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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28524180/aberrant-epigenetic-regulation-of-gabrp-associates-with-aggressive-phenotype-of-ovarian-cancer
#1
Hye Youn Sung, San-Duk Yang, Woong Ju, Jung-Hyuck Ahn
Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#2
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524178/transcriptome-analyses-of-chronic-traumatic-encephalopathy-show-alterations-in-protein-phosphatase-expression-associated-with-tauopathy
#3
Jeong-Sun Seo, Seungbok Lee, Jong-Yeon Shin, Yu Jin Hwang, Hyesun Cho, Seong-Keun Yoo, Yunha Kim, Sungsu Lim, Yun Kyung Kim, Eun Mi Hwang, Su Hyun Kim, Chong-Hyun Kim, Seung Jae Hyeon, Ji-Young Yun, Jihye Kim, Yona Kim, Victor E Alvarez, Thor D Stein, Junghee Lee, Dong Jin Kim, Jong-Il Kim, Neil W Kowall, Hoon Ryu, Ann C McKee
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524177/role-of-carbonic-anhydrases-in-skin-wound-healing
#4
Harlan Barker, Marleena Aaltonen, Peiwen Pan, Maria Vähätupa, Pirkka Kaipiainen, Ulrike May, Stuart Prince, Hannele Uusitalo-Järvinen, Abdul Waheed, Silvia Pastoreková, William S Sly, Seppo Parkkila, Tero Ah Järvinen
Skin wound closure occurs when keratinocytes migrate from the edge of the wound and re-epithelialize the epidermis. Their migration takes place primarily before any vascularization is established, that is, under hypoxia, but relatively little is known regarding the factors that stimulate this migration. Hypoxia and an acidic environment are well-established stimuli for cancer cell migration. The carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28524176/lentivirus-mediated-microrna-124-gene-modified-bone-marrow-mesenchymal-stem-cell-transplantation-promotes-the-repair-of-spinal-cord-injury-in-rats
#5
Jia-Lin Song, Wei Zheng, Wei Chen, Yun Qian, Yuan-Ming Ouyang, Cun-Yi Fan
Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496201/engulfment-signals-and-the-phagocytic-machinery-for-apoptotic-cell-clearance
#6
REVIEW
Seung-Yoon Park, In-San Kim
The clearance of apoptotic cells is an essential process for tissue homeostasis. To this end, cells undergoing apoptosis must display engulfment signals, such as 'find-me' and 'eat-me' signals. Engulfment signals are recognized by multiple types of phagocytic machinery in phagocytes, leading to prompt clearance of apoptotic cells. In addition, apoptotic cells and phagocytes release tolerogenic signals to reduce immune responses against apoptotic cell-derived self-antigens. Here we discuss recent advances in our knowledge of engulfment signals, the phagocytic machinery and the signal transduction pathways for apoptotic cell engulfment...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496200/microrna-200a-3p-increases-5-fluorouracil-resistance-by-regulating-dual-specificity-phosphatase-6-expression
#7
Heejin Lee, Chongtae Kim, Hoin Kang, Hyosun Tak, Sojin Ahn, Sungjoo Kim Yoon, Hyo-Jeong Kuh, Wook Kim, Eun Kyung Lee
Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496199/upregulation-and-biological-function-of-transmembrane-protein-119-in-osteosarcoma
#8
Zhen-Huan Jiang, Jun Peng, Hui-Lin Yang, Xing-Li Fu, Jin-Zhi Wang, Lei Liu, Jian-Nong Jiang, Yong-Fei Tan, Zhi-Jun Ge
Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496198/bone-forming-peptide-2-derived-from-bmp-7-enhances-osteoblast-differentiation-from-multipotent-bone-marrow-stromal-cells-and-bone-formation
#9
Hyung Keun Kim, Jun Sik Lee, Ji Hyun Kim, Jong Keun Seon, Kyung Soon Park, Myung Ho Jeong, Taek Rim Yoon
Strategies for efficient osteogenic differentiation and bone formation from stem cells would have clinical applications in treating nonunion fracture healing. Many researchers have attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. Therefore, development of specific stimulators of bone formation has therapeutic significance in the treatment of osteoporosis. To date, investigations of the mature forms of bone morphogenetic proteins (BMPs) have focused on regulation of bone generation...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28496197/helicobacter-pylori-derived-extracellular-vesicles-increased-in-the-gastric-juices-of-gastric-adenocarcinoma-patients-and-induced-inflammation-mainly-via-specific-targeting-of-gastric-epithelial-cells
#10
Hyun-Il Choi, Jun-Pyo Choi, Jiwon Seo, Beom Jin Kim, Mina Rho, Jin Kwan Han, Jae Gyu Kim
Evidence indicates that Helicobacter pylori is the causative agent of chronic gastritis and perhaps gastric malignancy. Extracellular vesicles (EVs) play an important role in the evolutional process of malignancy due to their genetic material cargo. We aimed to evaluate the clinical significance and biological mechanism of H. pylori EVs on the pathogenesis of gastric malignancy. We performed 16S rDNA-based metagenomic analysis of gastric juices either from endoscopic or surgical patients. From each sample of gastric juices, the bacteria and EVs were isolated...
May 12, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450738/dna-methylation-an-epigenetic-mark-of-cellular-memory
#11
REVIEW
Mirang Kim, Joseph Costello
DNA methylation is a stable epigenetic mark that can be inherited through multiple cell divisions. During development and cell differentiation, DNA methylation is dynamic, but some DNA methylation patterns may be retained as a form of epigenetic memory. DNA methylation profiles can be useful for the lineage classification and quality control of stem cells such as embryonic stem cells, induced pluripotent cells and mesenchymal stem cells. During cancer initiation and progression, genome-wide and gene-specific DNA methylation changes occur as a consequence of mutated or deregulated chromatin regulators...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450737/writing-erasing-and-reading-histone-lysine-methylations
#12
REVIEW
Kwangbeom Hyun, Jongcheol Jeon, Kihyun Park, Jaehoon Kim
Histone modifications are key epigenetic regulatory features that have important roles in many cellular events. Lysine methylations mark various sites on the tail and globular domains of histones and their levels are precisely balanced by the action of methyltransferases ('writers') and demethylases ('erasers'). In addition, distinct effector proteins ('readers') recognize specific methyl-lysines in a manner that depends on the neighboring amino-acid sequence and methylation state. Misregulation of histone lysine methylation has been implicated in several cancers and developmental defects...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450736/histone-lysine-demethylases-in-mammalian-embryonic-development
#13
REVIEW
Hongjie Shen, Wenqi Xu, Fei Lan
Post-translational modifications, such as methylation, acetylation and phosphorylation, of histone proteins play important roles in regulating dynamic chromatin structure. Histone demethylation has become one of the most active research areas of epigenetics in the past decade. To date, with the exception of histone H3 lysine 79 methylation, the demethylases for all major lysine methylation sites have been discovered. These enzymes have been shown to be involved in various biological processes, with embryonic development being an exciting emerging area...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450735/methylation-and-demethylation-of-dna-and-histones-in-chromatin-the-most-complicated-epigenetic-marker
#14
EDITORIAL
Hong-Duk Youn
No abstract text is available yet for this article.
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450734/modulation-of-gene-expression-dynamics-by-co-transcriptional-histone-methylations
#15
REVIEW
Hyeonju Woo, So Dam Ha, Sung Bae Lee, Stephen Buratowski, TaeSoo Kim
Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28450733/tet-family-dioxygenases-and-dna-demethylation-in-stem-cells-and-cancers
#16
REVIEW
Jungeun An, Anjana Rao, Myunggon Ko
The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine methylation, and also serve as stable epigenetic modifications that exert distinctive regulatory roles...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428633/inhibition-of-glutathione-metabolism-attenuates-esophageal-cancer-progression
#17
Liang Peng, Ruixia Linghu, Demeng Chen, Jing Yang, Xiaoxue Kou, Xiang-Zhen Wang, Yi Hu, Yi-Zhou Jiang, Junlan Yang
Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428632/cyclophosphamide-induced-hcn1-channel-upregulation-in-interstitial-cajal-like-cells-leads-to-bladder-hyperactivity-in-mice
#18
Qian Liu, Zhou Long, Xingyou Dong, Teng Zhang, Jiang Zhao, Bishao Sun, Jingzhen Zhu, Jia Li, Qingqing Wang, Zhenxing Yang, Xiaoyan Hu, Longkun Li
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28428631/an-overview-of-the-synergy-and-crosstalk-between-pentraxins-and-collectins-ficolins-their-functional-relevance-in-complement-activation
#19
REVIEW
Ying Jie Ma, Bok Luel Lee, Peter Garred
The complement system is an innate immune defense machinery comprising components that deploy rapid immune responses and provide efficient protection against foreign invaders and unwanted host elements. The complement system is activated upon recognition of pathogenic microorganisms or altered self-cells by exclusive pattern recognition molecules (PRMs), such as collectins, ficolins and pentraxins. Recent accumulating evidence shows that the different classes of effector PRMs build up a co-operative network and exert synergistic effects on complement activation...
April 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28408750/transcriptional-regulatory-networks-underlying-the-reprogramming-of-spermatogonial-stem-cells-to-multipotent-stem-cells
#20
Hoe-Su Jeong, Jinhyuk Bhin, Hyung Joon Kim, Daehee Hwang, Dong Ryul Lee, Kye-Seong Kim
Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs...
April 14, 2017: Experimental & Molecular Medicine
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