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G H Chen, H W Huang, Y Wang, H W Liu, L J Xu, X Ma, S L Xue, X F He, Y Wang, B Gu, C X Li, H Y Qiu, X W Tang, Z M Jin, M Miao, A N Sun, D P Wu
Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Songzhen He, Xiaoling Tong, Minjin Han, Yanmin Bai, Fangyin Dai
The tyrosine kinases (TKs) are important parts of metazoan signaling pathways and play significant roles in cell growth, development, apoptosis and disease. Genome-wide characterization of TKs has been conducted in many metazoans, however, systematic information about this family in Lepidoptera is still lacking. We retrieved 33 TK-encoding genes in silkworm and classified them into 25 subfamilies by sequence analysis, without members in AXL, FRK, PDGFR, STYK1 and TIE subfamilies. Although domain sequences in each subfamily are conserved, TKs in vertebrates tend to be remarkably conserved and stable...
March 21, 2018: International Journal of Molecular Sciences
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Linlin Yang, Jun Zhao, Xinling Yu, Ruilong Zhang, Guangmei Han, Renyong Liu, Zhengjie Liu, Tingting Zhao, Ming-Yong Han, Zhongping Zhang
Hydrogen sulfide (H2S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H2S mediates cellular signal transductions and organism functions; it also motivates the development of H2S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H2S in the entire cell space and live animals...
March 21, 2018: Analyst
Eva Ramos, Alejandro Romero, Javier Egea, José Marco-Contelles, Javier Del Pino, Cristóbal de Los Ríos
AIM: The 1,8-naphthyridine CR80 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b] [1,8]naphthyridine-3-carboxylate) has shown interesting neuroprotective properties in in vitro and in vivo models of neurodegeneration. In spite of these promising outcomes, the molecular and cellular mechanisms underlying CR80 actions need to be further explored. MATERIALS & METHODS: We herein report the signal transduction pathways involved in developmental, neuroprotective and stress-activated processes, as well as the gene expression regulation by CR80 in SH-SY5Y neuroblastoma cells...
March 21, 2018: Future Medicinal Chemistry
Og-Geum Woo, Soon-Hee Kim, Seok Keun Cho, Sang-Hoon Kim, Han Nim Lee, Taijoon Chung, Seong Wook Yang, Jae-Hoon Lee
BPH1 acts as a substrate receptor of CRL3 complex and negatively regulates ABA-mediated cellular responses. The study on its function provides information that helps further understand the relationship between ABA signaling and UPS. Abscisic acid (ABA) plays a crucial role in a variety of cellular processes, including seed dormancy, inhibition of seedling growth, and drought resistance in plants. Cullin3-RING E3 ligase (CRL3) complex is a type of multi-subunit E3 ligase, and BTB/POZ protein, a component of CRL3 complex, functions as a receptor to determine a specific substrate...
March 21, 2018: Plant Molecular Biology
Yawei Xu, Yan Zhou, Rui Yin, Cheng Wang, Haijiao Chu, Junling Wang
The balance of oxidation and reduction in the body requires the synergistic effect of various antioxidant enzymes. Therefore, the construction of enzyme mimics with multiple antioxidant activities is important and beneficial for further research on the synergistic effects of antioxidant enzymes and their mechanism of action. To explore the synergistic effect of superoxide dismutase (SOD) and glutathione peroxidase (GPx), a 76-mer selenium-containing peptide (Se-76P) mimic containing the active SOD and GPx centers was designed...
March 20, 2018: In Vitro Cellular & Developmental Biology. Animal
Kohei Nakamura, Kentaro Nakayama, Noriyoshi Ishikawa, Masako Ishikawa, Razia Sultana, Tohru Kiyono, Satoru Kyo
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4R24C , and hTERT . Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction...
February 27, 2018: Oncotarget
Simone Sello, Roberto Moscatiello, Norbert Mehlmer, Manuela Leonardelli, Luca Carraretto, Enrico Cortese, Filippo G Zanella, Barbara Baldan, Ildikò Szabò, Ute C Vothknecht, Lorella Navazio
Chloroplasts require a fine-tuned control of their internal Ca2+ concentration, which is crucial for many aspects of photosynthesis and for other chloroplast-localized processes. Increasing evidence suggests that calcium regulation within chloroplasts may also influence Ca2+ signalling pathways in the cytosol. To investigate the involvement of thylakoids in Ca2+ homeostasis and in the modulation of chloroplast Ca2+ signals in vivo, we targeted the bioluminescent Ca2+ reporter aequorin as a YFP fusion to the lumen and the stromal surface of thylakoids in Arabidopsis...
March 20, 2018: Plant Physiology
Kristina Busygina, Janina Jamasbi, Till Seiler, Hans Deckmyn, Christian Weber, Richard Brandl, Reinhard Lorenz, Wolfgang Siess
Interaction of Von Willebrand factor (VWF) with platelet glycoprotein (GP) Ib and of collagen with GPVI is essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk) which can irreversibly be blocked by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long term safety. We found that ibrutinib and the novel Btk-inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid...
March 20, 2018: Blood
Indranil Sarkar, Ravendra Garg, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes acute respiratory tract infections in infants, the elderly and immunocompromised individuals. No licensed vaccine is available against RSV. We previously reported that intranasal immunization of rodents and lambs with a RSV vaccine candidate (ΔF/TriAdj) induces protective immunity with a good safety profile. ΔF/TriAdj promoted innate immune responses in respiratory mucosal tissues in vivo, by local chemokine and cytokine production, as well as infiltration and activation of immune cells including macrophages...
March 17, 2018: Vaccine
Hai Xu, Xi Bao, Yiwei Wang, Yue Xu, Bihua Deng, Yu Lu, Jibo Hou
BACKGROUND: DNA delivery with bacteriophage by surface-displayed mammalian cell penetrating peptides has been reported. Although, various phages have been used to facilitate DNA transfer by surface displaying the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide), no similar study has been conducted using T7 phage. METHODS: In this study, we engineeredT7 phage as a DNA targeting delivery vector to facilitate cellular internalization...
March 20, 2018: Virology Journal
He Liu, Yue Gu, Tao Dong, Liuqing Yan, Xiaoyi Yan, Tingting Zhang, Nannan Lu, Zhiqian Xu, Haixin Xu, Zhiquan Zhang, Ting Bian
The combination of nanoparticles and biomarkers yields functional nanostructured biointerface, which is playing a notable role in biotechnology development. Due to the 5-fold twined structure in the Au-Pt star-shaped decahedra not only allowed it to act as efficient scaffold for immobilization of antibody, but it also exhibits superior electrocatalytic activity toward H2 O2 reduction, the nanocrystal as the efficient signal transduction label is first employed to construct an electrochemical immunosensor. Donor-π-Acceptor (D-π-A) linking fashion generates a dipolar push-pull system and assures superior intramolecular charge transfer...
March 13, 2018: Biosensors & Bioelectronics
Han-Yu Jiang, Jin-Lin Zhang, Jiang-Wei Yang, Hui-Ling Ma
Creeping bentgrass ( Agrostis stolonifera ) is the preferred green lawn grass, with excellent turf characteristics but poor disease resistance. At present, the mechanisms of disease resistance in creeping bentgrass are poorly understood, especially the ethylene signal transduction pathway under the induced systemic resistance (ISR) response. In this study, butanediol (BDO), as a new type of disease-resistance compound, was applied to creeping bentgrass seedlings to induce the ISR response. Then, we measured ethylene production and related enzyme activities...
March 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Lukas Zeininger, Maggie He, Stephen T Hobson, Timothy M Swager
We report γ-ray dosimeters using carbon nanotubes wrapped with metastable poly(olefin sulfone)s (POSs) that readily depolymerize when exposed to ionizing radiation. New POSs, designed for wrapping single-walled carbon nanotubes (SWCNTs), are synthesized and characterized. The resulting POS-SWCNT composites serve as the active transducer in a novel class of γ-ray dosimeters. In our devices, polymer degradation results in immediate changes in the electronic potential of the POS-SWCNT active layers by decreasing the electron tunneling barriers between individualized tubes and by creating enhanced cofacial π-π electron contacts...
March 20, 2018: ACS Sensors
Monika Lakk, Felix Vazquez-Chona, Oleg Yarishkin, David Križaj
Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell membranes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astroglia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegenerative disease...
February 2018: Neural Regeneration Research
Qiongshu Li, Muyun Liu, Man Wu, Xin Zhou, Shaobin Wang, Yuan Hu, Youfu Wang, Yixin He, Xiaoping Zeng, Junhui Chen, Qubo Liu, Dong Xiao, Xiang Hu, Weibin Liu
Placenta-specific 1 (PLAC1), a novel cancer-testis antigen (CTA), is expressed in a number of different human malignancies. It is frequently produced in breast cancer, serving a function in tumorigenesis. Adoptive immunotherapy using T cell receptor (TCR)-engineered T cells against CTA mediates objective tumor regression; however, to the best of our knowledge, targeting PLAC1 using engineered T cells has not yet been attempted. In the present study, the cDNAs encoding TCRα- and β-chains specific for human leukocyte antigen (HLA)-A*0201-restricted PLAC1 were cloned from a cytotoxic T-lymphocyte, generated by in vitro by the stimulation of CD8+ T cells using autologous HLA-A2+ dendritic cells loaded with a PLAC1-specific peptide (p28-36, VLCSIDWFM)...
April 2018: Oncology Letters
Elide Formentin, Cristina Sudiro, Giorgio Perin, Samantha Riccadonna, Elisabetta Barizza, Elena Baldoni, Enrico Lavezzo, Piergiorgio Stevanato, Gian Attilio Sacchi, Paolo Fontana, Stefano Toppo, Tomas Morosinotto, Michela Zottini, Fiorella Lo Schiavo
Salinity tolerance has been extensively investigated in recent years due to its agricultural importance. Several features, such as the regulation of ionic transporters and metabolic adjustments, have been identified as salt tolerance hallmarks. Nevertheless, due to the complexity of the trait, the results achieved to date have met with limited success in improving the salt tolerance of rice plants when tested in the field, thus suggesting that a better understanding of the tolerance mechanisms is still required...
2018: Frontiers in Plant Science
Hua Tao, Xu Zhou, Bin Zhao, Keshen Li
According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA ) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE)...
2018: Frontiers in Molecular Neuroscience
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