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Subcooled liquid nitrogen and nitrogen slush are often considered for high-speed cooling, but their preparation and maintenance are not easy. To address this issue, a unique device was designed to prepare subcooled liquid argon (SLA) using liquid nitrogen (LN). The cooling process was mathematically modeled to predict the preparation time. If the interlayer space between LN and liquid argon is filled with nitrogen gas, liquid argon could be cooled to 3.5 K subcooling within 1 h. If the interlayer is filled with air, 2 h are required to achieve the same subcooled state. An additional 1000 mL of LN was required for the preparation of 600 mL of 3.5 K SLA. The cooling tests of 3 µL microdroplets in 3 mm-6 mm capillary quartz tubes were duplicated to evaluate the potential of SLA. It was found that the cooling rate of microdroplet in the 3.5 K subcooled SLA is very close to that in the 3 K subcooled LN, higher than that in the saturated LN. The convenience of preparation and maintenance of SLA can make it good choice of cryogen for cryopreservation of biomaterials.
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Argón , Frío , Nitrógeno , Argón/química , Nitrógeno/química , Criopreservación/métodos , Crioprotectores/química , Crioprotectores/farmacologíaRESUMEN
Erzhi Wan (EZW), a classic Traditional Chinese Medicine formula, has shown promise as a potential therapeutic option for Alzheimer's disease (AD), yet its mechanism remains elusive. Herein, we employed an integrative in-silico approach to investigate the active components and their mechanisms against AD. We screened four active components with blood-brain barrier permeabilities from TCMSP, along with 307 corresponding targets predicted by SwissTargetPrediction, PharmMapper, and TCMbank websites. Then, we retrieved 2260 AD-related targets from Genecards, OMIM, and NCBI databases. Furthermore, we constructed the protein-protein interaction (PPI) network of the intersected targets via the STRING database and performed the GO and KEGG enrichment analyses using the "clusterProfiler" R package. The results showed that the intersected targets were intimately related to the p53/PI3K/Akt signaling pathway, serotonergic synapse, and response to oxygen level. Subsequently, 25 core targets were found differentially expressed in brain regions by bioinformatics analyses of GEO datasets of clinical samples from the Alzdata database. The binding sites and stabilities between the active components and the core targets were investigated by the molecular docking approach using Autodock 4.2.6 software, followed by pocket detection and druggability assessment via the DoGSiteScorer server. The results showed that acacetin, ß-sitosterol, and 3-O-acetyldammarenediol-II strongly interacted with the druggable pockets of AR, CASP8, POLB, and PREP. Eventually, the docking results were further cross-referenced with the literature research and validated by 100 ns of molecular dynamics simulations using GROMACS software. Binding free energies were calculated via MM/PBSA strategy combined with interaction entropy. The simulation results indicated stable bindings between four docking pairs including acacetin-AR, acacetin-CASP8, ß-sitosterol-POLB, and 3-O-acetyldammarenediol-II-PREP. Overall, our study demonstrated a theoretical basis for how three active components of EZW confer efficacy against AD. It provides a promising reference for subsequent research regarding drug discoveries and clinical applications.
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This study identified a novel virus in the family Partitiviridae infecting Polygonatum kingianum Coll. et Hemsl, which is tentatively named polygonatum kingianum cryptic virus 1 (PKCV1). PKCV1 genome has two RNA segments: dsRNA1 (1926 bp) has an open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) of 581 amino acids (aa), and dsRNA2 (1721 bp) has an ORF encoding a capsid protein (CP) of 495 aa. The RdRp of PKCV1 shares 20.70-82.50% aa identity with known partitiviruses, and the CP of PKCV1 shares 10.70-70.80% aa identity with known partitiviruses. Moreover, PKCV1 phylogenetically clustered with unclassified members of the Partitiviridae family. Additionally, PKCV1 is common in P. kingianum planting regions and has a high infection rate in P. kingianum seeds.
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Objective: This study aims to explore the pharmacodynamic mechanism of Yiguanjian (YGJ) decoction against Parkinson's disease (PD) through integrating the central nervous (inner brain) and peripheral system (outer brain) relationship spectrum. Methods: The active components of YGJ were achieved from the TCMSP, TCMID, and TCM@Taiwan databases. The blood-brain barrier (BBB) permeability of the active components along with their corresponding targets was evaluated utilizing the existing website, namely, SwissADME and SwissTargetPrediction. The targets of PD were determined through database retrieval. The interaction network was constructed upon the STRING database, followed by the visualization using Cytoscape software. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on potential targets. Finally, the molecular docking approach was employed to assess the binding affinity between key components and key targets. Results: Overall, we identified 79 active components, 128 potential targets of YGJ, and 97 potential targets of YGJ-BBB potentially suitable for the treatment of PD. GO and KEGG analyses showed that the YGJ treatment of PD mainly relied on PI3K-Akt pathway while the YGJ-BBB was mostly involved in endocrine resistance. The molecular docking results displayed high affinity between multiple compounds and targets in accordance with previous observations. Conclusions: Our study unveiled the potential mechanisms of YGJ against PD from a systemic perspective: (1) for the YGJ, they have potential exerting effects on the peripheral system and inhibiting neuronal apoptosis through regulating the PI3K-Akt pathway; (2) for the YGJ-BBB, they can directly modulate endocrine resistance of the central nervous and holistically enhance body resistance to PD along with YGJ on PI3K-Akt pathway.
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Medicamentos Herbarios Chinos , Enfermedad de Parkinson , Encéfalo , Medicamentos Herbarios Chinos/química , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Farmacología en Red , Enfermedad de Parkinson/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-aktRESUMEN
Cartilage transplantation is an effective way to repair, reconstruct, and replace damaged articular cartilage (AC) but its use is limited by the inability to preserve AC for long periods of time. Vitrification is an ideal choice for long-term storage of AC, and multiple cryoprotective agents (CPAs) with high concentration are usually used. To obtain high cell viability, chondrocytes at all locations inside AC should be protected properly by the CPAs during cooling and rewarming. Hence, it is important to know the mass transport properties of multiple CPAs as they synergistically infiltrate AC. In this study, a mathematical model to describe the mass transport behavior of multiple CPAs in AC was developed based on the mixture-averaged diffusion model. In addition, a methodology for the simultaneous determination of dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol by carbon-13 nuclear magnetic resonance was established. The model is applicable for predicting single- and multiple-CPA permeation into AC, and its accuracy was verified by a massive experimental dataset. Simulation results showed reverse diffusion in the multiple-CPA permeation process, which was not found in the single-CPA permeation process. This curious phenomenon shows the sharp contrast between the diffusion behavior of a binary mixture and a multicomponent mixture.
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Cartílago Articular , Crioprotectores , Criopreservación/métodos , Crioprotectores/farmacología , Dimetilsulfóxido , Glicol de Etileno , Glicerol/farmacología , Propilenglicol , VitrificaciónRESUMEN
Environmental tobacco smoke (ETS) has become one of the most important sources of indoor air pollution. The study aimed to obtain the variation characteristics of typical air pollutant concentrations when people smoke in a closed room and explore the effect of the air-conditioner. A closed and air-conditioned room of 21 m2 was taken as the research object. Fine particulate matter (PM2.5) and total volatile organic compound (TVOC) were measured while 10 cigarettes were burnt in smoldering or smoking mode, with the air-conditioner on or off. The contents of nicotine in condensate samples were obtained by liquid chromatography. The impact of ETS on indoor air quality lasted for hours, causing typical pollutant concentrations to far exceed the Chinese standard. The PM2.5 produced by smoking was 11 times higher than by smoldering, but the TVOC produced by smoldering was more than by smoking. After one hour of the cigarette burning off, the PM2.5 concentration would be decreased by 96.1% with the air-conditioner on, in contrast to 67.9% with the air-conditioner off. Nicotine was detected in all samples of condensate from the air-conditioner. It is concluded that smoking cigarettes cannot be replaced by smoldering to evaluate the pollution of ETS. The air-conditioner has a positive effect on reducing the concentration of air pollutants produced by cigarette burning. More than 10% of the indoor nicotine may be taken away by condensate discharge, and its possible pollution should be paid attention to.Implications: This study provides new evidence of the effect of the split-type air-conditioner on ETS. The TVOC concentrations, which were less considered previously, were measured. PM2.5 concentration in human breathing zone can be reduced more quickly with the air-conditioner on. This study shows that there is a big difference in the concentrations of typical pollutants between smoking and smoldering. And it could be a guide for the formulation of relevant research methods. This study also demonstrates that the air conditioning condensate from the smoking room may contain nicotine. Attention should be paid to the recovery and utilization of such condensate.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminantes Ambientales , Contaminación por Humo de Tabaco , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Humanos , Nicotina/análisis , Material Particulado/análisis , Fumar , Contaminación por Humo de Tabaco/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
Decabromodiphenyl ethane (DBDPE) is a novel retardant. DBDPE is used in various flammable consumer products such as electronics, building materials, textiles, and children's toys. The presence of DBDPE in humans makes it extremely urgent to assess the health effects of DBDPE exposure. Here, we used female mice as an animal model to investigate the effects of DBDPE on embryonic development and offspring health. The results showed that 50 µg/kg bw/day of DBDPE exposure did not affect spindle rotation in oocytes after fertilization, but led to a decrease of pronuclei (PN) in zygotes. Further investigation found that DBDPE interferes with the self-assembly of F-actin in PN, resulting in PN reduction, DNA damage, and reduced expression of zygotic genome activating genes, and finally leading to abnormal embryonic development. More importantly, we found that maternal DBDPE exposure did not affect the growth and development of the first generation of offspring (F1) mice, but resulted in behavioral defects in F1 mice. Female F1 mice from DBDPE-exposed mothers exhibited increased motor activity and deficits in social behavior. Both female and male F1 mice from DBDPE-exposed mothers exhibited cognitive memory impairment. These results suggest that DBDPE has developmental toxicity on embryos and has a cross-generational interference effect. It is suggested that people should pay attention to the reproductive toxicity of DBDPE. In addition, it also provides a reference for studying the origin of neurological diseases and indicates that adult diseases caused by environmental pollutants may have begun in the embryonic stage.
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Retardadores de Llama , Actinas , Adulto , Animales , Bromobencenos , Niño , Cognición , Desarrollo Embrionario , Femenino , Retardadores de Llama/toxicidad , Humanos , Masculino , Ratones , CigotoRESUMEN
Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.
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Resistencia a la Insulina , Pez Cebra , Animales , Ritmo Circadiano , Glucosa/metabolismo , Propionatos/toxicidad , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
AIMS: Fluorene-9-bisphenol (BHPF), as a substitute for bisphenol A, is used in many industries in daily life. Many studies have clarified its effects as an endocrine disruptor on organisms, but its effect on lipid metabolism of zebrafish larvae is not clear. Patients with non-alcoholic fatty liver disease (NAFLD) are more susceptible to external pollutants. It is not clear how BHPF perturbs lipid metabolism or promotes NAFLD progression. MAIN METHODS: We explored the biological effects of BHPF on locomotor activity, inflammatory response, endoplasmic reticulum (ER) stress and lipid metabolism in zebrafish, especially in the mechanism of lipid homeostasis disorder. In addition, the role of BHPF in the progression of non-alcoholic fatty liver disease (NAFLD) was further explored. KEY FINDINGS: We found that high concentration (100 nmol/L) BHPF caused retarded growth, mild lipid accumulation and reduced the locomotive activity of zebrafish larvae, accompanied by a decrease in endogenous cortisol level. At the same time, it caused the full activation of inflammation and ER stress. Rescue experiments by 25(OH)D3 demonstrated that high concentration of BHPF caused defects in 1,25(OH)2D3 metabolic pathway through downregulation of cyp2r1, which further damaged pgc1a-mediated fatty acid oxidation and mitochondrial function, resulting in lipid accumulation. In summary, exposure to BHPF could damage lipid homeostasis and worsen the diet-induced NAFLD. SIGNIFICANCE: Our findings provide new insights into the role of BHPF in development of overweight and obesity and also improve understanding of its toxicological mechanism. Our results play a warning role in the administration of environmental pollutants.
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Compuestos de Bencidrilo/toxicidad , Ácidos Grasos/química , Fluorenos/toxicidad , Larva/efectos de los fármacos , Trastornos del Metabolismo de los Lípidos/patología , Locomoción/efectos de los fármacos , Fenoles/toxicidad , Animales , Larva/metabolismo , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Trastornos del Metabolismo de los Lípidos/metabolismo , Pez CebraRESUMEN
Venlafaxine, a serotonin-noradrenaline reuptake inhibitor, is a widely used antidepressant drug routinely detected in aquatic environments. However, its potential impact on courtship behaviour in zebrafish is unknown. We tested the hypothesis that venlafaxine disrupts brain monoamine levels and molecular responses essential for courtship behaviour in zebrafish. Zebrafish (Danio rerio) were exposed to venlafaxine (1, 10, and 100 µg/L) for 20 days. We evaluated the molecular levels and neuronal basis of the effect of venlafaxine on courtship behaviour. Here, we show that venlafaxine inhibited courtship behaviour in zebrafish and increased the transcript levels of 5-ht1a and 5-ht2c while decreasing the transcript levels of genes involved in the dopaminergic system, including th1, th2, drd1b, and drd2b. Venlafaxine upregulated 5-HT levels and downregulated dopamine levels. Moreover, the subordinate fish from the venlafaxine-exposed group had significantly lower motor activity than the subordinate fish of the control group. Collectively, our results reveal that venlafaxine can disturb brain monoamine levels, affecting courtship behaviour in adult zebrafish.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Antidepresivos , Cortejo , Dopamina , Serotonina , Clorhidrato de Venlafaxina/toxicidad , Contaminantes Químicos del Agua/toxicidadRESUMEN
The suprachiasmatic nucleus (SCN) is the main control area of the clock rhythm in the mammalian brain. It drives daily behaviours and rhythms by synchronizing or suppressing the oscillations of clock genes in peripheral tissue. It is an important brain tissue structure that affects rhythm stability. SCN has high plasticity and is easily affected by the external environment. In this experiment, we found that exposure to the endocrine disruptor 17ß-trenbolone (17ß-TBOH) affects the rhythmic function of SCN in the brains of adolescent male balb/c mice. Behavioural results showed that exposure to 17ß-TBOH disrupted daily activity-rest rhythms, reduced the robustness of endogenous rhythms, altered sleep-wake-related behaviours, and increased the stress to light stimulation. At the cellular level, exposure to 17ß-TBOH decreased the c-fos immune response of SCN neurons to the large phase shift, indicating that it affected the coupling ability of SCN neurons. At the molecular level, exposure to 17ß-TBOH interfered with the daily expression of hormones, changed the expression levels of the core clock genes and cell communication genes in the SCN, and affected the expression of wake-up genes in the hypothalamus. Finally, we observed the effect of exposure to 17ß-TBOH on energy metabolism. The results showed that 17ß-TBOH reduced the metabolic response and affected the metabolic function of the liver. This study revealed the influence of environmental endocrine disrupting chemicals (EDCs) on rhythms and metabolic disorders, and provides references for follow-up research.
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Ritmo Circadiano , Disruptores Endocrinos , Animales , Encéfalo , Disruptores Endocrinos/toxicidad , Masculino , Ratones , Núcleo Supraquiasmático , Acetato de TrembolonaRESUMEN
Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 µg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.
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Trastornos Cronobiológicos , Melatonina , Animales , Bromobencenos , Ritmo Circadiano , Desarrollo Embrionario , Femenino , RatonesRESUMEN
Puberty is a critical period for growth and development. This period is sensitive to external stimuli, which ultimately affects the development of nerves and the formation of social behaviour. 17ß-Trenbolone (17ß-TBOH) is an endocrine disrupting chemicals (EDCs), which had been widely reported in aquatic vertebrates. But there is little known about the effects of 17ß-TBOH on mammals, especially on adolescent neurodevelopment. In this study, we found that 17ß-TBOH acute 1 h exposure can cause the activation of the dopamine circuit in pubertal male balb/c mice. At present, there is little known about the effects of puberty exposure of endocrine disruptors on these neurons/nerve pathways. Through a series of behavioural tests, exposure to 80 µgkg-1 d-1 of 17ß-TBOH during adolescence increased the anxiety-like behaviour of mice and reduced the control of wheel-running behaviour and the response of social interaction behaviour. The results of TH immunofluorescence staining showed that exposure to 17ß-TBOH reduced dopamine axon growth in the medial prefrontal cortex (mPFC). In addition, the results of real-time PCR showed that exposure to 17ß-TBOH not only down-regulated the expression of dopamine axon development genes, but also affected the balance of excitatory/inhibitory signals in mPFC. In this research, we reveal the effects of 17ß-TBOH exposure during adolescence on mammalian behaviour and neurodevelopment, and provide a reference for studying the origin of adolescent diseases.
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Disruptores Endocrinos , Acetato de Trembolona , Animales , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales , Masculino , Ratones , Conducta Social , Interacción SocialRESUMEN
This study investigated the indoor air quality (IAQ) during humid season in an old badminton hall, to explore the IAQ characteristics of natural ventilated sports buildings for public use. The indoor air parameters (temperature, relative humidity and air velocity) and indoor air pollutants (CO2, TVOC, PM2.5 and PM10) were measured. A subjective approach was carried out through questionnaire survey. 185 valid questionnaires were recovered, and 68.7% of the participants had exercised. Results show that the indoor air qualities obtained through objective and subjective approaches were obviously different. Indoor PM, TVOC and CO2 concentrations were normal, but 37.3% of the participants complained about the building materials' smell and 73.5% of the participants reported obvious sweaty odor. Physical activity might reduce a person's sensitivity to the environment. The participants generally felt warm and hot because of the high relative humidity. Post-exercise participants felt significantly hotter than those who did not exercise, and were generally more receptive to IAQ. The method of Fanger was employed to narrow the gap between subjective and objective approaches with a modified parameter, and to furtherly estimate the ventilation. The present study demonstrates the necessity to combine two approaches together to assess the IAQ in sports buildings.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Deportes de Raqueta , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Monitoreo del Ambiente , Humanos , Material Particulado/análisis , Estaciones del Año , VentilaciónRESUMEN
Melamine cyanuric acid (MCA) is a flame retardant linked by hydrogen bonds between melamine and cyanuric acid. MCA is used in an excellent series of phosphorus and nitrogen flame retardants. MCA can harm the kidney, liver, testis, and spleen cells. However, the effects of MCA on the emotions and behaviour of adolescent mice have not yet been investigated. In this article, male mice were exposed to MCA at 10, 20, and 40 mg/kg for four weeks. MCA exposure resulted in enhanced mouse locomotor and nocturnal activity. We also observed anxiety-like and depression-like behaviours. Moreover, after MCA exposure, the serum concentrations of thyroid-related hormones were changed, and the mRNA levels were affected. In short, MCA exposure can cause behavioural and emotion disorders.
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Conducta Animal/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Triazinas/toxicidad , Animales , Retardadores de Llama , Riñón , Masculino , Ratones , Bazo , TestículoRESUMEN
Psychoactive drugs discharged into the environment have different effects on the behavior of vertebrates. The objective of this study was to evaluate the effect of venlafaxine on the behavior of zebrafish, and whether melatonin could reverse the induction of venlafaxine. In this study, a series of venlafaxine concentrations (1 µg/L, 10 µg/L, 100 µg/L) was used to treat zebrafish embryos from 2 hours post-fertilization (hpf) to 5dpf. We found that venlafaxine (1 µg/L) can stimulate the growth of the head area, eye area, and body length of zebrafish. The light-dark test showed that venlafaxine (1 µg/L) could increase the activity of zebrafish larvae. What's more, venlafaxine (1 µg/L) upregulated the expression of steroid regulatory factors including steroidogenic acute regulatory protein (star), cytochrome P450 family member 11A1 (cyp11a1) and 11 ß hydroxylase (cyp11b1) by cAMP-pCREB pathway, affecting the function of the steroidogenic cells, which might be involved in the increased cortisol levels in zebrafish larvae. Whereas, melatonin (230 µg/L) restored the altered locomotion behavior induced by venlafaxine and recovered the altered gene expression. Our results demonstrate that venlafaxine at levels detected in the aquatic environment impacts behavior and may compromise the adaptive responses to the environment in zebrafish larvae.
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Antidepresivos de Segunda Generación/toxicidad , Conducta Animal/efectos de los fármacos , Clorhidrato de Venlafaxina/toxicidad , Animales , Antidepresivos de Segunda Generación/administración & dosificación , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Exposición a Riesgos Ambientales/efectos adversos , Hidrocortisona/metabolismo , Larva/efectos de los fármacos , Larva/fisiología , Melatonina/farmacología , Modelos Animales , Actividad Motora/efectos de los fármacos , Fosfoproteínas/genética , Esteroide 11-beta-Hidroxilasa/genética , Regulación hacia Arriba/efectos de los fármacos , Clorhidrato de Venlafaxina/administración & dosificación , Contaminantes Químicos del Agua/administración & dosificación , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/genética , Pez Cebra/crecimiento & desarrollo , Pez Cebra/fisiología , Proteínas de Pez Cebra/genéticaRESUMEN
Glyphosate (Gly) is the herbicide widely used in agricultural fields and landscaping. Mammalian exposure to glyphosate could cause neurotoxicity, blood, liver, kidney, endocrine, reproductive, genetic and other toxic effects. Melatonin (MT) is a neuroendocrine hormone secreted mainly by the pineal gland. It is unknown whether MT can improve reproductive defects and hormonal disorders in mice exposed to Gly. In this study, mice were exposed to 250 and 500 mg/kg Gly by intragastric administered and 15 mg/kg MT was treated via intraperitoneal injection for 7 days. Our results shown that the weight gain of mice, the ovarian coefficient and the ATP content in the ovaries were decreased significantly. Gly-treated oocytes showed that the first polar body extrusion failed, the level of oxidative stress increased, and the mitochondrial membrane potential (MMP) decreased. Subsequently, our results showed that increased expression level of BAX protein, reduced expression of BCL-2 protein, ATG12 and LC3 protein expression increased in ovaries after Gly treatment. At the same time, Gly exposure led to abnormal expression of Hypothalamic-Pituitary-Thyroid (HPT) axis-related genes and disrupted hormone homeostasis. After the injection of 15 mg/kg MT, the oocytes showed decreased oxidative stress level, increased mitochondrial membrane potential, incremental ATP content in the ovaries and the hormone levels were approached to the control group. Thus, our results demonstrated that melatonin can improve oocyte quality and maintain hormone homeostasis in mice exposed to glyphosate.
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Glicina/análogos & derivados , Hormonas/metabolismo , Melatonina/farmacología , Oocitos/patología , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Glicina/toxicidad , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/patología , Meiosis/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Biológicos , Oocitos/efectos de los fármacos , Ovario/patología , Especies Reactivas de Oxígeno/metabolismo , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , GlifosatoRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease. Damage to energy metabolism and reduced adenosine triphosphate (ATP) levels in dopaminergic neurons are common features of PD. Previous studies suggested that the occurrence of PD often affects glucose metabolism and ATP production in the brain, and increased glycolysis or ATP production protects dopaminergic neuronal degeneration in the brain of PD patients. These systems may provide new potential therapeutic targets for the prevention of PD. The present study investigated the inhibitory action of polydatin (PLD) on early dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PLD protected against MPTP-induced early dopaminergic neuronal degeneration. PLD reduced the MPTP-induced loss of dopaminergic neurons in substantia nigra and striatum, inhibited the occurrence of neural apoptosis, and restored motor function in mice. PLD also increased the continuous activity duration and rhythm amplitude in mice during the circadian activity test. PLD improved glucose metabolism in the brain and restored ATP production levels. These observations suggest that PLD attenuates MPTP-induced early PD-like symptoms, and its mechanism of action may be associated with the promotion of glucose metabolism in neurons.
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Neuronas Dopaminérgicas/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Glucósidos/uso terapéutico , Glucólisis/fisiología , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Estilbenos/uso terapéutico , Animales , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/farmacología , Glucósidos/farmacología , Glucólisis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Trastornos Parkinsonianos/patología , Estilbenos/farmacologíaRESUMEN
Parthenolide (PTL) is a natural compound with anti-inflammatory and antioxidant properties and is an active ingredient extracted from the medicinal plant Tanacetum parthenium. ACT001 is derived from parthenolide and is a fumarate form of dimethylaminomylide (DMAMCL). Its effect is equivalent to that of PTL, but it is more stable in plasma and has lower acquisition costs. Related reports indicate that NLRP3-mediated neuroinflammation is involved in the progression of Parkinson's disease (PD). In our research, we explored whether ACT001 alleviates NLRP3-mediated neuroinï¬ammation in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results revealed that ACT001 reduces movement impairment and cognitive deï¬cit in PD mice. In addition, it alleviates dopaminergic neurodegeneration in the nigrostriatal pathway and inhibits oxidative stress, the inflammatory response and activation of the NLRP3 inflammasome in the midbrain of MPTP-induced PD mice. Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinï¬ammation in PD mice induced by MPTP.
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Conducta Animal/efectos de los fármacos , Citocinas/efectos de los fármacos , Inflamasomas/efectos de los fármacos , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Trastornos Parkinsonianos/metabolismo , Sesquiterpenos de Guayano/farmacología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Ritmo Circadiano/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cuerpo Estriado/patología , Citocinas/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Inflamasomas/metabolismo , Inflamación/fisiopatología , Malondialdehído/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Trastornos Parkinsonianos/fisiopatología , Sustancia Negra/efectos de los fármacos , Sustancia Negra/metabolismo , Sustancia Negra/patología , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND: Nowadays, the research of doctor-patient communication is becoming increasingly important not only in China but also around the world. METHODS: The study designs a type of learning software to train the interns to advance their communication skills, and whose validity for improving doctor-patient communication in self-controlled trials is evaluated. With the aid of the new learning software, the self-controlled tests were carried out among 183 interns to assess the quality of their communication skill acquisition. The learning effectiveness of the preparation stage, information collection, information given, patient understanding, and inquisition ending was evaluated with the Set Elicit Give Understand End (SEGUE) framework after 3 months of training. RESULTS: More interns (37.16% vs. 10.98%, P < 0.001) could accurately identify the psychosocial or emotional factors contributing to the diseases. An increased number of interns (42.62% vs. 10.40%, P < 0.001) were able to openly discuss lifestyle issues and prevention strategies with patients. The study also revealed that interns who had completed training tended to allow patients more time to describe their feelings and concerns about their illnesses. In addition, more of the trained interns roved capable of being caring and respectful to patients and showing empathetic communication behavior (53.01% vs. 26.59%, P < 0.001). CONCLUSIONS: The doctor-patient communication software may help the interns known more about communication skills.