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Experimental & Molecular Medicine

Tae Woo Jung, Sung Hoon Lee, Hyoung-Chun Kim, Joon Seok Bang, A M Abd El-Aty, Ahmet Hacımüftüoğlu, Yong Kyoo Shin, Ji Hoon Jeong
Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1)...
September 13, 2018: Experimental & Molecular Medicine
Fang Zheng, Qing Tang, Xiao-Hua Zheng, JingJing Wu, HaiDing Huang, Haibo Zhang, Swei Sunny Hann
β-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3...
September 12, 2018: Experimental & Molecular Medicine
Ye Ran Yoon, Tae-Gul Lee, Mi-Hyun Choi, Seung Woo Shin, Young-Gyu Ko, Im Joo Rhyu, Dong-Hoon Kim, Je Kyung Seong, Ja-Hyun Baik
The melanocortin-4 receptor (MC4R) belongs to the G protein-coupled receptor (GPCR) family and plays an essential role in the control of energy homeostasis. Here, we identified a novel MC4R-interacting protein, glucose-regulated protein 78 (GRP78), from a pulldown assay using hypothalamic protein extracts and the third intracellular loop of MC4R. We found that MC4R interacted with GRP78 in both the cytosol and at the cell surface and that this interaction increased when MC4R was internalized in the presence of the agonist melanotan-II (MTII)...
September 12, 2018: Experimental & Molecular Medicine
Alejandro La Greca, Claudia Solari, Veronica Furmento, Antonella Lombardi, Maria Celeste Biani, Cyntia Aban, Lucia Moro, Marcela García, Alejandra Sonia Guberman, Gustavo Emilio Sevlever, Santiago Gabriel Miriuka, Carlos Luzzani
Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interesting alternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellular vesicles (EVs) are a potential suitable substitute for MSCs in future cell-free-based therapeutic approaches. Unlike cells, EVs do not elicit acute immune rejection, and they can be produced in large quantities and stored until ready to use. Although the therapeutic potential of MSC EVs has already been proven, a thorough characterization of MSC EVs is lacking...
September 10, 2018: Experimental & Molecular Medicine
Jaya Gautam, Suhrid Banskota, Hyunji Lee, Yu-Jeong Lee, Yong Hyun Jeon, Jung-Ae Kim, Byeong-Seon Jeong
Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer with poor prognosis. In the present study, we demonstrated that Src, a non-receptor tyrosine kinase, might provide an effective therapeutic strategy to overcome TNBC invasion and metastasis, which are mediated via the synergistic action of the lysosomal enzyme cathepsin S (CTSS) and gelatinase MMP-9. Knock-down of MMP-9 and CTSS using siRNAs resulted in a synergistic suppression of MDA-MB-231 cell invasion, which was similarly observed with pharmacological inhibitors...
September 5, 2018: Experimental & Molecular Medicine
Defang Pang, Lu Wang, Jing Dong, Xiaoyin Lai, Qijuan Huang, Richard Milner, Longxuan Li
We have previously demonstrated that in response to cerebral ischemia (CI), the growth factor angiopoietin-1 (Ang1) and α5β1 integrin are both induced in cerebral vessels, which likely provide positive signals driving the endogenous angiogenic response and vascular protection after CI. However, the precise relationship between endothelial Ang1 and α5β1 integrin after CI remains poorly understood. Here, we investigated the effects of the interaction between the Ang1/Tie2 system and α5β1 integrin on brain endothelial cells (BECs) under cerebral ischemic conditions in vivo and in vitro...
September 5, 2018: Experimental & Molecular Medicine
Xue-Feng Li, Zong-Qiang Wang, Long-Yun Li, Guo-Qing Zhao, Shao-Nan Yu
Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. During TKA, muscle cells suffer from prolonged oxygen deficiency, which leads to altered cell metabolism that reduces the energy demand and maintains cell homeostasis before blood flow is restored. This study focused on the role of the lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the potential associated mechanism...
September 5, 2018: Experimental & Molecular Medicine
Prachetash Ghosh, Truc Thanh Luong, Masaud Shah, Trung Thanh Thach, Sangdun Choi, Sangho Lee, Dong-Kwon Rhee
Streptococcus pneumoniae is a polysaccharide-encapsulated bacterium. The capsule thickens during blood invasion compared with the thinner capsules observed in asymptomatic nasopharyngeal colonization. However, the underlying mechanism regulating differential CPS expression remains unclear. CPS synthesis requires energy that is supplied by ATP. Previously, we demonstrated a correlation between ATP levels and adenylate kinase in S. pneumoniae (SpAdK). A dose-dependent induction of SpAdK in serum was also reported...
September 5, 2018: Experimental & Molecular Medicine
Hyun-Kyung Chang, Pyung-Hwan Kim, Dong Wook Kim, Hyun-Min Cho, Mi Jin Jeong, Dea Han Kim, Yoon Ki Joung, Kyung Seob Lim, Han Byul Kim, Han Cheol Lim, Dong Keun Han, Young Joon Hong, Je-Yoel Cho
Atherosclerotic plaques within the vasculature may eventually lead to heart failure. Currently, cardiac stenting is the most effective and least invasive approach to treat this disease. However, in-stent restenosis is a complex chronic side effect of stenting treatment. This study used coronary stents coated with stem cells secreting angiogenic growth factors via an inducible genome-editing system to reduce stent restenosis and induce re-endothelialization within the artery. The characteristics of the cells and their adhesion properties on the stents were confirmed, and the stents were transplanted into a swine model to evaluate restenosis and the potential therapeutic use of stents with stem cells...
September 3, 2018: Experimental & Molecular Medicine
Sang Hoon Jeong, Yoojun Nam, Hyerin Jung, Juryun Kim, Yeri Alice Rim, Narae Park, Kijun Lee, Seungjin Choi, Yeonsue Jang, Yena Kim, Ji-Hoi Moon, Seung Min Jung, Sung-Hwan Park, Ji Hyeon Ju
After online publication of this article, the authors noticed an error in the Figure section. The correct statement of this article should have read as below.
August 29, 2018: Experimental & Molecular Medicine
Joo-Hee Choi, Ah-Ra Jang, Dong-Il Kim, Min-Jung Park, Seul-Ki Lim, Myung-Sun Kim, Jong-Hwan Park
Protein arginine methylation is a novel form of posttranslational modification mediated by protein arginine methyltransferase (PRMTs). PRMT1, a major isoform of the PRMT family, is responsible for various biological functions, including cellular differentiation. Although the important function that PRMT1 plays in various tissues is being increasingly recognized, its role in receptor activation of NF-κB ligand (RANKL)-induced osteoclastogenesis or osteoporosis has not yet been described. Here, we show that PRMT1 is essential for RANKL-induced osteoclastogenesis in vitro and for bone loss in vivo...
August 28, 2018: Experimental & Molecular Medicine
Seobin Yoon, Eui-Hwan Choi, Jung-Woong Kim, Keun P Kim
An important event enabling meiotic prophase I to proceed is the close juxtaposition of conjoined chromosome axes of homologs and their assembly via an array of transverse filaments and meiosis-specific axial elements into the synaptonemal complex (SC). During meiosis, recombination requires the establishment of a platform for recombinational interactions between the chromosome axes and their subsequent stabilization. This is essential for ensuring crossover recombination and proper segregation of homologous chromosomes...
August 28, 2018: Experimental & Molecular Medicine
Jieying Liu, So Youn Kim, Sun Shin, Seung-Hyun Jung, Seon-Hee Yim, Ji Youl Lee, Sug-Hyung Lee, Yeun-Jun Chung
The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also examined TFF3 expression in 108 Korean PCa specimens and 106 normal prostate tissues by immunohistochemistry (IHC) analysis...
August 23, 2018: Experimental & Molecular Medicine
Young-Jun Park, Da-Sol Kuen, Yeonseok Chung
Recent advances in the understating of tumor immunology suggest that cancer immunotherapy is an effective treatment against various types of cancer. In particular, the remarkable successes of immune checkpoint-blocking antibodies in clinical settings have encouraged researchers to focus on developing other various immunologic strategies to combat cancer. However, such immunotherapies still face difficulties in controlling malignancy in many patients due to the heterogeneity of both tumors and individual patients...
August 22, 2018: Experimental & Molecular Medicine
Joon Haeng Hur, Sang-Hee Lee, A-Young Kim, Young Ho Koh
After online publication of this article, the authors noticed an error in the ACKNOWLEDGEMENTS section.
August 20, 2018: Experimental & Molecular Medicine
Young Cheol Kang, Minuk Son, Sora Kang, Suyeol Im, Ying Piao, Kwang Suk Lim, Min-Young Song, Kang-Sik Park, Yong-Hee Kim, Youngmi Kim Pak
An excess of reactive oxygen species (ROS) relative to the antioxidant capacity causes oxidative stress, which plays a role in the development of Parkinson's disease (PD). Because mitochondria are both sites of ROS generation and targets of ROS damage, the delivery of antioxidants to mitochondria might prevent or alleviate PD. To transduce the antioxidant protein human metallothionein 1A (hMT1A) into mitochondria, we computationally designed a cell-penetrating artificial mitochondria-targeting peptide (CAMP)...
August 17, 2018: Experimental & Molecular Medicine
Myung-Hee Moon, Jae-Kyo Jeong, Jae-Suk Seo, Jae-Won Seol, You-Jin Lee, Meilang Xue, Christopher J Jackson, Sang-Youel Park
After publication of this article, the authors noticed an error in the figure section.
August 17, 2018: Experimental & Molecular Medicine
Seung Un Seo, Kyoung-Jin Min, Seon Min Woo, Taeg Kyu Kwon
Multiple cancer cells highly express cathepsin S, which has pro-tumoral effects. However, it was previously unknown whether knockdown or a pharmacological inhibitor (ZFL) of cathepsin S acts as an inducer of ER stress. Here, ZFL and knockdown of cathepsin S markedly induced ER stress through the up-regulation of calcium levels in the cytosol. Induction of calcium levels by inhibition of cathepsin S is markedly blocked by an inhibitor of the IP3 receptor and the ryanodine receptor Ca2+ channel in the ER, but an inhibitor of a mitochondrial Ca2+ uniporter had no effect on ZFL-induced calcium levels...
August 17, 2018: Experimental & Molecular Medicine
Chaithanya Chelakkot, Jaewang Ghim, Sung Ho Ryu
The gastrointestinal tract is a specialized organ in which dynamic interactions between host cells and the complex environment occur in addition to food digestion. Together with the chemical barrier of the mucosal layer and the cellular immune system, the epithelial cell layer performs a pivotal role as the first physical barrier against external factors and maintains a symbiotic relationship with commensal bacteria. The tight junction proteins, including occludin, claudins, and zonula occludens, are crucial for the maintenance of epithelial barrier integrity...
August 16, 2018: Experimental & Molecular Medicine
Youngwoo Choi, Duy Le Pham, Dong-Hyun Lee, So-Hee Lee, Seung-Hyun Kim, Hae-Sim Park
Eosinophil extracellular traps (EETs), a complex of DNA fibers and cytotoxic granule proteins, are implicated in the development of asthma; however, the pathophysiological function of EETs in immune responses has not been fully determined. The present study investigated the characteristics of EETs from patients with non-severe asthma (NSA, n = 20) and severe eosinophilic asthma (SEA, n = 20) and evaluated EET function. The percentage of EET-forming peripheral blood eosinophils stimulated with IL-5 and LPS was significantly higher in patients with SEA than in those with NSA (P = 0...
August 16, 2018: Experimental & Molecular Medicine
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