Tracking and protection of transplanted stem cells using a ferrocenecarboxylic acid-conjugated peptide that mimics hTERT.

In vivo tracking of transplanted stem cells has been a central aim of stem cell therapy. Although many tracking systems have been introduced, no method has yet been validated for clinical applications. We developed a novel sophisticated peptide (GV1001) that mimics hTERT (human telomerase reverse transcriptase) and analysed its ability to track and protect stem cells after transplantation.

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage.

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth.

Neuroprotective Effects of an Erythropoietin-Derived Peptide in PC1 2 Cells under Oxidative Stress.

Erythropoietin (EPO) has been shown to be a key cytokine in the production of erythrocytes from erythroblasts. Recently, attempts have been made to adopt EPO as a drug target for neuroprotection in selected neurological pathologies. In the current study, a novel EPO-derived peptide which mimics the weak binding site of EPO to its receptor (MK-X) was generated.

Neuroprotective Effects of an Erythropoietin-Derived Peptide in PC12 Cells under Oxidative Stress.

Erythropoietin (EPO) has been shown to be a key cytokine in the production of erythrocytes from erythroblasts. Recently, attempts have been made to adopt EPO as a drug target for neuroprotection in selected neurological pathologies. In the current study, a novel EPO-derived peptide which mimics the weak binding site of EPO to its receptor (MK-X) was generated.

Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis.

Unlabelled: Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled.

Recombinant human erythropoietin in amyotrophic lateral sclerosis: a pilot study of safety and feasibility.

Background And Purpose: It has been shown that erythropoietin is neuroprotective in animal models of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The aim of this study was to determine the safety and feasibility of repetitive high-dose recombinant human erythropoietin (rhEPO) therapy in ALS patients.

Methods: Two consecutive studies were conducted.

Identification of peptides that selectively bind to myoglobin by biopanning of phage displayed-peptide library.

Biopanning of phage displayed-peptide library was performed against myoglobin, a marker for the early assessment of acute myocardial infarction (AMI), to identify peptides that selectively bind to myoglobin. Using myoglobin-conjugated magnetic beads, phages that bound to myoglobin were collected and amplified for the next round of screening. A 148-fold enrichment of phage titer was observed after five rounds of screening relative to the first round.

In vivo imaging of myocardial cell death using a peptide probe and assessment of long-term heart function.

During acute myocardial infarction (AMI), both apoptosis and necrosis of myocardial cells could occur and lead to left ventricular (LV) functional decline. Here we determined whether in vivo imaging signals of myocardial cell death by ApoPep-1 (CQRPPR), a peptide probe that binds to apoptotic and necrotic cells through histone H1, at an early stage after AMI showed correlation with the long-term heart function. AMI was induced using a rat model of ischemia and reperfusion (I/R) injury.

Differential cell death and Bcl-2 expression in the mouse retina after glutathione decrease by systemic D,L-buthionine sulphoximine administration.

Glutathione (GSH) plays a critical role in cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH decrease using [D, L]-buthionine sulphoximine (BSO) induces retinal cell death, but the underlying mechanisms of this are still unclear. Here, we demonstrated that retinal GSH level is closely related to retinal cell death as well as expression of an anti-apoptotic molecule, Bcl-2, in the retina.

Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear.

Exendin-4 protects against sulfonylurea-induced β-cell apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear.

The plasma membrane redox enzyme NQO1 sustains cellular energetics and protects human neuroblastoma cells against metabolic and proteotoxic stress.

The plasma membrane redox system (PMRS) of nicotinamide adenine dinucleotide (NADH)-related enzymes plays a key role in the maintenance of cellular energetics. During the aging process, neural cells are particularly sensitive to impaired energy metabolism and oxidative damage, but the involvement of the PMRS in these processes is unknown. Here, we used human neuroblastoma cells with either elevated or reduced levels of the PMRS enzyme NADH-quinone oxidoreductase 1 (NQO1) to investigate how the PMRS regulates neuronal stress responses.

Protective effect of aminophylline against cigarette smoke extract-induced apoptosis in human lung fibroblasts (MRC-5 cells).

Cigarette smoking is the principal cause of chronic obstructive pulmonary disease (COPD), especially emphysema, which is characterized by alveolar wall destruction and airspace enlargement. Apoptosis of lung structural cells is involved in the pathogenesis of COPD. Xanthine derivatives (aminophylline or theophylline) have been used for the treatment of COPD as a bronchodilator.

Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

Background: Recent studies have shown that erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling exist in both human and mouse hair follicles (HFs).

Objective: To investigate whether dermal papilla cells (DPCs) express functional EPOR and, if so, to investigate effects of EPO on hair shaft growth in cultured human scalp hair follicles and hair growth in mice.

Methods: EPOR expression in DPCs and follicular keratinocytes was examined by RT-PCR and immunoblot.

Extracellular signal-regulated kinase (ERK) inhibition attenuates cigarette smoke extract (CSE) induced-death inducing signaling complex (DISC) formation in human lung fibroblasts (MRC-5) cells.

Cigarette smoke (CS), a major risk factor in emphysema, causes cell death by incompletely understood mechanisms. Death-inducing signaling complex (DISC) formation is an initial event in Fas-mediated apoptosis. We demonstrated cigarette smoke extract (CSE) induced DISC formation in human lung fibroblasts (MRC-5).

The pro-angiogenic cytokine pleiotrophin potentiates cardiomyocyte apoptosis through inhibition of endogenous AKT/PKB activity.

Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated.

Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats.

Background: Systemic application of recombinant human erythropoietin (rhEPO) greatly limits cardiac tissue damage and attenuates left ventricular (LV) remodeling after experimentally induced myocardial infarction (MI). However, multiple injections of rhEPO stimulate red blood cell production and elevate the hematocrit (Htc), which might negatively affect the outcome of acute MI. We compared the outcome of experimental MI in rats treated with a single or multiple doses of rhEPO.

Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties.

Erythropoietin (EPO), a hematopoietic cytokine, possesses strong antiapoptotic, tissue-protective properties. For clinical applications, it is desirable to separate the hematopoietic and tissue-protective properties. Recently introduced carbamylated erythropoietin (CEPO) does not stimulate the erythropoiesis but retains the antiapoptotic and neuroprotective effects.

Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window.

Background: Recombinant human erythropoietin (rhEPO) protects tissue from ischemic damage, but translation of this finding into useful guidelines with respect to human trials for myocardial infarction (MI) requires a determination of the minimum effective rhEPO dose and the therapeutic window following MI.

Method And Results: Serial echocardiography revealed that during four weeks following MI, induced by a permanent coronary ligation in rats, the LV end-diastolic and end-systolic volumes in untreated rats expanded from 0.35 +/- 0.

Beneficial effects of chronic pharmacological manipulation of beta-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy.

Background: Studies in isolated cardiac myocytes have demonstrated that signaling via specific beta1-adrenergic receptor subtypes (beta1ARs) promotes but that signaling via beta2ARs protects from cell death. We hypothesized that prolonged beta(2)AR stimulation or beta1AR blockade would each protect myocytes from death and thereby ameliorate cardiac remodeling in chronic heart failure.

Methods And Results: A large myocardial infarction (MI) induced in rats by coronary artery ligation resulted in a dilated cardiomyopathy (DCM) characterized by infarct expansion and a progressive increase in left ventricular (LV) end-diastolic volume, accompanied by a reduction in ejection fraction (EF), as assessed by repeated echocardiography.

Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in C57BL/6 mice.

The ability to create experimental myocardial infarctions of reproducible size and location is tantamount to progress in multiple facets of ischemic heart disease research. Branches of the mouse left main descending coronary artery penetrate the myocardium close to their origin and require "blind" ligation. Our objective was to develop a technique for ligation of nonvisible coronary artery branches to permit the reliable creation of infarcts of uniformly small size and location.

Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats.

Erythropoietin (EPO), well known for its role in stimulation of erythropoiesis, has recently been shown to have a dramatic neuroprotective effect in animal models of cerebral ischemia, mechanical trauma of the nervous system, and excitotoxins, mainly by reducing apoptosis. We studied the effect of single systemic administration of recombinant human EPO (rhEPO) on left ventricular (LV) size and function in rats during 8 weeks after the induction of a myocardial infarction (MI) by permanent ligation of the left descending coronary artery. We found that an i.

Distribution of adenoviral vector in brain after intravenous administration.

The delivery of transgenes to the central nervous system (CNS) can be a valuable tool to treat CNS diseases. Various systems for the delivery to the CNS have been developed; vascular delivery of viral vectors being most recent. Here, we investigated gene transfer to the CNS by intravenous injection of recombinant adenoviral vectors, containing green fluorescence protein (GFP) as a reporter gene.

Plunc, a member of the secretory gland protein family, is up-regulated in nasal respiratory epithelium after olfactory bulbectomy.

Subtraction suppression hybridization was used with high throughput screening to identify transcripts of genes that are differentially expressed in nasal epithelium following lesioning of the olfactory bulb, termed bulbectomy. We isolated the rat homologue of plunc, a murine gene highly expressed in lung and nasopharyngeal regions, by this method. Rat plunc encodes a 270-amino acid protein containing a putative signal peptide.