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Qinghui Cheng, Zhi-Wen Hu, Katelynne E Doherty, Yuto J Tobin-Miyaji, Wei Qiang
Disruption of the synaptic plasma membrane (SPM) induced by the aggregation of β-amyloid (Aβ) peptides has been considered as a potential mechanism for the neurotoxicity of Aβ in Alzheimer's disease (AD). However, the molecular basis of such membrane disruption process remains unclear, mainly because of the severe systematic heterogeneity problem that prevents the high-resolution studies. Our previous studies using a two-component phosphatidylcholine (PC)/phosphatidylglycerol (PG) model liposome showed the presence of Aβ-induced membrane disruptions that were either on the pathway or off the pathway of fibril formation...
March 13, 2018: Biochimica et Biophysica Acta
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
Paul C Norris, Charles N Serhan
Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels...
March 7, 2018: Biochemical and Biophysical Research Communications
Ho Pan Sham, Katherine H Walker, Raja-Elie E Abdulnour, Nandini Krishnamoorthy, David N Douda, Paul C Norris, Ioanna Barkas, Sarah Benito-Figueroa, Jennifer K Colby, Charles N Serhan, Bruce D Levy
Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4 ), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and single Ig IL-1R-related molecule (SIGIRR)...
March 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Toshifumi Yamaguchi, Ken Kato, Kengo Nagashima, Satoru Iwasa, Yoshitaka Honma, Atsuo Takashima, Tetsuya Hamaguchi, Yoshinori Ito, Jun Itami, Narikazu Boku, Kazuhide Higuchi
BACKGROUND: While the standard treatment for stage II-III (non-T4) esophageal squamous cell carcinoma (ESCC) is neoadjuvant therapy followed by esophagectomy, definitive chemoradiation therapy (dCRT) is an option to treat ESCC patients who reject or may not tolerate surgical treatment. Second primary malignancy (SPM) is a problem for long-term survivors after achieving complete response (CR) by dCRT. METHODS: The source of the subjects in this study was the patients with stage II/III (excluding T4 disease) ESCC (UICC6th) who underwent dCRT from 2000 to 2011 at the National Cancer Center Hospital, Japan...
March 8, 2018: International Journal of Clinical Oncology
R Magliozzi, O W Howell, R Nicholas, C Cruciani, M Castellaro, C Romualdi, S Rossi, M Pitteri, M D Benedetti, A Gajofatto, F B Pizzini, S Montemezzi, S Rasia, R Capra, A Bertoldo, F Facchiano, S Monaco, R Reynolds, M Calabrese
OBJECTIVE: Grey matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in Multiple Sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS: To identify possible biomarkers linking meningeal inflammation, GM damage and disease severity, gene and protein expression were analysed in meninges and CSF from 27 post-mortem secondary progressive MS (SPMS) and 14 control cases...
March 8, 2018: Annals of Neurology
Zamzam Mahamud, Joachim Burman, Johan Zelano
BACKGROUND: The 2014 ILAE clinical definition of epilepsy allows diagnosis after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Multiple sclerosis (MS) carries an increased risk of epilepsy, but the risk after a first seizure is unknown. We aimed to investigate the risk of epilepsy in patients with MS who had suffered a first seizure. METHODS: We cross-referenced data from the Swedish MS-register with the national patient register for 15810 MS patients and 43635 controls and included 289 MS patients and 222 controls with a first diagnosis of seizure or status epilepticus (SE) without prior epilepsy or presumed symptomatic aetiology...
March 7, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Ganesh V Halade, Paul C Norris, Vasundhara Kain, Charles N Serhan, Kevin A Ingle
Inflammation promotes healing in myocardial infarction but, if unresolved, leads to heart failure. To define the inflammatory and resolving responses, we quantified leukocyte trafficking and specialized proresolving mediators (SPMs) in the infarcted left ventricle and spleen after myocardial infarction, with the goal of distinguishing inflammation from its resolution. Our data suggest that the spleen not only served as a leukocyte reservoir but also was the site where SPMs were actively generated after coronary ligation in mice...
March 6, 2018: Science Signaling
Giovanni Musso, Roberto Gambino, Maurizio Cassader, Elena Paschetta, Antonio Sircana
The resolution of necroinflammation and fibrosis remains a primary clinical target in nonalcoholic steatohepatitis (NASH), the most common chronic liver disease and a major cause of end-stage liver disease. Our understanding of the basic molecular mechanisms driving inflammation and fibrosis and their resolution in obesity-related conditions, including NASH, have led to the proposal of a novel, tractable therapeutic paradigm involving specialized proresolving mediators (SPMs), namely lipoxins (LXs), resolvins (Rvs), protectins (PDs), and maresins (MaRs)...
February 27, 2018: Trends in Pharmacological Sciences
Brian Wong, Jonathan Cahill, Syed Rizvi
Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease. The cause is unknown, but likely results from a combination of genetic predisposition and environmental exposures leading to autoimmune destruction of the brain and spinal cord. The most common phenotype of MS is relapsing-remitting (RRMS), characterized by episodes of neurological symptoms, typically lasting days to weeks, followed by symptom remission. After years of disease, the majority of RRMS cases transform into secondary progressive MS (SPMS), characterized by slowly worsening symptoms and progressive neurological disability, which may or may not be also accompanied by superimposed relapses...
March 1, 2018: Rhode Island Medical Journal
Carlos A M Silva, John T Belisle
The spectrum of clinical forms observed in leprosy and its pathogenesis are dictated by the host's immune response against Mycobacterium leprae , the etiological agent of leprosy. Previous results, based on metabolomics studies, demonstrated a strong relationship between clinical manifestations of leprosy and alterations in the metabolism of ω3 and ω6 polyunsaturated fatty acids (PUFAs), and the diverse set of lipid mediators derived from PUFAs. PUFA-derived lipid mediators provide multiple functions during acute inflammation, and some lipid mediators are able to induce both pro- and anti-inflammatory responses as determined by the cell surface receptors being expressed, as well as the cell type expressing the receptors...
2018: Frontiers in Immunology
Brita Kilburg-Basnyat, Sky W Reece, Miranda J Crouch, Bin Luo, Andria D Boone, Michael Yaeger, Myles Hodge, Christine Psaltis, Johanna L Hannan, Jonathan Manke, Michael L Armstrong, Nichole Reisdorph, Robert M Tighe, Saame Raza Shaikh, Kymberly M Gowdy
Exposure to ozone (O3) induces lung injury, pulmonary inflammation, and alters lipid metabolism. During tissue inflammation, specialized pro-resolving lipid mediators (SPMs) facilitate the resolution of inflammation. SPMs regulate the pulmonary immune response during infection and allergic asthma; however, the role of SPMs in O3-induced pulmonary injury and inflammation is unknown. We hypothesized that O3 exposure induces pulmonary inflammation by reducing SPMs. To evaluate this, male C57Bl/6J mice were exposed to filtered air (FA) or 1 ppm O3 for 3h and necropsied 24h after exposure...
February 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jaana Vuosku, Katja Karppinen, Riina Muilu-Mäkelä, Tomonobu Kusano, G H M Sagor, Komlan Avia, Emmi Alakärppä, Johanna Kestilä, Marko Suokas, Kaloian Nickolov, Leena Hamberg, Outi Savolainen, Hely Häggman, Tytti Sarjala
Background and Aims: Polyamines are small metabolites present in all living cells and play fundamental roles in numerous physiological events in plants. The aminopropyltransferases (APTs), spermidine synthase (SPDS), spermine synthase (SPMS) and thermospermine synthase (ACL5), are essential enzymes in the polyamine biosynthesis pathway. In angiosperms, SPMS has evolved from SPDS via gene duplication, whereas in gymnosperms APTs are mostly unexplored and no SPMS gene has been reported...
February 15, 2018: Annals of Botany
Asma Zaidi, Mercy Adewale, Lauren McLean, Paul Ramlow
The plasma membrane Ca 2+ -ATPase (PMCA) pumps play a critical role in the maintenance of calcium (Ca 2+ ) homeostasis, crucial for optimal neuronal function and cell survival. Loss of Ca 2+ homeostasis is a key precursor in neuronal dysfunction associated with brain aging and in the pathogenesis of neurodegenerative disorders. In this article, we review evidence showing age-related changes in the PMCAs in synaptic plasma membranes (SPMs) and lipid raft microdomains isolated from rat brain. Both PMCA activity and protein levels decline progressively with increasing age...
January 10, 2018: Neuroscience Letters
Violaine K Harris, James Stark, Tamara Vyshkina, Leslie Blackshear, Gloria Joo, Valentina Stefanova, Gabriel Sara, Saud A Sadiq
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system and is one of the leading causes of disability in young adults. Cell therapy is emerging as a therapeutic strategy to promote repair and regeneration in patients with disability associated with progressive MS. METHODS: We conducted a phase I open-label clinical trial investigating the safety and tolerability of autologous bone marrow mesenchymal stem cell-derived neural progenitor (MSC-NP) treatment in 20 patients with progressive MS...
February 3, 2018: EBioMedicine
Sara Vergel Posso, Nicolas Quesnot, João Alfredo Moraes, Lycia Brito-Gitirana, Emanuel Kennedy-Feitosa, Marina Valente Barroso, Luís Cristóvão Porto, Manuella Lanzetti, Samuel Santos Valença
Long-term exposure to cigarette smoke (CS) results in alveolar parenchyma destruction due to chronic inflammatory response and the imbalance between oxidants and antioxidants, and proteases and antiproteases. Emphysema is the main symptom of chronic obstructive pulmonary disease. Current treatment focuses on relieving respiratory symptoms, and inflammation resolution failure is an important pathophysiological element of the disease. Specialized pro-resolving mediators (SPMs) synthesized endogenously during resolution processes demonstrated beneficial effects in murine models of airway inflammation...
February 10, 2018: International Immunopharmacology
Burcu Zeydan, Xinyi Gu, Elizabeth J Atkinson, B Mark Keegan, Brian G Weinshenker, Jan-Mendelt Tillema, Daniel Pelletier, Christina J Azevedo, Christine Lebrun-Frenay, Aksel Siva, Darin T Okuda, Kejal Kantarci, Orhun H Kantarci
Objective: To assess whether cervical spinal cord atrophy heralds the onset of progressive MS. Methods: We studied 34 individuals with radiologically isolated syndrome (RIS) and 31 patients with relapsing-remitting MS (RRMS) age matched to 25 patients within a year of onset of secondary progressive MS (SPMS). Two raters independently measured (twice per rater) the cervical spinal cord average segmental area (CASA) (mm2 ) of axial T2-weighted images between C2 and C7 landmarks...
March 2018: Neurology® Neuroimmunology & Neuroinflammation
Lan-Yu Zhang, Ming-Rui Jia, Tao Sun
The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders...
February 8, 2018: Reviews in the Neurosciences
Ashwin Ganti, Max A Plitt, Edward C Kuan, Hannah N Kuhar, Pete S Batra, Bobby A Tajudeen
BACKGROUND: The 5-year overall survival rate for patients with sinonasal cancers has remained around 50% for the last 3 decades. Prior studies on head and neck cancers have suggested that 1 reason for poor survival is the frequent development of second primary malignancies (SPMs). The purpose of this study is to assess overall and site-specific risks of SPM following treatment of sinonasal malignancy. METHODS: A retrospective, population-based cohort study was performed on 2614 patients in the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with primary sinonasal malignancy between 1973 and 2014...
January 30, 2018: International Forum of Allergy & Rhinology
Korhan Buyukturkoglu, Lazar Fleyser, Desiree Byrd, Susan Morgello, Matilde Inglese
BACKGROUND AND PURPOSE: In this pilot study, we sought to investigate the pathological changes in the white matter (WM) of medically complex, combination antiretroviral therapy (cART)-treated patients with human immunodeficiency virus (HIV), comparing them to patients with long-standing, secondary progressive multiple sclerosis (SPMS). METHODS: Using diffusion kurtosis imaging (DKI)-derived WM tract integrity (WMTI) metrics, 15 HIV and 15 age- and sex-matched SPMS patients with similar disease duration underwent magnetic resonance imaging analysis...
January 30, 2018: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
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