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https://www.readbyqxmd.com/read/28110484/upregulation-of-20-hete-synthetic-cytochrome-p450-isoforms-by-oxygen-glucose-deprivation-in-cortical-neurons
#1
Hui Zhang, John R Falck, Richard J Roman, David R Harder, Raymond C Koehler, Zeng-Jin Yang
20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor, is a cytochrome P450 (CYP) 4A/4F-derived metabolite of arachidonic acid. Inhibition of 20-HETE synthesis protects brain from ischemic injury. However, that protection is not associated with changes in cerebral blood flow. The present study examined whether CYP4A isoforms are expressed in neurons, whether they produce 20-HETE in neurons, and whether neuronally derived 20-HETE exerts direct neurotoxicity after oxygen-glucose deprivation (OGD)...
January 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28110349/organochlorine-pesticides-in-gonad-brain-and-blood-of-mice-in-two-agricultural-areas-of-sinaloa
#2
Ernestina Perez-Gonzalez, Ulises-Giovanni Osuna-Martinez, Maria-Nancy Herrera-Moreno, Guadalupe-Durga Rodriguez-Meza, Hector-A Gonzalez-Ocampo, Marcos Bucio-Pacheco
The adverse effect of pesticides on non-target wildlife and human health is a primary concern in the world, but in Mexico, we do not know which wildlife species are at the greatest risk. The aim of this study was to determine organochlorine pesticides in mice of two agricultural fields in Sinaloa, Culiacan and Guasave. Procedures of extraction, analysis, and quantification were followed according to the modified EPA 8081b method. In three mouse tissues (gonad, brain, and blood), γBHC and decachlorobiphenyl with a frequency higher than 50% and endosulfan sulfate with 43% were observed...
January 21, 2017: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/28110219/tgf-%C3%AE-engineered-mesenchymal-stem-cells-tgf-%C3%AE-mscs-for-treatment-of-type-1-diabetes-t1d-mice-model
#3
Saeed Daneshmandi, Mohammad Hossein Karimi, Ali Akbar Pourfathollah
OBJECTIVE: Mesenchymal stem cells (MSCs) are advantageous candidates for cell therapy of Type 1 diabetes (T1D). Considering immunomodulatory effect of MSC, in this study, we engineered MSCs with TGF-β gene to increase MSC potency for T1D therapy in mouse model. MATERIALS AND METHODS: Two plans were designed for prevention and treatment of diabetes, respectively. In both of them, MSCs were injected i.v. and then, the diabetes features including serum insulin, blood glucose, glucose tolerance, splenocytes proliferation, and IL-4/IFN-γ production were evaluated...
January 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110213/cannabidiol-attenuates-ogd-r-induced-damage-by-enhancing-mitochondrial-bioenergetics-and-modulating-glucose-metabolism-via-pentose-phosphate-pathway-in-hippocampal-neurons
#4
Shanshan Sun, Fangyuan Hu, Jihong Wu, Shenghai Zhang
Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers...
December 31, 2016: Redox Biology
https://www.readbyqxmd.com/read/28110173/tuning-physical-properties-and-bmp-2-release-rates-of-injectable-hydrogel-systems-for-an-optimal-bone-regeneration-effect
#5
Bo-Bae Seo, Jeong-Tae Koh, Soo-Chang Song
For a substance to be used as a drug delivery carrier and tissue inducible material for a target disease, its drug release rate and physical properties should be optimized to facilitate the healing process. We developed multi-tunable hydrogel systems with various physical properties and release behaviors to determine the optimal conditions for bone regeneration. Five injectable poly(phosphazene) hydrogels were developed with different types and amounts of anionic side-chains. The five polymer hydrogels showed considerably different in vitro and in vivo performances for sol-gel phase transition, dissolution/degradation, water uptake, and pore size...
January 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28110136/impaired-muscle-force-production-and-higher-fatigability-in-a-mouse-model-of-sickle-cell-disease
#6
Benjamin Chatel, Christophe Hourdé, Julien Gondin, Alexandre Fouré, Yann Le Fur, Christophe Vilmen, Monique Bernard, Laurent A Messonnier, David Bendahan
Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability...
January 11, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28110114/tropoelastin-coated-plla-plga-scaffolds-promote-vascular-network-formation
#7
Shira Landau, Ariel A Szklanny, Giselle C Yeo, Yulia Shandalov, Elena Kosobrodova, Anthony S Weiss, Shulamit Levenberg
The robust repair of large wounds and tissue defects relies on blood flow. This vascularization is the major challenge faced by tissue engineering on the path to forming thick, implantable tissue constructs. Without this vasculature, oxygen and nutrients cannot reach the cells located far from host blood vessels. To make viable constructs, tissue engineering takes advantage of the mechanical properties of synthetic materials, while combining them with ECM proteins to create a natural environment for the tissue-specific cells...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28110104/quercetin-3-o-glucuronide-promotes-the-proliferation-and-migration-of-neural-stem-cells
#8
Samrat Baral, Ramesh Pariyar, Jaehyo Kim, Ho-Sub Lee, Jungwon Seo
Quercetin is a bioactive compound exerting therapeutic effects on in vivo animal models of neurodegeneration or neurotoxicity. However, the narrow therapeutic dose-range of quercetin has been a point of concern since previous studies have demonstrated that quercetin induces cytotoxicity in vitro. Quercetin is metabolized to quercetin glucuronates such as quercetin-3-O-glucuronide (Q3GA), primarily detected in the plasma and the brain. Here, we examined whether and how quercetin or Q3GA regulates neural stem cells (NSCs) in vivo and in vitro...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28110103/the-retromer-complex-system-in-a-transgenic-mouse-model-of-ad-influence-of-age
#9
Jin Chu, Domenico Praticò
Deficiencies of the retrograde transport mediated by the retromer complex have been described in Alzheimer's disease (AD). Genetic manipulation of retromer modulates brain amyloidosis in Tg2576 mice. However, whether the complex is altered during the development of the AD-like phenotype remains unknown. In this study we assayed the expression levels of the vacuolar sorting protein 35 (VPS35), VPS26, VPS29, and its cargo proteins, cation independent mannose 6-phosphate receptor, sortilin-related receptor in brains of Tg2576 and controls at the ages of 3, 8, and 14 months...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28110075/tlr9-mediated-regulatory-b10-cell-amplification-following-sub-total-body-irradiation-implications-in-attenuating-eae
#10
Jinsheng Hong, Jie Fang, Ruilong Lan, Qi Tan, Yeping Tian, Mei Zhang, Paul Okunieff, Lurong Zhang, Jianhua Lin, Deping Han
Autoimmunity and inflammation are controlled in part by regulatory B (Breg) cells, including the recently identified IL-10-competent B10 cell subset that represents 1%-3% of mouse spleen B cells. In this study, the influence of irradiation on Breg/B10 cell generation and IL-10 production mediated by TLR9 signaling pathways was investigated. Spleen and peritoneal cavity Breg/B10 cell frequencies were significantly expanded three weeks after sub-total body irradiation (sub-TBI, 5Gy or 10Gy) in adult male wild type (WT) C57BL/6(B6) mice but not in TLR9(-/-) mice...
January 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28110069/peptide-and-nucleic-acid-directed-self-assembly-of-cationic-nanovehicles-through-giant-unilamellar-vesicle-modification-targetable-nanocomplexes-for-in-vivo-nucleic-acid-delivery
#11
A D Tagalakis, R Maeshima, C Yu-Wai-Man, J Meng, F Syed, L-P Wu, A M Aldossary, D McCarthy, S M Moghimi, S L Hart
: One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90-140 nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes...
January 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28110063/curcumin-ameliorates-liver-damage-and-progression-of-nash-in-nash-hcc-mouse-model-possibly-by-modulating-hmgb1-nf-%C3%AE%C2%BAb-translocation
#12
Rejina Afrin, Somasundaram Arumugam, Azizur Rahman, Mir Imam Ibne Wahed, Vengadeshprabhu Karuppagounder, Meilei Harima, Hiroshi Suzuki, Shizuka Miyashita, Kenji Suzuki, Hiroyuki Yoneyama, Kazuyuki Ueno, Kenichi Watanabe
Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding...
January 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28109959/crispr-cas9-mediated-genome-editing-as-a-therapeutic-approach-for-leber-congenital-amaurosis-10
#13
Guo-Xiang Ruan, Elizabeth Barry, Dan Yu, Michael Lukason, Seng H Cheng, Abraham Scaria
As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28109957/adoptive-transfer-of-mrna-transfected-t-cells-redirected-against-diabetogenic-cd8%C3%A2-t-cells-can-prevent-diabetes
#14
Sigal Fishman, Mark D Lewis, L Khai Siew, Evy De Leenheer, Dimitri Kakabadse, Joanne Davies, Doron Ziv, Alon Margalit, Nathan Karin, Gideon Gross, F Susan Wong
Chimeric major histocompatibility complex (MHC) molecules supplemented with T cell receptor (TCR) signaling motifs function as activation receptors and can redirect gene-modified T cells against pathogenic CD8 T cells. We have shown that β2 microglobulin (β2m) operates as a universal signaling component of MHC-I molecules when fused with the CD3-ζ chain. Linking the H-2K(d)-binding insulin B chain peptide insulin B chain, amino acids 15-23 (InsB15-23) to the N terminus of β2m/CD3-ζ, redirected polyclonal CD8 T cells against pathogenic CD8 T cells in a peptide-specific manner in the non-obese diabetic (NOD) mouse...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28109944/synthesis-biological-evaluation-and-molecular-dynamics-md-simulation-studies-of-three-novel-f-18-labeled-and-focal-adhesion-kinase-fak-targeted-5-bromo-pyrimidines-as-radiotracers-for-tumor
#15
Yu Fang, Dawei Wang, Xingyu Xu, Jianping Liu, Aiqin Wu, Xiang Li, Qianqian Xue, Huan Wang, Hang Wang, Huabei Zhang
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N(2)-(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N(4)-(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC50 in the range of 91...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28109914/anti-inflammatory-and-toxicological-evaluation-of-essential-oil-from-piper-glabratum-leaves
#16
Lidiane Schultz Branquinho, Joyce Alencar Santos, Claudia Andrea Lima Cardoso, Jonas da Silva Mota, Ubirajara Lanza Junior, Cândida Aparecida Leite Kassuya, Arielle Cristina Arena
ETHNOPHARMACOLOGICAL RELEVANCE: Although some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited. AIM OF THE STUDY: This study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice. MATERIALS AND METHODS: The acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight...
January 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28109899/rgd-conjugated-liposome-hollow-silica-hybrid-nanovehicles-for-targeted-and-controlled-delivery-of-arsenic-trioxide-against-hepatic-carcinoma
#17
Weidong Fei, Yan Zhang, Shunping Han, Jiaoyang Tao, Hongyue Zheng, Yinghui Wei, Jiazhen Zhu, Fanzhu Li, Xuanshen Wang
The aim of our study was to construct an Arg-Gly-Asp (RGD)-conjugated liposome-hollow silica hybrid nanovehicle for targeted delivery and controlled release of arsenic trioxide (ATO), whose anti-solid tumor effect was hampered by poor pharmacokinetics and dose-limited toxicity. Hydrophobic interactions were used to attach intact lipid membrane to the surface of chlorodimethyloctadecylsilane-modified hollow mesoporous silica nanoparticles. The prepared nanovehicles (RGD-LP-CHMSN) were characterized for uniform structure (silica core of ∼140nm in diameter and liposomal shell of ∼6nm), comparable drug loading efficiency (6...
January 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28109879/selenomethionine-promoted-hippocampal-neurogenesis-via-the-pi3k-akt-gsk3%C3%AE-wnt-pathway-in-a-mouse-model-of-alzheimer-s-disease
#18
REVIEW
Rui Zheng, Zhong-Hao Zhang, Chen Chen, Yao Chen, Shi-Zheng Jia, Qiong Liu, Jia-Zuan Ni, Guo-Li Song
The maintenance of neural system integrity and function is the ultimate goal for the treatment of neurodegenerative disease such as Alzheimer's disease (AD). Neurogenesis plays an integral role in the maintenance of neural and cognitive functions, and its dysfunction is regarded as a major cause of cognitive impairment in AD. Moreover, the induction of neurogenesis by targeting endogenous neural stem cells (NSCs) is considered as one of the most promising treatment strategies. Our previous studies demonstrated that selenomethionine (Se-Met) was able to reduce β-amyloid peptide (Aβ) deposition, decrease Tau protein hyperphosphorylation and markedly improve cognitive functions in triple transgenic (3xTg) AD mice...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28109792/bisacodyl-and-its-cytotoxic-activity-on-human-glioblastoma-stem-like-cells-implication-of-inositol-1-4-5-triphosphate-receptor-dependent-calcium-signaling
#19
Jihu Dong, Francisco Aulestia, Suzana Assad Kahn, Maria Zeniou, Luiz Gustavo Dubois, Elias A El-Habr, François Daubeuf, Nassera Tounsi, Samuel H Cheshier, Nelly Frossard, Marie-Pierre Junier, Hervé Chneiweiss, Isabelle Néant, Marc Moreau, Catherine Leclerc, Jacques Haiech, Marie-Claude Kilhoffer
Glioblastoma is the most common malignant brain tumor. The heterogeneity at the cellular level, metabolic specificities and plasticity of the cancer cells are a challenge for glioblastoma treatment. Identification of cancer cells endowed with stem properties and able to propagate the tumor in animal xenografts has opened a new paradigm in cancer therapy. Thus, to increase efficacy and avoid tumor recurrence, therapies need to target not only the differentiated cells of the tumor mass, but also the cancer stem-like cells...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28109739/in%C3%A2-vivo-antianaerobe-activity-of-ds-8587-a-new-fluoroquinolone-against-fusobacterium-necrophorum-in-a-mouse-model
#20
Kentaro Nagaoka, Katsunori Yanagihara, Yoshitomo Morinaga, Yuichi Kurosaka, Kazuki Hoshino, Shigeru Kohno
DS-8587 is a novel parenteral fluoroquinolone, which has an activity equivalent to sitafloxacin against various pathogens including anaerobes. We examined the in vivo anti-anaerobic activity of DS-8587, and compared it with that of levofloxacin (LVFX), using a murine model of Fusobacterium necrophorum-induced liver abscess developed via blood borne infection. Mice with liver abscess infection caused by F. necrophorum were treated with saline (control), DS-8587 (0.8, 4, and 20 mg/kg twice daily), or LVFX (20 and 100 mg/kg) for a day...
January 18, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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