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https://www.readbyqxmd.com/read/28205629/mechanisms-of-chinese-medicine-xinmailong-s-protection-against-heart-failure-in-pressure-overloaded-mice-and-cultured-cardiomyocytes
#1
Jianyong Qi, Juan Yu, Yafang Tan, Renshan Chen, Wen Xu, Yanfen Chen, Jun Lu, Qin Liu, Jiashin Wu, Weiwang Gu, Minzhou Zhang
Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#2
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#3
Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6...
February 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28167794/gata4-potentiates-second-heart-field-proliferation-and-hedgehog-signaling-for-cardiac-septation
#4
Lun Zhou, Jielin Liu, Menglan Xiang, Patrick Olson, Alexander Guzzetta, Ke Zhang, Ivan P Moskowitz, Linglin Xie
GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28161810/mutation-screening-of-gata4-gene-in-ctd-patients-within-chinese-han-population
#5
Yang Liu, Bojian Li, Yuejuan Xu, Kun Sun
Conotruncal heart defect is a complex form of congenital heart disease and usually has a poor prognosis. Although previous studies have identified several missense variants in GATA4 gene that may cause CTD, it remains unclear whether they are involved in CTD pathogenesis because the study population was limited. The aim of the study was to investigate the mutations of GATA4 gene in isolated CTD Chinese Han patients and identify the pathomechanism of the missense mutations. In this report, the coding exons and exon-intron boundaries of the GATA4 gene were sequenced in 600 CTD patients and 300 controls...
February 4, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28152522/generation-and-characteristics-of-human-sertoli-cell-line-immortalized-by-overexpression-of-human-telomerase
#6
Liping Wen, Qingqing Yuan, Min Sun, Minghui Niu, Hong Wang, Hongyong Fu, Fan Zhou, Chencheng Yao, Xiaobo Wang, Zheng Li, Zuping He
Sertoli cells are required for normal spermatogenesis and they can be reprogrammed to other types of functional cells. However, the number of primary Sertoli cells is rare and human Sertoli cell line is unavailable. In this study, we have for the first time reported a stable human Sertoli cell line, namely hS1 cells, by overexpression of human telomerase. The hS1 cells expressed a number of hallmarks for human Sertoli cells, including SOX9, WT1, GDNF, SCF, BMP4, BMP6, GATA4, and VIM, and they were negative for 3β-HSD, SMA, and VASA...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138261/the-effects-of-exercise-training-and-caloric-restriction-on-the-cardiac-oxytocin-natriuretic-peptide-system-in-the-diabetic-mouse
#7
Tom L Broderick, Marek Jankowski, Jolanta Gutkowska
BACKGROUND: Regular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)-natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28135716/overexpression-of-cardiac-specific-kinase-tnni3k-promotes-mouse-embryonic-stem-cells-differentiation-into-cardiomyocytes
#8
Yin Wang, Shi-Qiang Wang, Li-Peng Wang, Yu-Hong Yao, Chun-Yan Ma, Jin-Feng Ding, Jue Ye, Xian-Min Meng, Rui-Xia Xu, Jian-Jun Li
: Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. METHODS: First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28131743/novel-genes-involved-in-pathophysiology-of-gonadotropin-dependent-adrenal-tumors-in-mice
#9
Milena Doroszko, Marcin Chrusciel, Kirstine Belling, Susanna Vuorenoja, Marlene Dalgaard, Henrik Leffers, H Bjørn Nielsen, Ilpo Huhtaniemi, Jorma Toppari, Nafis A Rahman
Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated...
January 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28115595/effect-of-lithium-on-ventricular-remodeling-in-infarcted-rats-via-the-akt-mtor-signaling-pathways
#10
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
Activation of phosphoinositide 3-kinase/Akt signaling is the molecular pathway driving physiological hypertrophy. As lithium, a phosphoinositide 3-kinase agonist, is highly toxic at regular doses, we assessed the effect of lithium at a low dose on ventricular hypertrophy after myocardial infarction.  Male Wistar rats after induction of myocardial infarction were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than therapeutic concentrations (0...
January 23, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28112363/hand1-loss-of-function-mutation-contributes-to-congenital-double-outlet-right-ventricle
#11
Li Li, Juan Wang, Xing-Yuan Liu, Hua Liu, Hong-Yu Shi, Xiao-Xiao Yang, Ning Li, Yan-Jie Li, Ri-Tai Huang, Song Xue, Xing-Biao Qiu, Yi-Qing Yang
Congenital heart defects (CHDs), a wide variety of developmental abnormalities in the structures of the heart and the great thoracic blood vessels, are the most common form of birth defect in humans worldwide. CHDs are accountable for substantial morbidity and are still the leading cause of birth defect‑related deaths. Recent studies have demonstrated the pivotal roles of genetic defects in the pathogenesis of CHDs, and a great number of genetic mutations have been associated with CHDs. Nevertheless, CHDs are a genetically heterogeneous disorder and the genetic basis underlying CHDs in an overwhelming majority of cases remains unclear...
January 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28111280/inhibition-of-gata4-and-tbx5-by-nicotine-mediated-dna-methylation-in-myocardial-differentiation
#12
Xue-Yan Jiang, Yu-Liang Feng, Li-Tong Ye, Xiao-Hong Li, Juan Feng, Meng-Zhen Zhang, Harnath S Shelat, Michael Wassler, Yangxin Li, Yong-Jian Geng, Xi-Yong Yu
Maternal nicotine exposure causes alteration of gene expression and cardiovascular programming. The discovery of nicotine-medicated regulation in cardiogenesis is of major importance for the study of cardiac defects. The present study investigated the effect of nicotine on cardiac gene expression and epigenetic regulation during myocardial differentiation. Persistent nicotine exposure selectively inhibited expression of two cardiac genes, Tbx5 and Gata4, by promoter DNA hypermethylation. The nicotine-induced suppression on cardiac differentiation was restored by general nicotinic acetylcholine receptor inhibition...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28106824/identification-of-the-muc2-promoter-as-a-strong-promoter-for-intestinal-gene-expression-through-generation-of-transgenic-quail-expressing-gfp-in-gut-epithelial-cells
#13
Rachel M Woodfint, Paula R Chen, Jinsoo Ahn, Yeunsu Suh, Seongsoo Hwang, Sang Suk Lee, Kichoon Lee
Identification of tissue- and stage-specific gene promoters is valuable for delineating the functional roles of specific genes in genetically engineered animals. Here, through the comparison of gene expression in different tissues by analysis of a microarray database, the intestinal specificity of mucin 2 (MUC2) expression was identified in mice and humans, and further confirmed in chickens by RT-PCR (reverse transcription-PCR) analysis. An analysis of cis-acting elements in avian MUC2 gene promoters revealed conservation of binding sites, within a 2...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28095922/long-noncoding-rna-braveheart-promotes-cardiogenic-differentiation-of-mesenchymal-stem-cells-in-vitro
#14
Jingying Hou, Huibao Long, Changqing Zhou, Shaoxin Zheng, Hao Wu, Tianzhu Guo, Quanhua Wu, Tingting Zhong, Tong Wang
BACKGROUND: Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2)...
January 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28094799/activation-of-wnt-%C3%AE-catenin-signalling-via-gsk3-inhibitors-direct-differentiation-of-human-adipose-stem-cells-into-functional-hepatocytes
#15
Jieqiong Huang, Xinyue Guo, Weihong Li, Haiyan Zhang
The generation of hepatocytes that are derived from human adipose stem cells (hASCs) represents an alternative to human hepatocytes for individualized therapeutic and pharmaceutical applications. However, the mechanisms facilitating hepatocyte differentiation from hASCs are not well understood. Here, we show that upon exposure to glycogen synthase kinase 3 (GSK3) inhibitors alone, the expression of definitive endoderm specific genes GATA4, FOXA2, and SOX17 in hASCs significantly increased in a manner with activation of Wnt/β-catenin signalling...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092181/impaired-redox-environment-modulates-cardiogenic-and-ion-channel-gene-expression-in-cardiac-resident-and-non-resident-mesenchymal-stem-cells
#16
Baskar Subramani, Sellamuthu Subbannagounder, Chithra Ramanathanpullai, Sekar Palanivel, Rajesh Ramasamy
Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2 or ascorbic acid at a concentration of 400 µmol/L...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28088180/nuclear-envelope-structural-proteins-facilitate-nuclear-shape-changes-accompanying-embryonic-differentiation-and-fidelity-of-gene-expression
#17
Elizabeth R Smith, Yue Meng, Robert Moore, Jeffrey D Tse, Arn G Xu, Xiang-Xi Xu
BACKGROUND: Nuclear size and shape are specific to a cell type, function, and location, and can serve as indicators of disease and development. We previously found that lamin A/C and associated nuclear envelope structural proteins were upregulated when murine embryonic stem (ES) cells differentiated to primitive endoderm cells. Here we further investigated the morphological changes of nuclei that accompany this differentiation. RESULTS: The nuclei of undifferentiated wild type cells were found shaped as flattened, irregular ovals, whereas nuclei of Gata4-positive endoderm cells were more spherical, less flattened, and with a slightly reduced volume...
January 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28071742/core-transcription-factors-micrornas-and-small-molecules-drive-transdifferentiation-of-human-fibroblasts-towards-the-cardiac-cell-lineage
#18
Nicolas Christoforou, Syandan Chakraborty, Robert D Kirkton, Andrew F Adler, Russell C Addis, Kam W Leong
Transdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28068351/phenotype-and-tissue-expression-as-a-function-of-genetic-risk-in-polycystic-ovary-syndrome
#19
Cindy T Pau, Tim Mosbruger, Richa Saxena, Corrine K Welt
Genome-wide association studies and replication analyses have identified (n = 5) or replicated (n = 10) DNA variants associated with risk for polycystic ovary syndrome (PCOS) in European women. However, the causal gene and underlying mechanism for PCOS risk at these loci have not been determined. We hypothesized that analysis of phenotype, gene expression and metformin response as a function of genotype would identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci...
2017: PloS One
https://www.readbyqxmd.com/read/28060734/let-7a-regulates-expression-of-%C3%AE-1-adrenoceptors-and-forms-a-negative-feedback-circuit-with-the-%C3%AE-1-adrenoceptor-signaling-pathway-in-chronic-ischemic-heart-failure
#20
Yue Du, Mingyu Zhang, Wei Zhao, You Shu, Ming Gao, Yanan Zhuang, Ti Yang, Wei Mu, Tingting Li, Xin Li, Fei Sun, Zhenwei Pan, Yanjie Lu
BACKGROUND: The aim of the present study was to investigate the role of microRNA (miRNA) let-7a in down-regulation of β1-adrenoceptors (β1-AR) and elucidate the underlying mechanism of chronic ischemia heart failure (CIHF) in rats. METHODS AND RESULTS: CIHF model was established by occlusion of coronary artery for 4 weeks. β1-AR level was obviously down-regulated and let-7a up-regulated in the failing heart 4 weeks after myocardial infarction. Overexpression of let-7a inhibited β1-AR expression in neonatal rat ventricular cells (NRVCs), which was abolished by anti-let-7a antisense inhibitor...
January 31, 2017: Oncotarget
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