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https://www.readbyqxmd.com/read/27935982/a-cost-effective-method-to-assemble-biomimetic-3d-cell-culture-platforms
#1
Sabreen Khalil, Nagwa El-Badri, Mohamed El-Mokhtaar, Saif Al-Mofty, Mohamed Farghaly, Radwa Ayman, Dina Habib, Noha Mousa
METHODS: We utilized the hAM to provide the biological and the three dimensional (3D) topographic components of the prototype. The 3D nano-roughness of the hAM was characterized using surface electron microscopy and surface image analysis (ImageJ and SurfaceJ). We developed additional macro-scale and micro-scale versions of the platform which provided additional shear stress factors to simulate the fluid dynamics of the in vivo extracellular fluids. RESULTS: Three models of varying complexities of the prototype were assembled...
2016: PloS One
https://www.readbyqxmd.com/read/27935870/changes-in-the-methylation-status-of-the-oct3-4-nanog-and-sox2-promoters-in-stem-cells-during-regeneration-of-rat-tracheal-epithelium-after-injury
#2
Ying Zhou, Nan Song, Xin Li, Ying Han, Zihan Ren, Jing-Xian Xu, Yu-Chen Han, Fang Li, Xinshan Jia
We investigated the relationship between promoter methylation and tracheal stem cell activation. We developed a model of rat tracheal epithelium regeneration after 5-fluorouracil (5-FU)-induced injury. Using immunohistochemistry and Western blotting, the expression levels of the stem cell pluripotency regulator Oct3/4 and differentiation marker CK14 were measured after 5-FU treatment. The methylation status of the Oct3/4, Nanog, and Sox2 promoters was investigated using methylation-specific PCR. Additionally, the effects of 5-azacytidine (5-azaC), a demethylating agent, on Oct3/4, Nanog, and Sox2 mRNA and protein expression were evaluated...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935818/prenatal-ethanol-exposure-phenocopies-cdon-mutation-by-impeding-shh-function-in-the-etiology-of-optic-nerve-hypoplasia
#3
Benjamin M Kahn, Tanya S Corman, Korah Lovelace, Mingi Hong, Robert S Krauss, Douglas J Epstein
Septo-optic dysplasia (SOD) is a congenital disorder characterized by optic nerve, pituitary and midline brain malformations. The clinical presentation of SOD is highly variable with a poorly understood etiology. The majority of SOD cases are sporadic, but in rare instances inherited mutations have been identified in a small number of transcription factors, some of which regulate the expression of Sonic hedgehog (Shh) during mouse forebrain development. SOD is also associated with young maternal age suggesting that environmental factors, including alcohol consumption at early stages of pregnancy, may increase the risk of developing this condition...
November 24, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#4
Paul Andrew Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stefanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phllip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27935326/role-of-cd56-in-normal-kidney-development-and-wilms-tumorigenesis
#5
Li-Wei Yap, Jesper Brok, Kathy Pritchard-Jones
The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56...
December 9, 2016: Fetal and Pediatric Pathology
https://www.readbyqxmd.com/read/27934689/differentiating-mouse-embryonic-stem-cells-into-embryoid-bodies-by-hanging-drop-cultures
#6
Richard Behringer, Marina Gertsenstein, Kristina Vintersten Nagy, Andras Nagy
Embryonic stem (ES) cells can develop into many types of differentiated tissues if they are placed into a differentiating environment. This can occur in vivo when the ES cells are injected into or aggregated with an embryo, or in vitro if their culture conditions are modified to induce differentiation. There are an increasing number of differentiating culture conditions that can bias the differentiation of ES cells into desired cell types. Determining the mechanisms that control ES cell differentiation into therapeutically important cell types is a quickly growing area of research...
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27934660/ezh2-deletion-in-early-mesenchyme-compromises-postnatal-bone-microarchitecture-and-structural-integrity-and-accelerates-remodeling
#7
Sarah Hemming, Dimitrios Cakouros, John Codrington, Kate Vandyke, Agneiszka Arthur, Andrew Zannettino, Stan Gronthos
In this study, we examined the functional importance of EZH2 during skeletal development and homeostasis using the conditional deletion of Ezh2 (Ezh2(fl/fl)) in early mesenchyme with the use of a Prrx-1-cre driver mouse (Ezh2(+/+)). Heterozygous (Ezh2(+/-)) newborn and 4-wk-old mice exhibited increased skeletal size, growth plate size, and weight when compared to the wild-type control (Ezh2(+/+)), whereas homozygous deletion of Ezh2 (Ezh2(-/-)) resulted in skeletal deformities, reduced skeletal size, growth plate size, and weight in newborns, and 4-wk-old mice...
December 1, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27934561/various-regimens-of-total-body-irradiation-for-hematopoietic-stem-cell-transplant
#8
Naoya Ishibashi, Toshiya Maebayashi, Takuya Aizawa, Masakuni Sakaguchi, Osamu Abe, Kazuyoshi Sakanishi, Yuji Endoh, Tsutomu Saito, Jiro Kawamori, Yoshiaki Tanaka
OBJECTIVES: We aimed to evaluate the safety of total body irradiation before bone marrow transplant. MATERIALS AND METHODS: We analyzed 110 patients (65 male, 45 female) who underwent total body irradiation for hematopoietic stem cell transplant between May 1998 and March 2013. Median age at total body irradiation was 17 years (range, 1-62 y). Median observation time was 777 days (range, 31-5494 d). Initial diagnoses were acute lymphoblastic leukemia (24 patients), acute myeloid leukemia (26 patients), chronic myeloid leukemia (7 patients), myelodysplastic syndrome (8 patients), malignant lymphoma (13 patients), mucopolysaccharidosis (12 patients), neuroblastoma (10 patients), and other diseases (10 patients)...
December 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27934481/minimum-transendothelial-electrical-resistance-thresholds-for-the-study-of-small-and-large-molecule-drug-transport-in-a-human-in-vitro-blood-brain-barrier-model
#9
Jennifer L Mantle, Lie Min, Kelvin H Lee
A human cell-based in vitro model that can accurately predict drug penetration into the brain as well as metrics to assess these in vitro models are valuable for the development of new therapeutics. Here, human induced pluripotent stem cells (hPSCs) are differentiated into a polarized monolayer that express blood-brain barrier (BBB)-specific proteins and have transendothelial electrical resistance (TEER) values greater than 2500 Ω·cm(2). By assessing the permeabilities of several known drugs, a benchmarking system to evaluate brain permeability of drugs was established...
December 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27933834/alginate-bead-based-hexagonal-close-packed-3d-implant-for-bone-tissue-engineering
#10
Tarun Agarwal, Prajna Kabiraj, Gautham Hari Narayana, Senthilguru Kulanthaivel, Uvanesh Kasiviswanathan, Kunal Pal, Supratim Giri, Tapas K Maiti, Indranil Banerjee
Success of bone tissue engineering (BTE) relies on the osteogenic microarchitecture of the biopolymeric scaffold and appropriate spatiotemporal distribution of therapeutic molecules (growth factors and drugs) inside it. However, the existing technologies have failed to address both the issues together. Keeping this perspective in mind, we have developed a novel three-dimensional (3D) implant prototype by stacking hexagonal close packed (HCP) layers of calcium alginate beads. The HCP arrangement of the beads lead to a patterned array of interconnected tetrahedral and octahedral pores of average diameter of 142...
November 30, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27933352/intracochlear-drug-delivery-in%C3%A2-combination-with-cochlear-implants-current-aspects
#11
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
December 8, 2016: HNO
https://www.readbyqxmd.com/read/27933304/preclinical-validation-lv-il-12-transduction-of-patient-leukemia-cells-for-immunotherapy-of-aml
#12
Ju Huang, Yuanfeng Liu, Bryan C Au, Dwayne L Barber, Andrea Arruda, Axel Schambach, Michael Rothe, Mark D Minden, Christopher J Paige, Jeffrey A Medin
Interleukin-12 (IL-12) is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933089/a-rare-inherited-15q11-2-q13-1-interstitial-duplication-with-maternal-somatic-mosaicism-renal-carcinoma-and-autism
#13
Nora Urraca, Brian Potter, Rachel Hundley, Eniko K Pivnick, Kathryn McVicar, Ronald L Thibert, Christopher Ledbetter, Reed Chamberlain, Leticia Miravalle, Carissa L Sirois, Stormy Chamberlain, Lawrence T Reiter
Chromosome 15q11-q13.1 duplication is a common copy number variant associated with autism spectrum disorder (ASD). Most cases are de novo, maternal in origin and fully penetrant for ASD. Here, we describe a unique family with an interstitial 15q11.2-q13.1 maternal duplication and the presence of somatic mosaicism in the mother. She is typically functioning, but formal autism testing showed mild ASD. She had several congenital anomalies, and she is the first 15q Duplication case reported in the literature to develop unilateral renal carcinoma...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27933075/a-non-specific-setaria-italica-lipid-transfer-protein-gene-plays-a-critical-role-under-abiotic-stress
#14
Yanlin Pan, Jianrui Li, Licong Jiao, Cong Li, Dengyun Zhu, Jingjuan Yu
Lipid transfer proteins (LTPs) are a class of cysteine-rich soluble proteins having small molecular weights. LTPs participate in flower and seed development, cuticular wax deposition, also play important roles in pathogen and abiotic stress responses. A non-specific LTP gene (SiLTP) was isolated from a foxtail millet (Setaria italica) suppression subtractive hybridization library enriched for differentially expressed genes after abiotic stress treatments. A semi-quantitative reverse transcriptase PCR analysis showed that SiLTP was expressed in all foxtail millet tissues...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27932790/motor-neurons-derived-from-als-related-mouse-ips-cells-recapitulate-pathological-features-of-als
#15
Ju-Hwang Park, Hang-Soo Park, Sunghoi Hong, Seongman Kang
Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain. Mutations in Cu/Zn superoxide dismutase 1 (SOD1) are known to induce ALS. Although many research models have been developed, the exact pathological mechanism of ALS remains unknown. The recently developed induced pluripotent stem (iPS) cell technology is expected to illuminate the pathological mechanisms and new means of treatment for neurodegenerative diseases...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932680/trans-spinal-direct-current-stimulation-modulates-migration-and-proliferation-of-adult-newly-born-spinal-cells-in-mice
#16
Sreyashi Samaddar, Kizzy Vazquez, Dipen Ponika, Pedro Toruno, Karim Sahbani, Sultana Begum, Ahmed Abouelela, Wagdy Mekhael, Zaghloul Ahmed
Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932474/recent-developments-in-stem-and-progenitor-cell-therapy-for-cardiac-repair
#17
John Zhao, Shahab Ghafghazi, Abdur Rahman Khan, Talha Ahmad Farid, Joseph B Moore
No abstract text is available yet for this article.
December 9, 2016: Circulation Research
https://www.readbyqxmd.com/read/27932422/significance-of-low-mtorc1-activity-in-defining-the-characteristics-of-brain-tumor-stem-cells
#18
Yi-Peng Han, Atsushi Enomoto, Yukihiro Shiraki, Shen-Qi Wang, Xiaoze Wang, Shinya Toyokuni, Naoya Asai, Kaori Ushida, Hosne Ara, Fumiharu Ohka, Toshihiko Wakabayashi, Jie Ma, Atsushi Natsume, Masahide Takahashi
BACKGROUND: The significance of mammalian target of rapamycin complex 1 (mTORC1) activity in the maintenance of cancer stem cells (CSCs) remains controversial. Previous findings showed that mTORC1 activation depleted the population of leukemia stem cells in leukemia, while maintaining the stemness in pancreatic CSCs. The purpose of this study was to examine the currently unknown role and significance of mTORC1 activity in brain tumor stem cells (BTSCs). METHODS: Basal mTORC1 activity and its kinetics were investigated in BTSC clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs)...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932392/digital-gene-expression-profiling-analysis-of-dna-repair-pathways-in-colon-cancer-stem-population-of-ht29-cells
#19
Wenxue Wang, Guoxiu Zhang, Jing Yang, Huan Gu, Lei Ding, Haijing Yu, Min Yu, Qinghua Cui, Xinglai Ji, Meizhang Li
Cancer stem cells (CSCs) contribute to the relapse and development of new neoplasm lesions. While most available clinical approaches, such as chemical and radiation therapies, will kill the majority of cancer cells, they do not kill them all. Some resisting cells, like CSCs, are able to survive due to their excellent self-maintaining capabilities, even in challenging environments. In the present study, we investigated the mRNA level of DNA repair genes of colon CSCs from the HT29 cell line in response to single-strand damage and double-strand breaks, as well as the evident upregulation of key genes in base excision repair, mismatch repair, non-homologous end-joining, and homologous recombination pathways in these cells...
December 7, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27932312/targeted-apoptosis-of-parietal-cells-is-insufficient-to-induce-metaplasia-in-stomach
#20
Joseph Burclaff, Luciana H Osaki, Dengqun Liu, James R Goldenring, Jason C Mills
Parietal cell atrophy is considered to cause metaplasia in the stomach. We developed mice that express the diphtheria toxin receptor specifically in parietal cells to induce their death, and found this to increase proliferation in the normal stem cell zone and neck but not to cause metaplastic reprogramming of chief cells. Furthermore, the metaplasia-inducing agents tamoxifen or DMP-777 still induced metaplasia even following previous destruction of parietal cells by diphtheria toxin. Atrophy of parietal cells alone is therefore not sufficient to induce metaplasia-completion of metaplastic reprogramming of chief cells requires mechanisms beyond parietal cell injury or death...
December 5, 2016: Gastroenterology
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