With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.
The effects of an ice wrap, applied to a knee for 20 minutes, on blood flow and bone metabolism were measured using triple-phase technetium bone scans. Twenty-one subjects between 29 and 63 years of age were studied. A commercially available ice wrap was applied to one knee 20 minutes before scanning, while an identical wrap left at room temperature was applied to the opposite knee to act as a control. Scans of the knees were obtained at the completion of cooling, and the images were quantified by computer image analysis for each knee at each phase of the scan. Percentage of decrease in blood flow and subsequent bone uptake of technetium for the iced knee as compared with the opposite knee were calculated. All iced knees demonstrated decreased arterial and soft tissue blood flow as well as decreased bone uptake, which is a reflection of changes in both bone blood flow and metabolism. The average decrease was 38.4% +/- 4.97 in arterial blood flow, 25.8% +/- 2.04 in soft tissue blood flow, and 19.3% +/- 2.0 (standard error of the mean in each) in bone uptake. This "ice effect" was not related to age, sex, knee circumference, or skin temperature after cooling. By decreasing blood flow and cell metabolism, ice theoretically can limit hemorrhage and cell death in the setting of acute traumatic injury. This study thus provides a scientific rationale for the use of ice as tested for such injuries to a large joint, whether in the soft tissues or bones.
While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.
In a previous study we used technetium-99m bone scans to show that cooling a knee for 20 minutes with a standard ice wrap will decrease soft tissue blood flow by a mean of 26%, and skeletal blood flow and metabolism by 19%. The present study examined the effects of shorter and longer icing periods to determine minimum cooling time for a measurable and consistent decrease, and time to produce maximal decrease within a safe period of icing (< 30 minutes). Thirty-eight subjects were studied. An ice wrap was applied to one knee for an assigned time (5, 10, 15, 20, or 25 minutes). Triple-phase bone scans of knees were obtained; mean percentages of decrease in the iced knee for each of the five time groups at each of the three phases of the bone scan were calculated and compared. Mean decreases of 11.1% in soft tissue blood flow, and 5.1% in skeletal metabolism and blood flow were measured at 5 minutes; maximums of 29.5% and 20.9%, respectively, were obtained at 25 minutes. A small but consistent decrease in soft tissue blood flow and skeletal blood flow and metabolism in a knee appear to be obtained with as little as 5 minutes of ice application. This effect is time-dependent and can be enhanced three- to four-fold by increasing the ice application time to 25 minutes.
Notch is a cell–cell signaling pathway that is involved in a host of activities including development, oncogenesis, skeletal homeostasis, and much more. More specifically, recent research has demonstrated the importance of Notch signaling in osteogenic differentiation, bone healing, and in the development of the skeleton. The craniofacial skeleton is complex and understanding its development has remained an important focus in biology. In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton, skull, and face develop. We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system, and what importance it may play in the future.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.