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Fatima-Zohra Boufroura, Carole Le Bachelier, Céline Tomkiewicz-Raulet, Dimitri Schlemmer, Jean-François Benoist, Pascal Grondin, Yann Lamotte, Olivier Mirguet, Sophie Mouillet-Richard, Jean Bastin, Fatima Djouadi
Carnitine Palmitoyl Transferase 2 (CPT2) deficiency is one of the most common inherited fatty acid oxidation (FAO) defects and represents a prototypical mitochondrial metabolic myopathy. Recent studies have suggested a pivotal role of AMPK in skeletal muscle plasticity and mitochondrial homeostasis. Thus, we tested the potential of GSK773, a novel direct AMPK activator, to improve or correct FAO capacities in muscle cells from patients harboring various mutations.We used control and patients' myotubes and studied parameters of fatty acid oxidation metabolism, of mitochondrial quantity and quality, and of differentiation...
July 11, 2018: Human Molecular Genetics
Jiahuan Zou, Mengwei Zhuang, Xiaopeng Yu, Na Li, Rudi Mao, Zhida Wang, Jianing Wang, Xiaoyan Wang, Huaiyu Zhou, Lining Zhang, Yongyu Shi
The effectiveness of immunotherapy targeting the immune checkpoint PD-L1/PD-1 pathway highlights importance of elucidating the regulatory mechanisms of PD-L1 expression in cancer cells. Previous studies demonstrate that oncogene MYC up-regulates PD-L1 expression in lymphomas. In the present study, we investigated the regulatory role of MYC in the PD-L1 expression induced by IFN-γ in HCC cells. Unexpectedly, knockdown of MYC expression using siRNA assay increased the inducible expression of PD-L1 both at mRNA and protein levels...
July 5, 2018: Molecular Immunology
Erik P Beadle, Joseph A Straub, Bruce A Bunnell, Jamie J Newman
Regulation of gene expression is critical for the maintenance of cell state and homeostasis. Aberrant regulation of genes can lead to unwanted cell proliferation or misdirected differentiation. Here we investigate the role of MED31, a highly conserved subunit of the Mediator complex, to determine the role this subunit plays in the maintenance of human mesenchymal stem cell (hMSC) state. Using siRNA-mediated knockdown of MED31 we demonstrate a decrease in self-renewal based on cell assays and monitoring of gene expression...
July 13, 2018: Molecular Biology Reports
Mathew S Eapen, Anudeep Kota, Howard Vindin, Kielan D McAlinden, Dia Xenaki, Brian G Oliver, Deepak A Deshpande, Sukhwinder Singh Sohal, Pawan Sharma
Increased airway smooth muscle (ASM) mass is observed in COPD which is correlated with disease severity and negatively impact lung function. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase  activated by various stress stimuli, including reactive oxygen species, tumor necrosis factor-α, and lipopolysaccharide and is known to regulate cell proliferation...
July 13, 2018: Clinical Science (1979-)
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be the leading cause of neonatal mortality and morbidities that can extend into adult life. Few treatment options stem from our incomplete understanding of the mechanisms of human labor and delivery. Activation of the inflammatory response in gestational tissues by inflammation and/or infection leads to the production of pro-inflammatory and pro-labor mediators, thus preterm birth. Interferon regulatory factor 5 (IRF5) has recently emerged as an important pro-inflammatory transcription factor involved in acute and chronic inflammation...
July 13, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Yu-Qian Wang, Aalia Batool, Su-Ren Chen, Yi-Xun Liu
Reduced contractility of the testicular peritubular myoid (PTM) cells may contribute to human male sub- or infertility. Transcription factor GATA4 in Sertoli and Leydig cells is essential for murine spermatogenesis; but limited attention has been paid to the potential role of GATA4 in PTM cells. In primary cultures of mouse PTM cells, siRNA knockdown of GATA4 increased the contractile activity, while GATA4 overexpression significantly attenuated the contractility of PTM cells using a collagen gel contraction assay...
July 13, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Darren M Hutt, Salvatore Loguercio, Daniela Martino Roth, Andrew I Su, William E Balch
Inherited and somatic rare diseases result from > 200,000 genetic variants leading to loss- or gain-of-toxic function, often caused by protein misfolding. Many of these misfolded variants fail to properly interact with other proteins. Understanding the link between factors mediating the transcription, translation, and protein folding of these disease-associated variants remains a major challenge in cell biology. Herein, we utilized the cystic fibrosis transmembrane conductance regulator (CFTR) protein as a model and performed a proteomics-based high-throughput screen (HTS) to identify pathways and components affecting the folding and function of the most common cystic fibrosis-associated mutation, the F508del variant of CFTR...
July 13, 2018: Journal of Biological Chemistry
Duo Zhang, Heedoo Lee, Xiaoyun Wang, Ashish Rai, Michael Groot, Yang Jin
Exosomes (EXOs) are a type of extracellular nanovesicles released from living cells. Accumulating evidence suggests that EXOs are involved in the pathogenesis of human diseases, including lung conditions. In recent years, the potential of EXO-mediated drug delivery has gained increasing interest. In this report, we investigated whether inhaled EXOs serve as an efficient and practical delivery vehicle to activate or inhibit alveolar macrophages (AMs), subsequently modulating pulmonary immune responses. We first identified the recipient cells of the inhaled EXOs, which were labeled with PKH26...
July 10, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Zhi-Bin Zhou, Bo Yang, Xiaohao Li, Hao Liu, Gang Lei
BACKGROUND Lysophosphatidic acid (LPA) is an active compound of oxidized low-density lipoprotein that serves as an endogenous TLR4 ligand. Ligand activation of TLR4 activates nuclear factor-kappaB (NF-κB) and the transcription of NF-κB-regulated inflammatory cytokines, which are involved in the development of atherosclerosis. MMP9 is a member of the MMP family and can affect plaque stability. However, the mechanism responsible for the effect of LPA on the expression and activation of MMP9 has not been fully elucidated...
July 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Seok Kim, Seung Un Seo, Kyoung-Jin Min, Seon Min Woo, Ju-Ock Nam, Peter Kubatka, Shin Kim, Jong-Wook Park, Taeg Kyu Kwon
Garcinol is a polyisoprenylated benzophenone derived from the Garcinia indica fruit that possess potential therapeutic effects such as inhibition of inflammation and tumor expansion. Here, we investigated whether garcinol induces TRAIL sensitization in renal carcinoma cells. Single treatment with garcinol or TRAIL did not effect on apoptosis. However, combined treatment with garcinol plus TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung carcinoma (A549), and hepatoma (SK-Hep1) cells...
July 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Pankaj Garg, Shambhavi Pandey, Seonwoo Hoon, Jang Kyeong Jae, Lee Myung Chul, Yun-Hoon Choung, Pill-Hoon Choung, Jong Hoon Chung
c-Jun N-terminal kinase 2 (JNK2) is primarily responsible for the oncogenic transformation of the transcription factor c-Jun. Expression of the proto-oncogene c-Jun progresses the cell cycle from G1 to S phase, but when its expression becomes awry it leads to uncontrolled proliferation and angiogenesis. Delivering a JNK2 siRNA (siJNK2) in tumor tissue was anticipated to reverse the condition with subsequent onset of apoptosis which predominantly requires an efficient delivering system capable of penetrating through the compact tumor mass...
July 9, 2018: International Journal of Biological Macromolecules
Zhiling Tang
PURPOSE: To investigate the effects of human enhancer of filamentation 1 (HEF1) gene on the proliferation, invasion and metastasis of bladder cancer cells. METHODS: Three human bladder cancer cell lines (T24, EJ and BIU-87) were selected to extract total RNA at logarithmic growth phase. The relative expression level of HEF1 in these cell lines was detected by semi-quantitative reverse transcription PCR (RT-PCR), and the cell lines with relatively high expression and relatively low expression level of HEF1 cells were identified...
May 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Xintai Zhong, Zhaolin Long, Shihao Wu, Meiling Xiao, Weilie Hu
PURPOSE: The purpose of this study was to investigate the expression of long-chain non-coding RNA (lncRNA) SNHG7 in bladder cancer tissues and cell lines, and to explore its impact on bladder cancer cell proliferation, apoptosis and invasion processes. METHODS: Bladder cancer tissues and near-cancer tissues were collected. The expression of lncRNA-SNHG7 in tissues and cell lines was detected by real-time PCR (RT-PCR). The expression of lncRNA-SNHG7 was downregulated by RNA interference (siRNA) as detected by RT-PCR that was used to detect the interference efficiency...
May 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Hongyang Jiang, Gaurab Pokhrel, Yinwei Chen, Tao Wang, Chunping Yin, Jihong Liu, Shaogang Wang, Zhuo Liu
Background: Solute-linked carrier 26 gene family 6 (SLC26A6), which is mainly expressed in intestines and kidneys, is a multifunctional anion transporter crucial in the transport of oxalate anions. This study aimed to investigate the role of kidney SLC26A6 in urolithiasis. Methods: Patients were divided into two groups: stone formers and nonstone formers. Samples were collected from patients following nephrectomy. Lentivirus with Slc26a6 (lentivirus-Slc26a6) sequence and lentivirus with siRNA-Slc26a6 (lentivirus-siRNA-Slc26a6) sequence were transfected into rats' kidneys respectively and Slc26a6 expression was detected using Western blot and immunohistochemical analyses...
2018: PeerJ
Pazit Y Cohen, Raphael Breuer, Shulamit B Wallach-Dayan
Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thy1-deficient mice with wild-type lymphocytes that Thy1-deficient fibroblasts accumulate and promote fibrosis and an "inflammation-free" environment. Here, we aimed to identify the critical effects of Thy1, or the absence of Thy1, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition...
2018: Mediators of Inflammation
Gabriele Domschke, Fabian Linden, Lukas Pawig, Anna Hafner, Mohammadreza Akhavanpoor, Jürgen Reymann, Andreas O Doesch, Christian Erbel, Christian Weber, Hugo A Katus, Heidi Noels, Holger Erfle, Christian A Gleissner, Heiko Runz
Macrophage-derived foam cells are key regulators of atherogenesis. They accumulate in atherosclerotic plaques and support inflammatory processes by producing cytokines and chemokines. Identifying factors that regulate macrophage lipid uptake may reveal therapeutic targets for coronary artery disease (CAD). Here, we establish a high-throughput screening workflow to systematically identify genes that impact the uptake of DiI-labeled low-density lipoprotein (LDL) into monocyte-derived primary human macrophages...
July 12, 2018: Scientific Reports
Kiyohito Sasa, Kentaro Yoshimura, Atsushi Yamada, Dai Suzuki, Yoichi Miyamoto, Hiroko Imai, Kazuhiro Nagayama, Koutaro Maki, Matsuo Yamamoto, Ryutaro Kamijo
Monocarboxylate transporter-1 (MCT-1) is a transmembrane transporter for monocarboxylates including lactate and pyruvate. Silencing Mct1 by its small interfering RNA (siRNA) suppressed the expression of marker genes for osteoblast differentiation, namely, Tnap, Runx2, and Sp7, induced by BMP-2 in mouse myoblastic C2C12 cells. Mct1 siRNA also suppressed alkaline phosphatase activity, as well as expressions of Tnap and Bglap mRNAs in mouse primary osteoblasts. On the other hand, Mct1 siRNA did not have effects on the Smad1/5 or ERK/JNK pathways in BMP-2-stimulated C2C12 cells, while it up-regulated the mRNA expression of p53 (Trp53) as well as nuclear accumulation of p53 in C2C12 cells in a BMP-2-independent manner...
July 12, 2018: Scientific Reports
Atul Kakrana, Sandra M Mathioni, Kun Huang, Reza Hammond, Lee Vandivier, Parth Patel, Siwaret Arikit, Olga Shevchenko, Alex E Harkess, Bruce Kingham, Brian D Gregory, James H Leebens-Mack, Blake C Meyers
In grasses, two pathways generate diverse and numerous 21-nt (pre-meiotic) and 24-nt (meiotic) phased siRNAs highly enriched in anthers, the male reproductive organs. These "phasiRNAs" are analogous to mammalian piRNAs, yet their functions and evolutionary origins remain largely unknown. The 24-nt meiotic phasiRNAs have only been described in grasses, wherein their biogenesis is dependent on a specialized Dicer (DCL5). To assess how evolution gave rise to this pathway, we examined reproductive phasiRNA pathways in non-grass monocots: garden asparagus, daylily and lily...
July 12, 2018: Genome Research
Pei Hu, Changzheng Ke, Xingrong Guo, Pan Ren, Yaoyao Tong, Sen Luo, Yulin He, Zhiqiang Wei, Bin Cheng, Ruiming Li, Jie Luo, Zhongji Meng
AIM: The aim of this study is to investigate the role of glypican-3(GPC3)/wnt/β-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin. METHODS: HepG2 cells were treated with various concentrations of curcumin and/or GPC3-targeting siRNA in the presence or absence of 3-MA. Cell proliferation and apoptosis were determined by MTT and TUNEL assay, respectively. Expression of GPC3, β-catenin, c-myc, LC3, and Beclin1 was determined by western blotting...
June 21, 2018: Digestive and Liver Disease
Motohiko Suzuki, Makoto Yokota, Tamami Matsumoto, Shinya Ozaki
BACKGROUND: We previously reported that siRNA-induced CD40-silenced dendritic cells (DCs) inhibit allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, synergic effects of gene silencing in DCs by ≥2 siRNAs have not been reported to control allergic diseases. Therefore, we investigated the synergistic effects of the silencing of CD40 and CD86 in DCs on allergic responses. METHODS: Mice were treated with CD40/CD86-silenced DCs, which were transfected with CD40/CD86 siRNAs and pulsed with ovalbumin (OVA) antigen...
July 12, 2018: International Archives of Allergy and Immunology
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