keyword
MENU ▼
Read by QxMD icon Read
search

Adeno associated

keyword
https://www.readbyqxmd.com/read/29932012/choroideremia-molecular-mechanisms-and-development-of-aav-gene-therapy
#1
Maria I Patrício, Alun R Barnard, Kanmin Xue, Robert E MacLaren
INTRODUCTION: Choroideremia is an X-linked inherited retinal degeneration that causes blindness in afflicted males by middle age. The causative gene, CHM, plays a key role in intracellular trafficking pathways, and its disruption impairs cell homeostasis. Areas covered: The mechanism by which mutations in CHM cause choroideremia is still under debate. Here we describe the molecular defects in choroideremia cells regarding both the deficiency of prenylation and the involvement of Rab GTPases...
June 22, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29931050/a-gene-therapeutic-approach-to-inhibit-cib1-ameliorates-maladaptive-remodeling-in-pressure-overload
#2
Andrea Grund, Malgorzata Szaroszyk, Janina K Döppner, Mona Malek Mohammadi, Badder Kattih, Mortimer Korf-Klingebiel, Anna Gigina, Michaela Scherr, George Kensah, Monica Jara-Avaca, Ina Gruh, Ulrich Martin, Kai C Wollert, Antje Gohla, Hugo A Katus, Oliver J Müller, Johann Bauersachs, Joerg Heineke
Aims: Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodeling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiomyocyte intracellular signaling proteins inducing pathological hypertrophy, therapeutic approaches to target these molecules are currently unavailable. In this study, we aimed to establish and test a therapeutic tool to counteract the 22kDa calcium and integrin binding protein (CIB) 1, which we have previously identified as nodal regulator of pathological cardiac hypertrophy and as activator of the maladaptive calcineurin/NFAT axis...
June 20, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29929787/t%C3%AE-4-increases-neovascularization-and-cardiac-function-in-chronic-myocardial-ischemia-of-normo-and-hypercholesterolemic-pigs
#3
Tilman Ziegler, Andrea Bähr, Andrea Howe, Katharina Klett, Wira Husada, Christian Weber, Karl-Ludwig Laugwitz, Christian Kupatt, Rabea Hinkel
Translations of new therapeutic options for cardiovascular disease from animal studies into a clinical setting have been hampered, in part by an improper reflection of a relevant patient population in animal models. In this study, we investigated the impact of thymosin β4 (Tβ4), which promotes collateralization and capillarization, during hypercholesterolemia, a known risk factor of coronary artery disease. Initial in vitro results highlighted an improved endothelial cell function upon Tβ4 treatment under control conditions and during hypercholesterolemic stress (scratch area [pixels]: oxidized low-density lipoprotein [oxLDL], 191,924 ± 7,717; and oxLDL + Tβ4, 105,621 ± 11,245)...
June 19, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29926204/molecular-therapies-for-muscular-dystrophies
#4
REVIEW
Ava Y Lin, Leo H Wang
PURPOSE OF REVIEW: To construct a framework to understand the different molecular interventions for muscular dystrophy. RECENT FINDINGS: The recent approval of antisense oligonucleotides treatment for Duchenne muscular dystrophy and spinal muscular atrophy and current clinical trials using recombinant adeno-associated virus for the treatment of those diseases suggests that we are at a tipping point where we are able to treat and potentially cure muscular dystrophies...
June 21, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29925692/double-stranded-rna-innate-immune-response-activation-from-long-term-adeno-associated-virus-vector-transduction
#5
Wenwei Shao, Lauriel F Earley, Zheng Chai, Xiaojing Chen, Junjiang Sun, Ting He, Meng Deng, Matthew L Hirsch, Jenny Ting, R Jude Samulski, Chengwen Li
Data from clinical trials for hemophilia B using adeno-associated virus (AAV) vectors have demonstrated decreased transgenic coagulation factor IX (hFIX) expression 6-10 weeks after administration of a high vector dose. While it is likely that capsid-specific cytotoxic T lymphocytes eliminate vector-transduced hepatocytes, thereby resulting in decreased hFIX, this observation is not intuitively consistent with restored hFIX levels following prednisone application. Although the innate immune response is immediately activated following AAV vector infection via TLR pathways, no studies exist regarding the role of the innate immune response at later time points after AAV vector transduction...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29920520/context-dependent-expression-of-a-conditionally-inducible-form-of-active-akt
#6
Soyeon Park, Robert E Burke, Tatyana Kareva, Nikolai Kholodilov, Pascaline Aimé, Thomas F Franke, Oren Levy, Lloyd A Greene
Akt kinases are key signaling components in proliferation-competent and post-mitotic cells. Here, we sought to create a conditionally-inducible form of active Akt for both in vitro and in vivo applications. We fused a ligand-responsive Destabilizing Domain (DD) derived from E. coli dihydrofolate reductase to a constitutively active mutant form of Akt1, Akt(E40K). Prior work indicated that such fusion proteins may be stabilized and induced by a ligand, the antibiotic Trimethoprim (TMP). We observed dose-dependent, reversible induction of both total and phosphorylated/active DD-Akt(E40K) by TMP across several cellular backgrounds in culture, including neurons...
2018: PloS One
https://www.readbyqxmd.com/read/29916143/mast-cell-proteases-activate-astrocytes-and-glia-neurons-and-release-interleukin-33-by-activating-p38-and-erk1-2-mapks-and-nf-%C3%AE%C2%BAb
#7
Duraisamy Kempuraj, Ramasamy Thangavel, Gvindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Smita Zaheer, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Iuliia Dubova, Gema Giler, Shelby Herr, Shankar S Iyer, Asgar Zaheer
Inflammatory mediators released from activated microglia, astrocytes, neurons, and mast cells mediate neuroinflammation. Parkinson's disease (PD) is characterized by inflammation-dependent dopaminergic neurodegeneration in substantia nigra. 1-Methyl-4-phenylpyridinium (MPP+ ), a metabolite of parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), induces inflammatory mediators' release from brain cells and mast cells. Brain cells' interaction with mast cells is implicated in neuroinflammation...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29915149/glycomic-and-proteomic-changes-in-aging-brain-nigrostriatal-pathway
#8
Rekha Raghunathan, Nicole K Polinski, Joshua A Klein, John D Hogan, Chun Shao, Kshitij Khatri, Deborah R Leon, Mark E McComb, Fredric P Manfredsson, Caryl E Sortwell, Joseph Zaia
Parkinson's disease (PD) is a neurological disorder characterized by the progressive loss of functional dopaminergic neurons in the nigrostriatal pathway in the brain.  While current treatments provide only symptomatic relief, gene therapy has the potential to slow or halt the degeneration of nigrostriatal dopamine neurons in PD patients. Adeno-associated viruses (AAV) are vectors of choice in gene therapy due to their well-characterized safety and efficacy profiles; however, while gene therapy has been successful in preclinical models of the disease, clinical trials in humans have failed to demonstrate efficacy...
June 18, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29914757/rnai-based-glun3a-silencing-prevents-and-reverses-disease-phenotypes-induced-by-mutant-huntingtin
#9
Sonia Marco, Alvaro Murillo, Isabel Pérez-Otaño
Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. HD symptoms include severe motor, cognitive, and psychiatric impairments that result from dysfunction and later degeneration of medium-sized spiny neurons (MSNs) in the striatum. A key early pathogenic mechanism is dysregulated synaptic transmission due to enhanced surface expression of juvenile NMDA-type glutamate receptors containing GluN3A subunits, which trigger the aberrant pruning of synapses formed by cortical afferents onto MSNs...
June 15, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29914415/map3k7-is-recurrently-deleted-in-pediatric-t-lymphoblastic-leukemia-and-affects-cell-proliferation-independently-of-nf-%C3%AE%C2%BAb
#10
David M Cordas Dos Santos, Juliane Eilers, Alfonso Sosa Vizcaino, Elena Orlova, Martin Zimmermann, Martin Stanulla, Martin Schrappe, Kathleen Börner, Dirk Grimm, Martina U Muckenthaler, Andreas E Kulozik, Joachim B Kunz
BACKGROUND: Deletions of 6q15-16.1 are recurrently found in pediatric T-cell acute lymphoblastic leukemia (T-ALL). This chromosomal region includes the mitogen-activated protein kinase kinase kinase 7 (MAP3K7) gene which has a crucial role in innate immune signaling and was observed to be functionally and prognostically relevant in different cancer entities. Therefore, we correlated the presence of MAP3K7 deletions with clinical parameters in a cohort of 327 pediatric T-ALL patients and investigated the function of MAP3K7 in the T-ALL cell lines CCRF-CEM, Jurkat and MOLT-4...
June 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29910724/cdk5-inhibitory-peptide-prevents-loss-of-dopaminergic-neurons-and-alleviates-behavioral-changes-in-an-mptp-induced-parkinson-s-disease-mouse-model
#11
Rongni He, Wei Huang, Yaowei Huang, Miaojing Xu, Pingping Song, Yinwei Huang, Huifang Xie, Yafang Hu
Parkinson's disease (PD) is one of the most affected neurodegenerative diseases in the world. Deregulation of cyclin-dependent kinase 5 (Cdk5) is believed to play an important role in neurodegenerative diseases including PD. p25 is a cleavage peptide of p35, a physiologic activator of Cdk5. p25 combines to Cdk5 and leads to the hyperactivity of Cdk5, which in turn hyperphosphorylates downstream substrates and leads to neuroinflammation and apoptosis of neurons. Previously, we have demonstrated that adeno-associated virus serotype-9 (AAV9) mediated Cdk5 inhibitory peptide (CIP) inhibits the activity of Cdk5/p25 complex and alleviates pathologic and behavioral changes in Alzheimer's disease mouse model...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29907232/intramuscular-e-selectin-adeno-associated-virus-gene-therapy-promotes-wound-healing-in-an-ischemic-mouse-model
#12
Punam P Parikh, Roberta M Lassance-Soares, Hongwei Shao, Manuela M Regueiro, Yan Li, Zhao-Jun Liu, Omaida C Velazquez
BACKGROUND: Poor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. METHODS: Adult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds...
August 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29904823/cardiomyocyte-proliferation-for-therapeutic-regeneration
#13
REVIEW
John P Leach, James F Martin
PURPOSE OF REVIEW: Current pharmacologic treatments for cardiovascular disease do not correct the underlying cellular defect, the loss of cardiomyocytes. With recent advancements in cardiac regenerative approaches, the induction of endogenous mature cardiomyocyte proliferation has emerged as a new possibility. Here, we review progress made toward the regeneration of cardiac tissue in the mammalian heart through the stimulation of mature cardiomyocyte renewal. RECENT FINDINGS: The targeting of several developmental and signaling pathways has been shown to stimulate cell cycle re-entry in mature cardiomyocytes...
June 14, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29904640/current-progress-of-adeno-associated-virus-based-therapy-for-the-treatment-of-cystic-fibrosis-in-humans
#14
R Bryan Sutton
No abstract text is available yet for this article.
2018: The Southwest respiratory and critical care chronicles
https://www.readbyqxmd.com/read/29902536/aldolase-promotes-the-development-of-cardiac-hypertrophy-by-targeting-ampk-signaling
#15
Yapeng Li, Dianhong Zhang, Lingyao Kong, Huiting Shi, Xinyu Tian, Lu Gao, Yuzhou Liu, Leiming Wu, Binbin Du, Zhen Huang, Cui Liang, Zheng Wang, Rui Yao, Yanzhou Zhang
Metabolic dysfunction is a hallmark of cardiac hypertrophy and heart failure. During cardiac failure, the metabolism of cardiomyocyte switches from fatty acid oxidation to glycolysis. However, the roles of key metabolic enzymes in cardiac hypertrophy are not understood fully. Here in the present work, we identified Aldolase A (AldoA) as a core regulator of cardiac hypertrophy. The mRNA and protein levels of AldoA were significantly up-regulated in transverse aortic constriction (TAC)- and isoproterenol (ISO)-induced hypertrophic mouse hearts...
June 11, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29901418/systemic-delivery-of-aavb1-gaa-clears-glycogen-and-prolongs-survival-in-a-mouse-model-of-pompe-disease
#16
Allison May Keeler, Marina Zieger, Sophia Todeasa, Angela Mccall, Jennifer Gifford, Samantha Bircsak, Sourav Roy Choudhury, Barry J Byrne, Miguel Sena-Esteves, Mai K ElMallah
Pompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease since a single systemic injection may correct both muscle and CNS pathologies. Using the Pompe mouse, we sought to explore if AAVB1, a newly engineered vector with a high affinity for muscle and CNS, reduces systemic weakness and improves survival in adult mice...
June 14, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29901096/telomerase-reverse-transcriptase-interference-synergistically-promotes-tumor-necrosis-factor%C3%A2-related-apoptosis%C3%A2-inducing-ligand%C3%A2-induced-oral-squamous-cell-carcinoma-apoptosis-and-suppresses-proliferation-in-vitro-and-in-vivo
#17
Xin Zhao, Cuicui Zhang, Zhiliang Le, Suyun Zeng, Chaobin Pan, Jianjie Shi, Jianguang Wang, Xiaopeng Zhao
Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is known to induce cell apoptosis in many types of cancer cells. However, some malignant cells still exhibit anti‑apoptosis features induced by TRAIL; thus the underlying mechanisms that regulate sensitivity and resistance of tumor cells to TRAIL‑induced apoptosis remain unclear. Human telomerase reverse transcriptase (hTERT) is overexpressed in most types of human tumors and is mostly inactive in somatic cells. The present study aimed to investigate the endogenous effects and mechanisms of hTERT inhibition and TRAIL overexpression on TRAIL‑induced apoptosis of human oral squamous cell carcinoma (OSCC) cells...
June 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29899171/novel-approaches-for-the-treatment-of-familial-hypercholesterolemia-current-status-and-future-challenges
#18
Long Jiang, Lu-Ya Wang, Xiao-Shu Cheng
Familial hypercholesterolemia (FH) is an autosomal-dominant disorder that is characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and an increased risk of cardiovascular disease. Despite the use of high-dose statins and the recent addition of proprotein convertase subtilisin/kexin type 9 inhibitors as a treatment option, many patients with homozygous FH fail to achieve optimal reductions of LDL-c levels. Gene therapy has become one of the most promising research directions for contemporary life sciences and is a potential treatment option for FH...
June 13, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29896090/activation-of-dorsomedial-hypothalamic-neurons-promotes-physical-activity-and-decreases-food-intake-and-body-weight-in-zucker-fatty-rats
#19
Ni Zhang, Liang Yang, Lanting Guo, Sheng Bi
Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker ( Lepr(fa) , ZF) and Koletsky ( Lepr(fak) , SHROB) rats...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29892443/synchronized-shift-of-oral-faecal-and-urinary-microbiotas-in-bats-and-natural-infection-dynamics-during-seasonal-reproduction
#20
Muriel Dietrich, Teresa Kearney, Ernest C J Seamark, Janusz T Paweska, Wanda Markotter
Seasonal reproduction is a period of extreme physiological and behavioural changes, yet we know little about how it may affect host microbial communities (i.e. microbiota) and pathogen transmission. Here, we investigated shifts of the bacterial microbiota in saliva, urine and faeces during the seasonal reproduction of bats in South Africa, and test for an interaction in shedding patterns of both bacterial ( Leptospira ) and viral (adeno- and herpesviruses) agents. Based on a comparative approach in two cave-dwelling bat species and high-throughput sequencing of the 16S rRNA gene, we demonstrated a clear signature in microbiota changes over the reproduction season, consistent across the multiple body habitats investigated, and associated with the sex, age and reproductive condition of bats...
May 2018: Royal Society Open Science
keyword
keyword
16475
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"