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https://www.readbyqxmd.com/read/28636088/multicompartment-drug-release-system-for-dynamic-modulation-of-tissue-responses
#1
Aaron H Morris, Rajwant S Mahal, Jillian Udell, Michelle Wu, Themis R Kyriakides
Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28636034/upregulation-of-heme-oxygenase-1-mediates-the-anti-inflammatory-activity-of-casein-glycomacropeptide-gmp-hydrolysates-in-lps-stimulated-macrophages
#2
Tiange Li, Xue Cheng, Min Du, Bin Chen, Xueying Mao
Recently, we have shown that casein glycomacropeptide hydrolysates (GHP) exhibit both anti-inflammatory and anti-oxidative activities in vitro. However, whether heme oxygenase-1 (HO-1) is involved in the cytoprotective effect of GHP against the inflammatory status remains unclear. Therefore, we hypothesized that HO-1 is a potential target of GHP, which mediates its anti-inflammatory effect. Here, GHP inhibited the intracellular reactive oxygen species (ROS) accumulation and NADPH oxidase 2 (NOX2) expression and enhanced reduced glutathione (GSH) levels in LPS-stimulated RAW264...
June 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28635594/translation-repression-via-modulation-of-the-cytoplasmic-poly-a-binding-protein-in-the-inflammatory-response
#3
Xu Zhang, Xiaoli Chen, Qiuying Liu, Shaojie Zhang, Wenqian Hu
Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs' 3'UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor...
June 21, 2017: ELife
https://www.readbyqxmd.com/read/28635366/redox-biology-of-leishmania-and-macrophage-targeted-nanoparticles-for-therapy
#4
Hafiz Shoaib Sarwar, Sohail Akhtar, Muhammad Farhan Sohail, Zaeema Naveed, Muhammad Rafay, Akhtar Nadhman, Masoom Yasinzai, Gul Shahnaz
Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#5
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634775/hydrophilic-acylated-surface-protein-a-haspa-of-leishmania-donovani-expression-purification-and-biophysico-chemical-characterization
#6
Manoj Kumar, Kishu Ranjan, Vijay Singh, Chandramani Pathak, Anju Pappachan, Desh Deepak Singh
Hydrophilic acylated surface proteins (HASPs) are acidic surface proteins which get localized on the surface of Leishmania parasite during infective stages through a "non-classical" pathway. In this study, we report the heterologous expression and purification of Leishmania donovani HASPA (r-LdHASPA) in E. coli system and its partial characterization. The structural aspects of the purified protein were analyzed using CD spectroscopy and modeling studies which indicate that r-LdHASPA consists of random coils...
June 21, 2017: Protein Journal
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#7
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#8
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634420/characterization-of-the-proinflammatory-profile-of-synovial-fluid-derived-exosomes-of-patients-with-osteoarthritis
#9
Rossana Domenis, Rossella Zanutel, Federica Caponnetto, Barbara Toffoletto, Adriana Cifù, Cinzia Pistis, Paolo Di Benedetto, Araldo Causero, Massimo Pozzi, Fabrizio Bassini, Martina Fabris, Kayvan R Niazi, Patrick Soon-Shiong, Francesco Curcio
The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634401/ohrr-of-mycobacterium-smegmatis-senses-and-responds-to-intracellular-organic-hydroperoxide-stress
#10
Omar A Garnica, Kishore Das, Subramanian Dhandayuthapani
Organic hydroperoxide reductase regulator (OhrR) in bacteria is a sensor for organic hydroperoxide stress and a transcriptional regulator for the enzyme organic hydroperoxide reductase (Ohr). In this study we investigated, using a GFP reporter system, whether Mycobacterium smegmatis OhrR has the ability to sense and respond to intracellular organic hydroperoxide stress. It was observed that M. smegmatis strains bearing the pohr-gfpuv fusion construct were able to express GFP only in the absence of an intact ohrR gene, but not in its presence...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634350/a-subset-of-cerebrovascular-pericytes-originates-from-mature-macrophages-in-the-very-early-phase-of-vascular-development-in-cns
#11
Seiji Yamamoto, Masashi Muramatsu, Erika Azuma, Masashi Ikutani, Yoshinori Nagai, Hiroshi Sagara, Bon-Nyeo Koo, Satomi Kita, Erin O'Donnell, Tsuyoshi Osawa, Hiroyuki Takahashi, Ken-Ichi Takano, Mitsuko Dohmoto, Michiya Sugimori, Isao Usui, Yasuhide Watanabe, Noboru Hatakeyama, Takahiro Iwamoto, Issei Komuro, Kiyoshi Takatsu, Kazuyuki Tobe, Shumpei Niida, Naoyuki Matsuda, Masabumi Shibuya, Masakiyo Sasahara
Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31(+)F4/80(+) hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634345/sirtuin-3-deficiency-does-not-alter-host-defenses-against-bacterial-and-fungal-infections
#12
Eleonora Ciarlo, Tytti Heinonen, Jérôme Lugrin, Hans Acha-Orbea, Didier Le Roy, Johan Auwerx, Thierry Roger
Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. SIRT3 deficiency has been reported to promote chronic inflammation-related disorders, but whether SIRT3 impacts on innate immune responses and host defenses against infections remains essentially unknown. This aspect is of primary importance considering the great interest in developing SIRT3-targeted therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#13
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634242/type-ii-secretion-substrates-of-legionella-pneumophila-translocate-out-of-the-pathogen-occupied-vacuole-via-a-semipermeable-membrane
#14
Hilary K Truchan, Harry D Christman, Richard C White, Nakisha S Rutledge, Nicholas P Cianciotto
Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#15
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28634205/macrophages-don-t-take-more-than-they-can-eat
#16
Annalisa M VanHook
Innate immune signaling feeds forward to control the rate at which macrophages phagocytose bacteria.
June 20, 2017: Science Signaling
https://www.readbyqxmd.com/read/28634079/relaxin-reduces-susceptibility-to-post-infarct-atrial-fibrillation-in-mice-due-to-anti-fibrotic-and-anti-inflammatory-properties
#17
Thomas Beiert, Vedat Tiyerili, Vincent Knappe, Verena Effelsberg, Markus Linhart, Florian Stöckigt, Sabine Klein, Robert Schierwagen, Jonel Trebicka, Georg Nickenig, Jan W Schrickel, René P Andrié
BACKGROUND: Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI). METHODS: Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28633932/%C3%AE-2-adrenoreceptor-stimulation-dampens-the-lps-induced-m1-polarization-in-pig-macrophages
#18
Elodie Bacou, Karine Haurogné, Marie Allard, Grégoire Mignot, Jean-Marie Bach, Julie Hervé, Blandine Lieubeau
The cross-talk between sympatho-adreno-medullar axis and innate immunity players was mainly studied in rodents. In intensive husbandry, pigs are exposed to multiple stressors inducing repeated releases of catecholamines that bind to adrenoreceptors (AR) on target cells. Among adrenoreceptors, the β2-AR is largely expressed by immune cells including macrophages. We report herein on the effects of catecholamines, through β2-AR stimulation, on pig macrophage functions activated by LPS. β2-AR stimulation of porcine macrophages prevented the LPS-induced increase in TNFα and IL-8 secretion while increasing IL-10 secretion...
June 17, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28633597/effect-of-t-2-toxin-injected-shrimp-muscle-extracts-on-mouse-macrophage-cells-raw264-7
#19
Zhanrui Huang, Yaling Wang, Mei Qiu, Lijun Sun, Jianmeng Liao, Rundong Wang, Xiaodong Sun, Siyuan Bi, Ravi Gooneratne
Following intramuscular injections of 0.1 mL, 3 mg kg(-1 )BW(-1)(1/10 LD50) T-2 toxin (T-2), the tissue concentration of T-2 in shrimp was quantitatively detected using LC-MS/MS. The biological half-time (t1/2) of T-2 in blood was 40.47 ± 0.24 min. The highest number of intramuscular T-2 shrimp could tolerate when given at blood t1/2 intervals was 4. The shrimps which were injected 5 T-2 died. The T-2 toxin highest accumulation was 0.471 ± 0.012 ng g(-1 )BW(-1). The effect of toxic shrimp muscle subjected to different processing conditions (high pressure, trifluoroacetic acid, acid and alkali digestions, artificial digestive juice [to simulate exposure to gastric and intestinal juices]) on mouse macrophage cells (RAW267...
February 10, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28633555/glutamine-administration-in-early-or-late-septic-phase-downregulates-lymphocyte-pd-1-pd-l1-expression-and-the-inflammatory-response-in-mice-with-polymicrobial-sepsis
#20
Ya-Mei Hu, Yuan-Chin Hsiung, Man-Hui Pai, Sung-Ling Yeh
BACKGROUND: Sepsis is a severe inflammatory response to infection. Excessive compensation to inflammation leads to dysregulated immune response that ultimately results in organ damage and lethality of sepsis. This study administered glutamine (GLN) in the early or late phase of sepsis to investigate its effects on regulating leukocyte programmed cell death 1 (PD-1) and its ligand (programmed cell death ligand 1 [PD-L1]) expression, macrophage function, inflammation, and acute kidney injury in sepsis...
March 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
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