http://cardiologia.publicacionmedica.com/contenido/images/stemi_aha_2013.pdf

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a)-positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.

/pdf/clearance-of-p16-ink4a-positive-senescent-cells-delays-41olwc1s7m.pdf

Clearance of p16 Ink4a -positive senescent cells delays ageing-associated disorders

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

1. Place animal in induction chamber and anesthetize the mouse and ensure sedation. 2. Once the animal is sedated, move it to a nose cone for hair removal using cream. Only apply cream to the area of the chest that will be utilized for imaging. Once the hair is removed, wipe area with wet gauze to ensure all hair is removed. 3. Move the animal to the imaging platform and tape its paws to the ECG lead plates and insert rectal probe. Body temperature should be maintained at 36-37°C. During imaging, reduce anesthesia to maintain proper heart rate. If the animal shows signs of being awake, use a higher concentration of anesthetic.

人唾液天疱疮抗原的纯化

Heart rate and cardiovascular mortality: The Framingham study

Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming

https://www.cell.com/cell-stem-cell/pdf/S1934-5909(12)00583-8.pdf

Metabolic plasticity in stem cell homeostasis and differentiation.

Background—Nuclear reprogramming provides an emerging strategy to produce embryo-independent pluripotent stem cells from somatic tissue. Induced pluripotent stem cells (iPS) demonstrate aptitude for de novo cardiac differentiation, yet their potential for heart disease therapy has not been tested. Methods and Results—In this study, fibroblasts transduced with human stemness factors OCT3/4, SOX2, KLF4, and c-MYC converted into an embryonic stem cell–like phenotype and demonstrated the ability to spontaneously assimilate into preimplantation host morula via diploid aggregation, unique to bona fide pluripotent cells. In utero, iPS-derived chimera executed differentiation programs to construct normal heart parenchyma patterning. Within infarcted hearts in the adult, intramyocardial delivery of iPS yielded progeny that properly engrafted without disrupting cytoarchitecture in immunocompetent recipients. In contrast to parental nonreparative fibroblasts, iPS treatment restored postischemic contractile performance, ventricular wall thickness, and electric stability while achieving in situ regeneration of cardiac, smooth muscle, and endothelial tissue. Conclusions—Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease. (Circulation. 2009;120:408-416.)

Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells

Patients With Heart Failure Have an Increased Risk of Incident Cancer

Nuclear reprogramming of somatic cells with ectopic stemness factors to bioengineer pluripotent autologous stem cells signals a new era in regenerative medicine. The study of developmental biology has provided a roadmap for cardiac differentiation from embryonic tissue formation to adult heart muscle rejuvenation. Understanding the molecular mechanisms of stem-cell-derived cardiogenesis enables the reproducible generation, isolation, and monitoring of progenitors that have the capacity to recapitulate embryogenesis and differentiate into mature cardiac tissue. With the advent of induced pluripotent stem (iPS) cell technology, patient-specific stem cells provide a reference point to systematically decipher cardiogenic differentiation through discrete stages of development. Interrogation of iPS cells and their progeny from selected cohorts of patients is an innovative approach towards uncovering the molecular mechanisms of disease. Thus, the principles of cardiogenesis can now be applied to regenerative medicine in order to optimize personalized therapeutics, diagnostics, and discovery-based science for the development of novel clinical applications.

Timothy J. Nelson

Papers

Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming

Metabolic plasticity in stem cell homeostasis and differentiation.

Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells

Patients With Heart Failure Have an Increased Risk of Incident Cancer

Induced pluripotent stem cells: developmental biology to regenerative medicine.