Without delicate postoperative management to control pulmonary vascular resistance, the modified Norwood procedure using the right ventricle-pulmonary shunt provides a stable systemic circulation as well as adequate pulmonary blood flow. This novel operation may be particularly beneficial to low-birth-weight infants with hypoplastic left heart syndrome.

Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has been significantly advanced in the past two decades. The approval of Patisiran (ONPATTRO™) for the treatment of transthyretin-mediated amyloidosis, the first approved siRNA drug, is a most important milestone. Since lipid-based nanoparticles (LNPs) are used in Patisiran, LNP-based siRNA delivery is now of significant interest for the development of the next siRNA formulation. In this review, we describe the design of LNPs for the improvement of siRNA properties, bioavailability, and pharmacokinetics. Recently, a number of siRNA-encapsulated LNPs were reported for the treatment of intractable diseases such as cancer, viral infection, inflammatory neurological disorder, and genetic diseases. We believe that these contributions address and will promote the development of an effective LNP-based siRNA delivery system and siRNA formulation.

An infusion as PEGylated liposomes augmented the cardioprotective effects of adenosine against ischemia/reperfusion injury and reduced its unfavorable hemodynamic effects. Liposomes are promising for developing new treatments for acute MI.

Abstract:Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood-retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/ nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.

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Abstract-Mammalian myocardial infarction is typically followed by scar formation with eventual ventricular dilation and heart failure. Here we present a novel model system in which mice constitutively expressing cyclin A2 in the myocardium elicit a regenerative response after infarction and exhibit significantly limited ventricular dilation with sustained and remarkably enhanced cardiac function. New cardiomyocyte formation was noted in the infarcted zones as well as cell cycle reentry of periinfarct myocardium with an increase in DNA synthesis and mitotic indices. The enhanced cardiac function was serially assessed over time by MRI. Furthermore, the constitutive expression of cyclin A2 appears to augment endogenous regenerative mechanisms via induction of side population cells with enhanced proliferative capacity. Key Words: cyclin A2 Ⅲ cardiac regeneration Ⅲ side-population cells Ⅲ heart failure Ⅲ cell cycle N ormal adaptive mechanisms in response to myocardial infarction (MI) commence with scar formation in the damaged wall progressing to hypertrophy of the unaffected regions which ultimately succumbs to ventricular dilation and heart failure. 1 Stem cell therapy to restore infarcted myocardium has been extensively studied, with numerous reports that hematopoietic 2,3 and mesenchymal 4 stem cells derived from bone marrow (BMCs) can give rise to new myocardium via transdifferentiation. This in turn has rapidly translated into a whirlwind of clinical activity aimed at duplicating these effects in the human heart. 5-8 However, 3 recent studies 9 -11 have rigorously challenged the conclusions of these reports by independently demonstrating that BMCs transplanted into damaged hearts could not give rise to cardiomyocytes. Balsam et al 9 have shown that not only do BMCs fail to give rise to cardiomyocytes, they actually develop into different blood cell types, despite being in the heart. The beneficial effects noted in earlier studies in terms of ventricular performance might be partially attributable to angioblast-mediated vasculogenesis 12 which could prevent apoptosis of native cardiomyocytes rather than by direct myogenesis.Given these limitations in BMCs, the search for naturally occurring authentic heart progenitor cells has begun in earnest, with several groups having reported on the existence of such cells. [13][14][15][16][17] These native progenitors are, at their naturally occurring prevalence and levels of activation, clearly inadequate in reversing the downward spiral of events culminating in heart failure. Their differentiation in response to environmental cues might be expected to generate cardiomyocytes of a postmitotic nature, hence limiting the ability of such endogenous processes to counter the massive myocyte death in MI.We have previously developed a model system in which constitutive expression of cyclin A2 in the myocardium led to an increase in cardiomyocyte mitoses, particularly during postnatal development. 18 The increase in postnatal mitoses was also accompanied by the presence of mononuc...

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Cancer chemotherapy targeted to angiogenic vessels is expected to cause indirect tumor regression through the damage of the neovasculature without the induction of drug resistance. To develop a tool for neovasculaturespeci®c drug delivery, we isolated novel peptides homing to angiogenic vessels formed by a dorsal air sac method from a phage-displayed peptide library. Three distinct phage clones that markedly accumulated in murine tumor xenografts presented PRPGAPLAGSWPGTS-, DRWRPALPVVLFPLH-or ASSSYPLIHWRPWARpeptide respectively. After the determination of the epitope sequences of these peptides, we modi®ed liposomes with epitope penta-peptides. Liposome modi®ed with APRPG-peptide showed high accumulation in murine tumor xenografts, and APRPG-modi®ed liposome encapsulating adriamycin eectively suppressed experimental tumor growth. Finally, speci®c binding of APRPG-modi®ed liposome to human umbilical endothelial cells, and that of PRP-containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor and glioblastoma, were demonstrated. The present study indicates the usefulness of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of cancer treatment.