Notes

Adenosine-induced transient blood circulation criminal arrest in transvenous embolization of cerebral arteriovenous malformations.
In Japan, hypertensive patients are speculated to be 40 million, and 30 million among them are poor controlled. Moreover, 20% of them are estimated as "resistant hypertension" those are above their target blood pressure even in the simultaneous use of three different classes anti-hypertensive drugs. Recently, aldosterone is recognized as one of the main causes of the etiology of "resistant hypertension." Therefore, it is important to discover novel drugs that inhibit the synthesis and secretion of aldosterone. We recently generated a stable H295R cell line expressing aldosterone synthase gene (CYP11B2) promoter (-1521~+2)/luciferase cDNA chimeric reporter construct. We thereafter established a high-throughput screening (HTS) system for the discovery of novel anti-hypertensive drugs that inhibit angiotensin II-induced CYP11B2 expression using the cell line. After confirmation of its validation (Z' score > 0.5), we performed HTS using Core Library (9,600 chemical compounds) and Validated Compound Library (1,979 chemical compounds) obtained from Drug Discovery Initiative (The University of Tokyo), and Tohoku University Chemical Library (5,562 chemical compounds), respectively. We obtained several hit compounds from each library, and focused on one compound (bortezomib) obtained from Validated Compound Library. The compound did not affect cell viability by WST-1 assay, and was demonstrated to lower blood pressure of Tsukuba Hypertensive Mice, significantly. The compound may therefore be a potential candidate of novel anti-hypertensive drugs in the future.Various artificial cells and artificial tissues can be generated from induced pluripotent stem cells (iPS cells). There is now an urgent need to standardize the quality evaluation and management of iPS cells. Recently, artificial intelligence (AI) technology such as machine learning is providing evaluation method for the quality of iPS cells and iPS cell-derived somatic cells based on optical microscopy. Light, which is the principle of optical microscopy, has an interesting and important feature. There are various kinds of interaction between light and molecule, and the scattered light includes internal information of the molecule. Raman scattering inheres all the vibration mode of molecular bonds composing a molecule, and second harmonic generation (SHG) light, which is one of second-order non-linear scattering light, is derived from electric polarizations in the molecule, in other words, carries structural information within the protein. While states of a cell are usually defined by protein/gene expression patterns, we have proposed to apply Raman spectra for cellular fingerprinting as an alternative for identifying the cell state, and now succeeded in predicting gene-expression of antibiotic resistant bacteria in combination with machine learning technology. Meanwhile, SHG microscopy has been used to visualize fiber structures in living specimens, such as collagen, and microtubules as a label-free modality. By utilizing the feature that SHG senses protein structure change, we developed a new method to measure actomyosin activity in cardiac cells. The most important advantage of the use of the scattering light is their non-labeling and non-invasive capability.Deep learning technology is rapidly advancing, and is now used to solve complex problems. induced pluripotent stem cells (iPSCs) can be used for several purposes such as regenerative medicine, disease modeling study and drug screening. It is inevitable to identify iPSC-derived differentiated cells in microscopy for any use. Here, we used deep learning to establish an automated method to identify endothelial cells derived from iPSCs, without the need for immunostaining or lineage tracing.It is reported that the incidence of atrial arrhythmias has been increasing year by year and it might increase from now on. Although not only aging but pharmaceutical drug treatments might relate to atrial arrhythmias, experimental method to detect drug-induced atrial arrhythmias has not been established so far. Therefore, we induced differentiation of atrial-like cardiomyocytes from human induced pluripotent stem (iPS) cell, and clarified their characteristics and verified their dug responsiveness. Atrial-like cardiomyocytes were induced by adding retinoic acid (RA) during the process of myocardial differentiation, and their character was compared to RA-untreated cardiomyocytes. In gene expression and membrane potential analysis, it was confirmed that the cells with or without RA treatment have the characters of atrial or ventricular like cardiomyocytes, respectively. In addition, it was also confirmed that atrial-like cardiomyocytes induced reentry-like conduction disorder, which is atrial arrhythmias. Furthermore, as a result of examining the responsiveness of various ion channel inhibitors using these cells, the inhibition of ultra-rapid delayed rectifier potassium current (IKur) specifically existed in atrial muscle induced prolongation of PWD30cF (membrane potential duration at 30% depolarization corrected by Fridericia formula) only in atrial-like cardiomyocytes. In addition, ventricular-like cardiomyocytes alone exhibited an early after depolarization by treatment of rapid rectifier potassium current (IKr) inhibitor which induced ventricular arrhythmia in clinical situation. Based on above evidences, current evaluation systems using human iPS cell-derived atrial-like cardiomyocytes might be a valuable tool for drug-induced atrial arrhythmias.Disease-specific iPS cells have been considered and used as platforms for disease modeling and drug discovery for intractable diseases. In the field of cardiovascular medicine, iPS cells have been generated from patients with heart diseases including inherited cardiomyopathy. The disease-specific iPS cells showed the certain parts of phenotype of the disease on culture dishes in in vitro systems, but the cells do not necessarily recapitulate patients' clinical properties, particularly those of physiological-/pathophysiological aspects. RK-701 clinical trial The point should be solved to establish disease reliable platforms. The discrepancy may be attributed to the lack of developmental process during culture procedure. To settle the problems, various techniques have been attempted such as culture dishes with specific structures. This review describes issues to be solved to recapitulate "heart diseases on culture dishes", introducing the phenotype of disease specific iPS-cells from patients with cardiomyopathy.
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