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Methods allow the enhancement of nanofibers via self-assembly are potentially important for new disciplines with many advantages, including multi-anchor interaction, intrinsic mechanical properties and versatility. Herein, a microfluidic-assisted self-assembly process to construct hydroxyl functionalized boron nitride nanosheets (OH-BNNS)/graphene oxide (GO)/thermoplastic polyurethane (TPU) composite nanofiber film, in which stable and precisely controlled self-assembly is fulfilled by the confined ultra-small-volume chip is demonstrated. Multiple fine structural analyses alongside with the density-functional theory (DFT) calculations are implemented to confirm the synergistic effect of noncovalent interactions (hydrogen bonding interaction, π - π stacking interaction, and van der Waals attraction) plays a critical role in the robust micro-structure and a massive 700% enhancement of mechanical strength via adding only 0.3 wt% OH-BNNS and GO. Importantly, profiled from broadband optical absorption ability, robust mechanical properties and outstanding flexibility, the self-assembled 3D OH-BNNS/GO/TPU nanofiber film reveals an adorable evaporation rate of 4.04 kg m-2 h-1 under one sun illumination with stable energy transfer efficiency (93.2%) by accompanying hydrogen bonding interaction. This microfluidic-assisted self-assembly strategy will provide a constructive entry point for the rational design of nanofibers and beyond.
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We present a snapshot temporal compressive light-sheet fluorescence microscopy system to capture high-speed microscopic scenes with a low-speed camera. A deep denoising network and total variation denoiser are incorporated into a plug-and-play framework to quickly reconstruct 20 high-speed video frames from a short-time measurement. Specifically, we can observe 1,000-frames-per-second (fps) microscopic scenes when the camera works at 50 fps to capture the measurement. The proposed method can potentially be applied to observe cell and tissue motions in thick living biological specimens.
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BACKGROUND: Clinical epidemiological studies have found that some patients with ulcerative colitis (UC) are prone to mental disorders. DSS-induced acute and chronic UC models are often used to evaluate the efficacy of anti-UC drugs. However, whether DSS has an effect on mouse behavior has not been reported. METHODS: Acute and chronic UC models were induced by 3% DSS and 1.5% DSS, respectively. The bloody stool, the changes in the colon length, and histopathological changes in the colon were used to evaluate the success of the animal model. The behavior of mice was evaluated by open field experiment, tail suspension experiment and Sucrose preference test. RESULTS: The weight of mice in 3% DSS group decreased significantly, the DAI score increased significantly, the colon length of mice was significantly shortened, and the structure of colonic crypts was abnormal, which showed inflammatory cell infiltration and shrinkage of crypts. Compared with the control group, the immobility time of 3%DSS group mice in the tail suspension test and forced swimming test had no effect, the number of running and grooming times was significantly reduced, and there was no significant difference in the number of standing times. No abnormality was observed in HE staining of the hippocampus. However, in 1.5% DSS-induced chronic UC model, behavioral and hippocampal abnormalities were observed not only UC symptoms. CONCLUSIONS: The acute UC model induced by 3% DSS has certain influence on the behavior of mice, but the mental state of mice is normal, which may be the abnormal behavior caused by UC symptoms; However, the chronic UC model induced by 1.5% DSS has a significant effect on the behavior of mice, and the mice have mental disorders, which are caused by mental disorders.
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Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Camundongos Endogâmicos C57BL , Colo/patologia , Modelos Animais de Doenças , Sulfato de Dextrana/efeitos adversos , Colite/induzido quimicamenteRESUMO
OBJECTIVE: Septic shock, the most severe stage of sepsis, is a deadly inflammatory disorder with high mortality. Ciclopirox (CPX) is a broad-spectrum antimycotic agent which also exerts anti-inflammatory effects in human diseases. However, whether CPX can relieve inflammatory response in LPS-induced septic shock remains unclear. MATERIALS AND METHODS: Male C57BL/6 mice LPS were injected intraperitoneally with LPS to simulate septic shock in vivo. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were subject to LPS treatment to simulate septic shock in vitro. ELISA was applied to detect the level of pro-inflammatory cytokines. Cell viability was assessed by CCK-8 assay. Protein levels was detected by western blotting. RESULTS: CPX enhanced the survival rate and attenuated inflammation in mice with LPS-induced septic shock. Similarly, CPX dose-dependently mitigated LPS-induced inflammation in BMDMs. It was also found that Sortilin 1 (SORT1) was upregulated in both in vivo and in vitro models of LPS-induced septic shock. In addition, SORT1 overexpression counteracted the alleviative effects of CPX on the inflammation response of LPS-challenged BMDMs by activating the Wnt/ß-Catenin signaling. Furthermore, BML-284 (a Wnt/ß-Catenin agonist) treatment also abrogated CPX-mediated moderation of LPS-triggered inflammatory reaction in BMDMs. CONCLUSIONS: In sum, we found that CPX protected against LPS-induced septic shock by mitigating inflammation via SORT1-mediated Wnt/ß-Catenin signaling pathway.
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Proteínas Adaptadoras de Transporte Vesicular , Ciclopirox , Inflamação , Choque Séptico , Via de Sinalização Wnt , Ciclopirox/farmacologia , Choque Séptico/induzido quimicamente , Choque Séptico/tratamento farmacológico , Lipopolissacarídeos , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Proteínas Adaptadoras de Transporte Vesicular/genética , Inflamação/tratamento farmacológicoRESUMO
As one of the traditional computer simulation techniques, molecular simulation can intuitively display and quantify molecular structure and explain experimental phenomena from the microscopic molecular level. When the simulation system increases, the amount of calculation will also increase, which will cause a great burden on the simulation system. Coarse-grained molecular dynamics is a method of mesoscopic molecular simulation, which can simplify the molecular structure and improve computational efficiency, as a result, coarse-grained molecular dynamics is often used when simulating macromolecular systems such as drug carrier materials. In this article, we reviewed the recent research results of using coarse-grained molecular dynamics to simulate drug carriers, in order to provide a reference for future pharmaceutical preparation research and accelerate the entry of drug research into the era of precision drug design.
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Portadores de Fármacos , Simulação de Dinâmica MolecularRESUMO
BACKGROUND: Gastrointestinal bleeding (GIB) is a potential contributing factor for poor prognosis of spontaneous basal ganglia hemorrhage (BGH). This study aimed to investigate the predictive value of new inflammatory biomarkers including neutrophil to lymphocytes (NLR) on admission and construct a nomogram for rapidly predicting GIB in acute BGH. METHODS: The retrospective study included all patients with acute BGH admitted from the emergency department in Huashan Hospital from July 2017 to January 2019. Multivariate analysis was conducted to evaluate the correlation between factors within 24 h and the occurrence of GIB within 7 days after BGH. The receiver operating characteristic (ROC) curve was performed to estimate the prediction ability of inflammatory biomarkers. A nomogram based on significant predictors was validated by ROC curve and calibration curve. RESULTS: A total of 122 patients were enrolled in this study, and the incidence of GIB was 23.0%. Patients with GIB had larger hematoma volume (≥30 ml), lower Glasgow Coma Scale (GCS) score (≤8) and increased inflammatory biomarkers on admission. ROC curve revealed that NLR had a high predictive value to the complication (area under the curve = 0.87). According to multivariate analysis, NLR, GCS score, and hematoma volume were main factors for nomogram, with good calibration and discrimination. CONCLUSIONS: Neutrophil-to-lymphocyte ratio and GCS score within 24 h after the onset of acute BGH are the independent risk factors for GIB. The nomogram developed by these predictors may assist surgeons in rapidly assessing and preventing of GIB for BGH patients in earlier stage.
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Hemorragia dos Gânglios da Base , Neutrófilos , Biomarcadores , Hemorragia Gastrointestinal/epidemiologia , Hematoma , Humanos , Linfócitos , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
Curcuma kwangsiensis, one species of Curcumae zedoaria Ros. c, is a commonly used traditional Chinese medicine (TCM) for treating cardiovascular disease, cancer, asthma and inflammation. Polar compounds are abundant in water decoction, which would be responsible for critical pharmacological effects. However, current research on polar compounds in Curcumae zedoaria Ros. c remains scarce. In this study, the polar fraction from Curcuma kwangsiensis was firstly profiled on G protein-coupled receptor 109A (GPR109A), ß2-adrenergic receptor (ß2-AR), neurotensin receptor (NTSR), muscarinic-3 acetylcholine receptor (M3) and G protein-coupled receptor 35 (GPR35), which were involved in its clinical indications and exhibited excellent ß2-AR and GPR109A receptor activities. Then, an offline two-dimensional reversed-phase liquid chromatography (RPLC) coupled with the hydrophilic interaction chromatography (HILIC) method was developed to separate polar compounds. By the combination of a polar-copolymerized XAqua C18 column and an amide-bonded XAmide column, an orthogonality of 47.6% was achieved. As a result of coupling with the mass spectrometry (MS), a four-dimensional data plot was presented in which 373 mass peaks were detected and 22 polar compounds tentatively identified, including the GPR109A agonist niacin. Finally, molecular docking of these 22 identified compounds to ß2-AR, M3, GPR35 and GPR109A receptors was performed to predict potential active ingredients, and compound 9 was predicted to have a similar interaction to the ß2-AR partial agonist salmeterol. These results were supplementary to the material basis of Curcuma kwangsiensis and facilitated the bioactivity research of polar compounds. The integration of RPLC×HILIC-MS and molecular docking can be a powerful tool for characterizing and predicting polar active components in TCM.
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Curcuma , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio , Cromatografia Líquida/métodos , Espectrometria de MassasRESUMO
We demonstrate the HfSe2 saturable absorber (SA) for the generation of ultrafast pulse laser. The HfSe2 SA device is fabricated by integrating HfSe2 nanosheets (NSs) with a microfiber. The material and optical characteristics of HfSe2 NSs show their high quality. The nonlinear optical absorption of HfSe2 SA is measured with a modulation depth of 5.8%. Stable soliton mode-locked laser based on HfSe2 SA is realized at the central wavelength of 1561.43 nm with pulse duration of 297 fs and the maximum pulse energy of 2.68 nJ. Our soliton fiber laser has a maximum output power of 48.5 mW with a high slope efficiency of 12.8%, which indicate that HfSe2 is a good candidate of SA for high efficient ultrashort pulses generation.
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Tefluthrin was the first pyrethroid developed for soil treatment. There was no report about the toxicity to terrestrial invertebrates at the enantiomer level. The main objective of the present study was to investigate the enantiomer-specific acute toxicity to the earthworm Eisenia fetida and potential mechanism via multilevel response. The filter paper contact and the artificial soil method were used to detect the acute toxicity of tefluthrin enantiomers to earthworms. Histopathological examination (H&E), biochemical criterion, and comet assay were used to identify the effects and potential mechanism of toxicity. The order of acute toxicity was Z-cis-(1S,3S)-(-)-tefluthrin < Rac-tefluthrin < Z-cis-(1R,3R)-(+)-tefluthrin. H&E stained images showed that intestinal cells were suffered seriously damaged after exposed to Rac-tefluthrin, and the Z-cis-(1R,3R)-(+)-isomer. Tefluthrin and enantiomers also enantioselectively disturbed reactive oxygen species (ROS) level and enzymatic activity. Additionally, Z-cis-(1R,3R)-(+)-tefluthrin significantly increased the olive tail moment (OTM) and Trail DNA% compared with the control and other treatment groups at the concentration of 0.1 mg/kg was observed. It can be concluded that intestinal damage, body weight changes, DNA damage caused by oxidative stress that might be the primary mechanisms of tefluthrin toxicity to earthworms. The results indicated the rational use of chiral compounds in agriculture to avoid damage to the soil ecosystem.
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Inseticidas , Oligoquetos , Piretrinas , Poluentes do Solo , Animais , Ciclopropanos , Ecossistema , Hidrocarbonetos Fluorados , Inseticidas/toxicidade , Piretrinas/toxicidade , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidadeRESUMO
Rapid development of gene sequencing technologies has led to an exponential increase in microbial sequencing data. Genome research of a single organism does not capture the changes in the characteristics of genetic information within a species. Pan-genome analysis gives us a broader perspective to study the complete genetic information of a species. Paenibacillus polymyxa is a Gram-positive bacterium and an important plant growth-promoting rhizobacterium with the ability to produce multiple antibiotics, such as fusaricidin, lantibiotic, paenilan, and polymyxin. Our study explores the pan-genome of 14 representative P. polymyxa strains isolated from around the world. Heap's law model and curve fitting confirmed an open pan-genome of P. polymyxa. The phylogenetic and collinearity analyses reflected that the evolutionary classification of P. polymyxa strains are not associated with geographical area and ecological niches. Few genes related to phytohormone synthesis and phosphate solubilization were conserved; however, the nif cluster gene associated with nitrogen fixation exists only in some strains. This finding is indicative of nitrogen fixing ability is not stable in P. polymyxa. Analysis of antibiotic gene clusters in P. polymyxa revealed the presence of these genes in both core and accessory genomes. This observation indicates that the difference in living environment led to loss of ability to synthesize antibiotics in some strains. The current pan-genomic analysis of P. polymyxa will help us understand the mechanisms of biological control and plant growth promotion. It will also promote the use of P. polymyxa in agriculture.
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Genoma de Planta/genética , Paenibacillus polymyxa/genética , Paenibacillus polymyxa/fisiologia , Desenvolvimento Vegetal , Fixação de Nitrogênio/genética , Paenibacillus polymyxa/classificação , Filogenia , Reguladores de Crescimento de Plantas/biossíntese , RizosferaRESUMO
Hypopigmentation disorders, such as vitiligo, are difficult for treatment due to complicated pathogenesis, resulting from multiple factors including neural and immune elements. 5-HT and IFN-γ both play crucial roles in these skin diseases. However, the interactions between 5-HT and IFN-γ in regulation of melanogenesis is still unknown. Our study aimed at exploring whether IFN-γ affects 5-HT-induced melanogenesis and searching the mechanism. In our study, IFN-γ attenuated 5-HT-induced pigmentation and green fluorescent protein (GFP) expression in zebrafishes. In addition, we found that IFN-γ decreased serum serotonin levels as well as the cutaneous expression of tryptophan hydroxylase 1 (TPH1), 5-HT1A receptor (5-HT1AR) and 5-HT1B receptor (5-HT1BR) in C57BL/6 mice. Moreover, IFN-γ attenuated 5-HT-induced melanin biosynthesis as well as the expression of 5-HT1AR, 5-HT1BR and 5-HT2A receptor (5-HT2AR) in B16F10 cells, which blocked by interferon-γ receptor 1 and interferon-γ receptor 2 (IFNGR1/IFNGR2) antibodies. In summary, IFN-γ not only affects melanogenesis alone, but also inhibits 5-HT response on melanin biosynthesis. Mediated by IFNGR1/IFNGR2, IFN-γ downregulated 5-HT receptors expression, which directly affect 5-HT-induced melanin biosynthesis. Our work may give insights into the drug development of hypopigmentation disorders with neuro-immune derangement.
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Regulação para Baixo , Interferon gama/farmacologia , Melaninas/biossíntese , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Serotonina/farmacologia , Animais , Células Cultivadas , Descoberta de Drogas , Expressão Gênica/efeitos dos fármacos , Hipopigmentação/tratamento farmacológico , Hipopigmentação/genética , Técnicas In Vitro , Camundongos Endogâmicos C57BL , Antagonistas da Serotonina , Peixe-ZebraRESUMO
The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.
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Compostos de Boro/química , Nanoestruturas/química , Polímeros/química , Tensoativos/química , Substâncias Macromoleculares/química , Estrutura Molecular , Tamanho da PartículaRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors due to errors in the data. The authors indicated that they expanded the original sample size from 12 to 50, to study blood circulation upon other types of burns. At the same time, they further verified the results reported in this paper. The decrease in blood volume of the experimental group was not significantly slowed compared to the control group as reported. Since that was the basis of this work, this flaw may shatter all resulting hemodynamic data measured by the PICCO method. The authors have been unable to determine the source of the error.
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Queimaduras/complicações , Permeabilidade Capilar/efeitos dos fármacos , Glicoproteínas/farmacologia , Hemodinâmica/efeitos dos fármacos , Inibidores de Serina Proteinase/farmacologia , Choque/terapia , Animais , Queimaduras/fisiopatologia , Cães , Feminino , Hidratação , Masculino , Distribuição Aleatória , Choque/etiologiaRESUMO
This study aims to reveal the potential relationship between 5-HT and oxidative stress in the organism. Our in vitro experiments in RIN-14B cells showed that anoxia leads the cells to the state of oxidative stress. Administration of exogenous 5-HT exacerbated this effect, whereas the inhibition of Tph1, LP533401 alleviated the oxidative stress. Several research articles reported that Cinnabar (consists of more than 96% mercury sulfide, HgS), which is widely used in both Chinese and Indian traditional medicine prescriptions, has been involved in the regulation of 5-HT. The present research revealed that HgS relieved the level of oxidative stress of RIN-14B cells. This pharmacological activity was also observed in the prescription drug Zuotai, in which HgS accounts for 54.5%, and these effects were found to be similar to LP533401, an experimental drug to treat pulmonary hypertension. Further, our in vivo experiments revealed that the administration of cinnabar or prescription drug Zuotai in zebrafish reduced the reactive oxygen species (ROS) induced by hypoxia and cured behavioral abnormalities. Taken together, in organisms with hypoxia induced oxidative stress 5-HT levels were found to be abnormally elevated, indicating that 5-HT could regulate oxidative stress, and the decrease in the 5-HT levels, behavioral abnormalities after treatment with cinnabar and Zuotai, we may conclude that the therapeutic and pharmacologic effect of cinnabar and Zuotai may be based on the regulation of 5-HT metabolism and relief of oxidative stress. Even though they aren't toxic at the present dosage in both cell lines and zebrafish, their dose dependent toxicities are yet to be evaluated.
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Compostos de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Larva/efeitos dos fármacos , Larva/metabolismo , Compostos de Mercúrio/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Modelos Biológicos , Oxirredução/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peixe-ZebraRESUMO
Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a racemic mixture and has an anxiolytic effect in rodents. Previously, we have shown that fluoxetine can up-regulate melanin synthesis in B16F10 melanoma cells and normal human melanocytes (NMHM). However, the role of r-fluoxetine and s-fluoxetine, in the regulation of melanin synthesis, is still unknown. Here, we show how r-fluoxetine plays a critical role in fluoxetine enhancing melanogenesis, both in vivo and vitro, by up-regulating tyrosinase (TYR) and the microphthalmia-associated transcription factor (MITF) expression, whereas, s-fluoxetine does not show any effect in the vivo and vitro systems. In addition, we found that r-fluoxetine induced melanin synthesis through the serotonin1A receptor (5-HT1A) and serotonin 2A receptor (5-HT2A). Furthermore, r-fluoxetine increased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), without affecting the phosphorylation of extracellularly responsive kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). These data suggest that r-fluoxetine may be used as a drug for skin hypopigmentation disorders.
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Fluoxetina/farmacologia , Melaninas/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Melanócitos/citologia , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Estereoisomerismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The stereoselective degradation behaviors of chiral triazole fungicides (hexaconazole, flutriafol and tebuconazole) in sediment were investigated under laboratory conditions. The enantiomers were completely separated by high-performance liquid chromatography on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux Cellulose-2) column. The mean recoveries of hexaconazole, flutriafol and tebuconazole in sediment ranged from 86.7% to 105.9%. The methods were successfully applied for the enantioselective degradation analysis of fungicides in sediment. The results showed that the dissipation of hexaconazole, flutriafol and tebuconazole stereoisomers in sediment followed first-order kinetics (R(2)>0.95). The degradation rate of the enantiomers was different in sediment, and the (-)-enantiomer (t(1/2) was 86 days for hexaconazole, 139 for flutriafol and 136 for tebuconazole) degraded faster than the (+)-enantiomer (t(1/2) was 94 days for hexaconazole, 144 for flutriafol and 151 for tebuconazole) in native condition. The fungicides were degraded slowly, and no significant enantioselective degradation were observed under sterilized conditions. The results may hold promising implications for the environmental and ecological risk assessment of three important chiral triazole fungicides.
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Poluentes Ambientais/metabolismo , Fungicidas Industriais/metabolismo , Triazóis/metabolismo , Biodegradação Ambiental , Celulose/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Cinética , Fenilcarbamatos , EstereoisomerismoRESUMO
OBJECTIVE: To investigate the relation of epicardial adipose tissue volume (EATV) determined by dual-source CT (DSCT) cardiac angiography and EAT-derived inflammatory factors to coronary heart disease (CHD) and vulnerable plaque. METHODS: A total of 260 patients underwent cardiac computed tomography to evaluate stenosis of coronary artery, and blood samples were obtained from each patient. CHD was confirmed in 180 patients by DSA and CHD was excluded in the remaining 80 patients (NCHD). Vascular remodeling index and plaque vulnerability parameters (fatty volume, fibrous volume and calcification volume and fiber volume) were measured in CHD patients and correlation with EATV was analyzed. Epicardial adipose tissue (EAT) and intrathoracic adipose tissue (TAT) were collected from 40 CHD patients undergoing CABG surgery, and, mRNA and protein expressions of leptin and MMP9 were detected by RT-PCR and Western blot analysis. RESULTS: (1) The EATV was significantly higher in the CHD group than in NCHD group ((121.2 ± 40.6) mm³ vs. (74.7 ± 18.1) mm³, P = 0.01). (2) Subgroup analysis of the CHD patients demonstrated that EATV was significantly higher in patients with positive remodeling than in patients without positive remodeling ((97.6 ± 42.0) cm³ vs. (75.5 ± 25.4) cm³, P = 0.01). Lipid plaque volume was positively correlated with EATV (r = 0.34, P = 0.002); however, fiber plaque volume was negatively correlated with EATV (r = -0.30, P = 0.008). (3) Logistic regression analysis indicated that EATV was an independent risk factor for positive vascular remodeling (OR = 2.01, 95% CI: 1.30-2.32, P = 0.01). (4) mRNA and protein expression of leptin and MMP9 in EAT was significantly upregulated in 40 CHD patients who received CABG surgery compared to 40 NCHD patients (P < 0.01). However, there was no significant difference (P > 0.05) in mRNA and protein expression of leptin and MMP9 from the SAT between CHD and NCHD patients. (5) In the CHD group, leptin and MMP9 levels in EAT and EATV were positively correlated with lipid plaque volume and fibrous plaque volume (P < 0.05). CONCLUSIONS: EATV is an independent risk factors of coronary heart disease and plaque vulnerability; EAT secretion of inflammatory cytokines from CHD patients is significant increased compared to NCHD patients, EAT secretion of inflammatory cytokines are positively correlated with EATV, both of which are determinants affecting vascular remodeling. Reducing EATV might help to attenuate inflammation and plaque vulnerability and reduce the risk of coronary heart disease.
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Tecido Adiposo , Doença da Artéria Coronariana/diagnóstico , Placa Aterosclerótica , Angiografia , Aterosclerose , Calcinose , Constrição Patológica , Fibrose , Humanos , Leptina , Pericárdio , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed.
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Proteínas Quinases Ativadas por AMP , Autofagia , Homeostase , Epitélio Pigmentado da Retina , Transdução de Sinais , Autofagia/fisiologia , Epitélio Pigmentado da Retina/metabolismo , Humanos , Homeostase/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/fisiologia , Estresse Oxidativo/fisiologiaRESUMO
Sepsis is a systemic illness for which there are no effective preventive or therapeutic therapies. Zerumbone, a natural molecule, has anti-oxidative and anti-inflammatory properties that may help to prevent sepsis. In the present study, we have assessed the protective effect of zerumbone against sepsis-induced acute lung injury (ALI) and its underlying mechanisms. During the experiment, mice were divided into five groups: a sham group, a sepsis-induced ALI group, and three sepsis groups that are pre-treated with zerumbone at different concentrations. We found that zerumbone greatly decreased the sepsis-induced ALI using histological investigations. Also, zerumbone treatment reduced the sepsis-induced inflammatory cytokine concentrations as well as the number of infiltrating inflammatory cells in BALF compared to non-treated sepsis animals. The zerumbone-pretreated sepsis groups had reduced pulmonary myeloperoxidase (MPO) activity than the sepsis groups. Moreover, the mechanism underlying the protective action of zerumbone on sepsis is accomplished by the activation of antioxidant genes such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutase (SOD), and heme oxygenase 1 (HO-1). The obtained results revealed that zerumbone inhibited the sepsis-induced ALI through its anti-inflammatory and antioxidative activity via inhibition of the NF-κB pathway and activation of HO-1 pathway. Our findings demonstrate that zerumbone pretreatment suppresses sepsis-induced ALI via antioxidative activities and anti-inflammatory, implying that zerumbone could be a viable preventive agent for sepsis-induced ALI.