KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Plasticity is a hallmark of cells of the myelomonocytic lineage. In response to innate recognition or signals from lymphocyte subsets, mononuclear phagocytes undergo adaptive responses. Shaping of monocyte-macrophage function is an essential component of resistance to pathogens, tissue damage and repair. The orchestration of myelomonocytic cell function is a key element that links inflammation and cancer and provides a paradigm for macrophage plasticity and function. A better understanding of the molecular basis of myelomonocytic cell plasticity will open new vistas in immunopathology and therapeutic intervention.

Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm

The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.

Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease

Review of recent research on hepatitis C therapy for 54th annual meeting of the American association for the study of liver diseases

There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.

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Mechanisms of NAFLD development and therapeutic strategies

An intravascular ultrasound (IVUS) and microbubble drug delivery system was evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the fluorophore DiI embedded in the shell as a model drug were infused into ex vivo swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen to the wall, followed by higher-intensity delivery pulses to release DiI into the vessel wall. Insonation with both the acoustic radiation force pulse and the delivery pulse increased DiI deposition 10-fold compared with deposition with the delivery pulse alone. Localized delivery of DiI was then demonstrated in an in vivo swine model. The theoretical transducer beam width predicted the measured angular extent of delivery to within 11%. These results indicate that low-frequency IVUS catheters are a viable method for achieving localized drug delivery with microbubbles.

/pdf/localized-in-vivo-model-drug-delivery-with-intravascular-2zeyyks1b8.pdf

Localized in vivo model drug delivery with intravascular ultrasound and microbubbles.

Substantial evidence exists supporting the role of chronic exercise in reducing the incidence and severity of coronary vascular disease. Physical inactivity is an independent risk factor for coronary heart disease suggesting that the cardioprotective effect of exercise is due, in part, to an intrinsic adaptation within the coronary vasculature. Surprisingly, a paucity of information exists regarding the intrinsic cellular changes within the coronary vasculature associated with exercise training and even less is known regarding the effect of physical activity on long-term phenotypic modulation of coronary smooth muscle (CSM). The purpose of this symposium is to provide a concise update on the current knowledge regarding CSM adaptation to exercise training and the potential for these adaptations to contribute to exercise-induced cardioprotection. The potential role of CSM in exercise-induced cardioprotection will be approached from two perspectives. First, endurance exercise training effects on the regulation of coronary vasomotor tone via changes in CSM calcium regulation will be reviewed, i.e. short-term functional adaptation. Secondly, we will discuss potential long-term consequences of this altered calcium regulation, i.e. exercise-induced phenotypic modulation of CSM. We propose that exercise training alters CSM intracellular calcium regulation to reduce Ca2+-dependent activation of the contractile apparatus and Ca2+-dependent gene transcription and increase activation of sarcolemmal potassium channels. The overall effect is to increase the gain of the vasomotor system and maintain a stable, contractile CSM phenotype.

Coronary smooth muscle adaptation to exercise: does it play a role in cardioprotection?

Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes

The present invention relates generally to medical devices with therapy eluting components and methods for making same. More specifically, the invention relates to implantable medical devices having at least one porous layer, and methods for making such devices, and loading such devices with therapeutic agents. A mixture or alloy is placed on the surface of a medical device, then one component of the mixture or alloy is generally removed without generally removing the other components of the mixture or alloy. In some embodiments, a porous layer is adapted for bonding non-metallic coating, including drug eluting polymeric coatings. A porous layer may have a random pore structure or an oriented or directional grain porous structure. One embodiment of the invention relates to medical devices, including vascular stents, having at least one porous layer adapted to resist stenosis or cellular proliferation without requiring elution of therapeutic agents. The invention also includes methods, devices, and specifications for loading of drugs and other therapeutic agents into nanoporous coatings.

Medical devices with nanoporous layers and topcoats

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2007.01.069

Brian R. Wamhoff

Papers

Localized in vivo model drug delivery with intravascular ultrasound and microbubbles.

Coronary smooth muscle adaptation to exercise: does it play a role in cardioprotection?

Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes

Medical devices with nanoporous layers and topcoats

RNA interference targeting α8 integrin attenuates smooth muscle cell growth