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Journal of Gene Medicine

Francielle Boçon de Araujo Munhoz, José Eduardo Baroneza, Alexandre Godoy-Santos, Túlio Diniz Fernandes, Filipe Polese Branco, Lupe Furtado Alle, Ricardo Lehtonen de Souza, Maria Cristina Leme Godoy Dos Santos
BACKGROUND: Posterior tibial tendon (PTT) is particularly vulnerable and its insufficiency is recognized as the main cause of adult acquired flat foot. Some patients have a predisposition without clinically recognized cause, suggesting that individual characteristics play an important role in tendinopathy. Objective was investigated whether genetic variants in matrix metalloproteinases (MMPs) are associated with PTT dysfunction. METHODS: 100 women who presented PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) confirming tendinopathy, while 100 asymptomatic women who present intact PPT at MRI constituted the control group were evaluated for MMP-13 g...
November 25, 2016: Journal of Gene Medicine
So Young Kim, Ah Reum Kim, Nayoung K D Kim, Chung Lee, Jin Hee Han, Min Young Kim, Eun-Hee Jeon, Woong-Yang Park, Rahul Mittal, Denise Yan, Xue Zhong Liu, Byung Yoon Choi
BACKGROUND: The symptoms of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) deficiency diseases have been reported to be alleviated by medication. Herein, we report biochemical data to favor PRPS1 deficiency-related hearing loss as a potential target for pharmaceutical treatment. METHODS: We recruited 42 probands from subjects under the age of 15 years with a moderate degree of nonsyndromic autosomal-recessive or sporadic sensorineural hearing loss (SNHL) in at least one side...
November 25, 2016: Journal of Gene Medicine
Bo Gao, Shuai Hao, Wuguo Tian, Yan Jiang, Mei Zhang, Lingjie Guo, Jianjie Zhao, Gang Zhang, Jie Yan, Donglin Luo
PURPOSE: We investigated the possible tumor suppressive effect of microRNA-107 (miR-107) in human breast cancer. METHODS: Gene expression of miR-107 in breast cancer cell lines and clinical breast tissues were evaluated by qRT-PCR. MiR-107 was stably overexpressed in MCF-7 and MDA-MB-231 cells through lentiviral transduction. Its role in regulating in vitro cancer proliferation, cell cycle, invasion and in vivo tumor growth was evaluated by MTT, flow-cytometry, transwell and in vivo tumorigenicity assays, respectively...
November 3, 2016: Journal of Gene Medicine
Xing Mao, Fang Li, Nianji Yang, Chenyang Qi, Steven Qian Zhang, Zhigang Zhang, Huijuan Wu
BACKGROUND: Studies concerning proteins are always a crucial part of renal research. Thanks to the current technologies, scientists have mastered several techniques to generate genetically modified animals. However, in most cases, accessing these animals is still time-consuming and oftentimes expensive. This makes the alteration of protein expression by in vivo plasmid transfection an easily-accessible alternative. However, there is still no comprehensive study describing where plasmids would be expressed when they are injected into the kidneys...
October 29, 2016: Journal of Gene Medicine
Monika Rak, Anna Ochałek, Ewa Bielecka, Joanna Latasiewicz, Katarzyna Gawarecka, Jolanta Sroka, Jarosław Czyż, Katarzyna Piwowarczyk, Marek Masnyk, Marek Chmielewski, Tadeusz Chojnacki, Ewa Swiezewska, Zbigniew Madeja
BACKGROUND: One of the major challenges limiting development of gene therapy is absence of efficient and safe gene carriers. Among the non-viral gene delivery methods, lipofection is considered as one of the most promising. In this study a set of cationic polyprenyl derivatives (trimethylpolyprenylammonium iodides - PTAI) with different lengths of polyprenyl chains (from 7, 8 and 11 to 15 isoprene units) was suggested as a component of efficient DNA vehicles. METHODS: Optimization studies were conducted for PTAI in combination with co-lipid DOPE (dioleoylphosphatidylethanolamine) on DU145 human prostate cancer cells using: size and zeta potential measurements, confocal microscopy, fluorescein diacetate/ethidium bromide test, cell counting, time-lapse monitoring of cell movement, gap junctional intracellular coupling analysis, antimicrobial activity assay, red blood cell hemolysis test...
October 5, 2016: Journal of Gene Medicine
Hena Khalique, Jorge López Marco, Filip Lim
BACKGROUND: Although Herpes Simplex Virus Type 1 (HSV-1) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of about 15.4 kilobases of DNA sequences which are duplicated in the HSV-1 genome, complicating vector construction and stability. METHODS: As a useful platform for building HSV-1 vectors, we have constructed a fully haploid HSV-1 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired...
September 27, 2016: Journal of Gene Medicine
Laleh Shariati, Hossein Khanahmad, Mansoor Salehi, Zahra Hejazi, Ilnaz Rahimmaesh, Mohammad Amin Tabatabaiefar, Mohammad Hossein Modarressi
BACKGROUND: β-thalassemia is a major group of human genetic disorders which involves decrease or cease in the normal synthesis of the β-globin chains of hemoglobin. KLF1 is a key regulatory molecule involved in the γ to β-globin gene switching process directly inducing the expression of beta globin gene and indirectly repressing gamma globin. This study was performed to investigate the ability of an engineered CRISPR/Cas9 system to disrupt the KLF1 gene to inhibit the γ to β hemoglobin switching process in K562 cells...
September 26, 2016: Journal of Gene Medicine
Tianbo Jin, Hongxing Zhang, Qi Yang, Lei Li, Yongri Ouyang, Min Yang, Fengjiao Wang, Zhenyuan Wang, Ji Zhang, Dongya Yuan
BACKGROUND: The number of heroin addicts is increasing in the world. The environmental and genetic factors both play critical roles in the process of heroin addiction. We sought to investigate the associations between single nucleotide polymorphisms (SNPs) in LIN7C, BDNFOS and BDNF genes and drug addiction in the Han Chinese population. METHODS: We conducted a case-control study among 692 cases and 700 healthy controls from Xi'an, China. Eight SNPs were selected and genotyped using Sequenom Mass-ARRAY technology...
September 19, 2016: Journal of Gene Medicine
Xiaohui Lin, Jihong Wang, Lixia Yun, Shuhong Jiang, Langen Li, Xiaohai Chen, Zhen Li, Qiang Lu, Yihui Zhang, Xiaocheng Ma
BACKGROUND: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. The objective of this study was to identify a possible connection between gene polymorphisms and the risk of developing DR. MATERIALS AND METHODS: A total of 319 patients with Type 2 Diabetes mellitus (T2DM) were selected. All patients underwent a complete eye examination. Based on this, the patients with T2DM were divided into two subgroups: 175 patients with retinopathy (DR) and 144 patients without retinopathy (NDR)...
September 8, 2016: Journal of Gene Medicine
Kenji Kokura, Yasushi Kuromi, Takeshi Endo, Naohiko Anzai, Yasuhiro Kazuki, Mitsuo Oshimura, Tetsuya Ohbayashi
BACKGROUND: Kidney injury molecule-1 (Kim-1) has been validated as a urinary biomarker for acute and chronic renal damage. The expression of Kim-1 mRNA is also activated by acute kidney injury induced by cisplatin in rodents and humans. To date, the measurement of Kim-1 expression has not fully allowed the detection of in vitro cisplatin nephrotoxicity in immortalized culture cells such as human kidney-2 cells and immortalized proximal tubular epithelial cells. METHODS: We measured the augmentation of Kim-1 mRNA expression after cisplatin addition using immortalized S3 cells established from the kidneys of transgenic mice harboring temperature-sensitive large T antigen from Simian virus 40...
September 3, 2016: Journal of Gene Medicine
Yongjun He, Xiyang Zhang, Xun Li, Jieli Du, Xue He, Zhiying Zhang, Yuan Zhang, Longli Kang, Tianbo Jin, Dongya Yuan
BACKGROUND: High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea-level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE...
September 2016: Journal of Gene Medicine
HariOm Singh, Shruti D Marathe, Vijay Nema, Manisha V Ghate, Raman R Gangakhedkar
BACKGROUND: Astrocytes are susceptible to HIV-1 infection. Neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Therefore, we evaluated the association of MMP-2(-735C > T) and MMP-9(-1562C > T) polymorphisms with respect to the susceptibility of developing HIV-associated neurocognitive disorders (HAND) and its severity. METHODS: We enrolled 50 HIV-infected individuals with HAND, 130 without HAND and 150 unrelated healthy controls...
September 2016: Journal of Gene Medicine
Jubayer A Hossain, Lars Rømo Ystaas, Jelena Mrdalj, Kristjan Välk, Kristoffer Riecken, Boris Fehse, Rolf Bjerkvig, Janne Grønli, Hrvoje Miletic
BACKGROUND: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation. METHODS: In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study...
September 2016: Journal of Gene Medicine
Lyudmila S Krassikova, Saida S Karshieva, Ivan B Cheglakov, Alexander V Belyavsky
BACKGROUND: The combination of stem cell-based gene therapy with chemotherapy comprises an advantageous strategy that results in a reduction of system toxicity effects and an improvement in the general efficacy of treatment. In the present study, we estimated the efficacy of adipose tissue-derived mesenchymal stem cells (AT-MSCs) expressing cytosine deaminase (CDA) combined with lysomustine chemotherapy in mice bearing late stage Lewis lung carcinoma (LLC). METHODS: Adipose tissue-derived mesenchymal stem cells were transfected with non-insert plasmid construct transiently expressing fused cytosine deaminase-uracil phosphoribosyltransferase protein (CDA/UPRT) or the same construct fused with Herpes Simplex Virus Type1 tegument protein VP22 (CDA/UPRT/VP22)...
September 2016: Journal of Gene Medicine
Xiaoyuan Jia, Yongyi Chen, Xin Zhao, Chunwei Lv, Jie Yan
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal malignancy. Vaccinia virus (VV) possessed many inherent advantages with respect to being engineered as a vector for cancer gene therapy, although the mechanism of action remains to be explored further. METHODS: We constructed a thymidine kinase gene insertional inactivated VV, named VV-Onco, and then tested its effects on cell viability, apoptosis and colony formation ability in a highly metastatic human hepatocellular carcinoma cell line MHCC97-H, and also investigated the potential cell signal pathways involved in this action...
September 2016: Journal of Gene Medicine
Pratigya Gautam, Robert D Foale, Asha Recino, Jing Zhao, Shu Uin Gan, Maja Wallberg, Roy Calne, Andrew M L Lever
BACKGROUND: The lack of an ideal cell type that can be easily acquired, modified to produce insulin, and re-implanted has been a limitation for ex vivo insulin gene therapy. Canine diabetes is currently treated with human insulin and is a good model for human diabetes. Mesenchymal stromal cells (MSCs) are a promising candidate cell type for gene therapy. Here we optimised insulin production using lentiviral transduced canine MSCs aiming to evaluate their ability for use as surrogate beta cells...
August 30, 2016: Journal of Gene Medicine
Xiaoyan Zheng, Yifei Lv, Shuang Li, Qiannan Zhang, Xueting Zhang, Zhiming Hao
BACKGROUND AND AIMS: Extracellular high mobility group box 1 (HMGB1) is crucially implicated in the pathogenesis of inflammatory bowel diseases (IBDs). A box domain of HMGB1 has been identified as a specific antagonist of HMGB1. In this study, we tested the effects of adeno-associated virus (AAV)-mediated colonic secretory expression of HMGB1 A box on murine experimental colitis. METHODS: Self-complementary AAV-2 carrying mouse IgGk leader-human HMGB1 A box (AAV-HMGB1 A box) was constructed...
August 30, 2016: Journal of Gene Medicine
Jie Jin, Yu Wang, Yang Xu, Xu Zhou, Yu Liu, Xiang Li, Jin Wang
BACKGROUND: In this study, we explored the functional roles of microRNA-144 (miR-144) upregulation and downregulation in human acute lymphoblastic leukemia (ALL). METHOD: Gene expression of miR-144 was examined by qRT-PCR in both ALL cell lines and T-leukemic cells of ALL patients. In ALL cell lines Molt-3 and Jurkat cells, miR-144 was either upregulated or downregulated through lentiviral transduction. The subsequent effects of miR-144 upregulation or downregulation on ALL proliferation, cell-cycle transition, and in vivo xenograft were assessed...
August 24, 2016: Journal of Gene Medicine
Volker M Betz, Oliver B Betz, Tom Rosin, Alexander Keller, Christian Thirion, Michael Salomon, Suzanne Manthey, Peter Augat, Volkmar Jansson, Peter E Müller, Stefan Rammelt, Hans Zwipp
BACKGROUND: Delivery of bone morphogenetic protein-7 (BMP-7) to bone defects can be improved by applying gene transfer methods. However, traditional ex vivo gene therapy approaches are cumbersome and costly, requiring the extraction and culturing of cells. Therefore, we evaluated a novel, expedited ex vivo BMP-7 gene transfer technology based on the use of fragments of subcutaneous fat tissue. METHODS: We created 5-mm mid-femoral bone defects in the right femora of 23 male, syngeneic Fischer 344 rats...
August 2016: Journal of Gene Medicine
Daisuke Sotobayashi, Hirohisa Kawahata, Natsuki Anada, Toshio Ogihara, Ryuichi Morishita, Motokuni Aoki
BACKGROUND: Limited range of motion (ROM) as a result of joint contracture in treatment associated with joint immobilization or motor paralysis is a critical issue. However, its molecular mechanism has not been fully clarified and a therapeutic approach is not yet established. METHODS: In the present study, we investigated its molecular mechanism, focusing on the role of a transcription factor, hypoxia inducible factor-1 (HIF-1), which regulates the expression of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF), and evaluated the possibility of molecular therapy to inhibit HIF-1 activation by ribbon-type decoy oligonucleotides (ODNs) for HIF-1 using immobilized knee animal models...
August 2016: Journal of Gene Medicine
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