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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(5): 660-666, 2024 Oct 01.
Article in English, Chinese | MEDLINE | ID: mdl-39304510

ABSTRACT

OBJECTIVES: This study aimed to evaluate the clinical outcomes of immediate implantation of single maxillary central incisor and explore factors affecting post-implant bone volume. METHODS: Clinical data and imaging records from pre-surgery, the day of surgery, and 6 months post-surgery of 100 patients (100 implants) with non-salvageable maxillary central incisors who underwent immediate implantation were collected. Bone thickness at the cervical, middle, and apical regions of the implant's labial and palatal sides were measured immediately post-surgery and at 6 months, and bone volume changes were observed. A regression analysis model was used to assess predictive factors for labial and palatal bone plate thickness. RESULTS: At 6 months post-surgery, the labial bone thicknesses at the cervical, middle, and apical regions were 2.35, 2.29, and 3.28 mm, respectively, and those of the palatal side were 0.00, 2.40, and 6.05 mm, respectively. The cervical region had the highest alveolar crest collapse rates, with 32.87% on the labial side and 62.20% on the palatal side. The regression model indicated that factors influencing the thickness of bone at the cervical labial side of the implant included initial bone thickness, the implant center to adjacent tooth center angle, implant diameter, and the type of implant closure (P<0.05). The initial bone thickness on the palatal side was the sole predictor for bone thickness on the palatal side (P<0.05). CONCLUSIONS: Immediate implantation of single maxillary central incisors yields effective clinical results. The thickness of new bone around the implant is influenced by multiple factors. A comprehensive consideration of these factors in the planning of immediate implantation is necessary to achieve optimal therapeutic outcomes.


Subject(s)
Incisor , Maxilla , Humans , Dental Implants, Single-Tooth , Alveolar Process , Cone-Beam Computed Tomography , Dental Implantation, Endosseous
2.
J Periodontol ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-39031651

ABSTRACT

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.

3.
ACS Appl Mater Interfaces ; 16(30): 39572-39579, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39036878

ABSTRACT

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.

4.
Adv Sci (Weinh) ; 11(18): e2307269, 2024 May.
Article in English | MEDLINE | ID: mdl-38445899

ABSTRACT

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.


Subject(s)
Immunomodulation , Mesenchymal Stem Cells , Osseointegration , Titanium , Osseointegration/drug effects , Animals , Titanium/chemistry , Immunomodulation/drug effects , Tannins/pharmacology , Tannins/chemistry , Surface Properties , Prostheses and Implants , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Osteogenesis/drug effects , Cell Differentiation/drug effects , Mice , Strontium/chemistry , Strontium/pharmacology , Models, Animal , Rats
5.
Eur J Pharmacol ; 971: 176519, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38522641

ABSTRACT

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.


Subject(s)
Melanoma, Experimental , Pyridines , Thiazoles , Animals , Mice , Mice, Nude , Melanoma, Experimental/drug therapy , Lipid Metabolism , Cholesterol/metabolism , Tumor Microenvironment
6.
Front Genet ; 14: 1231415, 2023.
Article in English | MEDLINE | ID: mdl-37867602

ABSTRACT

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.

7.
Chem Biol Interact ; 385: 110739, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37805176

ABSTRACT

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.


Subject(s)
Asthma , Dermatitis, Atopic , Gastrointestinal Microbiome , Hypersensitivity , Humans , Fatty Acids, Volatile/metabolism , Hypersensitivity/complications , Dermatitis, Atopic/complications
8.
Environ Sci Pollut Res Int ; 30(26): 68403-68416, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37121944

ABSTRACT

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.


Subject(s)
Carbon , Tandem Mass Spectrometry , Enrofloxacin , Chromatography, Liquid , Light , Titanium/chemistry , Catalysis
10.
Int J Oral Sci ; 14(1): 48, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36216801

ABSTRACT

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.


Subject(s)
Cell Encapsulation , Polyphenols , Anti-Bacterial Agents/pharmacology , Capsules/pharmacology , Cell Differentiation , Cells, Cultured , Ferric Compounds/pharmacology , Osteogenesis/physiology , Periodontal Ligament , Polyphenols/pharmacology , Stem Cells , Tannins/pharmacology
11.
Front Nutr ; 9: 992487, 2022.
Article in English | MEDLINE | ID: mdl-35967800

ABSTRACT

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

12.
Front Nutr ; 9: 928972, 2022.
Article in English | MEDLINE | ID: mdl-35799594

ABSTRACT

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.

13.
Front Bioeng Biotechnol ; 10: 916967, 2022.
Article in English | MEDLINE | ID: mdl-35837554

ABSTRACT

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.

14.
Nutrition ; 101: 111703, 2022 09.
Article in English | MEDLINE | ID: mdl-35700592

ABSTRACT

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.


Subject(s)
Dyslipidemias , Lipoproteins, HDL , Adult , Aged , China , Cholesterol, HDL , Dietary Supplements , Double-Blind Method , Dyslipidemias/drug therapy , Female , Humans , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/therapeutic use
15.
Sci Total Environ ; 829: 154519, 2022 Jul 10.
Article in English | MEDLINE | ID: mdl-35292317

ABSTRACT

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.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Airports , China , Environmental Monitoring , Particulate Matter/analysis , Vehicle Emissions/analysis
16.
EBioMedicine ; 70: 103533, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34392146

ABSTRACT

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.


Subject(s)
Anthocyanins/pharmacology , Dyslipidemias/drug therapy , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Adult , Aged , Anthocyanins/administration & dosage , Anthocyanins/therapeutic use , Dietary Supplements , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , P-Selectin/blood , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Reactive Oxygen Species/blood
17.
Thromb Haemost ; 121(7): 931-943, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33545736

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Cardiovascular Diseases/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Hydroxybenzoates/metabolism , Membrane Potential, Mitochondrial/drug effects , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Blood Platelets/metabolism , Calcium/metabolism , Catalase/metabolism , Humans , Hydrogen Peroxide , Mice , Mice, Inbred C57BL , Platelet Activation , Reactive Oxygen Species , Signal Transduction
18.
Food Funct ; 11(1): 139-152, 2020 Jan 29.
Article in English | MEDLINE | ID: mdl-31755492

ABSTRACT

Coenzyme Q10 (CoQ10) exists in a wide variety of foods and has promising cardiovascular benefits. However, its effects on platelets and integrin αIIbß3 signaling during atherosclerosis have not been previously explored. Here, apolipoprotein E-deficient (ApoE-/-) mice were fed a standard diet, high-fat diet (HFD) or CoQ10-supplemented HFD for 12 weeks. We found that CoQ10 supplementation in ApoE-/- mice significantly alleviated formation of HFD-induced atherosclerotic lesions, and attenuated platelet hyper-aggregation and granule secretion, including CD62P, CD63 and CD40 ligand (CD40L) expression and platelet factor-4, ß-thromboglobulin and activation normal T cell expressed and secreted (CCL5) release. CoQ10 supplementation decreased soluble fibrinogen and JON/A binding to αIIbß3 on activated platelets, indicating that αIIbß3-mediated inside-out signaling was attenuated. Additionally, CoQ10 down-regulated platelet αIIbß3 outside-in signaling including decreasing phosphorylation of the ß3 intracellular tail, cellular and sarcoma tyrosine-protein kinase (c-Src), and myosin light chain (MLC), and consistently attenuating platelet spreading and clot retraction. Importantly, platelet-monocyte aggregation that was primarily mediated by αIIbß3 and can be blocked using an αIIbß3-specific antagonist tirofiban was also markedly diminished by CoQ10. Thus, CoQ10 supplementation attenuates platelet hyper-reactivity via down-regulating both αIIbß3 inside-out and outside-in signaling, which may play important preventive roles in atherothrombosis.


Subject(s)
Atherosclerosis/drug therapy , Platelet Aggregation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Signal Transduction/drug effects , Ubiquinone/analogs & derivatives , Animals , Clot Retraction , Male , Mice , Mice, Knockout, ApoE , Ubiquinone/therapeutic use
19.
J Magn Reson ; 308: 106593, 2019 11.
Article in English | MEDLINE | ID: mdl-31520789

ABSTRACT

As a demonstration of the application of rapid-scan EPR to imaging at low frequency and magnetic field, a multi-compartment phantom containing six different samples was imaged. The samples were nitroxide radicals, trityl (substituted triarylmethyl) radicals, and the oxygen-sensitive solid lithium phthalocyanine (LiPc), all of which are useful for in vivo imaging. The 2D spectral-spatial image demonstration was performed at 250 MHz, with samples in sealed tubes of various sizes arranged in a 3D-printed plastic holder. Maximum gradients of 10 G/cm gave a spatial resolution of about 0.1 mm for the narrow trityl and LiPc signals and about 1 mm for the nitroxide. The importance of proper selection of resonator bandwidth and scan rate for obtaining accurate linewidth information is demonstrated for a case in which the phantom is composed of species with signal linewidths and relaxation times that differ by more than a factor of 10.


Subject(s)
Electron Spin Resonance Spectroscopy/methods , Magnetic Resonance Imaging/methods , Phantoms, Imaging , Electromagnetic Fields , Free Radicals , Indoles/chemistry , Nitrogen Oxides/chemistry , Organometallic Compounds/chemistry , Tritium , Trityl Compounds
20.
Mol Nutr Food Res ; 63(23): e1900662, 2019 12.
Article in English | MEDLINE | ID: mdl-31512815

ABSTRACT

SCOPE: Platelet integrin αIIbß3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat-soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbß3 signaling and thrombosis, the major cause of cardiovascular diseases. METHODS AND RESULTS: Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbß3 outside-in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3 )-induced thrombosis model in vivo. Importantly, the randomized, double-blind, placebo-controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbß3 outside-in signaling, leading to decreased platelet aggregation and granule release. CONCLUSION: Through upregulating the platelet cAMP/PKA pathway, and attenuating αIIbß3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/physiology , Cyclic AMP/physiology , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Thrombosis/prevention & control , Ubiquinone/analogs & derivatives , Adult , Animals , Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Double-Blind Method , Humans , Male , Mice , Mice, Inbred C57BL , Platelet Aggregation/drug effects , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Receptor, Adenosine A2A/physiology , Signal Transduction/physiology , Ubiquinone/pharmacology , Up-Regulation
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