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https://www.readbyqxmd.com/read/28437865/a-novel-role-of-astrocyte-elevated-gene-1-aeg-1-in-regulating-non-alcoholic-steatohepatitis-nash
#1
Jyoti Srivastava, Chadia L Robertson, Kareem Ebeid, Mikhail Dozmorov, Devaraja Rajasekaran, Rachel Mendoza, Ayesha Siddiq, Maaged A Akiel, Nidhi Jariwala, Xue-Ning Shen, Jolene J Windle, Mark A Subler, Nitai D Mukhopadhyay, Shah Giashuddin, Shobha Ghosh, Zhao Lai, Yidong Chen, Paul B Fisher, Aliasger K Salem, Arun J Sanyal, Devanand Sarkar
Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease in the Western world. However, an optimum therapy for NASH is yet to be established mandating more in-depth investigation into the molecular pathogenesis of NASH to identify novel regulatory molecules and develop targeted therapies. Here, we unravel a unique function of Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) in NASH using a transgenic mouse with hepatocyte-specific overexpression of AEG-1 (Alb/AEG-1) and a conditional hepatocyte-specific AEG-1 knockout mouse (AEG-1(ΔHEP) )...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437863/sirt3-acts-as-a-negative-regulator-of-autophagy-dictating-hepatocyte-susceptibility-to-lipotoxicity
#2
Songtao Li, Xiaobing Dou, Hua Ning, Qing Song, Wei Wei, Ximei Zhang, Chen Shen, Jiaxin Li, Changhao Sun, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be fully elucidated. SIRT3 is an NAD(+) -dependent deacetylase primarily located inside mitochondria. In this study, we demonstrated that a SFAs-rich high-fat diet (HFD) was more detrimental to the liver than an isocaloric unsaturated FAs-rich HFD. Unexpectedly, SIRT3 expression/activity were significantly elevated in the livers of mice exposed to the SFAs-rich HFD...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437526/prominin-1-is-a-novel-regulator-of-autophagy-in-the-human-retinal-pigment-epithelium
#3
Sujoy Bhattacharya, Jinggang Yin, Christina S Winborn, Qiuhua Zhang, Junming Yue, Edward Chaum
Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed in stem cell lineages, and has recently been implicated in cancer stem cell survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular dystrophy (STGD4). Despite the apparent structural role of Prom1 in photoreceptors, its role in other cells of the retina is unknown. The purpose of this study is to investigate the role of Prom1 in the highly metabolically active cells of the retinal pigment epithelium (RPE)...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28437476/clc-3-chloride-channel-mediates-the-role-of-parathyroid-hormone-1-34-on-osteogenic-differentiation-of-osteoblasts
#4
Xiaolin Lu, Yin Ding, Qiannan Niu, Shijie Xuan, Yan Yang, Yulong Jin, Huan Wang
INTRODUCTION: Different concentrations of parathyroid hormone [1-34] (PTH [1-34]) can have totally opposite effects on osteoblasts. Intermittent stimulation with PTH can significantly increase bone mineral density in vitro, mainly through the protein kinase A (PKA) signaling pathway, which phosphorylates runt-related transcription factor 2 (Runx2). The ClC-3 chloride channel, an important anion channel, can also promote osteogenesis via the Runx2 pathway based on recent studies. The purpose of our study, therefore, is to research whether the ClC-3 chloride channel has an effect on PTH osteodifferentiation in MC3T3-E1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#5
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28437248/protective-effect-of-calretinin-on-testicular-leydig-cells-via-the-inhibition-of-apoptosis
#6
Wendan Xu, Qian Zhu, Bei Zhang, Shan Liu, Xiaonan Dai, Chao Gao, Li Gao, Yugui Cui
The core mechanism of Late-onset hypogonadism (LOH) is the deficiency of androgen due to the functional and quantitative decline of testicular Leydig cells. Here we explored the protective effect of calretinin, a Ca(2+)-binding protein, on Leydig cells. We found in MLTC-1 cells transfected with LV-calb2, the cell viability and optical density (OD) were higher (p<0.05), cells in the S phase of the cell cycle were increased (p<0.01) and p-ERK1/2 and p-AKT levels were significantly higher (p<0.01 and p<0...
April 24, 2017: Aging
https://www.readbyqxmd.com/read/28436754/5-7-3-4-tetramethoxyflavone-protects-chondrocytes-from-er-stress-induced-apoptosis-through-regulation-of-the-ire1%C3%AE-pathway
#7
Longhuo Wu, Haiqing Liu, Linfu Li, Daohua Xu, Yun Gao, Yingjie Guan, Qian Chen
AIM OF THE STUDY: To investigate the roles of endoplasmic reticulum (ER) transmembrane sensor inositol-requiring enzyme-1 (IRE1)α signaling in ER stress-induced chondrocyte apoptosis, and to determine the molecular mechanisms underlying chondroprotective activity of 5,7,3',4'-tetramethoxyflavone (TMF) from Murraya Exotica. MATERIALS AND METHODS: IRE1α was knocked down by siRNA transfection in chondrocytes, which were harvested from rats' knee cartilages. Chondrocytes with IRE1α deficiency were administrated with tunicamycin (TM) and TMF...
April 24, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28436570/bre-enhances-osteoblastic-differentiation-by-promoting-the-mdm2-mediated-degradation-of-p53
#8
Fujun Jin, Yiliang Wang, Xiaojing Wang, Yanting Wu, Xiaoyan Wang, Qiuying Liu, Yexuan Zhu, Enqi Liu, Jianglin Fan, Yifei Wang
Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436437/allele-selective-suppression-of-mutant-huntingtin-in-primary-human-blood-cells
#9
James R C Miller, Edith L Pfister, Wanzhao Liu, Ralph Andre, Ulrike Träger, Lori A Kennington, Kimberly Lo, Sipke Dijkstra, Douglas Macdonald, Gary Ostroff, Neil Aronin, Sarah J Tabrizi
Post-transcriptional gene silencing is a promising therapy for the monogenic, autosomal dominant, Huntington's disease (HD). However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436029/wnt4-acts-downstream-of-bmp2-to-mediate-the-regulation-of-atra-signaling-on-runx1-expression-implications-for-terminal-differentiation-of-antler-chondrocytes
#10
Hong-Liang Zhang, Zhan-Qing Yang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well-known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA...
April 24, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28435473/downregulation-of-mitochondrial-cyclooxygenase-2-inhibits-the-stemness-of-nasopharyngeal-carcinoma-by-decreasing-the-activity-of-dynamin-related-protein-1
#11
Teng-Jian Zhou, Shi-Li Zhang, Cheng-Yong He, Qun-Ying Zhuang, Pei-Yu Han, Sheng-Wei Jiang, Huan Yao, Yi-Jun Huang, Wen-Hua Ling, Yu-Chun Lin, Zhong-Ning Lin
Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues...
2017: Theranostics
https://www.readbyqxmd.com/read/28435471/nucleolin-targeted-extracellular-vesicles-as-a-versatile-platform-for-biologics-delivery-to-breast-cancer
#12
Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28435469/interleukin-3-receptor-targeted-exosomes-inhibit-in-vitro-and-in-vivo-chronic-myelogenous-leukemia-cell-growth
#13
Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents...
2017: Theranostics
https://www.readbyqxmd.com/read/28435457/tumor-hypoxia-regulates-forkhead-box-c1-to-promote-lung-cancer-progression
#14
Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh
Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain. Increasing evidence indicates that FOXC1 is involved in tumor progression. However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans. Hypoxic stresses significantly induced FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsive element (HRE) in the FOXC1 promoter...
2017: Theranostics
https://www.readbyqxmd.com/read/28435453/sirna-delivery-with-pegylated-graphene-oxide-nanosheets-for-combined-photothermal-and-genetherapy-for-pancreatic-cancer
#15
Feng Yin, Kuan Hu, Yangzi Chen, Mengying Yu, Dongyuan Wang, Qianqian Wang, Ken-Tye Yong, Fei Lu, Yongye Liang, Zigang Li
Since the successful exfoliation of graphene from graphite in 2004, graphene and graphene oxide (GO) have been considered the most promising two-dimensional (2D) nanomaterials with distinguished physical and chemical characteristics and have attracted great attention in many different fields. Graphene oxide is well-known for its distinct physiochemical properties and shows only minimal cytotoxicity compared to carbon nanotubes. Until now, only limited efforts have been invested in utilizing GO for gene therapy in pancreatic cancer treatments...
2017: Theranostics
https://www.readbyqxmd.com/read/28435292/reg3a-promotes-the-proliferation-migration-and-invasion-of-gastric-cancer-cells
#16
Zhou-Feng Chen, Zhi-Ming Huang, Hai-Bo Xue, Xiu-Qing Lin, Ren-Ping Chen, Meng-Jun Chen, Rui-Fang Jin
The mechanism underlying the metastasis of gastric cancer (GC) cells remains elusive. REG3A is considered an oncogene in various cancers, but in GC its role is unclear. Here, we report that the expression of REG3A was significantly increased in the tumor tissues of patients with GC compared with the matched normal tissues. Knockdown of REG3A induced by specific small interfering RNA (siRNA) significantly repressed the proliferation of GC cells for 24 h or 48 h. Moreover, knockdown of REG3A significantly suppressed the migration, invasion, and adhesion of GC cells in vitro...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435150/ym155-down-regulates-survivin-and-induces-p53-up-regulated-modulator-of-apoptosis-puma-dependent-in-oral-squamous-cell-carcinoma-cells
#17
Xiang Yan, Han Su
BACKGROUND YM155, which inhibits the anti-apoptotic protein survivin, is known to exert anti-tumor effects in various cancers. However, there were few reports describing the inhibitory effect of YM155 on human oral squamous cell carcinoma (OSCC) cells that highly express survivin. In this study, we investigated the anti-tumor effects of YM155 on OSCC cells and then examined its molecular mechanisms. MATERIAL AND METHODS SCC9 cells of OSCC were treated with series of concentrations of YM155 (0.01, 0.1, 1, and 10 ng/ml) for 6, 12, and 24 h...
April 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28434945/prognostic-biomarker-identification-through-integrating-the-gene-signatures-of-hepatocellular-carcinoma-properties
#18
Jialin Cai, Bin Li, Yan Zhu, Xuqian Fang, Mingyu Zhu, Mingjie Wang, Shupeng Liu, Xiaoqing Jiang, Jianming Zheng, XinXin Zhang, Peizhan Chen
Many molecular classification and prognostic gene signatures for hepatocellular carcinoma (HCC) patients have been established based on genome-wide gene expression profiling; however, their generalizability is unclear. Herein, we systematically assessed the prognostic effects of these gene signatures and identified valuable prognostic biomarkers by integrating these gene signatures. With two independent HCC datasets (GSE14520, N=242 and GSE54236, N=78), 30 published gene signatures were evaluated, and 11 were significantly associated with the overall survival (OS) of postoperative HCC patients in both datasets...
April 12, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28434932/combinatorial-treatment-of-idiopathic-pulmonary-fibrosis-using-nanoparticles-with-prostaglandin-e-and-sirna-s
#19
O B Garbuzenko, V Ivanova, V Kholodovych, D C Reimer, K R Reuhl, E Yurkow, D Adler, T Minko
Inhalation delivery of prostaglandin E (PGE2) in combination with selected siRNA(s) was proposed for the efficient treatment of idiopathic pulmonary fibrosis (IPF). Nanostructured lipid carriers (NLC) were used as a delivery system for PGE2 with and without siRNAs targeted to MMP3, CCL12, and HIF1Alpha mRNAs. The model of IPF was developed in SKH1 mice by intratracheal administration of bleomycin at a dose of 1.5U/kg. Results showed that NLC-PGE2 in combination with three siRNAs delivered locally to the lungs by inhalation markedly reduced mouse body mass, substantially limited hydroxyproline content in the lungs and disturbances of the mRNAs and protein expression, restricted lung tissue damage and prevented animal mortality...
April 18, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28434297/efficiency-of-sirna-for-removal-of-transthyretin-v30m-in-a-ttr-leptomeningeal-animal-model
#20
Paula Gonçalves, Helena Martins, Susete Costelha, Maria J Saraiva
No abstract text is available yet for this article.
March 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
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