidance for optimizing ICH advertising strategies but also offers new directions for market expansion, contributing valuable insights into cultural heritage preservation, as well as the development and protection of ICH.
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This study comprehensively investigated mercury (Hg) contents of various environmental compartments in a typical antimony-coal mining area with intensive industrial activities over the past 120 years to analyze Hg environmental behaviors and evaluate Hg risks. The total mercury (THg) contents in river water, sediments, soils, PM10, dust falls, vegetables and corns were 1.16 ± 0.63 µg/L, 2.01 ± 1.64 mg/kg, 1.87 ± 3.88 mg/kg, 7.87 ± 18.68 ng/m3, 13.01 ± 14.53 mg/kg, 0.30 ± 0.34 mg/kg and 3.11 ± 0.51 µg/kg, respectively. The δ202Hg values in soils and dust falls were - 1.58 â¼ 0.12 and 0.25 â¼ 0.30, respectively. Environmental samples affected by industrial activities in the Xikuangshan (XKS) presented higher THg and δ202Hg values. Binary mixing model proved that atmospheric deposition with considerable Hg deposition flux (0.44 â¼ 6.40, 3.12 ± 2.20 mg/m2/y) in the XKS significantly contributed to Hg accumulations on surface soils. Compared with soils, sediments with more frequent paths and higher burst probabilities presented higher dynamic Hg risks. Children were faced higher health risk of multiple Hg exposure than adults. Furthermore, the health risk of THg by consuming leaf vegetables deserved more attention. These findings provided scientific basis for managing Hg contamination.
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Minas de Carvão , Mercúrio , Criança , Humanos , Mercúrio/análise , Antimônio , Ecossistema , Mineração , Monitoramento Ambiental , Sedimentos Geológicos , Solo , Verduras , PoeiraRESUMO
Although mechanochemical remediation of organic-contaminated soil has received substantial attention in recent years, the effects of soil properties on soil remediation performance are not clear. In this work, the properties and elemental components of 16 soils were tested, and the mechanochemical degradation performance of lindane in these soils was investigated through experiments. Most importantly, the relationships between soil variables and the mechanochemical degradation rates of lindane in the additive-free and CaO systems were elucidated. The results showed that the mechanochemical degradation efficiencies of lindane in the 16 soils were significantly different without additives, with a range of 31.0 %-97.2 % after 4 h. The mechanochemical degradation rates of lindane in the 16 soils varied from 0.7 h-1 to 15 h-1 after the addition of 9 % CaO. Correlation analysis, redundancy analysis and the partial least squares path modeling results clearly showed that the main factors affecting the reaction rate (k1) without additives were organic matter (-) > clay (+) > bound water (-) > Si (+). After the addition of 9 % CaO, the order in which the main factors affected the reaction rate (k2) was organic matter (-) > bound water (-) > Ti/Fe/Al (-) > pH (+) > clay (+). The established and corrected multiple nonlinear regression equations can be used to accurately predict the mechanochemical degradation performance of hexachlorocyclohexanes in actual soils with and without additives.
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In this study, total mercury (THg) contents and Hg isotope compositions in sediments were investigated in the Lianxi River, Zijiang River and South Dongting Lake to identify and quantify multiple Hg sources and evaluate the Hg environmental processes. The THg contents, δ202Hg and Δ199Hg values in sediments were 48.22 â¼ 4284.32 µg/kg, - 1.33 â¼ 0.04 and - 0.25 â¼ 0.03, respectively. Relatively distinct Hg isotope characteristics of sediments were presented in the Lianxi River, Zijiang River and South Dongting Lake, indicating the dominant Hg sources considerably varied in these regions. Source apportionment based on MixSIAR proved that Hg in sediments mainly originated from industrial activities, and the ternary mixing model concluded non-ferrous metal smelting was the dominant industrial Hg contributor in the Lianxi River. Compared with the Lianxi River, the relative contribution of Hg in sediments from industrial activities significantly decreased, while the relative contributions of Hg from background releases significantly increased in the Zijiang River and South Dongting Lake. Nonetheless, the contribution of industrial Hg in this study area deserves more attention. These results are conducive to further manage Hg pollution.
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In the area affected by non-ferrous metal mining activities, mercury (Hg) contamination in the water and sediments posed potential risks to ecology and human health. In this study, river water and sediment samples were collected in the Zijiang river - South Dongting Lake basin to analyze Hg residues, identify potential Hg sources and evaluate the ecological and health risks posed by Hg contamination. In this study, the average concentrations of THg, PHg, DHg and DMeHg in river water were 38.05 ± 27.13 ng/L, 25.18 ± 26.83 ng/L, 12.88 ± 9.64 ng/L and 0.29 ± 0.07 ng/L, respectively. The THg and MeHg contents in sediments were 234.24 ± 152.93 µg/kg and 0.48 ± 0.16 µg/kg, respectively. The more enrichment of Hg in sediments was observed in the Zijiang River than in the South Dongting Lake, especially in the upstream and midstream regions. Two potential Hg sources in the basin were identified by correlation matrix, principal component analysis (PCA) and positive matrix factorization (PMF) model. The comparable Hg flux with other rivers worldwide was found in the Zijiang River (0.53 Mg/y). Furthermore, it was found by the delayed geochemical hazard (DGH) model that the ecological risk of Hg was more significant in the Zijiang River with more frequent transformation pathways. For different populations, the health risk values caused by Hg were all lower than the USEPA's guideline value. This study provided sound evidence for further control of Hg contamination.
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Mercúrio , Poluentes Químicos da Água , Humanos , Mercúrio/análise , Lagos , Água/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , China , Medição de Risco , Sedimentos Geológicos/químicaRESUMO
In this study, surface seawater, bottom seawater and surface sediments were collected from the Yellow River Estuary Area (YREA) and the Laizhou Bay (LB) to investigate the occurrence, spatial distribution and geochemical control factors for total mercury (THg) and methylmercury (MeHg) in different phases. The geochemical characteristics of seawater and sediments suggested significant variances in the YREA and the LB. The high contamination of Hg in the YREA showed the discharge of the Yellow River (YR) contributed significantly to the Hg contamination in the LB. The partial least squares regression (PLSR) model was utilized to explore the complicated interactions between geochemical controls and methylation potentials in different phases. Although the ecological risk (ER) of Hg was not significant in this study area, the higher values of ER in the YREA suggested that the YR was the primary Hg contributor to LB. Therefore, the potential Hg risk should not be ignored.
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Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Estuários , Sedimentos Geológicos , Mercúrio/análise , Compostos de Metilmercúrio/análise , Poluentes Químicos da Água/análiseRESUMO
In this study, water and sediment samples from the Jiaozhou Bay and surrounding rivers were collected to analyze the seasonal occurrence and allocation of 12 organophosphate esters (OPEs) and the associated ecological risk. The higher contamination of OPEs in the adjacent rivers indicated the impact of terrestrial input. Tris(1-chloropropan-2-yl) phosphate (TCIPP) was the predominant OPE in the four environmental sample groups investigated. The spatial distribution of OPEs in seawater varied greatly seasonally and was mainly affected by terrestrial input, with OPEs being redistributed under the influence of tidal currents. The partition coefficients (log Koc) of the OPEs were calculated, and their strong correlation with the log Kow (octanol-water) values suggested that the water-sediment allocation was significantly affected by hydrophobicity. The homologous relationships among the 7 OPEs with detection frequencies greater than 40% were identified by principal component analysis (PCA). The partial least squares regression (PLSR) model explicated that ∑OPEs cycling dynamics and principal controlling factors were dissimilar in the bay versus surrounding rivers. The risk quotient (RQ) faced by typical organisms in seawater and river water indicated that short-term OPEs exposure was safe for green algae, daphnia and fish. The organisms in rivers faced the higher ecological risk of OPEs in spring than in summer and winter. Therefore, the terrestrial transport of OPEs in spring should be controlled.
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Retardadores de Chama , Poluentes Químicos da Água , Animais , Baías , China , Monitoramento Ambiental , Ésteres/análise , Retardadores de Chama/análise , Organofosfatos/análise , Estações do Ano , Poluentes Químicos da Água/análiseRESUMO
In this study, 26 surface seawater samples, 26 surface sediment samples and 114 organisms were collected to study the trophic transfer and dietary exposure risk of mercury (Hg) in organisms from the Jiaozhou Bay, which is a typical semi-enclosed urbanized bay. The total mercury (THg) and methylmercury (MeHg) concentrations did not exceed the threshold limits and performed as: fish > crustaceans > mollusks. The trophic level values (TLs) were less than 3 in all the groups, indicating simple structure of food chain. With the increasing δ15N value, THg and MeHg were significantly biomagnified in the mollusks and fish but not in the crustaceans. In addition, the bioaccumulation and biomagnification of MeHg were higher than inorganic mercury (IHg) in the aquatic food chain. Target hazard quotient (THQ) and provisional tolerable weekly intake (PTWI) indicated that Hg exposure via consumption of seafood from the Jiaozhou Bay did not pose significant health risks for general population. Consuming fish will face the higher health risk than crustaceans and mollusks, especially in urban regions. Moreover, the risk of MeHg caused by intaking seafood deserved more attention. Trophic transfer function (TTF) explicated the transfer of Hg in the ecosystem and higher trophic transfer efficiency of MeHg than IHg. TTF interpreted the terrestrial input of Hg should be controlled to ensure the safety of consuming seafood from the Jiaozhou Bay.
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Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Organismos Aquáticos , Exposição Dietética , Ecossistema , Monitoramento Ambiental , Peixes , Cadeia Alimentar , Humanos , Mercúrio/análise , Poluentes Químicos da Água/análiseRESUMO
The Jiaozhou Bay is a semi-enclosed bay located in the middle of the Yellow Sea. Effluents from wastewater treatment plants have been carried into the bay, which has significantly increased the deposition of mercury. The spatial distributions of total mercury (THg) and methylmercury (MeHg) in dissolved state, in suspended matters of seawater and surface sediments at 26 locations inside the Jiaozhou Bay and five surrounding rivers in April 2018 were examined. The contents of THg and MeHg found along the eastern coast were higher than those found along the western coast, which indicated the impact of human activities (river input) on the Jiaozhou Bay. The partition coefficient (LogKd) was used to express the distribution relationships of THg and MeHg in suspended matters and dissolved state, and it was concluded that suspended matter was the main reservoir of mercury in Jiaozhou Bay seawater. The correlations between contents and physicochemical properties of seawater showed that THg and MeHg concentrations in seawater decreased with increasing salinity and pH. The effects of the mean grain diameter (MGD) and sediment organic matter (SOM) on the THg and MeHg in surface sediments were also discussed. Principal component analysis (PCA) was used to obtain the factors determining the methylation proportion in the surface sediments, indicating that the combination of human activities and natural processes affected the degree of methylation in the sediments. The spatial distribution of THg, MeHg and MeHg% was suggested to be disturbed by the interaction of natural processes and human activities (river input) by the correlation analysis of the corresponding pollutant concentrations among seawater and. Although the concentrations of THg and MeHg in seawater and sediments of the Jiaozhou Bay did not exceed the Chinese regulatory standards, the pollution levels of THg and MeHg were comparable to those in other bays in the world.
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The importance of the circadian/melatonin signal in suppressing the metastatic progression of breast and other cancers has been reported by numerous laboratories including our own. Currently, the mechanisms underlying the antimetastatic actions of melatonin have not been well established. In the present study, the antimetastatic actions of melatonin were evaluated and compared on the ERα-negative, Her2-positive SKBR-3 breast tumor cell line and ERα-positive MCF-7 cells overexpressing a constitutively active HER2.1 construct (MCF-7Her2.1 cells). Activation of Her2 is reported to induce the expression and/or phosphorylation-dependent activation of numerous kinases and transcription factors that drive drug resistance and metastasis in breast cancer. A key signaling node activated by the Her2/Mapk/Erk pathway is Rsk2, which has been shown to induce numerous signaling pathways associated with the development of epithelial-to-mesenchymal transition (EMT) and metastasis including: Creb, Stat3, cSrc, Fak, Pax, Fascin, and actin polymerization. The data demonstrate that melatonin (both endogenous and exogenous) significantly represses this invasive/metastatic phenotype through a mechanism that involves the suppression of EMT, either by promoting mesenchymal-to-epithelial transition, and/or by inhibiting key signaling pathways involved in later stages of metastasis. These data, combined with our earlier in vitro studies, support the concept that maintenance of elevated and extended duration of nocturnal melatonin levels plays a critical role in repressing the metastatic progression of breast cancer. IMPLICATIONS: Melatonin inhibition of Rsk2 represses the metastatic phenotype in breast cancer cells suppressing EMT or inhibiting other mechanisms that promote metastasis; disruption of the melatonin signal may promote metastatic progression in breast cancer. Mol Cancer Res; 14(11); 1159-69. ©2016 AACR.
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Neoplasias da Mama/tratamento farmacológico , Melatonina/administração & dosagem , Receptor ErbB-2/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Melatonina/farmacologia , Camundongos , Metástase Neoplásica , Fosforilação , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Leiomyosarcoma (LMS) represents a highly malignant, rare soft tissue sarcoma with high rates of morbidity and mortality. Previously, we demonstrated that tissue-isolated human LMS xenografts perfused in situ are highly sensitive to the direct anticancer effects of physiological nocturnal blood levels of melatonin which inhibited tumour cell proliferative activity, linoleic acid (LA) uptake and metabolism to 13-hydroxyoctadecadienoic acid (13-HODE). Here, we show the effects of low pharmacological blood concentrations of melatonin following oral ingestion of a melatonin supplement by healthy adult human female subjects on tumour proliferative activity, aerobic glycolysis (Warburg effect) and LA metabolic signalling in tissue-isolated LMS xenografts perfused in situ with this blood. Melatonin markedly suppressed aerobic glycolysis and induced a complete inhibition of tumour LA uptake, 13-HODE release, as well as significant reductions in tumour cAMP levels, DNA content and [(3) H]-thymidine incorporation into DNA. Furthermore, melatonin completely suppressed the phospho-activation of ERK 1/2, AKT, GSK3ß and NF-kB (p65). The addition of S20928, a nonselective melatonin antagonist, reversed these melatonin inhibitory effects. Moreover, in in vitro cell culture studies, physiological concentrations of melatonin repressed cell proliferation and cell invasion. These results demonstrate that nocturnal melatonin directly inhibited tumour growth and invasion of human LMS via suppression of the Warburg effect, LA uptake and other related signalling mechanisms. An understanding of these novel signalling pathway(s) and their association with aerobic glycolysis and LA metabolism in human LMS may lead to new circadian-based therapies for the prevention and treatment of LMS and potentially other mesenchymally derived solid tumours.
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Glicólise/efeitos dos fármacos , Leiomiossarcoma/tratamento farmacológico , Melatonina/metabolismo , Animais , Sobrevivência Celular , Feminino , Humanos , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Metástase Neoplásica , Ratos , Ratos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The present review discusses recent work on melatonin-mediated circadian regulation, the metabolic and molecular signaling mechanisms that are involved in human breast cancer growth, and the associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin suppresses ERα mRNA expression and ERα transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of other members of the nuclear receptor superfamily, estrogen-metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (the Warburg effect) and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type-specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways, including inhibition of p38 MAPK and repression of epithelial-mesenchymal transition (EMT). Studies have demonstrated that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models has indicated that LEN-induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer and drives breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms that underpin the epidemiologic demonstration of elevated breast cancer risk in night-shift workers and other individuals who are increasingly exposed to LEN.
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Neoplasias da Mama/metabolismo , Ritmo Circadiano/fisiologia , Melatonina/metabolismo , Animais , Feminino , Humanos , Transdução de SinaisRESUMO
Chemotherapeutic resistance, particularly to doxorubicin (Dox), represents a major impediment to successfully treating breast cancer and is linked to elevated tumor metabolism and tumor over-expression and/or activation of various families of receptor- and non-receptor-associated tyrosine kinases. Disruption of circadian time structure and suppression of nocturnal melatonin production by dim light exposure at night (dLEN), as occurs with shift work, and/or disturbed sleep-wake cycles, is associated with a significantly increased risk of an array of diseases, including breast cancer. Melatonin inhibits human breast cancer growth via mechanisms that include the suppression of tumor metabolism and inhibition of expression or phospho-activation of the receptor kinases AKT and ERK1/2 and various other kinases and transcription factors. We demonstrate in tissue-isolated estrogen receptor alpha-positive (ERα+) MCF-7 human breast cancer xenografts, grown in nude rats maintained on a light/dark cycle of LD 12:12 in which dLEN is present during the dark phase (suppressed endogenous nocturnal melatonin), a significant shortening of tumor latency-to-onset, increased tumor metabolism and growth, and complete intrinsic resistance to Dox therapy. Conversely, a LD 12:12 dLEN environment incorporating nocturnal melatonin replacement resulted in significantly lengthened tumor latency-to-onset, tumor regression, suppression of nighttime tumor metabolism, and kinase and transcription factor phosphorylation, while Dox sensitivity was completely restored. Melatonin acts as both a tumor metabolic inhibitor and circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to Dox and drive tumor regression, indicating that dLEN-induced circadian disruption of nocturnal melatonin production contributes to a complete loss of tumor sensitivity to Dox chemotherapy.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Ritmo Circadiano/efeitos da radiação , Doxorrubicina/uso terapêutico , Luz , Melatonina/metabolismo , Animais , Western Blotting , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Feminino , Glucose/metabolismo , Humanos , Células MCF-7 , Camundongos Nus , Oxigênio/metabolismo , Ratos , Ratos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Early studies on rodents showed that short-term exposure to high-intensity light (> 70 lx) above 600 nm (red-appearing) influences circadian neuroendocrine and metabolic physiology. Here we addressed the hypothesis that long-term, low-intensity red light exposure at night (rLEN) from a 'safelight' emitting no light below approximately 620 nm disrupts the nocturnal circadian melatonin signal as well as circadian rhythms in circulating metabolites, related regulatory hormones, and physi- ologic parameters. Male Sprague-Dawley rats (n = 12 per group) were maintained on control 12:12-h light:dark (300 lx; lights on, 0600) or experimental 12:12 rLEN (8.1 lx) lighting regimens. After 1 wk, rats underwent 6 low-volume blood draws via cardiocentesis (0400, 0800, 1200, 1600, 2000, and 2400) over a 4-wk period to assess arterial plasma melatonin, total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin and corticosterone concentrations. Results revealed plasma melatonin levels (mean ± 1 SD) were high in the dark phase (197.5 ± 4.6 pg/mL) and low in the light phase (2.6 ± 1.2 pg/mL) of control condi- tions and significantly lower than controls under experimental conditions throughout the 24-h period (P < 0.001). Prominent circadian rhythms of plasma levels of total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were significantly (P < 0.05) disrupted under experimental conditions as compared with the corresponding entrained rhythms under control conditions. Therefore, chronic use of low-intensity rLEN from a common safelight disrupts the circadian organization of neuroendocrine, metabolic, and physiologic parameters indicative of animal health and wellbeing.
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Ritmo Circadiano/efeitos da radiação , Luz , Ratos Sprague-Dawley/fisiologia , Animais , Corticosterona/sangue , Dieta , Abrigo para Animais , Masculino , Melatonina/sangue , Ratos , Ratos Sprague-Dawley/sangue , Ratos Sprague-Dawley/crescimento & desenvolvimentoRESUMO
The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.
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Neoplasias da Mama , Proliferação de Células , Ritmo Circadiano , Glicólise , Melatonina/metabolismo , Glândula Pineal , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/prevenção & controle , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Transplante de Neoplasias , Glândula Pineal/metabolismo , Glândula Pineal/patologia , Glândula Pineal/fisiopatologia , Ratos , Ratos NusRESUMO
Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen.
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Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Ritmo Circadiano/fisiologia , Luz , Melatonina/sangue , Tamoxifeno/farmacologia , Animais , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Camundongos Nus , Distribuição Aleatória , Ratos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Melatonin has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its antiproliferative effects have been well studied in MCF-7 human breast cancer cells and several other estrogen receptor α (ERα)-positive human breast cancer cell lines. However, the MDA-MB-231 breast cancer cell line, an ERα-negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin's growth-suppressive effect in vitro. Here, we examined the effect of melatonin on the cell proliferation of several ERα-negative breast cancer cell lines including MDA-MB-231, BT-20, and SK-BR-3 cells. Although the MT1 G-protein-coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK-BR-3 cells without having any significant effect on the growth of MDA-MB-231 and BT-20 cells. We confirmed that the MT1-associated Gα proteins are expressed in MDA-MB-231 cells. Further studies demonstrated that the melatonin unresponsiveness in MDA-MB-231 cells may be caused by aberrant signaling downstream of the Gαi proteins, resulting in differential regulation of ERK1/2 activity.
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Melatonina/farmacologia , Receptor MT1 de Melatonina/genética , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fenótipo , Receptor MT1 de Melatonina/fisiologiaRESUMO
This paper describes a green versatile glucose-engineered precipitation-sintering process that allows for the selective and mass preparation of spongy porous ferrite (M = Fe, Zn, Co, Ni, Mn, etc.) micro-polyhedra with tunable morphology, texture, and composition. Some kinetic factors, such as the molar ratio of glucose to metal nitrates, reaction temperature, sintering temperature and time, and type of metal nitrates, can be expediently employed to modulate their aspect ratio, shape, size, composition, and textural properties. In this protocol, glucose functions as a reductant, protecting agent, structure-directing agent, and a sacrificial template to guide the assembly of sheet-like nuclei into polyhedral precursors and the formation of spongy porous structures. Owing to larger EM parameters, multiresonant behavior, and dissipative current, spongy porous Fe3O4 polyhedra exhibited enhanced microwave-absorbing properties. This endows them with important potential applications in magnetic devices, catalysis, sorption, photoluminescence, electromagnetic wave absorbing materials, anode materials, and so on. Meanwhile, this general approach can be extended to synthesize other porous sponges with regular geometric configuration because it is simple, inexpensive, environmentally benign, and suitable for extensive production.