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Monocyte/macrophage cell therapy

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https://www.readbyqxmd.com/read/29142307/genetic-polymorphism-related-to-monocyte-macrophage-function-is-associated-with-graft-versus-host-disease
#1
Kati Hyvärinen, Jarmo Ritari, Satu Koskela, Riitta Niittyvuopio, Anne Nihtinen, Liisa Volin, David Gallardo, Jukka Partanen
Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126881/triple-negative-breast-cancer-key-role-of-tumor-associated-macrophages-in-regulating-the-activity-of-anti-pd-1-pd-l1-agents
#2
REVIEW
Matteo Santoni, Emanuela Romagnoli, Tiziana Saladino, Laura Foghini, Stefania Guarino, Marco Capponi, Massimo Giannini, Paolo Decembrini Cognigni, Gerardo Ferrara, Nicola Battelli
Triple-negative breast cancer (TNBC) is associated with a poor prognosis, due to its aggressive behaviour and lack of effective targeted therapies. Immunocheckpoint inhibitors, such as anti-programmed cell death 1 (PD-1) and anti-PD-ligand(L)1 agents, are in course of investigation in TNBC, used alone or in combination with other systemic or local approaches. However, the high cost of these drugs and the lack of validated predictive biomarkers support the development of strategies aimed to overcome resistance and optimize the efficacy of these approaches...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29125067/evidence-of-size-dependent-effect-of-silica-micro-and-nano-particles-on-basal-and-specialized-monocyte-functions
#3
Mauricio C De Marzi, Martín Saraceno, Romina Mitarotonda, Marcos Todone, Marisa Fernandez, Emilio L Malchiodi, Martín F Desimone
AIM: To analyze the effect of silica particles on monocyte/macrophage functions. MATERIALS & METHODS: Silica micro- and nanoparticles were obtained by the Stöber method. Their effect on monocyte/macrophage proliferation, activation, membrane integrity and metabolic activity were determined. RESULTS: Silica particles inhibit cell proliferation while 10 nm nanoparticles (NPs) did not affect it. Similarly, silica particles induced strong cell activation...
December 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/29123113/talen-mediated-functional-correction-of-human-ipsc-derived-macrophages-in-context-of-hereditary-pulmonary-alveolar-proteinosis
#4
Alexandra Kuhn, Mania Ackermann, Claudio Mussolino, Toni Cathomen, Nico Lachmann, Thomas Moritz
Hereditary pulmonary alveolar proteinosis (herPAP) constitutes a rare, life threatening lung disease characterized by the inability of alveolar macrophages to clear the alveolar airspaces from surfactant phospholipids. On a molecular level, the disorder is defined by a defect in the CSF2RA gene coding for the GM-CSF receptor alpha-chain (CD116). As therapeutic options are limited, we currently pursue a cell and gene therapy approach aiming for the intrapulmonary transplantation of gene-corrected macrophages derived from herPAP-specific induced pluripotent stem cells (herPAP-iPSC) employing transcriptional activator-like effector nucleases (TALENs)...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122817/apo-a-i-apolipoprotein-a-i-vascular-gene-therapy-provides-durable-protection-against-atherosclerosis-in-hyperlipidemic-rabbits
#5
Bradley K Wacker, Nagadhara Dronadula, Lianxiang Bi, Alexis Stamatikos, David A Dichek
OBJECTIVE: Gene therapy that expresses apo A-I (apolipoprotein A-I) from vascular wall cells has promise for preventing and reversing atherosclerosis. Previously, we reported that transduction of carotid artery endothelial cells with a helper-dependent adenoviral (HDAd) vector expressing apo A-I reduced early (4 weeks) fatty streak development in fat-fed rabbits. Here, we tested whether the same HDAd could provide long-term protection against development of more complex lesions. APPROACH AND RESULTS: Fat-fed rabbits (n=25) underwent bilateral carotid artery gene transfer, with their left and right common carotids randomized to receive either a control vector (HDAdNull) or an apo A-I-expressing vector (HDAdApoAI)...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29118012/effects-and-mechanisms-of-caffeine-to-improve-immunologic-and-metabolic-abnormalities-in-diet-induced-obese-rats
#6
Chih-Wei Liu, Hung-Cheng Tsai, Chia-Chang Huang, Chang-Youh Tsai, Yen-Bo Su, Ming-Wei Lin, Kuei Chuan Lee, Yun-Cheng Hsieh, Tzu-Hao Li, Shiang-Fen Huang, Ying-Ying Yang, Ming-Chih Hou, Han-Chieh Lin, Fa-Yauh Lee, Shou-Dong Lee
In obesity, there are no effective therapies for parallel immune and metabolic abnormalities including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, anti-hepatic steatosis and anti-insulin-resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6-week of caffeine treatment (HFD-caf) on immunologic and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. In comparison with HFD-V rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule1 (ICAM-1) and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT) and muscle' macrophages and its intracellular cytokines levels...
November 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29097651/a-new-concept-of-the-old-inhibitor-nsc-74859-in-alleviating-cardiac-allograft-rejection-and-extending-allograft-survival-in-mice
#7
Yiquan Lai, Feng Kuang, Zhonggui Shan, Huaqing Liu
BACKGROUND STAT1/4 has been suggested to be involved in cardiac allograft rejection. However, no direct evidence regarding STAT3 has been established in cardiac allograft rejection. Here, we hypothesized that inhibition of STAT3 attenuates cardiac allograft rejection. MATERIAL AND METHODS To test our hypothesis, homotopic mouse heart transplantation was carried out in syngeneic C57BL/6 to C57BL/6 strain mice with or without oral gavage with NSC 74859, an inhibitor of STAT3. The immune response was investigated using real-time PCR for CD4 and CD8 surface makers of T cells and CD14 of monocytes and cytokines, including IL-2, IL-15, and IL-6 of allografts at 3, 6, and 9 days after transplantation...
November 3, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29095439/epothilone-b-impairs-functional-recovery-after-spinal-cord-injury-by-increasing-secretion-of-macrophage-colony-stimulating-factor
#8
Liang Mao, Wei Gao, Shurui Chen, Ying Song, Changwei Song, Zipeng Zhou, Haosen Zhao, Kang Zhou, Wei Wang, Kunming Zhu, Chang Liu, Xifan Mei
The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29077145/rosuvastatin-promotes-the-differentiation-of-peripheral-blood-monocytes-into-m2-macrophages-in-patients-with-atherosclerosis-by-activating-ppar-%C3%AE
#9
T Zhang, B Shao, G-A Liu
OBJECTIVE: To evaluate M2 marker changes in human circulating monocytes before and after rosuvastatin treatment, and to investigate the effects of rosuvastatin on the differentiation of monocytes into M2 macrophages by activating peroxisome proliferator-activated receptor-γ (PPAR-γ). PATIENTS AND METHODS: A total of 20 patients was administrated with rosuvastatin. The human peripheral blood mononuclear cells (PBMCs) were extracted by Ficoll-Hypaque density gradient centrifugation method...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29066542/mechanisms-of-cns-viral-seeding-by-hiv-cd14-cd16-monocytes-establishment-and-reseeding-of-viral-reservoirs-contributing-to-hiv-associated-neurocognitive-disorders
#10
Mike Veenstra, Rosiris León-Rivera, Ming Li, Lucio Gama, Janice E Clements, Joan W Berman
HIV reservoirs persist despite antiretroviral therapy (ART) and are established within a few days after infection. Infected myeloid cells in the central nervous system (CNS) may contribute to the establishment of a CNS viral reservoir. The mature CD14(+) CD16(+) monocyte subset enters the CNS in response to chemokines, including CCL2. Entry of infected CD14(+) CD16(+) monocytes may lead to infection of other CNS cells, including macrophages or microglia and astrocytes, and to release of neurotoxic early viral proteins and additional cytokines...
October 24, 2017: MBio
https://www.readbyqxmd.com/read/29058205/monocyte-mediated-drug-delivery-systems-for-the-treatment-of-cardiovascular-diseases
#11
REVIEW
Gil Aizik, Etty Grad, Gershon Golomb
Major advances have been achieved in understanding the mechanisms and risk factors leading to cardiovascular disorders and consequently developing new therapies. A strong inflammatory response occurs with a substantial recruitment of innate immunity cells in atherosclerosis, myocardial infarction, and restenosis. Monocytes and macrophages are key players in the healing process that ensues following injury. In the inflamed arterial wall, monocytes, and monocyte-derived macrophages have specific functions in the initiation and resolution of inflammation, principally through phagocytosis, and the release of inflammatory cytokines and reactive oxygen species...
October 20, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29056774/glucocorticoid-management-in-rheumatoid-arthritis-morning-or-night-low-dose
#12
REVIEW
Sabrina Paolino, Maurizio Cutolo, Carmen Pizzorni
Morning symptoms of rheumatoid arthritis (RA) are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a "replacement therapy". In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation...
2017: Reumatologia
https://www.readbyqxmd.com/read/29046677/defining-genome-wide-expression-and-phenotypic-contextual-cues-in-macrophages-generated-by-granulocyte-macrophage-colony-stimulating-factor-macrophage-colony-stimulating-factor-and-heat-killed-mycobacteria
#13
Samer Bazzi, Emale El-Darzi, Tina McDowell, Helmout Modjtahedi, Satvinder Mudan, Marcel Achkar, Charles Akle, Humam Kadara, Georges M Bahr
Heat-killed (HK) Mycobacterium obuense (NCTC13365) is currently being evaluated in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the molecular underpinnings underlying immunomodulatory properties of HK M. obuense are still largely undefined. To fill this void, we sought to perform immunophenotyping, chemokine/cytokine release analysis and genome-wide characterization of monocyte-derived macrophages (MDM) in which monocytes were originally isolated from healthy donors and differentiated by HK M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29042454/complement-activating-anti-hla-antibodies-in-kidney-transplantation-allograft-gene-expression-profiling-and-response-to-treatment
#14
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29042140/myeloid-cells-contribute-indirectly-to-vegf-expression-upon-hypoxia-via-activation-of-m%C3%A3-ller-cells
#15
Christina Nürnberg, Norbert Kociok, Claudia Brockmann, Timo Lischke, Sergio Crespo-Garcia, Nadine Reichhart, Susanne Wolf, Ria Baumgrass, Sabine A Eming, Sandra Beer-Hammer, Antonia M Joussen
Anti-VEGF-directed therapies have been a milestone for treating retinal vascular diseases. Depletion of monocyte lineage cells suppresses pathological neovascularization in the oxygen-induced retinopathy mouse model. However, the question whether myeloid-derived VEGF-A expression is responsible for the pathogenesis in oxygen-induced retinopathy remained unknown. We analyzed LysMCre-driven myeloid cell-specific VEGF-A knockout mice as well as mice with complete depletion of circulating macrophages through clodronate-liposome treatment in the oxygen-induced retinopathy model by immunohistochemistry, qPCR, and flow cytometry...
October 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29030487/macrophage-specific-expression-of-il-37-in-hyperlipidemic-mice-attenuates-atherosclerosis
#16
Sara McCurdy, Yvonne Baumer, Emma Toulmin, Bog-Hieu Lee, William A Boisvert
Atherosclerosis, the progressive buildup of plaque within arterial blood vessels, can lead to fatal downstream events, such as heart attack or stroke. A key event contributing to the development of atherosclerosis is the infiltration of monocytes and its associated inflammation, as well as the formation of lipid-laden macrophage foam cells within the vessel wall. IL-37 is recognized as an important anti-inflammatory cytokine expressed especially by immune cells. This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29027964/microglia-and-monocytes-macrophages-polarization-reveal-novel-therapeutic-mechanism-against-stroke
#17
REVIEW
Masato Kanazawa, Itaru Ninomiya, Masahiro Hatakeyama, Tetsuya Takahashi, Takayoshi Shimohata
Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke...
October 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29026137/opiate-use-inhibits-tlr9-signaling-pathway-in-vivo-possible-role-in-pathogenesis-of-hiv-1-infection
#18
Yanyan Liao, Junjun Jiang, Bingyu Liang, Fumei Wei, Jiegang Huang, Peijiang Pan, Jinming Su, Bo Zhou, Ning Zang, Li Ye, Hao Liang
The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28983775/deficiency-of-adenosine-deaminase-2-dada2-an-inherited-cause-of-polyarteritis-nodosa-and-a-mimic-of-other-systemic-rheumatologic-disorders
#19
REVIEW
Hasan Hashem, Susan J Kelly, Nancy J Ganson, Michael S Hershfield
PURPOSE OF REVIEW: A new autoinflammatory disease, deficiency of adenosine deaminase 2 (DADA2), caused by mutations in the CECR1 gene, was first reported in 2014. This review aims to update progress in defining, treating, and understanding this multi-faceted disorder. RECENT FINDINGS: DADA2 was first described in patients with systemic inflammation, mild immune deficiency, and vasculopathy manifested as recurrent stroke or polyarteritis nodosa (PAN). More than 125 patients have now been reported, and the phenotype has expanded to include children and adults presenting primarily with pure red cell aplasia (PRCA), or with antibody deficiency...
October 5, 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28979941/chemical-modulation-of-in-vivo-macrophage-function-with-subpopulation-specific-fluorescent-prodrug-conjugates
#20
Antonio Fernandez, Matthieu Vermeren, Duncan Humphries, Ramon Subiros-Funosas, Nicole Barth, Lara Campana, Alison MacKinnon, Yi Feng, Marc Vendrell
Immunomodulatory agents represent one of the most promising strategies for enhancing tissue regeneration without the side effects of traditional drug-based therapies. Tissue repair depends largely on macrophages, making them ideal targets for proregenerative therapies. However, given the multiple roles of macrophages in tissue homeostasis, small molecule drugs must be only active in very specific subpopulations. In this work, we have developed the first prodrug-fluorophore conjugates able to discriminate closely related subpopulations of macrophages (i...
September 27, 2017: ACS Central Science
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