Luca Cassetta, Kirsten Bruderek, Joanna Skrzeczynska-Moncznik, Oktawia Osiecka, Xiaoying Hu, Ida Marie Rundgren, Ang Lin, Kim Santegoets, Utku Horzum, Ana Godinho-Santos, Gennadiy Zelinskyy, Thalia Garcia-Tellez, Sunčica Bjelica, Bartłomiej Taciak, Astrid Olsnes Kittang, Benedikt Höing, Stephan Lang, Michael Dixon, Verena Müller, Jochen Sven Utikal, Derya Karakoç, Kerim Bora Yilmaz, Emilia Górka, Lubomir Bodnar, Olympia Evdoxia Anastasiou, Christine Bourgeois, Robert Badura, Monika Kapinska-Mrowiecka, Mirjana Gotic, Mark Ter Laan, Esther Kers-Rebel, Magdalena Król, Juan Francisco Santibañez, Michaela Müller-Trutwin, Ulf Dittmer, Ana Espada de Sousa, Güneş Esendağlı, Gosse Adema, Karin Loré, Elisabeth Ersvær, Viktor Umansky, Jeffrey W Pollard, Joanna Cichy, Sven Brandau
BACKGROUND: Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www...
September 2020: Journal for Immunotherapy of Cancer
Sayed Ali Sheikh
Background: Coronary artery diseases are the most important cause of premature death and it is predominantly related to atherosclerosis. Soluble lectin like oxidized low-density lipoprotein receptor-1 (sLOX-1) and microRNAs are closely associated with atherosclerotic coronary heart diseases. Aims: The current study investigated the relationship of plasma slOX-1and the severity of coronary artery disease patients (CAD) and association with microRNA-98. Study Design: Case control study...
September 2, 2020: Balkan Medical Journal
Tamara Sáez, Floor Spaans, Raven Kirschenman, Tatsuya Sawamura, Sandra T Davidge
The lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) has been shown to induce angiotensin II (AngII) type 1 receptor (AT1) activation, contributing to vascular dysfunction. Preeclampsia is a pregnancy complication characterized by vascular dysfunction and increased LOX-1 and AT1 activation; however, whether LOX-1 and AT1 activity contributes to vascular dysfunction in preeclampsia is unknown. We hypothesized that increased oxLDL levels during pregnancy lead to LOX-1 activation and subsequent AT1 activation, resulting in vascular dysfunction...
September 18, 2020: Clinical Science (1979-)
Junlin Zhang, Pu Yang, Hualin Wang, Qiang Huang, Ting Chen, Na Li, Hongyu Zhang, Zhiguo Liu
Excessive consumption of saturated fat leads to non-alcoholic fatty liver disease (NAFLD), which is attenuated by supplementation of n-3 polyunsaturated fatty acids (PUFAs). Endoplasmic reticulum (ER) stress is crucial in the development of NAFLD, but how high-saturated fat diet (HFD) causes ER stress and NAFLD remains unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in hepatic ER stress. We aimed to explore the roles of LOX-1 in HFD-induced ER stress. Male Sprague-Dawley rats were fed an HFD without or with supplementation of fish oil for 16 weeks...
August 24, 2020: Journal of Nutritional Biochemistry
Ekta Pandey, Aiah S Nour, Edward N Harris
Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells lining the sinusoidal capillaries of the hepatic system. LSECs are characterized with numerous fenestrae and lack basement membrane as well as a diaphragm. These unique morphological characteristics of LSECs makes them the most permeable endothelial cells of the mammalian vasculature and aid in regulating flow of macromolecules and small lipid-based structures between sinusoidal blood and parenchymal cells. LSECs have a very high endocytic capacity aided by scavenger receptors (SR), such as SR-A, SR-B (SR-B1 and CD-36), SR-E (Lox-1 and mannose receptors), and SR-H (Stabilins)...
2020: Frontiers in Physiology
Haruka Nasako, Yui Takashina, Hiroaki Eguchi, Ayaka Ito, Yoshinobu Ishikawa, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Claudin-1 (CLDN1), a tight junctional protein, is highly expressed in lung cancer cells and may contribute to chemoresistance. A drug which decreases CLDN1 expression could be a chemosensitizer for enhancing the efficacy of anticancer drugs, but there is no such drug known. We found that PMTPV, a short peptide, which mimics the structure of second extracellular loop (ECL2) of CLDN1, can reduce the protein level of CLDN1 without affecting the mRNA level in A549 cells derived from human lung adenocarcinoma. The PMTPV-induced decrease in CLDN1 expression was inhibited by monodansylcadaverine, a clathrin-mediated endocytosis inhibitor, and chloroquine, a lysosome inhibitor...
August 17, 2020: International Journal of Molecular Sciences
Fuyao Liu, Xiangsheng Zuo, Yi Liu, Yasunori Deguchi, Micheline J Moussalli, Weidong Chen, Peiying Yang, Bo Wei, Lin Tan, Philip L Lorenzi, Shen Gao, Jonathan C Jaoude, Amir Mehdizadeh, Lovie Ann Valentin, Daoyan Wei, Imad Shureiqi
APC mutation activation of Wnt/β-catenin drives initiation of colorectal carcinogenesis (CRC). Additional factors potentiate β-catenin activation to promote CRC. Western diets are enriched in linoleic acid (LA); LA-enriched diets promote chemically induced CRC in rodents. 15-Lipoxygenase-1 (15-LOX-1), the main LA-metabolizing enzyme, is transcriptionally silenced during CRC. Whether LA and 15-LOX-1 affect Wnt/β-catenin signaling is unclear. We report that high dietary LA promotes CRC in mice treated with azoxymethane or with an intestinally targeted Apc mutation (ApcΔ580 ) by upregulating Wnt receptor LRP5 protein expression and β-catenin activation...
August 18, 2020: Cell Reports
Xiaohong Xia, Qiong Xu, Mingke Liu, Xuke Chen, Xiaolin Liu, Jinchan He, Tumei Hu, Cuifu Yu, Hongbiao Huang, Shiming Liu, Ningning Liu
Atherosclerosis-associated cardiovascular diseases are main causes leading to high mortality worldwide. Macrophage-derived foam cell formation via uptaking modified lipoproteins is the initial and core step in the process of atherosclerosis. Meanwhile, scavenger receptor is indispensable for the formation of foam cells. UCHL1, a deubiquitinase, has been widely studied in multiple cancers. UCHL1 could be an oncogene or a tumor suppressor in dependent of tumor types. It remains unknown whether UCHL1 influences cellular oxLDL uptake...
August 15, 2020: Cell Death & Disease
Qian Li, Jianru Liu, Wenyi Liu, Yi Chu, Jinsheng Zhong, Ying Xie, Xinzhe Lou, Xiangying Ouyang
Porphyromonas gingivalis ( P. gingivalis ) is one of the main periodontal bacteria. This pathogen was reported to enhance monocyte migration and adhesion to endothelial cells in atherosclerosis. The scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays a pivotal role in atherogenesis. The aim of this study was to investigate whether LOX-1 modulates P. gingivalis -mediated monocyte migration and adhesion to endothelial cells and how it works. The results showed that the migration and adhesion of monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) were significantly enhanced when HUVECs or THP-1 cells were challenged with P...
2020: Frontiers in Cell and Developmental Biology
Dong Xu, Xang Sun, Yang Zhang, Li Cao
BACKGROUND: Acute lung injury (ALI) is a common critical respiratory disease that seriously threatens human health. Ketamine has good anti-inflammatory and immune-regulating properties that can delay the lung injury process. OBJECTIVES: High mobility group box protein 1 (HMGB1) plays an important role in the occurrence, development and treatment of ALI. Toll-like receptor 4 (TLR4) is the receptor for HMGB1. The aim of this study was to determine the role of the HMGB1 TLR4 signaling pathway in the treatment of ALI using ketamine...
July 28, 2020: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Tianqing Yan, Chang Liang, Haidi Fan, Wei Zhou, Linyan Huang, Suhua Qi, Wan Wang, Ping Ma
KRAB domain-associated protein 1 (KAP1) is highly expressed in atherosclerotic plaques. Here, we studied the role of KAP1 in atherosclerosis development using a cell model of endothelial dysfunction induced by oxidative low-density lipoprotein (OxLDL). The phosphorylation and protein levels of KAP1 were similar between OxLDL-treated and non-treated endothelial cells (ECs). KAP1 depletion significantly inhibited the production of OxLDL-enhanced reactive oxygen species and the expression of adhesion molecules in ECs...
July 29, 2020: Bioscience Reports
Valeria Tutino, Isabella Gigante, Rosa Anna Milella, Valentina De Nunzio, Riccardo Flamini, Mirko De Rosso, Maria Principia Scavo, Nicoletta Depalo, Elisabetta Fanizza, Maria Gabriella Caruso, Maria Notarnicola
Grapes contain many flavonoid and non-flavonoid compounds with anticancer effects. In this work we fully characterized the polyphenolic profile of two grape skin extracts (GSEs), Autumn Royal and Egnatia, and assessed their effects on Polyunsaturated Fatty Acid (PUFA) membrane levels of Caco2 and SW480 human colon cancer cell lines. Gene expression of 15-lipoxygenase-1 (15-LOX-1), and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as cell morphology, were evaluated. The polyphenolic composition was analyzed by Ultra-High-Performance Liquid Chromatography/Quadrupole-Time of Flight mass spectrometry (UHPLC/QTOF) analysis...
July 23, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ashim K Bagchi, Arun Surendran, Akshi Malik, Davinder S Jassal, Amir Ravandi, Pawan K Singal
Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake in a variety of physiological and pathological states. Given the anti-inflammatory role of the cytokine IL-10, we investigated its modulatory effect on the production of oxidized phosphatidylcholines (OxPCs) as well as lipid metabolic responses in global myocardial ischemia/reperfusion (I/R) injury. Increased OxPCs levels, by 1-Palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine (POVPC), promoted oxidative stress (OS) and cell death...
July 21, 2020: Scientific Reports
Ece Tavukcuoglu, Utku Horzum, Hamdullah Yanik, Aysegul Uner, Digdem Yoyen-Ermis, Safa K Nural, Busra Aydin, Cenk Sokmensuer, Derya Karakoc, Kerim Bora Yilmaz, Erhan Hamaloglu, Gunes Esendagli
In contrast to the mouse, functional assets of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the human spleen remain to be better elucidated. Here, we report that the spleen in gastric and pancreatic cancer adopts an immune regulatory character, harbors excessive amount of PMN-MDSC, and anatomically enables their interaction with T cells. Compared to the peripheral blood, the spleen from cancer patients contained significantly higher levels of low-density PMN-MDSC, but not early-stage MDSC (e-MDSC) and monocytic-MDSC (M-MDSC)...
July 20, 2020: European Journal of Immunology
Christina Gkolfinopoulou, Faye Soukou, Ioannis Dafnis, Tahsin F Kellici, Despina Sanoudou, Thomas Mavromoustakos, Efstratios Stratikos, Angeliki Chroni
Naturally occurring point mutations in apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), may affect plasma HDL-cholesterol levels and cardiovascular risk. Here, we evaluated the effect of human apoA-I mutations L144R (associated with low HDL-cholesterol), L178P (associated with low HDL-cholesterol and increased cardiovascular risk) and A164S (associated with increased cardiovascular risk and mortality without low HDL-cholesterol) on the structural integrity and functions of lipid-free and lipoprotein-associated apoA-I in an effort to explain the phenotypes of subjects carrying these mutations...
July 14, 2020: Cellular and Molecular Life Sciences: CMLS
Utku Horzum, Digdem Yoyen-Ermis, Ekim Z Taskiran, Kerim Bora Yilmaz, Erhan Hamaloglu, Derya Karakoc, Gunes Esendagli
Myeloid-derived suppressor cells (MDSC) populate the peripheral blood and contribute to immune regulation in cancer. However, there is limited knowledge on the myeloid cell types with proinflammatory capacities that may serve as opponents of MDSC. In the circulation of cancer patients, a monocyte subpopulation was identified with a specific immunophenotype and transcriptomic signature. They were predominantly CD14+ CD33hi CD16-/+ HLA-DR+/hi cells that typically expressed CD66b. In accordance with the transcriptomics data, NALP3, LOX-1 and PAI-1 levels were also significantly upregulated...
July 6, 2020: Cancer Immunology, Immunotherapy: CII
Jaewang Lee, Ji Hyeon You, Daiha Shin, Jong-Lyel Roh
PURPOSE: Tumor explant culture systems can mimic the in vivo tumor microenvironment, proposing as a substitute for preclinical studies for prediction of individual treatment response. Therefore, our study evaluated the potential usefulness of ex vivo tumor explants culture assembled into the cell sheets by anticancer drug screening in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Our model included tumor explants incorporated into cell sheet composing of epithelium and subepithelial stroma using tumor and mucosal samples obtained from the HNSCC patients who underwent surgery...
July 3, 2020: Journal of Cancer Research and Clinical Oncology
Yi Cai, Jie Liu, Shao-Kang Cai, Er-Ya Miao, Cheng-Qian Jia, Yong-Zhi Fan, Ying-Bo Li
Purpose: It is well known that diet Eicosapentaenoic acid (EPA) is beneficial to colon cancer (CC). However,  the underlying molecular mechanisms of EPA-relating miRNAs on genesis and development of this area is still unclear. Materials and Methods: This study tries to find the function and specific role of EPA in CC through quantitative PCR (qPCR), Western blotting, immunofluorescence (IF), mass spectrometry, and immunohistochemistry (IHC) assays. By these methods, the enrichment of 15-LOX-1 metabolites of EPA, the expression of miR-101 and Cox2, and the relationship among them in CC are measured...
2020: OncoTargets and Therapy
Yee Lian Tiong, Khuen Yen Ng, Rhun Yian Koh, Gnanajothy Ponnudurai, Soi Moi Chye
Background Cardiovascular disease (CVD) is one of the major cause of mortality in diabetic patients. Evidence suggests that hyperglycemia in diabetic patients contributes to increased risk of CVD. This study is to investigate the therapeutic effects of melatonin on glucose-treated human umbilical vein endothelial cells (HUVEC) and provide insights on the underlying mechanisms. Materials and methods Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and membrane potential was detected using 2',7'-dichlorofluorescein diacetate and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye staining, respectively...
June 29, 2020: Hormone Molecular Biology and Clinical Investigation
Guo-Qiang Zhu, Gui-Qiu Zhao, Cui Li, Jing Lin, Nan Jiang, Qian Wang, Qiang Xu, Xu-Dong Peng
AIM: To determine whether lectin-like ox-LDL receptor (LOX-1) regulates adhesion molecules expression and neutrophil infiltration in Aspergillus fumigatus ( A. fumigatus ) keratitis of C57BL/6 mice. METHODS: C57BL/6 mice were pretreated with a neutralizing antibody to LOX-1 (5 µg/5 µL) or control nonspecific IgG (5 µg/5 µL), LOX-1 inhibitor Poly-I (2 µg/5 µL) or PBS by subconjunctival injection. Fungal keratitis (FK) mouse models of C57BL/6 mice were established by scraping corneal central epithelium, smearing A...
2020: International Journal of Ophthalmology
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