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https://www.readbyqxmd.com/read/29055087/metabolism-and-tam-functions-it-takes-two-to-tango
#1
REVIEW
Massimiliano Mazzone, Alessio Menga, Alessandra Castegna
From the evidence on clinical studies and experimental mouse models we now know that tumor associated macrophages (TAMs) sustain tumor development in many different ways. They play a role in angiogenesis, tumor cell invasion and metastasis formation. Additionally, TAMs interfere with natural killer and T cell antitumoral activities, producing an immune suppressive environment that protects tumor cell growth. This indicates that the tumoricidal activity of macrophages within the tumor microenviroment is lost due to an imbalance of the regulatory mechanisms underpinning these cells' function...
October 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29055014/protein-acyltransferase-dhhc3-regulates-breast-tumor-growth-oxidative-stress-and-senescence
#2
Martin E Hemler, Chandan Sharma, Hong-Xing Wang, Qinglin Li, Konstantin Knoblich, Emily S Reisenbichler, Andrea L Richardson
DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29055013/a-synthetic-cd8%C3%AE-myd88-co-receptor-enhances-cd8-t-cell-responses-to-weakly-immunogenic-and-lowly-expressed-tumor-antigens
#3
Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy M Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzalez, Eduardo Davila
T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T cell efficacy, including suboptimal T cell receptor (TCR) activation and an immunosuppressive tumor environment. Here we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and co-stimulatory molecules in a tumor antigen-dependent manner...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29055012/type-i-interferon-enhances-necroptosis-of-salmonella-typhimurium-infected-macrophages-by-impairing-antioxidative-stress-responses
#4
Nina Judith Hos, Raja Ganesan, Saray Gutiérrez, Deniz Hos, Jennifer Klimek, Zeinab Abdullah, Martin Krönke, Nirmal Robinson
Salmonella enterica serovar Typhimurium exploits the host's type I interferon (IFN-I) response to induce receptor-interacting protein (RIP) kinase-mediated necroptosis in macrophages. However, the events that drive necroptosis execution downstream of IFN-I and RIP signaling remain elusive. In this study, we demonstrate that S Typhimurium infection causes IFN-I-mediated up-regulation of the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the transcription of Nrf2-dependent antioxidative genes...
October 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29055004/stat4-regulates-the-cd8-regulatory-t-cell-t-follicular-helper-cell-axis-and-promotes-atherogenesis-in-insulin-resistant-ldlr-mice
#5
Parésa L Taghavie-Moghadam, Tayab C Waseem, Julian Hattler, Lindsey M Glenn, Anca D Dobrian, Mark H Kaplan, Yi Yang, Roza Nurieva, Jerry L Nadler, Elena V Galkina
The metabolic syndrome and diabetic conditions support atherosclerosis, but the exact mechanisms for accelerated atherogenesis remain unclear. Although the proinflammatory role of STAT4 in atherosclerosis and diet-induced insulin resistance (IR) was recently established, the impact of STAT4 on atherogenesis in conditions of IR is not known. In this study, we generated Stat4(-/-)Ldlr(-/-) mice that were fed a diabetogenic diet with added cholesterol (DDC). DDC-fed Stat4(-/-)Ldlr(-/-) mice demonstrated improved glucose tolerance, insulin sensitivity, and a 36% reduction in atherosclerosis compared with Ldlr(-/-) controls...
October 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29054743/simultaneous-rna-seq-based-transcriptional-profiling-of-intracellular-brucella-abortus-and-b-abortus-infected-murine-macrophages
#6
Huynh Tan Hop, Lauren Togonon Arayan, Alisha Wehdnesday Bernardo Reyes, Tran Xuan Ngoc Huy, WonGi Min, Hu Jang Lee, Jee Soo Son, Suk Kim
Brucella is a zoonotic pathogen that survives within macrophages; however the replicative mechanisms involved are not fully understood. We describe the isolation of sufficient Brucella abortus RNA from primary host cell environment using modified reported methods for RNA-seq analysis, and simultaneously characterize the transcriptional profiles of intracellular B. abortus and bone marrow-derived macrophages (BMM) from BALB/c mice at 24 h (replicative phase) post-infection. Our results revealed that 25.12% (801/3190) and 16...
October 17, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29054699/silymarin-attenuated-paraquat-induced-cytotoxicity-in-macrophage-by-regulating-trx-txnip-complex-inhibiting-nlrp3-inflammasome-activation-and-apoptosis
#7
Zhenning Liu, Mingli Sun, Yu Wang, Lichun Zhang, Hang Zhao, Min Zhao
Oxidative stress and inflammation are involved in paraquat-induced cytotoxicity. Silymarin can exert a potent antioxidative and anti-inflammatory effect in various pathophysiological processes. The aim of this current study is to explore the protective effect and potential mechanism of silymarin in paraquat-induced macrophage injury. Cells were pretreated with different doses of silymarin for 3h before exposure to paraquat. At 24h after exposure to paraquat, the paraquat-induced cytotoxicity to macrophage was measured via the MTT assay and LDH release...
October 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29054682/liposomalization-of-oxaliplatin-induces-skin-accumulation-of-it-but-negligible-skin-toxicity
#8
Kentaro Nishida, Misaki Kashiwagi, Shunsuke Shiba, Kiwamu Muroki, Akihiro Ohishi, Yusuke Doi, Hidenori Ando, Tatsuhiro Ishida, Kazuki Nagasawa
Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil®, Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP...
October 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29054599/indoleamine-2-3-dioxygenase-expression-in-primary-cutaneous-melanoma-correlates-with-breslow-thickness-and-is-of-significant-prognostic-value-for-progression-free-survival
#9
Felicia Rubel, Johannes S Kern, Kristin Technau-Hafsi, Sibylle Uhrich, Kaethe Thoma, Georg Häcker, Nikolas von Bubnoff, Frank Meiss, Dagmar von Bubnoff
The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO-inhibitors were added to the regimen. Data on IDO-expression in primary human melanomas are however incomplete and conflicting. Here, we show that the level of IDO-expression in primary human melanoma cells significantly correlates with Breslow thickness (p = 0...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29054595/the-n-acylethanolamine-acid-amidase-inhibitor-arn077-suppresses-inflammation-and-pruritus-in-a-mouse-model-of-allergic-dermatitis
#10
O Sasso, M Summa, A Armirotti, S Pontis, C De Mei, D Piomelli
N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase highly expressed in macrophages and B-lymphocytes, catalyzes the degradation of palmitoylethanolamide (PEA). PEA is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α) and an important regulator of pain and innate immunity. In the present study, we investigated the properties of the NAAA inhibitor, ARN077, in a mouse model of allergic contact dermatitis. Acute topical applications of ARN077 attenuated key signs of DNFB-induced dermatitis in a dose-dependent manner...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29054529/development-of-amide-based-fluorescent-probes-for-selective-measurement-of-carboxylesterase-1-activity-in-tissue-extracts
#11
Sean D Kodani, Morgane Barthélemy, Shizuo G Kamita, Bruce Hammock, Christophe Morisseau
Carboxylesterases are well known for their role in the metabolism of xenobiotics. However, recent studies have also implicated carboxylesterases in regulating a number of physiological processes including metabolic homeostasis and macrophage development, underlying the need to quantify them individually. Unfortunately, current methods for selectively measuring the catalytic activity of individual carboxylesterases are not sufficiently sensitive to support many biological studies. In order to develop a more sensitive and selective method to measure the activity of human carboxylesterase 1 (hCE1), we generated and tested novel substrates with a fluorescent aminopyridine leaving group...
October 17, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/29054455/dadle-enhances-viability-and-anti-inflammatory-effect-of-human-mscs-subjected-to-serum-free-apoptotic-condition-in-part-via-the-dor-pi3k-akt-pathway
#12
L Vinod Kumar Reddy, Dwaipayan Sen
AIM: Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. MAIN METHODS: Cell viability was measured using MTT and Annexin V/PI assays...
October 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29054371/ragweed-pollen-as-an-oral-vaccine-delivery-system-mechanistic-insights
#13
Md Jasim Uddin, Harvinder Singh Gill
We have recently developed pollen grains (PGs) as a unique method to deliver vaccines orally. Extensive chemical processing ensures allergen-free pollen microcapsules that can be loaded with vaccine antigens. Successful oral vaccine delivery has been previously demonstrated by us in a mouse model. However, the underlying mechanisms that help the processed PGs to achieve this goal were not fully understood. In this study, we wanted to understand the effects of chemically processed ragweed pollen (Ambrosia elatior) on the innate immune system...
October 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29054343/aster-yomena-extract-ameliorates-pro-inflammatory-immune-response-by-suppressing-nf-%C3%AE%C2%BAb-activation-in-raw-264-7-cells
#14
Kyung-A Hwang, Yu-Jin Hwang, Jin Song
BACKGROUND: Aster yomena, an edible vegetable, is a perennial herb found in Korea, China, Japan, and Siberia. It is used as folk medicine to treat cough, bronchial asthma, and insect bites. A. yomena was recently shown to have antioxidant and anti-asthmatic activities. Studies have not yet evaluated the anti-inflammatory effects of the various solvent fractions of A. yomena. We investigated the anti-inflammatory activity of various solvent fractions (hexane, dichloromethane, ethyl acetate, and butanol) from ethanol extract of A...
October 18, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29053775/neuroinflammation-and-its-relationship-to-changes-in-brain-volume-and-white-matter-lesions-in-multiple-sclerosis
#15
Gourab Datta, Alessandro Colasanti, Eugenii A Rabiner, Roger N Gunn, Omar Malik, Olga Ciccarelli, Richard Nicholas, Eline Van Vlierberghe, Wim Van Hecke, Graham Searle, Andre Santos-Ribeiro, Paul M Matthews
Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients...
September 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053748/treatment-with-the-nr4a1-agonist-cytosporone-b-controls-influenza-virus-infection-and-improves-pulmonary-function-in-infected-mice
#16
Benoit Egarnes, Marie-Renée Blanchet, Jean Gosselin
The transcription factor NR4A1 has emerged as a pivotal regulator of the inflammatory response and immune homeostasis. Although contribution of NR4A1 in the innate immune response has been demonstrated, its role in host defense against viral infection remains to be investigated. In the present study, we show that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to mice infected with influenza virus (IAV) reduces lung viral loads and improves pulmonary function. Our results demonstrate that administration of Csn-B to naive mice leads to a modest production of type 1 IFN...
2017: PloS One
https://www.readbyqxmd.com/read/29053611/glucosylsphingosine-causes-hematological-and-visceral-changes-in-mice-evidence-for-a-pathophysiological-role-in-gaucher-disease
#17
Jan Lukas, Claudia Cozma, Fan Yang, Guido Kramp, Anja Meyer, Anna-Maria Neßlauer, Sabrina Eichler, Tobias Böttcher, Martin Witt, Anja U Bräuer, Peter Kropp, Arndt Rolfs
Glucosylceramide and glucosylsphingosine are the two major storage products in Gaucher disease (GD), an inherited metabolic disorder caused by a deficiency of the lysosomal enzyme glucocerebrosidase. The build-up of glucosylceramide in the endoplasmic reticulum and prominent accumulation in cell lysosomes of tissue macrophages results in decreased blood cell and platelet counts, and skeletal abnormalities. The pathological role of the deacylated form of glucosylceramide, glucosylsphingosine (lyso-Gb1), a recently identified sensitive and specific biomarker for GD, is not well investigated...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29053142/resolution-of-inflammation-and-sepsis-survival-are-improved-by-dietary-%C3%AE-3-fatty-acids
#18
Andreas Körner, Martin Schlegel, Julia Theurer, Hannes Frohnmeyer, Michael Adolph, Marieke Heijink, Martin Giera, Peter Rosenberger, Valbona Mirakaj
Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration...
October 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29053076/protective-effect-of-biodegradable-nerve-conduit-against-peripheral-nerve-adhesion-after-neurolysis
#19
Kosuke Shintani, Takuya Uemura, Kiyohito Takamatsu, Takuya Yokoi, Ema Onode, Mitsuhiro Okada, Hiroaki Nakamura
OBJECTIVE Peripheral nerve adhesion caused by extraneural and intraneural scar formation after neurolysis leads to nerve dysfunction. The authors previously developed a novel very flexible biodegradable nerve conduit composed of poly(L-lactide) and poly(ε-caprolactone) for use in peripheral nerve regeneration. In the present study, they investigated the effect of protective nerve wrapping on preventing adhesion in a rat sciatic nerve adhesion model. METHODS Rat sciatic nerves were randomly assigned to one of the following four groups: a no-adhesion group, which involved neurolysis alone without an adhesion procedure; an adhesion group, in which the adhesion procedure was performed after neurolysis, but no treatment was subsequently administered; a nerve wrap group, in which the adhesion procedure was performed after neurolysis and protective nerve wrapping was then performed with the nerve conduit; and a hyaluronic acid (HA) group, in which the adhesion procedure was performed after neurolysis and nerve wrapping was then performed with a 1% sodium HA viscous solution...
October 20, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29053067/the-proteome-of-pus-from-human-brain-abscesses-host-derived-neurotoxic-proteins-and-the-cell-type-diversity-of-cns-pus
#20
Bjørnar Hassel, Gustavo Antonio De Souza, Maria Ekman Stensland, Jugoslav Ivanovic, Øyvind Voie, Daniel Dahlberg
OBJECTIVE What determines the extent of tissue destruction during brain abscess formation is not known. Pyogenic brain infections cause destruction of brain tissue that greatly exceeds the area occupied by microbes, as seen in experimental studies, pointing to cytotoxic factors other than microbes in pus. This study examined whether brain abscess pus contains cytotoxic proteins that might explain the extent of tissue destruction. METHODS Pus proteins from 20 human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by proteomics mass spectrometry...
October 20, 2017: Journal of Neurosurgery
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