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BACKGROUND: Although previous studies have shown an association between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children, the results have been inconsistent. We summarize studies on the association between prenatal PFAS exposure and neurodevelopment in children in order to better understand the relationship. OBJECTIVE: We conducted a meta-analysis of prenatal PFAS exposure and developmental outcomes associated with intellectual, executive function and behavioral difficulty in children to explore the relationship between prenatal exposure to perfluorinated and polyfluoroalkyl substances (PFAS) and neurodevelopmental disorders in children. METHODS: We searched for articles published up to August 3, 2023, included and quantified original studies on PFAS and child Intelligence Quotient (IQ), executive function and behavioral difficulty during pregnancy, and systematically summarized articles that could not be quantified. CONCLUSION: There is evidence of sex-specific relationship between PFAS exposure and children's PIQ. We found that PFOS [ß = -1.56, 95% CI = -2.96, - 0.07; exposure = per 1 ln (ng/ml) increase], PFOA [ß = -1.87, 95% CI = -3.29, - 0.46; exposure = per 1 ln (ng/ml) increase], PFHxS [ß = -2.02, 95% CI = -3.23, - 0.81; exposure = per 1 ln (ng/ml) increase] decreased performance IQ in boys, but PFOS [ß = 1.56, 95% CI = 0.06, 3.06; exposure = per 1 ln (ng/ml) increase] increased performance IQ in girls. PFAS are associated with executive function impairments in children, but not related to behavioral difficulty in children.
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Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Feminino , Fluorocarbonos/toxicidade , Criança , Poluentes Ambientais/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/epidemiologia , Função Executiva/efeitos dos fármacos , Inteligência/efeitos dos fármacos , Masculino , Pré-Escolar , Exposição Materna/efeitos adversosRESUMO
BACKGROUND: Overweight and obesity lead to a range of noncommunicable diseases (NCDs), such as type 2 diabetes, cardiovascular disease, and stroke. Physical activity (PA) is an important lifestyle behavior for controlling body weight. Dietary inflammatory index (DII), which is associated with systemic inflammatory markers, is used to evaluate the potential of dietary inflammation. This is the first study to investigate the independent and joint associations of PA and DII with the risk of overweight/obesity among US adults. METHODS: Participants and data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, which is designed to examine the health and nutritional status of the non-institutionalized US population by a complex, multi-stage, probability sampling design. RESULTS: A total of 10723 US adults were selected. Physically active participants had lower overweight/obesity risk (total-time PA: OR = 0.756, 95% CI: 0.669-0.855; leisure-time PA: OR = 0.723, 95% CI: 0.643-0.813; and walk/bicycle-time PA: OR = 0.748, 95% CI: 0.639-0.875); however, those with work-time PA showed no significant association between PA and overweight/obesity. Compared with participants in the lowest DII group (Q1), those in the other three groups had high risks of overweight/obesity (Q2: OR = 1.218, 95% CI: 1.054-1.409; Q3: OR = 1.452, 95% CI: 1.245-1.693; Q4: OR = 1.763, 95% CI: 1.495-2.079). In joint analyses, PA was not eligible for reducing risks of weight/obesity if far more pro-inflammatory diet (Q4 of DII = 2.949-5.502) was taken in (total-time PA: OR = 1.725, 95% CI: 1.420-2.097; leisure-time PA: OR = 1.627, 95% CI: 1.258-2.105; walk/bicycle-time PA: OR = 1.583, 95% CI: 1.074-2.332; and work-time PA: OR = 1.919, 95% CI: 1.493-2.467). CONCLUSIONS: More leisure-time PA and walk/bicycle-time PA are associated with lower risk of overweight/obesity, and higher DII is associated with higher risk of overweight/obesity. In addition, higher DII impacts overweight/obesity substantially: once the DII score reached Q4, there is still risks of overweight/obesity even if PA is performed.
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Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Humanos , Sobrepeso/epidemiologia , Sobrepeso/etiologia , Inquéritos Nutricionais , Obesidade/epidemiologia , Obesidade/etiologia , Dieta , Exercício FísicoRESUMO
BACKGROUND/OBJECTIVES: To identify modifiable risk factors for type 2 diabetes mellitus and explore the relationship between diet sodium intake and blood glucose levels. MATERIALS/METHODS: Based on inclusion and exclusion criteria, we extracted, analyzed, and assessed the available crossover studies of dietary salt intake restriction and insulin resistance in PubMed, Web of Science, MEDLINE, Embase, Wanfang, and CNKI databases. RESULTS: We included 6 studies with 8 sets of data, covering 485 subjects. I2 statistics results showed insignificant heterogeneity among all data (I2 = 39.2% < 50%). Thus, a fixed-effect model was adopted for the final pooled effect size. Weighted mean difference and its 95% confidence interval (CI) value was 0.193 (95% CI, 0.129-0.257), and the test of the overall effect showed P < 0.001. The results revealed that the blood glucose levels in the subjects in the low-salt intake group were significantly higher than those in the normal or high-salt intake groups. We also found no significant change occurred after the removal of any study through sensitivity analysis, which confirmed that the outcome we calculated was prudent and credible. The quantitative Egger's test (P = 0.109 > 0.05) indicated that insignificant publication bias existed. CONCLUSION: This meta-analysis highlights the relationship between dietary sodium intake and blood glucose levels. Our findings show that higher blood glucose levels might be expected in hypertensive or normal people with low-salt consumption compared to those with normal or high-salt consumption, although these differences were not clinically significant. Trial Registration: PROSPERO Identifier: CRD42021256998.
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OBJECTIVE: Ultraviolet-B (UVB) radiation is an important factor in causing skin damage. The study is to explore whether 1,25-Dihydroxvitamin D3(1,25(OH)2D3) will attenuate the damage of human immortalised keratinocytes (HaCaT) cells caused by UVB and relevant underlying mechanisms. METHODS: CCK-8 was employed to determine the UVB irradiation intensity and 1,25(OH)2D3 concentration. Western blot was used to detect the expression of NF-κB, Caspase9, Caspase3, Bax, Bcl2, FADD, CytC, Beclin-1; Flowcytometry was applied to measure the production of ROS. RESULTS: The concentration of 1,25(OH)2D3 used in the study was 100 nM and the UVB irradiation intensity was 20 mJ/cm2. Compared with the HaCaT cells irradiated with UVB, the HaCaT cells that were pre-treated with 1,25(OH)2D3 had lower production of ROS, lower expression of NF-κB, Caspase9, Caspase3, Bax, FADD, CytC and Beclin-1(P < 0.05). CONCLUSION: 1,25(OH)2D3 could inhibit the development of oxidative stress and apoptosis in HaCaTs triggered by UVB. This inhibition might be achieved through the suppression of mitochondria-modulated apoptosis and autophagy. Vitamin D may be a potential UVB protective component.
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Queratinócitos , NF-kappa B , Humanos , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Proteína Beclina-1/metabolismo , Proteína X Associada a bcl-2/metabolismo , Queratinócitos/metabolismo , Apoptose/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
Perfluorooctanoic acid is an artificial and non-degradable chemical. It is widely used due to its stable nature. It can enter the human body through food, drinking water, inhalation of household dust and contact with products containing perfluorooctanoic acid. It accumulates in the human body, causing potential harmful effects on human health. Based on the biodegradability and bioaccumulation of perfluorooctanoic acid in the human body, there are increasing concerns about the adverse effects of perfluorooctanoic acid exposure on kidneys. Research shows that kidney is the main accumulation organ of Perfluorooctanoic acid, and Perfluorooctanoic acid can cause nephrotoxicity and produce adverse effects on kidney function, but the exact mechanism is still unknown. In this review, we summarize the relationship between Perfluorooctanoic acid exposure and kidney health, evaluate risks more clearly, and provide a theoretical basis for subsequent research.
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(1) Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant, and it is receiving increasing attention regarding its human health risks due to its extensive use. Endothelial dysfunction is a mark of cardiovascular disease, but the basic mechanism of PFOS-induced endothelial dysfunction is still not fully understood. Ferroptosis is a newly defined regulatory cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although ferroptosis has been shown to be involved in the pathogenesis of cardiovascular diseases, the involvement of ferroptosis in the pathogenesis of endothelial dysfunction caused by PFOS remains unclear. (2) Purpose: To explore the role of ferroptosis in the dysfunction of endothelial cells and underlying mechanisms. (3) Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to PFOS or PFOS and Fer-1. The viability, morphology change under electronic microscope, lipid-reactive oxygen species (lipid-ROS), and production of nitric oxide (NO) were determined. The expression of glutathione peroxidase 4(GPX4), ferritin heavy chain protein 1 (FTH1), heme oxygenase 1 (HO-1) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) were analyzed via Western blot analysis. (4) Results: PFOS was shown to cause a decrease in viability and morphological changes of mitochondria, and well as an increase in lipid droplets. The expression of GPX4, FTH1 and HO-1 was decreased, and that of ACSL4 was increased after exposure to PFOS. In addition to the above-mentioned ferroptosis-related manifestations, there was also a reduction in NO content. (5) Conclusions: PFOS induces ferroptosis by regulating the GPX4 and ACSL4 pathways, which leads to HUVEC dysfunction.
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Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant and environmental endocrine disruptor that has been shown to be associated with the development of many diseases; it poses a considerable threat to the ecological environment and to human health. PFOS is known to cause damage to renal cells; however, studies of PFOS-induced ferroptosis in cells have not been reported. We used the CCK-8 method to detect cell viability, flow cytometry and immunofluorescence methods to detect ROS levels and Western blot to detect ferroptosis, endoplasmic reticulum stress, antioxidant and apoptosis-related proteins. In our study, we found that PFOS could induce the onset of ferroptosis in HK-2 cells with decreased GPx4 expression and elevated ACSL4 and FTH1 expression, which are hallmarks for the development of ferroptosis. In addition, PFOS-induced ferroptosis in HK-2 cells could be reversed by Fer-1. We also found that endoplasmic reticulum stress and its mediated apoptotic mechanism and P53-mediated antioxidant mechanism are involved in the toxic damage of cells by PFOS. In this paper, we demonstrated for the first time that PFOS can induce ferroptosis in HK-2 cells. In addition, we preliminarily explored other mechanisms of cytotoxic damage by PFOS, which provides a new idea to study the toxicity of PFOS as well as the damage to the kidney and its mechanism.
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Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows that the liver is the major target of PFOS, and that PFOS can damage liver tissue and disrupt its function; however, the exact mechanisms remain unclear. In this study, we reviewed the adverse effects of PFOS on liver tissue and cells, as well as on liver function, to provide a reference for subsequent studies related to the toxicity of PFOS and liver injury caused by PFOS.
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Orchardgrass (Dactylis glomerata) is one of the top four perennial forages worldwide and, despite its large economic advantages, often threatened by various environmental stresses. WRKY transcription factors (TFs) can regulate a variety of plant processes, widely participate in plant responses to biotic and abiotic stresses, and are one of the largest gene families in plants. WRKYs can usually bind W-box elements specifically. In this study, we identified a total of 93 DgWRKY genes and 281 RGAs, including 65, 169 and 47 nucleotide-binding site-leucine-rich repeats (NBS-LRRs), leucine-rich repeats receptor-like protein kinases (LRR-RLKs), and leucine-rich repeats receptor-like proteins (LRR-RLPs), respectively. Through analyzing the expression of DgWRKY genes in orchardgrass under different environmental stresses, it was found that many DgWRKY genes were differentially expressed under heat, drought, submergence, and rust stress. In particular, it was found that the greatest number of genes were differentially expressed under rust infection. Consistently, GO and KEGG enrichment analysis of all genes showed that 78 DgWRKY TFs were identified in the plant-pathogen interaction pathway, with 59 of them differentially expressed. Through cis-acting element prediction, 154 RGAs were found to contain W-box elements. Among them, DG6C02319.1 (a member of the LRR-RLK family) was identified as likely to interact with 14 DGWRKYs. Moreover, their expression levels in susceptible plants after rust inoculation were first up-regulated and then down-regulated, while those in the resistant plants were always up-regulated. In general, DgWRKYs responded to both biotic stress and abiotic stress. DgWRKYs and RGAs may synergistically respond to the response of orchardgrass to rust. This study provides meaningful insight into the molecular mechanisms of WRKY proteins in orchardgrass.
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Many industries produce large amounts of glycerol-based wastewater, which always contains hazardous organic chlorides. Compared with complicated biological treatments or physical adsorption, membrane separation decreases the cost and saves energy. Strong swelling of traditional thin-film composite (TFC) membranes influence the performance in the separation of organic molecules. Here we prepared TFC membranes with an acrylamide-grafted PAN support layer to copolymerize with m-phenylenediamine (MPD) and trimesoyl chloride (TMC). The link of separative layer and support layer was created like a zipper stitching to enhance the stability and resistance for the removal of organic molecules. An aquatic grass-like layer of acrylamide enlarges the surface area and hydrophilicity with superior separation performances (15.8 LMH bar-1 flux, 72.0% rejection of dichloropropanol (DCP) and 64.6% rejection of glycerol (Gl)). The trade-off upper bound was improved to a high level. We also established the simulations of evaporation using Aspen Plus and mathematical models of reverse osmosis to calculate the energy consumption corresponding to the recycle of glycerol-based wastewater. The experimental and theoretical results illustrate the advantages of acrylamide-grafted TFC membranes in the ap-plications to concentrate organic solutes and treat wastewater.
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Solute purification, solvent recovery, solvent separation in organic solvents are more and more widely used in the chemical industries, pharmaceuticals and food processing. Fast and efficient separations can be realized using membrane separation technology. Materials with strong organic solvent resistance for membrane preparation have attracted growing research interest and have been regarded as a necessary approach for various environmental and energy-related separations. Kinds of novel polymers, metal/covalent-organic framework, carbon materials, polymers of intrinsic microporosity and conjugated microporous polymers provide possibilities and solutions to prepare organic solvent resistant membranes. In view of the tremendous progress made over the past few years, it is valuable to summarize the recent developments timely and systematically in this multidisciplinary field, from which researchers can forecast trends in the future. In this review, we firstly introduced advanced membrane separation technologies, including pervaporation, organic solvent ultrafiltration, organic solvent nanofiltration, organic solvent reverse osmosis and organic solvent forward osmosis. Then we highlighted novel membrane materials and preparations in recent years and introduced the applications in the dyes separation, petroleum industry, food processing, pharmaceuticals, separation of organic solvents and wastewater treatment. Lastly, some unsolved problems and challenges at the scientific and technical level related to perspectives are discussed, prompting the further development of next-generation organic solvent resistant membranes.
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Filtração , Preparações Farmacêuticas , Osmose , Solventes , UltrafiltraçãoRESUMO
Orchardgrass (Dactylis glomerata L.) is drought resistant and tolerant to barren landscapes, making it one of the most important forages for animal husbandry, as well as ecological restoration of rocky landscapes that are undergoing desertification. However, orchardgrass is susceptible to rust, which can significantly reduce its yield and quality. Therefore, understanding the genes that underlie resistance against rust in orchardgrass is critical. The evolution, cloning of plant disease resistance genes, and the analysis of pathogenic bacteria induced expression patterns are important contents in the study of interaction between microorganisms and plants. Genes with nucleotide binding site (NBS) structure are disease-resistant genes ubiquitous in plants and play an important role in plant attacks against various pathogens. Using sequence analysis and re-annotation, we identified 413 NBS resistance genes in orchardgrass. Similar to previous studies, NBS resistance genes containing TIR (toll/interleukin-1 receptor) domain were not found in orchardgrass. The NBS resistance genes can be divided into four types: NBS (up to 264 homologous genes, accounting for 64% of the total number of NBS genes in orchardgrass), NBS-LRR, CC-NBS, and CC-NBS-LRR (minimum of 26 homologous genes, only 6% of the total number of NBS genes in orchardgrass). These 413 NBS resistance genes were unevenly distributed across seven chromosomes where chromosome 5 had up to 99 NBS resistance genes. There were 224 (54%) NBS resistance genes expressed in different tissues (roots, stems, leaves, flowers, and spikes), and we did not detect expression for 45 genes (11%). The remaining 145 (35%) were expressed in some tissues. And we found that 11 NBS resistance genes were differentially expressed under waterlogging stress, 5 NBS resistance genes were differentially expressed under waterlogging and drought stress, and 1 NBS resistance was is differentially expressed under waterlogging and heat stress. Most importantly, we found that 65 NBS resistance genes were significantly expressed in different control groups. On the 7th day of inoculation, 23 NBS resistance genes were differentially expressed in high resistance materials alone, of which 7 NBS resistance genes regulate the "plant-pathogen interaction" pathway by encoding RPM1. At the same time, 2 NBS resistance genes that were differentially expressed in the high resistance material after inoculation were also differentially expressed in abiotic stress. In summary, the NBS resistance gene plays a crucial role in the resistance of orchardgrass to rust.
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Dactylis , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Estresse Fisiológico , Dactylis/genética , Dactylis/metabolismoRESUMO
BACKGROUND: Lipid infiltration and inflammatory response run through the occurrence of atherosclerosis. Differentiation into macrophages and foam cell formation are the key steps of AS. Aim of this study was that the differential gene expression between foam cells and macrophages was analyzed to search the key links of foam cell generation, so as to explore the pathogenesis of atherosclerosis and provide targets for the early screening and prevention of coronary artery disease (CAD). METHODS: The gene expression profiles of GSE9874 were downloaded from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9874) on GPL96 [HG-U133A] Affymetrix Human Genome U133. A total of 22,383 genes were analyzed for differentially expression genes (DEGs) by Bayes package. GO enrichment analysis and KEGG pathway analysis for DEGs were performed using KOBAS 3.0 software (Peking University, Beijing, China). STRING software (STRING 10.0; European Molecular Biology Laboratory, Heidelberg, Germany) was used to analyze the protein-protein interaction (PPI) of DEGs. RESULTS: A total of 167 DEGs between macrophages and foam cells were identified. Compared with macrophages, 102 genes were significantly upregulated and 65 genes were significantly downregulated (P < 0.01, fold-change > 1) in foam cells. DEGs were mainly enrich in 'sterol biosynthetic and metabolic process', 'cholesterol metabolic and biosynthetic process' by GO enrichment analysis. The results of KEGG pathway analysis showed all differential genes are involved in biological processes through 143 KEGG pathways. A PPI network of the DEGs was constructed and 10 outstanding genes of the PPI network was identified by using Cytoscape, which include HMGCR, SREBF2, LDLR, HMGCS1, FDFT1, LPL, DHCR24, SQLE, ABCA1 and FDPS. CONCLUSION: Lipid metabolism related genes and molecular pathways were the key to the transformation of macrophages into foam cells. Therefore, lipid metabolism disorder is the key to turn macrophages into foam cells, which plays a major role in CAD.
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Aterosclerose/genética , Células Espumosas/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de Proteínas , Transdução de Sinais/genética , Transcriptoma , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Bases de Dados Genéticas , Células Espumosas/patologia , HumanosRESUMO
We fabricate a time-multiplexed stereoscopic display, which is composed of a quantum dot-polymer (QDP) scanning backlight, 120 Hz liquid crystal display (LCD), and shutter glasses. Blue LEDs, which can excite QDP film to produce white light, are adopted to replace the traditional white LEDs. The QDP scanning backlight, LCD, and shutter glasses can be controlled by the synchronization signal and work together, enabling viewers to obtain parallax views. Crosstalk is about 1%, and luminance through the shutter glasses is higher than 150 nit. The color gamut can be widely extended to 77.98% rather than the traditional 55.75% in the ITU-R Recommendation BT.2020 (Rec.2020) color space, due to the excellent properties of QD material.
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To explore the role of NF-κB activation in the development of insulin resistance and investigate whether or not that the inhibition of NF-κB activation by PDTC will improve the insulin resistance of L6 cells exposed to H2O2. L6 cells were treated with H2O2, PDTC or both H2O2 and PDTC for 4 hours. The uptake of glucose with stimulation of insulin, the expression of P38-MAPK, p- P38-MAPK, NF-κBp65, p- NF-κBp65, IRS-1, IRS-2, p-IRS-2, PI3K, IκBα, p- IκBα, caspase-8 and GLUT4, the production of ROS, TNF-α, IL-6 and IL-1ß as well as the apoptosis rate of L6 cells were determined and compared in L6 treated with H2O2 alone or both H2O2 and PDTC. Compared with the L6 cells treated with H2O2 alone, the L6 cells treated with both H2O2 and PDTC showed (1) significantly lower production of ROS, TNF-α, IL-6 and IL-1ß; (2) significantly decreased expression of P38-MAPK, p- P38-MAPK and NF-κBp65, p- NF-κBp65, p- IκBα and caspase-8; (3) significantly lower rate of apoptosis; (4) significantly higher expression of IRS-2, p-IRS-2 (Tyr 612), PI3K and GLUT4; (5) significantly higher uptake of glucose with stimulation of insulin; (6) significantly increased expression of Bcl2 and decreased ratio of Bax to Bcl2. Based on the findings of the present study, inhibition of NF-κB activation by PDTC would improve the insulin resistance of L6 cells exposed to H2O2.
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Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Prolina/análogos & derivados , Tiocarbamatos/farmacologia , Absorção Fisiológica/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glucose/metabolismo , Peróxido de Hidrogênio/toxicidade , Mediadores da Inflamação/metabolismo , Cinética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , NF-kappa B/agonistas , NF-kappa B/metabolismo , Oxidantes/toxicidade , Prolina/farmacologia , RatosRESUMO
Paraquat (PQ) is a widely used herbicide, and lung is the primary target of PQ poisoning. Metallothionein (MT) is a potent antioxidant and free radical scavenger, and has been shown to play a protective role in lung injury induced by different stressors. This study was undertaken to evaluate the protective potential of MT against PQ-induced acute lung injury using MT-I/II null (MT(-/-)) mice. Wild-type (MT(+/+)) mice and MT(-/-) mice were given one intragastric administration of 50mg/kg PQ for 24h, and it was revealed that MT(-/-) mice were more susceptible to PQ-induced acute lung injury than MT(+/+) mice evidenced by the following findings. As compared with MT(+/+) mice, MT(-/-) mice presented more severe histopathological lesions in the lung, higher pulmonary malondialdehyde content, and more reduced pulmonary antioxidative enzymes activities. PQ also induced more apoptosis in pneumocytes from MT(-/-) mice, and the expressions of apoptosis-related proteins Bax, Bcl-2, cleaved-caspase-3, and the ratio of Bax/Bcl-2 were all more significantly increased in PQ-treated MT(-/-) mice. Our results clearly demonstrate that endogenous MT can attenuate PQ-induced acute lung injury, possibly through the mechanisms of anti-oxidation and anti-apoptosis.
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Lesão Pulmonar Aguda/prevenção & controle , Antioxidantes , Apoptose/fisiologia , Herbicidas/toxicidade , Metalotioneína/fisiologia , Paraquat/toxicidade , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/enzimologia , Animais , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Camundongos , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: Few studies have investigated the effects produced by combinations of polysaccharides and chemotherapeutic drugs in cancer treatment. We hypothesized that a combination of polysaccharides (COP) from Lentinus edodes and Tricholoma matsutake would improve the efficacy of 5-fluorouracil (5-FU)-mediated inhibition of H22 cell growth. METHODS: Mice were injected H22 cells and then treated with either 5-FU, polysaccharides from Tricholoma matsutake (PTM), polysaccharides from Lentinus edodes (PL), PTM+PL, 5-FU+PTM, 5-FU+ PL, or 5-FU + COP. The tumor weight and volume, and splenic CD4 + and CD8 + T cell frequencies, were determined. Additionally, splenic natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activities were assessed and the serum levels of tumor necrosis factor-alpha (TNF-alpha), Interleukin-2 (IL-2), and Interferon-gamma (IFN-gamma) were measured. RESULTS: Compared with mice from the control, 5-FU, PL, PTM, PTM + PL, 5-FU + PL, and 5-FU + PTM groups, mice treated with 5-FU + COP showed: (a) significantly reduced tumor weight and volume (P < 0.05); (b) significantly higher serum levels of TNF-alpha, IL-2, and IFN-gamma (P < 0.05); (c) significantly increased CD4+ and CD8+ T cell frequencies in the spleen (P < 0.05); and (d) significantly increased splenic NK cell and CTL activities (P < 0.05). The tumor weight and volume in mice treated with 5-FU+PL or 5-FU+PTM were significantly reduced compared with mice treated with 5-FU alone (P < 0.05). Serum levels of TNF-alpha, IL-2, and IFN-gamma, frequencies of CD4 + and CD8+ T cells in the spleen, and splenic NK and CTL activities were also significantly increased in mice treated with 5-FU+PL or 5-FU+PTM compared with mice treated with 5-FU alone (P < 0.05). CONCLUSION: Polysaccharides from Lentinus edodes and Tricholoma matsutake could enhance the efficacy of 5-FU-mediated H22 cell growth inhibition.
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Carcinoma Hepatocelular/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Cogumelos Shiitake/química , Tricholoma/química , Animais , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores do Crescimento/administração & dosagem , Humanos , Fatores Imunológicos/administração & dosagem , Imunomodulação/efeitos dos fármacos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Verduras/químicaRESUMO
In recent years, it has been an attractive challenge to fabricate multiple stimuli-responsive hybrid microgels composed of polymer microgel and gold nanoparticle (AuNP). Herein, we report on the detailed synthesis of poly(N-isopropylacrylamide-co-methacrylic acid)--Au hybrid microgels by in situ reduction of gold precursor in the presence of thiol-functionalized poly(N-isopropylacrylamide-co-methacrylic acid) microgels. The as-synthesized hybrid microgels showed well-defined swelling/deswelling transition in response to the surrounding temperature, pH, and light irradiation. The hybrid microgels had a unique microstructure where a large number of AuNP's distribute mainly in the interior of microgel with a fluff-like surface. The plasmonic property of the hybrid microgels can be modulated through the volume phase transition induced by the external triggers such as temperature and pH. In the reduction of 4-nitrophenol catalyzed by the hybrid microgels, it was found that the reaction rate did not increase monotonously with temperature but greatly decreased in a certain temperature range, showing a tunable catalytic activity.
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Persistent organic pollutant exposure is strongly associated with the development of diabetes. The development of diabetes or alteration in blood glucose levels is associated with insulin resistance that precedes diabetes for many years. Omethoate is a commonly used insecticide in most developing countries. The present study was designed to elucidate the potent role of omethoate in developing insulin resistance in rats. Male Wistar rats were exposed to omethoate at the concentration of 1.5mg/kg body weight (1/40 LD50), 3 mg/kg body weight (1/20 LD50) and 6 mg/kg body weight (1/10 LD50) through gastric injection for 60 days; control group rats received PBS through gastric injection. The results showed that the levels of MDA, TNF-α and IL-6 were increased and the activities of SOD and GSH-Px were decreased in the right thigh muscles of rats exposed to omethoate. However, JNK, p38 MAPK and NF-κB in right thigh muscles of rats exposed to omethoate were activated. This study suggested that omethoate had a potential to cause insulin resistance.
Assuntos
Dimetoato/análogos & derivados , Inseticidas/toxicidade , Resistência à Insulina , Animais , Glicemia/análise , Dimetoato/toxicidade , Glutationa Peroxidase/metabolismo , Insulina/sangue , Interleucina-6/sangue , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Malondialdeído/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Bone marrow mesenchymal stem cells (BMSCs) are potential therapy for diabetes. Owing to the oxidative stress caused by hyperglycemia, these transplanted BMSCs are with high rate of apoptotic death after transplantation. Ginkgo biloba L. extract (EGB) is a potent antioxidant which can remove free radicals. The study was to investigate whether EGB can protect BMSCs from oxidative stress in vitro and enhance the efficacy of BMSCs in lowering blood glucose levels after transplantation. BMSCs were cultured with H2O2, EGB, or H2O2 and EGB. Cell viability, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and cell death rates were determined. Diabetes was induced by single injection of streptozotocin (STZ) in male Wistar rats. Diabetic rats received EGB, BMSCs, or EGB/BMSCs. The serum levels of glucose, insulin, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), MDA, SOD, and GSH-Px were determined. PKCα expression and NF-κB activation in kidney were determined. The MDA levels and cell death rates in BMSCs cultured with H2O2 and EGB were significantly lower; cell viability, SOD, and GSH-Px activities were significantly higher compared with those with H2O2 alone. Compared with diabetic rats receiving BMSCs, diabetic rats receiving EGB before BMSCs transplantation showed (1) significantly lower levels of blood glucose, serum MDA, IL-6, and TNF-α, and higher levels of insulin, SOD, and GSH-Px activities; (2) significantly lower PKCα expression and NF-κB activation in the kidney. EGB administration before BMSC transplantation can enhance the effectiveness of BMSCs in lowering blood glucose levels and reversing oxidative stress in diabetic rats.