Direct Cardiac Reprogramming: A Novel Approach for Heart Regeneration

Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field. View Full-Tex

Behavior-level Analysis of a Successive Stochastic Approximation Analog-to-Digital Conversion System for Multi-channel Biomedical Data Acquisition

In the present paper, we propose a novel high-resolution analog-to-digital converter (ADC) for low-power biomedical analog frontends, which we call the successive stochastic approximation ADC. The proposed ADC uses a stochastic flash ADC (SF-ADC) to realize a digitally controlled variable-threshold comparator in a successive-approximationregister ADC (SAR-ADC), which can correct errors originating from the internal digital-to-analog converter in the SAR-ADC. For the residual error after SAR-ADC operation, which can be smaller than thermal noise, the SF-ADC uses the statistical characteristics of noise to achieve high resolution. The SF-ADC output for the residual signal is combined with the SAR-ADC output to obtain high-precision output data using the supervised machine learning method

Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

Direct Cardiac Reprogramming: A Novel Approach for Heart Regeneration

Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field

Carte de la partie du grand archipel d'Asie, reconnue par le contre-amiral Bruny-Dentrecasteaux, en 1792 et 1793 [cartographic material] /

Map of the islands of Timor and Sawu in Indonesia showing track of Recherche and Esperance in 1792. Relief shown by hachures.; In lower right margin: Grave par E. Collin.; Plate no. 38 from: Atlas du voyage de Bruny-Dentrecasteaux, contre-amiral de France, commandant les fregates la Recherche et l'Esperance, fait par ordre du gouvernement en 1791, 1792 et 1793 : publie par ordre de sa majeste l'empereur et roi, sous le ministere de son excellence le vice-amiral Decres ... / par C.F. Beautemps-Beaupre. Paris : Depot general des cartes et plans de la marine et des colonies, 1807.; Prime meridian: Paris.; Tooley, 1641; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.map-ra82-s39