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Margaret E Kirkling, Urszula Cytlak, Colleen M Lau, Kanako L Lewis, Anastasia Resteu, Alireza Khodadadi-Jamayran, Christian W Siebel, Hélène Salmon, Miriam Merad, Aristotelis Tsirigos, Matthew Collin, Venetia Bigley, Boris Reizis
The IRF8-dependent subset of classical dendritic cells (cDCs), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor FLT3 ligand (FLT3L) yields very few cDC1s (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing the Notch ligand Delta-like 1 (OP9-DL1) optimize FLT3L-driven development of cDC1s from murine immortalized progenitors and primary bone marrow cells...
June 19, 2018: Cell Reports
Farshid Yekani, Mahnaz Azarnia, Fereshteh Esfandiari, Seyedeh-Nafiseh Hassani, Hossein Baharvand
Optimization of an in vitro culture that supports blastocyst (BL) development from single blastomeres (SBs) is essential to generate additional embryos for farm animals and humans and unravel the mechanisms that underlie totipotency. In this study, we have examined BL development from SBs that were derived from 2-cell and 4-cell mouse embryos in different media. Moreover, BLs were assessed for inner cell mass (ICM) by staining with Oct4. We found that BL development was improved in a lower volume of medium (1 µL) compared with a higher volume (5 µL)...
June 20, 2018: Journal of Cellular Biochemistry
Emma Reece, Sean Doyle, Peter Greally, Julie Renwick, Siobhán McClean
Many cystic fibrosis (CF) airway infections are considered to be polymicrobial and microbe-microbe interactions may play an important role in disease pathology. Pseudomonas aeruginosa and Aspergillus fumigatus are the most prevalent bacterial and fungal pathogens isolated from the CF airway, respectively. We have previously shown that patients co-colonized with these pathogens had comparable outcomes to those chronically colonized with P. aeruginosa . Our objective was to examine the interactions between A...
2018: Frontiers in Microbiology
Alejandra Orihuel, Lucrecia Terán, Jenny Renaut, Graciela M Vignolo, André M De Almeida, María L Saavedra, Silvina Fadda
Human infection by Enterohemorrhagic Escherichia (E.) coli (EHEC) occurs through the ingestion of contaminated foods such as milk, vegetable products, water-based drinks, and particularly minced meats. Indeed EHEC is a pathogen that threatens public health and meat industry. The potential of different Lactic Acid Bacteria (LAB) strains to control EHEC in a meat-based medium was evaluated by using a simple and rapid method and by analyzing the growth kinetics of co-cultures (LAB-EHEC) in a meat-based medium...
2018: Frontiers in Microbiology
Beate M Rüger, Tanja Buchacher, Alexander Giurea, Bernd Kubista, Michael B Fischer, Johannes M Breuss
Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix. Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro , and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model...
2018: Frontiers in Physiology
Takuya Kato, Kazuhiro Noma, Toshiaki Ohara, Hajime Kashima, Yuki Katsura, Hiroaki Sato, Satoshi Komoto, Ryoichi Katsube, Takayuki Ninomiya, Hiroshi Tazawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
PURPOSE: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression. EXPERIMENTAL DESIGN: 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+ ) TILs by immunohistochemistry. We analyzed cytokines using murine or human fibroblasts and cancer cells...
June 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sara Donzelli, Elisa Milano, Magdalena Pruszko, Andrea Sacconi, Silvia Masciarelli, Ilaria Iosue, Elisa Melucci, Enzo Gallo, Irene Terrenato, Marcella Mottolese, Maciej Zylicz, Alicja Zylicz, Francesco Fazi, Giovanni Blandino, Giulia Fontemaggi
BACKGROUND: As crucial regulators of the immune response against pathogens, macrophages have been extensively shown also to be important players in several diseases, including cancer. Specifically, breast cancer macrophages tightly control the angiogenic switch and progression to malignancy. ID4, a member of the ID (inhibitors of differentiation) family of proteins, is associated with a stem-like phenotype and poor prognosis in basal-like breast cancer. Moreover, ID4 favours angiogenesis by enhancing the expression of pro-angiogenic cytokines interleukin-8, CXCL1 and vascular endothelial growth factor...
June 19, 2018: Breast Cancer Research: BCR
Sunhye Shin, Jung-Won Choi, Soyeon Lim, Seahyoung Lee, Eun-Young Jun, Hyun-Min Sun, Il-Kwon Kim, Hoon-Bum Lee, Sang Woo Kim, Ki-Chul Hwang
Adipose-derived stromal vascular fractions (SVFs) are a heterogeneous collection of cells, and their regenerative modality has been applied in various animal experiments and clinical trials. Despite the attractive advantages of SVFs in clinical interventions, the recent status of clinical studies involving the application of SVFs in many diseases has not been fully evaluated. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types despite their low numbers in heart tissue...
June 19, 2018: Cell Biochemistry and Function
Dominika Polak, Christine Hafner, Peter Briza, Claudia Kitzmüller, Adelheid Elbe-Bürger, Nazanin Samadi, Maria Gschwandtner, Wolfgang Pfützner, Gerhard J Zlabinger, Beatrice Jahn-Schmid, Barbara Bohle
BACKGROUND: Neutrophils and allergen-specific T-cells accumulate in allergic late-phase reactions (LPR). Their presence is associated with severe inflammation. Cytokines like GM-CSF, IFN-γ, and IL-3, typically found in allergic LPR, have been proposed to convert neutrophils into antigen-presenting cells (APC). OBJECTIVE: To assess the antigen-processing and presenting capacity of neutrophils from allergic patients. METHODS: Neutrophils were isolated from peripheral blood of birch pollen-allergic donors and stimulated with GM-CSF, IFN-γ, and IL-3...
June 16, 2018: Journal of Allergy and Clinical Immunology
Yu Shi, Xiangyu Guo, Jie Zhang, Hanchi Zhou, Bei Sun, Jing Feng
Type 2 diabetes mellitus (T2DM) complicated with obstructive sleep apnea (OSA) may cause neuronal apoptosis and cognitive deficits, but the underlying mechanisms remain unclear. We aimed to determine the relationship between the activation of microglia and the apoptosis of hippocampal neurons, specifically in terms of high mobility group box-1 (HMGB1), after high glucose (HG) and intermittent hypoxia (IH) exposure. Diabetic KK-Ay mice and non-diabetic C57BL/6J mice (C57 mice) underwent IH or normoxia (control) exposure for 4 weeks...
June 16, 2018: Brain, Behavior, and Immunity
Rebecca J Boohaker, Vijaya Sambandam, Isaac Segura, James Miller, Mark Suto, Bo Xu
We report here the rational design and validation of a peptide inhibitor to the PD-1/PD-L1 interaction as an attempt to develop a viable alternative to current inhibitory antibodies. We demonstrated, by biolayer interferometry and in silico docking simulations, that a PD-L1 peptide mimetic (PL120131) can interfere with the PD-1/PD-L1 interaction by binding to PD-1. We show that PL120131 is capable of inhibiting PD-1 mediated apoptotic signaling pathway and rescuing Jurkat cells and primary lymphocytes from apoptosis...
June 16, 2018: Cancer Letters
Lanlin Zhang, Yuan Qi, Kailin Xing, Song Qian, Ping Zhang, Xianghua Wu
The discovery of epidermal growth factor receptor (EGFR)‑sensitive mutations in non‑small cell lung cancer (NSCLC) and the successful clinical application of EGFR tyrosine kinase inhibitors (TKIs) have changed the regimen of lung cancer therapy from traditional cytotoxic chemotherapy to molecular‑targeted cancer therapy. However, the main limitation of EGFR‑TKI therapy is the heterogeneity of lung cancer harboring EGFR‑sensitive mutations. In addition, the synergistic effect of the administration of chemotherapy and EGFR‑TKIs, combined with tumor heterogeneity, on NSCLC remains unclear...
June 18, 2018: Oncology Reports
Xusheng Ding, Wenqi Xi, Jun Ji, Qu Cai, Jinling Jiang, Min Shi, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Cancer‑associated fibroblasts (CAFs) are predominate cells in tumor stroma and play a key role in tumor progression. Hepatocyte growth factor (HGF) is a cytokine mainly derived from fibroblasts. In the present study, we reported that HGF significantly promoted angiogenesis of human umbilical vein endothelial cells (HUVECs) and vasculogenic mimicry (VM) formation of gastric cancer cells, respectively, by increasing cell proliferation and migration. In addition, mosaic vessels formed by HUVECs and gastric cancer cells were also increased with treatment of recombinant human HGF and conditioned medium from CAFs...
June 18, 2018: Oncology Reports
Sozaburo Ihara, Yoshihiro Hirata, Yohko Hikiba, Aya Yamashita, Mayo Tsuboi, Masahiro Hata, Mitsuru Konishi, Nobumi Suzuki, Kosuke Sakitani, Hiroto Kinoshita, Yoku Hayakawa, Hayato Nakagawa, Hideaki Ijichi, Keisuke Tateishi, Kazuhiko Koike
Background and Aims: Disturbance of intestinal homeostasis is associated with the development of inflammatory bowel disease (IBD), and TGF-β signaling impairment in mononuclear phagocytes (MPs) causes murine colitis with goblet cell depletion. Here, we examined an organoid-MP co-culture system to study the role of MPs in intestinal epithelial differentiation and homeostasis. Methods: Intestinal organoids were co-cultured with lamina propria leukocytes and bone marrow-derived dendritic cells (BMDCs) from CD11c-cre Tgfbr2fl/fl mice...
June 16, 2018: Journal of Crohn's & Colitis
Bettina Hiemer, Martin Krogull, Thomas Bender, Josefin Ziebart, Simone Krueger, Rainer Bader, Anika Jonitz-Heincke
During joint movement and mechanical loading, electric potentials occur within cartilage tissue guiding cell development and regeneration. Exposure of cartilage exogenous electric stimulation (ES) may imitate these endogenous electric fields and promote healing processes. Therefore, the present study investigated the influence of electric fields on human chondrocytes, mesenchymal stem cells and the co‑culture of the two. Human chondrocytes isolated from articular cartilage obtained post‑mortally and human mesenchymal stem cells derived from bone marrow (BM‑MSCs) were seeded onto a collagen‑based scaffold separately or as co‑culture...
June 15, 2018: Molecular Medicine Reports
Huimin Wang, Lei Jiang, Zhenfu Li, Wei Wang, Chuanji Hao
Effective drugs and strategies for treating type 2 diabetes mellitus (2‑DM) are urgently required. The aim of the present study was to elucidate the mechanism underlying microRNA (miR)‑6835‑3p regulation of adiponectin receptor 1 (AdipoR1) expression and the miR‑6835‑3p/AdipoR1 signaling pathway in pancreatic islet cells. In addition, the potential anti‑diabetes effect of miR‑6835‑3p on insulin secretion was investigated. Luciferase activity analysis was performed to evaluate how miR‑6835‑3p targets the 3'‑untranslated region of AdipoR1...
June 15, 2018: International Journal of Molecular Medicine
Shuo Mi, Chunkai Gu, Pengfei Wu, Hongjuan Liu, Xiang Yan, Dongyue Li, Xiang Tang, Xiaorui Duan, Genyu Wang, Jianan Zhang
Butanol fermentation comprises two successive and distinct stages, namely acidogenesis and solventogenesis. The current lack of clarity regarding the underlying metabolic regulation of fermentation impedes improvements in biobutanol production. Here, a proteomics study was performed in the acidogenesis phase, the lowest pH point (transition point), and the solventogenesis phase in the butanol-producing symbiotic system TSH06. Forty-two Clostridium acetobutylicum proteins demonstrated differential expression levels at different stages...
June 18, 2018: Applied Microbiology and Biotechnology
Isabelle Martins, Syed Qasim Raza, Laurent Voisin, Haithem Dakhli, Awatef Allouch, Frédéric Law, Dora Sabino, Dorine De Jong, Maxime Thoreau, Elodie Mintet, Delphine Dugué, Mauro Piacentini, Marie-Lise Gougeon, Fanny Jaulin, Pascale Bertrand, Catherine Brenner, David M Ojcius, Guido Kroemer, Nazanine Modjtahedi, Eric Deutsch, Jean-Luc Perfettini
Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells...
June 18, 2018: Cell Death & Disease
Areumnuri Kim, Sehwan Shim, Min-Jung Kim, Jae Kyung Myung, Sunhoo Park
Radiation exposure severely damages the hematopoietic system. Although several radio-protectors have been proposed to prevent radiation-induced damage, most agents have limited efficacy. In the present study, we investigated whether mesenchymal stem cells (MSCs) could contribute to the expansion of hematopoietic cells and mitigate radiation-induced hematopoietic injury in vitro and in vivo. We found that co-culture with MSCs promoted hematopoietic progenitor/stem cell (HPSCs) maintenance by providing a bone marrow-like microenvironment...
June 18, 2018: Scientific Reports
Sharmeen Nishat, Leah M Wuescher, Randall G Worth
Staphylococcus aureus is a major human pathogen that can cause mild to severe life threatening infections in many tissues and organs. Platelets are known to participate in protection against S. aureus by directly killing and enhancing the activities of neutrophils and macrophages in clearing S. aureus infection. Platelets have also been shown to induce monocyte differentiation into dendritic cells and to enhance activation of dendritic cells. Therefore, in the present study, we explored the role of platelets in enhancing bone marrow derived dendritic cell (BMDC) function against S...
June 18, 2018: Infection and Immunity
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