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1.
Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-13C]PA and [13-13C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX. Dietary PA was completely oxidized during the HOA diet, but only about 40% was oxidized during the HPA diet. The [13-13C]PA/[1-13C]PA ratio of PA OX had an approximate value of 1.0 for either diet, but the ratio of the serum concentrations of MCACs to long-chain ACs (LCACs) was significantly higher during the HPA diet. Thus, direct measurement of PA OX did not confirm that the HPA diet caused incomplete PA OX, despite the modest, but statistically significant, increase in the ratio of MCACs to LCACs in blood.  相似文献   
2.
Here we explored the impact of hydrogen sulfide (H2S) on biophysical properties of the primary human airway smooth muscle (ASM)–the end effector of acute airway narrowing in asthma. Using magnetic twisting cytometry (MTC), we measured dynamic changes in the stiffness of isolated ASM, at the single-cell level, in response to varying doses of GYY4137 (1–10 mM). GYY4137 slowly released appreciable levels of H2S in the range of 10–275 μM, and H2S released was long lived. In isolated human ASM cells, GYY4137 acutely decreased stiffness (i.e. an indicator of the single-cell relaxation) in a dose-dependent fashion, and stiffness decreases were sustained in culture for 24 h. Human ASM cells showed protein expressions of cystathionine-γ-lyase (CSE; a H2S synthesizing enzyme) and ATP-sensitive potassium (KATP) channels. The KATP channel opener pinacidil effectively relaxed isolated ASM cells. In addition, pinacidil-induced ASM relaxation was completely inhibited by the treatment of cells with the KATP channel blocker glibenclamide. Glibenclamide also markedly attenuated GYY4137-mediated relaxation of isolated human ASM cells. Taken together, our findings demonstrate that H2S causes the relaxation of human ASM and implicate as well the role for sarcolemmal KATP channels. Finally, given that ASM cells express intrinsic enzymatic machinery of generating H2S, we suggest thereby this class of gasotransmitter can be further exploited for potential therapy against obstructive lung disease.  相似文献   
3.
In the present work we studied the effect of antioxidants of the SkQ1 family (10-(6′-plastoquinonyl)decyltriphenylphosphonium) on the oxidative hemolysis of erythrocytes induced by a lipophilic free radical initiator 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN) and a water-soluble free radical initiator 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH). SkQ1 was found to protect erythrocytes from hemolysis, 2 μM being the optimal concentration. Both the oxidized and reduced SkQ1 forms exhibited protective properties. Both forms of SkQ1 also inhibited lipid peroxidation in erythrocytes induced by the lipophilic free radical initiator AMVN as detected by accumulation of malondialdehyde. However, in the case of induction of erythrocyte oxidation by AAPH, the accumulation of malondialdehyde was not inhibited by SkQ1. In the case of AAPH-induced hemolysis, the rhodamine-containing analog SkQR1 exerted a comparable protective effect at the concentration of 0.2 μM. At higher SkQ1 and SkQR1 concentrations, the protective effect was smaller, which was attributed to the ability of these compounds to facilitate hemolysis in the absence of oxidative stress. We found that plastoquinone in the oxidized form of SkQ1 could be reduced by erythrocytes, which apparently accounted for its protective action. Thus, the protective effect of SkQ in erythrocytes, which lack mitochondria, proceeded at concentrations that are two to three orders of magnitude higher than those that were active in isolated mitochondria.  相似文献   
4.
PurposeTo propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes.DesignCross-sectional study.MethodsThe study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively.ResultsWhen adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls.ConclusionA portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls.  相似文献   
5.
4-vinyl-2, 6-dimethoxyphenol (canolol) is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002). Besides that, the mean tumor diameter was decreased from 6.5mm to 4.5mm (P<0.001) after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001). In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7.  相似文献   
6.

Objective

This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women.

Methods

Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D3 (25(OH)D3) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT.

Results

The median serum 25(OH)D3 level was 11.03 ng/mL, with an interquartile range of 8.22–14.70. A decreasing trend of serum 25(OH)D3 level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D3 level and C-IMT (r = –0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D3 level independently and negatively associated with C-IMT (Standard β = –0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D3 with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard β = –0.140, P = 0.018).

Conclusions

Serum 25(OH)D3 level was inversely correlated with C-IMT in Chinese postmenopausal women.  相似文献   
7.
8.
BackgroundHypertension, with a global prevalence of 40%, is a risk factor for cardiovascular diseases (CVD). We conducted an exploratory study in Zhejiang China to understand the prevention of CVD among hypertensive patients with a 10 year CVD risk of 20% or higher. We assessed current practices in a rural ‘township hospital’ (a primary care facility), and compared them with international evidence-based practice.MethodsA questionnaire survey was conducted to examine the use of modern drugs (antihypertensive drugs, statins and aspirin) and traditional drugs, compliance to medications and lifestyle among 274 hypertensive patients aged 40-74, with a CVD risk of 20% or higher (using the Asian Equation).ResultsThe majority (72%) were diagnosed with hypertension at township hospitals. Only 15% of study participants used two anti-hypertensive drugs, 0.7% took statin and 2.9% aspirin. Only 2.9% combined two types of modern drugs, while 0.4% combined three types (antihypertensives, statins and aspirin). Herbal compounds, sometimes with internationally rarely recommended drugs such as Reserpine were taken by 44%. Analysis of drug adherence showed that 9.8% had discontinued their drug therapy by themselves. 16% had missed doses and these were on less anti-hypertensive drugs than those who did not (t=-5.217, P=0.003). Of all participants, 28% currently smoked, 39% drank regularly and only 21% exercised frequently. The average salt intake per day was 7.1 (±3.8) g, while the national recommended level is 6g.ConclusionThe study revealed outdated and inadequate treatment and health education for hypertensive patients, especially for those who have high risk scores for CVD. There is a need to review the community-based guidelines for hypertension management. Health providers and patients should make a transition from solely treating hypertension, towards prevention of CVD. Health system issues need addressing including improving rural health insurance cover and primary care doctors’ capacity to manage chronic disease patients.  相似文献   
9.
Crop improvement is a multifaceted micro-evolutionary process, involving changes in breeding approaches, planting configurations and consumption preferences of human beings. Recent research has started to identify the specific genes or genomic regions correlate to improved agronomic traits, however, an apparent blank between the genetic structure of crop elite varieties and their improving histories in diverse modern breeding programs is still in existence. Foxtail millet (Setaria italica) was one of the earliest cereal crops to be domesticated and served as a staple crop for early civilizations in China, where it is still widely grown today. In the present trial, a panel of foxtail millet elite varieties, which were released in the last sixty years in different geographical regions of China, was characterized using microsatellite markers (SSRs). A clear separation of two subpopulations corresponding to the two eco-geographical regions of foxtail millet production in China was identified by the dataset, which also indicated that in more recently released elite varieties, large quantities of accessions have been transferred from spring-sowing to summer-sowing ecotypes, likely as a result of breeding response to planting configurations. An association mapping study was conducted to identify loci controlling traits of major agronomic interest. Furthermore, selective sweeps involved in improvement of foxtail millet were identified as multi-diverse minor effect loci controlling different agronomic traits during the long-term improvement of elite varieties. Our results highlight the effect of transition of planting configuration and breeding preference on genetic evolvement of crop species.  相似文献   
10.
The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117–125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117–125) mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117–125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117–125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.  相似文献   
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