摘要：
Background: Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. Methods and results: Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red 0 staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages. Conclusions: MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases. (C) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved.
摘要：
Melatonin is synthesized and secreted mainly by the pineal gland in a circadian fashion, and it thus mediates endogenous circadian rhythms and influences other physiological functions. Both the G-protein coupled receptors MT1 (encoded by MTNR1A) and MT2 (encoded by MTNR1B) in mammals mediate the actions of melatonin. Evidence from in vivo and in vitro studies proved a key role of melatonin in the regulation of glucose metabolism and the pathogenesis of diabetes, as further confirmed by the recent studies of human genetic variants of MTNR1B. Remarkably, it was also suggested that genetic variations within MTNR1B disordered beta-cells function directly, i.e. insulin secretion. This indicated the functional link between MT2 and T2D risk at the protein level, and it may represent the prevailing pathomechanism for how impaired melatonin signaling causes metabolic disorders and increases the T2D risk lt is speculated that melatonin and its receptors may be a new therapeutic avenue in diabetes. (C) 2014 Elsevier B.V. All rights reserved.
摘要：
In order to investigate Cd accumulation, subcellular distribution, and local-ization in soybean seedlings leaves, soybean seedlings were cultivated in solution containing different concentrations of Cd. The results showed that most Cd associ-ated with the cellwal s and soluble fractions, and a minor part of Cd presented in mitochondria fractions, nuclear and chloroplast fractions, especial y exposure to high Cd concentrations. Under 20.00 mg/L Cd stress, Cd subcellular distribution fol owed a sequence as： soluble fractions （55.00%）＆gt;cellwal s （30.0%）＆gt;mitochondria fractions （8.21%）＆gt;nuclear and chloroplast fractions （6.79%）. Deposited Cd black particles were observed in cellwal s, chloroplasts, nuclei, and vacuoles through electrical microscope slice. This fact indicated that the cellwal s of soybean leaves were the first protecting organel es from Cd toxicity, and the cellwal s and soluble fractions were the main place for Cd storage. Due to Cd accumulated in the organel es, the intercellular space was enlarged and the subcellular structure was damaged, especial y for the chloroplasts.
摘要：
This study is designed to investigate whether APJ receptor acts as a sensor in static pressure-induced cardiomyocyte hypertrophy and to investigate the mechanism of PI3K-autophagy pathway. The left ventricular hypertrophy rat model was established by coarctation of abdominal aorta. H9c2 rat cardiomyocytes were cultured in the presence of static pressure which was given by a custom-made pressure incubator. The results revealed that the expression of apelin/APJ system, PI3K, Akt and their phosphorylation were significantly increased in the operation group. Static pressure up-regulated the APJ expression, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression in cardiomyocytes. APJ shRNA pGPU6/Neo-rat-399, PI3K inhibitor LY294002, Akt inhibitor 1701-1 blocked the up-regulation of APJ, PI3K phosphorylation, Akt phosphorylation, LC3-II/I and beclin-1 expression, respectively. Moreover, static pressure increased the diameter, volume, protein content of cells, and these could be reversed when the cells were treated with pGPU6/Neo-rat-399, LY294002, and autophagy inhibitor 3-methyladenine, respectively. These results suggested that static pressure up-regulates APJ expression to promote cardiomyocyte hypertrophy by a PI3K-autophagy pathway.
作者机构：
[Xie, Feng; Lv, Deguan] Learning Key Laboratory for Pharmaco-proteomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;[Chen, Linxi] Learning Key Laboratory for Pharmaco-proteomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China lxchen6@126.com
通讯机构：
[Chen, L.] L;Learning Key Laboratory for Pharmaco-proteomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China
关键词：
hormones;cardiac development
摘要：
Human ELA consists of three exons on chromosome 4, which generates a transcript (AK092578) that is annotated as a non-coding RNA. However, Chng et al. [1] has found that this gene contains a conserved open reading frame predicted to express a conserved vertebrate protein of 54 amino acids (aa) consisting of a secretory signal and a mature 32-aa peptide, which was called as ELABELA (ELA). The sequence of human mature ELA is Gln-Arg-Pro-Val-Asn-Leu-Thr-Met-Arg-Arg-Lys-Leu-Arg-Lys-His-Asn-Cys-Leu-Gln-Arg-Arg-Cys-Met-Pro-Leu-His-Ser-Arg-Val-Pro-Phe-Pro. Phylogenetic analysis revealed that the 32-aa mature peptide is evolutionarily highly conserved, with the last 13 residues being nearly invariant in all vertebrate species. ELA has also been previously reported to be highly expressed in undifferentiated human embryonic stem cells (hESCs) and be sharply down-regulated during differentiation [2]. Chng et al. [1] used an allelic series of zebrafish ELA mutants to show that ELA deficiency leads to severe defects in cardiac morphogenesis and often results in the complete absence of a heart. ELA mutant displayed specific defects in the mesen-dodermal lineage during gastrulation, as observed by the reduction of gata5 and sox17 expression. Taking together, these results suggested that ELA plays a role in the regulation of heart development. Whereas till now, no hormonal peptides has been reported to be involved in early development, particularly in the formation of the three embryonic germ layers. Chng et al. [1] first discovered an endogenous peptide hormone with potent embryonic signaling activity, which has great prospects in therapeutic applications such as heart repair and gene therapy in development.
摘要：
Objectives: ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. This study was to determine the effects and potential mechanisms of Chlamydia pneumoniae (C. pneumoniae) on ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells. Methods and results: C. pneumoniae significantly decreased the expression of ABCA1 and reduced cholesterol efflux. Furthermore, we found that C. pneumoniae suppressed ABCA1 expression via upregulation of miR-33s. The inhibition of C. pneumoniae-induced NF-kappa B activation decreased miR-33s expression and enhanced ABCA1 expression. In addition, C. pneumoniae increased Toll-like receptor 2 (TLR2) expressions, inhibition of which by siRNA could also block NF-kappa B activation and miR-33s expression, and promot the expression of ABCA1. Conclusion: Taken together, these results reveal that C. pneumoniae may negatively regulate ABCA1 expression via TLR2-NF-kappa B and miR-33 pathways in THP-1 macrophage-derived foam cells, which may provide new insights for understanding the effects of C. pneumoniae on the pathogenesis of atherosclerosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
作者机构：
[Guan Wang; Hongquan Zhang; Qiuxia Huang; Liqiu Quan; zongbao Wang; Xing Zheng] Research Interest Group, University of South China, Hengyang 421001, China;[Qutong Zheng; Yun Wei; Ya Liu] Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China;[Jichang Xiao] Key Laboratory of Organofluorine Chemistry, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China;[zongbao Wang; Xing Zheng] Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China
摘要：
A novel gem-difluoromethylenated oleanolic acid was synthesized and its anti-hepatocellular carcinoma activity in vitro was tested.The results of biological test showed that gem-difluoromethylenated oleanolic acid possessed potential anticancer activity.
摘要：
Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and responsible for catalyzing lipolysis of triglycerides in lipoproteins. LPL is produced mainly in adipose tissue, skeletal and heart muscle, as well as in macrophage and other tissues. After synthesized, it is secreted and translocated to the vascular lumen. LPL expression and activity are regulated by a variety of factors, such as transcription factors, interactive proteins and nutritional state through complicated mechanisms. LPL with different distributions may exert distinct functions and have diverse roles in human health and disease with close association with atherosclerosis. It may pose a pro-atherogenic or an anti-atherogenic effect depending on its locations. In this review, we will discuss its gene, protein, synthesis, transportation and biological functions, and then focus on its regulation and relationship with atherosclerosis and potential underlying mechanisms. The goal of this review is to provide basic information and novel insight for further studies and therapeutic targets. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
