Stem/Progenitor Cells and Their Therapeutic Application in Cardiovascular Disease

Cardiovascular disease is the leading cause of death in the world. The stem/progenitor cell-based therapy has emerged as a promising approach for the treatment of a variety of cardiovascular diseases including myocardial infarction, stroke, peripheral arterial disease, and diabetes. An increasing number of evidence has shown that stem/progenitor cell transplantation could replenish damaged cells, improve cardiac and vascular functions, and repair injured tissues in many pre-clinical studies and clinical trials. In this review, we have outlined the major types of stem/progenitor cells, and summarized the studies in applying these cells, especially endothelial stem/progenitor cells and their derivatives, in the treatment of cardiovascular disease. Here the strategies used to improve the stem/progenitor cell-based therapies in cardiovascular disease and the challenges with these therapies in clinical applications are also reviewed

BRST-antifield-treatment of metric-affine gravity

The metric-affine gauge theory of gravity provides a broad framework in which gauge theories of gravity can be formulated. In this article we fit metric-affine gravity into the covariant BRST--antifield formalism in order to obtain gauge fixed quantum actions. As an example the gauge fixing of a general two-dimensional model of metric-affine gravity is worked out explicitly. The result is shown to contain the gauge fixed action of the bosonic string in conformal gauge as a special case.Comment: 19 pages LATEX, to appear in Phys. Rev.

Original Article MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell proliferation, invasion and cell cycle progression via p16-mediated PI3K-Akt signaling pathway in SHSY5Y cells

Abstract: Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription-associated transcript (LAT) region have been identified that play critical roles in the intricate host-pathogen interaction networks. Increasing evidences throw new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines. Decreased expression of miR-H4b was directly related to attenuated cell proliferation and invasion as well as malfunction of cell cycle in recombinant SHSY5Y cells that stably expressing miR-H4b. Bioinformatics analysis and luciferase assays demonstrated miR-H4b can directly target p16 mRNA. MiR-H4b exerts its pro-proliferation function through inhibition of the p16-related PI3K-Akt pathways. Our findings provide, for the first time, significant clues regarding the role of herpesvirus-encoded miRNAs as a viral modulator to host cells

Association of hyperuricemia and hypertension phenotypes in hypertensive patients without uric acid lowering treatment

Background Current study was to evaluate the association of hypertensive and hypertension phenotypes in hypertensive populations. Methods Patients with primary hypertension and without any uric acid (UA)-lowering treatment were enrolled. Baseline characteristics including office blood pressure (OBP), 24 h ambulatory blood pressure (ABP), and serum UA (SUA) were measured. According to SUA, patients were divided into normal SUA and hyperuricemia groups. Based on OBP and 24 h-ABP, hypertension phenotypes were classified as controlled hypertension (CH), white-coat uncontrolled hypertension (WCUH), masked uncontrolled hypertension (MUCH), and sustained uncontrolled hypertension (SUCH). Results Compared to patients with normal SUA (n = 336), patients with hyperuricemia (n = 284) were older and more likely to be men, obese, physically inactive, and have a higher prevalence of diabetes. C-reactive protein (CRP) level was higher in patients with hyperuricemia. The prevalence of CH, WCUH, and MUCH was similar between these two groups. However, the prevalence of SUCH was higher in patients with hyperuricemia than patients with normal SUA. Linear regression analysis indicated that increased SUA was significantly associated with 24 h-systolic BP and daytime-systolic BP. Normal SUA was served as the reference group, and presence of hyperuricemia was associated with higher odds of SUCH (odds ratio 1.46 and 95% confidence interval 1.27–1.93) after adjusted for potential covariates including age, male gender, obesity, diabetes, CRP, and antihypertensive drugs. Conclusion In hypertensive patients without UA-lowering treatment, presence of hyperuricemia was associated with higher odds of SUCH. Future studies are needed to evaluate whether lowering SUA can help to improve 24 h-ABP control

Lysyl Oxidase-Like Protein 2 Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer

Tumor lymphangiogenesis has been previously documented to predict regional lymph node metastasis and promote the spread to distant organs. However, the underlying mechanism initiating tumor lymphangiogenesis remains unclear. Here we described a novel role of tumor cell-derived Lysyl Oxidase-like protein 2 (LOXL2) in promoting lymphangiogenesis and lymph node metastasis in breast cancer. Immunohistochemistry (IHC) analysis of samples from breast cancer patients showed that the expression of LOXL2 was positively correlated with lymphatic vessel density and breast cancer malignancy. In animal studies, LOXL2-overexpressing breast cancer cells significantly increased lymphangiogenesis and lymph node metastasis, whereas knockdown of LOXL2 suppressed both processes. In order to study the mechanisms of lymphangiogenesis progression, we performed further in vitro investigations and the data revealed that LOXL2 significantly enhanced lymphatic endothelial cells (LECs) invasion and tube formation through directly activation of the Akt-Snail and Erk pathways. Moreover, LOXL2 also stimulated fibroblasts to secrete high level of pro- lymphangiogenic factors VEGF-C and SDF-1α. Taken together, our study elucidates a novel function of tumor cell secreted LOXL2 in lymphangiogenesis and lymph node metastasis, demonstrating that LOXL2 serves as a promising target for anti-lymphangiogenesis and anti-metastasis therapies for breast cancer

Modular structural elements in the replication origin region of Tetrahymena rDNA

Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophlla identified a potential initiation zone in the 5′ NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res . 22, 2479–2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryo-tic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites In super-coiled plasmid DNA were localized within the major DUE-IIke element predicted by thermodynamic analyses. Three restriction fragments of the 5′ NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresls on polyacrylamide gels. Restriction fragments containing the 5′NTS region bound Tetrahymena nuclear matrices in an In vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix In vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila , chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication.This article is from Nucleic Acids Research 23 (1995): 1766, doi: 10.1093/nar/23.10.1766. Posted with permission.</p