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https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#1
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
February 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#2
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28212172/cognitive-decline-associated-with-anesthesia-and-surgery-in-the-elderly-does-this-contribute-to-dementia-prevalence
#3
Lisbeth Evered, David A Scott, Brendan Silbert
PURPOSE OF REVIEW: To provide an update on the current state of research investigating the effects of anesthesia and surgery on cognition in the elderly, including consideration of overlap with cognitive disorders in the community. RECENT FINDINGS: The studies reviewed here identify detrimental effects of anesthesia and surgery on cognition in a proportion of elderly individuals. Animal models demonstrate an association between anesthetic agents and Alzheimer's disease pathology...
February 15, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28211497/the-inflammatory-cytokine-tnf-%C3%AE-promotes-the-premature-senescence-of-rat-nucleus-pulposus-cells-via-the-pi3k-akt-signaling-pathway
#4
Pei Li, Yibo Gan, Yuan Xu, Lei Song, Liyuan Wang, Bin Ouyang, Chengmin Zhang, Qiang Zhou
Premature senescence of nucleus pulposus (NP) cells and inflammation are two common features of degenerated discs. This study investigated the effects of the inflammatory cytokine TNF-α on the premature senescence of NP cells and the molecular mechanism behind this process. Rat NP cells were cultured with or without different concentrations of TNF-α for 1 and 3 days. The inhibitor LY294002 was used to determine the role of the PI3K/Akt pathway. NP cells that were incubated with TNF-α for 3 days followed by 3 days of recovery in the control medium were used to analyze cellular senescence...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209347/high-resolution-mass-spectrometry-based-method-applicable-for-a-wide-range-of-3-hydroxy-3-methyl-glutaryl-coenzyme-a-reductase-inhibitors-in-blood-serum-including-intermediates-and-products-of-the-cholesterol-biosynthetic-pathway
#5
Vít Kosek, Milena Stránská, Marie Fenclová, Tomáš Ruml, Libor Vítek, Jana Hajšlová
Statins belong to the major class of hypolipidemic drugs. They act as competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway. This inhibition not only leads to the depletion of cholesterol and its fatty acid esters, but also to the depletion of the intermediates of this metabolic pathway (mainly pyrophosphates), which can play an important role in tumor proliferation. The aim of the current study was to establish a versatile multi-analyte method capable of quantitative determination of various currently-used statins, together with free cholesterol (FC), cholesterol esters (CEs), and some key intermediates of the mevalonate pathway occurring in human serum...
January 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28199829/preclinical-efficacy-failure-of-human-cns-derived-stem-cells-for-use-in-the-pathway-study-of%C3%A2-cervical-spinal-cord-injury
#6
Aileen J Anderson, Katja M Piltti, Mitra J Hooshmand, Rebecca A Nishi, Brian J Cummings
We previously showed the efficacy of multiple research cell lines (RCLs) of human CNS neural stem cells (HuCNS-SCs) in mouse and rat models of thoracic spinal cord injury (SCI), supporting a thoracic SCI clinical trial. Experts recommend in vivo preclinical testing of the intended clinical cell lot/line (CCL) in models with validity for the planned clinical target. We therefore tested the efficacy of two HuCNS-SC lines in cervical SCI: one RCL, and one CCL intended for use in the Pathway Study of cervical SCI in man...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28197342/the-function-of-fgfr1-signalling-in-the-spinal-cord-therapeutic-approaches-using-fgfr1-ligands-after-spinal-cord-injury
#7
REVIEW
Barbara Haenzi, Lawrence D F Moon
Extensive research is ongoing that concentrates on finding therapies to enhance CNS regeneration after spinal cord injury (SCI) and to cure paralysis. This review sheds light on the role of the FGFR pathway in the injured spinal cord and discusses various therapies that use FGFR activating ligands to promote regeneration after SCI. We discuss studies that use peripheral nerve grafts or Schwann cell grafts in combination with FGF1 or FGF2 supplementation. Most of these studies show evidence that these therapies successfully enhance axon regeneration into the graft...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28197190/electroacupuncture-induces-acute-changes-in-cerebral-cortical-mirna-profile-improves-cerebral-blood-flow-and-alleviates-neurological-deficits-in-a-rat-model-of-stroke
#8
Hai-Zhen Zheng, Wei Jiang, Xiao-Feng Zhao, Jing Du, Pan-Gong Liu, Li-Dan Chang, Wen-Bo Li, Han-Tong Hu, Xue-Min Shi
Electroacupuncture has been shown to improve cerebral blood flow in animal models of stroke. However, it is unclear whether electroacupuncture alters miRNA expression in the cortex. In this study, we examined changes in the cerebral cortical miRNA profile, cerebral blood flow and neurological function induced by electroacupuncture in a rat model of stroke. Electroacupuncture was performed at Renzhong (GV26) and Neiguan (PC6), with a frequency of 2 Hz, continuous wave, current intensity of 3.0 mA, and stimulation time of 1 minute...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28197177/two-step-production-of-monoamines-in-monoenzymatic-cells-in-the-spinal-cord-a-different-control-strategy-of-neurotransmitter-supply
#9
REVIEW
Mengliang Zhang
Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28195036/gsk-3%C3%AE-inhibition-induced-neuroprotection-regeneration-and-functional-recovery-after-intracerebral-hemorrhagic-stroke
#10
Yingying Zhao, Zheng Zachory Wei, James Ya Zhang, Yongbo Zhang, Soonmi Won, Jinmei Sun, Shan Ping Yu, Jimei Li, Ling Wei
Hemorrhagic stroke is a devastating disease that lacks effective therapies. In the present investigation, we tested 6-bromoindirubin-3'-oxime (BIO) as a selective glycogen synthase kinase-3β (GSK-3β) inhibitor in a mouse model of intracerebral hemorrhage (ICH). ICH was induced by injection of collagenase IV into the striatum of 8 to 10-week old C57BL/6 mice. BIO (8 µg/kg, i.p.) was administered following either an acute delivery (0 - 2 hr delay) or a prolonged regimen (every 48 hrs starting at 3 days postICH)...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28194448/divergent-relationships-between-fecal-microbiota-and-metabolome-following-distinct-antibiotic-induced-disruptions
#11
Jocelyn M Choo, Tokuwa Kanno, Nur Masirah Mohd Zain, Lex E X Leong, Guy C J Abell, Julie E Keeble, Kenneth D Bruce, A James Mason, Geraint B Rogers
The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice...
January 2017: MSphere
https://www.readbyqxmd.com/read/28193779/combination-targeted-therapy-to-disrupt-aberrant-oncogenic-signaling-and-reverse-epigenetic-dysfunction-in-idh2-and-tet2-mutant-acute-myeloid-leukemia
#12
Alan H Shih, Cem Meydan, Kaitlyn Shank, Francine E Garrett-Bakelman, Patrick S Ward, Andrew Intlekofer, Abbas Nazir, Eytan Stein, Kristina Knapp, Jacob Glass, Jeremy Travins, Kim Straley, Camelia Gliser, Chris Mason, Katharine Yen, Craig B Thompson, Ari Melnick, Ross L Levine
Genomic studies in acute myeloid leukemias (AML) have identified mutations which drive altered DNA methylation, including TET2 and IDH2. Here we show that models of AMLs resulting from TET2 or IDH2 mutations combined with FLT3ITD mutations are sensitive to 5-Azacytidine or to the IDH2 inhibitor AG-221, respectively. 5-Azacytidine and AG-221 treatment induced an attenuation of aberrant DNA methylation and transcriptional output, and resulted in a reduction in leukemic blasts consistent with anti-leukemic activity...
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193481/epigenetic-and-transcriptomic-regulation-of-lung-repair-during-recovery-from-influenza-infection
#13
Derek A Pociask, Keven M Robinson, Kong Chen, Kevin J McHugh, Michelle E Clay, Grace T Huang, Panayiotis V Benos, Yvonne M W Janssen-Heininger, Jay K Kolls, Vikas Anathy, John F Alcorn
Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection...
February 9, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28193192/taking-care-of-oneself-by-regaining-control-a-key-to-continue-living-four-to-five-decades-after-a-suicide-attempt-in-severe-depression
#14
Lisa Crona, Margaretha Stenmarker, Agneta Öjehagen, Ulrika Hallberg, Louise Brådvik
BACKGROUND: Depression is a strong risk factor for suicide and suicide attempt. Several studies have examined the pathway to suicide attempt, but few studies have considered aspects important for overcoming being suicidal. The aim of the present study was to examine personal strategies to continue living after a suicide attempt. METHODS: A qualitative grounded theory approach was used. Thirteen former inpatients diagnosed with severe depression (1956-1969) participated in a follow-up 42-56 years after their last suicide attempt, which occurred between the ages of 21 and 45...
February 13, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28192833/energy-systems-contribution-in-the-running-based-anaerobic-sprint-test
#15
F Milioni, A M Zagatto, R A Barbieri, V L Andrade, J W Dos Santos, C A Gobatto, A S R da Silva, P R P Santiago, M Papoti
The aims of the present study were to verify the contributions of the energy systems during repeated sprints with a short recovery time and the associations of the time- and power-performance of repeated sprints with energetic contributions and aerobic and anaerobic variables. 13 healthy men performed the running-based anaerobic sprint test (RAST) followed by an incremental protocol for lactate minimum intensity determination. During the RAST, the net energy system was estimated using the oxygen consumption and the blood lactate responses...
February 13, 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28191609/complement-blockade-in-anca-associated-vasculitis-an-index-case-current-concepts-and-future-perspectives
#16
REVIEW
Lucio Manenti, Maria Letizia Urban, Federica Maritati, Maricla Galetti, Augusto Vaglio
Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery...
February 13, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28186990/ube2l6-ubch8-and-isg15-attenuate-autophagy-in-esophageal-cancer-cells
#17
Chloe M Falvey, Tracey R O'Donovan, Shereen El-Mashed, Michelle J Nyhan, Seamus O'Reilly, Sharon L McKenna
Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186165/netrin-1-improves-functional-recovery-through-autophagy-regulation-by-activating-the-ampk-mtor-signaling-pathway-in-rats-with-spinal-cord-injury
#18
Liangjie Bai, Xifan Mei, Zhaoliang Shen, Yunlong Bi, Yajiang Yuan, Zhanpeng Guo, Hongyu Wang, Haosen Zhao, Zipeng Zhou, Chen Wang, Kunming Zhu, Gang Li, Gang Lv
Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28185844/evaluation-of-various-glyphosate-concentrations-on-dna-damage-in-human-raji-cells-and-its-impact-on-cytotoxicity
#19
Michelle Townsend, Connor Peck, Wei Meng, Matthew Heaton, Richard Robison, Kim O'Neill
Glyphosate is a highly used active compound in agriculturally based pesticides. The literature regarding the toxicity of glyphosate to human cells has been highly inconsistent. We studied the resulting DNA damage and cytotoxicity of various glyphosate concentrations on human cells to evaluate DNA damaging potential. Utilizing human Raji cells, DNA damage was quantified using the comet assay, while cytotoxicity was further analyzed using MTT viability assays. Several glyphosate concentrations were assessed, ranging from 15 mM to 0...
February 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28183374/experiences-of-codeine-use-misuse-and-dependence-application-of-liese-and-franz-s-cognitive-developmental-model-of-substance-abuse
#20
Marie Claire Van Hout, Ian Norman, Eileen Rich, Michael Bergin
BACKGROUND: Misuse of codeine-containing medicines is an emerging public health issue. AIMS: We present the application of Liese and Franz's (1996) cognitive developmental model of substance abuse to the trajectory from legitimate codeine use for pain, towards that of therapeutic and other forms of misuse, and physical and psychological dependence. It illustrates a cognitive behavioural analysis of the experiences of codeine misusers - which 'surfaces' the specific beliefs, thoughts, emotions and behaviours of this group of hidden codeine dependent individuals, who are distinct and unique from other opioid-dependent cohorts...
February 10, 2017: Behavioural and Cognitive Psychotherapy
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