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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/27909337/optimization-of-the-optical-transparency-of-rodent-tissues-by-modified-pact-based-passive-clearing
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27741224/genome-editing-the-road-of-crispr-cas9-from-bench-to-clinic
#12
Ayman Eid, Magdy M Mahfouz
Molecular scissors engineered for site-specific modification of the genome hold great promise for effective functional analyses of genes, genomes and epigenomes and could improve our understanding of the molecular underpinnings of disease states and facilitate novel therapeutic applications. Several platforms for molecular scissors that enable targeted genome engineering have been developed, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and, most recently, clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated-9 (Cas9)...
October 14, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27713399/a-novel-anti-il4r%C3%AE-nanoparticle-efficiently-controls-lung-inflammation-during-asthma
#13
Rabih Halwani, Asma Sultana Shaik, Elaref Ratemi, Sibtain Afzal, Rosan Kenana, Saleh Al-Muhsen, Achraf Al Faraj
Drug resistance and the harmful side effects accompanying the prolonged corticosteroid treatment of chronic pulmonary diseases prompted the development of more specific anti-inflammatory approaches. Several strategies aiming to block IL4Rα, the receptor for a key pro-inflammatory pathway, were investigated. However, their efficiency was limited, mostly due to the systemic or subcutaneous route of administrations. In this paper, we examined the ability of an intranasal treatment with biocompatible nanoparticles targeting IL4Rα to control lung inflammation in ovalbumin (OVA)-sensitized mice...
October 7, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27713398/mechanisms-of-aging-related-proteinopathies-in-caenorhabditis-elegans
#14
Dong-Kyu Kim, Tae Ho Kim, Seung-Jae Lee
Aging is the most important risk factor for human neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Pathologically, these diseases are characterized by the deposition of specific protein aggregates in neurons and glia, representing the impairment of neuronal proteostasis. However, the mechanism by which aging affects the proteostasis system and promotes protein aggregation remains largely unknown. The short lifespan and ample genetic resources of Caenorhabditis elegans (C. elegans) have made this species a favorite model organism for aging research, and the development of proteinopathy models in this organism has helped us to understand how aging processes affect protein aggregation and neurodegeneration...
October 7, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27686285/cthrc1-promotes-angiogenesis-by-recruiting-tie2-expressing-monocytes-to-pancreatic-tumors
#15
Jaemin Lee, Jinhoi Song, Eun-Soo Kwon, Seongyea Jo, Min Kyung Kang, Yeon Jeong Kim, Yeonsil Hwang, Hosung Bae, Tae Heung Kang, Suhwan Chang, Hee Jun Cho, Song Cheol Kim, Seokho Kim, Sang Seok Koh
CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis...
September 30, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27659916/erk-mediated-phosphorylation-of-bis-regulates-nuclear-translocation-of-hsf1-under-oxidative-stress
#16
Hye Yun Kim, Yong-Sam Kim, Hye Hyeon Yun, Chang-Nim Im, Jeong-Heon Ko, Jeong-Hwa Lee
B-cell lymphoma (BCL)-2-interacting cell death suppressor (BIS) has diverse cellular functions depending on its binding partners. However, little is known about the effects of biochemical modification of BIS on its various activities under oxidative stress conditions. In this study, we showed that H2O2 reduced BIS mobility on SDS-polyacrylamide gels in a time-dependent manner via the activation of extracellular signaling-regulated kinase (ERK). The combined results of mass spectroscopy and computational prediction identified Thr285 and Ser289 in BIS as candidate residues for phosphorylation by ERK under oxidative stress conditions...
September 23, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27633092/adenovirus-mediated-foxp3-expression-in-lung-epithelial-cells-reduces-airway-inflammation-in-ovalbumin-and-cockroach-induced-asthma-model
#17
Soojin Park, Hwan-Suck Chung, Dasom Shin, Kyung-Hwa Jung, Hyunil Lee, Junghee Moon, Hyunsu Bae
Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma...
September 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27609031/msp-is-a-negative-regulator-of-inflammation-and-lipogenesis-in-ex-vivo-models-of-non-alcoholic-steatohepatitis
#18
Dipanjan Chanda, Jieyi Li, Yvonne Oligschlaeger, Mike L J Jeurissen, Tom Houben, Sofie M A Walenbergh, Ronit Shiri-Sverdlov, Dietbert Neumann
Non-alcoholic steatohepatitis (NASH), a metabolic disorder consisting of steatosis and inflammation, is considered the hepatic equivalent of metabolic syndrome and can result in irreversible liver damage. Macrophage-stimulating protein (MSP) is a hepatokine that potentially has a beneficial role in hepatic lipid and glucose metabolism via the activation of AMP-activated protein kinase (AMPK). In the current study, we investigated the regulatory role of MSP in the development of inflammation and lipid metabolism in various NASH models, both in vitro and ex vivo...
September 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27585719/osteoactivin-inhibition-of-osteoclastogenesis-is-mediated-through-cd44-erk-signaling
#19
Gregory R Sondag, Thomas S Mbimba, Fouad M Moussa, Kimberly Novak, Bing Yu, Fatima A Jaber, Samir M Abdelmagid, Werner J Geldenhuys, Fayez F Safadi
Osteoactivin is a heavily glycosylated protein shown to have a role in bone remodeling. Previous studies from our lab have shown that mutation in Osteoactivin enhances osteoclast differentiation but inhibits their function. To date, a classical receptor and a signaling pathway for Osteoactivin-mediated osteoclast inhibition has not yet been characterized. In this study, we examined the role of Osteoactivin treatment on osteoclastogenesis using bone marrow-derived osteoclast progenitor cells and identify a signaling pathway relating to Osteoactivin function...
September 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27585718/smad4-controls-bone-homeostasis-through-regulation-of-osteoblast-osteocyte-viability
#20
Young Jae Moon, Chi-Young Yun, Hwajung Choi, Sun-O Ka, Jung Ryul Kim, Byung-Hyun Park, Eui-Sic Cho
Regulation of osteoblast and osteocyte viability is essential for bone homeostasis. Smad4, a major transducer of bone morphogenetic protein and transforming growth factor-β signaling pathways, regulates apoptosis in various cell types through a mitochondrial pathway. However, it remains poorly understood whether Smad4 is necessary for the regulation of osteoblast and osteocyte viability. In this study, we analyzed Smad4Δ(Os) mice, in which Smad4 was subjected to tissue-specific disruption under the control of the 2...
September 2, 2016: Experimental & Molecular Medicine
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