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https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#1
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28315004/alex1-a-novel-tumor-suppressor-gene-inhibits-gastric-cancer-metastasis-via-the-par-1-rho-gtpase-signaling-pathway
#2
Li Pang, Jian-Fang Li, Liping Su, Mingde Zang, Zhiyuan Fan, Beiqin Yu, Xiongyan Wu, Chen Li, Min Yan, Zheng-Gang Zhu, Bingya Liu
BACKGROUND: The ALEX is a novel member of the armadillo family and ALEX1 was reported to be reduced or even lost in multiple solid tumors. However, its expression profile and oncogenic role in gastric cancer (GC) remains largely unknown. METHODS: ALEX1 expression was detected in 161 GC samples by immunohistochemistry staining. NCI-N87 cells transfected by ALEX1 lentivirus vectors and MKN28 cells transfected by ALEX1 shRNA were used for biological function investigation...
March 17, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#3
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28314283/stable-shrna-silencing-of-lactate-dehydrogenase-a-ldha-in-human-mda-mb-231-breast-cancer-cells-fails-to-alter-lactic-acid-production-glycolytic-activity-atp-or-survival
#4
Nzinga Mack, Elizabeth A Mazzio, David Bauer, Hernan Flores-Rozas, Karam F A Soliman
BACKGROUND: In the US, African Americans have a high death rate from triple-negative breast cancer (TNBC), characterized by lack of hormone receptors (ER, PR, HER2/ERRB2) which are otherwise valuable targets of chemotherapy. There is a need to identify novel targets that negatively impact TNBC tumorigenesis. TNBCs release an abundance of lactic acid, under normoxic, hypoxic and hyperoxic conditions; this referred to as the Warburg effect. Accumulated lactic acid sustains peri-cellular acidity which propels metastatic invasion and malignant aggressive transformation...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28306720/inhibition-of-androgen-receptor-by-decoy-molecules-delays-progression-to-castration-recurrent-prostate-cancer
#5
Jae-Kyung Myung, Gang Wang, Helen H L Chiu, Jun Wang, Nasrin R Mawji, Marianne D Sadar
Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir...
2017: PloS One
https://www.readbyqxmd.com/read/28304379/development-of-bioluminescent-chick-chorioallantoic-membrane-cam-models-for-primary-pancreatic-cancer-cells-a-platform-for-drug-testing
#6
Maria Rovithi, Amir Avan, Niccola Funel, Leticia G Leon, Valentina E Gomez, Thomas Wurdinger, Arjan W Griffioen, Henk M W Verheul, Elisa Giovannetti
The aim of the present study was to develop chick-embryo chorioallantoic membrane (CAM) bioluminescent tumor models employing low passage cell cultures obtained from primary pancreatic ductal adenocarcinoma (PDAC) cells. Primary PDAC cells transduced with lentivirus expressing Firefly-luciferase (Fluc) were established and inoculated onto the CAM membrane, with >80% engraftment. Fluc signal reliably correlated with tumor growth. Tumor features were evaluated by immunohistochemistry and genetic analyses, including analysis of mutations and mRNA expression of PDAC pivotal genes, as well as microRNA (miRNA) profiling...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303972/lentiviral-vectors-can-be-used-for-full-length-dystrophin-gene-therapy
#7
John R Counsell, Zeinab Asgarian, Jinhong Meng, Veronica Ferrer, Conrad A Vink, Steven J Howe, Simon N Waddington, Adrian J Thrasher, Francesco Muntoni, Jennifer E Morgan, Olivier Danos
Duchenne Muscular Dystrophy (DMD) is caused by a lack of dystrophin expression in patient muscle fibres. Current DMD gene therapy strategies rely on the expression of internally deleted forms of dystrophin, missing important functional domains. Viral gene transfer of full-length dystrophin could restore wild-type functionality, although this approach is restricted by the limited capacity of recombinant viral vectors. Lentiviral vectors can package larger transgenes than adeno-associated viruses, yet lentiviral vectors remain largely unexplored for full-length dystrophin delivery...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28301970/disclosing-the-parameters-leading-to-high-productivity-of-retroviral-producer-cells-lines-evaluating-random-vs-targeted-integration
#8
Vanessa Sofia Bandeira, Hélio A Tomás, Evren Alici, Manuel J C T Carrondo, Ana Sofia Coroadinha
Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T- and NK- cells to be used in immune-cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using Gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GalV pseudotyped gammaretroviral vector productivity in stable producer cells using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination)...
March 16, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28299895/deep-sequencing-and-variant-analysis-of-an-italian-pathogenic-field-strain-of-equine-infectious-anaemia-virus
#9
K Cappelli, R F Cook, V Stefanetti, F Passamonti, G L Autorino, M T Scicluna, M Coletti, A Verini Supplizi, S Capomaccio
Equine infectious anaemia virus (EIAV) is a lentivirus with an almost worldwide distribution that causes persistent infections in equids. Technical limitations have restricted genetic analysis of EIAV field isolates predominantly to gag sequences resulting in very little published information concerning the extent of inter-strain variation in pol, env and the three ancillary open reading frames (ORFs). Here, we describe the use of long-range PCR in conjunction with next-generation sequencing (NGS) for rapid molecular characterization of all viral ORFs and known transcription factor binding motifs within the long terminal repeat of two EIAV isolates from the 2006 Italian outbreak...
March 15, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28299330/erythropoietin-modification-enhances-the-protection-of-mesenchymal-stem-cells-on-diabetic-rat-derived-schwann-cells-implications-for-diabetic-neuropathy
#10
Shuyun Zhang, Baolin Shi
Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28298247/tissue-specific-inhibition-of-urokinase-type-plasminogen-activator-expression-in-the-testes-of-mice-by-inducible-lentiviral-rna-interference-causes-male-infertility
#11
Kai Zhao, Yan Liu, Zhe Xiong, Lian Hu, Cheng-Liang Xiong
Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1μgmL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6/TR) were co-microinjected into mouse testes to produce TetR&shuPA mice model. Though oral gavage by 0...
March 16, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28297724/intraocular-delivery-of-mir-146-inhibits-diabetes-induced-retinal-functional-defects-in-diabetic-rat-model
#12
Pei Zhuang, Chithra K Muraleedharan, Shunbin Xu
Purpose: Previously, we showed that microRNA-146 (miR-146) is a pivotal negative feedback regulator of multiple nuclear factor kappa-B (NF-κB) activation pathways in retinal endothelial cells (RECs). We hypothesized that miR-146 plays an important role in diabetic retinopathy (DR) by inhibiting diabetes-induced inflammatory response in the retina. The purpose of the current study is to test this hypothesis in vivo. Methods: Lentiviruses expressing rno-miR-146a, lenti-miR-146a, and negative control oligonucleotide with scrambled sequence, lenti-miR-neg ctl, were produced...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#13
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28295550/lncrna-malat-1-elevates-hmgb1-to-promote-autophagy-resulting-in-inhibition-of-tumor-cell-apoptosis-in-multiple-myeloma
#14
Da Gao, Zhen Xiao, Hui-Ping Li, Dong-Hai Han, Ya-Peng Zhang
BACKGROUND: Long non-coding RNAs (lncRNAs) can participate in the pathological process of multiple myeloma (MM) via regulation of specific gene expression and function. This research aimed to study the role of MALAT-1 and the underlying mechanism in MM. METHODS: In this study, the expression of MALAT-1 and HMGB1 protein in the bone marrow mononuclear cells from MM patients at different stages and in MM cell lines was determined by qRT-PCR and western blot, respectively...
March 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28293985/immortalized-sheep-microglial-cells-are-permissive-to-a-diverse-range-of-ruminant-viruses
#15
James B Stanton, Beryl Swanson, Edith Orozco, Juan F Muñoz-Gutiérrez, James F Evermann, Julia F Ridpath
BACKGROUND: Ruminants, including sheep and goats (small ruminants), are key agricultural animals in many parts of the world. Infectious diseases, including many viral diseases, are significant problems to efficient production of ruminants. Unfortunately, reagents tailored to viruses of ruminants, and especially small ruminants, are lacking compared to other animals more typically used for biomedical research. OBJECTIVE: The purpose of this study was to determine the permissibility of a stably immortalized, sheep microglial cell line to viruses that are reported to infect ruminants: bovine viral diarrhea virus (BVDV), bovine herpesvirus 1 (BoHV-1), small ruminant lentiviruses (SRLV), and bovine respiratory syncytial virus (BRSV)...
December 2017: Veterinary Quarterly
https://www.readbyqxmd.com/read/28292022/the-effects-of-the-long-non-coding-rna-malat-1-regulated-autophagy-related-signaling-pathway-on-chemotherapy-resistance-in-diffuse-large-b-cell-lymphoma
#16
Li-Juan Li, Ye Chai, Xiao-Jia Guo, Song-Lin Chu, Lian-Sheng Zhang
OBJECTIVE: Our study aimed to investigate the effects of the long non-coding RNA MALAT-1 (lncRNA MALAT-1) regulated autophagy-related signaling pathway on chemotherapy resistance in diffuse large B-cell lymphoma (DLBCL). METHODS: Human normal B lymphocytes (IM-9I) and DLBCL cell lines (Farage, Pfeiffer, Raji, Daud, Ly1, Ly3, Ly8 and Ly10) were chosen for our experiment. qRT-PCR was applied to detect the expression of lncRNA MALAT-1 in each DLBCL cell line. Farage and Daud cells were induced to be drug-resistant using 0...
March 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28291626/mus81-knockdown-sensitizes-colon-cancer-cells-to-chemotherapeutic-drugs-by-activating-chk1-pathway
#17
Fan Wu, Shu-Chao Su, Guo-Qian Tan, Lun Yan, Ting-Yue Li, Hao-Lu Zhang, Ji-Shang Yu, Bai-Lin Wang
PURPOSE: The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. METHODS AND MATERIALS: The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model...
March 10, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28289286/early-antibody-therapy-can-induce-long-lasting-immunity-to-shiv
#18
Yoshiaki Nishimura, Rajeev Gautam, Tae-Wook Chun, Reza Sadjadpour, Kathryn E Foulds, Masashi Shingai, Florian Klein, Anna Gazumyan, Jovana Golijanin, Mitzi Donaldson, Olivia K Donau, Ronald J Plishka, Alicia Buckler-White, Michael S Seaman, Jeffrey D Lifson, Richard A Koup, Anthony S Fauci, Michel C Nussenzweig, Malcolm A Martin
Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28286179/formation-of-hippocampal-mhtt-aggregates-leads-to-impaired-spatial-memory-hippocampal-activation-and-adult-neurogenesis
#19
L C Schwab, K Richetin, R A Barker, N Déglon
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of fronto-striatal circuits. However, emerging evidence suggests that some of the cognitive deficits in HD may have their origin in other structures including the hippocampus. Hippocampal abnormalities have been reported in HD mouse models particularly in terms of performance on the Morris Water Maze. However, in these animals, it is difficult to be certain whether the spatial memory deficits are due to local pathology within this structure or their poor mobility and motivation...
March 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28282033/pi3k%C3%AE-and-pi3k%C3%AE-isoforms-have-distinct-functions-in-regulating-pro-tumoural-signalling-in-the-multiple-myeloma-microenvironment
#20
R E Piddock, N Loughran, C R Marlein, S D Robinson, D R Edwards, S Yu, G E Pillinger, Z Zhou, L Zaitseva, M J Auger, S A Rushworth, K M Bowles
Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown and pharmacologic isoform-specific inhibition we investigated the role of the PI3K p110γ (PI3Kγ) subunit in regulating MM proliferation and bone marrow microenvironment-induced MM interactions. We compared this with inhibition of the PI3K p110δ (PI3kδ) subunit and with combined PI3kδ/γ dual inhibition. We found that MM cell adhesion and migration were PI3Kγ-specific functions, with PI3kδ inhibition having no effect in MM adhesion or migration assays...
March 10, 2017: Blood Cancer Journal
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