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https://www.readbyqxmd.com/read/29161771/tetramethylpyrazine-nitrone-activates-akt-creb-through-increasing-bdnf-expression-to-promote-post-ischemic-neuroregeneration-and-recovery-of-neurological-functions-in-rats
#1
Gaoxiao Zhang, Tao Zhang, Ning Li, Liangmiao Wu, Jianbo Gu, Cuimei Li, Chen Zhao, Wei Liu, Luchen Shan, Pei Yu, Xifei Yang, Yaohui Tang, Guo-Yuan Yang, Yuqiang Wang, Yewei Sun, Zaijun Zhang
BACKGROUND AND PURPOSE: Neuronal regeneration from endogenous precursors is an attractive strategy for the treatment of ischemic stroke; however, most stroke-generated new born neurons die over time. Therefore, a drug that is both neuroprotective and pro-neurogenic may be promising. In this study, we assessed the neurogenic and oligodendrogenic effects of tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, in a rat model of ischemic stroke. EXPERIMENTAL APPROACH: Sprague Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO)...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29161514/discovery-of-an-orally-bioavailable-benzofuran-analogue-that-serves-as-a-%C3%AE-amyloid-aggregation-inhibitor-for-the-potential-treatment-of-alzheimer-s-disease
#2
Heejin Ha, Dong Wook Kang, Hyuk-Min Kim, Jin-Mi Kang, Jihyae Ann, Hyae Jung Hyun, Joon Hwan Lee, Sae Hee Kim, Hee Kim, Kwanghyun Choi, Hyun-Seok Hong, Young Ho Kim, Dong-Gyu Jo, Jiyoun Lee, Jeewoo Lee
We developed an orally active and blood-brain barrier-permeable benzofuran analogue (8, MDR-1339) with potent anti-aggregation activity. Compound 8 restored cellular viability from Aβ-induced cytotoxicity but also improved the learning and memory function of AD model mice by reducing the Aβ aggregates in the brains. Given the high bioavailability and brain permeability demonstrated in our pharmacokinetic studies, compound 8 will provide a novel scaffold for an Aβ-aggregation inhibitor that may offer an alternative treatment for AD...
November 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29161463/the-il-21-mtor-axis-blocks-treg-differentiation-and-function-by-suppression-of-autophagy-in-patients-with-systemic-lupus-erythematosus
#3
Hiroshi Kato, Andras Perl
OBJECTIVES: The mechanistic target of rapamycin (mTOR) has become a therapeutic target in systemic lupus erythematosus (SLE). mTOR regulates normal T-cell lineage specification, including development of regulatory cells (Tregs). Therefore, we investigated whether mTOR is activated within Tregs and causes their depletion and dysfunction in patients with SLE. METHODS: Activities of mTOR complexes 1 (mTORC1) and 2 (mTORC2) were examined by phosphorylation of 4E-BP1, S6K, and Akt, respectively, in SLE patients relative to healthy control females age-matched for each experiment...
November 21, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29161204/effect-of-neoadjuvant-chemoradiotherapy-on-health-related-quality-of-life-in-esophageal-or-junctional-cancer-results-from-the-randomized-cross-trial
#4
Bo Jan Noordman, Mathilde G E Verdam, Sjoerd M Lagarde, Maarten C C M Hulshof, Pieter van Hagen, Mark I van Berge Henegouwen, Bas P L Wijnhoven, Hanneke W M van Laarhoven, Grard A P Nieuwenhuijzen, Geke A P Hospers, Johannes J Bonenkamp, Miguel A Cuesta, Reinoud J B Blaisse, Olivier R Busch, Fiebo J W Ten Kate, Geert-Jan M Creemers, Cornelis J A Punt, John Th M Plukker, Henk M W Verheul, Ernst J Spillenaar Bilgen, Herman van Dekken, Maurice J C van der Sangen, Tom Rozema, Katharina Biermann, Jannet C Beukema, Anna H M Piet, Caroline M van Rij, Janny G Reinders, Hugo W Tilanus, Ewout W Steyerberg, Ate van der Gaast, Mirjam A G Sprangers, J Jan B van Lanschot
Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and -Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively...
November 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29161200/early-placement-of-ventilation-tubes-in-infants-with-cleft-lip-and-palate-a-systematic-review
#5
Mark Felton, Jong Wook Lee, Darius D Balumuka, Jugpal S Arneja, Neil K Chadha
Objective Studies have shown that the majority of cleft lip and palate (CLP) children have middle ear fluid present at the time of lip repair (3-4 months). Despite hearing loss, the majority of children do not undergo ventilation tube treatment if required until the time of palate repair (9-12 months). We aimed to examine the effectiveness and potential complications of early ventilation tube placement prior to palatoplasty in infants with cleft lip and palate. Data Sources Medline (1946-2015), Embase (1980-2015), and EBM Reviews (Cochrane Central Register of Controlled)...
November 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29160904/three-dimensional-accuracy-of-digital-static-interocclusal-registration-by-three-intraoral-scanner-systems
#6
Kuan Yee Wong, Roxanna Jean Esguerra, Vanessa Ai Ping Chia, Ying Han Tan, Keson Beng Choon Tan
PURPOSE: Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three-dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function. MATERIALS AND METHODS: Three IOS systems compared were 3M(TM) True Definition Scanner (TDS), TRIOS Color (TRC), and CEREC AC with CEREC Omnicam (CER)...
November 21, 2017: Journal of Prosthodontics: Official Journal of the American College of Prosthodontists
https://www.readbyqxmd.com/read/29160844/altered-aconitase-2-activity-in-huntington-s-disease-peripheral-blood-cells-and-mouse-model-striatum
#7
Chiung-Mei Chen, Yih-Ru Wu, Kuo-Hsuan Chang
Huntington's disease (HD) is caused by an unstable cytosine adenine guanine (CAG) trinucleotide repeat expansion encoding a polyglutamine tract in the huntingtin protein. Previously, we identified several up- and down-regulated protein molecules in the striatum of the Hdh((CAG)150) knock-in mice at 16 months of age, a mouse model which is modeling the early human HD stage. Among those molecules, aconitase 2 (Aco2) located in the mitochondrial matrix is involved in the energy generation and susceptible to increased oxidative stress that would lead to inactivation of Aco2 activity...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29160569/reconstruction-of-bladder-function-and-prevention-of-renal-deterioration-by-means-of-end-to-side-neurorrhaphy-in-rats-with-neurogenic-bladder
#8
Yun Long Li, Jian Jun Wen, Yi Bo Wen, Xiang Fei He, Jun Wei Wu, Yan Wei Li, Zhong Jiang Han, Jin Jin Feng, Shao Hua Yan, Shou Lin Li, John Pfa Heesakkers, Wan Sheng Gao, Jian Guo Wen
AIMS: To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB). METHODS: Forty-two rats were assigned to the end-to-side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR...
November 21, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29160240/remapping-cortical-modulation-for-electrocorticographic-brain-computer-interfaces-a-somatotopy-based-approach-in-individuals-with-upper-limb-paralysis
#9
Alan D Degenhart, Shivayogi V Hiremath, Ying Yang, Stephen T Foldes, Jennifer L Collinger, Michael L Boninger, Elizabeth C Tyler-Kabara, Wei Wang
OBJECTIVE: Brain-computer interface (BCI) technology aims to provide individuals with paralysis a means to restore function. Electrocorticography (ECoG) uses disc electrodes placed on either the surface of the dura or the cortex to record field potential activity. ECoG has been proposed as a viable neural recording modality for BCI systems, potentially providing stable, long-term recordings of cortical activity with high spatial and temporal resolution. Previously we have demonstrated that a subject with spinal cord injury (SCI) could control an ECoG-based BCI system with up to three degrees of freedom [Wang et al...
November 21, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/29159834/linc00473-antagonizes-the-tumour-suppressor-mir-195-to-mediate-the-pathogenesis-of-wilms-tumour-via-ikk%C3%AE
#10
Shibo Zhu, Wen Fu, Liyu Zhang, Kai Fu, Jinhua Hu, Wei Jia, Guochang Liu
OBJECTIVES: Although dramatic improvements of overall survival has achieved in patients with favourable histology Wilms tumour, disease recurrence is still the main cause of cancer-related death in childhood. Long non-coding RNAs (lncRNAs) as oncogenes or tumour suppressors are dysregulated during carcinogenesis. However, the role of lncRNAs in the pathogenesis of Wilms tumour is unknown. Here, an lncRNA LINC00473 signature that functioned as oncogene was identified in Wilms tumour. METHODS: Wilms tumour (n = 15) and relative normal tissues were collected...
November 20, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29159830/erk5-plays-an-essential-role-in-gestational-beta-cell-proliferation
#11
Congde Chen, Suichun Wu, Xiaokun Lin, Dazhou Wu, Shane Fischbach, Xiangwei Xiao
OBJECTIVES: Restoring a functional beta-cell mass is a fundamental goal in treating diabetes. A complex signalling pathway network coordinates the regulation of beta-cell proliferation, although a role for ERK5 in this network has not been reported. This question was addressed in this study. MATERIALS AND METHODS: We studied the activation of extracellular-signal-regulated kinase 5 (ERK5) in pregnant mice, a well-known mouse model of increased beta-cell proliferation...
November 21, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29159825/modulation-of-the-intestinal-bile-acid-fxr-fgf15-axis-improves-alcoholic-liver-disease-in-mice
#12
Phillipp Hartmann, Katrin Hochrath, Angela Horvath, Peng Chen, Caroline T Seebauer, Cristina Llorente, Lirui Wang, Yazen Alnouti, Derrick E Fouts, Peter Stärkel, Rohit Loomba, Sally Coulter, Christopher Liddle, Ruth T Yu, Lei Ling, Stephen J Rossi, Alex M DePaoli, Michael Downes, Ronald M Evans, David A Brenner, Bernd Schnabl
Alcoholic liver disease is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to alcoholic liver disease. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an overrepresentation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29159800/effects-of-combined-helium-pre-post-conditioning-on-the-brain-and-heart-in-a-rat-resuscitation-model
#13
C Aehling, N C Weber, C J Zuurbier, B Preckel, R Galmbacher, K Stefan, M W Hollmann, E Popp, J Knapp
BACKGROUND: The noble gas helium induces cardio- and neuroprotection by pre- and post-conditioning. We investigated the effects of helium pre- and post-conditioning on the brain and heart in a rat resuscitation model. METHODS: After approval by the Animal Care Committee, 96 Wistar rats underwent cardiac arrest for 6 min induced by ventricular fibrillation. Animals received 70% helium and 30% oxygen for 5 min before cardiac arrest and for 30 min after restoration of spontaneous circulation (ROSC)...
November 20, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29159591/evaluation-of-the-associations-between-endothelial-dysfunction-inflammation-and-coagulation-in-crimean-congo-hemorrhagic-fever-patients
#14
Halef Okan Doğan, Seyit Ali Büyüktuna, Sercan Kapancik, Sevtap Bakir
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease. The aim of this study was to evaluate the association between inflammation, coagulation and endothelial dysfunction in CCHF. The study population consisted of 40 patients and 50 healthy controls. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), endocan, high sensitive C-reactive protein (hsCRP), international normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets values were determined in blood samples...
November 20, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29158841/autophagy-maintains-the-function-of-bone-marrow-mesenchymal-stem-cells-to-prevent-estrogen-deficiency-induced-osteoporosis
#15
Meng Qi, Liqiang Zhang, Yang Ma, Yi Shuai, Liya Li, Kefu Luo, Wenjia Liu, Yan Jin
Rationale: The impaired function of endogenous bone marrow mesenchymal stem cells (BMMSCs) is a determinant in the development of osteoporosis (OP). Recent researches have proved that autophagy plays an important role in maintenance of skeletal phenotype. However, whether autophagy affects the development of OP through regulating the function of BMMSCs remains elusive. Methods: Ovariectomy (OVX)-induced OP model and sham model were established in 8-week-old C57 mice. The differentiation and immunoregulation properties of BMMSCs from two models were examined by osteogenic/adipogenic induction in vitro and treatment of a dextran sulfate sodium (DSS)-induced mice colitis model in vivo...
2017: Theranostics
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#16
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29158637/marker-assisted-identification-of-restorer-gene-s-in-iso-cytoplasmic-restorer-lines-of-wa-cytoplasm-in-rice-and-assessment-of-their-fertility-restoration-potential-across-environments
#17
Amit Kumar, Prolay Kumar Bhowmick, Vikram Jeet Singh, Manoj Malik, Ashish Kumar Gupta, R Seth, M Nagarajan, S Gopala Krishnan, Ashok Kumar Singh
Iso-cytoplasmic restorers possess the same male sterile cytoplasm as the cytoplasmic male sterile (CMS) lines, thereby minimizing the potential cyto-nuclear conflict in the hybrids. Restoration of fertility of the wild abortive CMS is governed by two major genes namely, Rf3 and Rf4. Therefore, assessing the allelic status of these restorer genes in the iso-cytoplasmic restorers using molecular markers will not only help in estimating the efficiency of these genes either alone or in combination, in fertility restoration in the hybrids in different environments, but will also be useful in determining the efficacy of these markers...
October 2017: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/29158474/unc93b1-interacts-with-the-calcium-sensor-stim1-for-efficient-antigen-cross-presentation-in-dendritic-cells
#18
Sophia Maschalidi, Paula Nunes-Hasler, Clarissa R Nascimento, Ignacio Sallent, Valérie Lannoy, Meriem Garfa-Traore, Nicolas Cagnard, Fernando E Sepulveda, Pablo Vargas, Ana-Maria Lennon-Duménil, Peter van Endert, Thierry Capiod, Nicolas Demaurex, Guillaume Darrasse-Jèze, Bénédicte Manoury
Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158353/blood-pressure-control-by-a-secreted-fgfbp1-fibroblast-growth-factor-binding-protein
#19
Elena Tassi, En Yin Lai, Lingli Li, Glenn Solis, Yifan Chen, William E Kietzman, Patricio E Ray, Anna T Riegel, William J Welch, Christopher S Wilcox, Anton Wellstein
Fibroblast growth factors (FGFs) participate in organ development and tissue maintenance, as well as the control of vascular function. The paracrine-acting FGFs are stored in the extracellular matrix, and their release is controlled by a secreted FGF-binding protein (FGF-BP, FGFBP1, and BP1) that modulates FGF receptor signaling. A genetic polymorphism in the human FGFBP1 gene was associated with higher gene expression and an increased risk of familial hypertension. Here, we report on the effects of inducible BP1 expression in a transgenic mouse model...
November 20, 2017: Hypertension
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#20
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
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