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Wenlin Yuan, Jun Chen, Hongren Huang, Zhihui Cai, Qinjie Ling, Feng Huang, Zhi Huang
Arsenic (As) is a well-known environmental pollutant,while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood.Embryonic stem cells (ESCs) appear properties of stemness and serve as a popular model to investigate epigenetic modifiers includingenvironmental pollutants.Herein, the effect of low dose ATO on differentiation were evaluatedin vitro using a mouse ESCs (mESCs) cell line, CGR8...
May 16, 2018: Chemical Research in Toxicology
Nicholas Ekow Thomford, Kevin Dzobo, Nana Akyaa Yao, Emile Chimusa, Jonathan Evans, Emmanuel Okai, Paul Kruszka, Maximilian Muenke, Gordon Awandare, Ambroise Wonkam, Collet Dandara
Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated...
May 2018: Omics: a Journal of Integrative Biology
Jin Young Lee, Kyung-Rok Yu, Byung-Chul Lee, Insung Kang, Jae-Jun Kim, Eui-Jung Jung, Hyung-Sik Kim, Yoojin Seo, Soon Won Choi, Kyung-Sun Kang
Defects in the nuclear lamina occur during physiological aging and as. result of premature aging disorders. Aging is also accompanied by an increase in transcription of genes encoding cytokines and chemokines,. phenomenon known as the senescence-associated secretory phenotype (SASP). Progerin and prelamin. trigger premature senescence and loss of function of human mesenchymal stem cells (hMSCs), but little is known about how defects in nuclear lamin. regulate SASP. Here, we show that both progerin overexpression and ZMPSTE24 depletion induce paracrine senescence, especially through the expression of monocyte chemoattractant protein-1 (MCP-1), in hMSCs...
May 14, 2018: Experimental & Molecular Medicine
Emre Bektik, Adrienne Dennis, Gary Pawlowski, Chen Zhou, Danielle Maleski, Satoru Takahashi, Kenneth R Laurita, Isabelle Deschênes, Ji-Dong Fu
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming...
May 4, 2018: International Journal of Molecular Sciences
Wanwan Jia, Weijun Wu, Di Yang, Chenxi Xiao, Mengwei Huang, Fen Long, Zhenghua Su, Ming Qin, Xinhua Liu, Yi Zhun Zhu
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by abnormal inflammation, angiogenesis, and cartilage destruction. In RA, neoangiogenesis is an early and crucial event to promote the formation of pannus, causing further inflammatory cell infiltration. The transcription factor GATA4 is a critical regulator of cardiac differentiation-specific gene expression. We find that a higher level of GATA4 exists in synovium of rheumatoid arthritis (RA) patients, but the function of GATA4 in RA remains unclear...
May 2, 2018: Cell Death & Disease
Yuqiong Wu, Qihong Yang, Meng Chen, Ying Zhang, Zhenghong Zuo, Chonggang Wang
Fenbuconazole (FBZ), a triazole-containing fungicide, is widely used in agriculture and horticulture. In the present study, the development and cardiac functioning were observed and determined in zebrafish embryos exposed to FBZ at 5, 50 and 500 ng/L nominal concentrations for 72 h. The results showed that 500 ng/L FBZ significantly increased pericardial edema rate, spine curvature rate, disturbed cardiac function, and led a shortened lower jaw. The transcription of genes such as tbx5, nkx2.5, tnnt2, gata4, bmp2b, myl7 was altered, which might be responsible for the cardiac developmental and functioning defects in the larvae...
April 28, 2018: Ecotoxicology and Environmental Safety
Hao Jiang, Shuang Liang, Xue-Rui Yao, Yong-Xun Jin, Xing-Hui Shen, Bao Yuan, Jia-Bao Zhang, Nam-Hyung Kim
Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group...
April 23, 2018: Theriogenology
Teppei Nakamura, Masataka Chihara, Osamu Ichii, Saori Otsuka-Kanazawa, Ken-Ichi Nagasaki, Yaser Hosny Ali Elewa, Osamu Tatsumi, Yasuhiro Kon
MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection...
2018: PloS One
Houssein Ahmadi, Mahdi Eskandarian Boroujeni, Yousef Sadeghi, Mohammad Amin Abdollahifar, Fariba Khodagholi, Gholam Houssein Meftahi, Mohammadmehdi Hadipour, Amir-Hossein Bayat, Fatemeh Shaerzadeh, Abbas Aliaghaei
Huntington's disease (HD) is a genetically heritable disorder, linked with continuing cell loss and degeneration mostly in the striatum. Currently, cell therapy approaches in HD have essentially been focused on replenishing or shielding cells lost over the period of the disease. Herein, we sought to explore the in vitro and in vivo efficacy of primary rat Sertoli cells (SCs) and their paracrine effect against oxidative stress with emphasis on HD. Initially, SCs were isolated and immunophenotypically characterized by positive expression of GATA4...
April 21, 2018: Journal of Molecular Neuroscience: MN
Idoia Martinez de LaPiscina, Carmen de Mingo, Stefan Riedl, Amaia Rodriguez, Amit V Pandey, Mónica Fernández-Cancio, Nuria Camats, Andrew Sinclair, Luis Castaño, Laura Audi, Christa E Flück
Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism...
2018: Frontiers in Endocrinology
Bryan D Maliken, Onur Kanisicak, Jason Karch, Hadi Khalil, Xing Fu, Justin G Boyer, Vikram Prasad, Yi Zheng, Jeffery D Molkentin
Background -While c-Kit+ adult progenitor cells were initially reported to produce new cardiomyocytes in the heart, recent genetic evidence suggests that such events are exceedingly rare. However, to determine if these rare events represent true de novo cardiomyocyte formation we deleted the necessary cardiogenic transcription factors Gata4 and Gata6 from c-Kit-expressing cardiac progenitor cells (CPCs). Methods - Kit allele-dependent lineage tracing and fusion analysis was performed in mice following simultaneous Gata4 and Gata6 cell-type specific deletion to examine rates of putative de novo cardiomyocyte formation from c-Kit+ cells...
April 17, 2018: Circulation
Ying-Jia Xu, Ruo-Min Di, Qi Qiao, Xiu-Mei Li, Ri-Tai Huang, Song Xue, Xing-Yuan Liu, Juan Wang, Yi-Qing Yang
Congenital bicuspid aortic valve (BAV), the most common form of birth defect in humans, is associated with substantial morbidity and mortality. Increasing evidence demonstrates that genetic risk factors play a key role in the pathogenesis of BAV. However, BAV is a genetically heterogeneous disease and the genetic determinants underpinning BAV in an overwhelming majority of patients remain unknown. In the present study, the coding exons and flanking introns of the GATA6 gene, which encodes a zinc-finger transcription factor essential for the normal development of the aortic valves, were sequenced in 152 unrelated patients with congenital BAV...
April 10, 2018: Gene
Chengjian Cao, Liang Li, Huiming Li, Xueling He, Wu Geng, Yu Xiaoqin
A physical stimuli, it has been reported that cyclic tensile strain can promote bone marrow-derived mesenchymal stem cells (BMSCs) to differentiate into cardiomyocytes, but the underlying mechanisms have been poorly elucidated so far. Here, we used a mimicking loading strain, cyclic biaxial tensile strain (CBTS), and found it can promote BMSCs to differentiate into cardiomyocytes. When the CBTS were loaded, the cells expressed cardiac-specific markers GATA4, TNNT2, MEF-2c, and Cx43, meanwhile we found miR-27a decreased and stem cell factor (SCF) increased...
April 5, 2018: International Journal of Biochemistry & Cell Biology
Jie Xiao, Ranran Kong, Jingye Hu
MicroRNAs (miRNAs) have been documented as critical regulators in ischemia/reperfusion-induced neuronal death. A better understanding of miRNA-mediated molecular mechanisms in ischemia/reperfusion-induced neuronal death may provide therapeutic targets for cerebral ischemia/reperfusion injury. A growing body of evidence suggests that miR-429 is a apoptosis-related miRNA that is also induced by hypoxia. However, whether miR-429 is involved in regulating neuronal apoptosis during cerebral ischemia/reperfusion injury remains unclear...
April 5, 2018: Neuroreport
Milena N Leseva, Richard J Grand, Hagen Klett, Melanie Boerries, Hauke Busch, Alexandra M Binder, Karin B Michels
In humans the expression of lactase changes during post-natal development, leading to phenotypes known as lactase persistence and non-persistence. Polymorphisms within the lactase gene (LCT) enhancer, in particular the -13910C > T, but also others, are linked to these phenotypes. We were interested in identifying dynamic mediators of LCT regulation, beyond the genotype at -13910C > T. To this end, we investigated two levels of lactase regulation in human intestinal samples obtained from New England children and adolescents of mixed European ancestry: differential expression of transcriptional regulators of LCT, and variations in DNA methylation, and their relation to phenotype...
April 4, 2018: Scientific Reports
Christian Wiraja, David C Yeo, Khek-Chian Tham, Sharon W T Chew, Xinhong Lim, Chenjie Xu
Cellular reprogramming, the process by which somatic cells regain pluripotency, is relevant in many disease modeling, therapeutic, and drug discovery applications. Molecular evaluation of reprogramming (e.g., polymerase chain reaction, immunostaining) is typically disruptive, and only provides snapshots of phenotypic traits. Gene reporter constructs facilitate live-cell evaluation but is labor intensive and may risk insertional mutagenesis during viral transfection. Herein, the utilization of a non-integrative nanosensor is demonstrated to visualize key reprogramming events in situ within live cells...
April 3, 2018: Small
Yuan-Chuan Lin, Yu-Chen Lin, Wei-Wen Kuo, Chia-Yao Shen, Yi-Chang Cheng, Yueh-Min Lin, Ruey-Lin Chang, Vijaya V Padma, Chih-Yang Huang, Chih-Yang Huang
Platycodin D (PD) is the main active saponin isolated from Platycodon grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti-inflammation and anti-obesity biological effects. The current study aims to evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling pathway. Significant increases in the cardiac functional indices of left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric hypertrophy markers, such as CaMKII[Formula: see text] and calcineurin; and expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously hypertensive groups...
March 29, 2018: American Journal of Chinese Medicine
Wenjun You, Lijuan Song, Kun Wang
BACKGROUND/AIMS: GATA4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects. Here, we aimed to explore the functional impacts of GATA4 acetylation on osteoporosis (OS). METHODS: GATA4 acetylation in hFOB1.19 and 293T cells was detected after exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted to determine which HATs and HDACs was involved in the modulation of GATA4 acetylation/deacetylation, and to identify the acetylation site...
March 22, 2018: Cellular Physiology and Biochemistry
Yongxin Jin, Ying Liu, Zhenpeng Li, Katherine Santostefano, Jing Shi, Xinwen Zhang, Donghai Wu, Zhihui Cheng, Weihui Wu, Naohiro Terada, Shouguang Jin, Fang Bai
Virus-mediated expression of defined transcription factor (TF) genes can effectively induce cellular reprogramming. However, sustained expression of the TFs often hinders pluripotent stem cell (PSC) differentiation into specific cell types, as each TF exerts its effect on PSCs for a defined period of time during differentiation. Here, we applied a bacterial type III secretion system (T3SS)-based protein delivery tool to directly translocate TFs in the form of protein into human PSCs. This transient protein delivery technique showed high delivery efficiency for hPSCs, and it avoids potential genetic alterations caused by the introduction of transgenes...
2018: PloS One
Jing Xie, Chen Fan, Jing-Long Zhang, Shi-Qiang Zhang
H3K4me3 is an important epigenetic modification that plays a critical role in maintaining self-renewal of mouse embryonic stem cells (mESCs). H3K4me3 is catalyzed mainly by the mixed lineage leukemia (MLL) methyl-transferase complex. ASH2L, a core subunit of the MLL complex, participates in regulating the open state of chromatin in mESCs. There are two isoforms of the ASH2L protein: ASH2L-1 (80 kDa), which only exists in mouse embryonic fibroblasts and ASH2L-2 (65 kDa), which is the predominant isoform in mESCs...
March 20, 2018: Yi Chuan, Hereditas
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