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https://read.qxmd.com/read/30886813/therapeutic-remodeling-of-the-tumor-microenvironment-enhances-nanoparticle-delivery
#1
Yuanxin Chen, Xiujie Liu, Hengfeng Yuan, Zhaogang Yang, Christina A von Roemeling, Yaqing Qie, Hai Zhao, Yifan Wang, Wen Jiang, Betty Y S Kim
A major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability...
March 6, 2019: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/30886059/targeting-ve-ptp-phosphatase-protects-the-kidney-from-diabetic-injury
#2
Isabel A Carota, Yael Kenig-Kozlovsky, Tuncer Onay, Rizaldy Scott, Benjamin R Thomson, Tomokazu Souma, Christina S Bartlett, Yanyang Li, Daniele Procissi, Veronica Ramirez, Shinji Yamaguchi, Antoine Tarjus, Christine E Tanna, Chengjin Li, Vera Eremina, Dietmar Vestweber, Sunday S Oladipupo, Matthew D Breyer, Susan E Quaggin
Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability, inflammation, and endothelial cell loss and is associated with the development of diabetic complications. Here, we identified a mechanism to explain how TIE2 signaling is attenuated in diabetic animals. Expression of vascular endothelial protein tyrosine phosphatase VE-PTP (also known as PTPRB), which dephosphorylates TIE2, is robustly up-regulated in the renal microvasculature of diabetic rodents, thereby reducing TIE2 activity...
March 18, 2019: Journal of Experimental Medicine
https://read.qxmd.com/read/30886019/endothelial-adora2a-activation-promotes-blood-brain-barrier-breakdown-and-cognitive-impairment-in-mice-with-diet-induced-insulin-resistance
#3
Masaki Yamamoto, De-Huang Guo, Caterina M Hernandez, Alexis M Stranahan
Obesity and insulin resistance elicit blood-brain barrier (BBB) breakdown in humans and animal models, but the relative contributions of the two pathologies remain poorly understood. These studies initially addressed the temporal progression of cerebrovascular dysfunction relative to dietary obesity or diet-induced insulin resistance in male mice. Obesity increased BBB permeability to the low molecular weight fluorophore sodium fluorescein (NaFl), while diet-induced insulin resistance increased permeability to both NaFl and Evans Blue, which forms a high molecular weight complex with serum albumin...
March 18, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://read.qxmd.com/read/30885616/monomeric-%C3%AE-synuclein-induces-blood-brain-barrier-dysfunction-through-activated-brain-pericytes-releasing-inflammatory-mediators-in-vitro
#4
Shinya Dohgu, Fuyuko Takata, Junichi Matsumoto, Ikuya Kimura, Atsushi Yamauchi, Yasufumi Kataoka
Blood-brain barrier (BBB) disruption is often mediated by neuroinflammation, and occurs during various neurodegenerative diseases including Parkinson's disease (PD). PD is characterized by loss of dopaminergic neurons and aggregated α-synuclein protein in inclusions known as Lewy bodies. Misfolded α-synuclein has been implicated in neurodegeneration and neuroinflammation through activation of microglia and astrocytes. Pericytes are a key cellular regulator of the BBB, although it is not known if they participate in α-synuclein-associated PD pathology...
March 15, 2019: Microvascular Research
https://read.qxmd.com/read/30878197/a-novel-microscopic-assay-reveals-heterogeneous-regulation-of-local-endothelial-barrier-function
#5
Nadine Klusmeier, Hans-Joachim Schnittler, Jochen Seebach
Blood vessels are covered with endothelial cells on their inner surfaces, forming a selective and semipermeable barrier between the blood and the underlying tissue. Many pathological processes, such as inflammation or cancer metastasis, are accompanied by an increased vascular permeability. Progress in live cell imaging techniques has recently revealed that the structure of endothelial cell contacts is constantly reorganized and that endothelial junctions display high heterogeneities at a subcellular level even within one cell...
February 22, 2019: Biophysical Journal
https://read.qxmd.com/read/30877143/cd4-t-cell-sphingosine-1-phosphate-receptor-s1pr-1-and-s1pr4-and-endothelial-s1pr2-regulate-afferent-lymphatic-migration
#6
Yanbao Xiong, Wenji Piao, C Colin Brinkman, Lushen Li, Joseph M Kulinski, Ana Olivera, Andreane Cartier, Timothy Hla, Keli L Hippen, Bruce R Blazar, Susan R Schwab, Jonathan S Bromberg
Sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) regulate migration of lymphocytes out of thymus to blood and lymph nodes (LNs) to efferent lymph, whereas their role in other tissue sites is not known. Here, we investigated the question of how these molecules regulate leukocyte migration from tissues through afferent lymphatics to draining LNs (dLNs). S1P, but not other chemokines, selectively enhanced human and murine CD4 T cell migration across lymphatic endothelial cells (LECs). T cell S1PR1 and S1PR4, and LEC S1PR2, were required for migration across LECs and into lymphatic vessels and dLNs...
March 15, 2019: Science Immunology
https://read.qxmd.com/read/30876978/vitexin-protects-against-ischemia-reperfusion-induced-brain-endothelial-permeability
#7
Yu-Huan Cui, Xiao-Qing Zhang, Nai-Dong Wang, Mao-Dong Zheng, Juan Yan
Brain endothelial permeability plays a crucial role in blood-brain barrier (BBB), but the permeability enhancement in cerebral ischemia reperfusion (I/R). Vitexin has certain neuroprotective effects, but the effect brain endothelial permeability in I/R injury was unknown. In this study, the effects of Vitexin on endothelial permeability and the underlying mechanisms in human brain microvascular endothelial cells (HBMEc) I/R injury model were investigated. Cell viability, lactate dehydrogenase (LDH), inflammation and apoptosis were detected...
March 12, 2019: European Journal of Pharmacology
https://read.qxmd.com/read/30876401/capillary-leak-syndrome-triggered-by-maripa-virus-in-french-guiana-case-report-and-implication-for-pathogenesis
#8
Hatem Kallel, Séverine Matheus, Claire Mayence, Stéphanie Houcke, Cyrille Mathien, Anne Lavergne, Didier Hommel
BACKGROUND: We report hereby a severe case of Hantavirus Pulmonary Syndrome" (HPS) induced by Maripa virus in French Guiana and describe the mechanism of severity of the human disease. CASE PRESENTATION: A 47-year- old patient started presenting a prodromic period with fever, dyspnea, cough and head ache. This clinical presentation was followed by a rapid respiratory, hemodynamic and renal failure leading to admission in the ICU. Biological exams revealed an increased haematocrit level with a paradoxical low protein level...
March 15, 2019: BMC Infectious Diseases
https://read.qxmd.com/read/30873871/hydroxysafflor-yellow-a-attenuates-high-glucose-induced-human-umbilical-vein-endothelial-cell-dysfunction
#9
S Chen, J Ma, H Zhu, S Deng, M Gu, S Qu
High glucose (HG) induces vascular injury in diabetes. Hydroxysafflor yellow A (HSYA) has been used to ameliorate ischemic cardiovascular diseases in China for many years. In the present study, we assessed whether HSYA has a potential protective role in HG-induced human umbilical vein endothelial cell (HUVEC) injury. Cell viability was determined with an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Cell apoptosis was detected by fluorescein isothiocyanate/propidium iodide staining assay...
March 15, 2019: Human & Experimental Toxicology
https://read.qxmd.com/read/30872732/pro-angiogenic-ginsenosides-f1-and-rh1-inhibit-vascular-leakage-by-modulating-nr4a1
#10
Ji In Kang, Yoonjung Choi, Chang-Hau Cui, Daeyoup Lee, Sun Chang Kim, Ho Min Kim
Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, but VEGF-induced angiogenesis is often accompanied by a vascular permeability response. Ginsenosides are triterpenoid saponins from the well-known medicinal plant, ginseng, and have been considered a candidate for modulating angiogenesis. Here, we systemically investigated the effects of 10 different ginsenosides on human umbilical vein endothelial cells and newly identified that two PPT-type ginsenosides, F1 and Rh1 induce the migration and proliferation of endothelial cells...
March 14, 2019: Scientific Reports
https://read.qxmd.com/read/30867725/epidermal-growth-factor-treatment-has-protective-effects-on-the-integrity-of-the-blood-brain-barrier-against-cerebral-ischemia-injury-in-bend3-cells
#11
Shu Yang, Hong Jin, Zhi-Gang Zhao
Tight junctions (TJs) serve an important role in maintaining the integrity of the blood-brain barrier (BBB), while neurological disorders, including ischemic stroke, induce TJ disruption and increase BBB permeability; results include edema formation and hemorrhage transformation. Cerebral endothelium protection presents a promising approach in ischemic stroke therapy. In the current study, protective effects of the epidermal growth factor (EGF) on ischemia-induced disruption of BBB integrity were examined using an oxygen-glucose deprivation (OGD) model in bEnd3 cells...
March 2019: Experimental and Therapeutic Medicine
https://read.qxmd.com/read/30866689/degradation-of-glycocalyx-and-multiple-manifestations-of-endothelial-dysfunction-coincide-in-the-early-phase-of-endothelial-dysfunction-before-atherosclerotic-plaque-development-in-apolipoprotein-e-low-density-lipoprotein-receptor-deficient-mice
#12
Anna Bar, Marta Targosz-Korecka, Joanna Suraj, Bartosz Proniewski, Agnieszka Jasztal, Brygida Marczyk, Magdalena Sternak, Magdalena Przybyło, Anna Kurpińska, Maria Walczak, Renata B Kostogrys, Marek Szymonski, Stefan Chlopicki
Background The impairment of endothelium-dependent vasodilation, increased endothelial permeability, and glycocalyx degradation are all important pathophysiological components of endothelial dysfunction. However, it is still not clear whether in atherosclerosis, glycocalyx injury precedes other features of endothelial dysfunction or these events coincide. Methods and Results Herein, we demonstrate that in 4- to 8-week-old apolipoprotein E/low-density lipoprotein receptor-deficient mice, at the stage before development of atherosclerotic plaques, impaired acetylcholine-induced vasodilation, reduced NO production in aorta, and increased endothelial permeability were all observed; however, flow-mediated dilation in the femoral artery was fully preserved...
March 19, 2019: Journal of the American Heart Association
https://read.qxmd.com/read/30865689/the-natural-drug-diavit-is-protective-in-a-type-ii-mouse-model-of-diabetic-nephropathy
#13
Megan Stevens, Christopher R Neal, Elena C Craciun, Maria Dronca, Steven J Harper, Sebastian Oltean
There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT)...
2019: PloS One
https://read.qxmd.com/read/30863475/role-of-p120-catenin-in-epac1-induced-chronic-postsurgical-pain-in-rats
#14
Peng Pan, Sai-Sai Huang, Shi-Ren Shen, Cui-E Lu, Yi-Bin Qin, Jia-Long Zhang, Su Cao
Chronic postsurgical pain (CPSP) is a chronic pain state that is difficult to be treated clinically. A series of complicated changes have been produced from nociceptive stimulation to the occurrence and development of postsurgical pain. Many mechanisms remain unclear. In order to study the role of intercellular gap junctions in inducing inflammatory microenvironment at the beginning of nociceptor after operation, the model of skin/muscle incision and retraction (SMIR) was established. We observed the changes of the expression of exchange proteins directly activated by cAMP-1 (Epac1) and p120 catenin (p120), the quantities of macrophages and endothelial cells, vascular endothelial permeability, and mechanical withdrawal threshold (MWT)...
2019: Pain Research & Management: the Journal of the Canadian Pain Society
https://read.qxmd.com/read/30863410/inflammation-and-lymphatic-function
#15
REVIEW
Simon Schwager, Michael Detmar
The lymphatic vasculature plays a crucial role in regulating the inflammatory response by influencing drainage of extravasated fluid, inflammatory mediators, and leukocytes. Lymphatic vessels undergo pronounced enlargement in inflamed tissue and display increased leakiness, indicating reduced functionality. Interfering with lymphatic expansion by blocking the vascular endothelial growth factor C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) signaling axis exacerbates inflammation in a variety of disease models, including inflammatory bowel disease (IBD), rheumatoid arthritis and skin inflammation...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30855407/ligustilide-ameliorates-the-permeability-of-the-blood-brain-barrier-model-in-vitro-during-oxygen-glucose-deprivation-injury-through-hif-vegf-pathway
#16
Sipeng Wu, Ning Wang, Jing Li, Guangyun Wang, Sai Wang Seto, Dennis Chang, Huazheng Liang
Abstract Chuanxiong rhizome has been widely used for the treatment of cerebral vascular disease in traditional Chinese medicine. The integrity of blood-brain barrier (BBB) is closely linked to the cerebral vascular disease. The protective effects of ligustilide, the major bioactive component in Chuanxiong rhizome, on cerebral blood vessel has been reported previously, but its effects and potential mechanism on BBB has not been entirely clarified. In the current work, the effects of ligustilide on BBB permeability and the underlying molecular mechanisms had been investigated using the model of BBB established by co-culturing astrocytes and brain microvascular endothelial cells isolated from the rat brain...
March 6, 2019: Journal of Cardiovascular Pharmacology
https://read.qxmd.com/read/30855335/bone-morphogenetic-protein-and-blood-vessels-new-insights-into-endothelial-cell-junction-regulation
#17
Victoria L Bautch
PURPOSE OF REVIEW: BMP signaling is an important regulator of vascular development and homeostasis, and perturbations of BMP pathway components are linked to vascular disease. However, until recently BMP's broad requirements in many developmental programs delayed cause-and-effect and mechanistic studies of its vascular role in vivo. This review covers recent findings that illuminate the role of BMP signaling in endothelial cells of blood vessels, and highlights effects of BMP signaling on endothelial cell junctions and vascular barrier function...
March 6, 2019: Current Opinion in Hematology
https://read.qxmd.com/read/30853894/omi-htra2-protease-associated-cell-apoptosis-participates-in-blood-brain-barrier-dysfunction
#18
Yueyu Hu, Yong Bi, Danhua Yao, Pengfei Wang, Yousheng Li
Background : Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell apoptosis, translocating from mitochondria to the cytosol after an apoptotic insult. Our previous study indicated pre-treatment with UCF-101, a specific inhibitor of Omi/HtrA2, could significantly reduce neuronal apoptosis and attenuate sepsis-induced cognitive dysfunction. Various hypotheses involving blood-brain-barrier (BBB) disruption have been proposed to account for sepsis-associated encephalopathy (SAE)...
2019: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/30852795/canonical-wnt-pathway-maintains-blood-brain-barrier-integrity-upon-ischemic-stroke-and-its-activation-ameliorates-tissue-plasminogen-activator-therapy
#19
Noëmie Jean LeBlanc, Romain Menet, Katherine Picard, Geneviève Parent, Marie-Ève Tremblay, Ayman ElAli
Stroke induces blood-brain barrier (BBB) breakdown, which promotes complications like oedema and hemorrhagic transformation. Administration of recombinant tissue plasminogen activator (rtPA) within a therapeutic time window of 4.5 h after stroke onset constitutes the only existing treatment. Beyond this time window, rtPA worsens BBB breakdown. Canonical Wnt pathway induces BBB formation and maturation during ontogeny. We hypothesized that the pathway is required to maintain BBB functions after stroke; thus, its activation might improve rtPA therapy...
March 9, 2019: Molecular Neurobiology
https://read.qxmd.com/read/30852419/glucagon-like-peptide-1-attenuates-endothelial-barrier-injury-in-diabetes-via-camp-pka-mediated-down-regulation-of-mlc-phosphorylation
#20
Song-Tao Tang, Hai-Qin Tang, Huan Su, Yi Wang, Qing Zhou, Qiu Zhang, Yuan Wang, Hua-Qing Zhu
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) showed protective effects on endothelium-dependent dilatation. Since endothelial barrier dysfunction also plays a pivotal role in atherosclerosis, this study was designed to investigate the effects of GLP-1 on endothelial barrier function in diabetic aortic endothelium and explore the underlying mechanism. METHODS: For in vivo studies, diabetic rats were established and subjected to 12- and 24-week treatment of exenatide...
March 7, 2019: Biomedicine & Pharmacotherapy
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