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Although tension band wiring (TBW) is popular and recommended by the AO group, the high rate of complications such as skin irritation and migration of the K-wires cannot be ignored. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by biomechanical testing. We conducted a Synbone biomechanical model by using three fixation methods: DSTBW, intramedullary screw and tension band wiring (IM-TBW), and K-wire TBW, were simulated to fix the olecranon fractures. We compared the mechanical stability of DSTBW, IM-TBW, and TBW in the Mayo Type IIA olecranon fracture Synbone model using a single cycle loading to failure protocol or pullout force. During biomechanical testing, the average fracture gap measurements were recorded at varying flexion angles in three different groups: TBW, IM-TBW, and DSTBW. The TBW group exhibited measurements of 0.982 mm, 0.380 mm, 0.613 mm, and 1.285 mm at flexion angles of 0°, 30°, 60°, and 90° respectively. The IM-TBW group displayed average fracture gap measurements of 0.953 mm, 0.366 mm, 0.588 mm, and 1.240 mm at each of the corresponding flexion angles. The DSTBW group showed average fracture gap measurements of 0.933 mm, 0.358 mm, 0.543 mm, and 1.106 mm at the same flexion angles. No specimen failed in each group during the cyclic loading phase. Compared with the IM-TBW and TBW groups, the DSTBW group showed significant differences in 60° and 90° flexion angles. The mean maximum failure load was 1229.1 ± 110.0 N in the DSTBW group, 990.3 ± 40.7 N in the IM-TBW group, and 833.1 ± 68.7 N in the TBW group. There was significant difference between each groups (p < 0.001).The average maximum pullout strength for TBW was measured at 57.6 ± 5.1 N, 480.3 ± 39.5 N for IM-TBW, and 1324.0 ± 43.8 N for DSTBW. The difference between maximum pullout strength of both methods was significant to p < 0.0001. DSTBW fixation provides more stability than IM-TBW and TBW fixation models for olecranon fractures.
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Vis orthopédiques , Fils métalliques , Ostéosynthèse interne , Processus olécrânien , Humains , Processus olécrânien/traumatismes , Processus olécrânien/chirurgie , Phénomènes biomécaniques , Ostéosynthèse interne/méthodes , Ostéosynthèse interne/instrumentation , Fractures de l'ulna/chirurgie , Fractures de l'ulna/physiopathologie , Fractures osseuses/chirurgie ,RÉSUMÉ
Light and thermal detectors based on the laser-induced transverse voltage (LITV) effect have garnered significant interest for their rapid and broad spectral response. In this study, we prepared the La-doped SrTiO3(STO) epitaxial thin films on the 12° inclined single crystal LaAlO3(LAO) (100) substrates using our home-designed metal-organic chemical vapor deposition system. Under the illumination of a 248 nm laser, the LITV signals of LaxSr1-xTiO3films were observed and showed dependence on the La doping level, which can be explained by the changes in the light absorption coefficient, thermal conductivity, and optical penetration depth. The optimized LITV signal was observed with a peak voltage of 23.25 V and a decay time of 106 ns under the laser power density of 1.0 mJ mm-2. The high peak voltage and fast response time of LaxSr1-xTiO3show great potential in the field of light and thermal detection.
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Purpose: To propose and evaluate a comprehensive modeling approach combing radiomics, dosiomics and clinical components, for more accurate prediction of locoregional recurrence risk after radiotherapy for patients with locoregionally advanced HPSCC. Materials and methods: Clinical data of 77 HPSCC patients were retrospectively investigated, whose median follow-up duration was 23.27 (4.83-81.40) months. From the planning CT and dose distribution, 1321 radiomics and dosiomics features were extracted respectively from planning gross tumor volume (PGTV) region each patient. After stability test, feature dimension was further reduced by Principal Component Analysis (PCA), yielding Radiomic and Dosiomic Principal Components (RPCs and DPCs) respectively. Multiple Cox regression models were constructed using various combinations of RPC, DPC and clinical variables as the predictors. Akaike information criterion (AIC) and C-index were used to evaluate the performance of Cox regression models. Results: PCA was performed on 338 radiomic and 873 dosiomic features that were tested as stable (ICC1 > 0.7 and ICC2 > 0.95), yielding 5 RPCs and DPCs respectively. Three comprehensive features (RPC0, P<0.01, DPC0, P<0.01 and DPC3, P<0.05) were found to be significant in the individual Radiomic or Dosiomic Cox regression models. The model combining the above features and clinical variable (total stage IVB) provided best risk stratification of locoregional recurrence (C-index, 0.815; 95%CI, 0.770-0.859) and prevailing balance between predictive accuracy and complexity (AIC, 143.65) than any other investigated models using either single factors or two combined components. Conclusion: This study provided quantitative tools and additional evidence for the personalized treatment selection and protocol optimization for HPSCC, a relatively rare cancer. By combining complementary information from radiomics, dosiomics, and clinical variables, the proposed comprehensive model provided more accurate prediction of locoregional recurrence risk after radiotherapy.
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Background: Both catheter left atrial appendage occlusion combined with ablation (COA) and thoracoscopic surgical left atrial appendage clipping combined with ablation (TCA) have shown favorable outcomes in management of patients with atrial fibrillation (AFib). However, studies comparing the endpoints of both techniques are still lacking. Herein, a meta-analysis of safety and efficacy outcomes of COA versus TCA was performed in patients with AFib. Methods: Pubmed, Embase, Cochrane, and Web of Science databases were searched for retrieving potential publications. The primary outcome was the incidence of stroke during follow-up period of at least 12 months. Secondary outcomes were acute success rate of complete left atrial appendage (LAA) closure by COA or TCA, postprocedural mortality and complications, and all-cause mortality during follow-up period of at least 12 months. Results: 19 studies of COA containing 1,504 patients and 6 studies of TCA with 454 patients were eligible for analysis. No significant difference in stroke and all-cause mortality was found in patients undergoing COA versus TCA after at least a 12-month follow-up (stroke: p = 0.504; all-cause mortality: p = 0.611). COA group had a higher acute success rate compared with TCA group (p = 0.001). COA placed the patients at a higher risk of hemorrhage during the postprocedural period compared with TCA (p = 0.023). A similar risk of other postprocedural complications (stroke/transient ischemic attack and pericardial effusion) and mortality was found in the COA group in comparison with TCA group (p>0.05). Conclusion: This meta-analysis showed that COA and TCA did not differ in stroke prevention and all-cause mortality in patients with AFib after a follow-up of at least 12 months. Postprocedural complications and mortality were almost comparable between the two groups. In the near future, high-quality randomized controlled trials exploring the optimal surgical strategies for AFib and endpoints of different procedures are warranted. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022325497].
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Background: Balloon-based catheter ablations, including hot balloon ablation (HBA) and cryoballoon ablation (CBA), have rapidly emerged as alternative modalities to conventional catheter atrial fibrillation (AF) ablation owing to their impressive procedural advantages and better clinical outcomes and safety. However, the differences in characteristics, effectiveness, safety, and efficacy between HBA and CBA remain undetermined. This study compares the characteristic and prognosis differences between HBA and CBA. Methods: Electronic search was conducted in six databases (PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov, and medRxiv) with specific search strategies. Eligible studies were selected based on specific criteria; all records were identified up to June 1, 2021. The mean difference, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Heterogeneity and risk of bias were assessed using predefined criteria. Results: Seven studies were included in the final meta-analysis. Compared with CBA, more patients in the HBA group had residual conduction and required a higher incidence of touch-up ablation (TUA) [OR (95% CI) = 2.76 (2.02-3.77), P = 0.000]. The most frequent sites of TUA were the left superior pulmonary veins (PVs) in the HBA group vs. the right inferior PVs in the CBA group. During HBA surgery, the left and right superior PVs were more likely to have a higher fluid injection volume. Furthermore, the procedure time was longer in the HBA group than in the CBA group [weighted mean difference (95% CI) = 14.24 (4.39-24.09), P = 0.005]. Patients in the CBA group could have an increased risk of AF occurrence, and accepted more antiarrhythmic drug therapy; however, the result was insignificant. Conclusions: HBA and CBA are practical ablation approaches for AF treatment. Patients who received HBA had a higher incidence of TUA and longer procedure time. Clinical outcomes during the mid-term follow-up between HBA and CBA were comparable. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259487, identifier: CRD42021259487.
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Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the IFN response factors IRF3 and IRF7 played pivotal roles in DEP-induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP-induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR-independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters.
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Autophagie/physiologie , Facteur-3 de régulation d'interféron/physiologie , Facteur-7 de régulation d'interféron/physiologie , Complexe-1 cible mécanistique de la rapamycine/physiologie , Pneumopathie infectieuse/étiologie , Emissions des véhicules/toxicité , Animaux , Cytokines/biosynthèse , Souris , Souris de lignée C57BL , Récepteur à l'interféron alpha-bêta/physiologie , Sirolimus/pharmacologieRÉSUMÉ
Background: DNA sensors are innate immune receptors that detect intracellular endogenous or exogenous DNA. They are critical to trigger immune response against DNA viral and intracellular bacterial infection, and are involved in inflammatory diseases and tumorigenesis. Recent accumulating evidences indicated that DNA sensors are also crucial for controlling the development of colorectal cancer (CRC). However, a systematic study on the expression profile of DNA sensors in CRC and their clinical significance are still lacking. Methods: We investigated the expression profile of DNA sensors in CRC and their clinical significance by taking advantage of clinical CRC samples, mouse AOM/DSS treatment model, and Oncomine ® bioinformatics platform. Results: Our study identified that the expression of DNA sensors, including AIM2, DAI, as well as inflammasome molecules ASC/IL-18, TLR9 and adaptor MyD88, and DDX60 decreased in human CRC, whereas the expression of DHX9, DHX36, and DDX41 significantly increased. Among them, the expression of AIM2/ASC/IL-18, MyD88, DAI, DHX36, and DDX60 were associated with cancer stages. In addition, we also performed correlation analysis between DNA sensors and their main signaling molecules to explore the possible mechanisms. The results showed that there were positive correlations between AIM2 and ASC/IL-18, DHX9 and MAVS, and TLR9 and MyD88 expression. In addition, the gene expression patterns of some DNA sensors were confirmed by Western-blot analysis. Conclusions: Our study revealed that the expression of multiple DNA sensors was deregulated in CRC and might be involved in tumor development. More importantly, the study identified that, among all these DNA sensors, AIM2, DAI, and DDX60 could be potentially critical for diagnosis, prognosis, and therapy of CRC and deserve further investigation.
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Acute myocardial infarction is one of the most threatening disease in the world. In previous studies, numerous dysregulated lncRNAs exposed to ischemic reperfusion injury have been identified. In this differential lncRNAs, Gm2691 attracted our attention due to its high fold change. The aim of the study was to investigate the function and mechanism of lncRNA Gm2691 in ischemic reperfusion injury. AnaeroPack anaerobic system treated neonatal rat ventricular cardiomyocytes were used to analyze the function of lncRNA Gm2691 in vitro. Tunel, Caspase3, and inflammation markers were detected to evaluate apoptosis and inflammatory response. Rat acute myocardial infarction was performed to elucidate the function of lncRNA Gm2691 in vivo. The results showed that LncRNA Gm2691 improved the cardiac function and attenuated the inflammatory response in vivo. We also found that lncRNA Gm2691 reduced the apoptosis and improved cell survival rates in anaeroPack anaerobic system treated neonatal rat ventricular cardiomyocytes. Western blot analysis revealed that lncRNA Gm2691 decreased Akt and ERK1/2 activities, suggesting that lncRNA Gm2691 may functioned through Akt signaling pathway. We verified the function and mechanism of lncRNA Gm2691 and provide evidence that lncRNA Gm2691 may play important role in ischemic reperfusion injury, and understanding the precise role of Gm2691 will undoubtedly shed new light on the clinical treatment.
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Inflammation/génétique , Infarctus du myocarde/génétique , Lésion de reperfusion myocardique/génétique , ARN long non codant/génétique , Animaux , Apoptose/génétique , Régulation de l'expression des gènes , Humains , Inflammation/anatomopathologie , Infarctus du myocarde/anatomopathologie , Lésion de reperfusion myocardique/anatomopathologie , Myocytes cardiaques/métabolisme , Myocytes cardiaques/anatomopathologie , Phosphatidylinositol 3-kinases/génétique , Protéines proto-oncogènes c-akt/génétique , Rats , Transduction du signal/génétiqueRÉSUMÉ
BACKGROUND: RNA sensors represent the most important pattern recognition receptors (PRRs) to defend against RNA pathogens, such as RNA viruses. Recent studies revealed their critical roles in inflammatory and autoimmune diseases. Furthermore, more recent evidences indicated that RNA sensors mediate the development of colitis or colorectal cancer (CRC). However, a systematic understanding of RNA sensors in CRC is still lacking, especially the expression patterns in CRC. METHODS: Here, we analyzed RNA sensor expression, clinical significance, and possible mechanisms in CRC by combining bioinformatic analysis and the analysis on pre-cancerous animal model and clinical tissue samples. RESULTS: We found that most of the members of RNA sensors, including RNA-sensing Toll-like receptors (TLR3, TLR7, and TLR8) and RIG-I-like receptors (MDA5 and RIG-I), were down-regulated in CRC, while the expression of DDX21 were up-regulated in human CRC. In addition, we also analyzed the correlation between gene expression and cancer stages. We found that the expression of RNA-sensing TLRs, RIG-I, and DDX21 in CRC were associated with cancer stages. Finally, in order to explore the possible mechanisms, the correlation between RNA sensors and the main downstream signaling molecules were analyzed. A positive correlation was observed in TLR7/8 and MyD88, RIG-I/MDA5 and LGP2, while a negative correlation was observed in RIG-I/MDA5 and MAVS. CONCLUSIONS: This study reveals the potential values of RNA-sensing genes including TLRs, RIG-I and DDX21 as biomarkers of CRC formation, progression and therapy.
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This study was conducted to explore whether the renin C-5312T, angiotensin II type 1 receptor A1166C, and angiotensin-converting enzyme I/D polymorphisms were associated with ambulatory blood pressure (BP) and central hemodynamics in an untreated hypertensive population. A total of 471 participants with no previous treatment for raised BP were eligible for the study. Ambulatory and central BP were measured. DD carriers had the highest daytime systolic/diastolic BP, nighttime systolic BP, 24-hour systolic BP, and 24-hour diastolic BP values, whereas carriers of DD had higher central systolic BP and augmentation index compared with those with the II genotype. Multivariate regression analysis demonstrated that DD genotype was independently associated with 24-hour systolic BP, 24-hour diastolic BP, central systolic BP, and central augmentation index. There was an independent association of the angiotensin-converting enzyme polymorphism with central and ambulatory BP in Chinese patients with hypertension.
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Hypertension artérielle , Peptidyl-Dipeptidase A/génétique , Sujet âgé , Mesure de la pression artérielle/méthodes , Chine/épidémiologie , Femelle , Humains , Hypertension artérielle/diagnostic , Hypertension artérielle/épidémiologie , Hypertension artérielle/génétique , Hypertension artérielle/physiopathologie , Mâle , Adulte d'âge moyen , Polymorphisme génétique , Récepteur de type 1 à l'angiotensine-II/génétique , Rénine/génétique , Système rénine-angiotensine/génétiqueRÉSUMÉ
The soluble epoxide hydrolase (sEH) is a molecule necessary for the metabolism of endogenous constituents implicated in blood pressure regulation and vascular inflammation. Scientific evidences indicate that sEH inhibitors such as 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA) could be a possible therapeutic option for cardiovascular diseases such as restenosis and atherosclerosis. However, the nature of the biological effects of AUDA still remains unclear. Herein, we intended to scrutinize the influence of AUDA on proliferation and migration of TNF-α-induced human aortic smooth muscle cells (HASMCs) and the underlying molecular mechanism. Pretreatment with AUDA (0.5-8 µM) dose-dependently inhibited TNF-α-induced proliferation of HASMCs as revealed by the MTT assay and the decreased expression of Cyclin D1 and ß-tubulin. Transwell analyses showed that AUDA equally suppressed TNF-α-induced migration of HASMCs. Moreover, AUDA induced the expression of apoptotic proteins (Caspase 3, PARP) and inhibited the expression of autophagy related markers (LC3-II and Beclin 1). More interestingly, AUDA inhibited TNF-α-induced phosphorylation of mTOR, the silencing of which abolished the inhibitory effects of AUDA on TNF-α-induced HASMCs. The present results point toward an inhibitory effect of AUDA on the proliferation and migration of TNF-α-induced HASMCs by regulation of cell death related signaling pathways via downregulation of the mTOR signaling. Thus, AUDA may be an important regulator of inflammation in the atherosclerotic lesion and a novel therapeutic drug for the treatment of atherosclerosis, restenosis and other cardiovascular diseases.
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BACKGROUND: The effect of grape polyphenols on blood pressure remains unclear, which we aimed to address via a meta-analysis study. METHODS: We conducted study trial searches in PubMed, Embase, and the Cochrane Library databases. Summary estimates of weighted mean differences and 95% confidence intervals were obtained by using fixed-effects models. Subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the international database of prospectively registered systematic reviews (registration number CRD42015019196). RESULTS: Ten studies were included in the present meta-analysis. Our results showed daily grape polyphenol intake could significantly reduce systolic blood pressure by 1.48 mmHg when compared to control subjects (12 comparisons; -1.48 [-2.79 to -0.16] mmHg; P = 0.03). Subgroup analyses indicated larger reduction was identified in the intake of low-dose of grape polyphenols (< 733 mg/day, median level of the included studies) or patients with metabolic syndrome. Contrarily, diastolic blood pressure was not significantly decreased in the grape polyphenols group as compared to controls. No significant heterogeneity or publication bias was detected in the meta-analysis of either systolic or diastolic blood pressure. CONCLUSIONS: Daily grape polyphenol intake can significantly reduce the systolic blood pressure in humans, although the reduction is modest when compared with anti-hypertensive medications. Larger, better designed trials, that specifically include hypertensive subjects, are required to verify our results in the future.
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Pression sanguine/effets des médicaments et des substances chimiques , Polyphénols/pharmacologie , Vitis/composition chimique , Humains , Essais contrôlés randomisés comme sujetRÉSUMÉ
BACKGROUND: The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). METHODS: Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. RESULTS: Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. CONCLUSIONS: Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.
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Endothélium vasculaire/effets des médicaments et des substances chimiques , Polyphénols/usage thérapeutique , Vitis/composition chimique , Maladies cardiovasculaires/prévention et contrôle , Essais cliniques contrôlés comme sujet , HumainsRÉSUMÉ
Although heme oxygenase-1 (HO-1) has been implicated in protection against atherogenesis, its role in vulnerable plaques remains to be fully elucidated. This study was aimed to explore the effect of HO-1 on the progression and stabilization of vulnerable plaques and the possible mechanism. We established a vulnerable plaque model by local transfection with recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet. HO-1 activity was modulated by intraperitoneal injection of hemin or Sn-protoporphyrin IX (SnPP). HO-1 induction by hemin inhibited the progression of atherosclerotic lesions and changed the plaque morphology and composition into a more stable phenotype. In addition, hemin treatment is associated with a reduction in matrix metalloproteinase-9, interleukin-6 and tumor necrosis factor-α production, an increase in interleukin-10 level, as well as a decrease of TUNEL labeled apoptosis of smooth muscle cells in lesions. Compared with the control group, aortic nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity decreased markedly, whereas endothelial nitric oxide synthase (eNOS) activity increased significantly in the Hemin group. In contrast, inhibition of HO-1 by SnPP induced reversed effects and augmented plaque progression and vulnerability. After pharmacological triggering, the incidence of plaque disruption in SnPP group was significantly higher than that in control group (79% vs. 33%, P<0.05), while no plaque in Hemin group developed disruption (0% vs. 33%, P<0.05). These findings suggest that HO-1 induction could delay progression and enhance stability of atherosclerotic plaques, possibly through the attenuation of plaque inflammation and apoptosis, and the suppression of iNOS/NO production.
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Évolution de la maladie , Heme oxygenase-1/métabolisme , Plaque d'athérosclérose/enzymologie , Plaque d'athérosclérose/anatomopathologie , Animaux , Apoptose , Modèles animaux de maladie humaine , Régulation de l'expression des gènes codant pour des enzymes , Heme oxygenase-1/génétique , Inflammation/enzymologie , Inflammation/métabolisme , Mâle , Monoxyde d'azote/métabolisme , Nitric oxide synthase type II/métabolisme , Nitric oxide synthase type III/métabolisme , Phénotype , Plaque d'athérosclérose/génétique , Plaque d'athérosclérose/métabolisme , LapinsRÉSUMÉ
Probucol, a lipid-lowering agent with anti-oxidant properties, has been implicated in protection against atherogenesis, whereas its effect on plaques stability remains to be fully elucidated. The present study was aimed to test the hypothesis that probucol may attenuate inflammation and increase stability of vulnerable atherosclerotic plaques using a rabbit model. After abdominal aortic balloon injury, 45 rabbits were fed a 1% cholesterol diet for 24 weeks. From week 12 to week 24, the animals were treated with probucol (1% by weight in the diet), simvastatin (5 mg·kg(-1), positive control) or no drugs (control), respectively. At the end of week 22, recombinant-p53 adenovirus was injected into the abdominal aortic plaques. Two weeks later, plaque disruption was induced by injection of Chinese Russell's viper venom and histamine. The results showed that the incidence of plaque disruption in probucol or simvastatin groups was significantly lower than that in the control group (7.15% or 14.29% vs. 71.43% respectively, both P < 0.01). Probucol significantly increased the thickness of fibrous caps and decreased plaque vulnerability index. Serum concentrations of inflammatory cytokines and matrix metalloproteinases, and expression levels of Toll-like receptor (TLR)-2, TLR-4, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, scavenger receptor A, CD36 and oxidized low-density lipoprotein receptor 1 within the lesions were markedly lower in both treatment groups than in the control group. We conclude that probucol increases the stability of vulnerable plaques, possibly through its lipid lowering, anti-inflammation and scavenger receptors suppression effects, suggesting probucol as a promising pharmacologic approach to stabilize vulnerable plaques.
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Inflammation/complications , Inflammation/traitement médicamenteux , Plaque d'athérosclérose/complications , Plaque d'athérosclérose/traitement médicamenteux , Probucol/usage thérapeutique , Animaux , Aorte abdominale/imagerie diagnostique , Aorte abdominale/anatomopathologie , Marqueurs biologiques/sang , Chimiokine CCL2/génétique , Chimiokine CCL2/métabolisme , Test ELISA , Régulation de l'expression des gènes , Immunohistochimie , Inflammation/sang , Inflammation/anatomopathologie , Médiateurs de l'inflammation/métabolisme , Molécule-1 d'adhérence intercellulaire/génétique , Molécule-1 d'adhérence intercellulaire/métabolisme , Lipides/sang , Plaque d'athérosclérose/sang , Plaque d'athérosclérose/anatomopathologie , ARN messager/génétique , ARN messager/métabolisme , Lapins , Récepteurs éboueurs/métabolisme , Récepteur de type Toll-2/génétique , Récepteur de type Toll-2/métabolisme , Récepteur de type Toll-4/génétique , Récepteur de type Toll-4/métabolisme , ÉchographieRÉSUMÉ
BACKGROUND: Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. METHODS: Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks' atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. RESULTS: Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group (56% vs. 21%, 18% vs. 54%, respectively, both P < 0.01). In addition, the probucol group showed a smaller mean remodeling index relative to the control group (0.93 ± 0.13 vs. 1.05 ± 0.16, P < 0.01). Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S (all P < 0.01). CONCLUSIONS: These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.
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Anticholestérolémiants/pharmacologie , Aorte/anatomopathologie , Athérosclérose/traitement médicamenteux , Probucol/pharmacologie , Échographie interventionnelle/méthodes , Animaux , Apoptose/effets des médicaments et des substances chimiques , Athérosclérose/métabolisme , Athérosclérose/anatomopathologie , Lipides/sang , Macrophages/effets des médicaments et des substances chimiques , Macrophages/physiologie , Mâle , Matrix metalloproteinase 2/métabolisme , Matrix metalloproteinase 9/métabolisme , Stress oxydatif , LapinsRÉSUMÉ
The prevalence of type II diabetes mellitus (T2DM) in coronary artery disease (CAD) patients has been steadily increasing, especially in East Asian countries. Although many studies have suggested that certain genetic variants may predispose to the development of T2DM, very few studies investigated the genetic link with T2DM in CAD patients of East Asia. In this study, we investigated the relationship between Glu504Lys polymorphism in the acetaldehyde dehydrogenase 2 (ALDH2) gene, a key enzyme of alcohol metabolism, and the risk of having T2DM in Chinese Han CAD patients. We enrolled 542 CAD patients (180 women and 362 men) and 309 CAD-/DM- subjects (152 women and 157 men). T2DM was confirmed in 47.4% of CAD patients. Logistic and linear regression analyses showed that ALDH2 mutant genotypes ((*)1/(*)2 and (*)2/(*)2) were an independent risk factor for both T2DM in female CAD patients, even after controlling for alcohol consumption (OR=1.95, P=0.043), and fasting plasma glucose (FPG) in CAD-/DM- women (P=0.015), whereas the association with FPG disappeared after controlling for high-sensitivity C-reactive protein, a classic inflammatory biomarker. However, there was no relationship between the ALDH2 genetic polymorphism and T2DM or FPG in men. These findings suggest that the ALDH2 polymorphism is associated with an increased risk of T2DM in female CAD patients, and this association could be causal on the basis of the association between the polymorphism and FPG, which is partly explained by an increased inflammatory status. These findings will benefit the screening and treatment of a high-risk population in East Asians.
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Aldehyde dehydrogenase/génétique , Maladie des artères coronaires/complications , Maladie des artères coronaires/génétique , Diabète de type 2/épidémiologie , Diabète de type 2/génétique , Polymorphisme génétique/génétique , Sujet âgé , Consommation d'alcool , Aldehyde dehydrogenase, mitochondrial , Protéine C-réactive/métabolisme , Femelle , Fréquence d'allèle , Humains , Mode de vie , Mâle , Adulte d'âge moyen , Activité motrice , RisqueRÉSUMÉ
Notoginseng (Sanqi) is one of the most important components of famous Chinese recipe (Yunan Baiyao) and possesses a wide variety of applications in clinical practice. It has been found that Sanqi of different size exhibits different curative effects. Such a phenomenon may be attributed to that the chemical constituent from shell region is different from that of core region. To prove the above-mentioned hypothesis, Ultraviolet-Visible (UV-Vis), FTIR, fluorescence spectroscopy, together with high performance liquid chromatography (HPLC) and electrospray ionization mass spectroscopy (ESI-MS) were utilized to study the variation of chemical compositions from shell and core regions of Sanqi. The results demonstrate that the chemical compositions of Sanqi from shell and core regions are different. In summary, differences in chemical composition between Sanqi shell and core were manifested from versatile aspects. Such differences shed a light on the different curative effects of Sanqi.
Sujet(s)
Médicaments issus de plantes chinoises/composition chimique , Panax notoginseng/composition chimique , Structures de plante/composition chimique , Spectrophotométrie/méthodes , Chromatographie en phase liquide à haute performance , Spectrométrie de fluorescence , Spectrométrie de masse ESI , Spectrophotométrie UV , Spectroscopie infrarouge à transformée de FourierRÉSUMÉ
There have been numerous efforts to understand and control the resistance of materials to fracture by repeated or cyclic stresses. The micromechanical behaviours, particularly the distributions of stresses on the scale of grain size during or after mechanical or electrical fatigue, are crucial to a full understanding of the damage mechanisms in these materials. Whether a large microstress develops during cyclic deformation with a small amount of monotonic strain but a large amount of accumulated strain remains an open question. Here, we report a neutron diffraction investigation of the development of intergranular stresses, which vary as a function of grain orientations, in 316 stainless steel during high-cycle fatigue. We found that a large intergranular stress developed before cracks started to appear. With further increase of fatigue cycles, the intergranular stress decreased, while the elastic intragranular stored energy continued to grow. One implication of our findings is that the ratio between the intergranular and intragranular stored energies during various stages of fatigue deformation may validate the damage mechanism and can be used as a fingerprint for monitoring the state of fatigue damage in materials.