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https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#1
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212503/lactobacillus-buchneri-s-layer-as-carrier-for-an-ara-h-2-derived-peptide-for-peanut-allergen-specific-immunotherapy
#2
Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced...
February 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28212442/ecto-5-nucleotidase-cd73-nt5e-vitamin-d-receptor-and-fgf23-gene-polymorphisms-may-play-a-role-in-the-development-of-calcific-uremic-arteriolopathy-in-dialysis-patients-data-from-the-german-calciphylaxis-registry
#3
Hansjörg Rothe, Vincent Brandenburg, Margot Haun, Barbara Kollerits, Florian Kronenberg, Markus Ketteler, Christoph Wanner
INTRODUCTION: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. METHODS: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD)...
2017: PloS One
https://www.readbyqxmd.com/read/28212403/cerebrospinal-fluid-biomarkers-of-infantile-congenital-hydrocephalus
#4
David D Limbrick, Brandon Baksh, Clinton D Morgan, Gakwaya Habiyaremye, James P McAllister, Terrie E Inder, Deanna Mercer, David M Holtzman, Jennifer Strahle, Michael J Wallendorf, Diego M Morales
INTRODUCTION: Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value...
2017: PloS One
https://www.readbyqxmd.com/read/28212318/alcohol-%C3%A2-adipose%C3%A2-tissue%C3%A2-and%C3%A2-lipid%C3%A2-dysregulation
#5
Jennifer L Steiner, Charles H Lang
Chronic alcohol consumption perturbs lipid metabolism as it increases adipose tissue lipolysis and leads to ectopic fat deposition within the liver and the development of alcoholic fatty liver disease. In addition to the recognition of the role of adipose tissue derived fatty acids in liver steatosis, alcohol also impacts other functions of adipose tissue and lipid metabolism. Lipid balance in response to long-term alcohol intake favors adipose tissue loss and fatty acid efflux as lipolysis is upregulated and lipogenesis is either slightly decreased or unchanged...
February 16, 2017: Biomolecules
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#6
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211606/nrf2-a-novel-therapeutic-target-in-fragile-x-syndrome-is-modulated-by-nnz2566
#7
Robert M J Deacon, Michael J Hurley, Camila Martínez Rebolledo, Mike Snape, Francisco J Altimiras, Leandro Farías, Michael Pino, Rodolfo Biekofsky, Larry Glass, Patricia Cogram
Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autism. Progress in basic neuroscience has led to identification of molecular targets for treatment in FXS; however, there is a gap in translation to targeted therapies in humans. The present study introduces a novel therapeutic target for FXS: nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor known to induce expression of over 100 cytoprotective genes...
February 17, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#8
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211304/granisetron-and-carvedilol-can-protect-experimental-rats-againstadjuvant-induced-arthritis
#9
Yasmin Moustafa Ahmed, Basim Anwar Shehata Messiha, Ali Ahmed Abo-Saif
CONTEXT: Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications. OBJECTIVE: We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT3 receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats...
April 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28211138/nocturnal-autonomic-nervous-system-activity-and-morning-proinflammatory-cytokines-in-young-adult-african-americans
#10
Kimberly A Bell, Ihori Kobayashi, Yuanxiu Chen, Thomas A Mellman
Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C-reactive protein (CRP) and interleukin (IL)-6. Ninety-four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening...
February 17, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28211103/impaired-learning-and-memory-in-rats-induced-by-a-high-fat-diet-involvement-with-the-imbalance-of-nesfatin-1-abundance-and-copine-6-expression
#11
Zheng Chen, Ya-Yun Xu, Rui Wu, Yin-Xiu Han, Yue Yu, Jin-Fang Ge, Fei-Hu Chen
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and the behavior was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST), and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique...
February 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28210980/molecular-mechanisms-of-ire1%C3%AE-ask1-pathway-reactions-to-unfolded-protein-response-in-drn-neurons-of-post-traumatic-stress-disorder-rats
#12
Fanzhen Kong, Fang Han, Yanhao Xu, Yuxiu Shi
The goal of this study was to further elucidate the molecular mechanisms of post-traumatic stress disorder (PTSD) pathogenesis and to provide experimental evidence for new drug targets for effective PTSD treatment. Expression changes of IRE1α, ASK1, and other downstream molecules of the IRE1α-ASK1 endoplasmic reticulum stress (ERS) signaling pathway were investigated. JNK, P38, CHOP, Bcl-2, and Bax were analyzed at both protein and mRNA levels of dorsal raphe nucleus (DRN) neurons of PTSD rats. The rat PTSD model was established via the single-prolonged stress (SPS) method...
February 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28210976/regenerative-medicine-for-parkinson-s-disease-using-differentiated-nerve-cells-derived-from-human-buccal-fat-pad-stem-cells
#13
Haruka Takahashi, Hiroshi Ishikawa, Akira Tanaka
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks...
February 16, 2017: Human Cell
https://www.readbyqxmd.com/read/28210955/the-effects-of-igf-1-on-tnf-%C3%AE-treated-drg-neurons-by-modulating-atf3-and-gap-43-expression-via-pi3k-akt-s6k-signaling-pathway
#14
Lei Zhang, Yaping Yue, Meishuo Ouyang, Huaxiang Liu, Zhenzhong Li
Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28210912/inhibitory-effects-of-emodin-thymol-and-astragalin-on-leptospira-interrogans-induced-inflammatory-response-in-the-uterine-and-endometrium-epithelial-cells-of-mice
#15
Wenlong Zhang, Xiaojie Lu, Wei Wang, Zhuang Ding, Yunhe Fu, Xiaofei Zhou, Naisheng Zhang, Yongguo Cao
Leptospirosis is a systemic infection that causes, among others, acute kidney injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and reproductive loss. In an effort to reduce uterine inflammatory responses induced by Leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and astragalin in a mouse model. Our results showed that treatment with emodin, thymol, and astragalin alleviated uterine inflammation induced by leptospira infection via suppression of pro-inflammatory cytokine expression and prevented tissue damage...
February 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28210876/effect-of-hyperhomocysteinemia-on-redox-balance-and-redox-defence-enzymes-in-ischemia-reperfusion-injury-and-or-after-ischemic-preconditioning-in-rats
#16
Martin Petráš, Anna Drgová, Mária Kovalská, Zuzana Tatarková, Barbara Tóthová, Oľga Križanová, Ján Lehotský
Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0...
February 16, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28210620/association-of-ptpn22-haplotypes-1123g-c-1858c-t-with-rheumatoid-arthritis-in-western-mexican-population
#17
Yeniley Ruiz-Noa, Jorge Ramón Padilla-Gutiérrez, Jorge Hernández-Bello, Claudia Azucena Palafox-Sánchez, Yeminia Valle, Edith Oregón-Romero, Ana Laura Pereira-Suárez, Ana Guilaisne Bernard-Medina, José Francisco Muñoz-Valle
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (-1123G>C and +1858C>T) at PTPN22 gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28210568/clozapine-induced-hypersensitivity-myocarditis-presenting-as-sudden-cardiac-death
#18
Natraj Katta, Sudarshan Balla, Kul Aggarwal
Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia...
October 2016: Autopsy & case reports
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#19
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#20
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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