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This study aimed to compare the composition of fatty acids in goat milk during lactation with human milk, as well as analyze the differences in their interaction with odor and metabolites. Polyunsaturated fatty acids content was higher in human milk, while odd-chain, branched-chain, and monounsaturated fatty acids content were higher in goat milk with a decreasing trend during lactation. PUFAs in human milk undergo auto-oxidation to produce aldehydes (hexanal), giving it a mild aroma. Butyric acid in goat colostrum mediates the synthesis and auto-oxidation of PUFA, while taurine mediated the hydrolysis of amino acids. They produce a furanone compound (2(5H)-furanone) with a buttery flavor. The presence of butyric acid in goat transitional milk had an impact on flavor and metabolites. The medium chain fatty acid composition of the goat mature milk was affected by nucleic acid compounds, which then oxidized to produce methyl ketone (2-nonanone), giving it an unpleasant flavor.
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Goat milk is considered the optimal substitute for human milk and is characterized by variations in the lipid composition of its fat globules across lactation phases. Therefore, the objective of this study was to thoroughly analyze the differences between goat milk during different lactations and human milk, aiming to offer scientific guidance for the production of functional dairy products. Compared with transitional and mature milk, the findings indicated that the total membrane protein content in goat colostrum exhibited greater similarity to that found in human milk. Additionally, goat milk exhibited higher milk fat globule size, as well as a higher total lipid and protein content than human milk. A total of 1461 lipid molecules across 61 subclasses were identified in goat milk and human milk. The contents of glycerides and glycerophospholipids were higher in goat colostrum, whereas sphingolipids and fatty acids were more abundant in human milk. Meanwhile, the compositions of lipid subclasses were inconsistent. There were 584 differentially expressed lipids identified between human and goat milk, including 47 subclasses that were primarily involved in the metabolism of glycerophospholipids, sphingolipids, and triglycerides. In summary, for both the membrane protein and the lipid composition, there were differences between the milk of different goat lactations and human milk.
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Bisphenol G (BPG), bisphenol M (BPM) and bisphenol TMC (BPTMC), are newly recognized analogues of bisphenol A (BPA), which have been detected in multiple environmental media. However, the understanding of their negative impacts on environmental health is limited. In this study, zebrafish embryos were exposed to BPA and the three analogues (0.1, 10, and 1000 µg/L) to identify their developmental toxic effects. According to our results, all of the three analogues induced significant developmental disorders on zebrafish embryos including inhibited yolk sac absorption, altered heart rate, and teratogenic effects. Oil Red O staining indicated lipid accumulation in the yolk sac region of zebrafish after bisphenol analogues exposure, which was consistent with the delayed yolk uptake. Untargeted lipidomic analysis indicated the abundance of triacylglycerols, ceramides and fatty acids was significantly altered by the three analogues. The combined analysis of lipidomics and transcriptomics results indicated BPG and BPM affected lipid metabolism by disrupting peroxisome proliferator-activated receptor pathway and interfering with lipid homeostasis and transport. This partly explained the morphological changes of embryos after bisphenol exposure. In conclusion, our study reveals that BPG, BPM and BPTMC possess acute and developmental toxicity toward zebrafish, and the developmental abnormalities are associated with the disturbances in lipid metabolism.
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Compostos Benzidrílicos , Embrião não Mamífero , Metabolismo dos Lipídeos , Fenóis , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Teratogênicos/toxicidadeRESUMO
Phospholipids (PL) have garnered significant attention due to their physiological activities. Milk and other dairy products are important dietary sources for humans and have been extensively used to analyze the presence of PL by various analytical techniques. In this paper, the analysis techniques of PL were reviewed with the eight trigrams of phospholipidomics and a comprehensive fingerprint of 1295 PLs covering 8 subclasses in milk and other dairy products, especially. Technology is the primary productive force. Based on phospholipidomics technology, we further review the relationship between the composition of PL and factors that may be involved in processing and experimental operation, and emphasized the significance of the biological role played by PL in dietary supplements and biomarkers (production, processing and clinical research), and providing the future research directions.
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Blood-brain barrier breakdown and ROS overproduction are important events during the progression of ischemic stroke aggravating brain damage. Geraniol, a natural monoterpenoid, possesses anti-apoptotic, cytoprotective, anti-oxidant, and anti-inflammatory activities. Our study aimed to investigate the effect and underlying mechanisms of geraniol in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human brain microvascular endothelial cells (HBMECs). Apoptosis, caspase-3 activity, and cytotoxicity of HBMECs were evaluated using TUNEL, caspase-3 activity, and CCK-8 assays, respectively. The permeability of HBMECs was examined using FITC-dextran assay. Reactive oxygen species (ROS) production was measured using the fluorescent probe DCFH-DA. The protein levels of zonula occludens-1 (ZO-1), occludin, claudin-5, ß-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were determined by western blotting. Geraniol showed no cytotoxicity in HBMECs. Geraniol and ROS scavenger N-acetylcysteine (NAC) both attenuated OGD/R-induced apoptosis and increase of caspase-3 activity and the permeability to FITC-dextran in HBMECs. Geraniol relieved OGD/R-induced ROS accumulation and decrease of expression of ZO-1, occludin, claudin-5, and ß-catenin in HBMECs. Furthermore, we found that geraniol activated Nrf2/HO-1 pathway to inhibit ROS in HBMECs. In conclusion, geraniol attenuated OGD/R-induced ROS-dependent apoptosis and permeability in HBMECs through activating the Nrf2/HO-1 pathway.
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Monoterpenos Acíclicos , Apoptose , Células Endoteliais , Glucose , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Humanos , Apoptose/efeitos dos fármacos , Monoterpenos Acíclicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Glucose/metabolismo , Heme Oxigenase-1/metabolismo , Oxigênio/metabolismo , Encéfalo/metabolismo , Encéfalo/irrigação sanguínea , Microvasos/metabolismo , Microvasos/patologia , Microvasos/efeitos dos fármacosRESUMO
Since the avalanche phenomenon was first found in bulk materials, avalanche photodiodes (APDs) have been exclusively investigated. Among the many devices that have been developed, silicon APDs stand out because of their low cost, performance stability, and compatibility with CMOS. However, the increasing industrial needs pose challenges for the fabrication cycle time and fabrication cost. In this work, we proposed an improved fabrication process for ultra-deep mesa-structured silicon APDs for photodetection in the visible and near-infrared wavelengths with improved performance and reduced costs. The improved process reduced the complexity through significantly reduced photolithography steps, e.g., half of the steps of the existing process. Additionally, single ion implantation was performed under low energy (lower than 30 keV) to further reduce the fabrication costs. Based on the improved ultra-concise process, a deep-mesa silicon APD with a 140 V breakdown voltage was obtained. The device exhibited a low capacitance of 500 fF, the measured rise time was 2.7 ns, and the reverse bias voltage was 55 V. Moreover, a high responsivity of 103 A/W@870 nm at 120 V was achieved, as well as a low dark current of 1 nA at punch-through voltage and a maximum gain exceeding 1000.
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As the most prevalent mycotoxin in agricultural products, aflatoxin B1 not only causes significant economic losses but also poses a substantial threat to human and animal health. AFB1 has been shown to increase the risk of hepatocellular carcinoma (HCC) but the underlying mechanism is not thoroughly researched. Here, we explored the toxicity mechanism of AFB1 on human hepatocytes following low-dose exposure based on transcriptomics and lipidomics. Apoptosis-related pathways were significantly upregulated after AFB1 exposure in all three hES-Hep, HepaRG, and HepG2 hepatogenic cell lines. By conducting a comparative analysis with the TCGA-LIHC database, four biomarkers (MTCH1, PPM1D, TP53I3, and UBC) shared by AFB1 and HCC were identified (hazard ratio > 1), which can be used to monitor the degree of AFB1-induced hepatotoxicity. Simultaneously, AFB1 induced abnormal metabolism of glycerolipids, sphingolipids, and glycerophospholipids in HepG2 cells (FDR < 0.05, impact > 0.1). Furthermore, combined analysis revealed strong regulatory effects between PIK3R1 and sphingolipids (correlation coefficient > 0.9), suggesting potential mediation by the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (AKT) signaling pathway within mitochondria. This study revealed the dysregulation of lipid metabolism induced by AFB1 and found novel target genes associated with AFB-induced HCC development, providing reliable evidence for elucidating the hepatotoxicity of AFB as well as assessing food safety risks.
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Mycotoxin aflatoxin B1 (AFB1) has been proven to cause neurotoxicity, but its potential interference with the normal function of brain tissue is not fully defined. As the indispensable role of lipids in maintaining the normal function of brain tissue, the aim of this study is to clarify the effect of AFB1 short-term (7 days) exposure on brain tissue from the perspective of lipid metabolism. In this study, zebrafish were exposed to two concentrations (5, 20 µg/L). Through quantitative analysis of AFB1, the detection of AFB1 in zebrafish brain tissue was discovered for the first time, combined with the changes in zebrafish neurobehavior, the occurrence of brain injury was deduced. Subsequently, 1734 lipids in zebrafish brain tissue were mapped using ion mobility time-of-flight mass spectrometry (UPLC-QTOF-IMS-MS), which has great advantages in lipid detection. Comparative analysis of the abnormal lipid metabolism in zebrafish brain revealed 114 significantly changed lipids, mainly involving two pathways of sphingolipid metabolism and fatty acid degradation. This study discovered the detection of AFB1 in the brain and revealed a potential link between AFB1-induced behavioral abnormalities and lipid metabolism disorders in brain tissue, providing reliable evidence for elucidating the neurotoxicity of AFB1.
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Micotoxinas , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Aflatoxina B1/toxicidade , Lipidômica , Micotoxinas/metabolismo , LipídeosRESUMO
Short-wavelength infrared photodetectors based on metamorphic InGaAs grown on GaSb substrates and InP substrates are demonstrated. The devices have a pBn structure that employs an AlGaAsSb thin layer as the electron barrier to suppress dark current density. The strain effect on the electrical performance of the devices was specifically studied through the growth of the pBn structure on different substrates, e.g., InP and GaSb, via a specific buffering technique to optimize material properties and minimize dark current. A lower device dark current density, down to 1 × 10-2 A/cm2 at room temperature (295 K), was achieved for the devices grown on the GaSb substrate compared to that of the devices on the InP substrate (8.6 × 10-2 A/cm2). The improved properties of the high-In component InGaAs layer and the AlGaAsSb electron barrier give rise to the low dark current of the photodetector device.
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The widespread use of pesticides performs a vital role in safeguarding crop yields and quality, providing the opportunity for multiple pesticides to co-exist, which poses a significant potential risk to human health. To assess the toxic effects caused by exposures to individual pesticides (chlorpyrifos, carbofuran and acetamiprid), binary combinations and ternary combinations, individual and combined exposure models were developed using HepG2 cells and the types of combined effects of pesticide mixtures were assessed using concentration addition (CA), independent action (IA) and combination index (CI) models, respectively, and the expression of biomarkers related to oxidative stress, apoptosis and cell necrosis was further examined. Our results showed that both individual pesticides and mixtures exerted toxic effects on HepG2 cells. The CI model indicated that the toxic effects of pesticide mixtures exhibited synergistic effects. The results of the lactate dehydrogenase (LDH) release and apoptosis assay revealed that the pesticide mixture increased the release of LDH and apoptosis levels. Moreover, our results also showed that individual pesticides and mixtures disrupted redox homeostasis and that pesticide mixtures produced more intense oxidative stress effects. In conclusion, we have illustrated the enhanced combined toxicity of pesticide mixtures by in-vitro experiments, which provides a theoretical basis and scientific basis for further toxicological studies.
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Praguicidas , Humanos , Praguicidas/toxicidade , Células Hep G2 , Apoptose , Necrose/induzido quimicamente , Estresse OxidativoRESUMO
Emerging studies demonstrate that inflammation plays a crucial role in the pathogenesis of bipolar disorder (BD), but the underlying mechanism remains largely unclear. Given the complexity of BD pathogenesis, we performed high-throughput multi-omic profiling (metabolomics, lipidomics, and transcriptomics) of the BD zebrafish brain to comprehensively unravel the molecular mechanism. Our research proved that in BD zebrafish, JNK-mediated neuroinflammation altered metabolic pathways involved in neurotransmission. On one hand, disturbed metabolism of tryptophan and tyrosine limited the participation of the monoamine neurotransmitters serotonin and dopamine in synaptic vesicle recycling. On the other hand, dysregulated metabolism of the membrane lipids sphingomyelin and glycerophospholipids altered the synaptic membrane structure and neurotransmitter receptors (chrnα7, htr1b, drd5b, and gabra1) activity. Our findings revealed that disturbance of serotonergic and dopaminergic synaptic transmission mediated by the JNK inflammatory cascade was the key pathogenic mechanism in a zebrafish model of BD, provides critical biological insights into the pathogenesis of BD.
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Maternal exposure to antibiotics existing in the environment is a predisposing factor for developmental malformation with metabolic disorders in offspring. In this study, female zebrafish (3 months) were exposed to 0.05 mg/L and 0.5 mg/L florfenicol (FF) for 28 days. After pairing and spawning with healthy male fish, F1 embryos were collected and developed to 5 d post-fertilization (dpf) in clear water. And the adverse effects on the F1 generation were examined thoroughly. The fecundity of F0 female fish and the hatchability, mortality, and body length of F1 larvae significantly decreased in the treatment group. Meanwhile, multi-malformation types were found in the exposure group, including delayed yolk sac absorption, lack of swim bladder, and spinal curvature. Metabolomic and transcriptomic results revealed alterations in metabolism with dysregulation in tricarboxylase acid cycle, amino acid metabolism, and disordered lipid metabolism with elevated levels of glycerophospholipid and sphingolipid. Accompanying these metabolic derangements, decreased levels of ATP and disordered oxidative-redox state were observed. These results were consistent with the damaged mitochondrial membrane potential and respiratory chain function, suggesting that the developmental toxicity and perturbed metabolic signaling in the F1 generation were related to the mitochondrial injury after exposing F0 female zebrafish to FF. Our findings highlighted the potential toxicity of FF to offspring generations even though they were not directly exposed to environmental contaminants.
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Tianfenicol , Poluentes Químicos da Água , Animais , Masculino , Feminino , Peixe-Zebra/fisiologia , Tianfenicol/toxicidade , Larva , Redes e Vias Metabólicas , Mitocôndrias , Poluentes Químicos da Água/toxicidadeRESUMO
Sinensetin is a polymethoxylated flavone with anti-inflammatory and anti-oxidative activities. This work aimed to explore the function and mechanism of sinensetin in oxygen and glucose deprivation/reperfusion (OGD/R)-induced neurotoxicity. The overlapping target genes of cerebral stroke and sinensetin were determined according to GeneCards and ParmMapper tools and were subjected to Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Human cerebral microvascular endothelial cells (HCMECs) were stimulated with OGD/R. Neurotoxicity was investigated by Cell Counting Kit-8, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, qRT-PCR, and TUNEL analysis. The proteins (p38, JNK, and ERK) in mitogen-activated protein kinase (MAPK) signaling were measured using Western blotting. Total of 50 overlapping target genes of cerebral stroke and sinensetin were predicted. Pathway analysis showed they might be involved in the MAPK pathway. Sinensetin attenuated OGD/R-induced neurotoxicity by mitigating viability reduction, LDH release, ROS generation, inflammatory response, and apoptosis in HCMECs. Sinensetin weakened OGD/R-induced activation of the MAPK pathway via decreasing the phosphorylation of p38, JNK, and ERK. The pathway inhibitors mitigated the activation of the MAPK signaling, and sinensetin exacerbated this effect. The inhibitors reversed OGD/R-induced neurotoxicity in HCMECs, and sinensetin contributed to this role. Overall, sinensetin prevents OGD/R-induced neurotoxicity through decreasing the activation of MAPK pathway.
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Traumatismo por Reperfusão , Acidente Vascular Cerebral , Apoptose , Células Endoteliais , Flavonoides , Glucose/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Acidente Vascular Cerebral/metabolismoRESUMO
BACKGROUND: Inflammation-related diseases present a significant public health problem. Ginger is a flavoring spice and medicinal herb with anti-inflammatory activity. This study investigated the preventive effects of ginger extract (GE) and its main bioactive component, 6-gingerol (6G), on lipopolysaccharide (LPS)-induced intestinal barrier dysfunction and liver injury in mice. RESULTS: GE and 6G were orally administered to mice for seven consecutive days before LPS administration. After 24 h, the mice were sacrificed. GE and 6G were found to significantly reverse LPS-induced inflammation in the mouse ileum by modifying the NF-κB pathway. They also alleviated apoptosis in the ileum by downregulating Bax and cytochrome c gene expression and by inhibiting the caspase-3 pathway. Through the aforementioned mechanisms, GE and 6G restored the intestinal barrier by increasing ZO-1 and claudin-1 protein expressions. Gut-derived LPS induced inflammation and apoptosis in the liver; these effects were markedly reversed through GE and 6G treatment. 6G was the most abundant component in GE, as evidenced through liquid chromatography-mass spectrometry, and accounted for >50% of total gingerols and shogaols in GE. CONCLUSION: The current results support the use of GE and 6G as dietary supplements to protect against gut-derived endotoxemia-associated inflammatory response and disorders. © 2021 Society of Chemical Industry.
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Anti-Inflamatórios/administração & dosagem , Catecóis/administração & dosagem , Álcoois Graxos/administração & dosagem , Enteropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Zingiber officinale/química , Animais , Apoptose/efeitos dos fármacos , Humanos , Enteropatias/imunologia , Enteropatias/fisiopatologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/lesões , Lipopolissacarídeos/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/lesões , Hepatopatias/imunologia , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
Medicarpin, a pterocarpan class of naturally occurring phytoestrogen possesses various biological functions. However, the effect of medicarpin on oxygen-glucose deprivation-reoxygenation (OGD/R)-induced injury in human cerebral microvascular endothelial cells (HCMECs) remains largely unknown. Target genes of medicarpin were predicted from PharmMapper. Target genes of ischemic stroke were predicted from public databases GeneCards and DisGeNET. Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the intersecting targets was analyzed via DAVID 6.8. Cell viability was evaluated using CCK-8 assay. Malondialdehyde content, superoxide dismutase activity, and glutathione level were detected using corresponding commercially available kits. Cell death was assessed by TUNEL assays. Expression of protein kinase B (Akt), phosphorylated-Akt, forkhead box protein O1, phosphorylated-FoxO1, FoxO3a, and phosphorylated-FoxO3a (p-FoxO3a) was detected by western blot analysis. The intersecting targets of medicarpin and ischemic stroke were significantly enriched in phosphatidylinositol 3-kinase (PI3K)/Akt and FoxO pathways. Medicarpina attenuated OGD/R-evoked viability inhibition, oxidative stress, and cell death in HCMECs. Additionally, medicarpin activated the PI3K/Akt and FoxO pathways in OGD/R-induced HCMECs. Inhibition of PI3K/Akt pathway abrogated the neuroprotective effect of medicarpin on OGD/R-induced injury and activation of FoxO pathway in HCMECs. In conclusion, medicarpin suppressed OGD/R-induced injury in HCMECs by activating PI3K/Akt/FoxO pathway.
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Pterocarpanos , Traumatismo por Reperfusão , Apoptose , Células Endoteliais/metabolismo , Glucose/metabolismo , Humanos , Farmacologia em Rede , Oxigênio/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pterocarpanos/metabolismo , Pterocarpanos/farmacologia , Traumatismo por Reperfusão/metabolismoRESUMO
The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC50 value of 0.78 mg a.i. L-1) compared with FB1 (7-day LC50 value of 227.7 mg a.i. L-1). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod, cas9, bax, cc-chem, ERα, and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain.
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Fumonisinas , Zearalenona , Animais , Fumonisinas/toxicidade , Expressão Gênica , Humanos , Zearalenona/toxicidade , Peixe-Zebra/genéticaRESUMO
Neonicotinoid insecticides are widely used for pest control. However, they are highly water-soluble and easily ingested by organisms, posing potential health risks. In this study, cytotoxicity evaluations of imidacloprid and acetamiprid were conducted in Neuro-2a cells by obtaining their half maximal inhibitory concentration (IC50 values) (1152.1 and 936.5 µM, respectively). The toxic effects at the IC10 and IC20 on cell metabolism were determined by integrated non-targeted lipidomics and metabolomics analyses. Changes in the concentration of acetamiprid caused the most drastic perturbations of metabolism in Neuro-2a cells. Altogether, the detected lipids were mainly attributed to triglyceride, phosphatidylcholine (PC), and diglyceride. These three categories of lipids accounted for more than 67% of the sum in Neuro-2a cells. A total of 14 lipids and other 40 metabolites were screened as differential metabolites based on multivariate data analysis, and PCs were most frequently observed with a proportion of 25.9%. The results demonstrated that lipid metabolism should be paid considerable attention after imidacloprid and acetamiprid exposure. Pathway analysis showed that the metabolisms of glycerophospholipid, sphingolipid, and glutathione were the dominant pathways that were interfered. The present study is the first to investigate the cellular toxic mechanisms after separate imidacloprid and acetamiprid exposure by using lipidomics and metabolomics simultaneously. This research also provides novel insights into the evaluation of the ecological risk of imidacloprid and acetamiprid and contribute to the study of toxicity mechanism of these neonicotinoid insecticides to animals and humans in the future.
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Inseticidas , Lipidômica , Animais , Humanos , Inseticidas/toxicidade , Metabolômica , Neonicotinoides/toxicidade , Nitrocompostos/toxicidadeRESUMO
Difenoconazole, cypermethrin and triazophos are widely used pesticides in agricultural production and frequently detected in foods. The aim of this study was to determine the effect of these pesticides and their mixtures on cell viability, reactive oxygen species (ROS), lactate dehydrogenase (LDH) content, apoptosis rate and DNA fragmentation and synthesis in human hepatocellular carcinoma cells (HepG2). The order of inhibitory effects for the individual pesticides was ranked as difenoconazole > cypermethrin > triazophos. The enhanced expression of caspase-3, caspase-7 and PARP activity was observed in HepG2 cells, which was 1.7, 1.3 and 1.6-fold higher than the control, respectively, along with significant protein cleavage; and induced apoptosis in a concentration-dependent manner. Further, the pesticide mixtures significantly increased ROS level (up to 1.3-fold), induced DNA fragmentation (up to 1.8-fold), inhibited DNA synthesis (up to 53%), and damaged the cells by destroying the cell membrane and producing a large amount of LDH at concentration range of 10-30 µM. Specifically, mixtures containing difenoconazole showed stronger toxicities than individual pesticides, implying higher health risks associated with mixtures. Our results show that three widely used pesticides exhibited cytotoxicity and apoptosis through the ROS-related caspase pathway, providing a basis for evaluation of health risks from pesticide mixtures via food consumption.
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Apoptose/efeitos dos fármacos , Dioxolanos/toxicidade , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Triazóis/toxicidade , Caspase 3/metabolismo , Caspase 7/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , L-Lactato Desidrogenase/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismoRESUMO
Humans and wildlife are continuously and simultaneously exposed to various pesticides that have been identified as endocrine disruptors which interfere with regulations of sexual differentiation and fertility. Low-dose effects of combined exposure from mixtures of pesticides have been extensively reported and need to be addressed in the context of human health risk assessment. The objective of the study is to assess the individual and combined anti-androgenic effects of twelve widely used pesticides in MDA-kb2 cells. The order of potency for seven pesticides with moderate anti-androgenic activities was in the order: fenitrothionâ¯>â¯dimethomorphâ¯>â¯difenoconazoleâ¯>â¯bromopropylateâ¯>â¯prochlorazâ¯>â¯imazalilâ¯>â¯endosulfan, which was induced by the androgen receptor (AR) antagonism rather than cytotoxicity (with the exception of endosulfan which exhibited the highest cytotoxicity). The other five pesticides exhibited lower anti-androgenic activities. At 10% of AR antagonistic effect, three mixtures comprised of the seven pesticides (Mix-EC10, Mix-EC20, and Mix-EC25) at equi-effect concentrations showed summed concentrations of 6.75E-11, 17.63 and 25.21⯵M, respectively. The combined effects were essentially close to the predicted of concentration addition (CA) at realistically low concentrations. In addition, molecular docking simulation indicated that hydrophobic interaction and polar functional groups of the pesticides contributed to the binding energy, which might be responsible for the AR antagonism. Our findings provide a basis for defining similarly acting antagonists in the context of cumulative risk assessment for pesticides in foods.
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Antagonistas de Androgênios/toxicidade , Disruptores Endócrinos/toxicidade , Praguicidas/toxicidade , Medição de Risco/métodos , Antagonistas de Androgênios/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Disruptores Endócrinos/metabolismo , Humanos , Simulação de Acoplamento Molecular , Praguicidas/metabolismo , Receptores Androgênicos/metabolismoRESUMO
The economic emission dispatch (EED) problem aims to control generation cost and reduce the impact of waste gas on the environment. It has multiple constraints and nonconvex objectives. To solve it, the collective neurodynamic optimization (CNO) method, which combines heuristic approach and projection neural network (PNN), is attempted to optimize scheduling of an electrical microgrid with ten thermal generators and minimize the plus of generation and emission cost. As the objective function has non-derivative points considering valve point effect (VPE), differential inclusion approach is employed in the PNN model introduced to deal with them. Under certain conditions, the local optimality and convergence of the dynamic model for the optimization problem is analyzed. The capability of the algorithm is verified in a complicated situation, where transmission loss and prohibited operating zones are considered. In addition, the dynamic variation of load power at demand side is considered and the optimal scheduling of generators within 24 h is described.