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Journal of Gene Medicine

Yurou Chen, Fulin Liu, Kejia Wu, Wanrong Wu, Hanshu Wu, Wei Zhang
BACKGROUND: DPP8 is a member of the dipeptidyl peptidase IV family, which belongs to the S9b protease subfamily. It regulates cell proliferation, apoptosis, migration and invasion during cancer progression. MATERIALS AND METHODS: To study the role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer tissues and cells. The localization of DPP8 was determined by immunofluorescence staining. Subsequently, SiHa and HeLa cells were treated with siRNA-DPP8...
September 18, 2018: Journal of Gene Medicine
Xiaotong Liu, Shaoyou Yang, Lingwei Meng, Chunyu Chen, Xiang Hui, Yuxin Jiang, Xiaohui Jiao, Kewen Lv, Tao Song
BACKGROUND: Non-syndromic orofacial clefts (NSOC) is one of the most common congenital malformations, and its etiology involves both genetic and environmental factors. The aim of the present study was to investigate the association of six SNPs (rs10512248 in PTCH1, rs12681366 and rs958447 in RAD54B, rs13317 in FGFR1, rs1838105 and rs4968247 in WNT9B) with NSOC in a Northern Chinese population. METHODS: In our current study, the HI-SNP technology was used to conduct genotyping of the six SNPs (rs10512248, rs12681366, rs957448, rs13317, rs1838105 and rs4968247) in 596 patients with NSOC and 466 healthy individuals from a Northern Chinese population...
September 1, 2018: Journal of Gene Medicine
Nejat Düzgüneş, Jennifer Cheung, Krystyna Konopka
BACKGROUND: Cervical cancer is the third most common cause of cancer in women. The 5-year survival rate in oropharyngeal squamous cell carcinomas is about 50%, and this rate has not improved in the last several decades. These cancers are accessible to direct intervention. We examined the ability of a highly efficient non-viral vector, TransfeX, to deliver the suicide gene HSV-tk to cervical and oral cancer cells and induce cytotoxicity following the administration of the prodrug, ganciclovir...
September 1, 2018: Journal of Gene Medicine
Mahdi Noureddini, Narges Mobasseri, Mohammad Karimian, Mohaddeseh Behjati, Hossein Nikzad
BACKGROUND: The Arg399Gln polymorphism in X-ray repair cross-complementing group 1 (XRCC1) gene may alter the risk of prostate cancer (PCa). The aim of this study was to investigate the association of XRCC1-Arg399Gln polymorphism with prostate cancer risk in an Iranian population which followed by a meta-analysis and an in silico analysis. METHODS: In a case-control study, 360 subjects including 180 men with PCa and 180 healthy controls were included. XRCC1-Arg399Gln genotyping was performed by PCR-RFLP method...
August 30, 2018: Journal of Gene Medicine
Abdolhalim Rajabi, Pedram Khosravi, Seyed Abbas Motevalian, Mojtaba Farjam, Azadeh Shojaei
BACKGROUND: Cigarette smoking remains a serious public health problem. Environmental and genetic factors both play critical roles in the process of cigarette smoking. We aimed to investigate the associations between single nucleotide polymorphisms (SNP) in the BDNF gene and cigarette smoking in the Iranian population. METHODS: We conducted a case-control study. In total, 932 case and control subjects aged > 15 years were recruited in the present study in a simple random manner, including 523 lifetime cigarette smokers, 466 cigarette smokers within a 12-month period, 409 never cigarette smokers in their lifetime and 466 never cigarette smokers within a 12-month period...
August 21, 2018: Journal of Gene Medicine
Kevin G Haworth, Christina Ironside, Megan A Ramirez, Sarah Weitz, Brian C Beard, Jonathan Schwartz, Jennifer E Adair, Hans-Peter Kiem
BACKGROUND: Gene therapy approaches for the treatment of Fanconi anemia (FA) hold promise for patients without a suitably matched donor for an allogeneic bone marrow transplant. However, significant limitations include the collection of sufficient stem cell numbers from patients, fragility of these cells during ex vivo manipulation, and clinically meaningful engraftment following transplantation. With these challenges in mind, we were interested in determining if gene-corrected cells at progressively lower numbers can successfully engraft in FA, if low-dose conditioning facilitates this engraftment, and if these cells can artificially be selected for post-transplant...
August 21, 2018: Journal of Gene Medicine
Swati Ahir-Bist, Vijay Chavan, Padmaja Samant-Mavani, Ruchi Nanavati, Preeti Mehta, Jayanti Mania-Pramanik
BACKGROUND: Vertical HIV transmission does not occur in all exposed infants. Many infants remain HIV uninfected even after exposure. This is partly attributed to the host genes involving cytokine production, which is rarely documented in vertical transmission. METHODS: Here, an observational cohort study evaluated whether polymorphisms in cytokine, receptor and antagonist genes are associated with perinatal HIV transmission. Single nucleotide polymorphism (SNP) genotyping was performed via the polymerase chain reaction with sequence-specific primers method...
August 14, 2018: Journal of Gene Medicine
Hongling Zhu, Tao Wang, Robert John Lye, Brent A French, Brian H Annex
BACKGROUND: Following systemic delivery, AAV9-mediated gene expression is significantly increased in ischemic versus non-ischemic muscle, suggesting that AAV9 is an attractive vector for treating peripheral arterial disease. Potential mechanisms underlying ischemia-augmented expression include: (i) increased vascular permeability and (ii) "unmasking" of endogenous AAV9 receptors. In the present study, we aimed to reconstitute the ischemic induction of AAV9 in vivo, using local injection of histamine (to increase vascular permeability) and neuraminidase (to desialylate cell surface glycans)...
August 12, 2018: Journal of Gene Medicine
Yong Wook Jung, Eun Hee Ahn, Jung Oh Kim, Hui Jeong An, Sung Hwan Cho, Young Ran Kim, Woo Sik Lee, Nam Keun Kim
BACKGROUND: The present study was performed to investigate whether genetic variants of VEGF are associated with recurrent pregnancy loss (RPL) in Korean women and to provide insight into the role of VEGF in the pathogenesis of RPL development. METHODS: A cohort of 384 women with idiopathic RPL with a history of two or more uxexplained consecutive early pregnancy losses and 236 control women were recruited from an infertility center of university-teaching hospital in Korea between March 1999 and February 2010...
August 8, 2018: Journal of Gene Medicine
Mostafa Farzaneh, Mohammad Sayyah, Hamid Reza Eshraghi, Negar Panahi, Hadi Mirzapour Delavar, Hamid Gholami Pourbadie
BACKGROUND: The trisynaptic circuit (entorhinal cortex-dentate gyrus-CA3-CA1) is a key unidirectional network in the hippocampus. Damage to the hippocampus interrupts this circuit and causes neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest with respect to treating trisynaptic circuit pathologies. METHODS: We generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG-B2. The efficiency of the vector in the retrograde transduction of the rat hippocampal neurons (i...
August 3, 2018: Journal of Gene Medicine
Mohamed Sharaf-Eldein, Doaa Elghannam, Camelia Abdel-Malak
BACKGROUND: Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine modulating monocyte motility and a pleiotropic regulator of different biological and cellular processes. The MIF-173G/C (rs755622) polymorphism is found in the promoter region and affects its activity. The present study investigated the MIF polymorphism as a risk factor for the development of acute lymphoblastic leukemia (ALL) in Egyptian children. METHODS: We analyzed the MIF-173G/C (rs755622) polymorphism in 180 ALL cases and 150 healthy control children by amplification of the gene using a polymerase chain reaction followed by restriction endonuclease digestion and running on an agarose gel for visualization of the product...
July 11, 2018: Journal of Gene Medicine
Hanchao Li, Qian Li, Xueting Zhang, Xiaoyan Zheng, Qiannan Zhang, Zhiming Hao
BACKGROUND: The present study aimed to clarify the effects of thymosin β4 (Tβ4) on CCl4 -induced hepatic fibrosis in mice and to further explore the underlying mechanisms. METHODS: Expression of Tβ4 in fibrotic liver tissues was assessed by a quantitative real time-reverse transcriptase polymerase chain reaction and immunohistochemistry. The effects of intraperitoneal adeno-associated virus-Tβ4 (AAV-Tβ4) on CCl4 -induced hepatic fibrosis were observed by the evaluation of collagen deposition, hepatic stellate cell (HSC) activation and pro-fibrotic cytokine expression...
July 4, 2018: Journal of Gene Medicine
Volker M Betz, Bin Ren, Carolin Messmer, Volkmar Jansson, Oliver B Betz, Peter E Müller
BACKGROUND: Bone morphogenetic protein (BMP)-2 gene-activated muscle tissue fragments can regenerate large bone defects in preclinical animal models. The use of tissue fragments instead of isolated cells expedites gene-enhanced tissue engineering and may increase the possibility of clinical translation. The present in vitro study investigated whether the osteoinductive effect of BMP-2 on muscle tissue fragments can be enhanced using the heterodimers BMP-2/6 or BMP-2/7. METHODS: Skeletal muscle tissue fragments from rats were cultured in vitro for up to 20 days in normal medium, osteogenic medium or osteogenic medium supplemented with either a low (50 ng/ml) or high (200 ng/ml) concentration of recombinant human BMP-2, BMP-2/6 or BMP-2/7...
June 28, 2018: Journal of Gene Medicine
Benjamin Steinborn, Ines Truebenbach, Stephan Morys, Ulrich Lächelt, Ernst Wagner, Wei Zhang
BACKGROUND: Developing new drug delivery carriers addressing chemoresistance is still full of challenges and opportunities. As the rapid development of small interfering RNA (siRNA) provides promising therapeutic perspectives, nanocarriers for drug and siRNA co-delivery present new alternatives for cancer therapy. METHODS: A co-delivery nanosystem for methotrexate (MTX) or gamma-glutamylated derivatives (gE2 -MTX and gE5 -MTX) and antitumoral EG5 siRNA has been developed utilizing the sequence defined cationic lipo-oligomers 454, 1021 and 1027...
July 2018: Journal of Gene Medicine
Elizabeth M Everson, Jonah D Hocum, Grant D Trobridge
BACKGROUND: Previous studies have shown that foamy viral (FV) vectors are a promising alternative to gammaretroviral and lentiviral vectors and also that insulators can improve FV vector safety. However, in a previous analysis of insulator effects on FV vector safety, strong viral promoters were used to elicit genotoxic events. In the present study, we developed and analyzed the efficacy and safety of a high-titer, clinically relevant FV vector driven by the housekeeping promoter elongation factor-1α and insulated with an enhancer blocking A1 insulator (FV-EGW-A1)...
July 2018: Journal of Gene Medicine
Weihua Yuan, Jie Chen, Ying Cao, Lingcong Yang, Luxi Shen, Qi Bian, Shufang Bin, Panyuan Li, Jiawei Cao, Hezhi Fang, Haihua Gu, Hongzhi Li
BACKGROUND: The production of anti-Her2 chimeric antigen receptor (CAR) T cells needs to be optimized to make it a reliable therapy. METHODS: Three types of lentiviral vectors expressing anti-Her2 CAR together with packaging plasmids were co-transfected into 293 T-17 cells. The vector with the best packaging efficiency was selected, and the packaging cell culture system and packaging plasmid system were optimized. Centrifugation speed was optimized for the concentration of lentivirus stock...
July 2018: Journal of Gene Medicine
Mark D Unger, Josef Pleticha, Lukas F Heilmann, Laura K Newman, Timothy P Maus, Andreas S Beutler
INTRODUCTION: Intrathecal interleukin (IL)-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, is a potential therapeutic for various human diseases, and was found to be nontoxic in dogs, when the human IL-10 ortholog was tested. However, recent studies in swine testing porcine IL-10 demonstrated fatal neurotoxicity. The present study aimed to deliver vector-encoded human IL-10 in swine, measure expression of the transgene in cerebrospinal fluid and monitor animals for signs of neurotoxicity...
July 2018: Journal of Gene Medicine
Yunpeng Cai, Anna-Marie Makarova, Jesper Wengel, Kenneth A Howard
BACKGROUND: Antisense gapmer oligonucleotide drugs require delivery and biodistribution enabling technologies to increase in vivo efficacy. An attractive approach is their binding and consequent transport by the endogenous human serum albumin pool as mediated by fatty acid incorporation into the gapmer design. METHODS: The present study investigated the effect of palmitoyl modification and position on albumin-binding, cellular uptake and in vitro gene silencing of gapmers with either a phosphorothioate (PS) or phosphodiester (PO) backbone...
July 2018: Journal of Gene Medicine
Guo Ai, Weiming Yan, Haijing Yu, Fang Xiao, Dong Xi, Ke Ma, Jiaquan Huang, Xiaoping Luo, Xiaoyang Wan, Qin Ning
BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory disease caused by an aberrant immune response to hepatic self-antigens in which regulatory T cells (Tregs) are critical for maintaining immunosupression. The soluble form of fibrinogen-like protein 2 (sFGL2), a novel effector molecule of Treg, is rarely investigated in AIH. In the present study, we dissected the role of sFGL2 in autoimmune hepatitis and its potential mechanism underlying AIH progression. METHODS: Plasma and intrahepatic sFGL2 levels, as well as Treg cells, were measured in both AIH patients and experimental autoimmune hepatitis (EAH) mice...
July 2018: Journal of Gene Medicine
Julian Ramírez-Bello, Daniel Cadena-Sandoval, José Manuel Fragoso, Rosa Elda Barbosa-Cobos, Mario Adán Moreno-Eutímio, Miguel Ángel Saavedra-Salinas, Guillermo Valencia-Pacheco, Ricardo F López-Villanueva, Silvia Jiménez-Morales
BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention...
June 2018: Journal of Gene Medicine
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