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iPSCs hold great promise in that a large quantity of cardiomyocytes (iPSC-CM) can be generated and cultured in vitro for clinical purposes. These cells are currently being subjected to vigorous testing in animal transplantation models to ascertain their survivability and functional integration in the injured heart. So far, most of those studies have been conducted in small animals and sometimes in xenogeneic settings, and have produced mixed results. Representing a step forward, a recent study in Nature reported the transplantation of MHC-matched allogeneic monkey iPSC-CM. This was the first time iPSC-CM have been tested in a non-human primate model in an allogeneic setting, which is the next best thing to a human clinical trial.

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CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function. More recently, this technology has been increasingly applied to the study or treatment of human diseases, including Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, β-Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9) genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome (AIDS) or promoting anti-tumor immunotherapy. Furthermore, this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials, including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has been teamed with induced pluripotent stem (iPS) cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation. This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

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Immune checkpoint inhibition against advance malignancies was named breakthrough discovery by the science magazine in 2013. In numerous clinical studies, monoclonal antibodies against the immune checkpoints, CTLA4, PD1 and PD1 ligand PDL1 have shown promising tumor response in different type of metastatic malignancies. The adverse events are autoimmune-related. The endocrine disorders, hypophysitis and thyroiditis are among the most common side effects associated with immune checkpoint inhibition treatment. Hy-pophysitis, a very rare endocrine disorder occurs in about one tenth of the patients receiving anti-CTLA4 treatment. Thyroiditis, on the other hand, is more commonly seen in patients receiving anti-PD1 treatment. In addition, both thyroiditis and hypophysitis are common in patients receiving combination treatment with anti-CTLA4 and anti-PD1 treatment. The time to onset of hypophysitis and thyroiditis is short. Most of the endocrine disorders occur within 12 weeks after initiation of the immune checkpoint inhibition therapy. Hypophysitis can manifest as total anterior pituitary hormone deficiency or isolated pituitary hormone deficiency. Diabetes insipidus is rare. TSH and gonadotropin deficiencies may be reversible but ACTH deficiency appears permanent. Thyroiditis can present as hypothyroidism or thyrotoxicosis followed by hypothyroidism. Hypothyroidism appears irreversible. Early identifying the onset of hypophysitis and thyroiditis and proper management of these endocrine disorders will improve the quality of the life and the outcome of this novel immunotherapy.

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Atrial fibrillation is the most common sustained arrhythmia and remains as one of main challenges in current clinical practice. The disease may be induced secondary to other diseases such as hypertension, valvular heart disease, and heart failure, conferring an increased risk of stroke and sudden death. Epidemiological studies have provided evidence that genetic factors play an important role and up to 30% of clinically diagnosed patients may have a family history of atrial fibrillation. To date, several rare variants have been identified in a wide range of genes associated with ionic channels, calcium handling protein, fibrosis, conduction and inflammation. Important advances in clinical, genetic and molecular basis have been performed over the last decade, improving diagnosis and treatment. However, the genetics of atrial fibrillation is complex and pathophysiological data remains still unraveling. A better understanding of the genetic basis will induce accurate risk stratification and personalized clinical treatment. In this review, we have focused on current genetics basis of atrial fibrillation.

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Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.

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Irrespective of positive developments of cancer treatment, the mortality due to various cancers remains high and the mechanisms of cancer initiation and the development also remains mysterious. As we know that microRNAs are considered to be a short noncoding RNA molecules consisting of 21-25 nucleotides (nt) in length and they silence their target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3′-untranslated (UTR) region and play a very important role in cancer biology. Recent evidences indicate that miR-21 is over expressed in cancer stem cells and plays a vital role in cell proliferation, apoptosis, and invasion. Even though an increased expression level of miR-21 has been observed in cancer stem cells, studies related to the role of miR-21 in cancer stem cells are limited. The main aim of this mini review is to explain the potency of miR-21 in various cancer stem cells (CSCs) and as a new target for therapeutic interventions of cancer progression.

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Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer (NSCLC). Beta catenin abundance and transcriptional activity are significantly regulated by several factors. Though it is well known that Akt and Gsk3 beta are respective positive and negative regulators of beta catenin, however, no single study has so far documented how the expression and activity of both positive as well as negative regulators play favorable role on beta catenin expression and activity in NSCLC. In this study, we compared expression and activity of beta catenin and its regulators in normal lung cell WI38 and NSCLC cell A549 by western blot, qRT-PCR and luciferase assay. We observed that beta catenin positive regulators (Akt and Hsp90) and negative regulators (Gsk3 beta and microRNA-214) have differential expression and/or activity in NSCLC cell A549. However the differentially altered statuses of both the positive and negative regulators rendered cumulative positive effect on beta catenin expression and activity in A549. Our study thus suggests that chemotherapeutic modulations of regulating factors are crucial when abrogation and/or inhibition of key oncogenic proteins are necessary for cancer chemotherapy.

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Lipoprotein-associated phospholipase A₂ (Lp-PLA₂), a member of the phospholipase A₂ superfamily, isanenzymethathydrolysesphospholipids, isfoundinbloodcirculationasasign of inflammation, and takes a role in atherogenesis. There is an epidemiologic relation between increased Lp-PLA₂ levels and coronary heart disease. Lp-PLA₂ is an enzyme that is produced by macrophagesandtakesaroleasanindependentpredictorofacoronaryevent. Ageneticvariant of Val279Phe on the Lp-PLA₂ gene has been reported with various results in Japan, China, Korea, and Caucasian populations. This study aims to analyse the influence of the Val279Phe genetic variant on acute myocardial infarction (AMI) at Saiful Anwar Hospital, Indonesia. This study was conducted on 151 patients (111 AMI patients and 40 non-AMI patients). The genetic variant of Val279Phe was identified through a genotyping method. There were nosignificant differences in age, total cholesterol level, LDL-C (low-density lipoprotein cholesterol) level, and family history data between AMI and non-AMI patients. However, AMI patients had low HDL-C (high-density lipoprotein cholesterol), triglyceride levels, dyslipidaemia, and hypertension risk factors compared to non-AMI patients. The frequency of the GG genotype (279Val) was dominant in both AMI and non-AMI groups. Further analysis suggested that the GG genotype has a 2.9 times greater risk of AMI compared to the GT/TT genotype (279Phe). This study concluded that the Val279Phe genetic variant undoubtedly influenced AMI risk, which is a warrant for further development of early detection and improving strategy to prevent AMI in patients.

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Sickle cell disease has been shown to demonstrate extensive variability in disease severity among and between individuals, the variability highlighted by differing genetic haplotypes. Despite the abundance of reports of functional significance due to polymorphisms of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) genes, the role of these polymorphisms in mediating sickle cell disease pathophysiology among African Americans is presently unclear. To deconvolute their potential significance among African Americans with sickle cell disease, we examined the genetic diversity and haplotype frequency of eNOS and ET-1 polymorphisms in disease (n = 331) and control (n = 379) groups, with a polymerase echain reaction restriction fragment length polymorphism assay. We report that genotypic and allelic frequencies of eNOS variants are not significantly different between groups. eNOS homozygote mutants, which had been shown to have clinical significance elsewhere, showed no statistical significance in our study. On the other hand, and contrary to previous report among Africans with sickle cell disease, the endothelin-1 homozygous mutant variant showed significant difference in genotypic (p = 2.84E-12) and allelic frequencies (p = 2.20E-16) between groups. The most common haplotype is the combination of T786C homozygote wildtype variant with homozygote mutant variants of G5665T (ET-1) and Glu298Asp (eNOS). These results show that endothelin-1 (rs5370) polymorphism, rather than endothelial nitric oxide synthase polymorphism might play a significant role in disease severity or individual clinical outcomes among African Americans with sickle cell disease. This would have profound implications for designing and/or advancing personalized care for sickle cell patients and relieving disease complications.

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