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As alternatives to traditional per- and polyfluoroalkyl substances, perfluoroalkyl phosphonic acids (PFPiAs) are frequently detected in aquatic environments, but the neurotoxic effects and underlying mechanisms remain unclear. In this study, male zebrafish were exposed to 6:6 PFPiA (1 and 10 nM) for 28 days, which exhibited anxiety-like symptoms. Gut microbiome results indicated that 6:6 PFPiA significantly increased the abundance of Gram-negative bacteria, leading to enhanced levels of lipopolysaccharide (LPS) and inflammation in the gut. The LPS was delivered to the brain through the gut-brain axis (GBA), damaged the blood-brain barrier (BBB), stimulated neuroinflammation, and caused apoptosis as well as neural injury in the brain. This mechanism was verified by the fact that antibiotics reduced the LPS levels in the gut and brain, accompanied by reduced inflammatory responses and anxiety-like behavior. The BBB damage also resulted in the enhanced accumulation of 6:6 PFPiA in the brain, where it might bind strongly with and activate aryl hydrocarbon receptor (AhR) to induce brain inflammation directly. Additionally, as the fish received treatment with an inhibitor of AhR, the inflammation response and anxiety-like behavior decreased distinctly. This study sheds light on the new mechanisms of neurotoxicity-induced 6:6 PFPiA due to the interruption on GBA.
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Eje Cerebro-Intestino , Microbioma Gastrointestinal , Ácidos Fosforosos , Animales , Masculino , Inflamación , Lipopolisacáridos , Pez Cebra , Ácidos Fosforosos/toxicidadRESUMEN
Microcystin-leucine arginine (MCLR), a widespread environmental contaminant produced by cyanobacteria, poses a severe threat to the male reproductive system. However, the mechanisms of MCLR-induced testis injury accompanied by autophagy are still obscure. This study aimed to investigate the effects of MCLR on autophagy and apoptosis on the male reproductive system and its mechanism both in vitro and in vivo. MCLR caused damage to the testis of zebrafish, resulting in decreased hatching and growth retardation in the offspring. It also remarkably enhanced autophagic ï¬ux by elevating the expression of LC3BII, ATG5, and ATG12 proteins. The autophagic flux was also conï¬rmed through the formation of autophagosomes in the ultrastructure of the zebrafish testis and the accumulation of LC3-positive puncta in zebrafish testis and mouse TM4 cells. Further evaluations revealed that inhibition of autophagy by 3-methyladenine (3-MA) significantly attenuated MCLR-induced apoptosis. This finding indicated that autophagy plays an essential role in cell death in the male reproductive system. Besides, inhibiting endoplasmic reticulum (ER) stress using 4-phenylbutyrate (4-PBA) remarkably blocked autophagy and partially suppressed apoptosis in TM4 cells induced by MCLR. This phenomenon suggested that ER stress-related autophagy was involved in MCLR-induced apoptosis. This study reveals crosstalk between ER stress and autophagy via the PERK/eIF2α/ATF4 signaling pathway. It further suggests that ER stress-related autophagy contributes to MCLR-induced apoptosis and injury in the male reproductive system. These ï¬ndings provide a novel insight into MCLR-induced impairments of the testis.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Microcistinas/toxicidad , Testículo/efectos de los fármacos , Animales , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Línea Celular , Masculino , Ratones , Fenilbutiratos/farmacología , Transducción de Señal/efectos de los fármacos , Testículo/ultraestructura , Pez CebraRESUMEN
Radix Aconiti Lateralis Preparata (Fuzi) is an important, toxic traditional Chinese medicine that has been widely used in clinical practice. Due to the toxicity of its raw materials, it needs to be processed before application. The changes in the physicochemical properties of Fuzi starch during processing were evaluated by scanning electron microscopy, X-ray diffraction and differential scanning calorimetry. The results showed the following: morphological properties changed from spherical to irregular and polygonal particles, while the particle size increased significantly; amylose content and solubility decreased significantly; swelling power and water-binding capacity increased significantly; the X-ray diffraction peak disappeared, and the crystallinity decreased; and the gelatinization temperature and enthalpy decreased significantly. The properties of Fuzi starch were similar to those of pregelatinized starch. These results indicated that Fuzi starch undergone repeated processes of gelatinization and aging, which destroyed the original crystal structure of the starch.
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BACKGROUND: Organophosphate and carbamate pesticide residues in food and the environment pose a great threat to human health and have made the easy and rapid detection of these pesticide residues an important task. Discovering new enzyme sources from plants can help reduce the cost of large-scale applications of rapid pesticide detection via enzyme inhibition. RESULTS: Plant esterase from kidney beans was purified. Kidney bean esterase is identified as a carboxylesterase by substrate and inhibitor specificity tests and mass spectrometry identification. The kidney bean esterase demonstrates optimal catalytic activity at 40 °C, pH 6.5 and an enzyme concentration of 0.30 µg mL-1 . The kidney bean esterase can be inhibited by organophosphate and carbamate pesticides, which can be substituted for acetylcholinesterase. The limit of detection of the purified kidney bean esterase was two- to 20-fold higher than that of the crude one. The method detection limit meets the detection requirement for the maximum residue limits (MRL) in actual samples. CONCLUSION: The findings of the present study provide a new source of enzymes for pesticides detection by enzyme inhibition. © 2018 Society of Chemical Industry.
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Carbamatos/química , Carboxilesterasa/química , Organofosfatos/química , Plaguicidas/química , Phaseolus/enzimología , Proteínas de Plantas/química , Biocatálisis , Carboxilesterasa/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Cinética , Phaseolus/química , Proteínas de Plantas/antagonistas & inhibidoresRESUMEN
BACKGROUND: Enzyme inhibition-based detection is the most widely used method for rapid detection of organophosphorus pesticides (OPs) in food and agricultural products. However, the accuracy of the method is negatively affected by low inhibitory activities of OPs with PS moiety on acetylcholinesterase. RESULTS: We demonstrated that oxidation pretreatments with bromine, hydrogen peroxide, or calcium hypochlorite significantly enhanced the enzyme inhibitory activities of these OPs. Especially, calcium hypochlorite (0.05%) pretreatment converted the PS moiety in OPs to PO and produced the most potent and steady inhibitory effect on the enzyme. This, in turn, resulted in a dramatic increase in the sensitivity of enzyme inhibition-based detection of these OPs by as much as 2 to 7 orders of magnitude. Importantly, this enhanced detection of OPs was validated in various vegetable samples. CONCLUSION: Our findings provide a solid basis to use calcium hypochlorite pretreatment for the improved detection of OPs by the enzyme inhibition-based method. © 2017 Society of Chemical Industry.
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Acetilcolinesterasa/química , Compuestos de Calcio/química , Inhibidores de la Colinesterasa/química , Pruebas de Enzimas/métodos , Compuestos Organofosforados/química , Plaguicidas/química , Oxidación-ReducciónRESUMEN
Microcystins (MCs) are common toxins produced by freshwater cyanobacteria, and they represent a potential health risk to aquatic organisms and animals, including humans. Specific inhibition of protein phosphatases 1 and 2A is considered the typical mechanism of MCs toxicity, but the exact mechanism has not been fully elucidated. To further our understanding of the toxicological mechanisms induced by MCs, this study is the first to use a chemical proteomic approach to screen proteins that exhibit special interactions with MC-arginine-arginine (MC-RR) from zebrafish (Danio rerio) liver. Seventeen proteins were identified via affinity blocking test. Integration of the results of previous studies and this study revealed that these proteins play a crucial role in various toxic phenomena of liver induced by MCs, such as the disruption of cytoskeleton assembly, oxidative stress, and metabolic disorder. Moreover, in addition to inhibition of protein phosphate activity, the overall toxicity of MCs was simultaneously modulated by the distribution of MCs in cells and their interactions with other target proteins. These results provide new insight into the mechanisms of hepatotoxicity induced by MCs. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1206-1216, 2016.
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Hígado/efectos de los fármacos , Microcistinas/toxicidad , Proteoma/efectos de los fármacos , Proteómica , Pez Cebra/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Cianobacterias/metabolismo , Citoesqueleto/efectos de los fármacos , Electroforesis en Gel Bidimensional , Humanos , Hígado/metabolismo , Toxinas Marinas , Microcistinas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteína Fosfatasa 1/antagonistas & inhibidores , Proteína Fosfatasa 1/metabolismo , Proteína Fosfatasa 2/antagonistas & inhibidores , Proteína Fosfatasa 2/metabolismo , Proteoma/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Hepatotoxic microcystins (MCs) are produced by cyanobacteria in diverse water bodies and the pathophysiology includes induction of reactive oxygen species and adenosine triphosphate (ATP) depletion in cells. In this study, we evaluated MCs induced changes in the oxidative phosphorylation (OXPHOS) system in mitochondria of crucian carp liver. Fish were subdivided into two groups that were intraperitoneally injected with two doses of MCs (50 and 200 MC-LReq µg/kg bw) and were sacrificed at 1, 3, 12, 24, and 48 h postinjection. The activities of five enzyme complexes of electron transport chain and mRNA expression of mitochondrial-encoded genes (cox1, cox2, cox3, and atp6) were significantly reduced in a time-dependent pattern after injection. There were also changes in mitochondrial ultrastructure, decreases in ATPase activities and reduction in antioxidant level after MCs exposure. Disorder in the OXPHOS system and decreased activities of antioxidative enzymes might contribute to bioenergy deficiency and consequent hepatocyte damage induced by MCs.
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Carpa Dorada/metabolismo , Microcistinas/toxicidad , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Animales , Antioxidantes/metabolismo , Cianobacterias/metabolismo , Transporte de Electrón/efectos de los fármacos , Inyecciones Intraperitoneales , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Mitocondrias Hepáticas/enzimología , Mitocondrias Hepáticas/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The health risks associated with combined exposure to microplastics (MPs) and cyanobacteria toxins have gained increasing attention due to the large-scale prevalence of cyanobacterial blooms and accumulation of MPs in aquatic environments. Therefore, we explored the cardiovascular toxic effects of microcystin-LR (MC-LR, 1, 10, 100 µg/L) in the presence of 5 µm polystyrene microplastics (PS-MPs, 100 µg/L) and 80 nm polystyrene nanoplastics (PS-NPs, 100 µg/L) in zebrafish models. Embryos were exposed to certain PS-MPs and PS-NPs conditions in water between 3 h post-fertilization (hpf) and 168 hpf. Compared to MC-LR alone, a significant decrease in heart rate was observed as well as notable pericardial edema in the MC-LR + PS-MPs/NPs groups. At the same time, sinus venosus and bulbus arteriosus (SV-BA) distances were significantly increased. Furthermore, the addition of PS-MPs/NPs caused thrombosis in the caudal vein and more severe vascular damage in zebrafish larvae compared to MC-LR alone. Our findings revealed that combined exposure to PS-NPs and MC-LR could significantly decreased the expression of genes associated with cardiovascular development (myh6, nkx2.5, tnnt2a, and vegfaa), ATPase (atp1a3b, atp1b2b, atp2a1l, atp2b1a, and atp2b4), and the calcium channel (cacna1ab and ryr2a) compared to exposure to MC-LR alone. In addition, co-exposure with PS-MPs/NPs exacerbated the MC-LR-induced reactive oxygen species (ROS) production, as well as the ROS-stimulated apoptosis and heightened inflammation. We also discovered that astaxanthin (ASTA) treatment partially attenuated these cardiovascular toxic effects. Our findings confirm that exposure to MC-LR and PS-MPs/NPs affects cardiovascular development through calcium signaling interference and ROS-induced cardiovascular cell apoptosis. This study highlights the potential environmental risks of the co-existence of MC-LR and PS-MPs/NPs for fetal health, particularly cardiovascular development.
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Embrión no Mamífero , Toxinas Marinas , Microcistinas , Microplásticos , Estrés Oxidativo , Poliestirenos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Microcistinas/toxicidad , Microplásticos/toxicidad , Toxinas Marinas/toxicidad , Poliestirenos/toxicidad , Embrión no Mamífero/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidadRESUMEN
Microcystins (MCs) are highly liver-specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC-LR exposure under hypoxic (1% O2 ) and normoxic (21% O2 ) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC-LR in normoxia although decreased in hypoxia. MC-LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC-LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c-IAP2) was significantly up-regulated by MC-LR under normoxic condition, suggesting that c-IAP2 played an important role in the promotion of cell proliferation by MC-LR. These results indicate that MC-LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Microcistinas/toxicidad , Oxígeno/metabolismo , Carcinógenos/toxicidad , Caspasa 3/genética , Caspasa 3/metabolismo , Hipoxia de la Célula , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Hígado/citología , Hígado/patología , Toxinas Marinas , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
COVID-19 has greatly affected various aspects of societies worldwide, including the mental health and quality of education for students. Different studies investigated the consequences of the pandemic, but only a few studies have addressed the negative psychological and educational impacts of Corona Virus Anxiety (CVA). This study addresses the effects of CVA on Chinese students and explores university perceptions of its consequences. A mixed-methods research design was used, with 440 university students selected through convenience sampling. The researchers used the CVA scale, generalized anxiety scale, mental health questionnaire, and a self-report scale to assess the students' educational attainment. In addition, 14 students were interviewed for the qualitative phase of the study. Data from the quantitative phase were analyzed using Pearson correlation and descriptive statistics, while content analysis techniques were employed for analyzing the qualitative data. Results showed that CVA is negatively associated with students' anxiety, stress, and depression. Furthermore, stress, anxiety, depression, and CVA were found to be negatively associated with students' GPAs. Qualitative findings revealed that CVA negatively affected students' GPAs, research projects, classroom engagement, and graduations. The findings are theoretically and practically important to universities, schools, and educational centers to avoid the effects of the CVA on students' educational attainment and mental health through appropriate planning and providing facilities to the students during the lockdown.
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Microcystin-leucine-arginine (MC-LR) adversely affects male reproduction and interferes with the development of the offspring. Here, we establish a zebrafish (Danio rerio) model to understand the cross-generational effects of MC-LR in a male-lineage transmission pattern. F0 embryos were reared in water containing MC-LR (0, 5, and 25 µg/L) for 90 days and the developmental indices of F1 and F2 embryos were then measured with no MC-LR treatment. The results show that paternal MC-LR exposure reduced the hatching rate, heart rate and body weight in F1 and F2 generations. Global DNA methylation significantly increased in sperm and testes with the elevation expressions of DNA methyltransferases. Meanwhile, DNA methylation of brain-derived neurotrophic factor (bdnf) promoter was increased in sperm after paternal MC-LR exposure. Subsequently, increased DNA methylation of bdnf promoter and decreased gene expression of bdnf in the brain of F1 male zebrafish were detected. F1 offspring born to F0 males exhibit the depression of BDNF/AKT/CREB pathway and recapitulate these paternal neurodevelopment phenotypes in F2 offspring. In addition, the DNA methylations of dio3b and gad1b promoters were decreased and gene expressions of gad1b and dio3b were increased, accompanied with neurotransmitter disturbances in the brain of F1 male zebrafish after paternal MC-LR exposure. These data revealed that MC-LR displays a potential epigenetic impact on the germ line, reprogramming the epigenetic and transcriptional regulation of brain development, and contributing to aberrant expression of neurodevelopment-related genes and behavior disorders.
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Microcistinas , Pez Cebra , Animales , Masculino , Microcistinas/toxicidad , Leucina , Pez Cebra/fisiología , Arginina , Factor Neurotrófico Derivado del Encéfalo , Semen , Epigénesis Genética , Encéfalo , Expresión GénicaRESUMEN
MC-LR can interfere with thyroid function in ï¬sh, but the underlying mechanism is still unclear. Current study focuses to study the intergenerational inheritance of MC-LR-induced thyroid toxicity in zebrafish and in rat thyroid cells. In vivo experiments, adult female zebrafish (F0) were exposed to MC-LR (0, 5, and 25 µg/L) for 90 days and mated with male zebrafish without MC-LR exposure to generate F1 generation. F1 embryos were allowed to develop normally to 7 days post-fertilization (dpf) in clear water. In the F0 generation, MC-LR induced disturbance of the hypothalamic-pituitary-thyroid (HPT) axis, leading to a decrease in the production of thyroid hormones. Maternal MC-LR exposure also induced growth inhibition by altering thyroid hormones (THs) homeostasis and interfering with thyroid metabolism and development in F1 offspring. Mechanistically, MC-LR caused excessive accumulation of ROS and induced ER stress that further lead to activation of UPR in the F0 and F1 offspring of zebrafish. Interestingly, our ï¬ndings suggested that MC-LR exposure hampered thyroglobulin turnover by triggering IRE1 and PERK pathway in zebrafish and FRTL-5 thyroid cells, thus disturbing the thyroid endocrine system and contributing to the thyroid toxicity from maternal to its F1 offspring of zebrafish. Particularly, inhibition of the IRE1 pathway by siRNA could alleviate thyroid development injury induced by MC-LR in FRTL-5 cells. In addition, MC-LR induced thyroid cell apoptosis by triggering ER stress. Taken together, our results demonstrated that maternal MC-LR exposure causes thyroid endocrine disruption by ER stress contributing to transgenerational effects in zebraï¬sh offspring.
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Estrés del Retículo Endoplásmico , Microcistinas , Glándula Tiroides , Animales , Femenino , Masculino , Apoptosis , Microcistinas/toxicidad , Microcistinas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/farmacología , Tiroglobulina/metabolismo , Tiroglobulina/farmacología , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Hormonas Tiroideas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Pez Cebra/metabolismoRESUMEN
Microcystin-RR (MC-RR) is a commonly encountered cyanotoxin and receives increasing attention due to the risk of its bioaccumulation in aquatic animals like fish. This study investigated the protein profiles of zebrafish (Danio rerio) testes after intraperitoneal injection (i.p.) with 0.5 LD(50) (2000 µg/kg). MC-RR caused a noticeable damage to testicular ultrastructure, showing widened intercellular junction, distention of mitochondria. The testes showed a rapid response of its defense systems to the oxidative stress caused by MC-RR. This is the first to use a proteomic approach to obtain an overview of the effects of MC-RR on the testes of zebrafish. The proteomic results revealed that toxin exposure remarkably altered the abundance of 24 proteins that were involved in cytoskeleton assembly, oxidative stress, glycolysis metabolism, calcium ion binding and other biological functions. In conclusion, MC-RR damaged the testes and was toxic to the reproductive system of male zebrafish mainly through causing oxidative stress.
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Microcistinas/toxicidad , Proteoma/análisis , Testículo/efectos de los fármacos , Pez Cebra/metabolismo , Animales , Glucólisis , Inyecciones Intraperitoneales , Proteínas de Filamentos Intermediarios/metabolismo , Dosificación Letal Mediana , Masculino , Toxinas Marinas , Microcistinas/administración & dosificación , Microscopía Electrónica de Transmisión , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo , Proteoma/metabolismo , Proteómica/métodos , Testículo/metabolismo , Testículo/ultraestructura , Tubulina (Proteína)/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified. We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1-5 µM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 µg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injuries. In addition, PT injection strongly decreased the number of TUNEL-positive cells in the endothelium of atherosclerotic plaque from apoE(-/-) mice. OxLDL increased reactive oxygen species (ROS) levels, NF-κB activation, p53 accumulation, apoptotic protein levels and caspases-9 and -3 activities and decreased mitochondrial membrane potential (MMP) and cytochrome c release in HUVECs. These alterations were attenuated by pretreatment with PT. PT inhibited the expression of lectin-like oxLDL receptor-1 (LOX-1) expression in vitro and in vivo. Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease. PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis.
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Apoptosis/efectos de los fármacos , Aterosclerosis/tratamiento farmacológico , Células Endoteliales/citología , Lipoproteínas LDL/toxicidad , Sustancias Protectoras/farmacología , Estilbenos/farmacología , Animales , Aterosclerosis/metabolismo , Aterosclerosis/fisiopatología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sustancias Protectoras/administración & dosificación , Estilbenos/administración & dosificaciónRESUMEN
Long noncoding RNAs are vital to a variety of biological and physiological processes through multiple modes of functional interaction with DNA, RNA, and proteins. In chickens, numerous lncRNAs were discovered to be important to growth or disease progression. However, the detailed molecular function and role of lncRNAs remain less explored. Here, we performed lncRNA sequencing on abdominal adipose tissues from broiler lines divergently selected for abdominal fat content, and significantly differentially expressed lncRNAs were found, including lncPRDM16, a divergently transcribed and conserved lncRNA near PRDM16. Full lengths of two transcripts of lncPRDM16 were obtained, and their genomic structures were compared. Expression dynamics of lncPRDM16 in different tissues and during preadipocyte proliferation and differentiation were profiled. Moreover, a 250-nucleotide sequence at 5'-end was found to be inevitable to the function of lncPRDM16 in inhibiting preadipocyte proliferation and regulating the promoter activities of both lncPRDM16 and PRDM16. Taken together, we identified the 5'-end functional elements of lncPRDM16 and their potential importance in inhibiting preadipocyte proliferation. Our findings provide the foundation for further exploration of lncPRDM16 function and potential improvement of chicken muscle quality.
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ARN Largo no Codificante , Animales , Diferenciación Celular , Proliferación Celular , Pollos/genética , ARN Largo no Codificante/genética , ARN MensajeroRESUMEN
Background: Multiple chalazia are common in children, and many are treated by surgery. However, the distribution of different types of multiple chalazia has not been studied. This research aimed to investigate the location and number of multiple chalazia in pediatrics who need surgical treatments. Methods: Patients with multiple chalazia treated by incision and curettage surgery (I&C) in a tertiary children's hospital between June and December 2016 were reviewed. Demographic data, locations, and numbers of chalazia were recorded. Data were analyzed using generalized linear models of the counts and the occurrences of chalazia. Hypotheses were tested using likelihood ratio tests appropriate for each type of data. Results: The study included 128 subjects, most of which were 1-3 years old. The majority of patients had bilateral chalazia (95.3%), and the proportions of patients with internal, external, and marginal chalazion differed dramatically (99.2%, 61.7%, and 2.3%, respectively). The number of internal and external chalazia did not vary significantly with gender, age, or residence of the patients. Internal chalazia were located more frequently in the upper lids (p<0.001). External chalazia showed no preference of localization. The average number of internal chalazia in each eyelid did not relate to the presence of external chalazia. Conclusions: Multiple chalazia are common among younger children in southeast China. The anatomical distribution varies depending on the type of chalazion. Multiple chalazia often occur bilaterally and internally. If doctors are more aware of the anatomical distribution of chalazia, this might result in a higher success rate of I&C.
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Microcystin-LR (MCLR) induced impairment to male reproductive system and revealed the effects of transgenerational toxicity on offspring. But very little is known about the inheritance of these effects to offspring and the mechanisms involved. Here, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and microarray to characterize whole-genome DNA methylation and mRNA expression patterns in zebrafish testis after 6-week exposure to 5 and 20 µg/L MCLR. Accompanied with these analyses it revealed that MAPK pathway and ER pathway significantly enriched in zebrafish testes. Apoptosis and testicular damage were also observed in testis. Next, we test the transmission of effects to compare control-father and MCLR exposure-father progenies. DNA methylation analyses (via reduced representation bisulfite sequencing) reveal that the enrichment of differentially methylated regions on neurodevelopment after paternal MCLR exposure. Meanwhile, several genes associated with neurodevelopment were markedly downregulated in zebrafish larvae, and swimming speed was also reduced in the larvae. Interestingly, paternal MCLR exposure also triggered activation the phosphorylation of mitogen-activated protein kinase (MAPK) pathway which is also associated with neurodevelopmental disorders. These results demonstrated the significant effect that paternal MCLR exposure may have on gene-specific DNA methylation patterns in testis. Inherited epigenetic alterations through the germline may be the mechanism leading to developmental neurotoxicity in the offspring.
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Exposición Paterna , Pez Cebra , Animales , Epigénesis Genética , Humanos , Masculino , Toxinas Marinas , Microcistinas/toxicidad , Proteínas Quinasas Activadas por Mitógenos , Pez Cebra/genéticaRESUMEN
Microcystins-LR (MCLR) is a potent reproductive system toxin. We have previously shown that MCLR induced endoplasmic reticulum (ER) stress and apoptosis in testis. ER is the main calcium storage site in cells, and its calcium homeostasis plays an important role in the regulation of apoptosis. Hence, in the present study, we have investigated the role of calcium (Ca2+) in inducing apoptosis and how it affect the mitochondria and endoplasmic reticulum in TM4 cells. Our study found that MCLR induced an increase in Ca2+ concentration in TM4 cells. Compared to the controls, MCLR induced phosphorylation of calmodulin-dependent protein kinase II (CaMKII) which was involved in MAPKs activation, resulting in the induction of mitochondrial apoptosis pathways. Ca2+ chelator Bapta-AM partially reversed MCLR-induced apoptosis, conï¬rming the possible involvement of calcium homeostasis disruption after MCLR exposure. Meanwhile, MCLR activated unfolded protein response and activated the ER apoptotic pathway by activating caspase-12. In addition, exposure to MCLR causes mitochondrial defects and increased apoptosis by up-regulating caspase 3 and cytosol cytochrome c expression. Collectively, these results demonstrated that MCLR disturbed calcium homeostasis, which caused ER-mitochondria dysfunction, ultimately promoted cell apoptosis in Sertoli cells.
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Calcio , Estrés del Retículo Endoplásmico , Apoptosis , Homeostasis , Masculino , Microcistinas , Células de SertoliRESUMEN
Phthalate esters (PAEs) are a type of persistent organic pollutants and have received widespread concerns due to their adverse effects on human health. Dicyclohexyl phthalate (DCHP) and its metabolite monocyclohexyl phthalate (MCHP) were selected to explore the mechanism for interaction of PAEs with human serum albumin (HSA) through molecular docking and several spectroscopic techniques. The results showed that DCHP/MCHP can spontaneously occupy site I to form a binary complex with HSA, and DCHP exhibited higher binding affinity to HSA than MCHP. At 298 K, the binding constants (Kb) of DCHP and MCHP to HSA were 24.82 × 104 and 1.04 × 104 M-1, respectively. Hydrogen bonds and van der Waals forces were the major driving forces in DCHP/MCHP-HSA complex. The presence of DCHP/MCHP induced the secondary structure changes in HSA, and the pi electrons of the benzene ring skeleton of DCHP/MCHP played a key role in this binding processes. Exposure of DCHP/MCHP to TM4 cells revealed that interactions between PAEs and serum albumin can affect their cytotoxicity; DCHP showed higher toxicity than MCHP. The binding affinity of PAEs with HSA may be a valuable parameter for rapid assessment of their toxicity to organisms.
Asunto(s)
Contaminantes Orgánicos Persistentes/metabolismo , Ácidos Ftálicos/metabolismo , Albúmina Sérica Humana/metabolismo , Humanos , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , Contaminantes Orgánicos Persistentes/química , Ácidos Ftálicos/química , Unión Proteica , Conformación Proteica/efectos de los fármacos , Albúmina Sérica Humana/química , Espectrometría de Fluorescencia , Electricidad EstáticaRESUMEN
OBJECTIVE: To analyse the results and methods on proficiency testing(PT) for determination of Fe, Mn in drinking water and to discuss the influencing factors. With a view to the laboratory for accurate determination of drinking water iron and manganese to provide technical support. METHODS: 180 labs from 30 provinces (cities), autonomous regions took part in the PT. Based on methods of PT, statistical analysis of the results, to find the causes of dissatisfactory results. RESULTS: According to the results of the report for the first time, the PT showed that 85.56% labs presented satisfactory results of determination of Fe and 87.71% labs presented satisfactory results of determination of Mn. In addition to ICP/MS, it showed that 76.00%, 88.89%, 93.75% respectively presented satisfactory results of the methods of AAS, ICP-AES and chemical of determination of Fe. It showed that 79.23%, 94.29%, 72.73% respectively presented satisfactory results of the methods of chemical, AAS and ICP-AES of determination of Mn. The initial results of 37 labs had dissatisfactory. Results of statistics showed that iron, manganese at the same time [ZB] > or = 3 for the 11 labs. CONCLUSION: Most of the labs that took part in the PT have good competence in analyzing Fe, Mn. The main reasons of the dissatisfactory results were larger systematic errors, experimental blank, matrix interference and feeble control ability of the key point of the experiment.