1,342 research outputs found

    MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats.

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    Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymographic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm

    Correlated Hybrid Fluctuations from Inflation with Thermal Dissipation

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    We investigate the primordial scalar perturbations in the thermal dissipative inflation where the radiation component (thermal bath) persists and the density fluctuations are thermally originated. The perturbation generated in this model is hybrid, i.e. it consists of both adiabatic and isocurvature components. We calculate the fractional power ratio (SS) and the correlation coefficient (cosΔ\cos\Delta) between the adiabatic and the isocurvature perturbations at the commencing of the radiation regime. Since the adiabatic/isocurvature decomposition of hybrid perturbations generally is gauge-dependent at super-horizon scales when there is substantial energy exchange between the inflaton and the thermal bath, we carefully perform a proper decomposition of the perturbations. We find that the adiabatic and the isocurvature perturbations are correlated, even though the fluctuations of the radiation component is considered uncorrelated with that of the inflaton. We also show that both SS and cosΔ\cos \Delta depend mainly on the ratio between the dissipation coefficient Γ\Gamma and the Hubble parameter HH during inflation. The correlation is positive (cosΔ>0\cos\Delta > 0) for strong dissipation cases where Γ/H>0.2\Gamma/H >0.2, and is negative for weak dissipation instances where Γ/H<0.2\Gamma/H <0.2. Moreover, SS and cosΔ\cos \Delta in this model are not independent of each other. The predicted relation between SS and cosΔ\cos\Delta is consistent with the WMAP observation. Other testable predictions are also discussed.Comment: 18 pages using revtex4, accepted for publication in PR

    Maize straw application as an interlayer improves organic carbon and total nitrogen concentrations in the soil profile: A four-year experiment in a saline soil

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    Soil salinization is a critical environmental issue restricting agricultural production. Deep return of straw to the soil as an interlayer (at 40 cm depth) has been a popular practice to alleviate salt stress. However, the legacy effects of straw added as an interlayer at different rates on soil organic carbon (SOC) and total nitrogen (TN) in saline soils still remain inconclusive. Therefore, a four-year (2015–2018) field experiment was conducted with four levels (i.e., 0, 6, 12 and 18 Mg ha–1) of straw returned as an interlayer. Compared with no straw interlayer (CK), straw addition increased SOC concentration by 14–32 and 11–57% in the 20–40 and 40–60 cm soil layers, respectively. The increases in soil TN concentration (8–22 and 6–34% in the 20–40 and 40–60 cm soil layers, respectively) were lower than that for SOC concentration, which led to increased soil C:N ratio in the 20–60 cm soil depth. Increases in SOC and TN concentrations in the 20–60 cm soil layer with straw addition led to a decrease in stratification ratios (0–20 cm:20–60 cm), which promoted uniform distributions of SOC and TN in the soil profile. Increases in SOC and TN concentrations were associated with soil salinity and moisture regulation and improved sunflower yield. Generally, compared with other treatments, the application of 12 Mg ha–1 straw had higher SOC, TN and C:N ratio, and lower soil stratification ratio in the 2015–2017 period. The results highlighted that legacy effects of straw application as an interlayer were maintained for at least four years, and demonstrated that deep soil straw application had a great potential for improving subsoil fertility in salt-affected soils.publishedVersio

    Inhibition of MicroRNA-124 Reduces Cardiomyocyte Apoptosis Following Myocardial Infarction via Targeting STAT3

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    Background/Aims: MicroRNAs play an important role in regulating myocardial infarction (MI)-induced cardiac injury. MicroRNA-124 (miR-124) plays a vital role in regulating cellular proliferation, differentiation and apoptosis. Although the alteration of miR-124 was confirmed in peripheral blood of MI patients, little is known regarding the biological functions of miR-124 in cardiomyocytes. This study was designed to explore the role of miR-124 in MI and its underlying mechanisms. Methods: Real-time PCR was used to quantify the microRNAs levels. TUNEL and Flow cytometry were performed to measure cell apoptosis. Western blot analysis was employed to detect expression of Bcl-2, Bax, Caspase-3 and STAT3 proteins. Results: We revealed that miR-124 was significantly up-regulated in a mice model of MI and in neonatal rat ventricular myocytes (NRVMs) with H2O2 treatment. H2O2 treatment induced cardiomyocyte injury with reduced cell viability and enhanced apoptotic cell death, whereas silencing expression of miR-124 by AMO-124 (antisense inhibitor oligodeoxyribonucleotides) alleviated these deleterious changes. AMO-124 decreased the expression of Bax and cleaved-caspase-3 and upregulated the expression of Bcl-2 in H2O2-treated NRVMs. Besides, AMO-124 improved mitochondrial dysfunction of NRVMs induced by H2O2 treatment. Moreover, antagomir-124 markedly decreased the infarct area and apoptotic cardiomyocytes and improved cardiac function in MI mice. Furthermore, we identified STAT3 as a direct target of miR-124, and downregulation of miR-124 ameliorated the diminished levels of STAT3 and p-STAT3 (Tyr705) in response to H2O2 or MI. STAT3 inhibitor, stattic, was shown to attenuate the elevation of p-STAT3 in NRVMs with AMO-124 transfection. Inhibiting of STAT3 activity by stattic abrogated protective effects of AMO-124 on H2O2-induced cardiomyocytes apoptosis. Conclusion: Taken together, our data demonstrate that downregulation of miR-124 inhibits MI-induced apoptosis through upregulating STAT3, which suggests the therapeutic potential of miR-124 for myocardial infarction

    Metabolomic profiling combined with network analysis of serum pharmacochemistry to reveal the therapeutic mechanism of Ardisiae Japonicae Herba against acute lung injury

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    Introduction: Acute lung injury (ALI) is a common and devastating respiratory disease associated with uncontrolled inflammatory response and transepithelial neutrophil migration. In recent years, a growing number of studies have found that Ardisiae Japonicae Herba (AJH) has a favorable anti-inflammatory effect. However, its serum material basis and molecular mechanism are still unknown in ALI treatment. In this study, metabolomics and network analysis of serum pharmacochemistry were used to explore the therapeutic effect and molecular mechanism of AJH against lipopolysaccharide (LPS)-induced ALI.Methods: A total of 12 rats for serum pharmacochemistry analysis were randomly divided into the LPS group and LPS + AJH-treated group (treated with AJH extract 20 g/kg/d), which were administered LPS (2 mg/kg) by intratracheal instillation and then continuously administered for 7 days. Moreover, 36 rats for metabolomic research were divided into control, LPS, LPS + AJH-treated (5, 10, and 20 g/kg/d), and LPS + dexamethasone (Dex) (2.3 × 10−4 g/kg/d) groups. After 1 h of the seventh administration, the LPS, LPS + AJH-treated, and LPS + Dex groups were administered LPS by intratracheal instillation to induce ALI. The serum pharmacochemistry profiling was performed by UPLC-Orbitrap Fusion MS to identify serum components, which further explore the molecular mechanism of AJH against ALI by network analysis. Meanwhile, metabolomics was used to select the potential biomarkers and related metabolic pathways and to analyze the therapeutic mechanism of AJH against ALI.Results: The results showed that 71 serum components and 18 related metabolites were identified in ALI rat serum. We found that 81 overlapping targets were frequently involved in AGE-RAGE, PI3K-AKT, and JAK-STAT signaling pathways in network analysis. The LPS + AJH-treated groups exerted protective effects against ALI by reducing the infiltration of inflammatory cells and achieved anti-inflammatory efficacy by significantly regulating the interleukin (IL)-6 and IL-10 levels. Metabolomics analysis shows that the therapeutic effect of AJH on ALI involves 43 potential biomarkers and 14 metabolic pathways, especially phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism pathways, to be influenced, which implied the potential mechanism of AJH in ALI treatment.Discussion: Our study initially elucidated the material basis and effective mechanism of AJH against ALI, which provided a solid basis for AJH application

    Personalized objects can optimize the diagnosis of EMCS in the assessment of functional object use in the CRS-R: A double blind, randomized clinical trial

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    peer reviewedBackground: Behavioral assessment has been acted as the gold standard for the diagnosis of disorders of consciousness (DOC) patients. The item "Functional Object Use" in the motor function sub-scale in the Coma Recovery Scale-Revised (CRS-R) is a key item in differentiating between minimally conscious state (MCS) and emergence from MCS (EMCS). However, previous studies suggested that certain specific stimuli, especially something self-relevant can affect DOC patients' scores of behavioral assessment scale. So, we attempted to find out if personalized objects can improve the diagnosis of EMCS in the assessment of Functional Object Use by comparing the use of patients' favorite objects and other common objects in MCS patients. Methods: Twenty-one post-comatose patients diagnosed as MCS were prospectively included. The item "Functional Object Use" was assessed by using personalized objects (e.g., cigarette, paper) and non-personalized objects, which were presented in a random order. The rest assessments were performed following the standard protocol of the CRS-R. The differences between functional uses of the two types of objects were analyzed by the McNemar test. Results: The incidence of Functional Object Use was significantly higher using personalized objects than non-personalized objects in the CRS-R. Five out of the 21 MCS studied patients, who were assessed with non-personalized objects, were re-diagnosed as EMCS with personalized objects (χ2 = 5, df=1, p<0.05). Conclusions: Personalized objects employed here seem to be more effective to elicit patients' responses as compared to non-personalized objects during the assessment of Functional Object Use in DOC patients.National High Technology Research and Development Program of Chin

    The Initiation of Swallowing Can Indicate the Prognosis of Disorders of Consciousness: A Self-Controlled Study.

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    Objective: To detect the initiation of swallowing in patients with disorders of consciousness (DOC) as well as the relationship between the initiation of swallowing and the prognosis of DOC patients. Methods: Nineteen DOC patients were included in this study, and a self-controlled trial compared five different stimuli. The five different stimuli were as follows: (1) one command, as recommended by the Coma Recovery Scale-Revised (CRS-R), which was "open your mouth"; (2) placing a spoon in front of the patient's mouth without a command; (3) placing a spoon filled with water in front of the patient's mouth without a command; (4) one command-"there is a spoon; open your mouth"-with a spoon in front of the patient's mouth; (5) one command, "there is a spoon with water; open your mouth," with a spoon filled with water in front of the patient's mouth. All 19 patients were given these five stimuli randomly, and any one of the commands was presented four times to a patient, one at a time, at 15-s intervals. The sensitivity and specificity of the initiation of swallowing in detecting conscious awareness were determined. Results: None of the patients responded to the first four stimuli. However, six patients showed initiated swallowing toward the fifth stimulus. Among those six, five patients showed improvement in their consciousness state 6 months later. The sensitivity and specificity of the initiation of swallowing for DOC patients was 83.33% [95% CIs (36%, 100%)] and 92.31% [95% CIs (64%, 100%)], respectively. Conclusions: The initiation of swallowing can be an early indication of conscious behavior and can likely provide evidence of conscious awareness. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03508336; Date of registration: 2018/4/16

    Left ventricular morphology and function in adolescents: Relations to fitness and fatness.

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    BACKGROUND: Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. METHODS: LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18kg/m(2)-25kg/m(2)] and 9 obese [BMI equivalent to ≥30kg/m(2)]); 13.3±1.1years, 45% female, Tanner puberty stage 3 [2-4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. RESULTS: Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r=0.49-0.71, P<0.05). CONCLUSION: Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. CLINICAL TRIAL REGISTRATION: NCT01991106
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