Human cardiac organoids: A recent revolution in disease modeling and regenerative medicine

Three-dimensional (3D) myocardial tissues for studying human heart biology, physiology and pharmacology have recently received lots of attention. Organoids as 3D mini-organs are created from multiple cell types (i.e. induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs)) with other supporting co-cultured cells such as endothelial cells or fibroblasts. Cardiac organoid culture technologies are bringing about significant advances in organ research and allows for the establishment of tissue regeneration and disease modeling. The present review provides an overview of the recent advances in human cardiac organoid platforms in disease biology and for cardiovascular regenerative medicine

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cardenolide-rich fraction of Pergularia tomentosa as a novel Antiangiogenic agent mainly targeting endothelial cell migration

Purpose Angiogenesis related abnormalities underlie several life-threatening disorders. Despite approved therapies, scientists have yet to develop highly efficient, low cost approaches with minimal side effects.Methods We evaluated the antiangiogenic activity of 50% hydroalcoholic extracts of Pergularia tomentosa L. root and aerial parts along with their EtOAc and water fractions, in vivo and in vitro. Transgenic zebrafish line Tg(fli1:EGFP) was used for in vivo assay and human umbilical vein endothelial cell (HUVEC) migration test along with possibility of tube formation were performed as in vitro tests. Furthermore, microvasculature in chicken chorioallantoic membrane (CAM) was assessed under P. tomentosa treatment. The fractionation of the 50% hydroalcoholic extracts was led to the identification of the best active fraction in this study. The metabolite profiling of the active fraction was also carried out using LC-HRESIMS analysis.Results Pergularia tomentosa markedly inhibited intersegmental vessel (ISV) formation at 48 h post-fertilization (hpf) embryos in zebrafish. The water fraction of root hydroalcoholic extract (PtR2), showed strong antiangiogenic effect with minimal adverse viability impacts. Over 80% of embryos showed more than 50% inhibition in their ISV development at 20 and 40 mu g/mL. PtR2 at 20 mu g/mL substantially reduced human umbilical vein endothelial cell (HUVEC) migration up to 40%, considerable destruction of the formed tubes in the tube formation and microvasculature in CAM assays. Immunocytochemistry showed a marked reduction in vascular endothelial cadherin (VE-cadherin) abundance at cell junctions concurrent with substantial reduction of phospho-Akt (p-Akt) and beta-catenin protein expressions. Phytochemical profile of PtR2 showed a rich source of cardenolide structures, including ghalakinoside, calactin and calotropin derivatives.Conclusion Thus, the P. tomentosa cardenolide-rich fraction (PtR2) may hold a considerable promise for an antiangiogenic impact by impairment of endothelial cell (EC) migration and viability

Effects of hawthorn (Crataegus pentagyna) leaf extract on electrophysiologic properties of cardiomyocytes derived from human cardiac arrhythmia-specific induced pluripotent stem cells

Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn (Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells. The hydroalcoholic extract resulted in a dose-dependent negative chronotropic effect in all CM preparations leading to a significant reduction at 1000 mu g/ml. This was accompanied by prolongation of field potential durations, although with different magnitudes in CMs from different human embryonic stem cell and iPSC lines. Hawthorn further prolonged field potential durations in LQTS2 CMs but reduced the beating frequencies and occurrence of immature field potentials triggered by beta(1)-adrenergic stimulation in CPVT1 CMs at 300 and 1000 mu g/ml. Furthermore, isoquercetin and vitexin flavonoids significantly slowed down isoproterenol (5 mu M)-induced beating frequencies at 3 and 10 mu g/ml. Therefore, C. pentagyna leaf extract and its isoquercetin and vitexin flavonoids may be introduced as a novel nutraceutical with antiarrhythmic potential for CPVT1 patients

Role of long noncoding RNAs in pathological cardiac remodeling after myocardial infarction: An emerging insight into molecular mechanisms and therapeutic potential

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence of ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, and inflammatory responses occur. In the next stage, the proliferation and activation of cardiac fibroblasts results in myocardial fibrosis and HF progression. Therefore, developing a novel therapeutic strategy is urgently warranted to restrict the progression of pathological cardiac remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided a novel insight into treating several disorders. In this regard, numerous investigations have indicated that several lncRNAs could participate in the pathogenesis of MI-induced cardiac remodeling, suggesting their potential therapeutic applications. In this review, we summarized lncRNAs displayed in the pathophysiology of cardiac remodeling after MI, emphasizing molecular mechanisms. Also, we highlighted the possible translational role of lncRNAs as therapeutic targets for this condition and discussed the potential role of exosomes in delivering the lncRNAs involved in post-MI cardiac remodeling