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https://www.readbyqxmd.com/read/28504320/photosensitization-priming-of-tumor-microenvironments-improves-delivery-of-nanotherapeutics-via-neutrophil-infiltration
#1
Dafeng Chu, Xinyue Dong, Qi Zhao, Jingkai Gu, Zhenjia Wang
Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition...
May 15, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28487567/a-robust-in-vitro-model-for-trans-lymphatic-endothelial-migration
#2
Yanbao Xiong, C Colin Brinkman, Konrad S Famulski, Emmanuel F Mongodin, Colin J Lord, Keli L Hippen, Bruce R Blazar, Jonathan S Bromberg
Trans-endothelial migration (TEM) is essential for leukocyte circulation. While much is known about trans-blood endothelial migration, far less is known about trans-lymphatic endothelial migration. We established an in vitro system to evaluate lymphatic TEM for various cell types across primary mouse and human lymphatic endothelial cells (LEC), and validated the model for the murine LEC cell line SVEC4-10. T cells exhibited enhanced unidirectional migration from the basal (abluminal) to the apical (luminal) surface across LEC, whereas for blood endothelial cells (BEC) they migrated similarly in both directions...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487203/mmps-timps-imbalances-in-the-peripheral-blood-and-cerebrospinal-fluid-are-associated-with-the-pathogenesis-of-hiv-1-associated-neurocognitive-disorders-a-pilot-study
#3
Yanyan Xing, Nicole Shepherd, Jie Lan, Wei Li, Sushmita Rane, Samir K Gupta, Shanxiang Zhang, Jun Dong, Qigui Yu
HIV-1-associated neurocognitive disorders (HAND) continue to be a major concern in the infected population, despite the widespread use of combined antiretroviral therapy (cART). Growing evidence suggests that an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs) contributes to the pathogenesis of HAND. In our present study, we examined protein levels and enzymatic activities of MMPs and TIMPs in both plasma and cerebrospinal fluid (CSF) samples from HIV-1 patients with or without HAND and HIV-1-negative controls...
May 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28484055/endothelial-cd2ap-binds-the-receptor-icam-1-to-control-mechanosignaling-leukocyte-adhesion-and-the-route-of-leukocyte-diapedesis-in-vitro
#4
Antje Schaefer, Trynette J van Duijn, Jisca Majolee, Keith Burridge, Peter L Hordijk
Inflammation is driven by excessive transmigration (diapedesis) of leukocytes from the blood to the tissue across the endothelial cell monolayer that lines blood vessels. Leukocyte adhesion, crawling, and transmigration are regulated by clustering of the endothelial mechanosensitive receptor intercellular adhesion molecule-1 (ICAM-1). Whereas several proteins are known to promote ICAM-1 function, the molecular mechanisms that limit ICAM-1-mediated adhesion to prevent excessive leukocyte transmigration remain unknown...
May 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28467903/locally-triggered-release-of-the-chemokine-ccl21-promotes-dendritic-cell-transmigration-across-lymphatic-endothelia
#5
Kari Vaahtomeri, Markus Brown, Robert Hauschild, Ingrid De Vries, Alexander Franz Leithner, Matthias Mehling, Walter Anton Kaufmann, Michael Sixt
Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28458030/dexamethasone-conjugated-dna-nanotubes-as-anti-inflammatory-agents-in%C3%A2-vivo
#6
Sabine Sellner, Samet Kocabey, Tao Zhang, Katharina Nekolla, Saskia Hutten, Fritz Krombach, Tim Liedl, Markus Rehberg
The biopolymer DNA allows to create nanoscale, biocompatible structures, which can be designed in a target-specific and stimuli-responsive manner. DNA carrier systems with these characteristics hold a great potential for nanomedical applications, such as for the treatment of inflammatory diseases. Here we used a DNA-based drug carrier system for the pH-dependent delivery of the glucocorticoid dexamethasone into macrophages, a cell type with a key role in the regulation of inflammation. Dexamethasone (Dex) nanotubes were internalized within minutes by MH-S macrophages in vitro and by tissue resident macrophages in the mouse cremaster muscle in vivo and localized in their endosomes...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28453484/can-better-management-of-periodontal-disease-delay-the-onset-and-progression-of-alzheimer-s-disease
#7
Alice Harding, Sarita Robinson, StJohn Crean, Sim K Singhrao
A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28452683/mechanisms-and-pathways-of-toxoplasma-gondii-transepithelial-migration
#8
Emily J Jones, Tamas Korcsmaros, Simon R Carding
Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established...
January 2, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28448444/role-of-the-vanins-myeloperoxidase-axis-in-colorectal-carcinogenesis
#9
REVIEW
Francesco Mariani, Luca Roncucci
The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28430717/multilateral-functional-alterations-of-human-neutrophils-in-sepsis-from-the-point-of-diagnosis-to-the-seventh-day
#10
Akira Endo, Miko Okamura, Shunsuke Yoshikawa, Yasuhiro Otomo, Tomohiro Morio
Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in fifty-nine sepsis patients...
April 20, 2017: Shock
https://www.readbyqxmd.com/read/28429235/regulation-of-human-brain-microvascular-endothelial-cell-adhesion-and-barrier-functions-by-memantine
#11
Fei Wang, Zhirong Zou, Yi Gong, Dong Yuan, Xun Chen, Tao Sun
Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α)...
April 20, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28425867/chemokines-and-relevant-micrornas-in-the-atherogenic-process
#12
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Chemokines play a significant role in initial and advanced steps of atherogenesis. In early steps, chemokines control the adhesion of leukocytes to endothelial cells (ECs) followed by transmigration of monocytes and their deposition in the intima where they differentiate to proinflammatory macrophages. Except proinflammatory activity, chemokines are responsible for homeostasis and homing of progenitor cells. Recently, microRNAs (miRs) were found to control expression and activity of chemokines in ECs, vascular smooth muscle cells (VSMCs), and macrophages at different steps of atherogenesis...
April 19, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28413983/peripheral-blood-mononuclear-cells-of-alzheimer-s-disease-patients-control-ccl4-and-cxcl10-levels-in-a-human-blood-brain-barrier-model
#13
Julie Vérité, Thierry Janet, Adrien Julian, Damien Chassaing, Guylène Page, Marc Paccalin
BACKGROUND: Alzheimer's disease (AD) is accompanied by a neuroinflammation triggering chemoattractant signals towards peripheral blood mononuclear cells (PBMCs), in turn could reduce amyloid plaques after transmigration through the blood brain barrier (BBB). But the chemotactic environment remains unclear. OBJECTIVE: To analyze five chemokines known to be involved in AD in three different cellular models to better understand the cellular and molecular interactions in the BBB...
April 17, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28409823/an-s1p1-agonist-asp4058-suppresses-intracranial-aneurysm-through-promoting-endothelial-integrity-and-blocking-macrophage-transmigration
#14
Rie Yamamoto, Tomohiro Aoki, Hirokazu Koseki, Miyuki Fukuda, Jun Hirose, Keiichi Tsuji, Katsumi Takizawa, Shinichiro Nakamura, Haruka Miyata, Nozomu Hamakawa, Hidetoshi Kasuya, Kazuhiko Nozaki, Yoshitaka Hirayama, Ichiro Aramori, Shuh Narumiya
BACKGROUND AND PURPOSE: Intracranial aneurysm (IA), common in general public, causes lethal subarachnoid hemorrhage on rupture. Prevention of rupture of IA is therefore socially important. However, there is currently no medical treatment. Recent studies suggest that IA is a disease of chronic inflammation in the arterial wall caused by endothelial dysfunction and infiltrated macrophages. Sphingosine-1-phosphate receptor type 1 (S1P1 ) is present on the endothelium and promotes its barrier function...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28391344/is-there-a-role-for-tnf%C3%AE-blockade-in-anca-associated-vasculitis-and-glomerulonephritis
#15
Stephen P McAdoo, Charles D Pusey
Tumour necrosis factor alpha (TNFα) is a cytokine that is pivotal in the inflammatory response. Blockade of TNFα has been shown to be effective in a number of human autoimmune diseases, including rheumatoid arthritis, raising the question of whether this approach may be effective in inflammatory kidney disease, such as ANCA-associated vasculitis (AAV). In AAV, there is considerable evidence for the role of TNFα in the pathophysiology of disease, including increased expression of TNFα mRNA in leucocytes and in renal tissue...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28379166/phospholipase-d-from-loxosceles-laeta-spider-venom-induces-il-6-il-8-cxcl1-gro-%C3%AE-and-ccl2-mcp-1-production-in-human-skin-fibroblasts-and-stimulates-monocytes-migration
#16
José M Rojas, Tomás Arán-Sekul, Emmanuel Cortés, Romina Jaldín, Kely Ordenes, Patricio R Orrego, Jorge González, Jorge E Araya, Alejandro Catalán
Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD) from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD) and lipid inflammatory mediators ceramide 1-phosphate (C1P) and lysophosphatidic acid (LPA), and the evaluation of their roles in monocyte migration...
April 5, 2017: Toxins
https://www.readbyqxmd.com/read/28377412/astrocyte-shed-extracellular-vesicles-regulate-the-peripheral-leukocyte-response-to-inflammatory-brain-lesions
#17
Alex M Dickens, Luis B Tovar-Y-Romo, Seung-Wan Yoo, Amanda L Trout, Mihyun Bae, Marlene Kanmogne, Bezawit Megra, Dionna W Williams, Kennith W Witwer, Mar Gacias, Nino Tabatadze, Robert N Cole, Patrizia Casaccia, Joan W Berman, Daniel C Anthony, Norman J Haughey
Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response...
April 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28345319/vascular-cell-adhesion-molecule-1-intercellular-adhesion-molecule-1-and-cluster-of-differentiation-146-levels-in-patients-with-type-2-diabetes-with-complications
#18
F Sinem Hocaoglu-Emre, Devrim Saribal, Guven Yenmis, Guvenc Guvenen
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multisystemic, chronic disease accompanied by microvascular complications involving various complicated mechanisms. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and cluster of differentiation-146 (CD146) are mainly expressed by endothelial cells, and facilitate the adhesion and transmigration of immune cells, leading to inflammation. In the present study, we evaluated the levels of soluble adhesion molecules in patients with microvascular complications of T2DM...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28337205/high-interferon-%C3%AE-uniquely-in-v%C3%AE-1-t-cells-correlates-with-markers-of-inflammation-and-axonal-damage-in-early-multiple-sclerosis
#19
Avadhesh Kumar Singh, Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Zetterberg, Jan Lycke, Susanna L Cardell
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#20
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
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