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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28082743/adipose-stem-cell-derived-nanovesicles-inhibit-emphysema-primarily-via-an-fgf2-dependent-pathway
#1
You-Sun Kim, Ji-Young Kim, RyeonJin Cho, Dong-Myung Shin, Sei Won Lee, Yeon-Mok Oh
Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100 nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082742/gene-metabolite-network-analysis-in-different-nonalcoholic-fatty-liver-disease-phenotypes
#2
Xiao-Lin Liu, Ya-Nan Ming, Jing-Yi Zhang, Xiao-Yu Chen, Min-De Zeng, Yi-Min Mao
We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082741/bioinformatic-identification-of-prognostic-signature-defined-by-copy-number-alteration-and-expression-of-ccne1-in-non-muscle-invasive-bladder-cancer
#3
Bic-Na Song, Seon-Kyu Kim, In-Sun Chu
Non-muscle invasive bladder cancer (NMIBC) patients frequently fail to respond to treatment and experience disease progression because of their clinical and biological diversity. In this study, we identify a prognostic molecular signature for predicting the heterogeneity of NMIBC by using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profiles of 404 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. Of the 14 molecules with significant copy number alterations that were previously reported, 13 were significantly correlated with copy number and expression changes...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082740/epigenetic-regulation-and-chromatin-remodeling-in-learning-and-memory
#4
REVIEW
Somi Kim, Bong-Kiun Kaang
Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27980343/il-17a-exacerbates-diabetic-retinopathy-by-impairing-m%C3%A3-ller-cell-function-via-act1-signaling
#5
Ao-Wang Qiu, Zheng Bian, Ping-An Mao, Qing-Huai Liu
Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27980342/evaluation-of-a-tyrosine-kinase-peptide-microarray-for-tyrosine-kinase-inhibitor-therapy-selection-in-cancer
#6
Mariette Labots, Kristy J Gotink, Henk Dekker, Kaamar Azijli, Johannes C van der Mijn, Charlotte M Huijts, Sander R Piersma, Connie R Jiménez, Henk M W Verheul
Personalized cancer medicine aims to accurately predict the response of individual patients to targeted therapies, including tyrosine kinase inhibitors (TKIs). Clinical implementation of this concept requires a robust selection tool. Here, using both cancer cell lines and tumor tissue from patients, we evaluated a high-throughput tyrosine kinase peptide substrate array to determine its readiness as a selection tool for TKI therapy. We found linearly increasing phosphorylation signal intensities of peptides representing kinase activity along the kinetic curve of the assay with 7...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932791/migration-and-invasion-of-drug-resistant-lung-adenocarcinoma-cells-are-dependent-on-mitochondrial-activity
#7
Ji Hoon Jeon, Dong Keon Kim, Youngmi Shin, Hee Yeon Kim, Bomin Song, Eun Young Lee, Jong Kwang Kim, Hye Jin You, Heesun Cheong, Dong Hoon Shin, Seong-Tae Kim, Jae-Ho Cheong, Soo Youl Kim, Hyonchol Jang
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932790/motor-neurons-derived-from-als-related-mouse-ips-cells-recapitulate-pathological-features-of-als
#8
Ju-Hwang Park, Hang-Soo Park, Sunghoi Hong, Seongman Kang
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932789/the-maintenance-ability-and-ca-2-availability-of-skeletal-muscle-are-enhanced-by-sildenafil
#9
Mei Huang, Keon Jin Lee, Kyung-Jin Kim, Mi Kyoung Ahn, Chung-Hyun Cho, Do Han Kim, Eun Hui Lee
Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca(2+) imaging experiments and cellular and biochemical studies...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27909337/optimization-of-the-optical-transparency-of-rodent-tissues-by-modified-pact-based-passive-clearing
#10
Jiwon Woo, Mirae Lee, Jeong Min Seo, Hyo Suk Park, Yong Eun Cho
Recently, a bio-electrochemical technique known as CLARITY was reported for three-dimensional phenotype mapping within transparent tissues, allowing clearer whole-body and organ visualization with CB-perfusion (CUBIC) and leading to the development of whole-body clearing and transparency of intact tissues with the PACT (passive clarity technique) and PARS (perfusion-assisted agent release in situ) methodologies. We evaluated the structure-function relationships in circuits of the whole central nervous system (CNS) and various internal organs using improved methods with optimized passive clarity...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#11
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27885255/tfap2c-mediated-upregulation-of-tgfbr1-promotes-lung-tumorigenesis-and-epithelial-mesenchymal-transition
#12
Wanyeon Kim, EunGi Kim, Sungmin Lee, Daehoon Kim, Jahyun Chun, Kang Hyun Park, HyeSook Youn, BuHyun Youn
TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27885254/aldehyde-dehydrogenase-is-used-by-cancer-cells-for-energy-metabolism
#13
Joon Hee Kang, Seon-Hyeong Lee, Dongwan Hong, Jae-Seon Lee, Hee-Sung Ahn, Ju-Hyun Ahn, Tae Wha Seong, Chang-Hun Lee, Hyonchol Jang, Kyeong Man Hong, Cheolju Lee, Jae-Ho Lee, Soo-Youl Kim
We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27857068/a-phosphorylation-pattern-recognizing-antibody-specifically-reacts-to-rna-polymerase-ii-bound-to-exons
#14
Jungwon Han, Jong-Hyuk Lee, Sunyoung Park, Soomin Yoon, Aerin Yoon, Do B Hwang, Hwa K Lee, Min S Kim, Yujean Lee, Won J Yang, Hong-Duk Youn, Hyori Kim, Junho Chung
The C-terminal domain of RNA polymerase II is an unusual series of repeated residues appended to the C-terminus of the largest subunit and serves as a flexible binding scaffold for numerous nuclear factors. The binding of these factors is determined by the phosphorylation patterns on the repeats in the domain. In this study, we generated a synthetic antibody library by replacing the third heavy chain complementarity-determining region of an anti-HER2 (human epidermal growth factor receptor 2) antibody (trastuzumab) with artificial sequences of 7-18 amino-acid residues...
November 18, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27833096/immunoproteasome-induction-is-suppressed-in-hepatitis-c-virus-infected-cells-in-a-protein-kinase-r-dependent-manner
#15
In Soo Oh, Kathrin Textoris-Taube, Pil Soo Sung, Wonseok Kang, Xenia Gorny, Thilo Kähne, Seon-Hui Hong, Young Joon Choi, Clemens Cammann, Michael Naumann, Jong Hoon Kim, Su-Hyung Park, Ook Joon Yoo, Peter M Kloetzel, Ulrike Seifert, Eui-Cheol Shin
By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8(+) cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells...
November 11, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27811936/transglutaminase-2-is-dispensable-but-required-for-the-survival-of-mice-in-dextran-sulfate-sodium-induced-colitis
#16
Eui Man Jeong, Young Hoon Son, Yewon Choi, Jin-Hee Kim, Jin-Haeng Lee, Sung-Yup Cho, In-Gyu Kim
Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes crosslinking, polyamination or deamidation of glutamine residues in proteins. It has been reported that TG2 is involved in the pathogenesis of various inflammatory diseases including celiac disease, pulmonary fibrosis, cystic fibrosis, multiple sclerosis and sepsis. Recently, using a mouse model of bleomycin-induced lung fibrosis, we showed that TG2 is required to trigger inflammation via the induction of T helper type 17 (Th17) cell differentiation in response to tissue damage...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27811935/integrated-computational-approach-to-the-analysis-of-rna-seq-data-reveals-new-transcriptional-regulators-of-psoriasis
#17
Alena Zolotarenko, Evgeny Chekalin, Alexandre Mesentsev, Ludmila Kiseleva, Elena Gribanova, Rohini Mehta, Ancha Baranova, Tatiana V Tatarinova, Eleonora S Piruzian, Sergey Bruskin
Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27811934/ros-homeostasis-and-metabolism-a-critical-liaison-for-cancer-therapy
#18
REVIEW
Jongdoo Kim, Jaehong Kim, Jong-Sup Bae
Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27765950/therapeutic-effects-of-adipose-derived-stem-cells-pretreated-with-pioglitazone-in-an-emphysema-mouse-model
#19
Yoonki Hong, You-Sun Kim, Seok-Ho Hong, Yeon-Mok Oh
There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice...
October 21, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27741225/high-yields-and-soluble-expression-of-superoxide-dismutases-in-escherichia-coli-due-to-the-hiv-1-tat-peptide-via-increases-in-mrna-transcription
#20
Yangdong Sun, Qiao Ye, Min Wu, Yonghong Wu, Chenggang Zhang, Weiqun Yan
This study aimed to validate the high yield and soluble expression of proteins carrying the transactivator of transcription (Tat) peptide tag, and further explored the potential mechanism by which the Tat tag increases expression. Escherichia coli superoxide dismutase (SOD) proteins, including SodA, SodB and SodC, were selected for analysis. As expected, the yields and the solubility of Tat-tagged proteins were higher than those of Tat-free proteins, and similar results were observed for the total SOD enzyme activity...
October 14, 2016: Experimental & Molecular Medicine
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