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https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#1
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29141824/inhibition-of-neurogenesis-in-a-case-of-marburg-variant-multiple-sclerosis
#2
Celia Oreja-Guevara, Ulises Gómez-Pinedo, Julia García-López, Rafael Sánchez-Sánchez, Roberto Valverde-Moyano, Alberto Rabano-Gutierrez, Jordi A Matías-Guiu, Ines González-Suárez, Jorge Matías-Guiu
INTRODUCTION: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS. METHODS: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29138679/modulatory-mechanism-of-polyphenols-and-nrf2-signaling-pathway-in-lps-challenged-pregnancy-disorders
#3
REVIEW
Tarique Hussain, Bie Tan, Gang Liu, Ghulam Murtaza, Najma Rahu, Muhammad Saleem, Yulong Yin
Early embryonic loss and adverse birth outcomes are the major reproductive disorders that affect both human and animals. The LPS induces inflammation by interacting with robust cellular mechanism which was considered as a plethora of numerous reproductive disorders such as fetal resorption, preterm birth, teratogenicity, intrauterine growth restriction, abortion, neural tube defects, fetal demise, and skeletal development retardation. LPS-triggered overproduction of free radicals leads to oxidative stress which mediates inflammation via stimulation of NF-κB and PPARγ transcription factors...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29134111/periodontitis-induced-by-bacterial-infection-exacerbates-features-of-alzheimer-s-disease-in-transgenic-mice
#4
Naoyuki Ishida, Yuichi Ishihara, Kazuto Ishida, Hiroyuki Tada, Yoshiko Funaki-Kato, Makoto Hagiwara, Taslima Ferdous, Mohammad Abdullah, Akio Mitani, Makoto Michikawa, Kenji Matsushita
Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29132542/impact-of-inflammation-on-the-blood-neural-barrier-and-blood-nerve-interface-from-review-to-therapeutic-preview
#5
Stephen D Skaper
A number of nervous system disorders are characterized by a state of inflammation (neuroinflammation) in which members of the innate immune system, most notably mast cells and microglia-acting as single entities and in unison-produce inflammatory molecules that play major roles. A neuroinflammatory environment can weaken not only blood-nerve and blood-brain barrier (BBB) integrity but also that of the blood-spinal cord barrier. Mast cells, with their distribution in peripheral nerves and the central nervous system, are positioned to influence blood-nerve barrier characteristics...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29126071/%C3%AE-lipoic-acid-improves-abnormal-behavior-by-mitigation-of-oxidative-stress-inflammation-ferroptosis-and-tauopathy-in-p301s-tau-transgenic-mice
#6
Yan-Hui Zhang, Da-Wei Wang, Shuang-Feng Xu, Shuai Zhang, Yong-Gang Fan, Ying-Ying Yang, Shi-Qi Guo, Shan Wang, Tian Guo, Zhan-You Wang, Chuang Guo
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs) composed of Tau protein. α-Lipoic acid (LA) has been found to stabilize the cognitive function of AD patients, and animal study findings have confirmed its anti-amyloidogenic properties. However, the underlying mechanisms remain unclear, especially with respect to the ability of LA to control Tau pathology and neuronal damage. Here, we found that LA supplementation effectively inhibited the hyperphosphorylation of Tau at several AD-related sites, accompanied by reduced cognitive decline in P301S Tau transgenic mice...
November 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/29125499/mast-cells-in-the-brain%C3%A2-old-cells-new-target
#7
Giovanna Traina
Mast cells (MCs) are mainly known for their involvement on allergic reactions through degranulation and release of vasoactive, inflammatory and nociceptive mediators. Upon encountering an allergen, MCs are first responders, true sensors of the environment, actually they respond to a wide range of "danger" signals both immunological and non-immunological in rapid and selective manner. They secrete both preformed and newly synthesized mediators acting as effectors in relationship between nervous, vascular and immune systems...
November 7, 2017: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/29118502/bilateral-sensorineural-hearing-loss-secondary-to-sympathetic-ophthalmia-in-a-human-leukocyte-antigen-a2-positive-patient
#8
Konstantinos T Tsaousis, Vasileios E Konidaris, Theodoros Empeslidis
We report a case of sympathetic ophthalmia 1 month following trauma in a 71-year-old immunocompetent female patient of Indian origin. The patient was hospitalized with signs and symptoms of meningism, ataxia, and neurosensory deafness. We explore and provide further clinical evidence in supporting the hypothesis of antigen cross-reactivity derived from tissues with common neural crest embryological background such as the uvea and cells of the labyrinth. The patient was human leukocyte antigen-A2 positive and treatment with oral steroids and cyclosporine has managed to have favorable results and control the inflammation...
September 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/29117499/preclinical-chorioamnionitis-dysregulates-cxcl1-cxcr2-signaling-throughout-the-placental-fetal-brain-axis
#9
REVIEW
Tracylyn R Yellowhair, Shahani Noor, Jessie R Maxwell, Christopher V Anstine, Akosua Y Oppong, Shenandoah Robinson, Erin D Milligan, Lauren L Jantzie
In the United States, perinatal brain injury (PBI) is a major cause of infant mortality and childhood disability. For a large proportion of infants with PBI, central nervous system (CNS) injury begins in utero with inflammation (chorioamnionitis/CHORIO) and/or hypoxia-ischemia. While studies show CHORIO contributes to preterm CNS injury and is also a common independent risk factor for brain injury in term infants, the molecular mechanisms mediating inflammation in the placental-fetal-brain axis that result in PBI remain a gap in knowledge...
November 5, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29110213/correction-to-neuroimmune-response-in-ischemic-preconditioning
#10
Ashley McDonough, Jonathan R Weinstein
Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Toll-like receptors and type 1 interferons. Brain ischemia results in release of pro- and anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammatory response, resolution of inflammation, and transition to neurological recovery and regeneration...
November 6, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29102164/soy-isoflavone-genistein-attenuates-lipopolysaccharide-induced-cognitive-impairments-in-the-rat-via-exerting-anti-oxidative-and-anti-inflammatory-effects
#11
Seyed-Mohamad-Sadegh Mirahmadi, Alireza Shahmohammadi, Ali-Mohammad Rousta, Mohammad-Reza Azadi, Javad Fahanik-Babaei, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer's and Parkinson's diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory, anti-oxidative, and protective properties. In this research study, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated...
October 25, 2017: Cytokine
https://www.readbyqxmd.com/read/29098642/oxidation-induced-increase-in-photoreactivity-of-bovine-retinal-lipid-extract
#12
A Koscielniak, M Serafin, M Duda, T Oles, A Zadlo, A Broniec, O Berdeaux, S Gregoire, L Bretillon, T Sarna, A Pawlak
The mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species...
November 2, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29093707/add-on-pyridostigmine-enhances-cd4-t-cell-recovery-in-hiv-1-infected-immunological-non-responders-a-proof-of-concept-study
#13
Sergio I Valdés-Ferrer, José C Crispín, Pablo F Belaunzarán-Zamudio, Carlos A Rodríguez-Osorio, Bernardo Cacho-Díaz, Jorge Alcocer-Varela, Carlos Cantú-Brito, Juan Sierra-Madero
Background: In human immunodeficiency virus (HIV)-infection, persistent T-cell activation leads to rapid turnover and increased cell death, leading to immune exhaustion and increased susceptibility to opportunistic infections. Stimulation of the vagus nerve increases acetylcholine (ACh) release and modulates inflammation in chronic inflammatory conditions, a neural mechanism known as the cholinergic anti-inflammatory pathway (CAP). Pyridostigmine (PDG), an ACh-esterase inhibitor, increases the half-life of endogenous ACh, therefore mimicking the CAP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29081002/minocycline-directly-enhances-the-self-renewal-of-adult-neural-precursor-cells
#14
Anri Kuroda, Takahiro Fuchigami, Satoshi Fuke, Natsu Koyama, Kazuhiro Ikenaka, Seiji Hitoshi
Minocycline not only has antibacterial action but also produces a variety of pharmacological effects. It has drawn considerable attention as a therapeutic agent for symptoms caused by inflammation in many neurological disorders, leading to several clinical trials. Although some of these effects are mediated through its function of suppressing microglial activation, it is not clear whether minocycline acts on other cell types in the adult brain. In this study, we utilized a colony-forming neurosphere assay, in which neural stem cells (NSCs) clonally proliferate to form floating colonies, called neurospheres...
October 28, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29080525/neuroprotection-through-flavonoid-enhancement-of-the-glyoxalase-pathway
#15
Joel R Frandsen, Prabagaran Narayanasamy
The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal...
October 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/29064422/systemic-interleukin-4-administration-after-spinal-cord-injury-modulates-inflammation-and-promotes-neuroprotection
#16
Rui Lima, Susana Monteiro, José P Lopes, Pedro Barradas, Natália L Vasconcelos, Eduardo D Gomes, Rita C Assunção-Silva, Fábio G Teixeira, Mónica Morais, Nuno Sousa, António J Salgado, Nuno A Silva
Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, but also at shaping the immune response in order to protect, repair and promote regeneration of spared neural tissue. One of those promising strategies is the intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to promote a phenotype on specific immune cells associated with neuroprotection and repair...
October 24, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29060071/a-pilot-study-of-planar-coil-based-magnetic-stimulation-using-acute-hippocampal-slice-in-mice
#17
H J Park, H K Kang, M Wang, J Jo, E Chung, S Kim
Micromagnetic stimulation using small-sized implantable coils has recently been studied. The main advantage of this method is that it can provide sustainable stimulation performance even if a fibrotic encapsulation layer is formed around the implanted coil by inflammation response, because indirectly induced currents are used to induce neural responses. In previous research, we optimized the geometrical and control parameters used in implantable magnetic stimulation. Based on those results, we fabricated the planar coil and studied the LTP effect in the hippocampal slice by two different magnetic stimulation protocols using the quadripulse stimulation (QPS) pattern...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29058702/direction-of-leukocyte-polarization-and-migration-by-the-phosphoinositide-transfer-protein-tipe2
#18
Svetlana A Fayngerts, Zhaojun Wang, Ali Zamani, Honghong Sun, Amanda E Boggs, Thomas P Porturas, Weidong Xie, Mei Lin, Terry Cathopoulis, Jason R Goldsmith, Anastassios Vourekas, Youhai H Chen
The polarization of leukocytes toward chemoattractants is essential for the directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity after encountering chemical gradients is not well understood. We found here that leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for phosphoinositide second messengers. TIPE2 functioned as a local enhancer of phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase Rac, which promoted trailing-edge polarization...
December 2017: Nature Immunology
https://www.readbyqxmd.com/read/29055361/the-pathophysiology-of-dry-eye-disease-what-we-know-and-future-directions-for-research
#19
REVIEW
Stephen C Pflugfelder, Cintia S de Paiva
Clinical and laboratory studies performed over the past few decades have discovered that dry eye is a chronic inflammatory disease that can be initiated by numerous extrinsic or intrinsic factors that promote an unstable and hyperosmolar tear film. These changes in tear composition, in some cases combined with systemic factors, lead to an inflammatory cycle that causes ocular surface epithelial disease and neural stimulation. Acute desiccation activates stress signaling pathways in the ocular surface epithelium and resident immune cells...
November 2017: Ophthalmology
https://www.readbyqxmd.com/read/29053743/in-vitro-modeling-of-experimental-succinic-semialdehyde-dehydrogenase-deficiency-ssadhd-using-brain-derived-neural-stem-cells
#20
Kara R Vogel, Garrett R Ainslie, Erwin E Jansen, Gajja S Salomons, Jean-Baptiste Roullet, K Michael Gibson
We explored the utility of neural stem cells (NSCs) as an in vitro model for evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase-deficient (SSADHD) mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH). Multiple parameters were evaluated including: (1) production of GHB (γ-hydroxybutyrate), the biochemical hallmark of SSADHD; (2) rescue from cell death with the dual mTOR (mechanistic target of rapamycin) inhibitor, XL-765, an agent previously shown to rescue aldh5a1-/- mice from premature lethality; (3) mitochondrial number, total reactive oxygen species, and mitochondrial superoxide production, all previously documented as abnormal in aldh5a1-/- mice; (4) total ATP levels and ATP consumption; and (5) selected gene expression profiles associated with epilepsy, a prominent feature in both experimental and human SSADHD...
2017: PloS One
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