Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Background: Acute coronary syndrome leads to systemic responses, including activation of the sympathetic nervous system, inflammation of atherosclerotic lesions, changes in metabolism and gene expressions of remote organs such as the spleen, bone marrow, and liver. Clinical trials and experimental studies have demonstrated that therapy with adipose-derived regenerative cells (ADRCs) attenuates myocardial ischemia/reperfusion (I/R) injury. The aim of this study is to investigate the role of ADRCs in regulating systemic reactions following I/R.Methods: Isolated ADRCs were obtained from green fluorescent protein transgenic male mice. Flow cytometry revealed that freshly isolated ADRCs expressed stem cell markers CD90 and Sca-1, and mesenchymal lineage marker. These cells exhibited multilineage differentiation into adipogenic, osteogenic, and chondrogenic lineages. Wild-type mice were subjected to 30 min of left ascending coronary ischemia and 24 h reperfusion. Freshly isolated ADRCs (105 cells) or vehicle (VEH), were administered intravenously through the tail at the time of reperfusion.Results: Compared to VEH, administration of ADRCs significantly reduced circulating troponin levels 24 h after I/R. Using quantitative real-time polymerase chain reaction analysis, the present study confirms that I/R-induced increase of factor X mRNA expression in the liver and was significantly inhibited by ADRCs compared to VEH. Administration of ADRCs significantly reduced the I/R-induced increase in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-18 seen in mice receiving VEH.Conclusions: These results suggest that administration of ADRCs could have an important role in reducing myocardial injury and regulating the hepatic gene expression profile following I/R

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

Objective: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. © Published by the BMJ Publishing Group Limited

Polymer synthesis /

Includes bibliographical references (p. 189-210) and indexes

Supramolecular polymer gels formed from polyamidine and random copolymer of n‐butyl acrylate and acrylic acid.

We have prepared the amidinium‐carboxylate salt bridge‐based supramolecular polymer gels from random copolymer of n‐butyl acrylate and acrylic acid and a linear polyamidine having N,N′‐di‐substituted acetamidine group in the main chain. The supramolecular polymer gel with equimolar amounts of carboxy and amidine groups shows a high G′ value of 1.6 MPa at 25°C. In contrast, the gel prepared from the carboxy polymer and linear polyethyleneimine instead of the polyamidine shows liquid‐like fluidity with a G′ value of 0.01 MPa at 25°C. The robustness of the amidine‐based supramolecular polymer gels is attributed to the high stability of the amidinium‐carboxylate salt bridge. Replacing the random copolymer with carboxy‐terminated telechelic poly(n‐butyl acrylate) results in a significant decrease in G′ as well as |η*|, which may arise from the difference in the network structure due to the arrangement of carboxy groups.Asahi Glass FoundationJapan Society for the Promotion of Science. Grant Number: 18K0525

Diastereoselective Imine-Bond Formation through Complementary Double-Helix Formation

Optically active amidine dimer strands having a variety of chiral and achiral linkers with different stereostructures are synthesized and used as templates for diastereoselective imine-bond formations between two achiral carboxylic acid monomers bearing a terminal aldehyde group and racemic 1,2-cyclohexanediamine, resulting in a preferred-handed double helix stabilized by complementary salt bridges. The diastereoselectivity of the racemic amine is significantly affected by the chirality of the amidine residues along with the rigidity and/or chirality of the linkers in the templates. NMR and kinetic studies reveal that the present imine-bond formation involves a two-step reversible reaction. The second step involves formation of a preferred-handed complementary double helix assisted by the chiral amidine templates and determines the overall reaction rate and diastereoselectivity of the amine

Reversible Cross-Linking and De-Cross-Linking System of Polystyrenes Bearing the Monohydrate Structure of Vicinal Tricarbonyl Group through Water–Alcohol Exchange Reactions at Ambient Conditions

We describe in this paper reversible cross-linking and de-cross-linking system based on a polystyrene derivative bearing monohydrate structure of vicinal tricarbonyl groups with 1,6-hexanediol utilizing the direct water–alcohol exchange reactions on the vicinal tricarbonyl groups. By employing diphenylpropanetrione as a unit model compound for the polymer, we have demonstrated that the water–alcohol exchange reactions could be carried out reversibly in both directions by changing solvents. Notably, the water–alcohol exchange reactions proceeded without any catalysts and under mild conditions. For example, an equimolar mixture of the hydrate of diphenylpropanetrione and benzyl alcohol in chloroform (0.5 M) reached equilibrium after standing at ambient temperature within 48 h, where the content ratio of the benzyl alcohol adduct increased up to 49%. The reaction rate and the position of the equilibrium were highly affected by the concentrations of the substrates as well as the reaction temperature. By virtue of the above characteristic features of the water–alcohol exchange reactions, the polystyrene derivative bearing monohydrate structure of vicinal tricarbonyl group (2.0 M) was cross-linked with 1,6-hexanediol (0.2 equiv of OH group to the tricarbonyl unit) in acetone at ambient temperature for 5 days to afford the networked polymer in almost quantitative yield. On the other hand, the networked polymer was treated with an excess of water at ambient temperature for 3 days to afford the original linear polymer in high yield as a result of de-cross-linking through the water–alcohol exchange reaction. The cross-linking and de-cross-linking behavior was also evidenced by SEC analysis of the reaction mixture