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151.
KB Cullberg T Christiansen SK Paulsen JM Bruun SB Pedersen B Richelsen 《Obesity (Silver Spring, Md.)》2013,21(3):454-460
Background:
Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).Methods:
In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.Results:
Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.Conclusions:
Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation. 相似文献152.
c-di-GMP是细菌中广泛存在的第二信使,可通过效应蛋白参与调控细菌的生物被膜形成、运动性和毒力等生物学特性。YeaI因含有能结合c-di-GMP分子的EGEVF基序,可能作为c-di-GMP效应蛋白发挥作用。[目的] 研究yeaI基因缺失对奶牛源大肠杆菌临床分离株NJ17生物学特性的影响。[方法] 构建NJ17的yeaI缺失株(NJ17ΔyeaI)及回复株cNJ17ΔyeaI,分析yeaI对NJ17生物学特性(如生长特性、生物被膜形成能力和对小鼠乳腺上皮细胞(EpH4-Ev)的黏附)的影响。[结果] 成功构建NJ17的yeaI缺失株(NJ17ΔyeaI)及其回复株(cNJ17ΔyeaI);与野生株NJ17相比,缺失株NJ17ΔyeaI生长特性及耐药性无显著变化,生物被膜形成能力显著下降,运动性显著升高(P<0.05);透射电镜检测结果表明,yeaI缺失影响NJ17菌毛和鞭毛的形成;实时定量PCR(qPCR)结果显示,yeaI基因显著抑制NJ17鞭毛基因filG和motB的转录水平(P<0.05);血清杀菌实验表明,yeaI缺失能显著增强其抵抗血清杀菌作用(P<0.05);对EpH4-Ev细胞黏附实验表明,yeaI缺失对NJ17黏附性无显著影响(P>0.05)。[结论] yeaI对奶牛源大肠杆菌NJ17的生物学特性具有重要的调控作用。 相似文献
153.
Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high- cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6Chigh monocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis. 相似文献
154.
Ingrid C. Rulifson Ping Cao Li Miao David Kopecky Linda Huang Ryan D. White Kim Samayoa Jonitha Gardner Xiaosu Wu Kui Chen Trace Tsuruda Oliver Homann Helene Baribault Harvey Yamane Tim Carlson Jed Wiltzius Yang Li 《PloS one》2016,11(2)
Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer’s disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia. 相似文献
155.
Possible target‐related proteins and signal network of bufalin in A549 cells suggested by both iTRAQ‐based and label‐free proteomic analysis 下载免费PDF全文
Dong‐Mei Zhang Li‐Xing Feng Miao Liu Wen‐Hai Jin Ji Luo Ai‐Ying Nie Yue Zhou Yin Li Wan‐Ying Wu Bao‐Hong Jiang Min Yang Xuan Liu 《Proteomics》2016,16(6):935-945
Bufalin (BF) exhibited antiproliferation and antimigration effects on human A549 lung cancer cells. To search its target‐related proteins, protein expression profiles of BF‐treated and control cells were compared using two quantitative proteomic methods, iTRAQ‐based and label‐free proteomic analysis. A total of 5428 proteins were identified in iTRAQ‐based analysis while 6632 proteins were identified in label‐free analysis. The number of common identified proteins of both methods was 4799 proteins. By application of 1.20‐fold for upregulated and 0.83‐fold for downregulated cutoff values, 273 and 802 differentially expressed proteins were found in iTRAQ‐based and label‐free analysis, respectively. The number of common differentially expressed proteins of both methods was 45 proteins. Results of bioinformational analysis using MetacoreTM showed that the two proteomic methods were complementary and both suggested the involvement of oxidative stress and regulation of gene expression in the effects of BF, and fibronectin‐related pathway was suggested to be an important pathway affected by BF. Western blotting assay results confirmed BF‐induced change in levels of fibronectin and other related proteins. Overexpression of fibronectin by plasmid transfection ameliorated antimigration effects of BF. Results of the present study provided information about possible target‐related proteins and signal network of BF. 相似文献
156.
Weiping?Zhu Yiming?Zhao Jiamin?Zhou Xin?Wang Qi?Pan Ning?Zhang Longrong?Wang Miao?Wang Dihua?Zhan Zeyang?Liu Xigan?He Dening?Ma Shuang?Liu Lu?WangEmail author 《Journal of hematology & oncology》2016,9(1):127
Background
Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.Methods
In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.Results
The expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGLhigh group was markedly poorer than that for the MAGLlow group in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.Conclusions
Our findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.157.
In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches. 相似文献
158.
Xiao-Qing Li Ning Ma Xin-Gang Li Bo Wang Shu-Sen Sun Feng Gao Da-Peng Mo Li-Gang Song Xuan Sun Lian Liu Xing-Quan Zhao Yi-Long Wang Yong-Jun Wang Zhi-Gang Zhao Zhong-Rong Miao 《PloS one》2016,11(2)
Background and Purpose
Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.Methods
Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.Results
A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.Conclusions
PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events. 相似文献159.
Huajun Zheng Hong Liang Yuezhu Wang Maohua Miao Tao Shi Fen Yang Enuo Liu Wei Yuan Zai-Si Ji De-Kun Li 《PloS one》2016,11(11)
Eczema is frequently the first manifestation of an atopic diathesis and alteration in the diversity of gut microbiota has been reported in infants with eczema. To identify specific bacterial communities associated with eczema, we conducted a case-control study of 50 infants with eczema (cases) and 51 healthy infants (controls). We performed high-throughput sequencing for V3–V4 hypervariable regions of the 16S rRNA genes from the gut fecal material. A total of 12,386 OTUs (operational taxonomic units) at a 97% similarity level were obtained from the two groups, and we observed a difference in taxa abundance, but not the taxonomic composition, of gut microbiota between the two groups. We identified four genera enriched in healthy infants: Bifidobacterium, Megasphaera, Haemophilus and Streptococcus; and five genera enriched in infants with eczema: Escherichia/Shigella, Veillonella, Faecalibacterium, Lachnospiraceae incertae sedis and Clostridium XlVa. Several species, such as Faecalibacterium prausnitzii and Ruminococcus gnavus, that are known to be associated with atopy or inflammation, were found to be significantly enriched in infants with eczema. Higher abundance of Akkermansia muciniphila in eczematous infants might reduce the integrity of intestinal barrier function and therefore increase the risk of developing eczema. On the other hand, Bacteroides fragilis and Streptococcus salivarius, which are known for their anti-inflammatory properties, were less abundant in infants with eczema. The observed differences in genera and species between cases and controls in this study may provide insight into the link between the microbiome and eczema risk. 相似文献
160.
Haiyang Geng Feng Wu Lingtao Kong Yanqing Tang Qian Zhou Miao Chang Yifang Zhou Xiaowei Jiang Songbai Li Fei Wang 《PloS one》2016,11(2)