Retinoblastoma associated with orbital pseudocellulitis and high-risk retinoblastoma: a study of 32 eyes

International Ophthalmology - To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. Retrospective study of 32 patients...     

Reduced Cardiovascular Risk Following Bariatric Surgeries is Related to a Partial Recovery from “Adiposopathy”

Background  

Altered cytokine secretion from dysfunctional adipose tissue or “adiposopathy” is implicated in obesity related inflammation and may mediate reduced cardiovascular disease (CVD) risk in response to weight loss after bariatric surgery. We hypothesized that bariatric surgery reduces CVD risk by favorably altering the pro-inflammatory profile of adipose tissue as a result of weight loss.     

Crosslinguistic semantic and translation priming in normal bilingual individuals and bilingual aphasia

The present study examined lexical representation in early Spanish-English bilinguals using an unmasked semantic and translation priming paradigm. In Experiment 1, participants were divided into two groups based on performance (more-balanced bilinguals, MB and less-balanced bilinguals, LB) on the experimental task. In Experiment 2, four patients with bilingual aphasia (BA) performed the same experiment. Results from both experiments revealed that all groups were more accurate for English targets (S-E direction) than Spanish targets (S-E direction). In Experiment 1, semantic priming was observed from English to Spanish in both the LB and MB groups although the effect was greater for the LB group. Further, only the LB group showed priming from Spanish to English. For both normal groups, there was no difference between translation and semantic priming effects. In Experiment 2, patients with bilingual aphasia demonstrated different patterns of activation with no clear trends. Two participants demonstrated greater priming from Spanish to English whereas two participants demonstrated the opposite effect.     

Regulation of endothelial cell activation and angiogenesis by injectable peptide nanofibers

RAD16-II peptide nanofibers are promising for vascular tissue engineering and were shown to enhance angiogenesis in vitro and in vivo, although the mechanism remains unknown. We hypothesized that the pro-angiogenic effect of RAD16-II results from low-affinity integrin-dependent interactions of microvascular endothelial cells (MVECs) with RAD motifs. Mouse MVECs were cultured on RAD16-II with or without integrin and MAPK/ERK pathway inhibitors, and angiogenic responses were quantified. The results were validated in vivo using a mouse diabetic wound healing model with impaired neovascularization. RAD16-II stimulated spontaneous capillary morphogenesis, and increased β₃ integrin phosphorylation and VEGF expression in MVECs. These responses were abrogated in the presence of β₃ and MAPK/ERK pathway inhibitors or on the control peptide without RAD motifs. Wide-spectrum integrin inhibitor echistatin completely abolished RAD16-II-mediated capillary morphogenesis in vitro and neovascularization and VEGF expression in the wound in vivo. The addition of the RGD motif to RAD16-II did not change nanofiber architecture or mechanical properties, but resulted in significant decrease in capillary morphogenesis. Overall, these results suggest that low-affinity non-specific interactions between cells and RAD motifs can trigger angiogenic responses via phosphorylation of β₃ integrin and MAPK/ERK pathway, indicating that low-affinity sequences can be used to functionalize biocompatible materials for the regulation of cell migration and angiogenesis, thus expanding the current pool of available motifs that can be used for such functionalization. Incorporation of RAD or similar motifs into protein engineered or hybrid peptide scaffolds may represent a novel strategy for vascular tissue engineering and will further enhance design opportunities for new scaffold materials.     

Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury

Ischemic heart disease is a leading cause of death, with few options to retain ventricular function following myocardial infarction. Hematopoietic-derived progenitor cells contribute to angiogenesis and tissue repair following ischemia reperfusion injury. Motivated by the role of bone marrow extracellular matrix (BM-ECM) in supporting the proliferation and regulation of these cell populations, we investigated BM-ECM injection in myocardial repair. In BM-ECM isolated from porcine sternum, we identified several factors important for myocardial healing, including vascular endothelial growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-BB. We further determined that BM-ECM serves as an adhesive substrate for endothelial cell proliferation. Bone marrow ECM was injected in a rat model of myocardial infarction, with and without a methylcellulose carrier gel. After one day, reduced infarct area was noted in rats receiving BM-ECM injection. After seven days we observed improved fractional shortening, decreased apoptosis, and significantly lower macrophage counts in the infarct border. Improvements in fractional shortening, sustained through 21 days, as well as decreased fibrotic area, enhanced angiogenesis, and greater c-kit-positive cell presence were associated with BM-ECM injection. Notably, the concentrations of BM-ECM growth factors were 10(3)-10(8) fold lower than typically required to achieve a beneficial effect, as reported in pre-clinical studies that have administered single growth factors alone.     

Cell behavior on a CCN1 functionalized elastin-mimetic protein polymer

We report the design of an elastin-mimetic triblock copolymer with the ability to guide endothelial cell adhesion, spreading, and migration while maintaining the elastomeric properties of the protein polymer. The V2 ligand sequence from matricellular protein CCN1 (cysteine-rich 61, CYR61) was multimerized and cloned into elastin polymer LysB10, creating LysB10.V2. Cell adhesion studies demonstrated that a LysB10.V2 surface density of at least 40 pmol/cm² was required to elicit cell attachment. Peptide blocking studies confirmed V2 specific engagement with integrin receptor α_vβ₃ (P < 0.05) and we observed the formation of actin stress fiber networks and vinculin clustering, characteristic of focal adhesion assembly. Haptotatic migration assays demonstrated the ability of LysB10.V2 surfaces to stimulate migration of endothelial cells (P < 0.05). Significantly, we illustrated the ability of LysB10.V2 to support a quiescent endothelium. The CCN1 molecule functions to support many key biological processes necessary for tissue repair and thus presents a promising target for bioengineering applications. Collectively, our results demonstrate the potential to harness CCN1 specific function in the design of new scaffold materials for applications in regenerative medicine.