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https://www.readbyqxmd.com/read/28726057/macrophage-migration-inhibitory-factor-mif-modulates-trophic-signaling-through-interaction-with-serine-protease-htra1
#1
Åsa Fex Svenningsen, Svenja Löring, Anna Lahn Sørensen, Ha Uyen Buu Huynh, Simone Hjæresen, Nellie Martin, Jesper Bonnet Moeller, Maria Louise Elkjær, Uffe Holmskov, Zsolt Illes, Malin Andersson, Solveig Beck Nielsen, Eirikur Benedikz
Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cellular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the serine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF...
July 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28724943/aim2-inflammasome-mediated-pyroptosis-in-enterovirus-a71-infected-neuronal-cells-restricts-viral-replication
#2
Thinesshwary Yogarajah, Kien Chai Ong, David Perera, Kum Thong Wong
Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724779/chronic-pain-alters-spatiotemporal-activation-patterns-of-forearm-muscle-synergies-during-the-development-of-grip-force
#3
Nagarajan Manickaraj, Leanne M Bisset, Venkata S P T Devanaboyina, Justin J Kavanagh
It is largely unknown how the CNS regulates multiple muscle systems in the presence of pain. This study used muscle synergy analysis to investigate multiple forearm muscles in individuals with chronic elbow pain during the development of grip force. Eleven individuals with chronic elbow pain and 11 healthy age-matched controls developed grip force to 15% and 30% of MVC. Surface EMG was obtained from six forearm muscles during force development before non-negative matrix factorization was performed. The relationship between muscle synergies and standard clinical tests of elbow pain were examined using linear regression...
July 19, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28722336/evidence-for-the-modulation-of-nociception-in-mice-by-central-mast-cells
#4
C L Kissel, K J Kovács, A A Larson
BACKGROUND: Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. METHODS: We examined the central effect of two hyperalgesic compounds that induce mast cell degranulation and of stabilized mast cells using cromolyn. RESULTS: Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1-17) (opioid compound) each correlated with the per cent of thalamic mast cells that were degranulated...
July 19, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28721049/the-potential-role-of-vagus-nerve-stimulation-in-the-treatment-of-hiv-associated-depression-a-review-of-literature
#5
REVIEW
William C Nicholson, Mirjam-Colette Kempf, Linda Moneyham, David E Vance
Depression is the most common comorbidity and neuropsychiatric complication in HIV. Estimates suggest that the prevalence rate for depression among HIV-infected individuals is three times that of the general population. The association between HIV and clinical depression is complex; however, chronic activation of inflammatory mechanisms, which disrupt central nervous system (CNS) function, may contribute to this association. Disruptions in CNS function can result in cognitive disorders, social withdrawal, fatigue, apathy, psychomotor impairment, and sleep disturbances, which are common manifestations in depression and HIV alike...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28721014/determining-optimal-dosing-regimen-of-oral-administration-of-dicloxacillin-using-monte-carlo-simulation
#6
Wei Yu, Jinru Ji, Tingting Xiao, Chaoqun Ying, Jiaheng Fang, Ping Shen, Yonghong Xiao
BACKGROUND: Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and low level of toxicity. The objective of this study was to obtain optimal dosing regimen of oral administration of dicloxacillin by analyzing the pharmacokinetic (PK) index in healthy volunteers and in vitro antibacterial activity by using Monte Carlo simulation. MATERIALS AND METHODS: A total of 867 clinical isolates from community-onset infections were collected from 31 secondary hospitals in People's Republic of China...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28719951/neuronal-apoptosis-pathological-basis-of-behavioral-dysfunctions-induced-by-angiostrongylus-cantonensis-in-rodents-model
#7
Shiqi Luo, Lisi OuYang, Jie Wei, Feng Wu, Zhongdao Wu, Wanlong Lei, Dongjuan Yuan
Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted...
June 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28719178/the-therapeutic-role-and-drug-delivery-potential-of-neuroinflammation-as-a-target-in-neurodegenerative-disorders
#8
Abhijeet Singh, Ankit Chokriwal, Madan Mohan Sharma, Devendra Jain, Juhi Saxena, Bjorn John Stephen
Neuroinflammation, the condition associated with the hyper activity of immune cells within the CNS (central nervous system) has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the Blood Brain Barrier for the delivery of drugs...
July 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28718326/cns-anticancer-drug-discovery-and-development-2016-conference-insights
#9
Victor A Levin, Lauren E Abrey, Timothy P Heffron, Peter J Tonge, Arvin C Dar, William A Weiss, James M Gallo
CNS Anticancer Drug Discovery and Development November 2016, AZ, USA The 2016 second CNS Anticancer Drug Discovery and Development Conference addressed diverse viewpoints about why new drug discovery/development focused on CNS cancers has been sorely lacking. Despite more than 70,000 individuals in the USA being diagnosed with a primary brain malignancy and 151,669-286,486 suffering from metastatic CNS cancer, in 1999, temozolomide was the last drug approved by the US FDA as an anticancer agent for high-grade gliomas...
July 18, 2017: CNS Oncology
https://www.readbyqxmd.com/read/28717866/mir-30a-positively-regulates-the-inflammatory-response-of-microglia-in-experimental-autoimmune-encephalomyelitis
#10
Xue Fang, Dingya Sun, Zhihong Wang, Zhongwang Yu, Weili Liu, Yingyan Pu, Dan Wang, Aijun Huang, Mingdong Liu, Zhenghua Xiang, Cheng He, Li Cao
Multiple sclerosis (MS) is a classical inflammatory demyelinating disease of the central nervous system (CNS). Microglia are the main resident immune cells in the CNS and are closely associated with the pathogenesis of MS. In the present study, we found that miR-30a was highly expressed in jellyfish-like microglia in chronic active lesions of MS patients, as well as in the microglia of mice with experimental autoimmune encephalomyelitis (EAE) at the chronic phase. In vitro, the conditioned supernatant of mouse microglia overexpressing miR-30a promoted the apoptosis of oligodendrocyte precursor cells (OPCs), and inhibited OPC differentiation...
July 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28716943/visualizing-context-dependent-calcium-signaling-in-encephalitogenic-t-cells-in-vivo-by-two-photon-microscopy
#11
Nikolaos I Kyratsous, Isabel J Bauer, Guokun Zhang, Marija Pesic, Ingo Bartholomäus, Marsilius Mues, Ping Fang, Miriam Wörner, Stephanie Everts, Joachim W Ellwart, Joanna M Watt, Barry V L Potter, Reinhard Hohlfeld, Hartmut Wekerle, Naoto Kawakami
In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716624/mitochondrial-aminoacyl-trna-synthetases-in-human-disease
#12
REVIEW
Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue...
July 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28716552/is-heterotopic-ossification-getting-nervous-the-role-of-the-peripheral-nervous-system-in-heterotopic-ossification
#13
Eleanor L Davis, Alan R Davis, Zbigniew Gugala, Elizabeth A Olmsted-Davis
Heterotopic ossification (HO), or de novo bone formation in soft tissue, is often observed following traumatic injury. Recent studies suggest that peripheral nerves may play a key functional role in this process. The results supporting a neurological basis for HO are examined in this article. Evidence supports the fact that BMPs released from bone matrix possess the capacity to induce HO. However, the process cannot be recapitulated using recombinant proteins without extremely high doses suggesting other components are required for this process...
July 14, 2017: Bone
https://www.readbyqxmd.com/read/28716263/exogenous-acrolein-intensifies-sensory-hypersensitivity-after-spinal-cord-injury-in-rat
#14
Breanne Butler, Glen Acosta, Riyi Shi
Acrolein, an α,β-unsaturated aldehyde associated with oxidative stress, is also a major toxic component of tobacco cigarette smoke, which has been reported in the clinic to coincide with the exacerbation of neuropathic pain after SCI. Previous reports have shown that acrolein involvement in spinal cord injury (SCI) is crucial to the development and persistence of neuropathic pain. Through the activation and upregulation of the transient receptor protein ankyrin-1 (TRPA1) cation channel, acrolein is capable of sensitizing the central nervous system in the acute and chronic stages of SCI...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715006/substitution-reactions-of-iron-ii-carbamoyl-thioether-complexes-related-to-mono-iron-hydrogenase
#15
Zhu-Lin Xie, Gummadi Durgaprasad, Azim K Ali, Michael J Rose
A C,N,S pincer complex has been synthesized for structural modeling of the organometallic active site of mono-[Fe] hydrogenase (HMD). The C,N,S chelate allows for systematic investigation of the substitution reactions of CO and other exogenous X/L-type ligands, as well as examination of the exact roles of the Fe-carbamoyl and {Fe(CO)2}(2+) units in stabilizing the low-spin Fe(ii) center. Reaction of the 'apo-ligand' 6-(2-(methylthio)phenyl)pyridin-2-amine ((H2N)N(py)S(Me)) with [Fe(CO)4(Br)2] affords the organometallic complex [((O[double bond, length as m-dash])C(NH)N(py)S(Me))Fe(CO)2(Br)] (1)...
July 17, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28714865/microglia-in-prion-diseases
#16
Adriano Aguzzi, Caihong Zhu
Prion diseases are a group of progressive and fatal neurodegenerative disorders characterized by deposition of scrapie prion protein (PrPSc) in the CNS. This deposition is accompanied by neuronal loss, spongiform change, astrogliosis, and conspicuous microglial activation. Here, we argue that microglia play an overall neuroprotective role in prion pathogenesis. Several microglia-related molecules, such as Toll-like receptors (TLRs), the complement system, cytokines, chemokines, inflammatory regulators, and phagocytosis mediators, are involved in prion pathogenesis...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713781/the-metalloprotease-mpr1-engages-annexina2-to-promote-the-transcytosis-of-fungal-cells-across-the-blood-brain-barrier
#17
Sarisa Na Pombejra, Michelle Salemi, Brett S Phinney, Angie Gelli
Eukaryotic pathogens display multiple mechanisms for breaching the blood-brain barrier (BBB) and invading the central nervous system (CNS). Of the fungal spp., that cause disease in mammals, only some cross brain microvascular endothelial cells which constitute the BBB, and invade the brain. Cryptococcus neoformans, the leading cause of fungal meningoencephalitis, crosses the BBB directly by transcytosis or by co-opting monocytes. We previously determined that Mpr1, a secreted fungal metalloprotease, facilitates association of fungal cells to brain microvascular endothelial cells and we confirmed that the sole expression of CnMPR1 endowed S...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28713283/excitatory-modulation-of-the-preb%C3%A3-tzinger-complex-inspiratory-rhythm-generating-network-by-endogenous-hydrogen-sulfide
#18
Glauber S F da Silva, João P J Sabino, Vishaal Rajani, Tucaauê S Alvares, Silvia Pagliardini, Luiz G S Branco, Gregory D Funk
Hydrogen Sulfide (H2S) is one of three gasotransmitters that modulate excitability in the CNS. Global application of H2S donors or inhibitors of H2S synthesis to the respiratory network has suggested that inspiratory rhythm is modulated by exogenous and endogenous H2S. However, effects have been variable, which may reflect that the RTN/pFRG (retrotrapezoid nucleus, parafacial respiratory group) and the preBötzinger Complex (preBötC, critical for inspiratory rhythm generation) are differentially modulated by exogenous H2S...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28713245/multifaceted-roles-of-metzincins-in-cns-physiology-and-pathology-from-synaptic-plasticity-and-cognition-to-neurodegenerative-disorders
#19
REVIEW
Patrycja Brzdak, Daria Nowak, Grzegorz Wiera, Jerzy W Mozrzymas
The extracellular matrix (ECM) and membrane proteolysis play a key role in structural and functional synaptic plasticity associated with development and learning. A growing body of evidence underscores the multifaceted role of members of the metzincin superfamily, including metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs), A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs) and astacins in physiological and pathological processes in the central nervous system (CNS)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28713239/increased-white-matter-inflammation-in-aging-and-alzheimer-s-disease-brain
#20
Divya Raj, Zhuoran Yin, Marjolein Breur, Janine Doorduin, Inge R Holtman, Marta Olah, Ietje J Mantingh-Otter, Debby Van Dam, Peter P De Deyn, Wilfred den Dunnen, Bart J L Eggen, Sandra Amor, Erik Boddeke
Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis...
2017: Frontiers in Molecular Neuroscience
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