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1.
Int J Mol Sci ; 25(19)2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39409101

RESUMEN

The phenotype of albino tea plants (ATPs) is significantly influenced by temperature regimes and light conditions, which alter certain components of the tea leaves leading to corresponding phenotypic changes. However, the regulatory mechanism of temperature-dependent changes in photosynthetic pigment contents and the resultant leaf colors remain unclear. Here, we examined the chloroplast microstructure, shoot phenotype, photosynthetic pigment content, and the expression of pigment synthesis-related genes in three tea genotypes with different leaf colors under different temperature conditions. The electron microscopy results revealed that all varieties experienced the most severe chloroplast damage at 15 °C, particularly in albino cultivar Baiye 1 (BY), where chloroplast basal lamellae were loosely arranged, and some chloroplasts were even empty. In contrast, the chloroplast basal lamellae at 35 °C and 25 °C were neatly arranged and well-developed, outperforming those observed at 20 °C and 15 °C. Chlorophyll and carotenoid measurements revealed a significant reduction in chlorophyll content under low temperature treatment, peaking at ambient temperature followed by high temperatures. Interestingly, BY showed remarkable tolerance to high temperatures, maintaining relatively high chlorophyll content, indicating its sensitivity primarily to low temperatures. Furthermore, the trends in gene expression related to chlorophyll and carotenoid metabolism were largely consistent with the pigment content. Correlation analysis identified key genes responsible for temperature-induced changes in these pigments, suggesting that changes in their expression likely contribute to temperature-dependent leaf color variations.


Asunto(s)
Camellia sinensis , Carotenoides , Clorofila , Regulación de la Expresión Génica de las Plantas , Genotipo , Hojas de la Planta , Temperatura , Camellia sinensis/genética , Camellia sinensis/metabolismo , Camellia sinensis/crecimiento & desarrollo , Clorofila/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Carotenoides/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Fotosíntesis/genética , Pigmentación/genética , Color , Fenotipo
2.
Nanomaterials (Basel) ; 14(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38869569

RESUMEN

Aluminosilicates, abundant and crucial in both natural environments and industry, often involve uncontrollable chemical components when derived from minerals, making further chemical purification and reaction more complicated. This study utilizes pure alumina and fumed silica powders as more controllable sources, enhancing aluminosilicate reactivity through room temperature (non-firing) processing and providing a robust framework that resists mechanical stress and high temperature. By embedding iron-based metal-organic frameworks (Fe-MOF/non-firing aluminosilicate membranes) within the above matrix, these ceramic membranes not only preserve their mechanical robustness but also gain significant chemical functionality, enhancing their capacity to removing phytochromes from the vegetables. Sodium hydroxide and sodium silicate were selected as activators to successfully prepare high-strength, non-firing aluminosilicate membranes. These membranes demonstrated a flexural strength of 8.7 MPa under wet-culture conditions with a molar ratio of Al2O3:SiO2:NaOH:Na2SiO3 at 1:1:0.49:0.16. The chlorophyll adsorption of spinach conducted on these membranes showed a removal rate exceeding 90% at room temperature and pH = 9, highlighting its potential for the selective adsorption of chlorophyll. This study underscores the potential of MOF-enhanced aluminosilicate ceramic membranes in environmental applications, particularly for agricultural pollution control.

3.
J Cancer Res Clin Oncol ; 150(4): 214, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662050

RESUMEN

PURPOSE: Core 1ß1,3-galactosyltransferase 1 (C1GALT1) exhibits elevated expression in multiple cancers. The present study aimed to elucidate the clinical significance of C1GALT1 aberrant expression and its impact on radiosensitivity in lung adenocarcinoma (LUAD). METHODS: The C1GALT1 expression and its clinical relevance were investigated through public databases and LUAD tissue microarray analyses. A549 and H1299 cells with either C1GALT1 knockdown or overexpression were further assessed through colony formation, gamma-H2A histone family member X immunofluorescence, 5-ethynyl-2'-deoxyuridine incorporation, and flow cytometry assays. Bioinformatics analysis was used to explore single cell sequencing data, revealing the influence of C1GALT1 on cancer-associated cellular states. Vimentin, N-cadherin, and E-cadherin protein levels were measured through western blotting. RESULTS: The expression of C1GALT1 was significantly higher in LUAD tissues than in adjacent non-tumor tissues both at mRNA and protein level. High expression of C1GALT1 was correlated with lymph node metastasis, advanced T stage, and poor survival, and was an independent risk factor for overall survival. Radiation notably upregulated C1GALT1 expression in A549 and H1299 cells, while radiosensitivity was increased following C1GALT1 knockdown and decreased following overexpression. Experiment results showed that overexpression of C1GALT1 conferred radioresistance, promoting DNA repair, cell proliferation, and G2/M phase arrest, while inhibiting apoptosis and decreasing E-cadherin expression, alongside upregulating vimentin and N-cadherin in A549 and H1299 cells. Conversely, C1GALT1 knockdown had opposing effects. CONCLUSION: Elevated C1GALT1 expression in LUAD is associated with an unfavorable prognosis and contributes to increased radioresistance potentially by affecting DNA repair, cell proliferation, cell cycle regulation, and epithelial-mesenchymal transition (EMT).


Asunto(s)
Adenocarcinoma del Pulmón , Galactosiltransferasas , Neoplasias Pulmonares , Tolerancia a Radiación , Humanos , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/radioterapia , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal , Galactosiltransferasas/genética , Galactosiltransferasas/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Pronóstico , Tolerancia a Radiación/genética
4.
CNS Neurosci Ther ; 30(3): e14697, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38544474

RESUMEN

AIMS: Neuroinflammation and pyroptosis are key mediators of cerebral ischemia/reperfusion (I/R) injury-induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I/R injury in mice are unclear. METHODS: Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion/reperfusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I/R injury in vivo and in vitro. RESULTS: BRCC3 protein expression peaked 24 h after MCAO and OGD/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N- and C-terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation. CONCLUSION: BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I/R injury.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Animales , Humanos , Ratones , Isquemia Encefálica/metabolismo , Enzimas Desubicuitinizantes , Infarto de la Arteria Cerebral Media/patología , Inflamasomas/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis/fisiología , Daño por Reperfusión/metabolismo
5.
Cell Commun Signal ; 22(1): 76, 2024 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-38287382

RESUMEN

The crosstalk between astrocytes and microglia plays a pivotal role in neuroinflammation following ischemic stroke, and phenotypic distribution of these cells can change with the progression of ischemic stroke. Peroxiredoxin (PRDX) 6 phospholipase A2 (iPLA2) activity is involved in the generation of reactive oxygen species(ROS), with ROS driving the activation of microglia and astrocytes; however, its exact function remains unexplored. MJ33, PRDX6D140A mutation was used to block PRDX6-iPLA2 activity in vitro and vivo after ischemic stroke. PRDX6T177A mutation was used to block the phosphorylation of PRDX6 in CTX-TNA2 cell lines. NAC, GSK2795039, Mdivi-1, U0126, and SB202190 were used to block the activity of ROS, NOX2, mitochondrial fission, ERK, and P38, respectively, in CTX-TNA2 cells. In ischemic stroke, PRDX6 is mainly expressed in astrocytes and PRDX6-iPLA2 is involved in the activation of astrocytes and microglia. In co-culture system, Asp140 mutation in PRDX6 of CTX-TNA2 inhibited the polarization of microglia, reduced the production of ROS, suppressed NOX2 activation, and inhibited the Drp1-dependent mitochondrial fission following OGD/R. These effects were further strengthened by the inhibition of ROS production. In subsequent experiments, U0126 and SB202190 inhibited the phosphorylation of PRDX6 at Thr177 and reduced PRDX6-iPLA2 activity. These results suggest that PRDX6-iPLA2 plays an important role in the astrocyte-induced generation of ROS and activation of microglia, which are regulated by the activation of Nox2 and Drp1-dependent mitochondrial fission pathways. Additionally, PRDX6-iPLA2 activity is regulated by MAPKs via the phosphorylation of PRDX6 at Thr177 in astrocytes.


Asunto(s)
Astrocitos , Butadienos , Accidente Cerebrovascular Isquémico , Nitrilos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Astrocitos/metabolismo , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Peroxiredoxina VI/genética , Peroxiredoxina VI/metabolismo
6.
Int J Ophthalmol ; 16(7): 1034-1040, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465502

RESUMEN

AIM: To evaluate effects of endogenous dopamine induced by low concentration atropine eye drops on choroidal neovascularization (CNV) in high myopia mice. METHODS: The C57BL/6J mice were deprived of the right eye for 4wk, and the high myopia was diagnosed by optometry, the diopter was less than -6.00 D, and CNV was induced by 532 nm laser. The changes of dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), and vascular endothelial growth factor A (VEGFA) were detected by Western blot technology at 0.5, 1, 2h, and 7d after 0.01%, 0.05%, and 0.1% atropine eye drops, respectively, the area of CNV was measured. RESULTS: Significant increases were observed on the expression of DRD2 in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). Significant decreases were observed on the expression of DRD1 and VEGFA in mouse high myopia model at 0.5, 1, 2h, 7d with 0.05% and 0.1% atropine eye drops (P<0.05). The area of CNV induced by laser in the drug-treated group was significantly smaller than that in the control group, and the higher the concentration, the more significant the inhibitory effect (P<0.05). CONCLUSION: The 0.01%, 0.05%, 0.1% atropine eye drops can decrease the level of VEGFA and inhibit high myopia CNV indirectly by up-regulating the level of DRD2 and down-regulating the level of DRD1, and the effect of 0.05% and 0.1% atropine eye drops is more significant.

7.
Int J Mol Sci ; 24(7)2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37047745

RESUMEN

P2ry12 is a microglial marker gene. Recently, increasing evidence has demonstrated that its expression levels can vary in response to different CNS disorders and can affect microglial functions, such as polarization, plasticity, and migration. However, the expression and function of P2ry12 in microglia during ischemia-reperfusion injury (IRI) remain unclear. Here, we developed a computational method to obtain microglia-specific P2ry12 genes (MSPGs) using sequencing data associated with IRI. We evaluated the change in comprehensive expression levels of MSPGs during IRI and compared it to the expression of P2ry12 to determine similarity. Subsequently, the MSPGs were used to explore the P2ry12 functions in microglia through bioinformatics. Moreover, several animal experiments were also conducted to confirm the reliability of the results. The expression of P2ry12 was observed to decrease gradually within 24 h post injury. In response, microglia with reduced P2ry12 expression showed an increase in the expression of one receptor-encoding gene (Flt1) and three ligand-encoding genes (Nampt, Igf1, and Cxcl2). Furthermore, double-labeling immunofluorescence staining revealed that inhibition of P2ry12 blocked microglial migration towards vessels during IRI. Overall, we employ a combined computational and experimental approach to successfully explore P2ry12 expression and function in microglia during IRI.


Asunto(s)
Microglía , Daño por Reperfusión , Animales , Microglía/metabolismo , Reproducibilidad de los Resultados , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo
8.
Front Oncol ; 12: 1015302, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36605427

RESUMEN

Background: Chemotherapy combined with immune checkpoints inhibitors (ICIs) has been established as a standard treatment for locally advanced, metastatic, or recurrent esophageal squamous cell cancer (ESCC). However, the optimal chemotherapy regimen in combination therapy is still unclear. Purpose: To investigate the efficacy and adverse events of the fluorouracil plus platinum (FP) and taxane plus platinum (TP) regimens in ESCC patients receiving chemo-immunotherapy, we conducted this systematic review and meta-analysis. Methods: Potentially eligible studies were searched from Medline, Embase, Web of Science, and the Cochrane Library. Pooled rates of overall response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events were compared between ICIs+TP and ICIs+FP groups in ESCC patients receiving first-line chemo-immunotherapy. Results: A total of 10 clinical trials were included, of which 5 were randomized controlled trials. Compared with chemotherapy alone, chemo-immunotherapy significantly improved the OS of ESCC patients (pooled HR=0.69; 95% CI, 0.63-0.76; p<0.01). Pooled analysis revealed that ESCC patients receiving ICIs+TP had significantly higher ORR, DCR, PFS, and OS rates than those receiving ICIs+FP. No statistically significant difference in the pooled incidence rate of treatment-related death was found (2.3% vs 0.9%, P=0.08). ICIs+TP had significantly higher rates of hematologic toxicity but lower rates of gastrointestinal toxicity than ICIs+FP. Conclusions: Based on the current data, the first-line treatment using ICIs+TP may be a better option than ICIs+FP in advanced, metastatic, or recurrent ESCC.

9.
Environ Sci Pollut Res Int ; 29(2): 2480-2492, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34374012

RESUMEN

Non-thermal plasma (NTP) is gaining attention as a powerful tool to induce various reactions. The combination of NTP with catalysts has been successfully used to degrade volatile organic compounds (VOCs) for pollution control. In this study, a series of TiO2-C/5A catalysts, synthesized by carbon dots (C-dots) that decorate TiO2 by sol-gel and wetness impregnation methods, were incorporated with a dielectric barrier discharge (DBD) reactor in a single-stage structure to degrade toluene at atmospheric pressure and room temperature. A proton-transfer reaction mass spectrometer and a CO2 analyzer were used to monitor the concentration variations of organic by-products and CO2 online. The effects of input power, mass ratio of C-dots/TiO2 (TiO2/5A (0 wt%), TiO2-C1/5A (2.5 wt%), TiO2-C2/5A (5 wt%), TiO2-C3/5A (10 wt%)), gas flow rate, initial concentration of toluene on the toluene degradation efficiency, and CO2 selectivity were studied. The plasma-catalyst hybrid system could effectively improve the energy efficiency and reaction selectivity, attaining a maximum toluene degradation efficiency of 99.6% and CO2 selectivity of 83.0% compared to 79.5% and 37.5%, respectively, using the conventional plasma alone. Moreover, the generation of organic by-products also declined dramatically, averaging only half as much in plasma alone. The results also indicated that the appropriate amount of C-dot doping could greatly improve the catalyst efficiency in the hybrid plasma system. This is because the interaction between C-dots and TiO2 favors the formation of photoelectron holes and reduces the energy band gap and the recombination rate of photogenerated electron holes, which facilitates the generation of more active species on the catalyst surface, thereby leading to a more effective degradation reaction. These observations will provide guidance for the interaction studies between NTP and catalysts, not only for the exploration of new chemical mechanisms of aromatic compounds, but also for the screening of favorable materials for the desired reactions.


Asunto(s)
Gases em Plasma , Catálisis , Titanio , Tolueno
10.
Saudi J Biol Sci ; 28(1): 163-169, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33424293

RESUMEN

The photodegradation of 2-chlorobenzoic acid (2-CBA) in suspensions of TiO2 was examined under different operational parameters. The optimal condition could be obtained through the experiment, i.e. that the concentration of 2-CBA was 30 mg/L and the dosing quantity of TiO2 was 0.01 g under UV light in the case of pH 3.5. Above reaction process was in accordance with first order kinetics model. The influence on photocatalytic degradation caused by typical anions in eutrophicated water body such as NO3 - and H2PO4 - was explored in this work, which revealed that both two anions had inhibitory effect on the degradation process. In addition, alcohol was introduced into the process to identify the degradation mechanism of 2-CBA with TiO2, and the reaction route of 2-CBA could be predicted through the analysis on the intermediate.

11.
Materials (Basel) ; 13(17)2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32878091

RESUMEN

A thermosetting resin system, based on bismaleimide (BMI), has been developed via copolymerization of 4,4'-diaminodiphenylsulfone with a newly synthesized graphene oxide modified using epoxy silane (ES-GO). The effect of ES-GO on the thermomechanical and mechanical properties of cured modified resin was studied. To evaluate the efficiency of the modified BMI systems, the composite samples using glass fiber cloth were molded and tested. Thermogravimetric analysis indicates that the cured sample systems displays a high char yield at lower concentrations of ES-GO (≤0.5 wt.%), suggesting an improved thermal stability. Using dynamic mechanical analysis, a marked increase in glass transition temperature (Tg) with increasing ES-GO content was observed. Analysis of mechanical properties reveals a possible effect of ES-GO as a toughener. The results also showed that the addition of 0.3 wt.% ES-GO maximizes the toughness of the modified resin systems, which was further confirmed by the result of analysis of fracture surfaces. At the same time, a molded composite with ES-GO showed improved mechanical properties and retention rate at 150 °C as compared to that made with neat resin.

12.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31306800

RESUMEN

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.


Asunto(s)
Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/efectos adversos , Guanina/análogos & derivados , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Resultado del Tratamiento
13.
Water Res ; 171: 115379, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31869692

RESUMEN

Sewage sludge is a primary pathway for microplastics (MPs) entering into terrestrial ecosystems. However, a standardized method to analyze MP in sludge is lacking due to its high organic matter. This study investigated the extraction efficiency of six MPs in five solid matrices, i.e. sewage sludge, cattle manure, soil, sediment and silicon dioxide. Results show lower extraction efficiency of 87.2% for MPs in sludge compared with that in other matrices, especially polyethylene terephthalate (PET) (only 27.8%). The possible reason was that the presence of extracellular polymeric substances within the sludge hinders the MPs to float. Therefore, five protocols, i.e. hydrogen peroxide (H2O2), Fenton, nitric acid (HNO3), hydrochloric acid (HCl) and sodium hydroxide (NaOH) were used to pretreat the sludge and optimize the MP extraction. The sludge pretreated by H2O2, Fenton and 1 M of acids had higher MP extraction efficiency than the raw sludge due to higher extraction of the PET. The MP extraction efficiency in the sludge first increased, and subsequently decreased with the soluble chemical oxygen demand (SCOD) content, implying that moderate dissolution of sludge organic matter is beneficial to the MP extraction. Quantitative analysis of the changes in the MP physicochemical characteristics after the pretreatments indicated that polyamide (PA) and PET are not resistant to acid and alkali treatment, respectively. Principal component analysis shows that the effect of pretreatments on the MPs follows a decreasing sequence: alkali > high concentration of acids > low concentration of acids > H2O2 and Fenton. Additionally, the susceptibility of the MPs to the pretreatments follows a decreasing sequence: PET, PA and polymethyl methacrylate (PMMA) > polystyrene (PS) > polyethylene (PE) and polypropylene (PP). The findings supply novel insights into the effect of chemical pretreatments on MP extraction in sewage sludge.


Asunto(s)
Plásticos , Aguas del Alcantarillado , Animales , Bovinos , Ecosistema , Peróxido de Hidrógeno , Microplásticos
14.
Front Physiol ; 8: 819, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29104543

RESUMEN

Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process. Objective: In this study, we characterized with high spatio-temporal resolution the development of discordant alternans patterns in transmembrane voltage (Vm) and intracellular calcium concentration ([Cai]+2) as a function of pacing period in rabbit hearts. Then we compared the dynamics to that of the latest state-of-the-art model for ventricular action potentials and calcium transients to better understand the underlying mechanisms of discordant alternans and compared the experimental data to the mathematical models representing Vm and [Cai]+2 dynamics. Methods and Results: We performed simultaneous dual optical mapping imaging of Vm and [Cai]+2 in Langendorff-perfused rabbit hearts with higher spatial resolutions compared with previous studies. The rabbit hearts developed discordant alternans through decreased pacing period protocols and we quantified the presence of multiple nodal points along the direction of wave propagation, both in APD and CaD, and compared these findings with results from theoretical models. In experiments, the nodal lines of CaD alternans have a steeper slope than those of APD alternans, but not as steep as predicted by numerical simulations in rabbit models. We further quantified several additional discrepancies between models and experiments. Conclusions: Alternans in CaD have nodal lines that are about an order of magnitude steeper compared to those of APD alternans. Current action potential models lack the necessary coupling between voltage and calcium compared to experiments and fail to reproduce some key dynamics such as, voltage amplitude alternans, smooth development of calcium alternans in time, conduction velocity and the steepness of the nodal lines of APD and CaD.

15.
Heart Rhythm ; 14(8): 1254-1262, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28502873

RESUMEN

BACKGROUND: Low-energy anti-fibrillation pacing (LEAP) has been suggested as an alternative treatment in symptomatic fibrillation patients. It significantly lowers the energy required compared with standard 1-shock defibrillation. OBJECTIVE: In this study, we investigated the mechanism of arrhythmia termination by LEAP and systematically analyzed the influence of shock period and timing on the success rate of LEAP. METHODS: We induced atrial and ventricular fibrillation in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2-dimensional bidomain human atrial model. RESULTS: The ex vivo experiments showed successful termination of atrial fibrillation and ventricular fibrillation using LEAP, with an average 88% and 81% energy reduction, respectively, and both experiments and simulations verified that synchronization from virtual electrodes is the key mechanism for termination of arrhythmia by LEAP using modified Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed in simulations that LEAP is more effective when the shock period is close to the dominant period and the first shock is delivered when FTE is decreasing. CONCLUSIONS: Our results support synchronization as the mechanism for arrhythmia termination by LEAP, and its effectiveness can be improved by adjusting shock period and timing.


Asunto(s)
Fibrilación Atrial/terapia , Estimulación Cardíaca Artificial/métodos , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Animales , Fibrilación Atrial/fisiopatología , Simulación por Computador , Modelos Animales de Enfermedad , Perros , Atrios Cardíacos , Factores de Tiempo
16.
Microbiol Res ; 188-189: 106-112, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27296968

RESUMEN

Pseudomonas fluorescens FD6 has been shown to possess many beneficial traits involved in the biocontrol of fungal plant pathogens, such as Botrytis cinerea and Monilinia fructicola. Vfr (virulence factor regulator) a highly conserved global regulator of gram-negative bacteria, such as the human pathogen Pseudomonas aeruginosa, is required for the expression of many important virulence traits. The role of Vfr in the regulation of biocontrol traits, such as the production of antibiotics to control fungal pathogens by antagonistic bacteria, has not been elucidated. This study investigated the effect of a vfr mutant derived from P. fluorescens FD6 to better understand the regulation of some important biocontrol traits associated with the bacterium. Biochemical studies indicated that the production of the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin and pyoluteorin, was markedly enhanced in the vfr mutant. The vfr mutation also increased biofilm production, swimming motility and the expression of exopolysaccharide-associated gene (pelA, pslA and pslB) transcripts, but reduced protease production. Wheat rhizosphere and root tip colonization by the vfr mutant was higher than that by the wild type at 7 and 21days after inoculation. These findings demonstrate that Vfr modulates the expression of several key traits and the production of important antibiotics involved in the biocontrol potential of P. fluorescens FD6.


Asunto(s)
Antifúngicos/metabolismo , Proteína Receptora de AMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica , Fenoles/metabolismo , Floroglucinol/análogos & derivados , Pseudomonas fluorescens/metabolismo , Pirroles/metabolismo , Pirrolnitrina/metabolismo , Antibiosis , Proteína Receptora de AMP Cíclico/genética , Técnicas de Inactivación de Genes , Humanos , Control Biológico de Vectores , Floroglucinol/metabolismo , Pseudomonas fluorescens/genética , Pseudomonas fluorescens/fisiología , Microbiología del Suelo , Triticum/microbiología
17.
Hepat Mon ; 15(8): e29183, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26322110

RESUMEN

BACKGROUNDS: Serum hepatitis B surface antigen (HBsAg) levels are associated with fibrosis in patients with chronic hepatitis B (CHB) infection. OBJECTIVES: The aim of our study was to evaluate serum HBsAg level as a biomarker for compensated cirrhosis in hepatitis B e antigen (HBeAg) positive CHB patients. PATIENTS AND METHODS: Two-hundred and one HBeAg-positive Chinese CHB patients with or without cirrhosis were enrolled in this retrospective study. Cirrhosis was diagnosed based on liver biopsy. Furthermore, patients with decompensated cirrhosis were excluded. A statistical analysis was performed regarding the association between serum HBsAg level and compensated cirrhosis. RESULTS: Patients with compensated cirrhosis had a significantly lower mean serum HBsAg level compared to those without cirrhosis (3.27 Log10 IU/mL VS 4.17 Log10 IU/mL, P < 0.001). Furthermore, examining the correlation with compensated cirrhosis revealed that lower level of serum HBsAg was a significant factor in multivariate analysis. The area under the receiver operating characteristics curve of serum HBsAg was 0.856 for compensated cirrhosis. A positive predictive value of 66.2% and negative predictive value of 90.7% were obtained with a cut-off value of < 3.60 Log10 IU/mL (4000 IU/mL) of serum HBsAg. Moreover, the rate of compensated cirrhosis increased to 75.0% after combining with APRI > 2. CONCLUSIONS: In HBeAg positive CHB patients, low serum HBsAg level is a useful predictor of compensated cirrhosis.

18.
PLoS One ; 10(8): e0135699, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26317204

RESUMEN

Heart failure (HF) affects over 5 million Americans and is characterized by impairment of cellular cardiac contractile function resulting in reduced ejection fraction in patients. Electrical stimulation such as cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) have shown some success in treating patients with HF. Computer simulations have the potential to help improve such therapy (e.g. suggest optimal lead placement) as well as provide insight into the underlying mechanisms which could be beneficial. However, these myocyte models require a quantitatively accurate excitation-contraction coupling such that the electrical and contraction predictions are correct. While currently there are close to a hundred models describing the detailed electrophysiology of cardiac cells, the majority of cell models do not include the equations to reproduce contractile force or they have been added ad hoc. Here we present a systematic methodology to couple first generation contraction models into electrophysiological models via intracellular calcium and then compare the resulting model predictions to experimental data. This is done by using a post-extrasystolic pacing protocol, which captures essential dynamics of contractile forces. We found that modeling the dynamic intracellular calcium buffers is necessary in order to reproduce the experimental data. Furthermore, we demonstrate that in models the mechanism of the post-extrasystolic potentiation is highly dependent on the calcium released from the Sarcoplasmic Reticulum. Overall this study provides new insights into both specific and general determinants of cellular contractile force and provides a framework for incorporating contraction into electrophysiological models, both of which will be necessary to develop reliable simulations to optimize electrical therapies for HF.


Asunto(s)
Acoplamiento Excitación-Contracción , Insuficiencia Cardíaca/fisiopatología , Modelos Cardiovasculares , Sístole , Función Ventricular , Animales , Insuficiencia Cardíaca/metabolismo , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología
19.
ChemSusChem ; 8(17): 2867-71, 2015 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-26043428

RESUMEN

The conversion of bioethanol into valuable products is an important area in the conversion of biomass. We demonstrate the successful synthesis of bimetallic gold-palladium (Au-Pd) nanoparticles encapsulated within S-1 zeolite crystals (AuPd@S-1) by a solvent-free strategy. This strategy allows highly efficient use of the noble metals, with more than 96 % of the gold and palladium being loaded into the final samples. Electron microscopy characterization and investigations with probe molecules confirm that the Au-Pd nanoparticles are encapsulated inside the S-1 crystals. The AuPd@S-1 catalyst is very active for the aerobic oxidation of bioethanol, giving 100 % conversion and 99 % selectivity to acetic acid. Even in the presence of 90 % water, the catalyst still gives a conversion higher than 80 % and a selectivity of 95 %. More importantly, the AuPd@S-1 catalyst exhibits excellent stability in the oxidation of bioethanol. These features are important for future practical applications of the AuPd@S-1 catalyst.


Asunto(s)
Biocombustibles , Etanol/química , Oro/química , Nanopartículas del Metal , Paladio/química , Zeolitas/síntesis química , Cristalización , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Solventes/química , Difracción de Rayos X , Zeolitas/química
20.
World J Gastroenterol ; 21(2): 653-60, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25605989

RESUMEN

AIM: To observe the effect of response-guided add-on therapy with adefovir (ADV) and lamivudine (LAM) in cirrhotic hepatitis B (CHB) patients. METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus (HBV) DNA level after 24 wk LAM monotherapy: Arm A (complete response, HBV DNA ≤ 60 IU/mL, n = 49), Arm B (partial response, HBV DNA: 60-2000 IU/mL, n = 31) and Arm C (inadequate response, HBV DNA > 2000 IU/mL, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated. RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24 was associated with maintained viral suppression (undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations (mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/mL. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV. CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.


Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , Biomarcadores/sangre , China , ADN Viral/sangre , Farmacorresistencia Viral , Quimioterapia Combinada , Femenino , Genotipo , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Mutación , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
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