To investigate the role of JNK1 in metabolism, male ob/ob and diet-induced obese mice were treated with a JNK1-specific antisense oligonucleotide (ASO) or control ASO at 25 mg/kg or saline twice/wk for 6 and 7 wk, respectively. JNK1 ASO reduced JNK1 mRNA and activity by 65-95% in liver and fat tissues in both models. Compared with controls, treatment with JNK1 ASO did not change food intake but...

Increasing survival of motor neuron 2, centromeric (SMN2) exon 7 inclusion to express more full-length SMN protein in motor neurons is a promising approach to treat spinal muscular atrophy (SMA), a genetic neurodegenerative disease. Previously, we identified a potent 2'-O-(2-methoxyethyl) (MOE) phosphorothioate-modified antisense oligonucleotide (ASO) that blocks an SMN2 intronic splicing silen...

Purpose: Lipid nanoparticle (LNP) formulations facilitate tumor uptake and intracellular processing through an enhanced permeationand retentioneffect (EPR), and currentlymultipleproducts are undergoing clinical evaluation. Clusterin (CLU) is a cytoprotective chaperone induced by androgen receptor (AR) pathway inhibition to facilitate adaptive survival pathway signaling and treatment resistance....

Vascular endothelial growth factor (VEGF) strongly promotes angiogenesis, and monocyte-colony stimulating factor (M-CSF) regulates the differentiation, proliferation, and survival of monocytes. Both VEGF and M-CSF are expressed in atherosclerotic lesions. The present study was performed to clarify the role of VEGF and M-CSF in the development of peripheral artery disease (PAD). The serum VEGF a...

BACKGROUND Congenital heart disease consumes significant health care resources; however, there are limited data regarding factors affecting resource utilization. The purpose of this study was to evaluate variation between centers in total hospital costs for 4 congenital heart operations of varying complexity and associated factors. METHODS AND RESULTS The Premier Database was used to evaluate...

Fasting hyperglycemia, a prominent finding in diabetes, is primarily due to increased gluconeogenesis. The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. Synthetic, optimized antisense oligonucleotides (ASOs) specifically inhibit Foxo1 expression. He...

BACKGROUND Coronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfus...

INTRODUCTION Percutaneous closure of atrial septal defects (ASD) is becoming more frequent. PATIENTS AND METHOD From October 1997 to October 2002, 209 patients, age 0.4-70 (mean 19.5) years, were catheterized to close an ASD or patent foramen ovale (PFO). Transesophageal echocardiography was performed simultaneously in all patients. Two hundred and six patients had ASD (25 multiple ASDs) and ...

We hereby report a child with transposition of great arteries and regressed ventricle who underwent arterial switch operation (ASO) with the aid of cardiopulmonary bypass and "integrated" extracorporeal membrane oxygenation (ECMO) circuit. The significance of lactate clearance as a guide to initiate and terminate veno-arterial ECMO in a post ASO child with regressed left ventricle is discussed.

PURPOSE A wide variety of tumors depend on the dysregulation of Bcl-2 family proteins for survival. The resulting apoptotic block can often provide a mechanism for resistance to anticancer treatments, such as chemotherapy and radiation. This current study evaluates the efficacy of combining systemically delivered Bcl-2 phosphorothioate antisense (Bcl-2 ASO) and radiation for nasopharyngeal canc...