Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors.

Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors. Int Immunopharmacol. 2015 Mar 10;25(2):528-537 Authors: Xu Z, Wu J, Zheng J, Ma H, Zhang H, Zhen X, Zheng LT, Zhang X Abstract Neuroinflammation is involved in the process of several central nervous system (CNS) diseases such as Parkinson's disease, Alzheimer's disease, ischemia and multiple sclerosis. As the macrophages in the central nervous system, microglial cell function in the innate immunity of the brain and are largely responsible for the inflammation-mediated neurotoxicity. Prevention of microglia activation might alleviate neuronal damage and degeneration under the inflammatory conditions, and therefore, represents a possible therapeutic approach to the aforementioned CNS diseases. Here we report the synthesis of a number of non-steroidal anti-inflammatory drug (NSAID) conjugates, and the evaluation of their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and primary mouse microglial cells. Among the tested analogues, compounds 8 and 11 demonstrated potent inhibition of nitric oxide production with no or weak cell toxicity. Compound 8 also significantly suppressed the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, cyclooxygenase (COX)-2 as well as inducible nitric oxide synthase (iNOS) in LPS-stimulated BV-2 microglial cells. Further mechanistic stud...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research

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Authors: Edman MC, Janga SR, Kakan SS, Okamoto CT, Freire D, Feigenbaum D, Lew M, Hamm-Alvarez SF Abstract Tears are a known source of biomarkers for both ocular and systemic diseases with particular advantages; specifically, the noninvasiveness of sample collection and a unique and increasingly better-defined protein composition. Here, we discuss our rationale for use of tears for discovery of biomarkers for Parkinson's disease (PD). These reasons include literature supporting changes in tear flow and composition in PD, and the interconnections between the ocular surface system and neurons affected in PD. We highl...
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
ConclusionsBased on these results, we suggest that DSS play a positive effective role in increasing DHA content by up-regulating iPLA2 and 15-LOX, resulting in ameliorating oxidative stress and inflammation and finally ameliorating cognition deficits in APP/PS1 mice.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS The results indicate that, although persons with disabilities can exhibit a wide functional range, they remain at risk of PUs and should be evaluated for proper preventive measures, including support surfaces and wheelchair cushions.
Source: Advances in Skin and Wound Care - Category: Dermatology Tags: ORIGINAL INVESTIGATION Source Type: research
Authors: Kulshreshtha D, Ganguly J, Jog M Abstract Introduction: Autonomic dysfunction is an integral part of Parkinson disease (PD) complex and can be seen both in early and advanced stages. There is a paucity of medicines available to manage autonomic dysfunction in PD and this adds to the considerable morbidity associated with the illness.Areas covered: The pathophysiology and the available therapeutic options of autonomic dysfunction seen in PD are discussed in detail. The potential targets for novel regimens are reviewed and the available literature on the drugs emerging in management of autonomic dysfunction ...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research
Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Helen M. Melo, Gisele da S. Seixas da Silva, Marcella Ramos Sant’Ana, Camila Vieira Ligo Teixeira, Julia R. Clarke, Vivian S. Miya Coreixas, Bruno C. de Melo, Juliana T.S. Fortuna, Leticia Forny-Germano, José Henrique Ledo, Maíra S. Oliveira, Claudia P. Figueiredo, Raphaelle Pardossi-Piquard, Frédéric Checler, José María Delgado-García, Agnès Gruart, Licio A. Velloso, Marcio L.F. Balthazar, Dennys E. Cintra, Sergio T. FerreiraSummaryObesity has been associated with cognitive dec...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Christin Suenkel, Daniel Cavalli, Simone Massalini, Federico Calegari, Nikolaus RajewskySummarycircSLC45A4 is the main RNA splice isoform produced from its genetic locus and one of the highest expressed circRNAs in the developing human frontal cortex. Knockdown of this highly conserved circRNA in a human neuroblastoma cell line is sufficient to induce spontaneous neuronal differentiation, measurable by increased expression of neuronal marker genes. Depletion of circSlc45a4 in the developing mouse cortex causes a significant reduction ...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Rocco Lucero, Valentina Zappulli, Alessandro Sammarco, Oscar D. Murillo, Pike See Cheah, Srimeenakshi Srinivasan, Eric Tai, David T. Ting, Zhiyun Wei, Matthew E. Roth, Louise C. Laurent, Anna M. Krichevsky, Xandra O. Breakefield, Aleksandar MilosavljevicSummaryGlioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor micro...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: Available online 19 February 2020Source: International Review of NeurobiologyAuthor(s): Daniel J. van Wamelen, Yi-Min Wan, K. Ray Chaudhuri, Peter JennerAbstractStress is ubiquitous with many factors contributing to its effects, including psychological responses and associated biological factors, including cortisol related physiological responses, and inflammation. Also in Parkinson's disease there is growing evidence for the role of stress in some key symptoms, even stretching to the prodromal stage. Here we discuss the possible contributions of the range and nature of stress in PD and we aim to summariz...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
ConclusionThe six paradigmatic examples described in this manuscript show that availability of laboratory resources may considerably catalyze the demand, thus underscoring that inappropriate use of laboratory resources may be commonplace in routine laboratories all across Europe and most probably beyond. They also demonstrate that the application of simple strategies may assist in overcoming this issue. We believe that laboratory specialists need to refocus on the extra-analytical parts of the testing process and engage more in interdisciplinary patient-care.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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