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Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.
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Fibrilación Atrial , Humanos , Proteína C-Reactiva/metabolismo , Interleucina-6/metabolismo , Estudios de Casos y Controles , Inflamación , Biomarcadores , Estrés Oxidativo , PerfusiónRESUMEN
BACKGROUND/AIM: Injuries to the primary dentition affect children's esthetics, function, and mental health. They may also affect the development of the permanent teeth. The knowledge of dentists about deciduous tooth trauma is rarely evaluated. The aim of this study was to evaluate the knowledge and attitude of dentists in China regarding traumatic dental injuries to primary teeth. MATERIAL AND METHODS: A self-administered online questionnaire containing questions on demographic data and knowledge based on a clinical scenario was given to a purposive sample of dentists, recruited by a non-probability convenience sampling method. The chi-square test was used for statistical analysis, with the significance level set at P <.05. RESULTS: A total of 394 out of 409 dentists provided valid data. There was no significant difference in demographic data. Questions about the treatment of hard dental tissue injuries in primary teeth presented a correct-response rate of 66.4%, with the highest correct-response rate for enamel fracture (n = 368, 93.4%) and lowest for complicated crown-root fracture with pulp exposure (n = 104, 26.4%). Questions about treatment of luxation injuries in primary teeth presented a correct-response rate of 66.6%, with subluxation presenting the highest correct-response rate (n = 391, 99.2%). Factors associated with higher correct-response rates were specialist disciplines, educational qualifications, workplaces, experience of injured teeth treated, and educational experience about primary tooth trauma. No significant differences were found in the correct-response rates of dentists with different years of work experience. Lack of cooperation from children was considered a major obstacle for treatment. Special lectures and Internet courses were the most preferred methods of obtaining knowledge. CONCLUSION: The results suggest that it is necessary to enhance dental trauma education for dentists in China. More attention needs to be paid to trauma in primary dentition to ensure adequate treatment for traumatized primary teeth.
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Avulsión de Diente , Traumatismos de los Dientes , Niño , China , Estudios Transversales , Odontólogos , Humanos , Avulsión de Diente/terapia , Traumatismos de los Dientes/terapia , Diente PrimarioRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Data on LA/LAA thrombus resolution after rivaroxaban treatment has not been established. The aim of the present study was to compare the efficacy and safety on the resolution of LA/LAA thrombus between rivaroxaban and warfarin in nonvalvular atrial fibrillation (AF) patients. 80 AF patients with LA/LAA thrombus between January 2013 and June 2016 were randomized divided into warfarin group (n = 40) and rivaroxaban group (n = 40). Compared to warfarin group, thrombin time (TT; p < 0.0001), plasma prothrombin time (PT; p < 0.0001), and activated partial thromboplastin time (APTT; p = 0.0019) were significantly lower, and fibrinogen (FIB; p < 0.0001) was significantly higher in rivaroxaban group. TEE shown the average length (p < 0.0001), average width (p = 0.0008) and average area (p < 0.0001) of thrombus were significantly lower in rivaroxaban group compared to warfarin group after 6-week treatments. No major or fatal bleeding and ischemic stroke occurred in both two groups. The 20 mg dose Rivaroxaban is more effective than warfarin on the resolution of LA/LAA thrombus in nonvalvular AF patients especially after 6-week treatments. The results suggest that rivaroxaban is a potential option for the treatment of LA/LAA thrombus in patients with nonvalvular AF.
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Apéndice Atrial/patología , Fibrilación Atrial/complicaciones , Rivaroxabán/uso terapéutico , Trombosis/tratamiento farmacológico , Adulto , Anciano , Pruebas de Coagulación Sanguínea , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Rivaroxabán/efectos adversos , Trombosis/diagnóstico por imagen , Resultado del Tratamiento , Warfarina/efectos adversos , Warfarina/uso terapéuticoRESUMEN
Safety concerns are impeding the applications of lithium metal batteries. Flame-retardant electrolytes, such as organic phosphates electrolytes (OPEs), could intrinsically eliminate fire hazards and improve battery safety. However, OPEs show poor compatibility with Li metal though the exact reason has yet to be identified. Here, the lithium plating process in OPEs and Li/OPEs interface chemistry were investigated through ex situ and in situ techniques, and the cause for this incompatibility was revealed to be the highly resistive and inhomogeneous interfaces. Further, a nitriding interface strategy was proposed to ameliorate this issue and a Li metal anode with an improved Li cycling stability (300â h) and dendrite-free morphology is achieved. Meanwhile, the full batteries coupled with nickel-rich cathodes, such as LiNi0.8 Co0.1 Mn0.1 O2 , show excellent cycling stability and outstanding safety (passed the nail penetration test). This successful nitriding-interface strategy paves a new way to handle the incompatibility between electrode and electrolyte.
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The conductive framework is generating considerable interest for lithium metal anodes to accommodate Li+ deposition, due to its ability to reduce electrode current density by increasing the deposition area. However, in most cases, the electroactive surface area is not fully utilized for the nucleation of Li in 3D current collectors, especially under high current densities. Herein, uniform nucleation of Li in the conductive skeleton is achieved by a two-step synergetic process arising from CuBr- and Br-doped graphene-like film. The modified electrode regulates Li nucleating in uniform pancake-like seeds and growing into a granular Li metal ascribed to the excellent lithiophilicity of CuBr- and Br-doping sites and the low Li diffusion barrier on the surface of generated LiBr, as confirmed by the experimental and computational results. Therefore, the modified anode endows small nucleation overpotential, a high-reversibility Li plating/stripping process, and excellent performance in full batteries with industrially significant cathode loading. This work suggests that a two-step cooperative strategy opens a viable route to the development of a Li anode with high reversibility for stable cycling Li metal batteries.
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Lithium (Li) metal is a promising anode material for high-energy density batteries. However, the unstable and static solid electrolyte interphase (SEI) can be destroyed by the dynamic Li plating/stripping behavior on the Li anode surface, leading to side reactions and Li dendrites growth. Herein, we design a smart Li polyacrylic acid (LiPAA) SEI layer high elasticity to address the dynamic Li plating/stripping processes by self-adapting interface regulation, which is demonstrated by inâ situ AFM. With the high binding ability and excellent stability of the LiPAA polymer, the smart SEI can significantly reduce the side reactions and improve battery safety markedly. Stable cycling of 700â h is achieved in the LiPAA-Li/LiPAA-Li symmetrical cell. The innovative strategy of self-adapting SEI design is broadly applicable, providing opportunities for use in Li metal anodes.
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Lithium metal is a promising battery anode. However, inhomogeneous mass and charge transfers across the Li/electrolyte interface result in formation of dendritic Li and "dead" Li, and an unstable solid electrolyte interphase, which incur serious problems to impede its service in rechargeable batteries. Here, we show that the above problems can be mitigated by regulating the interfacial mass/charge transfer. The key to our strategy is hybrid Li storage in onion-like, graphitized spherical C granules wired on a three-dimensional conducting skeleton, which enhances the negativity of surface charge of the C host to contribute to a uniform Li plating while also forming stable Li/C intercalation compounds to offset any irreversible Li loss during cycling. As a result, the anode shows a suppressed dendrite formation and a high Li utilization >95%, enabling a practical Li battery to strike a long lifespan of 1000 cycles at a surplus Li of merely 5%.
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Electrochemical biosensors based on enzymatic reaction have been applied to a wide range of fields. As the trend continues to grow, these biosensors are approaching the limit imposed by physics and chemistry. To further improve the performance of biosensors, the interplay of mass transport and enzymatic reaction kinetics, especially in enzyme cascade systems, should be considered in the design of biosensors. Herein, we propose a simple approach to studying the influence of mass transport and enzyme molecule motion on the kinetics of enzyme cascade reactions. ß-Galactosidase (ß-Gal) and glucose oxidase (GOx) of the enzyme cascade reaction are precisely immobilized onto the disk and ring electrodes, respectively, of a rotating ring-disk electrode (RRDE) via covalent attachment. At a low rotating speed (<600 rpm), convective transport promotes the enzyme cascade reaction. When the rotating speed is higher than 600 rpm, the cascade reaction becomes kinetically controlled. Further increase of the rotating speed results in a slow decline in reaction rate, possibly due to the production inhibition effect. In addition, the effect of conformation change of the enzyme at higher centrifugal forces on enzyme activity should be considered. This study would shine light on the effect of convective force on regulation of kinetics of enzyme cascade reaction, offering an ideal platform for studying other enzyme cascade reactions and providing fundamentals to design high-performance biosensors, biofuel cells, and bioelectronics.
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Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Enzimas Inmovilizadas/química , Glucosa Oxidasa/química , beta-Galactosidasa/química , Aspergillus niger/enzimología , Aspergillus oryzae/enzimología , Técnicas Biosensibles/instrumentación , Difusión , Técnicas Electroquímicas/instrumentación , Electrodos , Glucosa/química , Cinética , Lactosa/química , RotaciónRESUMEN
Resveratrol (RSV), a phytoalexin, has shown to prevent endothelial dysfunction and reduce diabetic vascular complications and the risk of cardiovascular diseases. The aim of this study was to investigate the signaling mechanisms underlying the protecting effects of RSV against endothelial dysfunction during hyperglycemia in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with RSV, and then exposed to high glucose (HG, 30 mmol/L). Akt-Ser473 phosphorylation, eNOS-Ser1177 phosphorylation, and PTEN protein levels in the cells were detected using Western blot. For in vivo studies, WT and Akt-/- mice were fed a normal diet containing RSV (400 mg·kg-1·d-1) for 2 weeks, then followed by injection of STZ to induce hyperglycemia (300 mg/dL). Endothelial function was evaluated using aortic rings by assessing ACh-induced vasorelaxation. RSV (5-20 µmol/L) dose-dependently increased Akt-Ser473 phosphorylation, accompanied by increased eNOS-Ser1177 phosphorylation in HUVECs; these effects were more prominent under HG stimulation. Transfection with Akt siRNA abolished RSV-enhanced eNOS phosphorylation and NO release. Furthermore, RSV (5-20 µmol/L) dose-dependently decreased the levels of PTEN, which was significantly increased under HG stimulation, and PTEN overexpression abolished RSV-stimulated Akt phosphorylation in HG-treated HUVECs. Moreover, RSV dramatically increased 26S proteasome activity, which induced degradation of PTEN. In in vivo studies, pretreatment with RSV significantly increased Akt and eNOS phosphorylation in aortic tissues and ACh-induced vasorelaxation, and improved diabetes-induced endothelial dysfunction in wild-type mice but not in Akt-/- mice. RSV attenuates endothelial function during hyperglycemia via activating proteasome-dependent degradation of PTEN, which increases Akt phosphorylation, and consequentially upregulation of eNOS-derived NO production.
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Endotelio Vascular/efectos de los fármacos , Hiperglucemia/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estilbenos/farmacología , Acetilcolina/farmacología , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Glucosa/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , ARN Interferente Pequeño/farmacología , Resveratrol , Vasodilatación/efectos de los fármacosRESUMEN
Radiofrequency catheter ablation (RFCA) in the treatment of AF is currently based on pulmonary vein isolation (PVI). Some studies have investigated the efficacy of empiric SVC isolation (SVCI) in addition to conventional PVI in order to improve success rates and reduce recurrence rates. However, the results of the studies have given conflicting data.We performed a meta-analysis to evaluate the efficacy and safety of the empiric SVCI compared with conventional SVCI for paroxysmal atrial fibrillation (PAF) ablation.We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Database from the period January 1986 to August 2016 and identified qualified studies. The primary clinical outcome was the recurrence rate of atrial tachyarrhythmias, and the secondary clinical outcomes were procedure time, fluoroscopy time, and complications.We identified 3 randomized controlled trials (RCTs) and one nonrandomized, observational study (nROS) involving 245 patients with empiric SVCI and 269 patients with conventional SVCI. The empiric SVCI group had a lower recurrence rate of atrial tachyarrhythmia after a single procedure compared with the conventional SVCI group (16.7% versus 29.4%, OR: 0.48, 95%CI: 0.31 to 0.74, P = 0.0009). There was no significant difference in fluoroscopic time (P = 0.22), procedure time (P = 0.32), or clinical complications (P = 0.33) between the two groups.Empiric SVCI is more effective than conventional SVCI in terms of the long-term outcomes of PAF patients after a single PVI procedure, with the same fluoroscopic time, procedure time, and clinical complications.
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Fibrilación Atrial/cirugía , Venas Pulmonares/cirugía , Vena Cava Superior/cirugía , Fibrilación Atrial/fisiopatología , Ablación por Catéter/métodos , Sistema de Conducción Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/cirugía , Humanos , Resultado del TratamientoRESUMEN
The spatial positioning of enzymes and mass transport play crucial roles in the functionality and efficiency of enzyme cascade reactions. To fully understand the mass transport regulating kinetics of enzyme cascade reactions, we investigated the contribution of convective and diffusive transports to a cascade reaction of ß-galactosidase (ß-Gal)/glucose oxidase (GOx) confined in a microchannel. ß-Gal and GOx are assembled on two separated gold films patterned in a polydimethylsiloxane (PDMS) microchannel with a controllable distance from 50 to 100 µm. Experimental results demonstrated that the reaction yield increases with decreasing distance between two enzymes and increasing substrate flow rate. Together with the simulation results, we extracted individual reaction kinetics of the enzyme cascade reaction and found that the reaction rate catalyzed by ß-Gal occurred much faster than by GOx, and thus, the ß-Gal catalytic reaction showed diffusion controll, whereas the GOx catalytic reaction showed kinetic controll. Since the decrease in the enzymes distance shortens the transport length of intermediate glucose to GOx, the amount of glucose reaching GOx will be increased in the unit time, and in turn, the enzyme cascade reaction yield will be increased with decreasing the gap distance. This phenomenon is similar to the intermediates pool of tricarboxylic acid (TCA) cycle in the metabolic system. This study promotes the understanding of the metabolic/signal transduction processes and active transport in biological systems and promises to design high performance biosensors and biofuel cells systems.
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Glucosa Oxidasa/metabolismo , beta-Galactosidasa/metabolismo , Biocatálisis , Técnicas Biosensibles , Difusión , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Glucosa Oxidasa/química , Oro , Cinética , Nanopartículas del Metal/química , Especificidad por Sustrato , beta-Galactosidasa/químicaRESUMEN
Water molecules possess discontinuous properties in confined surroundings as compared to the bulk, their transport velocity shows a step change with the increase in the radius of hydrophobic carbon nanotubes (CNTs). Here, we report that the chain of water molecules in CNTs behaves as a "spring" owing to hydrogen bonding. Thus, the transport of water molecules in confined systems proceeds as a wave motion with eigen frequencies in the terahertz region which is determined by the CNT size. Water velocities derived from molecular dynamics (MD) fit well with the ones from finite element methods (FEM) on consideration of both the no-slip and slip boundary conditions for CNT diameters less than 1 nm and more than 1 nm, respectively. The present work helps clarify the features of mass and momentum transfers in confined surroundings, and provides perspectives for mass transfer applications.
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Hollow waveguides(HWG)have recently emerged as a novel concept serving as an efficient optical waveguide and a highly miniaturized gas cell. Compared with conventional multi-pass gas cells, HWG gas cell has the advantages of facilitating gas exchanging because of its small size and fast responding speed. In this paper, we poposed an ammonia sensor based on tunable diode laser absorption spectroscopy(TDLAS) using HWG as the gas cell. The sensor employs wavelength modulation spectrum(WMS) with simultaneous detection of the second harmonic(2f) signal and the first hamonic(1f) signal. Normalization of the 2f signal by the 1f signal enables the sensor for calibration free measurement. The sensor performance is tested with gas standards and the result shows good linearity with correlation coefficient of 0.999 8, and the detection limit is 26 ppb with an integration time of 18 s. The sensor based on HWG gas cell is suitable for sensative and real-time monitoring ammonia in the air.
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Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.
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Consumer devices are increasingly used to monitor peripheral body temperature (PBT) for menstrual cycle tracking, but the link between PBT and hormone variations remains underexplored. This study examines the relationship between these variables with a focus on nightly wrist skin temperature (WST). Fifty participants provided physiological and self-reported data, including WST, daily step counts, glucose levels, hormone levels (E3G, LH), and diary entries. Results show a negative correlation between WST and hormone levels when E3G and LH are below average, and this trend was robust to demographics and self-reported stress. Increased variance between mid-cycle hormonal peaks and WST fluctuations may stem from differences between basal body temperature (BBT) and WST. This research suggests that algorithms reliant on body temperature for tracking hormonal changes or other aspects of the menstrual cycle may need to account for increased variance in WST trends if they are meant to be deployed on wearable devices.
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This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.
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Osteogénesis , Ligamento Periodontal , Células Madre , Diente Primario , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Humanos , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Diente Primario/citología , Células Madre/efectos de los fármacos , Lipopolisacáridos/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inflamación , Transducción de Señal/efectos de los fármacos , Células Cultivadas , Reacción en Cadena en Tiempo Real de la Polimerasa , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/análisisRESUMEN
The purpose of this research was to assess the association between sleep disorders and coronary heart disease (CHD) using data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study included 9886 eligible participants with valid data on sleep disorders and CHD from the NHANES from 2011 to 2014. The complex NHANES sampling led to use of sample weights in analyses. Various statistical methods and covariates were utilized. Significance was set at Pâ <â .05. Receiver operating characteristic curves were used to assess the diagnostic efficacy of sleep disorders in relation to CHD. Sleep disorders were significantly associated with CHD (Pâ <â .001). In the model corrected for age, sex, race, hypertension, diabetes, and uric acid as covariates, sleep disorders and CHD remained significantly associated (Pâ <â .001, odds ratioâ =â 1.83 [95% confidence interval: 1.31-2.58]). The correlation between sleep disorders and CHD varies by age and gender. Sleep disorders have some predictive value for CHD (0.5â <â area under curveâ ≤â 0.7). Sleep disorders were associated with and predictive of CHD risk, warranting consideration in clinical assessments.
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Enfermedad Coronaria , Encuestas Nutricionales , Trastornos del Sueño-Vigilia , Humanos , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Enfermedad Coronaria/epidemiología , Adulto , Trastornos del Sueño-Vigilia/epidemiología , Estados Unidos/epidemiología , Anciano , Factores de Riesgo , Adulto Joven , Curva ROC , Factores de Edad , Factores SexualesRESUMEN
Background: Cyperus rotundus (CR) is widely used in traditional Chinese medicine to prevent and treat a variety of diseases. However, its functions and mechanism of action in osteoarthritis (OA) has not been elucidated. Here, a comprehensive strategy combining network pharmacology, molecular docking, molecular dynamics simulation and in vitro experiments was used to address this issue. Methods: The bioactive ingredients of CR were screened in TCMSP database, and the potential targets of these ingredients were obtained through Swiss Target Prediction database. Genes in OA pathogenesis were collected through GeneCards, OMIM and DisGeNET databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using DAVID database. STRING database and Cytoscape 3.10 software were used to construct "component-target-pathway" network, and predict the core targets affected by CR. The binding affinity between bioactive components and the core targets was evaluated by molecular docking and molecular dynamics simulation. The therapeutic activity of kaempferol on chondrocytes in inflammatory conditions was verified by in vitro experiments. Results: Fifteen CR bioactive ingredients were obtained, targeting 192 OA-related genes. A series of biological processes, cell components, molecular functions and pathways were predicted to be modulated by CR components. The core targets of CR in OA treatment were AKT serine/threonine kinase 1 (AKT1), interleukin 1 beta (IL1B), SRC proto-oncogene, non-receptor tyrosine kinase (SRC), BCL2 apoptosis regulator (BCL2), signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), hypoxia-inducible factor 1 subunit alpha (HIF1A), matrix metallopeptidase 9 (MMP9), estrogen receptor 1 (ESR1) and PPARG orthologs from vertebrates (PPARG), and the main bioactive ingredients of CR showed good binding affinity with these targets. In addition, kaempferol, one of the CR bioactive components, weakens the effects of IL-1ß on the viability, apoptosis and inflammation of chondrocytes. Conclusion: Theoretically, CR has great potential to ameliorate the symptoms and progression of OA, via multiple components, multiple targets, and multiple downstream pathways.
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BACKGROUND: Endothelial activation plays an important role in sepsis-mediated inflammation, but the triggering factors have not been fully elucidated. Microvesicles carrying mitochondrial content (mitoMVs) have been implicated in several diseases and shown to induce endothelial activation. AIM: To explore whether mitoMVs constitute a subset of MVs isolated from plasma of patients with sepsis and contribute to endothelial activation. METHODS: MVs were isolated from human plasma and characterized by confocal microscopy and flow cytometry. Proinflammatory cytokines, including interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, and soluble vascular cell adhesion molecule (sVCAM)-1 were detected by ELISA. Human umbilical vein endothelial cells (HUVECs) were stimulated with the circulating MVs to evaluate their effect on endothelial activation. RESULTS: MitoMVs were observed in plasma from patients with sepsis. Compared with those in healthy controls, expression of MVs, mitoMVs, proinflammatory cytokines and sVCAM-1 was increased. The number of mitoMVs was positively associated with TNF-α and sVCAM-1. In vitro, compared with MVs isolated from the plasma of healthy controls, MVs isolated from the plasma of patients with sepsis induced expression of OAS2, RSAD2, and CXCL10 in HUVECs. MitoMVs were taken up by HUVECs, and sonication of MVs significantly reduced the uptake of mitoMVs by HUVECs and expression of the above three type I IFN-dependent genes. CONCLUSION: MitoMVs are increased in the plasma of patients with sepsis, which induces elevated expression of type I IFN-dependent genes. This suggests that circulating mitoMVs activate the type I IFN signalling pathway in endothelial cells and lead to endothelial activation.