Abstract: Developing effective therapies for serious neurological insults remains a major challenge for biomedical research. Despite intense efforts, the ability to promote functional recovery after contusion injuries, ischemic insults, or the onset of neurodegenerative diseases in the brain and spinal cord remains very limited even while the need for such therapies is increasing with an aging population. Recent studies suggest that cellular therapies utilizing mesenchymal stem cells (MSCs) may provide a functional benefit in a wide range of neurological insults. MSCs derived from a variety of tissue sources have been therapeutically evaluated in animal models of stroke, spinal cord injury, and multiple sclerosis. In each situation, treatment with MSCs results in substantial functional benefit and these pre-clinical studies have led to the initiation of a number of clinical trials worldwide in neural repair. ... Read more

Abstract: The idea of promoting angiogenesis in ischemic tissues remains an undisputed therapeutic approach for the treatment of myocardium and skeletal muscles that lack sufficient blood supply. However, clinical experiences from several large trials indicated that delivery of proangiogenic factors to patients suffering from myocardial infarction and leg ischemia has not shown significant benefits. Despite continuous success in various animal disease models, why has this simple principle not shown proof of concept in patients? What has been missing in the trial deign? What are the differences between animal models and patients? What are the optimal components for promoting functional collateral networks? This brief review discusses molecular mechanisms underlying arteriogenesis and proposes novel approaches for improvement of therapeutic outcomes. ... Read more

Abstract: Human gene therapy has made substantial progress since the initiation of the first clinical trials 20 years ago. Here, we summarized important applications of gene transfer protocols in the treatment of various human diseases using different viral vectors. Recent successful trials on the treatment of ocular diseases and inherited immune deficiencies are particularly encouraging and have raised hopes that human gene therapy as a standard treatment option will finally become a reality. While immune responses and insertional mutagenesis pose obstacles for this novel form of molecular medicine, continuous progress suggests that a wider range of diseases can be treated with gene therapy in the future. ... Read more

Abstract: Anti-platelet drugs play a key role in cardiovascular medicine since the introduction of aspirin as an anti-thrombotic agent some 50 years ago. After many years of a "monopoly" of aspirin, ADP receptor P2Y12 inhibitors were introduced with a significant improvement in clinical outcome. Nowadays dual anti-platelet therapy is the common practice for both acute events and secondary prevention in selected groups of patients. The improved efficacy of multiple drug therapy is associated with an increased risk of bleeding, which raises the issue of the dosing of these drugs. Recently, numerous studies have reported a variable laboratory response to aspirin and clopidogrel, which correlates with clinical outcome. Several mechanisms for causing this variable response have been proposed, including genetic variability, disease burden, and others. A major obstacle in this field is the lack of a standardized method for testing these responses. New drugs are currently under different stages of development, including new P2Y12 receptors inhibitors, thrombaxane receptor blockers, direct thrombin inhibitors, and inhibitors for other signaling pathways including oral GPIIbIIIa inhibitors. Thus anti-platelet therapy is currently under intensive developments toward multiple drug therapy and personal dose adjustment, which may improve clinical outcome. ... Read more

Abstract: Vitamin K antagonists (VKA), such as warfarin, have been the only available oral anticoagulants despite their many limitations. The greatest medical need is to find a replacement for warfarin for long-term therapy, particularly for stroke prevention in atrial fibrillation (AF) patients. Emerging oral anticoagulants are free from many of warfarin's drawbacks and may offer a convenient alternative. Drugs in advanced development target factor Xa (rivaroxaban, apixaban) or thrombin (dabigatran etexilate). Recently, the RE-LY phase III study found dabigatran etexilate was an effective and convenient alternative to warfarin in stroke prevention for AF patients. Within the next two years, similar studies comparing rivaroxaban and apixaban versus warfarin in AF patients will become available. This paper reviews warfarin's limitations, discusses the pharmacokinetics of emerging anticoagulants in advanced development, and summarizes trials with an emphasis on head-to-head studies comparing novel anticoagulants to warfarin. ... Read more

Abstract: Interleukin-21 (IL-21), a cytokine produced by activated CD4+ T cells, activated natural killer T cells, and T follicular cells, has been reported to play a crucial role in the tissue-damaging T cell response in various organs, such as gut, skin, pancreas, and joints. This pathogenic effect is strictly linked to the ability of IL-21 to enhance the functional activities of multiple immune and non-immune cells. Consistently, studies from various laboratories have shown that blockade of IL-21 limits the progression of T cell-mediated inflammatory diseases in mice. Here we review the present knowledge on the expression and role of IL-21 in T cell-mediated pathologies. ... Read more

Abstract: Hemophilia A is an X-linked bleeding disorder caused by defective coagulation Factor VIII (FVIII). Although the efficacies of existing treatment using purified or recombinant FVIII are good, there remain shortcomings in using this particular form of treatment. A few FVIII gene therapy clinical trials have been initiated with modest improvements recorded, but these are no longer being continued due to insufficient efficacy. However, with the progress in the development of gene delivery vectors and the availability of mouse and canine hemophilia A models, gene therapy of hemophilia A remains an area of hot pursuit. ... Read more

Abstract: There are defined windows of opportunities during which stroke can be treated. Various clinical trials testing a variety of drugs and the overall management of stroke are discussed. ... Read more

Abstract: Pulmonary hypertension is a disease that eventually leads to lung and/or heart failure. Because the causes were largely unknown, it has been called "idiopathic" pulmonary hypertension. Armed with new research tools and technologies, such as genetic and genomic analyses, scientists are now uncovering the causes and pathogenesis of the disease. New understandings of mechanisms of the disease are summarized. ... Read more

Stem cells modulate tissue formation and repair based on a complex interaction of cell autonomous and non-autonomous regulatory mechanisms. While reductionist approaches to understanding stem cell control continue to be extremely productive, understanding the physiological contexts in which stem cells function, will ultimately require definition of the microenvironments in which they live. The location of stem or precursor populations within numerous solid tissues has been described, but delineating specific associated cells and how they participate in regulating stem cell function has generally been lacking for mammalian tissues. However, the use of invertebrate-based models has created particularly productive systems in which ... Read more