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https://www.readbyqxmd.com/read/28207788/self-complementary-adeno-associated-virus-serotype-6-mediated-knockdown-of-adamts4-induces-long-term-and-effective-enhancement-of-aggrecan-in-degenerative-human-nucleus-pulposus-cells-a-new-therapeutic-approach-for-intervertebral-disc-disorders
#1
Demissew Shenegelegn Mern, Anja Tschugg, Sebastian Hartmann, Claudius Thomé
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs...
2017: PloS One
https://www.readbyqxmd.com/read/28202570/aav-mediated-delivery-of-optogenetic-constructs-to-the-macaque-brain-triggers-humoral-immune-responses
#2
Skyler D Mendoza, Yasmine El-Shamayleh, Gregory D Horwitz
Gene delivery to the primate central nervous system via recombinant adeno-associated viral vectors (AAV) allows neurophysiologists to control and observe neural activity precisely. A current limitation of this approach is variability in vector transduction efficiency. Low levels of transduction can foil experimental manipulations, prompting vector readministration. The ability to make multiple vector injections into the same animal, even in cases where successful vector transduction has already been achieved, is also desirable...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28199828/hucns-sc-human-nscs-fail-to-differentiate-form-ectopic-clusters-and-provide-no-cognitive-benefits-in-a-transgenic-model-of-alzheimer-s-disease
#3
Samuel E Marsh, Stephen T Yeung, Maria Torres, Lydia Lau, Joy L Davis, Edwin S Monuki, Wayne W Poon, Mathew Blurton-Jones
Transplantation of neural stem cells (NSCs) can improve cognition in animal models of Alzheimer's disease (AD). However, AD is a protracted disorder, and prior studies have examined only short-term effects. We therefore used an immune-deficient model of AD (Rag-5xfAD mice) to examine long-term transplantation of human NSCs (StemCells Inc.; HuCNS-SCs). Five months after transplantation, HuCNS-SCs had engrafted and migrated throughout the hippocampus and exhibited no differences in survival or migration in response to β-amyloid pathology...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28194092/paradoxes-of-the-ephb1-receptor-in-malignant-brain-tumors
#4
REVIEW
Wenqiang Wei, Hongju Wang, Shaoping Ji
Eph receptors are a subfamily of receptor tyrosine kinases. Eph receptor-mediated forward and ephrin ligand-mediated reverse signalings are termed bidirectional signaling. Increasing evidence shows that Eph/ephrin signaling regulates cell migration, adhesion, morphological changes, differentiation, proliferation and survival through cell-cell communication. Some recent studies have started to implicate Eph/ephrin signaling in tumorigenesis, metastasis, and angiogenesis. Previous studies have shown that EphB1 receptor and its ephrin ligands are expressed in the central nervous system...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28193841/dual-roles-of-akirin2-during-xenopus-neural-development
#5
Xiaoliang Liu, Yingjie Xia, Jixin Tang, Li Ma, Chaocui Li, Pengcheng Ma, Bingyu Mao
To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here, we show that Akirin2 is required for neural development in Xenopus and knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28192527/the-efficacy-of-a-scaffold-free-bio-3d-conduit-developed-from-human-fibroblasts-on-peripheral-nerve-regeneration-in-a-rat-sciatic-nerve-model
#6
Hirofumi Yurie, Ryosuke Ikeguchi, Tomoki Aoyama, Yukitoshi Kaizawa, Junichi Tajino, Akira Ito, Souichi Ohta, Hiroki Oda, Hisataka Takeuchi, Shizuka Akieda, Manami Tsuji, Koichi Nakayama, Shuichi Matsuda
BACKGROUND: Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. METHODS: We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer...
2017: PloS One
https://www.readbyqxmd.com/read/28187911/what-kaplan-meier-survival-curves-don-t-tell-us-about-cns-disease
#7
Katelyn D Miller, Glenn F Rall
Central nervous system consequences of viral infections are rare, but when they do occur, they are often serious and clinically challenging to manage. Our awareness of the perils of neuroinvasion by viruses is growing: the recently appreciated impact of Ebola and Zika virus infections on CNS integrity, decreases in vaccination coverage for potentially neurotropic viruses such as measles, and increased neurovirulence of some influenza strains collectively highlight the need for a better understanding of the viral-neural interaction...
February 3, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28185790/immune-regulation-of-antibody-access-to-neuronal-tissues
#8
REVIEW
Akiko Iwasaki
This review highlights recent advances in how the innate and adaptive immune systems control the blood-brain barrier (BBB) and the blood-nerve barrier (BNB). Interferons and TAM receptors play key roles in innate immune control of the BBB. Cells of the adaptive immune system, particularly CD4(+) T cells, take distinct routes to enter neural tissues and mediate immune surveillance. Furthermore, T cell-mediated opening of the BBB and the BNB is crucial to allow antibody access and thereby block the replication of neurotropic viruses...
February 6, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28170004/inflammation-and-the-neural-diathesis-stress-hypothesis-of-schizophrenia-a-reconceptualization
#9
REVIEW
O D Howes, R McCutcheon
An interaction between external stressors and intrinsic vulnerability is one of the longest standing pathoaetiological explanations for schizophrenia. However, novel lines of evidence from genetics, preclinical studies, epidemiology and imaging have shed new light on the mechanisms that may underlie this, implicating microglia as a key potential mediator. Microglia are the primary immune cells of the central nervous system. They have a central role in the inflammatory response, and are also involved in synaptic pruning and neuronal remodeling...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28163053/myocyte-enhancer-factor-2c-and-its-directly-interacting-proteins-a-review
#10
REVIEW
Chen Dong, Xue-Zhou Yang, Chen-Yan Zhang, Yang-Yang Liu, Ren-Bin Zhou, Qing-Di Cheng, Er-Kai Yan, Da-Chuan Yin
Myocyte enhancer factor 2C (MEF2C) is a transcription factor of MADS box family involved in the early development of several human cells including muscle (i.e., skeletal, cardiac, and smooth), neural, chondroid, immune, and endothelial cells. Dysfunction of MEF2C leads to embryo hypoplasia, disorganized myofibers and perinatal lethality. The main role of MEF2C is its regulation of muscle development. It has been reported that MEF2C-knockout mice die on embryonic day 9.5 from unnatural development of cardiovascular...
February 2, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28155640/prediction-of-hiv-1-protease-cleavage-site-using-a-combination-of-sequence-structural-and-physicochemical-features
#11
Onkar Singh, Emily Chia-Yu Su
BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) aspartic protease is an important enzyme owing to its imperative part in viral development and a causative agent of deadliest disease known as acquired immune deficiency syndrome (AIDS). Development of HIV-1 protease inhibitors can help understand the specificity of substrates which can restrain the replication of HIV-1, thus antagonize AIDS. However, experimental methods in identification of HIV-1 protease cleavage sites are generally time-consuming and labor-intensive...
December 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28155242/sensory-neuron-regulation-of-gastrointestinal-inflammation-and-bacterial-host-defence
#12
N Y Lai, K Mills, I M Chiu
Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage...
February 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28154949/differential-gene-expression-associated-with-honey-bee-grooming-behavior-in-response-to-varroa-mites
#13
Mollah Md Hamiduzzaman, Berna Emsen, Greg J Hunt, Subhashree Subramanyam, Christie E Williams, Jennifer M Tsuruda, Ernesto Guzman-Novoa
Honey bee (Apis mellifera) grooming behavior is an important mechanism of resistance against the parasitic mite Varroa destructor. This research was conducted to study associations between grooming behavior and the expression of selected immune, neural, detoxification, developmental and health-related genes. Individual bees tested in a laboratory assay for various levels of grooming behavior in response to V. destructor were also analyzed for gene expression. Intense groomers (IG) were most efficient in that they needed significantly less time to start grooming and fewer grooming attempts to successfully remove mites from their bodies than did light groomers (LG)...
February 3, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28154011/involvement-of-gut-microbiota-in-the-association-between-glp-1-glp-1-receptor-expression-and-gastrointestinal-motility
#14
Mo Yang, Hirokazu Fukui, Hirotsugu Eda, Xin Xu, Yoshitaka Kitayama, Ken Hara, Mio Kodani, Toshihiko Tomita, Tadayuki Oshima, Jiro Watari, Hiroto Miwa
Microbiota in the gut is known to play a pivotal role in host physiology by interacting with the immune and neuroendocrine systems in gastrointestinal (GI) tissues. Glucagon-like peptide 1 (GLP-1), a gut hormone, is involved in metabolism as well as GI motility. We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points...
February 2, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28148846/tumor-homing-cytotoxic-human-induced-neural-stem-cells-for-cancer-therapy
#15
Juli R Bagó, Onyi Okolie, Raluca Dumitru, Matthew G Ewend, Joel S Parker, Ryan Vander Werff, T Michael Underhill, Ralf S Schmid, C Ryan Miller, Shawn D Hingtgen
Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSC(TE)), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSC(TE) in patient-derived GBM models of surgical and nonsurgical disease...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28148680/the-plasma-proteome-is-associated-with-anthropometric-status-of-undernourished-nepalese-school-aged-children
#16
Sun Eun Lee, Christine P Stewart, Kerry J Schulze, Robert N Cole, Lee S-F Wu, James D Yager, John D Groopman, Subarna K Khatry, Ramesh Kant Adhikari, Parul Christian, Keith P West
BACKGROUND: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology. OBJECTIVE: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children. METHODS: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age...
February 1, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28144278/altered-sympathovagal-balance-and-pain-hypersensitivity-in-tnbs-induced-colitis
#17
Katarzyna Ciesielczyk, Agata Furgała, Łukasz Dobrek, Kajetan Juszczak, Piotr Thor
INTRODUCTION: Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). MATERIAL AND METHODS: The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability - HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis...
February 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28141971/paracrine-maturation-and-migration-of-sh-sy5y-cells-by-dental-pulp-stem-cells
#18
P Gervois, E Wolfs, Y Dillen, P Hilkens, J Ratajczak, R B Driesen, T Vangansewinkel, A Bronckaers, B Brône, T Struys, I Lambrichts
Neurological disorders are characterized by neurodegeneration and/or loss of neuronal function, which cannot be adequately repaired by the host. Therefore, there is need for novel treatment options such as cell-based therapies that aim to salvage or reconstitute the lost tissue or that stimulate host repair. The present study aimed to evaluate the paracrine effects of human dental pulp stem cells (hDPSCs) on the migration and neural maturation of human SH-SY5Y neuroblastoma cells. The hDPSC secretome had a significant chemoattractive effect on SH-SY5Y cells as shown by a transwell assay...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28135684/evaluation-of-the-immunogenicity-of-human-ips-cell-derived-neural-stem-progenitor-cells-in-vitro
#19
Masahiro Ozaki, Akio Iwanami, Narihito Nagoshi, Jun Kohyama, Go Itakura, Hiroki Iwai, Soraya Nishimura, Yuichiro Nishiyama, Soya Kawabata, Keiko Sugai, Tsuyoshi Iida, Kohei Matsubayashi, Miho Isoda, Rei Kashiwagi, Yoshiaki Toyama, Morio Matsumoto, Hideyuki Okano, Masaya Nakamura
To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries...
January 19, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28131792/interleukin-1-signaling-in-the-basolateral-amygdala-is-necessary-for-heroin-conditioned-immunosuppression
#20
Lee W Hutson, Christina L Lebonville, Meghan E Jones, Rita A Fuchs, Donald T Lysle
Heroin administration suppresses the production of inducible nitric oxide (NO), as indicated by changes in splenic inducible nitric oxide synthase (iNOS) and plasma nitrate/nitrite. Since NO is a measure of host defense against infection and disease, this provides evidence that heroin can increase susceptibility to pathogens by directly interacting with the immune system. Previous research in our laboratory has demonstrated that these immunosuppressive effects of heroin can also be conditioned to environmental stimuli by repeatedly pairing heroin administration with a unique environmental context...
January 25, 2017: Brain, Behavior, and Immunity
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