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Changming Liu, Liangen Mao, Zepeng Ping, Tingting Jiang, Chong Wang, Zhongliang Chen, Zhongjie Li, Jicheng Li
Yin-deficiency-heat (YDH) syndrome is a concept in Traditional Chinese Medicine (TCM) for describing subhealth status. However, there are few efficient diagnostic methods available for confirming YDH syndrome. To explore the novel method for diagnosing YDH syndrome, we applied iTRAQ to observe the serum protein profiles in YDH syndrome rats and confirmed protein levels by ELISA. A total of 92 differentially expressed proteins (63 upregulated proteins and 29 downregulated proteins), which were mainly involved in complement and coagulation cascades and glucose metabolism pathway, were identified by the proteomic experiments...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Marine Dancer, Cyrielle Caussy, Mathilde Di Filippo, Philippe Moulin, Christophe Marçais, Sybil Charrière
BACKGROUND AND AIMS: APOC3 is a major regulator of triglycerides metabolism. Several APOC3 variants are associated with hypertriglyceridemia (HTG). Our aim was to establish the potential regulation of APOC3 3'UTR variants associated with HTG by liver or intestinal miRNAs. METHODS: We sequenced APOC3 3'UTR in 100 type 2 diabetic (TD2) patients with severe HTG (TG > 15 mmol/L) (HTG group) compared to 100 normotriglyceridemic patients (NTG group). We performed in silico studies to identify potential loss of miRNA binding induced by APOC3 3'UTR variants...
December 2016: Atherosclerosis
Vinit Shah, Michael E Lassman, Ying Chen, Haihong Zhou, Omar F Laterza
RATIONALE: In quantitative analysis of protein biomarkers and therapeutic proteins by liquid chromatography/mass spectrometry (LC/MS), it is a preferred and well-established approach to digest with proteolytic enzymes to produce smaller peptide fragments which are more suitable for LC/MS analysis than the intact protein. In-solution digestion is one widely used method for protein digestion. Proteolytically resistant proteins often require digestion times that extend beyond normal working hours and prohibit same day analysis...
January 30, 2017: Rapid Communications in Mass Spectrometry: RCM
Vani P Sanon, Yehuda Handelsman, Son V Pham, Robert Chilton
IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder...
October 2016: Clinical Diabetes: a Publication of the American Diabetes Association
J C Cohen
Genetic variation arises through multiple different alleles that vary in frequency and severity of effect. Mutations that give rise to Mendelian disorders, such as the LDL receptor (LDLR) mutations that result in familial hypercholesterolaemia, are efficiently winnowed from the population by purifying selection and are almost inevitably rare. Conversely, alleles that are common in the population (such that homozygotes for the minor allele are present even in modest sample sizes) typically have very modest phenotypic effects...
October 14, 2016: Journal of Internal Medicine
Sha Li, Xi Zhao, Yan Zhang, Cheng-Gang Zhu, Yuan-Lin Guo, Na-Qiong Wu, Rui-Xia Xu, Ping Qing, Ying Gao, Jing Sun, Geng Liu, Qian Dong, Jian-Jun Li
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System...
October 4, 2016: Oncotarget
Yanzhe Wang, Xiaoyu Yin, Lei Li, Shumin Deng, Zhiyi He
The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case-control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically...
2016: PloS One
Mehrpouya B Mobin, Stefanie Gerstberger, Daniel Teupser, Benedetta Campana, Klaus Charisse, Markus H Heim, Muthiah Manoharan, Thomas Tuschl, Markus Stoffel
The liver is essential for the synthesis of plasma proteins and integration of lipid metabolism. While the role of transcriptional networks in these processes is increasingly understood, less is known about post-transcriptional control of gene expression by RNA-binding proteins (RBPs). Here, we show that the RBP vigilin is upregulated in livers of obese mice and in patients with fatty liver disease. By using in vivo, biochemical and genomic approaches, we demonstrate that vigilin controls very-low-density lipoprotein (VLDL) secretion through the modulation of apolipoproteinB/Apob mRNA translation...
September 26, 2016: Nature Communications
Kailian Xu, Shiyu Guo, Tianjing Zhao, Huapei Zhu, Hanwei Jiao, Qiaoyun Shi, Feng Pang, Yaying Li, Guohua Li, Dongmei Peng, Xin Nie, Ying Cheng, Kebang Wu, Li Du, Ke Cui, Wenguang Zhang, Fengyang Wang
Hepatitis E virus- (HEV-) mediated hepatitis has become a global public health problem. An important regulatory protein of HEV, ORF3, influences multiple signal pathways in host cells. In this study, to investigate the function of ORF3 from the swine form of HEV (SHEV), high-throughput RNA-Seq-based screening was performed to identify the differentially expressed genes in ORF3-expressing HepG2 cells. The results were validated with quantitative real-time PCR and gene ontology was employed to assign differentially expressed genes to functional categories...
2016: BioMed Research International
Sen-Lin Hu, Guang-Lin Cui, Jin Huang, Jian-Gang Jiang, Dao-Wen Wang
Apolipoprotein C-III (APOC3) is a key regulator of plasma triglycerides levels. Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease. However, these favorable mutations were extremely distribution discrepant among different ethnics. In this study, the APOC3 gene was resequenced and we identified a common variant which located in the microRNA-binding site in APOC3 and would affect its expression and the risk of coronary heart disease (CHD)...
2016: Scientific Reports
Yun Tao, Yisong Xiong, Huimin Wang, Shaopeng Chu, Renqian Zhong, Jianxin Wang, Guihua Wang, Xiumei Ren, Juan Yu
BACKGROUND: The fatality rate for cardiovascular disease (CVD) has increased in recent years and higher levels of triglyceride have been shown to be an independent risk factor for atherosclerotic CVD. Dysfunction of endothelial cells (ECs) is also a key factor of CVD. APOC3 is an important molecule in lipid metabolism that is closely associated with hyperlipidemia and an increased risk of developing CVD. But the direct effects of APOC3 on ECs were still unknown. This study was aimed at determining the effects of APOC3 on inflammation, chemotaxis and exudation in ECs...
September 13, 2016: Lipids in Health and Disease
Claudio Rabacchi, Federico Bigazzi, Mariarita Puntoni, Francesco Sbrana, Tiziana Sampietro, Patrizia Tarugi, Stefano Bertolini, Sebastiano Calandra
BACKGROUND: Homozygous familial hypercholesterolemia is a rare clinical phenotype with a variable expression, which is characterized by extremely elevated plasma low-density lipoprotein (LDL), tendon and skin xanthomas, and a progressive atherosclerosis. In 95% of patients, homozygous familial hypercholesterolemia is due to mutations in low-density lipoprotein receptor (LDLR) gene, which abolish (receptor-negative) or greatly reduce (receptor-defective) LDLR function. OBJECTIVE: The objective of the study was the molecular and phenotypic characterization of 4 siblings with severe hypercholesterolemia...
July 2016: Journal of Clinical Lipidology
Anthony W H Chan, Grace L H Wong, Hoi-Yun Chan, Joanna H M Tong, Yau-Hei Yu, Paul C L Choi, Henry L Y Chan, Ka-Fai To, Vincent W S Wong
BACKGROUND & AIMS: Concurrent fatty liver in hepatitis B virus (HBV)-infected patients without significant alcohol intake is a frequent and increasingly alarming problem due to the non-alcoholic fatty liver disease (NAFLD) pandemic. Concomitant obesity and diabetes increase the risk of HBV-related hepatocellular carcinoma (HCC) development. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically-proven fatty liver in HBV hepatocarcinogenesis...
August 22, 2016: Journal of Gastroenterology and Hepatology
Sumeet A Khetarpal, Arman Qamar, John S Millar, Daniel J Rader
Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III...
September 2016: Current Atherosclerosis Reports
Juliana D Perez, Maísa M Sakata, Juliana A Colucci, Gláucio A Spinelli, Claudia R Felipe, Valdemir M Carvalho, Karina Helena M Cardozo, José O Medina-Pestana, Hélio Tedesco-Silva, Nestor Schor, Dulce E Casarini
UNLABELLED: Renal transplant is the best treatment for patients with chronical kidney disease however acute graft rejection is the major impediment to success in renal transplantation leading to loss of the organ the first year after transplantation. The aim of this study was to identify plasma proteins that may be early biomarkers of acute rejection of renal allograft, developing a diagnostic model that avoids the loss of the transplanted organ. Shotgun proteomics (LC-MS/MS) method was used to analyze a set of thirty-one plasma samples, including 06 from patients with acute graft rejection after transplantation (rejection group/Rej-group) and twenty-five from renal transplant patients with stable renal graft function (control group/Ct-group)...
August 1, 2016: Life Sciences
Yan Li, Chao Li, Jie Gao
BACKGROUND: It has been reported that three common loci, SstI, C-482T, and T-455C, in the apolipoprotein C3 (APOC3) gene might be associated with an increased risk of coronary heart disease (CHD). Considering the inconsistent results and ethnicity variations, we performed a systematic meta-analysis to evaluate the association between three single nucleotide polymorphisms (SNPs) and the risk of CHD. METHODS: We searched HuGE Navigator and PubMed databases to screen for the related literature published before 25 September, 2015...
September 2016: Meta Gene
Esther Sok Hwee Cheow, Woo Chin Cheng, Chuen Neng Lee, Dominique de Kleijn, Vitaly Sorokin, Siu Kwan Sze
Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions...
August 2016: Molecular & Cellular Proteomics: MCP
Yun-Zi Liu, Xiaoyun Cheng, Ting Zhang, Sojin Lee, Jun Yamauchi, Xiangwei Xiao, George Gittes, Shen Qu, Chun-Lei Jiang, H Henry Dong
Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects...
July 8, 2016: Journal of Biological Chemistry
Sharon A Miller, Amanda J Hooper, George A Mantiri, David Marais, Donald M Tanyanyiwa, James McKnight, John R Burnett
BACKGROUND: One genetic cause of markedly low plasma concentrations of apolipoprotein (apo) B and low density lipoprotein (LDL)-cholesterol is familial hypobetalipoproteinemia. OBJECTIVE: We aimed to determine the molecular basis for the marked hypocholesterolemia consistent with heterozygous familial hypobetalipoproteinemia in a black female subject of Xhosa lineage. METHODS: Coding regions of APOB, MTTP, PCSK9,ANGPTL3, SAR1B and APOC3 were sequenced, and APOE was genotyped...
May 2016: Journal of Clinical Lipidology
Laura C R Aranalde, Bruna S Pederzoli, Thais Marten, Flavio C Barros, Rossana P Basso, Jussara M Silveira, Sandra C Valle, Simone Pieniz, Ronaldo C Araujo, Edgar J Paredes-Gamero, Ines Schadock, Augusto Schneider, Carlos C Barros
The hypothesis of the present study is that the polymorphisms in the APOC3, CEPT, ACE, and ACTN3 genes can affect the outcome of nutritional intervention and the plasma lipid profile of HIV+ patients. To test the hypothesis, genetic material was collected from buccal cells, and serum was collected for biochemical analysis. Sixty-five patients were analyzed. The incorporation of protease inhibitor (PI) was more frequent in women (77% vs 33% in men). Nutritional intervention improved anthropometric parameters independent of the genotype...
June 2016: Nutrition Research
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