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https://www.readbyqxmd.com/read/29158825/noninvasive-imaging-of-cd206-positive-m2-macrophages-as-an-early-biomarker-for-post-chemotherapy-tumor-relapse-and-lymph-node-metastasis
#1
Chenran Zhang, Xinhe Yu, Liquan Gao, Yang Zhao, Jianhao Lai, Dehua Lu, Rui Bao, Bing Jia, Lijun Zhong, Fan Wang, Zhaofei Liu
Tumor relapse after initial regression post-chemotherapy is a major challenge in cancer treatment, as it usually leads to local-regional recurrence or inoperable distant metastasis. M2 macrophages diminish the tumor-inhibitory effect of chemotherapy and correlate with distant metastasis and poor prognosis. In this study, we investigated whether molecular imaging of M2 macrophages could serve as an early biomarker for tumor relapse after chemotherapy and tumor lymph node metastasis in preclinical mouse models...
2017: Theranostics
https://www.readbyqxmd.com/read/29141038/depot-specific-inflammation-with-decreased-expression-of-atm2-in-white-adipose-tissues-induced-by-high-margarine-lard-intake
#2
Nannan Wang, Jie Guo, Fuding Liu, Mingxia Wang, Chuntao Li, Lihong Jia, Lingling Zhai, Wei Wei, Yinglong Bai
A high-fat diet has been recognized as an important risk factor of obesity, with variable impacts of different fatty acid compositions on the physiological process. To understand the effects of a high-margarine/lard diet, which is a major source of trans fatty acids (TFAs)/ saturated fatty acids (SFAs), elaidic acid as a biomarker of margarine intake was used to screen affected adipokines on mature human adipocytes in vitro. Weaned male Wistar rats were fed a high-fat diet enriched with margarine/lard to generate obesity-prone (OP) and obesity-resistant (OR) models, which were then used to explore the inflammatory responses of depot-specific white adipose tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29137420/anti-angiogenic-and-anti-tumor-effects-of-metronomic-use-of-novel-liposomal-zoledronic-acid-depletes-tumor-associated-macrophages-in-triple-negative-breast-cancer
#3
Xin-Jun Cai, Zeng Wang, Jia-Wei Cao, Jian-Jun Ni, Ying-Ying Xu, Jun Yao, Hong Xu, Fang Liu, Gao-Yi Yang
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137411/a-novel-polyamine-blockade-therapy-activates-an-anti-tumor-immune-response
#4
Eric T Alexander, Allyson Minton, Molly C Peters, Otto Phanstiel, Susan K Gilmour
Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4(+) and CD8(+) T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132376/ezh2-suppression-in-glioblastoma-shifts-microglia-toward-m1-phenotype-in-tumor-microenvironment
#5
Yatao Yin, Shuwei Qiu, Xiangpen Li, Bo Huang, Yun Xu, Ying Peng
BACKGROUND: Glioblastoma multiforme (GBM) induces tumor immunosuppression through interacting with tumor-infiltrating microglia or macrophages (TAMs) with an unclear pathogenesis. Enhancer of zeste homolog 2 (EZH2) is abundant in GBM samples and cell lines and is involved in GBM proliferation, cell cycle, and invasion, whereas its association with innate immune response is not yet reported. Herein, the aim of this study was to investigate the role of EZH2 in GBM immune. METHODS: Co-culturing models of human/murine GBM cells with PBMC-derived macrophages/primary microglia were employed...
November 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29126792/in-vivo-cellular-and-molecular-gastroprotective-mechanisms-of-chrysin-emphasis-on-oxidative-stress-inflammation-and-angiogenesis
#6
Mina Y George, Ahmed Esmat, Mariane G Tadros, Ebtehal El-Demerdash
Gastric ulcer is one of the major gastrointestinal disorders affecting people worldwide. Despite medical advances, management of gastric ulcer and its complications remains a challenge facing medicine nowadays. In addition, currently available medicines exhibit limited efficacy and several side effects. In the current study, the potential protective effects of chrysin -naturally occurring flavonoid- were tested against indomethacin-induced gastric ulcer model in rats. It was found that chrysin in both doses; 50 and 100mg/kg were effective in promoting mucus secretion and preventing the rise in ulcer and lesion indices, acid production and histologic changes induced by indomethacin...
November 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29124400/characterization-of-m1-and-m2-polarization-of-macrophages-in-vascularized-human-dermo-epidermal-skin-substitutes-in-vivo
#7
Agnes S Klar, Katarzyna Michalak-Mićka, Thomas Biedermann, Claudia Simmen-Meuli, Ernst Reichmann, Martin Meuli
AIMS AND OBJECTIVES: Vascularized bio-engineered human dermo-epidermal skin substitutes (vascDESS) hold promise for treating burn patients, including those with severe full-thickness wounds. We have previously shown that vascDESS promote wound healing by enhanced influx of macrophages and granulocytes. Immediately following transplantation, macrophages infiltrate the graft and differentiate into a pro-inflammatory (M1) or a pro-healing M2 phenotype. The aim of this study was to characterize the activation state of macrophages infiltrating skin transplants at distinct time points following transplantation...
November 9, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/29121663/apoptosis-inhibitor-of-macrophage-depletion-decreased-m1-macrophage-accumulation-and-the-incidence-of-cardiac-rupture-after-myocardial-infarction-in-mice
#8
Shohei Ishikawa, Takahisa Noma, Hai Ying Fu, Takashi Matsuzaki, Makoto Ishizawa, Kaori Ishikawa, Kazushi Murakami, Naoki Nishimoto, Akira Nishiyama, Tetsuo Minamino
BACKGROUND: Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI...
2017: PloS One
https://www.readbyqxmd.com/read/29119707/impaired-expression-of-cxcl5-and-matrix-metalloproteinases-in-the-lungs-of-mice-with-high-susceptibility-to-streptococcus-pneumoniae-infection
#9
Rubia I Mancuso, Eliane N Miyaji, Cristiane C F Silva, Fernanda V Portaro, Alessandra Soares-Schanoski, Orlando G Ribeiro, Maria Leonor S Oliveira
INTRODUCTION: Streptococcus pneumoniae colonizes the nasopharynx of healthy individuals establishing a commensal relationship with the host. In some conditions, bacteria invade the lower respiratory tract and innate immune responses are crucial to avoid diseases such as pneumonia, sepsis, or meningitis. METHODS: Here, we compared the susceptibility to pneumococcal respiratory infection of two outbred mouse lines, AIRmin and AIRmax, selected for low or high acute inflammatory responses, respectively...
November 9, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29116108/precision-targeting-of-tumor-macrophages-with-a-cd206-binding-peptide
#10
Pablo Scodeller, Lorena Simón-Gracia, Sergei Kopanchuk, Allan Tobi, Kalle Kilk, Pille Säälik, Kaarel Kurm, Mario Leonardo Squadrito, Venkata Ramana Kotamraju, Ago Rinken, Michele De Palma, Erkki Ruoslahti, Tambet Teesalu
Tumor-associated macrophages (TAMs) expressing the multi-ligand endocytic receptor mannose receptor (CD206/MRC1) contribute to tumor immunosuppression, angiogenesis, metastasis, and relapse. Here, we describe a peptide that selectively targets MRC1-expressing TAMs (MEMs). We performed in vivo peptide phage display screens in mice bearing 4T1 metastatic breast tumors to identify peptides that target peritoneal macrophages. Deep sequencing of the peptide-encoding inserts in the selected phage pool revealed enrichment of the peptide CSPGAKVRC (codenamed "UNO")...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29113923/effects-of-spinal-non-viral-interleukin-10-gene-therapy-formulated-with-d-mannose-in-neuropathic-interleukin-10-deficient-mice-behavioral-characterization-mrna-and-protein-analysis-in-pain-relevant-tissues
#11
Arden G Vanderwall, Shahani Noor, Melody S Sun, Jacob E Sanchez, Xuexian O Yang, Lauren L Jantzie, Nikolaos Mellios, Erin D Milligan
Studies show that spinal (intrathecal; i.t.) interleukin-10 (IL-10) gene therapy reverses neuropathic pain in animal models, and co-administration with the mannose receptor (MR; CD206) ligand d-mannose (DM) greatly improves therapeutic efficacy. However, the actions of endogenous IL-10 may be required for enduring pain control observed following i.t. IL-10 gene therapy, potentially narrowing the application of this non-viral transgene delivery approach. Here, we show that i.t. application of naked plasmid DNA expressing the IL-10 transgene co-injected with DM (DM/pDNA-IL-10) for the treatment of peripheral neuropathic pain in IL-10 deficient (IL-10 KO) mice results in a profound and prolonged bilateral pain suppression...
November 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29113324/unfolded-protein-response-signaling-impacts-macrophage-polarity-to-modulate-breast-cancer-cell-clearance-and-melanoma-immune-checkpoint-therapy-responsiveness
#12
David R Soto-Pantoja, Adam S Wilson, Kenysha Yj Clear, Brian Westwood, Pierre L Triozzi, Katherine L Cook
The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization. Specifically, PERK targeting enhanced macrophage proliferation and macrophage-mediated killing but not GRP78 or IRE1. Targeting UPR in cancer cells also differentially affected macrophage cytolytic capacity. Tumoral IRE1 or GRP78 inhibition enhanced macrophage-mediated cancer cell clearance. Conditioned media from GRP78-silenced cancer cells caused reciprocal regulation of CD80 and CD206, suggesting control of plasticity by secreted factors...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29109719/phenotypic-characterization-of-human-monocytes-following-macronutrient-intake-in-healthy-humans
#13
Awad Alshahrani, Abdalmalik Bin Khunayfir, Mohammed Al Rayih, Hasan Al Sayed, Abdullah Alsadoon, Mohammed Al Dubayee, Mahmoud Zahra, Yousof Alrumayyan, Maha Al Zayer, Amre Nasr, Ahmad Aljada
Background: Three subsets of human monocytes in circulation have been identified and their characterization is still ill-defined. Although glucose and lipid intakes have been demonstrated to exert pro-inflammatory effects on mononuclear cells (MNCs) of healthy subjects, characterization of monocytes phenotypes following macronutrient (glucose, protein, and lipid) intake in humans remains to be determined. Methods: Thirty-six healthy, normal weight volunteers were recruited in the study...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29107327/microglia-are-continuously-activated-in-the-circumventricular-organs-of-mouse-brain
#14
Shohei Takagi, Eriko Furube, Yousuke Nakano, Mitsuhiro Morita, Seiji Miyata
Microglia are the primary resident immune cells of the brain parenchyma and transform into the amoeboid form in the "activated state" under pathological conditions from the ramified form in the "resting state" under physiologically healthy conditions. In the present study, we found that microglia in the circumventricular organs (CVOs) of adult mice displayed the amoeboid form with fewer branched cellular processes even under normal conditions; however, those in other brain regions showed the ramified form, which is characterized by well-branched and dendritic cellular processes...
October 19, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29101873/cathelicidin-wa-polarizes-e-coli-k88-induced-m1-macrophage-to-m2-like-macrophage-in-raw264-7-cells
#15
Shan Chen, Zeqing Lu, Fengqin Wang, Yizhen Wang
Immune cells - macrophages induced by E. coli K88 will lead to a pro-inflammatory response, which is important in host defense. Cathelicidin-WA (CWA) is an efficient antimicrobial peptide (AMP) and can exert immunomodulatory properties. Many studies have demonstrated that AMP can modulate cellular subsets but whether CWA can regulate macrophage polarization by transferring E. coli K88-induced M1 macrophage towards M2 one that of anti-inflammation remains unclear. In this study, E. coli K88 increased the expression of pro-inflammatory cytokines interleukin-6, interleukin-1β, tumor necrosis factor-α and chemokine CCL3 in RAW264...
November 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29101376/antibiotics-induce-polarization-of-pleural-macrophages-to-m2-like-phenotype-in-patients-with-tuberculous-pleuritis
#16
Sisi Wang, Jian Zhang, Liyan Sui, Hao Xu, Qianling Piao, Ying Liu, Xinglong Qu, Ying Sun, Lei Song, Dan Li, Liping Peng, Shucheng Hua, Guangan Hu, Jianzhu Chen
Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29096831/endothelial-function-and-gene-expression-in-perivascular-adipose-tissue-from-internal-mammary-arteries-of-obese-patients-with-coronary-artery-disease
#17
Maria Cybularz, Heike Langbein, Birgit Zatschler, Coy Brunssen, Andreas Deussen, Klaus Matschke, Henning Morawietz
BACKGROUND AND AIMS: Obesity is a risk factor for endothelial dysfunction and atherosclerosis. However, perivascular adipose tissue can release adipokines and other unknown adipose-derived relaxing factors. Therefore, we investigated the impact of obesity on vascular function and expression of genes in perivascular adipose tissue from internal mammary arteries of patients with coronary artery disease undergoing coronary artery bypass grafting. METHODS: The vessel function was compared between groups of patients with a body-mass index (BMI) between 25 and 30 kg/m(2)...
November 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/29093636/agmatine-modulates-the-phenotype-of-macrophage-acute-phase-after-spinal-cord-injury-in-rats
#18
Jae Hwan Kim, Jae Young Kim, Chin Hee Mun, Minah Suh, Jong Eun Lee
Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29089751/characteristics-and-potential-role-of-m2-macrophages-in-copd
#19
Shengyang He, Lihua Xie, Junjuan Lu, Shenghua Sun
BACKGROUND: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role. MATERIALS AND METHODS: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE)...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29079517/cathepsin-b-mediated-activation-of-trypsinogen-in-endocytosing-macrophages-increases-severity-of-pancreatitis-in-mice
#20
Matthias Sendler, Frank-Ulrich Weiss, Janine Golchert, Georg Homuth, Cindy van den Brandt, Ujjwal M Mahajan, Lars-Ivo Partecke, Paula Döring, Ilya Gukovsky, Anna S Gukovskaya, Preshit R Wagh, Markus M Lerch, Julia Mayerle
BACKGROUND & AIMS: Acute pancreatitis is characterized by premature intracellular activation of digestive proteases within pancreatic acini and a consecutive systemic inflammatory response. We investigated how these processes interact during severe pancreatitis in mice. METHODS: Pancreatitis was induced in C57Bl/6 wild-type (control), cathepsin B-knockout, and cathepsin L-knockout mice by partial pancreatic duct ligation with supramaximal caerulein injection, or by repetitive supramaximal caerulein injections alone...
October 24, 2017: Gastroenterology
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