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https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#1
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27924991/improving-cell-penetration-of-helical-peptides-stabilized-by-n-terminal-crosslinked-aspartic-acids
#2
Hui Zhao, Yanhong Jiang, Yuan Tian, Dan Yang, Xuan Qin, Zigang Li
Cell penetration and nucleus translocation efficiency are important for the cellular activities of peptide therapeutics. For helical peptides stabilized by N-terminal crosslinked aspartic acid, correlations between their penetration efficiency/nucleus translocation and physicochemical properties were studied. An increase in hydrophobicity and isoelectric point will promote cellular uptake and nucleus translocation of stabilized helices.
December 7, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27923655/development-of-a-novel-catalytic-amyloid-displaying-a-metal-dependent-atpase-like-activity
#3
Octavio Monasterio, Esteban Nova, Rodrigo Diaz-Espinoza
Amyloids are protein aggregates of highly regular structure that are involved in diverse pathologies such as Alzheimer's and Parkinson's disease. Recent evidence has shown that under certain conditions, small peptides can self-assemble into amyloids that exhibit catalytic reactivity towards certain compounds. Here we report a novel peptide with a sequence derived from the active site of RNA polymerase that displays hydrolytic activity towards ATP. The catalytic reaction proceeds in the presence of the divalent metal manganese and the products are ADP and AMP...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27923639/disruption-of-a-putative-intersubunit-electrostatic-bond-enhances-agonist-efficacy-at-the-human-%C3%AE-1-glycine-receptor
#4
Brian T Welsh, Jelena Todorovic, Dean Kirson, Hunter M Allen, Michelle D Bayly, S John Mihic
Partial agonists have lower efficacies than compounds considered 'full agonists', eliciting submaximal responses even at saturating concentrations. Taurine is a partial agonist at the glycine receptor (GlyR), a member of the cys-loop ligand-gated ion channel superfamily. The molecular mechanisms responsible for agonism are not fully understood but evidence suggests that efficacy at these receptors is determined by conformational changes that occur early in the process of receptor activation. We previously identified a residue located near the human α1 glycine binding site (aspartate-97; D97) that, when mutated to arginine (D97R), results in GlyR channels opening spontaneously with a high open probability, mimicking the effects of saturating glycine concentrations on wildtype GlyR...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923538/liver-enzymes-as-mediators-of-association-between-obesity-and-diabetes-the-guangzhou-biobank-cohort-study
#5
Lin Xu, Chao Qiang Jiang, Catherine Mary Schooling, Wei Sen Zhang, Kar Keung Cheng, Tai Hing Lam
PURPOSE: To assess the proportion of the association between obesity and diabetes mediated by liver enzymes such as gamma-glutamyltransferase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST). METHODS: Mediation analysis was used with adjustment for age, education, physical activity, smoking, and alcohol use. RESULTS: A total of 9748 participants from Phase III of the Guangzhou Biobank Cohort Study were recruited in 2006-2008...
November 20, 2016: Annals of Epidemiology
https://www.readbyqxmd.com/read/27922872/18f-fluorodeoxyglucose-uptake-in-anti-n-methyl-d-aspartate-receptor-encephalitis-associated-with-an-immature-teratoma
#6
Ryusuke Nakamoto, Yuji Nakamoto, Takayoshi Ishimori, Yasutaka Fushimi, Kaori Togashi
We report a case of anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis associated with an immature teratoma developed in a 38-year-old woman. Positron emission tomography (PET) revealed focal intense uptake of F-fluorodeoxyglucose in an area of the brain corresponding to the right medial temporal lobe as well as an intrapelvic tumor. After the PET examination, the patient complained of disorientation and short-term memory loss. The ovarian tumor was resected and diagnosed as an immature teratoma. The cerebrospinal fluid analysis was positive for anti-NMDAR antibody...
December 3, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27922762/nonchemotherapy-drug-induced-agranulocytosis-in-children-detected-by-a-prospective-pharmacovigilance-program
#7
Nicolás Medrano-Casique, Hoi Y Tong, Alberto M Borobia, Antonio J Carcas, Jesús Frías, Elena Ramírez
OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA...
December 6, 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27922000/membrane-pyrophosphatases-from-thermotoga-maritima-and-vigna-radiata-suggest-a-conserved-coupling-mechanism
#8
Kun-Mou Li, Craig Wilkinson, Juho Kellosalo, Jia-Yin Tsai, Tommi Kajander, Lars J C Jeuken, Yuh-Ju Sun, Adrian Goldman
Membrane-bound pyrophosphatases (M-PPases), which couple proton/sodium ion transport to pyrophosphate synthesis/hydrolysis, are important in abiotic stress resistance and in the infectivity of protozoan parasites. Here, three M-PPase structures in different catalytic states show that closure of the substrate-binding pocket by helices 5-6 affects helix 13 in the dimer interface and causes helix 12 to move down. This springs a 'molecular mousetrap', repositioning a conserved aspartate and activating the nucleophilic water...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921428/-promising-molecules-for-treatment-of-hyperglycemia-in-patients-with-type-2-diabetes
#9
Milan Kvapil
New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that "better" the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide)...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27921402/developing-a-rat-model-of-dilated-cardiomyopathy-with-improved-survival
#10
Li-Juan Shen, Shu Lu, Yong-Hua Zhou, Lan Li, Qing-Min Xing, Yong-Liang Xu
To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27921110/multifunctional-pei-entrapped-gold-nanoparticles-enable-efficient-delivery-of-therapeutic-sirna-into-glioblastoma-cells
#11
Lingdan Kong, Jieru Qiu, Wenjie Sun, Jia Yang, Mingwu Shen, Lu Wang, Xiangyang Shi
RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells...
December 6, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27921022/the-protective-effect-of-hydro-alcoholic-extract-of-mangrove-avicennia-marina-l-leaves-on-kidney-injury-induced-by-carbon-tetrachloride-in-male-rats
#12
Naser Mirazi, Seyedeh-Nahid Movassagh, Mahmoud Rafieian-Kopaei
BACKGROUND: Materials can cause liver and kidney damage which carbon tetrachloride is one of these substances. Medicinal plants and their essential oils and extracts have been used to a large extent as drugs to better control and management of kidney diseases. OBJECTIVES: The aim of this study was to investigate the effect of hydro-alcoholic extract of Avicennia marina leaves in the treatment of renal toxicity induced by carbon tetrachloride. METHODS: Forty-two male rats were randomly divided into 6 groups (n = 7): control (taking normal saline, 0...
October 2016: Journal of Nephropathology
https://www.readbyqxmd.com/read/27920977/neurochemical-changes-in-patients-with-chronic-low-back-pain-detected-by-proton-magnetic-resonance-spectroscopy-a-systematic-review
#13
REVIEW
Xianjing Zhao, Maosheng Xu, Kristen Jorgenson, Jian Kong
BACKGROUND: Low back pain is a highly prevalent health problem around the world, affecting 50% to 85% of people at some point in life. The purpose of this systematic review is to summarize the previous proton magnetic resonance spectroscopy studies on brain chemical changes in patients with chronic low back pain (CLBP). METHODS: We identified relevant studies from a literature search of PubMed and EMBASE from 1980 to March 2016. Data extraction was performed on the subjects' characteristics, MRS methods, spectral analyses, cerebral metabolites and perceptual measurements...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27920819/co-administration-of-metformin-and-n-acetylcysteine-with-dietary-control-improves-the-biochemical-and-histological-manifestations-in-rats-with-non-alcoholic-fatty-liver
#14
Naglaa Mohamed El-Lakkany, Sayed Hassan Seif El-Din, Abdel-Nasser Abdel-Aal Sabra, Olfat Ali Hammam, Fatma Abdel-Latif Ebeid
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27920803/bone-pain-mechanism-in-osteoporosis-a-narrative-review
#15
REVIEW
Consalvo Mattia, Flaminia Coluzzi, Ludovica Celidonio, Renato Vellucci
Bone pain in elderly people dramatically affects their quality of life, with osteoporosis being the leading cause of skeletal related events. Peripheral and central mechanisms are involved in the pathogenesis of the nervous system sensitization. Osteoporosis in the elderly has been associated with increased density of bone sensory nerve fibers and their pathological modifications, together with an over-expression of nociceptors sensitized by the lowering pH due to the osteoclastic activity. The activation of N-methyl-D-aspartate (NMDA) receptors and the microglia, as a response to a range of pathological conditions, represent the leading cause of central sensitization...
May 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/27920479/ceruloplasmin-a-reliable-marker-of-fibrosis-in-chronic-hepatitis-b-virus-patients-with-normal-or-minimally-raised-alanine-aminotransferase
#16
Da-Wu Zeng, Jing Dong, Jia-Ji Jiang, Yue-Yong Zhu, Yu-Rui Liu
AIM: To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin (CP) levels and liver fibrosis in chronic hepatitis B (CHB) patients with normal or minimally raised alanine aminotransferase (ALT). METHODS: Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group (n = 97) and a validation group (n = 96)...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#17
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919830/newly-acquired-and-reactivated-contextual-fear-memories-are-more-intense-and-prone-to-generalize-after-activation-of-prelimbic-cortex-nmda-receptors
#18
Ana C Vanvossen, Marina A M Portes, Rafael Scoz-Silva, Hugo B Reichmann, Cristina A J Stern, Leandro J Bertoglio
Activity in the rodent prelimbic (PL) cortex contributes to consolidation, retrieval and reconsolidation of learned fear. The PL cortex is considered homologous to the primate dorsal anterior cingulate cortex (dACC). In patients with post-traumatic stress disorder (PTSD), the dACC is often reported to be hyperactive after acquisition and/or around the retrieval of the traumatic memory. It is still unknown, however, whether there is a relationship between altered dACC functioning at these time points and PTSD-associated behavioral outcomes, such as fear overgeneralization...
December 2, 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27919740/metabolic-differences-between-cold-stored-and-machine-perfused-porcine-kidneys-a-1-h-nmr-based-study
#19
Jay Nath, Tom B Smith, Kamlesh Patel, Sam R Ebbs, Alex Hollis, Daniel A Tennant, Christian Ludwig, Andrew R Ready
Hypothermic machine perfusion (HMP) and static cold storage (SCS) are the two methods used to preserve deceased donor kidneys prior to transplant. This study seeks to characterise the metabolic profile of HMP and SCS porcine kidneys in a cardiac death donor model. Twenty kidneys were cold flushed and stored for two hours following retrieval. Paired kidneys then underwent 24 h of HMP or SCS or served as time zero controls. Metabolite quantification in both storage fluid and kidney tissue was performed using one dimensional (1)H NMR spectroscopy...
December 2, 2016: Cryobiology
https://www.readbyqxmd.com/read/27919056/autoimmune-choreas
#20
REVIEW
Francisco Cardoso
Chorea, a movement disorder characterised by a continuous flow of unpredictable muscle contractions, has a myriad of genetic and non-genetic causes. Although autoimmune processes are rare aetiology of chorea, they are relevant both for researchers and clinicians. The aim of this article is to provide a review of the epidemiology, clinical and laboratory features, pathogenesis and management of the most common autoimmune causes of chorea. Emphasis is given particularly to Sydenham's chorea, systemic lupus erythematosus, primary antiphospolipid antibody syndrome, paraneoplastic chorea and anti-N-methyl-d-aspartate receptor encephalitis...
December 1, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
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