The Rotator Cuff and the Superior Capsule: Why We Need Both.

Tears of the rotator cuff are frequent. An estimated 250,000 to 500,000 repairs are performed annually in the United States. Rotator cuff repairs have been successful despite fatty infiltration and atrophy of the rotator cuff muscles.

Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart.

Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation.

A New Method to Stabilize C-Kit Expression in Reparative Cardiac Mesenchymal Cells.

Cell therapy improves cardiac function. Few cells have been investigated more extensively or consistently shown to be more effective than c-kit sorted cells; however, c-kit expression is easily lost during passage. Here, our primary goal was to develop an improved method to isolate c-kit(pos) cells and maintain c-kit expression after passaging.

Induction of activating transcription factor 3 limits survival following infarct-induced heart failure in mice.

Numerous fibrotic and inflammatory changes occur in the failing heart. Recent evidence indicates that certain transcription factors, such as activating transcription factor 3 (ATF3), are activated during heart failure. Because ATF3 may be upregulated in the failing heart and affect inflammation, we focused on the potential role of ATF3 on postinfarct heart failure.

MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.

Derangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown.

Metabolomic analysis of pressure-overloaded and infarcted mouse hearts.

Background: Cardiac hypertrophy and heart failure are associated with metabolic dysregulation and a state of chronic energy deficiency. Although several disparate changes in individual metabolic pathways have been described, there has been no global assessment of metabolomic changes in hypertrophic and failing hearts in vivo. Hence, we investigated the impact of pressure overload and infarction on myocardial metabolism.

High fat feeding in mice is insufficient to induce cardiac dysfunction and does not exacerbate heart failure.

Preclinical studies of animals with risk factors, and how those risk factors contribute to the development of cardiovascular disease and cardiac dysfunction, are clearly needed. One such approach is to feed mice a diet rich in fat (i.e.

Cardiomyocyte Ogt is essential for postnatal viability.

The singly coded gene O-linked-β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt) resides on the X chromosome and is necessary for embryonic stem cell viability during embryogenesis. In mature cells, this enzyme catalyzes the posttranslational modification known as O-GlcNAc to various cellular proteins. Several groups, including our own, have shown that acute increases in protein O-GlcNAcylation are cardioprotective both in vitro and in vivo.

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells.

Cranberry extracts may provide beneficial health effects in the treatment of various diseases, including cancer. However, the underlying molecular mechanisms of antineoplastic properties are not understood. We report the effect of a proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1) as a therapeutic agent with dual activity to target both ovarian cancer viability and angiogenesis in vitro.

Oral RKS262 reduces tumor burden in a neuroblastoma xenograft animal model and mediates cytotoxicity through SAPK/JNK and ROS activation in vitro.

Patients diagnosed with high-risk neuroblastoma (NB), an extracranial solid tumor in children, have metastases and low survival (30%) despite aggressive multi-modal therapy. Therefore new therapies are urgently needed. We show significant in vitro and in vivo antitumor efficacy of RKS262 in NB.