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https://www.readbyqxmd.com/read/29244194/arid5a-stabilizes-ox40-mrna-in-murine-cd4-t-cells-by-recognizing-a-stem-loop-structure-in-its-3-utr
#1
Hamza Hanieh, Kazuya Masuda, Hozaifa Metwally, Jaya P Chalise, Maged Mohamed, Kishan K Nyati, Daron M Standley, Songling Li, Mitsuru Higa, Mohammad M Zaman, Tadamitsu Kishimoto
AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remains unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4+ T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation...
December 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29242722/recent-progress-in-the-development-of-tspo-pet-ligands-for-neuroinflammation-imaging-in-neurological-diseases
#2
REVIEW
Md Maqusood Alam, Jihye Lee, Sang-Yoon Lee
Neuroinflammation is heavily associated with various neurological diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke. It is strongly characterized by the activation of microglia which can be visualized using position emission tomography (PET). Traditionally, translocator protein 18 kDa (TSPO) has been the preferred target for imaging the inflammatory progression of the microglial component. TSPO is expressed in the outer mitochondrial membrane and present in very low concentrations in the healthy human brain, but is markedly upregulated in response to brain injury and inflammation...
December 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29242274/sema4d-plexinb1-inhibition-ameliorates-blood-brain-barrier-damage-and-improves-outcome-after-stroke-in-rats
#3
Yi-Fan Zhou, Ya-Nan Li, Hui-Juan Jin, Jie-Hong Wu, Quan-Wei He, Xu-Xia Wang, Hao Lei, Bo Hu
The inflammatory process in stroke is the major contributor to blood-brain barrier (BBB) breakdown. Previous studies indicated that semaphorin 4D (Sema4D), an axon guidance molecule, initiated inflammatory microglial activation and disrupted endothelial function in the CNS. However, whether Sema4D disrupts BBB integrity after stroke remains unclear. To study the effect of Sema4D on BBB disruption in stroke, rats were subjected to transient middle cerebral artery occlusion and targeted injection of lentivirus-mediated clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene disruption of PlexinB1...
December 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29239076/allogeneic-hematopoietic-stem-cell-transplantation-is-associated-with-cure-and-durable-remission-of-late-onset-primary-isolated-central-nervous-system-hemophagocytic-lymphohistiocytosis
#4
Sajad Khazal, Veronika Polishchuk, Gary Soffer, Samantha Prinzing, Jonathan Gill, Kris M Mahadeo
Primary isolated CNS presentation of HLH is exceedingly rare and typically associated with significant morbidity and mortality. We describe an adolescent patient with late-onset, primary isolated CNS HLH and a compound heterozygous PRF1 mutation (c50delT (p.L17 fs); c.1229G>C (p.R410P)), not previously reported with this phenotype. He was successfully treated with allogeneic HSCT following a reduced-intensity conditioning regimen, despite a high pre-HSCT comorbidity index. Two years after transplant, he is alive and in disease remission...
December 13, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29238967/potent-anti-inflammatory-and-pro-resolving-effects-of-anabasum-in-a-human-model-of-self-resolving-acute-inflammation
#5
Madhur P Motwani, Frances Bennett, Paul C Norris, Alexander A Maini, Marc J George, Justine Newson, Alice Henderson, Adrian J Hobbs, Mark Tepper, Barbara White, Charles N Serhan, Raymond MacAllister, Derek W Gilroy
Anabasum is a synthetic analogue of Δ8 - tetrahydrocannabinol (THC)-11-oic acid that in pre-clinical models of experimental inflammation exerts potent anti-inflammatory actions with minimal CNS cannabimimetic activity. Here we used a novel model of acute inflammation driven by i.d. UV-killed E. coli in healthy humans and found that Anabasum (5mg) exerted a potent anti-inflammatory effect equivalent to that of prednisolone in terms of inhibiting neutrophil infiltration, the hallmark of acute inflammation. These effects arose from the inhibition of the neutrophil chemoattractant LTB4 , while the inhibition of anti-phagocytic prostanoids (PGE2 , TxB2 and PGF2 α) resulted in enhanced clearance of inflammatory stimulus from the injected site...
December 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29238350/differentiation-and-transmigration-of-cd4-t-cells-in-neuroinflammation-and-autoimmunity
#6
REVIEW
Sandip Ashok Sonar, Girdhari Lal
CD4+ T cells play a central role in orchestrating protective immunity and autoimmunity. The activation and differentiation of myelin-reactive CD4+ T cells into effector (Th1 and Th17) and regulatory (Tregs) subsets at the peripheral tissues, and their subsequent transmigration across the blood-brain barrier (BBB) into the central nervous system (CNS) parenchyma are decisive events in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. How the Th1, Th17, and regulatory Tregs transmigrate across the BBB into the CNS and cause CNS inflammation is not clearly understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29237803/anti-tumor-activity-of-entrectinib-a-pan-trk-ros1-and-alk-inhibitor-in-etv6-ntrk3-positive-acute-myeloid-leukemia
#7
Kristen M Smith, Patrick C Fagan, Elena Pomari, Giuseppe Germano, Chiara Frasson, Colin Walsh, Ian M Silverman, Paolo Bonvini, Gang Li
Activation of tropomyosin receptor kinase (TRK) family tyrosine kinases by chromosomal rearrangement has been shown to drive a wide range of solid tumors and hematologic malignancies. TRK fusions are actionable targets as evidenced by recent clinical trial results in solid tumors. Entrectinib (RXDX-101) is an investigational, orally available, CNS-active, highly potent and selective kinase inhibitor against TRKA/B/C, ROS1 and ALK kinase activities. Here, we demonstrate that TRK kinase inhibition by entrectinib selectively targets preclinical models of TRK fusion-driven hematologic malignancies...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29237388/crigler-najjar-syndrome-current-perspectives-and-the-application-of-clinical-genetics
#8
Ammar Ebrahimi, Fakher Rahim
Crigler-Najjar syndrome (CNS, OMIM: 218800) is the paradigm of an inborn error of metabolism and a rare genetic disease with an estimated incidence of 0.6-1.0 per million live births. Discrimination between CNS subtypes is usually done on the basis of the clinical criteria, such as response to phenobarbital treatment and other molecular and functional characteristics. The identification of four novel pathogenic mutations and the analysis of residual activity of missense in UGT1A1 gene are useful for clinical diagnosis, and may reveal a new insight in enzyme activity, whereas the identification of pathogenic mutations will accelerate genetic counseling for newly identified CNS patients...
December 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29237087/type-frequency-and-spatial-distribution-of-immune-cell-infiltrates-in-cns-germinomas-evidence-for-inflammatory-and-immunosuppressive-mechanisms
#9
Pia Zapka, Evelyn Dörner, Verena Dreschmann, Noriaki Sakamato, Glen Kristiansen, Gabriele Calaminus, Christian Vokuhl, Ivo Leuschner, Torsten Pietsch
Central nervous system germinomas are characterized by a massive immune cell infiltrate. We systematically characterized these immune cells in 28 germinomas by immunophenotyping and image analysis. mRNA expression was analyzed by Nanostring technology and in situ RNA hybridization. Tumor infiltrating lymphocytes (TILs) were composed of 61.8% ± 3.1% (mean ± SE) CD3-positive T cells, including 45.2% ± 3.5% of CD4-positive T-helper cells, 23.4% ± 1.5% of CD8-positive cytotoxic T cells, 5.5% ± 0...
December 11, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29236326/knockdown-of-ski-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#10
Xin Zhao, Kai-Sheng Zhou, Zhong-Hao Li, Wei Nan, Jing Wang, Ya-Yi Xia, Hai-Hong Zhang
Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236237/outcome-of-children-and-adolescents-with-central-nervous-system-tumors-in-phase-i-trials
#11
Fernando Carceller, Francisco Bautista, Irene Jiménez, Raquel Hladun-Álvaro, Cécile Giraud, Luca Bergamaschi, Madhumita Dandapani, Isabelle Aerts, François Doz, Didier Frappaz, Michela Casanova, Bruce Morland, Darren R Hargrave, Gilles Vassal, Andrew D J Pearson, Birgit Geoerger, Lucas Moreno, Lynley V Marshall
Central nervous system (CNS) tumors are a leading cause of death in pediatric oncology. New drugs are desperately needed to improve survival. We evaluated the outcome of children and adolescents with CNS tumors participating in phase I trials within the Innovative Therapies for Children with Cancer (ITCC) consortium. Patients with solid tumors aged < 18 years at enrollment in their first dose-finding trial between 2000 and 2014 at eight ITCC centers were included retrospectively. Survival was evaluated using univariate/multivariate analyses...
December 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29234527/sphingosine-1-phosphate-receptor-1-modulates-cntf-induced-axonal-growth-and-neuroprotection-in-the-mouse-visual-system
#12
Sandrine Joly, Deniz Dalkara, Vincent Pernet
The lack of axonal regeneration and neuronal cell death causes permanent neurological deficits in the injured CNS. Using the classical CNS injury model of optic nerve crush in mice, ciliary neurotrophic factor (CNTF) was found to stimulate retinal ganglion cell (RGC) survival and axonal growth, but in an incomplete fashion. The elucidation of molecular mechanisms impairing CNTF-induced axonal regeneration is paramount to promote visual recovery. In the present study, we sought to evaluate the contribution of sphingosine 1-phosphate receptor 1 (S1PR1) to the neuroprotective and regenerative effects of CNTF...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29234443/psychotropic-effects-of-an-alcoholic-extract-from-the-leaves-of-albizia-zygia-leguminosae-mimosoideae
#13
Patrick Amoateng, Dorcas Osei-Safo, Kennedy Kwami Edem Kukuia, Samuel Adjei, Obed Awintuma Akure, Constance Agbemelo-Tsomafo, Shirley Nyarko Adu-Poku, Kenneth Yaw Agyeman-Badu
Background: Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia (AZE) may possess antipsychotic and antidepressant properties. Method: The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234384/screening-of-natural-bioactive-metabolites-and-investigation-of-antioxidant-antimicrobial-antihyperglycemic-neuropharmacological-and-cytotoxicity-potentials-of-litsea-polyantha-juss-ethanolic-root-extract
#14
Nripendra Nath Biswas, Amit Kumar Acharzo, Shams Anamika, Shamsunnahar Khushi, Bishwajit Bokshi
This study was designed to identify some bioactive phytochemicals from ethanolic extract of roots of Litsea polyantha and to evaluate some of its pharmacological activities. Phytochemical tests indicated the presence of reducing sugar, combined reducing sugar, tannins, flavonoids, alkaloids, terpenoids, and phenol. In the antioxidant assay using 2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging method, the IC50 value was found to be 82.31 μg/mL. Total content of phenolic compounds, flavonoid, and tannin was found to be 152...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234010/loss-of-the-molecular-clock-in-myeloid-cells-exacerbates-t-cell-mediated-cns-autoimmune-disease
#15
Caroline E Sutton, Conor M Finlay, Mathilde Raverdeau, James O Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A J O'Neill, Kingston H G Mills, Annie M Curtis
The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE)...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29231805/understanding-host-parasite-relationship-the-immune-central-nervous-system-microenvironment-and-its-effect-on-brain-infections
#16
Laura Adalid-Peralta, Brenda Sáenz, Gladis Fragoso, Graciela Cárdenas
The central nervous system (CNS) has been recognized as an immunologically specialized microenvironment, where immune surveillance takes a distinctive character, and where delicate neuronal networks are sustained by anti-inflammatory factors that maintain local homeostasis. However, when a foreign agent such as a parasite establishes in the CNS, a set of immune defences is mounted and several immune molecules are released to promote an array of responses, which ultimately would control the infection and associated damage...
December 12, 2017: Parasitology
https://www.readbyqxmd.com/read/29229703/orai1-plays-a-crucial-role-in-central-sensitization-by-modulating-neuronal-excitability
#17
Yannong Dou, Jingsheng Xia, Ruby Gao, Xinghua Gao, Frances M Munoz, Dongyu Wei, Yuzhen Tian, James E Barrett, Seena Ajit, Olimpia Meucci, James W Putney, Yue Dai, Huijuan Hu
Pathological pain is a common and debilitating condition that is often poorly managed. Central sensitization is an important mechanism underlying pathological pain. However, candidate molecules involved in central sensitization remain unclear. Store-operated calcium channels (SOCs) mediate important calcium signals in non-excitable and excitable cells. SOCs have been implicated in a wide variety of human pathophysiological conditions including immunodeficiency, occlusive vascular diseases and cancer. However, the role of SOCs in central nervous system (CNS) disorders has been relatively unexplored...
December 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29228979/contrasting-effect-of-the-latency-reversing-agents-bryostatin-1-and-jq1-on-astrocyte-mediated-neuroinflammation-and-brain-neutrophil-invasion
#18
Alizé Proust, Corinne Barat, Mathieu Leboeuf, Jean Drouin, Michel J Tremblay
BACKGROUND: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. METHODS: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29228131/synaptic-potentiation-at-basal-and-apical-dendrites-of-hippocampal-pyramidal-neurons-involves-activation-of-a-distinct-set-of-extracellular-and-intracellular-molecular-cues
#19
Patrycja Brzdak, Olga Wójcicka, Monika Zareba-Koziol, Daniel Minge, Christian Henneberger, Jakub Wlodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
In the central nervous system, several forms of experience-dependent plasticity, learning and memory require the activity-dependent control of synaptic efficacy. Despite substantial progress in describing synaptic plasticity, mechanisms related to heterogeneity of synaptic functions at local circuits remain elusive. Here we studied the functional and molecular aspects of hippocampal circuit plasticity by analyzing excitatory synapses at basal and apical dendrites of mouse hippocampal pyramidal cells (CA1 region) in acute brain slices...
December 8, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29227527/m2-muscarinic-receptor-activation-inhibits-cell-proliferation-and-migration-of-rat-adipose-mesenchymal-stem-cells
#20
Roberta Piovesana, Simona Melfi, Mario Fiore, Valerio Yi, Ada Maria Tata
Mesenchymal stem cells (MSCs), also known as stromal mesenchymal stem cells, are multipotent cells, which can be found in many tissues and organs as bone marrow, adipose tissue and other tissues. In particular MSCs derived from Adipose tissue (ADSCs) are the most frequently used in regenerative medicine because they are easy to source, rapidly expandable in culture and excellent differentiation potential into adipocytes, chondrocytes and other cell types. Acetylcholine (ACh), is one of the most important neurotransmitter in central (CNS) and peripheral nervous system (PNS), playing important roles also in non-neural tissue, but its functions in MSCs are still not investigated...
December 11, 2017: Journal of Cellular Physiology
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