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Experimental & Molecular Medicine

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
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
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
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
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
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
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
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
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
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
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
Dae Kyoung Kim, Eun Jin Seo, Eun J Choi, Su In Lee, Yang Woo Kwon, Il Ho Jang, Seung-Chul Kim, Ki-Hyung Kim, Dong-Soo Suh, Kim Seong-Jang, Sang Chul Lee, Jae Ho Kim
Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2...
2016: Experimental & Molecular Medicine
Hye Jin Heo, Hyoung Kyu Kim, Jae Boum Youm, Sung Woo Cho, In-Sung Song, Sun Young Lee, Tae Hee Ko, Nari Kim, Kyung Soo Ko, Byoung Doo Rhee, Jin Han
Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0)...
2016: Experimental & Molecular Medicine
Cheol Yi Hong, Hyun-Ju Lee, Nu-Ri Choi, Sung-Hoon Jung, Manh-Cuong Vo, My Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins...
2016: Experimental & Molecular Medicine
Young C Chung, Won-Ho Shin, Jeong Y Baek, Eun J Cho, Hyung H Baik, Sang R Kim, So-Yoon Won, Byung K Jin
The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay...
2016: Experimental & Molecular Medicine
Jeong Ah Lim, Yong-Sung Juhnn
Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells...
2016: Experimental & Molecular Medicine
Su-Kang Kong, Byung Soo Kim, Tae Gi Uhm, Hun Soo Chang, Jong Sook Park, Sung Woo Park, Choon-Sik Park, Il Yup Chung
Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin...
2016: Experimental & Molecular Medicine
Mee-Sup Yoon, Cheol Soo Choi
Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance...
2016: Experimental & Molecular Medicine
Jae-Hyun Yang, Tae-Yang Song, Chanhee Jo, Jinyoung Park, Han-Young Lee, Ilang Song, Suji Hong, Kwan Young Jung, Jaehoon Kim, Jeung-Whan Han, Hong-Duk Youn, Eun-Jung Cho
Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells...
2016: Experimental & Molecular Medicine
Hee Gyung Kang, Hyun Kyung Lee, Yo Han Ahn, Je-Gun Joung, Jaeyong Nam, Nayoung K D Kim, Jung Min Ko, Min Hyun Cho, Jae Il Shin, Joon Kim, Hye Won Park, Young Seo Park, Il-Soo Ha, Woo Yeong Chung, Dae-Yeol Lee, Su Young Kim, Woong Yang Park, Hae Il Cheong
Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end-stage renal failure during childhood and adolescence and exhibits an autosomal recessive pattern of inheritance. Genetic diagnosis is quite limited owing to genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step-wise screening of Sanger sequencing and targeted exome sequencing for the genetic diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by Sanger sequencing in phenotypically classified patients...
2016: Experimental & Molecular Medicine
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