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https://www.readbyqxmd.com/read/28213069/a-pilot-study-of-cell-mediated-gene-therapy-for-spinal-cord-injury-in-mini-pigs
#1
Islamov Rustem Robertovich, Sokolov Mikhail Evgenyevich, Bashirov Farid Vagizovich, Fadeev Filip Olegovich, Shmarov Maxim Michaylovich, Naroditskiy Boris Savelyevich, Povysheva Tatyana Vyacheslavovna, Shaymardanova Gulnara Ferdinantovna, Yakupov Radik Albertovich, Chelyshev Yuri Aleksandrovich, Lavrov Igor Aleksandrovich
Currently, in clinical practice there is no efficient way to overcome the sequences of neurodegeneration after spinal cord traumatic injury. Using a new experimental model of spinal cord contusion injury on miniature pigs, we proposed to deliver therapeutic genes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) to the damaged area, using umbilical cord blood mononuclear cells (UCBC). In this study, genetically engineered UCBC (2×10(6) cells in 200 ml of saline) were injected intrathecally to mini-pigs 10days after SCI...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28211494/hepatocyte-secreted-extracellular-vesicles-modify-blood-metabolome-and-endothelial-function-by-an-arginase-dependent-mechanism
#2
Felix Royo, Laura Moreno, Justyna Mleczko, Laura Palomo, Esperanza Gonzalez, Diana Cabrera, Angel Cogolludo, Francisco Perez Vizcaino, Sebastiaan van-Liempd, Juan M Falcon-Perez
Hepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although the importance of EVs in the intercellular communication is already recognized, the metabolic impact of the enzymes carried by these vesicles is still unclear. We evaluated the global effect of the enzymatic activities of EVs by performing untargeted metabolomic profiling of serum samples after their exposure to EVs. This approach revealed a significant change in the abundance of 94 serum metabolic signals...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209213/invited-review-relationship-between-cattle-transport-immunity-and-respiratory-disease
#3
B Earley, K Buckham Sporer, S Gupta
The association between transportation and the occurrence of the bovine respiratory disease complex (BRDC) has long been recognised. Many hypotheses regarding this association have been declared through the past decades, and it is agreed upon by most researchers that the multiple stressors that calves experience during transportation result in an overall immunosuppression that allows the respiratory tract to be invaded by numerous opportunistic pathogens. Furthermore, the innate immune cells, neutrophils, may be trapped in a paradox whereby their crucial defence and pathogen-killing activities are counteracted by excessive inflammation and tissue damage that may exacerbate disease, including the BRDC...
March 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28207964/impaired-nephrogenesis-in-neonatal-rats-with-oxygen-induced-retinopathy
#4
Mayu Nakagawa, Naoto Nishizaki, Amane Endo, Tomonosuke Someya, Yuta Saito, Akira Mizutani, Taichi Hara, Yayoi Murano, Koji Sakuraya, Satoshi Hara, Daisuke Umino, Daishi Hirano, Shuichiro Fujinaga, Yoshiyuki Ohtomo, Toshiaki Shimizu
OBJECTIVES: Preterm neonates are born while nephrogenesis is ongoing and are commonly exposed to factors in a hyperoxic environment that can impair renal development. Oxidative stress has also been implicated in the development of retinopathy of prematurity (ROP). The rat model of oxygen-induced retinopathy (OIR) is the most clinically relevant model of ROP because its biologic features closely resemble those of ROP in preterm infants. We investigated impaired renal development in a rat model of OIR...
February 16, 2017: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/28203236/the-deubiquitinating-enzyme-cylindromatosis-dampens-cd8-t-cell-responses-and-is-a-critical-factor-for-experimental-cerebral-malaria-and-blood-brain-barrier-damage
#5
Ursula Schmid, Werner Stenzel, Josephin Koschel, Maria Raptaki, Xu Wang, Michael Naumann, Kai Matuschewski, Dirk Schlüter, Gopala Nishanth
Cerebral malaria is a severe complication of human malaria and may lead to death of Plasmodium falciparum-infected individuals. Cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. Although CD8(+) T cells have been implicated in the development of murine experimental cerebral malaria (ECM), several other studies have shown that CD8(+) T cells confer protection against blood-stage infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28202860/hepatic-sinusoidal-obstruction-syndrome-induced-by-non-transplant-chemotherapy-for-non-hodgkin-lymphoma
#6
Miho Sakumura, Kazuto Tajiri, Shigeharu Miwa, Kohei Nagata, Kengo Kawai, Takayoshi Miyazono, Kotaro Arita, Akinori Wada, Jun Murakami, Toshiro Sugiyama
Hepatic sinusoidal obstruction syndrome (SOS), a serious complication that mainly occurs after hematopoietic-stem cell transplantation (HSCT), is caused by damage to the sinusoidal endothelial cells after the obstruction of the sinusoid. Recently, hepatic SOS was reported to occur after non-HSCT chemotherapies. This report describes a patient who experienced hepatic SOS after non-HSCT chemotherapy for non-Hodgkin lymphoma. A liver biopsy showed the slight dilatation of the hepatic sinusoid, which may be indicative of hepatic SOS...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28201843/regression-of-liver-fibrosis
#7
Lara Campana, John P Iredale
Liver fibrosis is the final common pathway of chronic or iterative liver damage. Advanced chronic fibrosis is described as cirrhosis with a loss of architecture and attendant functional failure and the development of life-threatening complications. However, compelling evidence from rodent models and human studies indicates that if the injury is removed liver fibrosis is reversible. Hepatocytes, activated hepatic stellate cells, endothelial and immune cells, particularly macrophages, cooperate in the establishment and resolution of liver fibrosis...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28196816/bone-marrow-derived-microrna-223-works-as-an-endocrine-genetic-signal-in-vascular-endothelial-cells-and-participates-in-vascular-injury-from-kawasaki-disease
#8
Maoping Chu, Rongzhou Wu, Shanshan Qin, Wenfeng Hua, Zhen Shan, Xing Rong, Jingjing Zeng, Lanlan Hong, Yeying Sun, Ying Liu, Wen Li, Shenming Wang, Chunxiang Zhang
BACKGROUND: Kawasaki disease (KD) is now the most common cause of acquired cardiac disease in children due to permanent coronary artery damage with unknown etiology. The study sought to determine the role of blood microRNA miR-223 in KD and KD-induced injuries in vascular endothelial cells (ECs) as well as the mechanisms involved. METHODS AND RESULTS: MicroRNA profiles in serum from patients with KD and from healthy controls were assessed by microarray analysis...
February 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28194878/platelet-activated-serum-might-have-a-therapeutic-effect-on-damaged-articular-cartilage
#9
Munetaka Yokoyama, Masato Sato, Yoshiki Tani, Miyuki Yokoyama, Mami Kokubo, Masayuki Yamato, Teruo Okano, Joji Mochida
Platelet-activated serum (PAS) was collected from rabbits. This contains high concentrations of growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, and transforming growth factor-beta (TGF-β). PAS was injected into the knee joints of Japanese White rabbits subjected to anterior cruciate ligament transection (ACL-T) to investigate its therapeutic effects on articular cartilage. The effect of Avastin (an anti-VEGF monoclonal antibody) on VEGF expression was also investigated...
February 14, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#10
Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28194438/a-role-for-muscarinic-receptors-in-neutrophil-extracellular-trap-formation-and-levamisole-induced-autoimmunity
#11
Carmelo Carmona-Rivera, Monica M Purmalek, Erica Moore, Meryl Waldman, Peter J Walter, H Martin Garraffo, Karran A Phillips, Kenzie L Preston, Jonathan Graf, Mariana J Kaplan, Peter C Grayson
Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28194256/retinal-diseases-associated-with-oxidative-stress-and-the-effects-of-a-free-radical-scavenger-edaravone
#12
REVIEW
Tomomi Masuda, Masamitsu Shimazawa, Hideaki Hara
Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28193577/tissue-plasminogen-activator-t-pa-and-plasminogen-activator-inhibitor-type-1-pai-1-in-diabetic-foot-syndrome
#13
Arleta Kulwas, Beata Lisewska, Wiesław Jundziłł, Barbara Ruszkowska, Wanda Drewniak, Zofia Ruprecht, Grażyna Gadomska, Danuta Rość
PURPOSE: The aim was to evaluate tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) concentration using enzyme linked immunosorbent assay method (ELISA) in diabetic foot syndrome (DFS) as compared to a group of healthy people and patients with diabetes mellitus without symptomatic vascular complications (DM2T). MATERIAL/METHODS: Venous blood samples were collected from 90 patients with type 2 diabetes mellitus (30 - DM2T; 60 - DFS)...
February 10, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28192115/substance-p-enhances-proliferation-and-paracrine-potential-of-adipose-derived-stem-cells-in%C3%A2-vitro
#14
Suna Kim, Jiyuan Piao, Youngsook Son, Hyun Sook Hong
Stem cells have tremendous promise to treat intractable diseases. Notably, adipose-derived stem cells (ADSCs) are actively being investigated because of ease of sampling and high repopulation capacity in vitro. ADSCs can exert a therapeutic effect through differentiation and paracrine potential, and these actions have been proven in many diseases, including cutaneous and inflammatory diseases. Transplantation of ADSCs necessitates therapeutic quantities and thus, long term ex vivo culture of ADSCs. However, this procedure can impair the activity of ADSCs and provoke cellular senescence, leading to low efficacy in vivo...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28190474/salvianolic-acid-a-inhibits-calpain-activation-and-enos-uncoupling-during-focal-cerebral-ischemia-in-mice
#15
Qaisar Mahmood, Guang-Fa Wang, Gang Wu, Huan Wang, Chang-Xin Zhou, Hong-Yu Yang, Zhi-Rong Liu, Feng Han, Kui Zhao
BACKGROUND: Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases. HYPOTHESIS: The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling. STUDY DESIGN: SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28188764/modulation-of-cerebral-rage-expression-following-nitric-oxide-synthase-inhibition-in-rats-subjected-to-focal-cerebral-ischemia
#16
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Fabio Blandini, Diana Amantea, Cristina Tassorelli
The receptor for advanced glycation endproducts (RAGE) is a key mediator of neuroinflammation following cerebral ischemia. Nitric oxide (NO) plays a dualistic role in cerebral ischemia, depending on whether it originates from neuronal, inducible or endothelial synthase. Although a dynamic interplay between RAGE and NO pathways exists, its relevance in ischemic stroke has not been investigated. The aim of this study is to evaluate the effect of the NO synthase (NOS) inhibition on RAGE expression in rats subjected to transient middle cerebral artery occlusion (tMCAo)...
February 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28187980/patients-with-hypertension-associated-thrombotic%C3%A2-microangiopathy-may-present-with%C3%A2-complement-abnormalities
#17
Sjoerd A M E G Timmermans, Myrurgia A Abdul-Hamid, Joris Vanderlocht, Jan G M C Damoiseaux, Chris P Reutelingsperger, Pieter van Paassen
Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28186692/targeted-genome-engineering-to-control-vegf-expression-in-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-potential-implications-for-the-treatment-of-myocardial-infarction
#18
Hyun-Min Cho, Pyung-Hwan Kim, Hyun-Kyung Chang, Yi-Ming Shen, Kwaku Bonsra, Byung-Jae Kang, Soo-Young Yum, Joo-Hyun Kim, So-Yeong Lee, Min-Cheol Choi, Hyongbum Henry Kim, Goo Jang, Je-Yoel Cho
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) exhibit potency for the regeneration of infarcted hearts. Vascular endothelial growth factor (VEGF) is capable of inducing angiogenesis and can boost stem cell-based therapeutic effects. However, high levels of VEGF can cause abnormal blood vessel growth and hemangiomas. Thus, a controllable system to induce therapeutic levels of VEGF is required for cell therapy. We generated an inducible VEGF-secreting stem cell (VEGF/hUCB-MSC) that controls the expression of VEGF and tested the therapeutic efficacy in rat myocardial infarction (MI) model to apply functional stem cells to MI...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28182324/clumping-factor-a-von-willebrand-factor-binding-protein-and-von-willebrand-factor-anchor-staphylococcus-aureus-to-the-vessel-wall
#19
J Claes, L Liesenborghs, M Peetermans, T R Veloso, D Missiakas, O Schneewind, S Mancini, J M Entenza, M F Hoylaerts, R Heying, P Verhamme, T Vanassche
OBJECTIVE: When establishing endovascular infections, Staphylococcus aureus (S. aureus) overcomes shear forces of flowing blood by binding to von Willebrand factor (VWF). Staphylococcal VWF-binding protein (vWbp) interacts with VWF, but it is unknown how this secreted protein binds to the bacterial cell wall. We hypothesized that vWbp interacts with a staphylococcal surface protein, mediating the adhesion of S. aureus to VWF and vascular endothelium under shear stress. METHODS: We studied the binding of S...
February 9, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28181929/corneal-endothelial-cell-integrity-in-precut-human-donor-corneas-enhanced-by-autocrine-vasoactive-intestinal-peptide
#20
Shay-Whey M Koh, Timothy Coll, Dante Gloria, Nicholas Sprehe
PURPOSE: To demonstrate that vasoactive intestinal peptide (VIP), a corneal endothelial (CE) cell autocrine factor, maintains the integrity of corneal endothelium in human donor corneoscleral explants precut for endothelial keratoplasty. METHODS: Twelve paired human donor corneoscleral explants used as control versus VIP-treated explants (10 nM, 30 minutes, 37°C) were shipped (4°C) to the Lions Eye Institute for Transplantation and Research for precutting (Moria CBM-ALTK Keratome), shipped back to the laboratory, and cultured in ciliary neurotrophic factor (CNTF, 0...
February 8, 2017: Cornea
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