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https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#1
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28063798/evaluation-of-biological-properties-of-3-3-4-4-benzophenonetetracarboxylic-dianhydride-derivatives-and-their-ability-to-inhibit-hexokinase-activity
#2
Krzysztof Kochel, Mateusz D Tomczyk, Rui F Simões, Tomasz Frączek, Adrian Soboń, Paulo J Oliveira, Krzysztof Z Walczak, Aneta Koceva-Chyła
This investigation has explored the properties of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BDTA) derivatives with regard to their being prospective inhibitors of hexokinase II (HKII). A pluripotent embryonic carcinoma cell line P19 (ECC), was used as the biological target for newly generated potential inhibitors of HKII. The results obtained from Virtual High-Throughput Screening (VHTS), molecular modeling and biological activity studies showed BDTA to be a promising leading structure with a good binding score and simplest functionalization...
December 25, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28054967/expression-purification-and-biophysical-characterization-of-a-secreted-anthrax-decoy-fusion-protein-in-nicotiana-benthamiana
#3
Kalimuthu Karuppanan, Sifti Duhra-Gill, Muchena J Kailemia, My L Phu, Carlito B Lebrilla, Abhaya M Dandekar, Raymond L Rodriguez, Somen Nandi, Karen A McDonald
Anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. In this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (CMG2) protein fused via a linker to the fragment crystallizable (Fc) domain of human immunoglobulin G1 in Nicotiana benthamiana plants using a transient expression system. Using the Cauliflower Mosaic Virus (CaMV) 35S promoter and co-expression with the p19 gene silencing suppressor, we were able to achieve a high level of recombinant CMG2-Fc-Apo (rCMG2-Fc-Apo) protein accumulation...
January 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28049897/expression-and-regulation-of-tal2-during-neuronal-differentiation-in-p19-cells
#4
Takanobu Kobayashi
 T-cell acute lymphocytic leukemia 2 (Tal2) is a gene encoding a member of the basic helix-loop-helix transcription factor family, which is essential for the normal development of the mouse brain. We found that Tal2 was induced during neural differentiation in P19 cells, which are pluripotent mouse embryonal carcinoma cells that differentiate into the neural lineage upon both exposure to all-trans retinoic acid (atRA) and the formation of cell aggregation. Tal2 expression during neural differentiation in P19 cells was detected within 3 h after induction with atRA and retinoic acid receptor α (RARα)...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28043778/neuritogenic-activity-of-bi-functional-bis-tryptoline-triazole
#5
Jutamas Jiaranaikulwanitch, Sarin Tadtong, Piyarat Govitrapong, Valery V Fokin, Opa Vajragupta
Alzheimer's disease (AD) is a common neurodegenerative disorder, one of the hallmarks of which is the deposition of aggregated β-amyloid peptides (Aβ40,42) as plaques in the brain. Oligomers of these peptides have been reported to be toxic and to inhibit neurite outgrowth, as evidenced by neurite dystrophy and significant loss of synaptic connectivity of neurons in the AD brain resulting in cognitive decline. These peptides also react with biological metal in the brain to generate free radicals, thereby aggravating neuronal cell injury and death...
December 23, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28042732/the-potential-utility-of-tildrakizumab-an-interleukin-23-inhibitor-for-the-treatment-of-psoriasis
#6
Zenas Z N Yiu, Richard B Warren
The approved biologic therapies are effective for the treatment of psoriasis, but have limitations. Tildrakizumab has a different mechanism of action and is a humanized immunoglobulin G1κ that binds to the p19 subunit of IL23. Areas covered: Phase I, II and III clinical trials investigated the pharmacokinetics, efficacy, safety and immunogenicity of tildrakizumab for patients with psoriasis. The mean half-life of tildrakizumab is between 20.2 to 28.2 days. Tildrakizumab achieved a PASI 75 of 66% and 74% at week 16 for the doses of 100 mg and 200 mg respectively in a phase IIb randomised clinical trial (RCT), and PASI 75 of 61%/64% and 62%/66% at week 12 for 100 mg and 200 mg respectively in two phase III RCTs...
January 1, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28039042/role-of-low-voltage-activated-calcium-current-and-extracellular-calcium-in-controlling-the-firing-pattern-of-developing-ca1-pyramidal-neurons
#7
Alberto Sánchez-Aguilera, José Luis Sánchez-Alonso, María Ángeles Vicente-Torres, Asunción Colino
The firing pattern of individual neurons is an important element for information processing and storing. During the first weeks of development, there is a transitional period during which CA1 pyramidal neurons display burst-spiking behavior in contrast to the adult regular-firing pattern. Spike after-depolarizations (ADPs) constitute a major factor underlying burst-spiking behavior. Using current-clamp recordings, we studied ADP waveforms and firing patterns in CA1 pyramidal neurons of Wistar rats from 9 to 19 postnatal days (P9-19)...
December 28, 2016: Neuroscience
https://www.readbyqxmd.com/read/28013042/production-of-stable-gfp-expressing-neural-cells-from-p19-embryonal-carcinoma-stem-cells
#8
Hedayatollah Shirzad, Fariba Esmaeili, Shabnam Bakhshalizadeh, Marzieh Ebrahimie, Esmaeil Ebrahimie
Murine P19 embryonal carcinoma (EC) cells are convenient to differentiate into all germ layer derivatives. One of the advantages of P19 cells is that the exogenous DNA can be easily inserted into them. Here, at the first part of this study, we generated stable GFP-expressing P19 cells (P19-GFP(+)). FACS and western-blot analysis confirmed stable expression of GFP in the cells. We previously demonstrated the efficient induction of neuronal differentiation from mouse ES and EC cells by application of a neuroprotective drug, selegiline In the second part of this study selegiline was used to induce differentiation of P19-GFP(+) into stable GFP-expressing neuron-like cells...
December 21, 2016: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/27999597/construction-of-a-dual-fluorescence-reporter-system-to-monitor-the-dynamic-progression-of-pluripotent-cell-differentiation
#9
Wu-Sheng Sun, Ju-Lan Chun, Jeong-Tae Do, Dong-Hwan Kim, Jin-Seop Ahn, Min-Kyu Kim, In-Sul Hwang, Dae-Jin Kwon, Seong-Soo Hwang, Jeong-Woong Lee
Oct4 is a crucial germ line-specific transcription factor expressed in different pluripotent cells and downregulated in the process of differentiation. There are two conserved enhancers, called the distal enhancer (DE) and proximal enhancer (PE), in the 5' upstream regulatory sequences (URSs) of the mouse Oct4 gene, which were demonstrated to control Oct4 expression independently in embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). We analyzed the URSs of the pig Oct4 and identified two similar enhancers that were highly consistent with the mouse DE and PE...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27990359/effect-of-endothelial-progenitor-cells-derived-from-human-umbilical-cord-blood-on-oxygen-induced-retinopathy-in-mice-by-intravitreal-transplantation
#10
Dan Wang, Bo Zhang, Hui Shi, Wei Yang, Ming-Chao Bi, Xiang-Fu Song, Chen Zhang, Jian-Hui Cheng, Ji-Long Hao, E Song
AIM: To investigate the effect of endothelial progenitor cells (EPCs) labeled by carboxy fluorescein diacetate succinimidyl ester (CFSE) on murine oxygen-induced retinopathy (OIR) by intravitreal transplantation. METHODS: After isolated from human umbilical cord blood mononuclear cells, EPCs were cultivated and then labeled with CFSE in vitro. C57BL/6J mice were placed to 75% hyperoxia chamber from P7 to P12 to establish OIR model. At P12, OIR mice were intravitreally injected with 1 µL suspension contained 2×10(5) EPCs (EPCs group) or isometric phosphate buffered saline (PBS group)...
2016: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/27939990/apomorphine-prevents-lps-induced-il-23-p19-mrna-expression-via-inhibition-of-jnk-and-atf4-in-hapi-cells
#11
Hirokazu Hara, Dai Kimoto, Miho Kajita, Chisato Takada, Tetsuro Kamiya, Tetsuo Adachi
Inflammation has been reported to be closely related to exaggeration of cerebral ischemia and neurodegenerative diseases. Microglia, resident immune cells in the central nervous system, can be activated in response to neuronal injury and produce proinflammatory cytokines, resulting in further aggravation of neuronal injury. Interleukin (IL)-23, which consists of p19 and IL-12 p40 subunits, has been shown to be involved in brain injury associated with neuroinflammation. Apomorphine (Apo), a nonselective dopamine receptor agonist, has been used for clinical therapy of Parkinson's disease...
December 9, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27931146/d-cycloserine-restores-experience-dependent-neuroplasticity-after-tbi-in-the-developing-rat-brain
#12
Naomi Sulit Sta Maria, Maxine Lane Reger, Yan Cai, Mary Anne Tezheart Mercado Baquing, Floyd Buen, Aditya Ponnaluri, David Hovda, Neil G Harris, Christopher C Giza
Traumatic brain injury (TBI) in children can cause persisting cognitive and behavioral dysfunction and inevitably raises concerns about lost potential in these injured youths. Lateral fluid percussion injury (FPI) in weanling rats pathologically affects hippocampal NMDAR- and AMPAR-mediated glutamatergic neurotransmission subacutely, within the first post-injury week. FPI to weanling rats has also been shown to impair enriched-environment (EE) induced enhancement of Morris water maze (MWM) learning and memory in adulthood...
December 8, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#13
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27889761/cilostazol-suppresses-il-23-production-in-human-dendritic-cells-via-an-ampk-dependent-pathway
#14
Quanxing Shi, Zhao Yin, Peilin Liu, Bei Zhao, Zhong Zhang, Shuai Mao, Tengfei Wei, Mengmeng Rao, Liguo Zhang, Shouli Wang
BACKGROUND/AIMS: Cilostazol has been previously demonstrated to inhibit IL-23 production in human synovial macrophages via a RhoA/ROCK-dependent pathway. However, whether cilostazol affects IL-23 production in human dendritic cells remains largely unknown. The present study was designed to investigate this question and elucidate the possible underlying mechanisms. METHODS: Human monocyte-derived dendritic cells (mo-DCs) were pretreated with or without cilostazol and then incubated with zymosan...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27879259/unexpected-role-for-p19ink4d-in-post-transcriptional-regulation-of-gata1-and-modulation-of-human-terminal-erythropoiesis
#15
Xu Han, Jieying Zhang, Yuanliang Peng, Minyuan Peng, Xiao Chen, Huiyong Chen, Jianhui Song, Xiao Hu, Mao Ye, Jianglin Li, Vijay G Sankaran, Christopher D Hillyer, Narla Mohandas, Xiuli An, Jing Liu
Terminal erythroid differentiation is tightly coordinated with cell cycle exit, which is regulated by cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19(INK4d), a member of CDKI family, is abundantly expressed in erythroblasts and that p19(INK4d) knockdown delayed erythroid differentiation, inhibited cell growth, led to increased apoptosis and generation of abnormally nucleated late stage erythroblasts...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27871935/a-sonic-hedgehog-coreceptor-boc-regulates-neuronal-differentiation-and-neurite-outgrowth-via-interaction-with-abl-and-jnk-activation
#16
Tuan Anh Vuong, Young-Eun Leem, Bok-Geon Kim, Hana Cho, Sang-Jin Lee, Gyu-Un Bae, Jong-Sun Kang
Neurite outgrowth is a critical step for neurogenesis and remodeling synaptic circuitry during neuronal development and regeneration. An immunoglobulin superfamily member, BOC functions as Sonic hedgehog (Shh) coreceptor in canonical and noncanonical Shh signaling in neuronal development and axon outgrowth/guidance. However signaling mechanisms responsible for BOC action during these processes remain unknown. In our previous studies, a multiprotein complex containing BOC and a closely related protein CDO promotes myogenic differentiation through activation of multiple signaling pathways, including non-receptor tyrosine kinase ABL...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27867385/expanding-diversity-in-molecular-structures-and-functions-of-the-il-6-il-12-heterodimeric-cytokine-family
#17
REVIEW
Hideaki Hasegawa, Izuru Mizoguchi, Yukino Chiba, Mio Ohashi, Mingli Xu, Takayuki Yoshimoto
The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they comprise two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than six cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12 (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein-Barr virus-induced protein 3 (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27861613/non-serotonergic-neurotoxicity-by-mdma-ecstasy-in-neurons-derived-from-mouse-p19-embryonal-carcinoma-cells
#18
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
https://www.readbyqxmd.com/read/27832210/gm-csf-producing-th-cells-in-rats-sensitive-and-resistant-to-experimental-autoimmune-encephalomyelitis
#19
Zorica Stojić-Vukanić, Ivan Pilipović, Ivana Vujnović, Mirjana Nacka-Aleksić, Raisa Petrović, Nevena Arsenović-Ranin, Mirjana Dimitrijević, Gordana Leposavić
Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment...
2016: PloS One
https://www.readbyqxmd.com/read/27825391/oestrous-cycle-dependent-equine-uterine-immune-response-to-induced-infectious-endometritis
#20
Christina D Marth, Simon M Firestone, Lisa Y Glenton, Glenn F Browning, Neil D Young, Natali Krekeler
Infectious endometritis is a major cause of reduced pregnancy rates in horses. The objectives of this study were to establish a timeline of the innate immune response in the uterus of healthy horses and to investigate the oestrous cycle effect on this. Endometrial biopsies were collected from five horses before and at 3, 12, 24, 48 and 72 h after inoculation of Escherichia coli, once in oestrus and once in dioestrus. They were analysed by quantitative real-time PCR, microbiology and histology. Neutrophil numbers increased from very low levels in the absence of inflammation to severe neutrophilia 3 h after inoculation...
November 8, 2016: Veterinary Research
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