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https://www.readbyqxmd.com/read/28441409/a-hypomorphic-piga-gene-mutation-causes-severe-defects-in-neuron-development-and-susceptibility-to-complement-mediated-toxicity-in-a-human-ipsc-model
#1
Xuan Yuan, Zhe Li, Andrea C Baines, Eleni Gavriilaki, Zhaohui Ye, Zhexing Wen, Evan M Braunstein, Leslie G Biesecker, Linzhao Cheng, Xinzhong Dong, Robert A Brodsky
Mutations in genes involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis underlie a group of congenital syndromes characterized by severe neurodevelopmental defects. GPI anchored proteins have diverse roles in cell adhesion, signaling, metabolism and complement regulation. Over 30 enzymes are required for GPI anchor biosynthesis and PIGA is involved in the first step of this process. A hypomorphic mutation in the X-linked PIGA gene (c.1234C>T) causes multiple congenital anomalies hypotonia seizure syndrome 2 (MCAHS2), indicating that even partial reduction of GPI anchored proteins dramatically impairs central nervous system development, but the mechanism is unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28440453/scrg1-suppresses-lps-induced-ccl22-production-through-erk1-2-activation-in-mouse-macrophage-raw264-7-cells
#2
Manabu Inoue, Junko Yamada, Emiko Aomatsu-Kikuchi, Kazuro Satoh, Hisatomo Kondo, Akira Ishisaki, Naoyuki Chosa
Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage‑like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages...
April 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440309/glypican-2-levels-in-cerebrospinal-fluid-predict-the-status-of-adult-hippocampal-neurogenesis
#3
S Lugert, T Kremer, R Jagasia, A Herrmann, S Aigner, C Giachino, I Mendez-David, A M Gardier, J P Carralot, H Meistermann, A Augustin, M D Saxe, J Lamerz, G Duran-Pacheco, A Ducret, V Taylor, D J David, C Czech
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439952/comparison-of-cytotoxicity-genotoxicity-and-immunological-inflammatory-biomarker-activity-of-several-endodontic-sealers-against-immortalized-human-pulp-cells
#4
F C Martinho, S E A Camargo, A M M Fernandes, M S Campos, R F Prado, C H R Camargo, M C Valera
AIM: To establish an SV40 T-Ag-transfected cell line of human pulp-derived cells in order to compare the cytotoxicity, genotoxicity and to investigate the activities of immunological biomarkers of several endodontic sealers. METHODOLOGY: Primary human pulp cells and transfected cells were cultured. Cell morphology and proliferation were analyzed, and the expression of cell-specific gene transcripts and proteins was detected by RT-PCR and immunohistochemistry. Transfection of human pulp-derived cells resulted in an immortalized cell line retaining phenotypic characteristics from the primarily cells tested...
April 25, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28439892/cerebrospinal-fluid-cyto-chemokine-profile-during-acute-herpes-simplex-virus-induced-anti-n-methyl-d-aspartate-receptor-encephalitis-and-in-chronic-neurological-sequelae
#5
Kavitha Kothur, Deepak Gill, Melanie Wong, Shekeeb S Mohammad, Sushil Bandodkar, Susan Arbunckle, Louise Wienholt, Russell C Dale
AIM: To examine the cytokine/chemokine profile of cerebrospinal fluid (CSF) during acute herpes simplex virus-induced N-methyl-d-aspartate receptor (NMDAR) autoimmunity and in chronic/relapsing post-herpes simplex virus encephalitis (HSE) neurological syndromes. METHOD: We measured longitudinal serial CSF cyto-/chemokines (n=34) and a glial marker (calcium-binding astroglial protein, S100B) in one patient during acute HSE and subsequent anti-NMDAR encephalitis, and compared the results with those from two patients with anti-NMDAR encephalitis without preceding HSE...
April 25, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28439267/pulmonary-delivery-of-virosome-bound-antigen-enhances-antigen-specific-cd4-t-cell-proliferation-compared-to-liposome-bound-or-soluble-antigen
#6
Rebecca A M Blom, Mario Amacker, R Maarten van Dijk, Christian Moser, Philip A Stumbles, Fabian Blank, Christophe von Garnier
Pulmonary administration of biomimetic nanoparticles loaded with antigen may represent an effective strategy to directly modulate adaptive immune responses in the respiratory tract. Depending on the design, virosomes may not only serve as biomimetic antigen carriers but are also endowed with intrinsic immune-stimulatory properties. We designed fluorescently labeled influenza-derived virosomes and liposome controls coupled to the model antigen ovalbumin to investigate uptake, phenotype changes, and antigen processing by antigen-presenting cells exposed to such particles in different respiratory tract compartments...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28439064/immunotherapy-of-dual-function-vector-with-both-immunostimulatory-and-b-cell-lymphoma-2-bcl-2-silencing-effects-on-gastric-carcinoma
#7
Lanying Ma, Mei Han, Zumureti Keyoumu, Hua Wang, Saifuding Keyoumu
BACKGROUND Tumorigenesis is a kind of pathology marked by infinite proliferation and restrained apoptosis compared with normal cells. The abnormal expression of some proto-oncogenes and apoptosis inhibition are essential for tumor growth, which has been confirmed by molecular biologic and immunologic studies. The hypofunction of the host immune system also drives the development and metastasis of malignant tumors. Bcl-2, which has a critical role in regulating apoptosis, is overexpressed in several cancers...
April 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#8
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#9
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE is also faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
April 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#10
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28437178/a-novel-injectable-recombinant-collagen-i-peptide-based-macroporous-microcarrier-allows-superior-expansion-of-c2c12-and-human-bone-marrow-derived-mesenchymal-stromal-cells-and-supports-deposition-of-mineralized-matrix
#11
Davide Confalonieri, Margherita La Marca, Elisabeth Marianna Wilhelmina Maria van Dongen, Heike Walles, Franziska Ehlicke
The development of scaffold formulations based on extracellular matrix-inspired synthetic materials constitutes an important resource for the advance of cell-based therapies in bone tissue engineering approaches, where both cell and scaffold implantation are often needed. Culturing cells on porous microcarriers (MCs) allows cell expansion in a three-dimensional microenvironment and constitutes a possible solution for minimally invasive cell and scaffold simultaneous delivery, but the reduced pore dimension and pore interconnection diameter of several commercially available microcarriers limits de facto cell ingrowth, and ultimately their suitability for in vivo cell delivery...
March 3, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28436949/p14arf-interacts-with-the-focal-adhesion-kinase-and-protects-cells-from-anoikis
#12
M Vivo, R Fontana, M Ranieri, G Capasso, T Angrisano, A Pollice, V Calabrò, G La Mantia
The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436481/fusions-of-tumor-derived-endothelial-cells-with-dendritic-cells-induces-antitumor-immunity
#13
Yingying Huang, Qiqi Mao, Jian He, Jing Su, Yi Peng, Wei Liang, Zixi Hu, Sufang Zhou, Xiaoling Lu, Yongxiang Zhao
To explore dendritic cells/tumor-derived endothelial cells (DC/EC) fusion cells are potent stimulators of T cells to impact tumor progression. ECs were isolated from mice hepatoma cell line (H22) Xenograft, and dendritic cells were isolated from bone marrow of BALB/c mice, then the isolated ECs were cultured and detected the endothelial surface expression of CD105 by flow cytometry. The endothelial characteristics of ECs were detected by tube formation assay and Dil-Ac-LDL uptake assay. After the fusion with polyethylene glycol (PEG), we used DCs, ECs, DCs mixed ECs as the control groups, DC/EC fusion cells as the experimental group, Secretion of IFN-α and IFN-γ was evaluated, T lymphocyte proliferation and cytotoxic T lymphocytes (CTL) were detected in vitro...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436457/fasciola-hepatica-glycoconjugates-immuneregulate-dendritic-cells-through-the-dendritic-cell-specific-intercellular-adhesion-molecule-3-grabbing-non-integrin-inducing-t-cell-anergy
#14
Ernesto Rodríguez, Hakan Kalay, Verónica Noya, Natalie Brossard, Cecilia Giacomini, Yvette van Kooyk, Juan J García-Vallejo, Teresa Freire
Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435295/silencing-cdr1as-inhibits-colorectal-cancer-progression-through-regulating-microrna-7
#15
Wentao Tang, Meiling Ji, Guodong He, Liangliang Yang, Zhengchuan Niu, Mi Jian, Ye Wei, Li Ren, Jianmin Xu
An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28434702/inhibition-or-deletion-of-angiotensin-ii-type-1-receptor-suppresses-elastase-induced-experimental-abdominal-aortic-aneurysms
#16
Haojun Xuan, Baohui Xu, Wei Wang, Hiroki Tanaka, Naoki Fujimura, Masaaki Miyata, Sara A Michie, Ronald L Dalman
OBJECTIVE: Angiotensin (Ang) II type 1 receptor (AT1) activation is essential for the development of exogenous Ang II-induced abdominal aortic aneurysms (AAAs) in hyperlipidemic animals. Experimental data derived from this modeling system, however, provide limited insight into the role of endogenous Ang II in aneurysm pathogenesis. Consequently, the potential translational value of AT1 inhibition in clinical AAA disease management remains incompletely understood on the basis of the existing literature...
April 20, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#17
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#18
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28433861/c-reactive-protein-and-enzymatically-modified-ldl-cooperatively-promote-dendritic-cell-mediated-t-cell-activation
#19
Wei He, Yong Ren, Xiao Wang, Qiao Chen, Shifang Ding
BACKGROUND: Enzymatically modified low density lipoprotein (eLDL), C reactive protein (CRP), dendritic cells (DCs), and T cells were shown to be involved in the pathogenesis of atherosclerosis. This study aimed to investigate whether eLDL and CRP could cooperatively promote DC-mediated T cell activation and proliferation. METHOD: Low density lipoprotein was isolated from healthy human plasma and treated with proteases and cholesterol esterase. CD14(+) monocytes were isolated from human peripheral blood by gradient centrifugation and enriched with CD14 Microbeads, which were then induced with recombinant human IL-4 and granulocyte-macrophage colony-stimulating factor before treated with eLDL and/or CRP...
April 7, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28433769/healing-activity-evaluation-of-the-galactomannan-film-obtained-from-cassia-grandis-seeds-with-immobilized-cratylia-mollis-seed-lectin
#20
Priscilla B S Albuquerque, Paulo A G Soares, Adelmo C Aragão-Neto, Giwellington S Albuquerque, Luís C N Silva, Maria H M Lima-Ribeiro, Jacinto C Silva Neto, Luana C B B Coelho, Maria T S Correia, José A C Teixeira, Maria G Carneiro-da-Cunha
Galactomannan films from Cassia grandis seeds, associated or not with Cramoll 1,4, were used on topical wounds of rats for the evaluation of the healing process during 14 days. All of the films were evaluated by cytotoxic assay, FTIR and lectin hemagglutinating activity (HA). Forty-five male rats were submitted to aseptic dermal wounds (Ø=0.8cm) and divided in groups (n=15): control, test 1, and test 2, treated respectively with saline, galactomannan film and film with immobilized Cramoll 1,4. Macroscopic evaluations were performed by clinical observations and area measurements, and microscopic analysis by histological criteria...
April 19, 2017: International Journal of Biological Macromolecules
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