Cardiovascular disease, a leading cause of mortality in developed countries, is mainly caused by atherosclerosis, a chronic inflammatory disease. Macrophages, which differentiate from monocytes that are recruited from the blood, account for the majority of leukocytes in atherosclerotic plaques. Apoptosis and the suppressed clearance of apoptotic macrophages (efferocytosis) are associated with vulnerable plaques that are prone to rupture, leading to thrombosis. Based on the central functions of macrophages in atherogenesis, cytokines, chemokines, enzymes, or microRNAs related to or produced by macrophages have become important clinical prognostic or diagnostic biomarkers. This paper discusses the impact of monocyte-derived macrophages in early atherogenesis and advanced disease. The role and possible future development of macrophage inflammatory biomarkers are also described.

The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond appropriately, especially during the epithelial-mesenchymal transition (EMT). EMT is an important process during embryonic development, fibrosis, and tumor progression in which epithelial cells acquire mesenchymal, fibroblast-like properties and show reduced intercellular adhesion and increased motility. TGF-β signaling is the first pathway to be described as an inducer of EMT, and its relationship with the Smad family is already well characterized. Studies of four members of the MAPK family in different biological systems have shown that the MAPK and TGF-β signaling pathways interact with each other and have a synergistic effect on the secretion of additional growth factors and cytokines that in turn promote EMT. In this paper, we present background on the regulation and function of MAPKs and their cascades, highlight the mechanisms of MAPK crosstalk with TGF-β signaling, and discuss the roles of MAPKs in EMT.

The role of microRNAs (miRNAs) in vascular calcification is currently unclear. To examine how miRNAs are involved in vascular smooth muscle cell (VSMC) calcification, we explored the alteration of miRNAs in VSMC calcification in vitro and in vivo. Klotho homozygous mutant mice (kl/kl) display vascular calcification and have perturbations of calcium handling. We therefore hypothesized that the calcium perturbations in VSMCs could be mediated by miRNAs. Using an miRNA array analysis, we demonstrated that miRNAs are aberrantly expressed in the aortic media of 3-week-old kl/kl mice compared with wild-type (WT) mice. The expression levels of miR-135a*, miR-762, miR-714, and miR-712* in the aortic media of kl/kl mice were significantly higher than in WT mice. We used quantitative real-time reverse transcriptase polymerase chain reaction to further confirm that these miRNAs were increased in the aortic media of kl/kl mice and in cultured VSMCs treated with high phosphate and calcium. A search of the miRNA database indicated that the Ca 2 þ efflux proteins NCX1, PMCA1, and NCKX4 frequently appeared as potential targets of these miRNAs. The transfection of miRNA mimics into cultured VSMCs reduced the protein levels of each potential target. Conversely, miRNA inhibitors reduced phosphate and calcium-induced VSMC calcification. Furthermore, these inhibitors decreased the intracellular Ca 2 þ concentration in cultured VSMCs after treatment with phosphate and calcium. Our results suggest that increased expression of miR-135a*, miR-762, miR-714, and miR-712* in VSMCs may be involved in VSMC calcification by disrupting Ca 2 þ efflux proteins.

Microcystin-LR (MC-LR) is one of the hepatotoxins produced by cyanobacteria in the eutrophicated fresh water. In this work, the minor groove binding mode of MC-LR to plasmid DNA was explored by using UV and fluorescence spectra, and the binding characteristics of MC-LR for plasmid DNA were calculated via the fluorescence quenching of ethidium bromide (EB) and mole ratio method. Furthermore, atomic force microscopy (AFM) was used to observe DNA morphology change in the presence of MC-LR. With the increasing concentration of MC-LR, circle DNA strands twined gradually to rod condensates. The possible reason for the condensation might be the masking of the electrostatic repulsion between DNA double strands by MC-LR. The present study might provide useful information for the pathopoiesis mechanism of MC-LR. More, because the condensation of DNA could affect the progresses of gene expression and protein transcription, it may implicate another trend to explore the nosogenesis of MC-LR.

Background: Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods: HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta [MAP 1LC3B]), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results: HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism.

were purchased from Alfa Aesar. Ammonium peroxydisulfate ((NH 4) 2 S 2 O 8) was purchased from Xilong Chemical Industry Co. Ltd. (Guangdong, China). Concentrated sulfuric acid (H 2 SO 4) and ammonium fluoride (NH 4 F) were obtained from Beijing Chemical Factory (Beijing, China). Unless otherwise stated, other reagents were of analytical grade and were used without further purification. All aqueous solutions were prepared with ultrapure water (>18 MΩ) from an automatic double distillation system (Shanghai, China). 1.2 Apparatus Electronic Supplementary Material (ESI) for Nanoscale.

This study demonstrates a cocaine sensing method employing graphene oxide (GO), gold nanoparticles and a structure switching aptamer, which can fold into a three-way junction in the presence of cocaine. On the observation of gold nanoparticles (Au NPs) induced graphene oxide fluorescence quenching, a structure switching aptamer of cocaine was introduced as the linker between the two parts. Firstly, two fragments of a cocaine aptamer were immobilized covalently onto GO and Au NPs, respectively. Then when the three-way junction formed, the Au NPs were drawn near to the GO surface and induced a fluorescence intensity decrease. The limit of detection was 0.1 μM for cocaine in purified water, and well defined results were also obtained in biological fluids and the specificity experiment, which expands the feasibility of the as-prepared sensor for practical applications.

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