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https://www.readbyqxmd.com/read/28822354/3d-brain-organoids-derived-from-pluripotent-stem-cells-promising-experimental-models-for-brain-development-and-neurodegenerative-disorders
#1
REVIEW
Chun-Ting Lee, Raphael M Bendriem, Wells W Wu, Rong-Fong Shen
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials...
August 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#2
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28821762/multi-tissue-interactions-in-an-integrated-three-tissue-organ-on-a-chip-platform
#3
Aleksander Skardal, Sean V Murphy, Mahesh Devarasetty, Ivy Mead, Hyun-Wook Kang, Young-Joon Seol, Yu Shrike Zhang, Su-Ryon Shin, Liang Zhao, Julio Aleman, Adam R Hall, Thomas D Shupe, Andre Kleensang, Mehmet R Dokmeci, Sang Jin Lee, John D Jackson, James J Yoo, Thomas Hartung, Ali Khademhosseini, Shay Soker, Colin E Bishop, Anthony Atala
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819378/hif-is-not-essential-for-suppression-of-experimental-tumor-growth-by-mtor-inhibition
#4
Karl X Knaup, Regina Guenther, Johanna Stoeckert, Juliana M Monti, Kai-Uwe Eckardt, Michael S Wiesener
The Hypoxia Inducible Transcription Factor (HIF) is the master regulator of cellular response to hypoxic adaptation. Solid tumors inevitably harbour hypoxic regions with subsequent stabilization and activation of HIF and HIF target genes due to poor vascularization and rapid growth. The mammalian target of rapamycin (mTOR) is a global regulator of cellular growth and proliferation, which can also regulate HIF expression independantly of hypoxia via specific activation of cellular translation and transcription...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819257/cytolytic-dna-vaccine-encoding-lytic-perforin-augments-the-maturation-of-and-antigen-presentation-by-dendritic-cells-in-a-time-dependent-manner
#5
Danushka K Wijesundara, Wenbo Yu, Ben J C Quah, Preethi Eldi, John D Hayball, Kerrilyn R Diener, Ilia Voskoboinik, Eric J Gowans, Branka Grubor-Bauk
The use of cost-effective vaccines capable of inducing robust CD8(+) T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8(+) T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8(+) T cell immunity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817971/effects-of-solid-acellular-type-i-iii-collagen-biomaterials-on-in-vitro-and-in-vivo-chondrogenesis-of-mesenchymal-stem-cells
#6
Liang Gao, Patrick Orth, Magali Cucchiarini, Henning Madry
Type-I/III collagen membranes are advocated for clinical use in articular cartilage repair as being able of inducing chondrogenesis, a technique termed autologous matrix-induced chondrogenesis (AMIC). Area covered: The current in vitro and translational in vivo evidence for chondrogenic effects of solid acellular type-I/III collagen biomaterials. Expert commentary: In vitro, mesenchymal stem cells (MSCs) adhere to the fibers of the type-I/III collagen membrane. No in vitro study provides evidence that a type-I/III collagen matrix alone may induce chondrogenesis...
August 18, 2017: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/28817787/evaluation-of-the-electron-transfer-flavoprotein-etf-as-an-antibacterial-target-in-burkholderia-cenocepacia
#7
Maria S Stietz, Christina Lopez, Osasumwen Osifo, Marcelo Tolmasky, Silvia T Cardona
There are hundreds of essential genes in multidrug resistant bacterial genomes, but only a few of their products are exploited as antibacterial targets. An example is the electron flavoprotein (ETF) which is required for growth and viability in <i>Burkholderia cenocepacia</i>. Here, we evaluated ETF as an antibiotic target for <i>Burkholderia cepacia</i> complex (Bcc). Depletion of the bacterial ETF during infection of <i>Caenorhabditis elegans</i> significantly extended survival of the nematodes, proving that ETF is essential for survival of <i>B...
August 17, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28817687/morphologic-phenotypic-and-transcriptomic-characterization-of-classically-and-alternatively-activated-canine-blood-derived-macrophages-in-vitro
#8
Franziska Heinrich, Annika Lehmbecker, Barbara B Raddatz, Kristel Kegler, Andrea Tipold, Veronika M Stein, Arno Kalkuhl, Ulrich Deschl, Wolfgang Baumgärtner, Reiner Ulrich, Ingo Spitzbarth
Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28816543/mir-541-5p-regulates-lung-fibrosis-by-targeting-cyclic-nucleotide-phosphodiesterase-1a
#9
Liqin Ren, Chunyan Yang, Yongfeng Dou, Renhui Zhan, Yi Sun, Yan Yu
AIM OF THE STUDY: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. MATERIALS AND METHODS: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation...
August 17, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28816413/porcine-spermatogonial-stem-cells-self-renew-effectively-in-a-three-dimensional-culture-microenvironment
#10
Ji Eun Park, Min Hee Park, Min Seong Kim, Yeo Reum Park, Jung Im Yun, Hee Tae Cheong, Minseok Kim, Jung Hoon Choi, Eunsong Lee, Seung Tae Lee
Generally, self-renewal of spermatogonial stem cells (SSCs) is maintained in vivo in a three-dimensional (3D) microenvironment consisting of the seminiferous tubule basement membrane, indicating the importance of the 3D microenvironment for in vitro culture of SSCs. Here, we report a 3D culture microenvironment that effectively maintains porcine SSC self-renewal during culture. Porcine SSCs were cultured in an agarose-based 3D hydrogel and in 2D culture plates either with or without feeder cells. Subsequently, the effects of 3D culture on the maintenance of undifferentiated SSCs were identified by analyzing cell colony formation and morphology, AP activity, and transcriptional and translational regulation of self-renewal-related genes and the effects on proliferation by analyzing cell viability and single cell-derived colony number...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28814646/the-intracellular-immune-receptor-sw-5b-confers-broad-spectrum-resistance-to-tospoviruses-through-recognition-of-a-conserved-21-amino-acid-viral-effector-epitope
#11
Min Zhu, Lei Jiang, Baohui Bai, Wenyang Zhao, Xiaojiao Chen, Jia Li, Yong Liu, Zhengqiang Chen, Boting Wang, Chunli Wang, Qian Wu, Qian-Hua Shen, Savithramma P Dinesh-Kumar, Xiaorong Tao
Plants use both cell surface-resident pattern-recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors to detect various pathogens. Plant PRRs typically recognize conserved pathogen-associated molecular patterns (PAMPs) to provide broad-spectrum resistance. By contrast, plant NLRs generally detect pathogen strain-specific effectors and confer race-specific resistance. Here, we demonstrate that the tomato NLR Sw-5b confers broad-spectrum resistance against American type tospoviruses by recognizing a conserved 21-amino-acid peptide region within viral movement protein NSm (NSm21)...
August 16, 2017: Plant Cell
https://www.readbyqxmd.com/read/28814126/detection-of-ingested-nitromethane-and-reliable-creatinine-assessment-using-multiple-common-analytical-methods
#12
Christine M Murphy, John J Devlin, Michael C Beuhler, Paul Cheifetz, Susan Maynard, Michael D Schwartz, Sherri Kacinko
AIM: Nitromethane, found in fuels used for short distance racing, model cars, and model airplanes, produces a falsely elevated serum creatinine with standard creatinine analysis via the Jaffé method. Erroneous creatinine elevation often triggers extensive testing, leads to inaccurate diagnoses, and delayed or inappropriate medical interventions. Multiple reports in the literature identify "enzymatic assays" as an alternative method to detect the true value of creatinine, but this ambiguity does not help providers translate what type of enzymatic assay testing can be done in real time to determine if there is indeed false elevation...
August 17, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28813136/targeting-of-cellular-organelles-by-fluorescent-plasmid-dna-nanoparticles
#13
Diana Costa, Carolina Costa, Margarida Vaz Caldeira, Luisa Maria Cortes, João A Queiroz, Carla Cruz
The development of a suitable delivery system and the targeting of intracellular organelles are both essential for the success of drug and gene therapies. The conception of fluorescent ligands, displaying targeting specificity together with low toxicity, is an emerging and reliable tool to develop innovative delivery systems. Biocompatible BSA or pDNA/ligand nanoparticles were synthesized by a co-precipitation method and were shown to display adequate sizes and morphology for delivery purposes, and positive surface charges...
August 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28812968/jnk-pathway-in-osteoarthritis-pathological-and-therapeutic-aspects
#14
Hong-Xing Ge, Fu-Man Zou, Yan Li, An-Min Liu, Min Tu
CONTEXT: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway. OBJECTIVE: In this study, we have reviewed the recent updates on the association of JNK pathway with OA. METHODS: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28809922/increased-signaling-by-the-autism-related-engrailed-2-protein-enhances-dendritic-branching-and-spine-density-alters-synaptic-structural-matching-and-exaggerates-protein-synthesis
#15
Asma Soltani, Solène Lebrun, Gilles Carpentier, Giulia Zunino, Sandrine Chantepie, Auriane Maïza, Yuri Bozzi, Claire Desnos, François Darchen, Olivier Stettler
Engrailed 1 (En1) and 2 (En2) code for closely related homeoproteins acting as transcription factors and as signaling molecules that contribute to midbrain and hindbrain patterning, to development and maintenance of monoaminergic pathways, and to retinotectal wiring. En2 has been suggested to be an autism susceptibility gene and individuals with autism display an overexpression of this homeogene but the mechanisms remain unclear. We addressed in the present study the effect of exogenously added En2 on the morphology of hippocampal cells that normally express only low levels of Engrailed proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28809727/models-of-non-alcoholic-fatty-liver-disease-and-potential-translational-value-the-effects-of-3-5-l-diiodothyronine
#16
Elena Grasselli, Laura Canesi, Piero Portincasa, Adriana Voci, Laura Vergani, Ilaria Demori
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28809486/assembling-glycan-charged-dolichol-phosphates-chemoenzymatic-synthesis-of-a-haloferax-volcanii-n-glycosylation-pathway-intermediate
#17
Yifat Elharar, Ananda R Podilapu, Ziqiang Guan, Suvarn S Kulkarni, Jerry Eichler
N-glycosylation, the covalent attachment of glycans to select protein target Asn residues, is a post-translational modification performed by all three domains of life. In the halophilic archaea Haloferax volcanii, where understanding of this universal protein-processing event is relatively well-advanced, genes encoding the components of the Agl (archaeal glycosylation) pathway responsible for the assembly and attachment of an N-linked pentasaccharide have been identified. As elsewhere, the N-linked glycan is assembled on phosphodolichol carriers before transfer to target Asn residues...
August 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28809479/natural-seminal-amyloids-as-targets-for-development-of-synthetic-inhibitors-of-hiv-transmission
#18
Daniel A Sheik, Stephen Dewhurst, Jerry Yang
Amyloids refer to a class of protein or peptide aggregates that are heterogeneous in size, morphology, and composition, and are implicated to play a central role in many neurodegenerative and systemic diseases. The strong correlation between biological activity and extent of aggregation of amyloidogenic proteins and peptides has led to an explosion of research efforts to target these materials with synthetic molecules or engineered antibodies to try to attenuate their function in disease pathology. Although many of these efforts to attenuate amyloid function have shown great promise in laboratory settings, the vast majority of work has been focused on targeting amyloids associated with neurologic diseases, which has been met with significant additional challenges that preclude clinical evaluation...
August 15, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28809115/an-intuitive-approach-for-predicting-potential-human-health-risk-with-the-tox21-10k-library
#19
Nisha S Sipes, John F Wambaugh, Robert Pearce, Scott S Auerbach, Barbara Anne Wetmore, Jui-Hua Hsieh, Andrew J Shapiro, Daniel Svoboda, Michael J DeVito, Stephen S Ferguson
In vitro-in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited. This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28808258/hexahydroquinolines-are-antimalarial-candidates-with-potent-blood-stage-and-transmission-blocking-activity
#20
Manu Vanaerschot, Leonardo Lucantoni, Tao Li, Jill M Combrinck, Andrea Ruecker, T R Santha Kumar, Kelly Rubiano, Pedro E Ferreira, Giulia Siciliano, Sonia Gulati, Philipp P Henrich, Caroline L Ng, James M Murithi, Victoria C Corey, Sandra Duffy, Ori J Lieberman, M Isabel Veiga, Robert E Sinden, Pietro Alano, Michael J Delves, Kim Lee Sim, Elizabeth A Winzeler, Timothy J Egan, Stephen L Hoffman, Vicky M Avery, David A Fidock
Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes...
August 14, 2017: Nature Microbiology
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