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https://www.readbyqxmd.com/read/29223853/role-of-mir-195-in-cigarette-smoke-induced-chronic-obstructive-pulmonary-disease
#1
Wenchao Gu, Yaping Yuan, Hua Yang, Hao Wu, Linxuan Wang, Zhijun Tang, Qiang Li
Chronic obstructive pulmonary disease (COPD) is regarded as a persistent respiratory symptom, mainly caused by cigarette smoking. Recent data have suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we found that miR-195 was significantly upregulated in the lung tissues of patients with COPD compared to in never smokers. miR-195 expression was also upregulated in cigarette smoke (CS)-exposed mice. Lentivirus-mediated knockdown of miR-195 alleviated CS-induced lung pathological changes and reduced inflammatory cell infiltration as well as production of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid...
December 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29221804/the-impact-of-the-cd9-tetraspanin-on-lentivirus-infectivity-and-exosome-secretion
#2
Kai O Böker, Nicolas Lemus-Diaz, Rafael Rinaldi Ferreira, Lara Schiller, Stefan Schneider, Jens Gruber
Efficient transduction tools are a hallmark for both research and therapy development. Here, we introduce new insights into the generation of lentiviral vectors with improved performance by utilizing producer cells with increased production rates of extracellular vesicles through CD9 overexpression. Most human cells secrete small vesicles from their surface (microvesicles) or intraluminal endosome-derived membranes (exosomes). In particular, enhanced levels of the tetraspanin CD9 result in significantly increased numbers of extracellular vesicles with exosome-like features that were secreted from four different human cell lines...
November 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29220380/hexokinase-2-hk2-the-tumor-promoter-in-glioma-is-downregulated-by-mir-218-bmi1-pathway
#3
Hui Liu, Nan Liu, Yingduan Cheng, Weilin Jin, Pengxing Zhang, Xin Wang, Hongwei Yang, Xiaoshan Xu, Zhen Wang, Yanyang Tu
In cancer, glycolysis driving enzymes and their regulating microRNAs are one of the key focus of oncology research lately. The glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioma, the most common malignant brain tumor. In the present study, we studied the tumorigenic role of HK2 in glioma, and clarified the mechanism of miR-218 induced HK2 regulation in glioma development. The HK2 expression in patient derived glioma and non neoplastic brain tissue was quantified. The HK2 silenced U87 and U251 cell lines were assessed for their proliferation, migration and invasive potential in vitro, while the tumor forming potential of U87 cells was evaluated in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/29218098/overexpression-of-microrna-145-protects-against-rat-myocardial-infarction-through-targeting-pdcd4
#4
Hao Xu, Heng Cao, Guoqing Zhu, Shaowen Liu, Hongli Li
Myocardial infarction (MI) is a common cardiovascular disease with high mortality. The aim of the present study was to determine the biological role of miR-145 in MI rats and hypoxia-injured cardiomyocytes and to elucidate the potential mechanism. MI rats were induced by left anterior descending artery (LAD) ligation. qRT-PCR and western blot analysis were performed to determine the mRNA and protein levels, respectively. Compared with sham group, miR-145 levels in MI group were significantly decreased. We observed that lentivirus-mediated overexpression of miR-145 significantly improves cardiac function, reduces infarcted tissue size and prevents post-infarction induced apoptosis in rats after MI...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29218001/upregulation-of-cdh1-attenuates-isoflurane-induced-neuronal-apoptosis-and-long-term-cognitive-impairments-in-developing-rats
#5
Xuan Li, Kai Wei, Rong Hu, Bo Zhang, Li Li, Li Wan, Chuanhan Zhang, Wenlong Yao
Neonatal exposure to isoflurane can result in neuroapoptosis and persistent cognitive impairments. However, the underlying mechanisms remain elusive. Anaphase-promoting complex/cyclosome (APC/C) and its co-activator Cdh1 are E3 ubiquitin ligases that play important roles in the central nervous system, including in the regulation of neuronal survival, synaptic development, and mammalian learning and memory. However, whether APC/C-Cdh1 is involved in isoflurane-induced neurotoxicity in developing rats remains unclear...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29215720/gsk3%C3%AE-regulates-ameloblast-differentiation-via-wnt-and-tgf-%C3%AE-pathways
#6
Yaling Yang, Ziyue Li, Guoqing Chen, Jie Li, Hui Li, Mei Yu, Weiping Zhang, Weihua Guo, Weidong Tian
Wnt and TGF-β signaling pathways participate in regulating a variety of cell fates during organogenesis, including tooth development. Despite well-documented, the specific mechanisms, especially how these two pathways act coordinately in regulating enamel development, remain unknown. In this study, we identified Glycogen Synthase Kinase 3 beta (GSK3β), a negative regulator of Wnt signal pathway, participated in ameloblast differentiation via Wnt and TGF-β pathways during enamel development. In vitro rat mandible culture treated with specific GSK3β inhibitor SB415286 displayed enamel defects, accompanied by disrupted ameloblasts polarization, while odontoblasts and dentin appeared to be unaffected...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215185/potential-of-autologous-adipose-derived-stem-cells-to-regenerate-atrophied-muscle-in-a-rat-model
#7
Ji Ung Park, Sung Tack Kwon
Muscle atrophy results in severe functional impairment and is a significant clinical problem. We examined and characterized the therapeutic effects of autologous adipose-derived stem cells (ADCSs) using an in vivo muscle atrophy rat model. To identify the effect of injected ADSCs into muscle, we developed the following two models of muscle atrophy in rats: induction of denervation by sciatic nerve defects; and nerve repair after severing the sciatic nerve. The inguinal fat pads were harvested from each rat and autologous ADSCs were cultured and ADSCs were injected in the right hind limbs as the experimental group, while normal saline was injected in the left hind limbs, which served as the control group...
December 7, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29214451/stmn1-is-overexpressed-in-adrenocortical-carcinoma-and-promotes-a-more-aggressive-phenotype-in-vitro
#8
Anna Aronova, Irene M Min, Michael J P Crowley, Suraj J Panjwani, Brendan M Finnerty, Theresa Scognamiglio, Yi-Fang Liu, Timothy G Whitsett, Shipra Garg, Michael J Demeure, Olivier Elemento, Rasa Zarnegar, Thomas J Fahey Iii
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis and few therapeutic options. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. We aimed to evaluate expression of STMN1 in ACC and to elucidate how this may contribute to its malignant phenotype...
December 6, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29212573/knockdown-of-nf-%C3%AE%C2%BAb1-by-shrna-inhibits-the-growth-of-renal-cell-carcinoma-in-vitro-and-in-vivo
#9
Amanda Ikegami, Luiz Felipe S Teixeira, Marina S Braga, Matheus Henrique Dos S Dias, Eduardo C Lopes, Maria Helena Bellini
Renal cell carcinoma (RCC) accounts for approximately 2-3% of human malignancies and is the most aggressive among urologic tumors. Biological heterogeneity, drug resistance and chemotherapy side effects are the biggest obstacles to the effective treatment of RCC. The NF-кB transcription factor is one of several molecules identified to be responsible for the aggressive phenotype of this tumor. In the past decade, several studies have demonstrated the activation of NF-kB in RCC, and many implicated NF-κB1 (p50) as an important molecule in tumor progression and metastasis...
December 1, 2017: Oncology Research
https://www.readbyqxmd.com/read/29212357/manufacture-of-third-generation-lentivirus-for-preclinical-use-with-process-development-considerations-for-translation-to-good-manufacturing-practice-gmp
#10
Carolina Gándara, Valerie Affleck, Elizabeth Ann Stoll
Lentiviral vectors are used in laboratories around the world for in vivo and ex vivo delivery of gene therapies, and increasingly used for clinical investigation as well as preclinical applications. The third-generation lentiviral vector system has many advantages, including high packaging capacity, stable gene expression in both dividing and post-mitotic cells, and low immunogenicity in the recipient organism. Yet the manufacture of these vectors is challenging, especially at high titres required for direct use in vivo, and further challenges are presented by the process of translating preclinical gene therapies toward manufacture of products for clinical investigation...
December 6, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29212239/effects-of-lentivirus-mediated-endostatin-on-endothelial-progenitor-cells
#11
Jing Ai, Jun-Hui Sun, Jian Ma, Ke Yao
Endothelial progenitor cells (EPCs) are candidates for gene therapies against retinal neovascularization (NV). The aim of present study was to investigate the effects of endostatin transfection on EPC function. In the present study, the EPCs were infected with lentivirus overexpressing endostatin. The transfection effects of endostatin overexpression on the proliferation, migratory, differentiation, apoptosis and the cell cycle of this cell line were determined. The real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays showed high expression levels of endostatin...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209168/direct-neuronal-glucose-uptake-is-required-for-contextual-fear-acquisition-in-the-dorsal-hippocampus
#12
Liang Kong, Yan Zhao, Wen-Juan Zhou, Hui Yu, Shuai-Wen Teng, Qi Guo, Zheyu Chen, Yue Wang
The metabolism of glucose is a nearly exclusive source of energy for maintaining neuronal survival, synaptic transmission and information processing in the brain. Two glucose metabolism pathways have been reported, direct neuronal glucose uptake and the astrocyte-neuron lactate shuttle (ANLS), which can be involved in these functions simultaneously or separately. Although ANLS in the dorsal hippocampus (DH) has been proved to be required for memory consolidation, the specific metabolic pathway involved during memory acquisition remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29207136/exploiting-novel-valve-interstitial-cell-lines-to-study-calcific-aortic-valve-disease
#13
Hiu-Gwen Tsang, Lin Cui, Colin Farquharson, Brendan M Corcoran, Kim M Summers, Vicky E Macrae
Calcific aortic valve disease (CAVD) involves progressive valve leaflet thickening and severe calcification, impairing leaflet motion. The in vitro calcification of primary rat, human, porcine and bovine aortic valve interstitial cells (VICs) is commonly employed to investigate CAVD mechanisms. However, to date, no published studies have utilised cell lines to investigate this process. The present study has therefore generated and evaluated the calcification potential of immortalized cell lines derived from sheep and rat VICs...
November 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29207034/role-of-inhibitor-of-growth-4-in-the-suppression-of-human-melanoma-cells-through-the-fas-fasl-mediated-apoptosis-pathway
#14
Limin Cai, Haiyan Li, Cui Chen, Xue Cheng, Yu Wang, Jing Liu, Yongchen Wang, Lijun Hao
Melanoma, the most aggressive form of skin cancer, is notoriously resistant to all current available therapies. Inhibitor of growth 4 (ING4), a novel member of the ING family of proteins, has previously been shown to play a critical role in the development of multiple tumors by regulating apoptosis, proliferation, cell cycle progress, migration and invasion. However, the functional role of ING4 in human melanoma remains unclear. To fully understand its potential role in human melanoma, in the present study, lentivirus (LV)‑ING4 and LV‑ING4‑short hairpin RNA were constructed and transfected into human melanoma A375 cells...
November 20, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#15
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29206844/restoration-of-the-prolyl-hydroxylase-domain-protein-3-oxygen-sensing-mechanism-is-responsible-for-regulation-of-hif2%C3%AE-expression-and-induction-of-sensitivity-of-myeloma-cells-to-hypoxia-mediated-apoptosis
#16
Gilberto Gastelum, Aleksandra Poteshkina, Mysore Veena, Edgar Artiga, Geraldine Weckstein, Patrick Frost
Multiple myeloma (MM) is an incurable disease of malignant plasma B-cells that infiltrate the bone marrow (BM), resulting in bone destruction, anemia, renal impairment and infections. Physiologically, the BM microenvironment is hypoxic and this promotes MM progression and contributes to resistance to chemotherapy. Since aberrant hypoxic responses may result in the selection of more aggressive tumor phenotypes, we hypothesized that targeting the hypoxia-inducible factor (HIF) pathways will be an effective anti-MM therapeutic strategy...
2017: PloS One
https://www.readbyqxmd.com/read/29204860/dec1-is-required-for-anti-apoptotic-activity-of-gastric-cancer-cells-under-hypoxia-by-promoting-survivin-expression
#17
Yanfei Jia, Rui Hu, Ping Li, Yan Zheng, Yunshan Wang, Xiaoli Ma
BACKGROUND: Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1), which has been reported to be overexpressed in several types of cancer, is associated with tumorigenesis through participation in several biological processes. However, the complex mechanisms underlying DEC1 during carcinogenesis are controversial, and its roles in the development and malignancy of gastric cancer (GC) remain unclear. METHODS: We measured DEC1 expression in human GC cell lines...
December 4, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/29204184/viral-cre-loxp-tools-aid-genome-engineering-in-mammalian-cells
#18
Ranjita Sengupta, Amy Mendenhall, Nandita Sarkar, Chandreyee Mukherjee, Amirali Afshari, Joseph Huang, Biao Lu
Background: Targeted nucleases have transformed genome editing technology, providing more efficient methods to make targeted changes in mammalian genome. In parallel, there is an increasing demand of Cre-LoxP technology for complex genome manipulation such as large deletion, addition, gene fusion and conditional removal of gene sequences at the target site. However, an efficient and easy-to-use Cre-recombinase delivery system remains lacking. Results: We designed and constructed two sets of expression vectors for Cre-recombinase using two highly efficient viral systems, the integrative lentivirus and non-integrative adeno associated virus...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29203150/retroviral-and-lentiviral-safety-analysis-of-gene-modified-t-cell-products-and-infused-hiv-and-oncology-patients
#19
Katherine T Marcucci, Julie K Jadlowsky, Wei-Ting Hwang, Megan Suhoski-Davis, Vanessa E Gonzalez, Irina Kulikovskaya, Minnal Gupta, Simon F Lacey, Gabriela Plesa, Anne Chew, J Joseph Melenhorst, Bruce L Levine, Carl H June
Replication-competent retrovirus/lentivirus (RCR/L) and insertional oncogenesis are potential safety risks with integrating viruses in gene-modified cell therapies. As such, the Food and Drug Administration guidances outline RCR/L-monitoring methods throughout the entire gene therapy treatment cycle. We present data for 17 vector lots, 375 manufactured T cell products, and 308 patients post-infusion across both HIV and oncology indications, showing no evidence of RCR/L. Given our data, a Poisson probability model estimates that a single patient, or a group of patients, would need to be followed for at least 52...
October 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29201225/long-non-coding-rna-anril-promotes-the-proliferation-migration-and-invasion-of-human-osteosarcoma-cells
#20
Shuo Cheng, Tao Huang, Pengcheng Li, Wei Zhang, Zhihang Wang, Yao Chen
The long antisense non-coding RNA ANRIL is 3.8 kb in length and serves an important role in the tumorigenesis and progression of a number of malignancies. However, its function in human osteosarcoma remains unknown. The present study investigated the role of ANRIL in human osteosarcoma cell lines and clinical tumor samples. The expression of ANRIL was analyzed in 19 osteosarcoma and paired adjacent non-cancerous tissues using reverse transcription-quantitative polymerase chain reaction. Knockdown of ANRIL expression using lentivirus-mediated small interfering RNA was performed to investigate the role of ANRIL in tumor proliferation and metastasis using MTT, colony formation and transwell assays...
November 2017: Experimental and Therapeutic Medicine
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