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https://read.qxmd.com/read/30763737/regulatory-effect-of-host-mir-101b-3p-on-parasitism-of-nematode-angiostrongylus-cantonensis-via-superoxide-dismutase-3
#1
Dongjuan Yuan, Shiqi Luo, Lian Xu, Xingda Zeng, Zhongdao Wu
MicroRNA plays a vital role in the regulation of host-parasite interaction. In recent years, genomic and transcriptomic resources have become increasingly available for many helminths, but only a limited number of reports in this area are on the regulatory effects of host microRNAs on parasitic nematodes. In this work, we screened increased expression of host microRNAs after nematode infection from miRNA-seq data and predicted target genes by combined bioinformatics analysis and transcriptional profiling. We elucidated regulatory effects of one host miRNA on nematode infection using miRNA inhibitor and adeno-associated virus (AAV)-based TuD miRNA inhibitor...
February 11, 2019: Biochimica et biophysica acta. Gene regulatory mechanisms
https://read.qxmd.com/read/30763670/adeno-associated-virus-9-mediated-rna-interference-targeting-socs3-alleviates-diastolic-heart-failure-in-rats
#2
Jie Gao, Yulin Guo, Yingqi Chen, Jian Zhou, Yan Liu, Pixiong Su
OBJECTIVE: To explore the effect of adeno-associated virus 9-mediated RNA interference targeting SOCS3 (AAV9-SOCS3 siRNA) on the treatment of diastolic heart failure (DHF). METHOD: A rat DHF model was established, and cardiac function and hemodynamic changes were measured. HE, Sirius red and TUNEL staining were applied to observe the pathological changes in the myocardium. Immunoblotting and immunohistochemical staining were utilized to detect SOCS3 expression. The expression levels of various factors, including fibrosis-related factors (collagen I, collagen II, α-SMA and TGF-β), inflammatory-related factors (IL-1β, IL-6, TNF-α, p-p65 and ICAM-1) and factors related to the JAK/STAT signal pathway were analyzed by immunoblotting and/or qPCR...
February 11, 2019: Gene
https://read.qxmd.com/read/30761996/characteristics-and-advantages-of-adeno-associated-virus-vector-mediated-gene-therapy-for-neurodegenerative-diseases
#3
REVIEW
Yuan Qu, Yi Liu, Ahmed Fayyaz Noor, Johnathan Tran, Rui Li
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system...
June 2019: Neural Regeneration Research
https://read.qxmd.com/read/30759996/bola3-deficiency-controls-endothelial-metabolism-and-glycine-homeostasis-in-pulmonary-hypertension
#4
Qiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Vinny Negi, Miranda K Culley, Jyotsna Pilli, Wei Sun, Karin Brugger, Johannes Mayr, Rajeev Saggar, Rajan Saggar, W Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, John Sembrat, Mauricio Rojas, Omar F Khan, James E Dahlman, Masataka Sugahara, Nobuyuki Kagiyama, Taijyu Satoh, Manling Zhang, Ning Feng, John Gorcsan Iii, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Thomas Bertero, Stephen Y Chan
BACKGROUND: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. The BolA Family Member 3 (BOLA3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. METHODS: In vitro assessment of BOLA3 regulation and gain and loss of function assays were performed in human pulmonary artery endothelial cells (PAECs) using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3...
February 14, 2019: Circulation
https://read.qxmd.com/read/30759231/delivering-sacas9-mrna-by-lentivirus-like-bionanoparticles-for-transient-expression-and-efficient-genome-editing
#5
Baisong Lu, Parisa Javidi-Parsijani, Vishruti Makani, Farideh Mehraein-Ghomi, Walaa Mohamed Sarhan, Dongjun Sun, Kyung Whan Yoo, Zachary P Atala, Pin Lyu, Anthony Atala
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system discovered using bacteria has been repurposed for genome editing in human cells. Transient expression of the editor proteins (e.g. Cas9 protein) is desirable to reduce the risk of mutagenesis from off-target activity. Using the specific interaction between bacteriophage RNA-binding proteins and their RNA aptamers, we developed a system able to package up to 100 copies of Staphylococcus aureus Cas9 (SaCas9) mRNA in each lentivirus-like bionanoparticle (LVLP)...
February 13, 2019: Nucleic Acids Research
https://read.qxmd.com/read/30755583/in-vivo-transduction-of-etv2-improves-cardiac-function-and-induces-vascular-regeneration-following-myocardial-infarction
#6
Sunghun Lee, Dong Hun Lee, Bong-Woo Park, Riyoun Kim, Anh Duc Hoang, Sang-Keun Woo, Wenjun Xiong, Yong Jin Lee, Kiwon Ban, Hun-Jun Park
Vascular regeneration in ischemic hearts has been considered a target for new therapeutic strategies. It has been reported that ETV2 is essential for vascular development, injury-induced neovascularization and direct cell reprogramming of non-endothelial cells into endothelial cells. Thus, the objective of this study was to explore the therapeutic potential of ETV2 in murine models of myocardial infarction in vivo. Direct myocardial delivery of lentiviral ETV2 into rodents undergoing myocardial infarction dramatically upregulated the expression of markers for angiogenesis as well as anti-fibrosis and anti-inflammatory factors in vivo...
February 12, 2019: Experimental & Molecular Medicine
https://read.qxmd.com/read/30748001/viral-vector-mediated-cre-recombinase-expression-in-substantia-nigra-induces-lesions-of-the-nigrostriatal-pathway-associated-with-perturbations-of-dopamine-related-behaviors-and-hallmarks-of-programmed-cell-death
#7
Sara Rezai Amin, Carole Gruszczynski, Bruno P Guiard, Jacques Callebert, Jean-Marie Launay, Franck Louis, Catalina Betancur, Vincent Vialou, Sophie Gautron
Cre/loxP recombination is a widely used approach to study gene function in vivo, using mice models expressing the Cre recombinase under the control of specific promoters or through viral delivery of Cre-expressing constructs. A profuse literature on transgenic mouse lines points out the deleterious effects of Cre expression in various cell types and tissues, presumably by acting on illegitimate loxP-like sites present in the genome. However, most studies reporting the consequences of Cre-lox gene invalidation often omit adequate controls to exclude the potential toxic effects of Cre, compromising the interpretation of data...
February 12, 2019: Journal of Neurochemistry
https://read.qxmd.com/read/30747033/human-bone-marrow-mesenchymal-stem-cells-functionalized-by-hybrid-baculovirus-adeno-associated-viral-vectors-for-targeting-hypopharyngeal-carcinoma
#8
Jun Wang, Liying Zhu, Xinwei Chen, Ruofei Huang, Shili Wang, Pin Dong
Hypopharyngeal carcinoma is a common malignant tumor of the head and neck with a very poor prognosis; the median survival time for curatively treated patients was 17.2 months in India. However, cell-based gene therapy holds promise to improve patient outcomes. In this study, we investigated whether human bone marrow mesenchymal stem cells (BMSCs) possess potential homing capacity for hypopharyngeal carcinoma. To monitor the efficiency of BMSC transplantation therapy via reporter gene imaging, we employed a hybrid baculovirus vector containing the Luc-P2A-eGFP fusion or sodium iodide symporter (NIS) sequence under the control of the cytomegalovirus promoter...
February 12, 2019: Stem Cells and Development
https://read.qxmd.com/read/30745824/metformin-promotes-the-survival-of-random-pattern-skin-flaps-by-inducing-autophagy-via-the-ampk-mtor-tfeb-signaling-pathway
#9
Hongqiang Wu, Jian Ding, Shihen Li, Jinti Lin, Renhao Jiang, Chen Lin, Li Dai, Chenglong Xie, Dingsheng Lin, Huazi Xu, Weiyang Gao, Kailiang Zhou
Random-pattern skin flaps are widely used to close defects in reconstructive and plastic surgeries; however, they are vulnerable to necrosis, particularly in the distal portion of the flap. Here, we examined the effects of metformin on flap survival and the mechanisms underlying these effects. Following metformin treatment, the survival area, blood flow, and number of microvessels present in skin flaps were increased on postoperative day 7, whereas tissue edema was reduced. In addition, metformin promoted angiogenesis, inhibited apoptosis, relieved oxidative stress, and increased autophagy in areas of ischemia; these effects were reversed by autophagy inhibitors 3-methyladenine (3MA) or chloroquine (CQ)...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30745213/whole-brain-patterns-of-the-presynaptic-inputs-and-axonal-projections-of-bdnf-neurons-in-the-paraventricular-nucleus
#10
Fang Luo, Yuling Mu, Cuicui Gao, Yan Xiao, Qian Zhou, Yiqing Yang, Xinyan Ni, Wei L Shen, Jiajun Yang
Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions...
January 26, 2019: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://read.qxmd.com/read/30742069/adeno-associated-virus-2-bound-to-its-cellular-receptor-aavr
#11
Ran Zhang, Lin Cao, Mengtian Cui, Zixian Sun, Mingxu Hu, Rouxuan Zhang, William Stuart, Xiaochu Zhao, Zirui Yang, Xueming Li, Yuna Sun, Shentao Li, Wei Ding, Zhiyong Lou, Zihe Rao
Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR recognition is in immediate demand. Taking advantage of a particle-filtering algorithm, we report here the cryo-electron microscopy structure of the AAV2-AAVR complex at 2.8 Å resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike region of the AAV2 capsid adjacent to the icosahedral three-fold axis...
February 11, 2019: Nature Microbiology
https://read.qxmd.com/read/30740517/centrifugal-innervation-of-the-olfactory-bulb-a-reappraisal
#12
Estelle E In 't Zandt, Hillary L Cansler, Heather B Denson, Daniel W Wesson
The inter-regional connectivity of sensory structures in the brain allows for the modulation of sensory processing in manners important for perception. In the olfactory system, odor representations in the olfactory bulb (OB) are modulated by feedback centrifugal innervation from several olfactory cortices, including the piriform cortex (PCX) and anterior olfactory nucleus (AON). Previous studies reported that an additional olfactory cortex, the olfactory tubercle (OT), also centrifugally innervates the OB and may even shape the activity of OB output neurons...
January 2019: ENeuro
https://read.qxmd.com/read/30736827/differences-in-neurotropism-and-neurotoxicity-among-retrograde-viral-tracers
#13
Leqiang Sun, Yajie Tang, Keji Yan, Jinsong Yu, Yanyan Zou, Weize Xu, Ke Xiao, Zhihui Zhang, Weiming Li, Beili Wu, Zhe Hu, Kening Chen, Zhen F Fu, Jinxia Dai, Gang Cao
BACKGROUND: Neurotropic virus-based tracers have been extensively applied in mapping and manipulation of neural circuits. However, their neurotropic and neurotoxic properties remain to be fully characterized. METHODS: Through neural circuit tracing, we systematically compared the neurotropism discrepancy among different multi-trans-synaptic and mono-synaptic retrograde viral tracers including pseudorabies virus (PRV), rabies virus (RV), and the newly engineered retro adeno-associated virus (rAAV2-retro) tracers...
February 8, 2019: Molecular Neurodegeneration
https://read.qxmd.com/read/30735971/sustained-somatostatin-gene-expression-reverses-kindling-induced-increases-in-the-number-of-dividing-type-1-neural-stem-cells-in-the-hippocampi-of-behaviorally-responsive-rats
#14
Jeffrey A Leibowitz, Gowri Natarajan, Junli Zhou, Paul R Carney, Brandi K Ormerod
Neurogenesis persists throughout life in the hippocampi of all mammals, including humans. In the healthy hippocampus, relatively quiescent Type-1 neural stem cells (NSCs) can give rise to more proliferative Type-2a neural progenitor cells (NPCs), which generate neuronal-committed Type-2b NPCs that mature into Type-3 neuroblasts. Many Type-3 neuroblasts survive and mature into functionally integrated granule neurons over several weeks. In kindling models of epilepsy, neurogenesis is drastically upregulated and many new neurons form aberrant connections that could support epileptogenesis and/or seizures...
January 11, 2019: Epilepsy Research
https://read.qxmd.com/read/30735101/bax-inhibitor-1-overexpression-in-prelimbic-cortex-protects-rats-against-depression-like-behavior-induced-by-olfactory-bulbectomy-and-reduces-apoptotic-and-inflammatory-signals
#15
Dao Li, Zhou Cai, Ji Wu, Yan Zhang
BACKGROUND AND PURPOSE: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in the impairment of learning and memory. Bax inhibitor-1 (BI-1) has been reported to be involved in the pathological mechanisms for neurodegenerative disorders including depression. Here, we aimed to investigate the role of BI-1 in regulating depression-like behavior induced by olfactory bulbectomy (OB) in rats and the possible mechanism...
February 8, 2019: Neurological Research
https://read.qxmd.com/read/30734931/pink1-regulates-fkbp5-interaction-with-akt-phlpp-and-protects-neurons-from-neurotoxin-stress-induced-by-mpp
#16
Wassamon Boonying, Alvin Joselin, En Huang, Dianbo Qu, Farzaneh Safarpour, Grace O Iyirhiaro, Yasmilde Rodriguez Gonzalez, Steve M Callaghan, Ruth S Slack, Daniel Figeys, Young-Hwa Chung, David S Park
Loss of function mutations in the PTEN-induced putative kinase 1 (Pink1) gene have been linked with an autosomal recessive familial form of early onset Parkinson's disease (PD). However, the underlying mechanism(s) responsible for degeneration remains elusive. Presently, using co-immunoprecipitation in HEK (Human embryonic kidney) 293 cells, we show that Pink1 endogenously interacts with FK506-binding protein 51 (FKBP51) FKBP5 and directly phosphorylates FKBP5 at Serine in an in vitro kinase assay. Both FKBP5 and Pink1 have been previously associated with protein kinase B (AKT) regulation...
February 8, 2019: Journal of Neurochemistry
https://read.qxmd.com/read/30734588/the-detection-of-biologically-relevant-low-titer-neutralizing-antibodies-against-aav-require-sensitive-in-vitro-assays
#17
Anita Kruzik, Herwig Koppensteiner, Damir Fetahagic, Bettina Hartlieb, Sebastian Dorn, Stefan Romeder-Finger, Sogué Coulibaly, Alfred Weber, Werner Höllriegl, Frank M Horling, Friedrich Scheiflinger, Birgit M Reipert, Maurus de la Rosa
Patients with preexisting anti-adeno-associated virus 8 (AAV8) neutralizing antibodies (NAbs) are currently excluded from AAV8 gene therapy trials. Therefore, the assessment of biologically relevant AAV8-NAb titers is critical for product development in gene therapy. However, standardized assays have not been routinely used to determine anti-AAV8-NAb titers, contributing to a wide range of reported anti-AAV8 prevalences. Using a clinical in vitro NAb assay in a separate study, we found a higher than expected anti-AAV8-NAb prevalence in international cohorts of about 50%...
February 8, 2019: Human Gene Therapy Methods
https://read.qxmd.com/read/30734456/glutamatergic-neurons-in-the-medial-prefrontal-cortex-mediate-the-formation-and-retrieval-of-cocaine-associated-memories-in-mice
#18
Tong Zhang, Junko Yanagida, Hironori Kamii, Shintaro Wada, Masaki Domoto, Hitoki Sasase, Satoshi Deyama, Takeshi Takarada, Eiichi Hinoi, Kenji Sakimura, Akihiro Yamanaka, Takashi Maejima, Michihiro Mieda, Takeshi Sakurai, Naoya Nishitani, Kazuki Nagayasu, Shuji Kaneko, Masabumi Minami, Katsuyuki Kaneda
In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm...
February 7, 2019: Addiction Biology
https://read.qxmd.com/read/30733670/transduction-of-adeno-associated-virus-vectors-targeting-hair-cells-and-supporting-cells-in-the-neonatal-mouse-cochlea
#19
Xi Gu, Renjie Chai, Luo Guo, Biao Dong, Wenyan Li, Yilai Shu, Xinsheng Huang, Huawei Li
Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expression patterns of AAV with different serotypes or promoters in hair cells and supporting cells in the neonatal mouse cochlea, we examined the expression of enhanced green fluorescent protein (eGFP) for five different types of AAV vectors [serotypes 2, 9, and Anc80L65 with promoter cytomegalovirus (CMV)-beta-Globin and serotypes 2 and 9 with promoter chicken beta-actin (CBA)] in in vitro cochlear explant cultures and we tested the transduction of AAV2/2-CBA, AAV2/9-CBA, and AAV2/Anc80L65-CMV by in vivo microinjection into the scala media of the cochlea...
2019: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/30723782/intrapleural-gene-therapy-for-alpha-1-antitrypsin-deficiency-related-lung-disease
#20
Katie M Stiles, Dolan Sondhi, Stephen M Kaminsky, Bishnu P De, Jonathan B Rosenberg, Ronald G Crystal
Alpha-1 antitrypsin deficiency (AATD) manifests primarily as early-onset emphysema caused by the destruction of the lung by neutrophil elastase due to low amounts of the serine protease inhibitor alpha-1 antitrypsin (AAT). The current therapy involves weekly intravenous infusions of AAT-derived from pooled human plasma that is efficacious, yet costly. Gene therapy applications designed to provide constant levels of the AAT protein are currently under development. The challenge is for gene therapy to provide sufficient amounts of AAT to normalize the inhibitor level and anti-neutrophil elastase capacity in the lung...
August 17, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
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