β3-Adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation.

β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism.

A novel protective mechanism for mitochondrial aldehyde dehydrogenase (ALDH2) in type i diabetes-induced cardiac dysfunction: role of AMPK-regulated autophagy.

Mitochondrial aldehyde dehydrogenase (ALDH2) is known to offer myocardial protection against stress conditions including ischemia-reperfusion injury, alcoholism and diabetes mellitus although the precise mechanism is unclear. This study was designed to evaluate the effect of ALDH2 on diabetes-induced myocardial injury with a focus on autophagy. Wild-type FVB and ALDH2 transgenic mice were challenged with streptozotozin (STZ, 200mg/kg, i.

Selective inhibition of inositol hexakisphosphate kinases (IP6Ks) enhances mesenchymal stem cell engraftment and improves therapeutic efficacy for myocardial infarction.

5-Diphosphoinositol pentakisphosphate (IP7), formed by a family of inositol hexakisphosphate kinases (IP6Ks), has been demonstrated to be a physiologic inhibitor of Akt. IP6K inhibition may increase Akt activation in mesenchymal stem cells (MSCs), resulting in enhanced cardiac protective effect after transplantation. The aim of this study was to investigate the role of IP6Ks for improving MSCs' functional survival and cardiac protective effect after transplantation into infarcted mice hearts.

Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-β aggregation and cytotoxicity.

Alzheimer's disease (AD), the most common neurodegenerative disease, is caused by an accumulation of amyloid-β (Aβ) plaque deposits in the brains. Evidence is increasingly showing that epigallocatechin-3-gallate (EGCG) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. In order to better understand the process of Aβ aggregation and amyloid fibril disaggregation and reduce the cytotoxicity of EGCG at high doses, we attached EGCG onto the surface of selenium nanoparticles (EGCG@Se).

Se/Ru nanoparticles as inhibitors of metal-induced Aβ aggregation in Alzheimer's disease.

Amyloid β (Aβ) aggregates are considered as possible targets for therapy of Alzheimer's disease (AD). Metal ions play an important role in amyloid aggregation and neurotoxicity in the AD pathogenesis. Disruption of the interactions between these metal ions and peptides holds considerable promise as a therapeutic strategy for AD treatment.

Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal stem cells by inhibiting Akt signaling.

Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been proposed as an ideal autologous stem cell source for cell-based therapy for myocardial infarction (MI). However, decreased viability and impaired function of aged MSCs hampered the therapeutic efficacy of engrafted MSCs, and the underlying mechanisms remain unclarified. Here, we investigated the role of inositol phosphates 6 kinase (IP6Ks) inhibition on the therapeutic efficacy of BM-MSCs and its underlying mechanism.

Literature mining of protein phosphorylation using dependency parse trees.

As one of the most common post-translational modifications (PTMs), protein phosphorylation plays an important role in various biological processes, such as signaling transduction, cellular metabolism, differentiation, growth, regulation and apoptosis. Protein phosphorylation is of great value not only in illustrating the underlying molecular mechanisms but also in treatment of diseases and design of new drugs. Recently, there is an increasing interest in automatically extracting phosphorylation information from biomedical literatures.

Inhibition of tumor growth and vasculature and fluorescence imaging using functionalized ruthenium-thiol protected selenium nanoparticles.

Here we reported the high tumor targeting efficacy of luminescent Ru(II)-thiols protected selenium nanoparticles (Ru-MUA@Se). We have shown that a dual-target inhibitor Ru-MUA@Se directly suppress the tumor growth but also block blood-vessel growth. We also determined that the nanoparticles entered the cells via clathrin-mediated endocytosis pathway.

[Analysis on chemical components from water extract of paeoniae radix alba by high performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry].

This experiment was performed to establish a qualitative analysis on chemical composition in water extract of Paeoniae Radix Alba by HPLC-ESI-Q-TOF-MS. The analysis was conducted on a C18 (Hanbon Lichrospher, 4.6 mm x 250 mm, 5 microm) column with methanol-0.

Ruthenium (II) polypyridyl complexes stabilize the bcl-2 promoter quadruplex and induce apoptosis of Hela tumor cells.

In the present study, the interaction between GC-rich sequence of bcl-2 gene P1 promoter (Pu39) and two ruthenium (II) polypyridyl complexes, [Ru(bpy)₂(tip)]²⁺ (1) and [Ru(phen)₂(tip)]²⁺ (2), was investigated by UV-Visible, fluorescence spectroscopy, circular dichroism, fluorescence resonance energy transfer melting assay and polymerase chain reaction stop assay. Those experimental results indicated that the two complexes can effectively stabilize the G-quadruplex of Pu39. It was found that the complex 2 exhibited greater cytotoxic activity than 1 against human Hela cells and can enter into Hela cells in a short period of time to effectively induce apoptosis of cells.

Ruthenium(II) polypyridyl complexes as G-quadruplex inducing and stabilizing ligands in telomeric DNA.

Two ruthenium(ii) polypyridyl complexes [Ru(phen)2(4idip)](ClO4)2 () and [Ru(bpy)2(4idip)](ClO4)2 () (phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, 4idip = 4-indoleimidazo[4,5-f][1,10]phenanthroline) designed as telomeric G-quadruplex ligands have been synthesized and characterized. The interaction of human telomeric G-quadruplex DNA (HTG21) with the designed ligands was explored by fluorescence analysis, absorption spectroscopy, continuous variation, circular dichroism spectroscopy, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay, telomerase repeat amplification protocol (TRAP), and visual studies. The results showed that both complexes could induce and stabilize different G-quadruplex structures by using a 1 : 1 [quadruplex]/[complex] binding mode ratio.

Rosuvastatin enhances the therapeutic efficacy of adipose-derived mesenchymal stem cells for myocardial infarction via PI3K/Akt and MEK/ERK pathways.

The poor viability of transplanted stem cells hampers their therapeutic efficacy for treatment of myocardial infarction. The aim of this study was to investigate whether rosuvastatin improved survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. AD-MSCs isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein were transplanted into infarcted hearts with or without rosuvastatin administration.

Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism.

Impaired cardiac microvascular function contributes to cardiovascular complications in diabetes. Glucagon-like peptide-1 (GLP-1) exhibits potential cardioprotective properties in addition to its glucose-lowering effect. This study was designed to evaluate the impact of GLP-1 on cardiac microvascular injury in diabetes and the underlying mechanism involved.

Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter.

Rationale: Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes.

Objective: The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtained by firefly luciferase and human sodium-iodide symporter labeling of cardiosphere-derived cells were investigated.

Chiral ruthenium(II) polypyridyl complexes: stabilization of g-quadruplex DNA, inhibition of telomerase activity and cellular uptake.

Two ruthenium(II) complexes, Λ-[Ru(phen)(2)(p-HPIP)](2+) and Δ-[Ru(phen)(2)(p-HPIP)](2+), were synthesized and characterized via proton nuclear magnetic resonance spectroscopy, electrospray ionization-mass spectrometry, and circular dichroism spectroscopy. This study aims to clarify the anticancer effect of metal complexes as novel and potent telomerase inhibitors and cellular nucleus target drug. First, the chiral selectivity of the compounds and their ability to stabilize quadruplex DNA were studied via absorption and emission analyses, circular dichroism spectroscopy, fluorescence-resonance energy transfer melting assay, electrophoretic mobility shift assay, and polymerase chain reaction stop assay.

The effects of luminescent ruthenium(II) polypyridyl functionalized selenium nanoparticles on bFGF-induced angiogenesis and AKT/ERK signaling.

Anti-angiogenesis is an effective strategy for cancer treatment because uncontrolled tumor growth depends on tumor angiogenesis and sufficient blood supply. Thus, blocking angiogenesis could be a strategy to arrest tumor growth. The function and mechanism of luminescent ruthenium-modified selenium nanoparticles (Ru-SeNPs) in angiogenesis have not been elucidated to date.

Adipose stromal cells amplify angiogenic signaling via the VEGF/mTOR/Akt pathway in a murine hindlimb ischemia model: a 3D multimodality imaging study.

Although adipose-derived stromal cell (ADSC) transplantation has been demonstrated as a promising therapeutic strategy for peripheral arterial disease (PAD), the mechanism of action behind the observed therapeutic efficacy of ADSCs remains unclear. This study was designed to investigate the long-term outcome and therapeutic behavior of engrafted ADSCs in a murine hindlimb ischemia model using multimodality molecular imaging approaches. ADSCs (1.

Multimodality imaging evaluation of functional and clinical benefits of percutaneous coronary intervention in patients with chronic total occlusion lesion.

Aims: To determine the effects of percutaneous coronary intervention (PCI) on cardiac perfusion, cardiac function, and quality of life in patients with chronic total occlusion (CTO) lesion in left anterior descending (LAD) coronary artery.

Methods And Results: Patients (n=99) with CTO lesion in the LAD coronary artery who had successfully undergone PCI were divided into three groups based on the SPECT/CTCA fusion imaging: (a) no severe cardiac perfusion defects (n=9); (b) reversible cardiac perfusion defects (n=40); or (c) fixed cardiac perfusion defects (n=50). No statistical difference of perfusion abnormality was observed at 6 months and 1 year after PCI in group (a).

Liver X receptor activation attenuates plaque formation and improves vasomotor function of the aortic artery in atherosclerotic ApoE(-/-) mice.

Aim: The severity of atherosclerosis is primarily determined by overall lipid metabolism and the degree of inflammation present within the vessel wall. We evaluated the effects of T-0901317, a liver X receptor agonist, on the atherosclerosis process, and especially on the endothelial function in ApoE(-/-) mice.

Methods And Results: ApoE(-/-) mice were treated with LXR agonist T-0901317 (1 μmol/L) for 6 weeks.

Effects of hepatocyte growth factor overexpressed bone marrow-derived mesenchymal stem cells on prevention from left ventricular remodelling and functional improvement in infarcted rat hearts.

Bone marrow-derived mesenchymal stem cells (BM-MSCs ) transplantation has been reported to be a promising therapy for myocardial infarction (MI). However, low survival rate of BM-MSCs in infarcted heart is one of the major limitations for the perspective clinical application. In this study, we aimed to investigate the effect of hepatocyte growth factor (HGF) on left ventricular function improvement of HGF gene-modified BM-MSCs (HGF-MSCs) after its delivery into the infarcted rat hearts.

The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice.

Aim: To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.

Methods: Db/db mice (n = 40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.

Luteolin limits infarct size and improves cardiac function after myocardium ischemia/reperfusion injury in diabetic rats.

Background: The present study was to investigate the effects and mechanism of Luteolin on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in diabetic rats with myocardial ischemia/reperfusion (I/R) injury.

Methodology/principal Findings: Diabetic rats underwent 30 minutes of ischemia followed by 3 h of reperfusion. Animals were pretreated with or without Luteolin before coronary artery ligation.

Stabilization of G-quadruplex DNA, inhibition of telomerase activity and live cell imaging studies of chiral ruthenium(II) complexes.

Telomerase inhibition is an attractive strategy for cancer chemotherapy. In the current study, we have synthesized and characterized two chiral ruthenium(II) complexes, namely, Λ-[Ru(phen)(2)(p-MOPIP)](2+) and Δ-[Ru(phen)(2)(p-MOPIP)](2+), where phen is 1,10-phenanthroline and p-MOPIP is 2-(4-methoxyphenyl)-imidazo[4,5f][1,10]phenanthroline. The chiral selectivity of the compounds and their ability to discriminate quadruplex DNA were investigated by using UV/Vis, fluorescence spectroscopy, circular dichroism spectroscopy, fluorescence resonance energy transfer melting assay, polymerase chain reaction stop assay and telomerase repeat amplification protocol.

Effect of autologous bone marrow mononuclear cells transplantation in diabetic patients with ST-segment elevation myocardial infarction.

Background: To investigate the efficacy and proposed mechanism of bone marrow mononuclear cells (BMMNCs) transplantation for diabetic and non-diabetic patients with ST-segment elevation myocardial infarction (STEMI).

Methods: One hundred and sixteen patients with STEMI who had successfully undergone percutaneous coronary intervention (PCI) were divided into a diabetic group (n=51) and non-diabetic group (n=65). All of the patients received intracoronary injection of BMMNCs.

Effects of ghrelin on homocysteine-induced dysfunction and inflammatory response in rat cardiac microvascular endothelial cells.

Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs.