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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
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
R Bryan Sutton
No abstract text is available yet for this article.
2018: The Southwest respiratory and critical care chronicles
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
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
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
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
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
Xue-Yin Pan, Yang Yang, Hong-Wu Meng, Hai-di Li, Xin Chen, Hui-Min Huang, Fang-Tian Bu, Hai-Xia Yu, Qin Wang, Cheng Huang, Xiao-Ming Meng, Jun Li
The activation of hepatic stellate cells (HSCs) is a central event in the progression of liver fibrosis. Multiple studies proved that DNA methylation might accelerate HSCs activation. However, the specific pathogenesis of liver fibrosis remains not fully addressed. Our laboratory performed Genome methylation screening to find out the methylated gene in mice with liver fibrosis. The pilot experiments showed that the promoter of prostacyclin synthase ( PTGIS ) gene was hypermethylated in CCl4 -induced liver fibrosis mouse model...
2018: Frontiers in Pharmacology
Jenny Greig, Jayme Nordin, John White, Qiang Wang, Erin Bote, Tamara Goode, Roberto Calcedo, Samuel Wadsworth, Lili Wang, James M Wilson
Hemophilia A is a common hereditary bleeding disorder that is characterized by a deficiency of human blood coagulation factor VIII (hFVIII). Previous studies with adeno-associated viral (AAV) vectors identified two liver-specific promoter and enhancer combinations (E03.TTR and E12.A1AT) that drove high level expression of a codon-optimized, B-domain-deleted hFVIII transgene in a mouse model of the disease. Here, we further evaluated these enhancer/promoter combinations in cynomolgus macaques using two different AAV capsids (AAVrh10 and AAVhu37)...
June 11, 2018: Human Gene Therapy
Yun Zhang, Yan Wang, Zoran Sosic, Li Zang, Svetlana Bergelson, Wei Zhang
A simple and rapid identity test of adeno-associated virus (AAV) serotypes is important for supporting the AAV gene therapy development, as it relates to its efficacy and safety. The current mass spectrometry-based identity tests require extensive sample preparation steps, relatively large sample quantities and long analysis time. Herein, we describe a simple and novel microfluidic ZipChip CE/MS method used to characterize AAV capsid proteins. The three capsid proteins of AAV2 were separated and identified within 4 min using 5 nL of sample directly from a polysorbate-containing formulation buffer...
June 8, 2018: Analytical Biochemistry
Jing-Ying Guo, Lu He, Teng-Fei Qu, Yu-Ying Liu, Ke Liu, Guo-Peng Wang, Shu-Sheng Gong
Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) has been shown to be a useful approach to local drug delivery into the inner ear. The goal of this article is to describe, in detail, the surgical techniques involved in canalostomy in both adult and neonatal mice. As indicated by fast-green dye and adeno-associated virus serotype 8 with the green fluorescent protein gene, the canalostomy facilitated broad distribution of injected reagents in the cochlea and vestibular end-organs with minimal damage to hearing and vestibular function...
May 25, 2018: Journal of Visualized Experiments: JoVE
Jian Zhang, Liming Yu, Yinli Xu, Yu Liu, Zhi Li, Xiaodong Xue, Song Wan, Huishan Wang
BACKGROUND: Myocardial infarction (MI) is one of the most common causes of cardiac morbidity and mortality. Many evidences suggest that hypothermia have a more pronounced impact as an adjunctive therapy for MI to reduce infarct size. However, the function of long non-coding RNAs (lncRNA) in therapeutic hypothermia for MI remains poorly understood. METHODS: In this study, we investigated the expression of lncRNA-UIHTC (upregulated in hypothermia treated cardiomyocytes, NONHSAT094064) in ischemic heart tissues...
September 1, 2018: International Journal of Cardiology
Yoshihide Sehara, Kuniko Shimazaki, Fumio Kurosaki, Naoki Kaneko, Ryosuke Uchibori, Masashi Urabe, Kensuke Kawai, Hiroaki Mizukami
Adeno-associated virus (AAV) is an ideal vector for gene transduction into the central nervous system because of its safety and efficiency. While it is currently widely used for clinical trials and is expected to become more widespread, the appropriate combination of viral serotypes and promoters have not been fully investigated. In this study, we compared the transduced gene expression of AAVrh10 to AAV5 in gerbil hippocampus using three different promoters, including cytomegalovirus (CMV), chicken β-actin promoter with the CMV immediate-early enhancer (CAG), and the Synapsin 1 (Syn1) promoter...
June 6, 2018: Neuroscience Letters
Florian Kahles, Ana Liberman, Constantin Halim, Matthias Rau, Julia Möllmann, Robert Werner Mertens, Marcia Rückbeil, Irmgard Diepolder, Benedikt Walla, Sebastian Diebold, Mathias Burgmaier, Corinna Lebherz, Nikolaus Marx, Michael Lehrke
OBJECTIVE: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists...
May 23, 2018: Molecular Metabolism
Mercè Obach, Azadeh Hosseini-Tabatabaei, Joel Montane, Katarina Wind, Galina Souchkatcheva, Derek Dai, John J Priatel, Paul C Orban, C Bruce Verchere
Overexpression of the X-linked inhibitor of apoptosis (XIAP) prevents islet allograft rejection. We constructed an adeno-associated virus expressing XIAP driven by the rat insulin promoter (dsAAV8-RIP-XIAP) for long-term beta-cell gene expression in vivo. Pancreatic delivery of dsAAV8-RIP-XIAP prevented autoimmune diabetes in 70% of NOD mice, associated with decreased insulitis. Islets from Balb/c mice transduced with dsAAV8-RIP-XIAP were protected following transplantation into streptozotocin (STZ)-diabetic Bl/6 recipients, associated with decreased graft infiltration...
June 5, 2018: Molecular and Cellular Endocrinology
Eiko Saijou, Yutaka Enomoto, Michitaka Matsuda, Cindy Yuet-Yin Kok, Shizuo Akira, Minoru Tanaka, Atsushi Miyajima
Tribbles pseudokinase 1 ( Trib1 ) is a negative regulator of CCAAT/enhancer binding protein α (C/EBPα) and is known to induce granulopoiesis while suppressing monocyte differentiation. Loss of Trib1 was previously shown to increase the neutrophil population in the spleen but lead to M2-like macrophage reduction. Because M2 macrophages are anti-inflammatory and promote tissue repair by producing fibrogenic factors, we investigated liver fibrosis in Trib1 -deficient mice. Interestingly, loss of Trib1 suppressed fibrosis in the CCl4 -induced chronic liver injury model...
June 2018: Hepatology Communications
J Mahlangu, M Cerquiera, A Srivastava
The therapeutic options for people with haemophilia (PWH) have rapidly evolved in the last 5 years. Moving on from conventional plasma-derived and recombinant clotting factor concentrates (CFC), there now are extended half-life CFCs (~1.8× for FVIII and ~4.5× for FIX) to as well as several novel haemostasis agents administered subcutaneously (weekly to monthly) such as bispecific antibody which brings together FIXa with FX like FVIII, a liver-targeted siRNA against antithrombin which can reduce its levels enough to allow significant haemostasis and an antibody against tissue factor pathway inhibitor which then also enhances haemostasis...
May 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
H Evens, M K Chuah, T VandenDriessche
Haemophilia is an attractive disease target for gene therapy that fostered the development of the field at large. The delivery of the clotting factor genes into the patients' cells could be accomplished using different types of gene delivery vehicles or vectors. Adeno-associated viral vectors (AAV) and lentiviral vectors represent some of the most promising gene delivery technologies that allow for a relatively efficient delivery of the therapeutic FVIII and FIX transgenes into the relevant target cells. To reduce the risks associated with insertional mutagenesis due to random vector integration, gene-editing approaches have also been considered based primarily on zinc finger nuclease (ZFN) and CRISPR/Cas...
May 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Jessica M Johnston, Sheila E Francis, Endre Kiss-Toth
Background: Murine models of atherosclerosis have been invaluable to gain mechanistic understanding of this chronic disease. Induction of atherosclerosis with relative ease in ApoE-/- and Ldlr-/- mice fed a Western-type diet to cause hyperlipidaemia has provided researchers with popular tools to manipulate and characterise the action of genes that affect atherogenesis. Seminal studies and reviews have discussed key phenotypic differences between different models and "target levels of hyperlipidaemia" have also been published...
June 5, 2018: Cardiovascular Research
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