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1.
Appl Magn Reson ; 50(1-3): 333-345, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30799909

RESUMEN

A 25 mm diameter 250 MHz crossed-loop resonator was designed for rapid scan electron paramagnetic resonance imaging. It has a saddle coil for the driven resonator and a fine wire, loop gap resonator for the sample resonator. There is good separation of E and B fields and high isolation between the two resonators, permitting a wide range of sample types to be measured. Applications to imaging of nitroxide, trityl, and LiPc samples illustrate the utility of the resonator. Using this resonator and a trityl sample the signal-to-noise of a rapid scan absorption spectrum is about 20 times higher than for a first-derivative CW spectrum.

2.
Adv Exp Med Biol ; 977: 327-334, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28685462

RESUMEN

The triarylmethyl radical OX063d24 is currently used for pulsed electron paramagnetic resonance oximetry at 250 MHz. Both 1/T 1 and 1/T 2 increase with increasing oxygen concentration. The dependence of 1/T 1 on probe concentration is smaller than for 1/T 2. To inform the selection of the optimum frequency for in vivo oximetry 1/T 1, 1/T 2 and signal-to-noise were measured as a function of frequency between 400 and 1000 MHz on a variable-frequency spectrometer with an adjustable-frequency cross-loop resonator. 1/T 1 and 1/T 2 decrease with increasing frequency and signal-to-noise increases with increasing frequency, which are all favourable for imaging at higher frequencies. However, depth of penetration of the radio frequency (RF) into an animal decreases with increasing frequency. Assuming that the RF loss in the animal to be studied determines the resonator Q, our results indicate that the optimum frequency for in vivo imaging will be determined by the desired depth of penetration in the tissue.


Asunto(s)
Electrones , Oximetría/métodos , Compuestos de Sulfhidrilo/química , Deuterio/química , Espectroscopía de Resonancia por Spin del Electrón/métodos , Indenos/química , Ondas de Radio , Relación Señal-Ruido , Compuestos de Tritilo/química
3.
Z Phys Chem (N F) ; 231(4): 923-937, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28392627

RESUMEN

In vivo oximetry by pulsed electron paramagnetic resonance is based on measurements of changes in electron spin relaxation rates of probe molecules, such as the triarylmethyl radicals. A series of experiments was performed at frequencies between 250 MHz and 1.5 GHz to assist in the selection of an optimum frequency for oximetry. Electron spin relaxation rates for the triarylmethyl radical OX063 as a function of radical concentration, salt concentration, and resonance frequency were measured by electron spin echo 2-pulse decay and 3-pulse inversion recovery in the frequency range of 250 MHz-1.5 GHz. At constant OX063 concentration, 1/T1 decreases with increasing frequency because the tumbling dependent processes that dominate relaxation at 250 MHz are less effective at higher frequency. 1/T2 also decreases with increasing frequency because 1/T1 is a significant contribution to 1/T2 for trityl radicals in fluid solution. 1/T2-1/T1, the incomplete motional averaging contribution to 1/T2, increases with increasing frequency. At constant frequency, relaxation rates increase with increasing radical concentration due to contributions from collisions that are more effective for 1/T2 than 1/T1. The collisional contribution to relaxation increases as the concentration of counter-ions in solution increases, which is attributed to interactions of cations with the negatively charged radicals that decrease repulsion between trityl radicals. The Signal-to-Noise ratio (S/N) of field-swept echo-detected spectra of OX063 were measured in the frequency range of 400 MHz-1 GHz. S/N values, normalized by √Q, increase as frequency increases. Adding salt to the radical solution decreased S/N because salt lowers the resonator Q. Changing the temperature from 19 to 37 °C caused little change in S/N at 700 MHz. Both slower relaxation rates and higher S/N at higher frequencies are advantageous for oximetry. The potential disadvantage of higher frequencies is the decreased depth of penetration into tissue.

4.
Concepts Magn Reson Part B Magn Reson Eng ; 46B(3): 123-133, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28190987

RESUMEN

A spectrometer was designed and constructed to facilitate measurements of T1, T2, spin echo signal-to-noise, and resonator quality factor, Q, between about 400 and 1000 MHz. Pulse patterns are generated at 250 MHz and mixed with the output from a second source to perform excitation and detection. A cross-loop resonator was constructed in which the same sample could be measured in the same resonator over the full range of frequencies. An air-core, 4-coil, water-cooled electromagnet with a large experimental volume was built.

5.
Radiat Meas ; 85: 57-63, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26834505

RESUMEN

The radicals in six 60Co γ-irradiated solids: malonic acid, glycylglycine, 2,6 di-t-butyl 4-methyl phenol, L-alanine, dimethyl malonic acid, and 2-amino isobutyric acid, were studied by rapid scan electron paramagnetic resonance at L-band (1.04 GHz) using a customized Bruker Elexsys spectrometer and a locally-designed dielectric resonator. Sinusoidal scans with widths up to 18.2 mT were generated with the recently described coil driver and Litz wire coils. Power saturation curves showed that the rapid scan signals saturated at higher powers than did conventional continuous wave signals. The rapid scan data were deconvolved and background subtracted to obtain absorption spectra. For the same data acquisition time the signal-to-noise for the absorption spectra obtained in rapid scans were 23 to 37 times higher than for first-derivative spectra obtained by conventional continuous wave electron paramagnetic resonance.

6.
J Periodontol ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031651

RESUMEN

BACKGROUND: To explore the correlation between short-chain fatty acids (SCFAs) in the peri-implant sulcular fluid (PISF) and peri-implant diseases. METHODS: PISF samples were obtained from implants that have been placed for at least 5 years, and peri-implant clinical parameters were examined. Gas chromatography-mass spectrometry and high-performance liquid chromatography were used to detect SCFAs in PISF. The correlation between SCFAs and clinical parameters was analyzed by Spearman's correlation. SCFAs related to peri-implant disease were identified by logistic regression and ranked by random forest analysis. RESULTS: Eighty-six implants were divided into a peri-implant health group (PIH-group, 35 implants), peri-implant mucositis group (PIM-group, 25 implants), and peri-implantitis group (PI-group, 26 implants) according to clinical and radiographic examination results. The PIM-group had significantly lower formic acid detection rate than the other two groups (p < 0.001). The PIM-group had significantly higher levels of acetic, propionic, and isovaleric acids than the PIH-group (p < 0.05). The PI-group had significantly higher levels of propionic, butyric, isobutyric, valeric, and isovaleric acids than the PIH-group (p < 0.05). The PI-group had significantly higher levels of butyric, isobutyric, and isovaleric acids than the PIM-group (p < 0.05). SCFAs (apart from hexanoic and succinic acids) were significantly and positively correlated with clinical parameters (p < 0.05). SCFAs related to peri-implant disease were ranked as follows: butyric, isovaleric, isobutyric, propionic, acetic, formic, and lactic acids. CONCLUSIONS: Elevated specific SCFAs are correlated with peri-implant disease. Recognition of this correlation may help in early identification of peri-implant disease and guide further clinical interventions.

7.
Adv Sci (Weinh) ; 11(18): e2307269, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38445899

RESUMEN

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.


Asunto(s)
Inmunomodulación , Células Madre Mesenquimatosas , Oseointegración , Titanio , Oseointegración/efectos de los fármacos , Animales , Titanio/química , Inmunomodulación/efectos de los fármacos , Taninos/farmacología , Taninos/química , Propiedades de Superficie , Prótesis e Implantes , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratones , Estroncio/química , Estroncio/farmacología , Modelos Animales , Ratas
8.
Eur J Pharmacol ; 971: 176519, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38522641

RESUMEN

Aberrant lipid metabolism impacts intratumoral T cell-mediated immune response and tumor growth. Fatostatin functions as an inhibitor of sterol regulatory element binding protein (SREBP) activation. However, the complex effects of fatostatin on cholesterol metabolism in the tumor microenvironment (TME) and its influence on T cell anti-tumor immunity remain unclear. In this study, fatostatin effectively suppressed B16 melanoma, MC38 colon cancer, and Lewis lung cancer (LLC) transplanted tumor growth in immunocompetent mice by reducing SREBPs-mediated lipid metabolism, especially cholesterol levels. Mechanistically, fatostatin decreased intracellular cholesterol accumulation and inhibited X-box binding protein 1 (XBP1)-mediated endoplasmic reticulum (ER) stress, reducing Treg cells and alleviating CD8+ T cell exhaustion in the TME, exerting anti-tumor activity. Nevertheless, this effect was impaired in immunodeficient nude mice, suggesting fatostatin's anti-tumor efficacy in transplanted tumors partly relies on T cell-mediated anti-tumor immunity. Our study highlights SREBP2-mediated cholesterol metabolism as a potential strategy for anti-tumor immunotherapy, and confirms fatostatin's promise in tumor immunotherapy.


Asunto(s)
Melanoma Experimental , Piridinas , Tiazoles , Animales , Ratones , Ratones Desnudos , Melanoma Experimental/tratamiento farmacológico , Metabolismo de los Lípidos , Colesterol/metabolismo , Microambiente Tumoral
9.
ACS Appl Mater Interfaces ; 16(30): 39572-39579, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39036878

RESUMEN

Flexible photodetectors are pivotal in contemporary optoelectronic technology applications, such as data reception and image sensing, yet their performance and yield are often hindered by the challenge of heterogeneous integration between photoactive materials and flexible substrates. Here, we showcase the potential of an electrostatic force-assisted transfer printing technique for integrating Si PIN photodiodes onto flexible substrates. This clean and dry process eliminates the need for chemical etchants, making it a highly desirable method for manufacturing high-performance flexible photodetector arrays, expanding their widespread applications in electronic eyes, robotics, and human-machine interaction. As a demonstration, a 5 × 5 flexible Si photodetector focal plane array is constructed for imaging sensors and shaped into a convex semicylindrical form to achieve a π field of view with long-term mechanical and thermal stability. Such an approach provides a high yield rate and consistent performance, with the single photodetector demonstrating exceptional characteristics, including a responsivity of 0.61 A/W, a response speed of 39.77 MHz, a linear dynamic range of 108.53 dB, and a specific detectivity of 2.75 × 1012 Jones at an applied voltage of -3 V at 940 nm.

10.
Front Genet ; 14: 1231415, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37867602

RESUMEN

Stomach Adenocarcinoma (STAD) is a leading cause of death worldwide. Somatic Copy Number Alterations (SCNAs), which result in Homologous recombination (HR) deficiency in double-strand break repair, are associated with the progression of STAD. However, the landscape of frequent breakpoints of SCNAs (hotspots) and their functional impacts remain poorly understood. In this study, we aimed to explore the frequency and impact of these hotspots in 332 STAD patients and 1,043 cancer cells using data from the Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE). We studied the rates of DSB (Double-Strand Breaks) loci in STAD patients by employing the Non-Homogeneous Poisson Distribution (λ), based on which we identified 145 DSB-hotspots with genes affected. We further verified DNA cytosine deamination as a critical process underlying the burden of DSB in STAD. Finally, we illustrated the clinical impact of the significant biological processes. Our findings highlighted the relationship between DNA cytosine deamination and SCNA in cancer was associated with recurrent Somatic Copy Number Alterations in STAD.

11.
Environ Sci Pollut Res Int ; 30(26): 68403-68416, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37121944

RESUMEN

Multilayer strontium-doped TiO2/carbon dots (CDs) materials (TC) were produced via sol-gel-layered carbonization method. A thorough analysis of the fabricated composites via XRD, SEM, and XPS revealed that strontium ions, TiO2 and CDs, were combined with each other to form layered structures. According to the UV-Vis diffuse reflectance spectrograms and (αhv)1/2 vs. hv plots, the electron-donor property of strontium ions caused a more positive TC conduction band position than that in the pure TiO2, thereby increasing the visible-light absorption range of TC. Based on the photocatalytic degradation data, the degradation rate of enrofloxacin was 84.7% at the dosage of 0.05 g·L-1 and the concentration of 10 mg·L-1. The capture experiments and ESR results showed that ·O2- and e- played a major role in the degradation process of TC. The possible degradation mechanism of enrofloxacin was explained in terms of decarboxylation and defluorination, as was detected via ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis.


Asunto(s)
Carbono , Espectrometría de Masas en Tándem , Enrofloxacina , Cromatografía Liquida , Luz , Titanio/química , Catálisis
12.
Chem Biol Interact ; 385: 110739, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37805176

RESUMEN

Allergy is a growing global public health problem with a high socio-economic impact. The incidence of allergic diseases is increasing year by year, which has attracted more and more attention. In recent years, a number of epidemiological investigations and gut microbiota studies have shown that gut microbiota dysbiosis is associated with an increased prevalence of various allergic diseases, such as food allergy, asthma, allergic rhinitis, and atopic dermatitis. However, the underlying mechanisms are complex and have not been fully clarified. Metabolites are one of the main ways in which the gut microbiota functions. Short-chain fatty acids (SCFAs) are the main metabolites of intestinal flora fermentation and are beneficial to human health. Studies have shown that SCFAs play an important role in maintaining intestinal homeostasis and regulating immune responses by recognizing receptors and inhibiting histone deacetylases, and are key molecules involved in the occurrence and development of allergic diseases. In addition, research on the regulation of gut microbiota and the application of SCFAs in the treatment of allergic diseases is also emerging. This article reviews the clinical and experimental evidence on the correlation between SCFAs and allergic diseases and the potential mechanisms by which SCFAs regulate allergic diseases. Furthermore, SCFAs as therapeutic targets for allergic diseases are also summarized and prospected.


Asunto(s)
Asma , Dermatitis Atópica , Microbioma Gastrointestinal , Hipersensibilidad , Humanos , Ácidos Grasos Volátiles/metabolismo , Hipersensibilidad/complicaciones , Dermatitis Atópica/complicaciones
13.
Sci Total Environ ; 829: 154519, 2022 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-35292317

RESUMEN

Large airport operation release harmful air pollutants and have adverse impact on local air quality. As one of the world's top 30 busiest airports, Xinzheng International Airport (CGO) located in Zhengzhou City, China, its emission impacts needs particular attention. To identify the possible impacts and quantify the contribution of CGO airport to air pollution, a comprehensive approach including emission inventory, continuous monitoring, coupled with statistical modelling was adopted in this study. We estimated a more detailed emissions inventory for CGO, including hourly and annual emissions from engines and auxiliary power units of aircrafts during landing and take-off flight, and airside ground support equipment (GSE) in 2019. The results indicate that almost all the CGO specific parameters including operating hours, fuel consumption and unit LTO emissions at different modes were lower than ICAO reference values. The annual total emissions of NOx, CO, HC, SO2 and PM from CGO from aircrafts and GSE were 1207.7, 921.3, 123.7, 268.3 and 36.2 tons, respectively. In addition to SO2, the main engines of the aircraft accounted for 80.3%, 62.6%, 45.5% and 74.3% of the total emissions, respectively. Meanwhile, a continuous monitoring campaign was conducted for one year in the vicinity of CGO airport. The monitoring data were analyzed using generalized additive model (GAM) to quantify the impact of NOx emissions from airport activities on air quality at CGO. The results showed that even the influence of environmental and meteorological variables was greater, nearly 13% of the ambient NOx concentrations were explained by emissions from airport activities, indicating the importance of airport-related emissions as the major source affecting local air quality.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Aeropuertos , China , Monitoreo del Ambiente , Material Particulado/análisis , Emisiones de Vehículos/análisis
14.
Int J Oral Sci ; 14(1): 48, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36216801

RESUMEN

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with FeIII/tannic acid coordination network to obtain spheroid@[FeIII-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.


Asunto(s)
Encapsulación Celular , Polifenoles , Antibacterianos/farmacología , Cápsulas/farmacología , Diferenciación Celular , Células Cultivadas , Compuestos Férricos/farmacología , Osteogénesis/fisiología , Ligamento Periodontal , Polifenoles/farmacología , Células Madre , Taninos/farmacología
15.
Front Nutr ; 9: 992487, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967800

RESUMEN

[This corrects the article DOI: 10.3389/fnut.2022.928972.].

16.
Front Bioeng Biotechnol ; 10: 916967, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35837554

RESUMEN

Sufficient bone volume is indispensable to achieve functional and aesthetic results in the fields of oral oncology, trauma, and implantology. Currently, guided bone regeneration (GBR) is widely used in reconstructing the alveolar ridge and repairing bone defects owing to its low technical sensitivity and considerable osteogenic effect. However, traditional barrier membranes such as collagen membranes or commercial titanium mesh cannot meet clinical requirements, such as lack of space-preserving ability, or may lead to more complications. With the development of digitalization and three-dimensional printing technology, the above problems can be addressed by employing customized barrier membranes to achieve space maintenance, precise predictability of bone graft, and optimization of patient-specific strategies. The article reviews the processes and advantages of three-dimensional computer-assisted surgery with GBR in maxillofacial reconstruction and alveolar bone augmentation; the properties of materials used in fabricating customized bone regeneration sheets; the promising bone regeneration potency of customized barrier membranes in clinical applications; and up-to-date achievements. This review aims to present a reference on the clinical aspects and future applications of customized barrier membranes.

17.
Front Nutr ; 9: 928972, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35799594

RESUMEN

Sesame seed hull is the major by-product of sesame seed processing and is rich in polysaccharides. In this work, sesame hull polysaccharides (SHP) were extracted by ultrasound-assisted alkali extraction methods with a yield of 6.49%. Three purified polysaccharide fractions were obtained after decolorization, deproteinization, and column chromatography. Then, their main composition and antioxidant activity were investigated. The dominant fraction was SHP-2 with a yield of 3.78%. It was composed of galacturonic acid (51.3%), glucuronic acid (13.8%), rhamnose (8.9%), glucose (8.4%), and others. The linkage types of SHP-2 have the α-D-GalpA-(1,4)-linked, α-D-GlcpA-(1,2)-linked, ß-T-D-Rhap-linked, ß-D-Glcp-(1,6)-linked, ß-T-D-Galp-linked, α-L-Xylp-(1,4)-linked, α-L-Araf-(1,3,5)-linked, and ß-D-Manp-(1,4)-linked. This study might provide some useful basic data for developing applications for sesame seed hull polysaccharides in the food and pharmaceutical industries.

18.
Nutrition ; 101: 111703, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35700592

RESUMEN

OBJECTIVES: Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia. METHODS: A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein-mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk. RESULTS: CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus -0.12±2.94; P = 0.014) and reduced HII (mean change, -0.32±0.58 versus -0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention. CONCLUSIONS: This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.


Asunto(s)
Dislipidemias , Lipoproteínas HDL , Adulto , Anciano , China , HDL-Colesterol , Suplementos Dietéticos , Método Doble Ciego , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ubiquinona/uso terapéutico
19.
Thromb Haemost ; 121(7): 931-943, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33545736

RESUMEN

Oxidative stress plays crucial roles in initiating platelet apoptosis that facilitates the progression of cardiovascular diseases (CVDs). Protocatechuic acid (PCA), a major metabolite of anthocyanin cyanidin-3-O-ß-glucoside (Cy-3-g), exerts cardioprotective effects. However, underlying mechanisms responsible for such effects remain unclear. Here, we investigate the effect of PCA on platelet apoptosis and the underlying mechanisms in vitro. Isolated human platelets were treated with hydrogen peroxide (H2O2) to induce apoptosis with or without pretreatment with PCA. We found that PCA dose-dependently inhibited H2O2-induced platelet apoptosis by decreasing the dissipation of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and decreasing phosphatidylserine exposure. Additionally, the distributions of Bax, Bcl-xL, and cytochrome c mediated by H2O2 in the mitochondria and the cytosol were also modulated by PCA treatment. Moreover, the inhibitory effects of PCA on platelet caspase-3 cleavage and phosphatidylserine exposure were mainly mediated by downregulating PI3K/Akt/GSK3ß signaling. Furthermore, PCA dose-dependently decreased reactive oxygen species (ROS) generation and the intracellular Ca2+ concentration in platelets in response to H2O2. N-Acetyl cysteine (NAC), a ROS scavenger, markedly abolished H2O2-stimulated PI3K/Akt/GSK3ß signaling, caspase-3 activation, and phosphatidylserine exposure. The combination of NAC and PCA did not show significant additive inhibitory effects on PI3K/Akt/GSK3ß signaling and platelet apoptosis. Thus, our results suggest that PCA protects platelets from oxidative stress-induced apoptosis through downregulating ROS-mediated PI3K/Akt/GSK3ß signaling, which may be responsible for cardioprotective roles of PCA in CVDs.


Asunto(s)
Apoptosis/efectos de los fármacos , Enfermedades Cardiovasculares/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hidroxibenzoatos/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Plaquetas/metabolismo , Calcio/metabolismo , Catalasa/metabolismo , Humanos , Peróxido de Hidrógeno , Ratones , Ratones Endogámicos C57BL , Activación Plaquetaria , Especies Reactivas de Oxígeno , Transducción de Señal
20.
EBioMedicine ; 70: 103533, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34392146

RESUMEN

BACKGROUND: Dyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia. METHODS: A double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks. FINDINGS: Compared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P < 0.05). Moreover, compared to placebo group, anthocyanins at 320 mg/day inhibited collagen-induced platelet aggregation (-7.05±2.38%), ADP-induced platelet aggregation (-7.14±2.00%), platelet ROS levels (-14.55±1.86%), and mitochondrial membrane potential (7.40±1.56%) (P < 0.05). There were dose-response relationships between anthocyanins and the attenuation of platelet aggregation, mitochondrial membrane potential and ROS levels (P for trend <0.05). Furthermore, significantly positive correlations were observed between changes in collagen-induced (r = 0.473) or ADP-induced (r = 0.551) platelet aggregation and ROS levels in subjects with dyslipidemia after the 12-week intervention (P < 0.05). INTERPRETATION: Anthocyanin supplementation dose-dependently attenuates platelet function, and 12-week supplementation with 80 mg/day or more of anthocyanins can reduce platelet function in individuals with dyslipidemia. FUNDING: None.


Asunto(s)
Antocianinas/farmacología , Dislipidemias/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Adulto , Anciano , Antocianinas/administración & dosificación , Antocianinas/uso terapéutico , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Especies Reactivas de Oxígeno/sangre
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