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https://www.readbyqxmd.com/read/27920668/getting-mirna-therapeutics-into-the-target-cells-for-neurodegenerative-diseases-a-mini-review
#1
REVIEW
Ming Ming Wen
miRNAs play important roles in modulating gene expression in varying cellular processes and disease pathogenesis, including neurodegenerative diseases. Several miRNAs are expressed in the brain, control brain development and are identified as important biomarkers in the pathogenesis of motor-and neuro-cognitive diseases such as Alzheimer's (AD), Huntington's and Parkinson's diseases (PD) and amyotrophic lateral sclerosis. These remarkable miRNAs could be used as diagnostic markers and therapeutic targeting potential for many stressful and untreatable progressive neurodegenerative diseases...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27918067/systematic-approach-to-understanding-the-pathogenesis-of-systemic-sclerosis
#2
REVIEW
Xiao Xia Zuo, Li Hua Zhang, Hui Luo, Yisha Li, Honglin Zhu
Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc...
December 5, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27913752/expression-and-bioactivity-of-human-alpha-fetoprotein-in-a-bac-to-bac-system
#3
Bo Lin, Kun Liu, Wenting Wang, Wei Li, Xu Dong, Yi Chen, Yan Lu, Junli Guo, Mingyue Zhu, Mengsen Li
Alpha-fetoprotein (AFP) is an early serum growth factor in fetal embryonic development and hepatic oncogenesis. A growing number of investigations of AFP as a tumor-specific biomarker have concluded that AFP is an important target for cancer treatment. AFP also plays an immunomodulatory role in the treatment of several autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, and thyroiditis. In an effort to support biochemical screening and drug design and discovery, we attempted to express and purify human AFP in a Bac-to-Bac system...
December 2, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27911122/an-update-on-the-use-of-cerebrospinal-fluid-analysis-as-a-diagnostic-tool-in-multiple-sclerosis
#4
Matteo Gastaldi, Elisabetta Zardini, Diego Franciotta
Intrathecal B-lymphocyte activation is a hallmark of multiple sclerosis (MS), a multi-factorial inflammatory-demyelinating disease of the central nervous system. Such activation has a counterpart in the cerebrospinal fluid (CSF) oligoclonal IgG bands (OCB), whose diagnostic role in MS has been downgraded within the current McDonald's criteria. With a theoretico-practical approach, the authors review the physiopathological basis of the CSF dynamics, and the state-of-the-art of routine CSF analysis and CSF biomarkers in MS...
December 2, 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/27908171/automated-detection-of-white-matter-hyperintensities-of-all-sizes-in-cerebral-small-vessel-disease
#5
Mohsen Ghafoorian, Nico Karssemeijer, Inge W M van Uden, Frank-Erik de Leeuw, Tom Heskes, Elena Marchiori, Bram Platel
PURPOSE: White matter hyperintensities (WMH) are seen on FLAIR-MRI in several neurological disorders, including multiple sclerosis, dementia, Parkinsonism, stroke and cerebral small vessel disease (SVD). WMHs are often used as biomarkers for prognosis or disease progression in these diseases, and additionally longitudinal quantification of WMHs is used to evaluate therapeutic strategies. Human readers show considerable disagreement and inconsistency on detection of small lesions. A multitude of automated detection algorithms for WMHs exists, but since most of the current automated approaches are tuned to optimize segmentation performance according to Jaccard or Dice scores, smaller WMHs often go undetected in these approaches...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27906756/optic-neuritis-the-eye-as-a-window-to-the-brain
#6
Thomas M Jenkins, Ahmed T Toosy
PURPOSE OF REVIEW: Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease...
November 30, 2016: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27863511/analysis-of-complement-biomarkers-in-systemic-sclerosis-indicates-a-distinct-pattern-in-scleroderma-renal-crisis
#7
Marcin Okrój, Martin Johansson, Tore Saxne, Anna M Blom, Roger Hesselstrand
BACKGROUND: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. METHODS: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters...
November 18, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27855220/disease-type-and-status-specific-alteration-of-csf-metabolome-coordinated-with-clinical-parameters-in-inflammatory-demyelinating-diseases-of-cns
#8
Soo Jin Park, In Hye Jeong, Byung Soo Kong, Jung-Eun Lee, Kyoung Heon Kim, Do Yup Lee, Ho Jin Kim
Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach...
2016: PloS One
https://www.readbyqxmd.com/read/27829982/new-insights-into-the-role-of-oxidative-stress-mechanisms-in-the-pathophysiology-and-treatment-of-multiple-sclerosis
#9
REVIEW
Bożena Adamczyk, Monika Adamczyk-Sowa
Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27819517/polymorphisms-in-cd14-gene-may-modify-soluble-cd14-levels-and-represent-risk-factors-for-multiple-sclerosis
#10
Mehrdad Farrokhi, Pedram Moeini, Mohammad Fazilati, Habibollah Nazem, Shahla Faraji, Zahra Saadatpour, Elyas Fadaei, Leila Saadatpour, Ali Rezaei, Sadra Ansaripour, Ali Amani-Beni
BACKGROUND: Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population...
November 7, 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27813441/primary-progressive-multiple-sclerosis-current-therapeutic-strategies-and-future-perspectives
#11
Alberto Gajofatto, Marco Turatti, Maria Donata Benedetti
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents...
November 4, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27811233/defective-cholesterol-metabolism-in-amyotrophic-lateral-sclerosis
#12
Jonas Abdel-Khalik, Eylan Yutuc, Peter J Crick, Jan-Åke Gustafsson, Margaret Warner, Gustavo Roman, Kevin Talbot, Elizabeth Gray, William J Griffiths, Martin R Turner, Yuqin Wang
As neurons die cholesterol is released in the central nervous system (CNS), hence this sterol and its metabolites may represent a biomarker of neurodegeneration, including in amyotrophic lateral sclerosis (ALS) in which altered cholesterol levels have been linked to prognosis. More than 40 different sterols were quantified in serum and cerebrospinal fluid (CSF) from ALS patients and healthy controls. In CSF the concentration of cholesterol was found to be elevated in ALS samples. When CSF metabolite levels were normalised to cholesterol, the cholesterol metabolite 3beta,7alpha-dihydroxycholest-5-en-26-oic acid, along with its precursor 3beta-hydroxycholest-5-en-26-oic acid and product 7alpha-hydroxy-3-oxocholest-4-en-26-oic acid were reduced in concentration, whereas metabolites known to be imported from the circulation into the CNS were not found to differ in concentration between groups...
November 3, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27808577/topoisomerase-i-peptide-loaded-dendritic-cells-induce-autoantibody-response-as-well-as-skin-and-lung-fibrosis
#13
Heena Mehta, Philippe-Olivier Goulet, Vinh Nguyen, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
DNA Topoisomerase I (TopoI) is a candidate autoantigen for diffuse cutaneous systemic sclerosis (dcSSc) associated with fatal lung disease. Dendritic cells (DCs) contribute to bleomycin-induced lung fibrosis. However, the possibility that TopoI-loaded DCs are involved in the initiation and/or perpetuation of dcSSc has not been explored. Here, we show that immunization with TopoI peptide-loaded DCs induces anti-TopoI autoantibody response and long-term fibrosis. Mice were repeatedly immunized with unpulsed DCs or DCs loaded with either TOPOIA or TOPOIB peptides, selected from different regions of TopoI...
November 3, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27799738/alemtuzumab-in-the-treatment-of-multiple-sclerosis-patient-selection-and-special-considerations
#14
REVIEW
Jan Dörr, Karl Baum
Multiple sclerosis (MS) is among the most common chronic inflammatory diseases of the central nervous system. Although not curable, the constantly increasing armamentarium of disease-modifying drugs now allows control of disease activity in many patients. The humanized monoclonal antibody alemtuzumab is a powerful drug licensed for the treatment of MS. Upon binding to the CD52 surface protein on CD4(+) and CD8(+) T cells, B cells, and monocytes, circulating CD52(+) cells are eliminated via antibody- and complement-mediated lysis, and a less autoreactive adaptive immune system is reconstituted...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27794524/progressive-multiple-sclerosis-from-pathogenic-mechanisms-to-treatment
#15
Jorge Correale, María I Gaitán, María C Ysrraelit, Marcela P Fiol
During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus...
October 29, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27774920/panel-of-oxidative-stress-and-inflammatory-biomarkers-in-als-a-pilot-study
#16
Hélène Blasco, Guillaume Garcon, Franck Patin, Charlotte Veyrat-Durebex, Judith Boyer, David Devos, Patrick Vourc'h, Christian R Andres, Philippe Corcia
BACKGROUND: Pathophysiological mechanisms that contribute to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) include oxidative stress and inflammation. We conducted a preliminary study to explore these mechanisms, to discuss their link in ALS, and to determine the feasibility of incorporating this combined analysis into current biomarkers research. METHODS: We enrolled 10 ALS patients and 10 controls. We measured the activities of glutathione peroxidase, glutathione reductase, superoxyde dismutase (SOD), and the levels of serum total antioxidant status (TAS), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and glutathione status (e...
October 24, 2016: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/27757816/blood-biomarkers-as-outcome-measures-in-inflammatory-neurologic-diseases
#17
Nabil K El Ayoubi, Samia J Khoury
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. Only a few biomarkers are available in MS clinical practice, such as cerebrospinal fluid oligoclonal bands and immunoglobulin index, serum anti-aquaporin 4 antibodies, and serum anti-John Cunningham virus antibodies. Thus, there is a significant unmet need for biomarkers to assess prognosis, response to therapy, or potential treatment complications. Here we describe emerging biomarkers that are in development, focusing on those from peripheral blood...
October 18, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27756506/transforming-growth-factor-%C3%AE-1-in-the-cerebrospinal-fluid-of-patients-with-distinct-neurodegenerative-diseases
#18
Tomoyuki Masuda, Junko Itoh, Takuya Koide, Yasushi Tomidokoro, Yosuke Takei, Kazuhiro Ishii, Akira Tamaoka
A chronic inflammatory condition may underlie neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease (AD). For example, both PD and AD patients show an increase in transforming growth factor-β1 (TGF-β1) levels in their cerebrospinal fluid (CSF). TGF-β1 is a cytokine that inhibits inflammation. In the present study, using an enzyme-linked immunosorbent assay, we tested the hypothesis that the level of TGF-β1 in the CSF of patients with amyotrophic lateral sclerosis (ALS), spinocerebellar degeneration (SCD), or multiple system atrophy-cerebellar subtype (MSA-C) would be elevated compared with that of normal controls...
October 15, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27749243/the-relationship-between-vascular-biomarkers-and-disease-characteristics-in-systemic-sclerosis-elevated-mcp-1-is-predominantly-associated-with-fibrotic-manifestations
#19
Yasemin Yalçinkaya, Suzan Çinar, Bahar Artim-Esen, Sevil Kamali, Lale Öcal, Günnur Deniz, Murat Inanç
OBJECTIVES: To determine the relationship between vascular biomarkers reflecting the vascular injury and organ involvement in systemic sclerosis (SSc). METHODS: Seventy-two SSc patients (66 female) fulfilling 2013 ACR/EULAR Criteria were evaluated. Serum samples of patients were collected for flow-cytometric analysis of sCD40L, tPA, MCP-1, sE-selectin, IL-8, IL-6, VEGF, sP-selectin, TGF-β1 and VCAM levels (Bender MedSystems) in SSc patients and 20 healthy controls...
September 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27744392/effects-of-longterm-treatment-with-bosentan-and-iloprost-on-nailfold-absolute-capillary-number-fingertip-blood-perfusion-and-clinical-status-in-systemic-sclerosis
#20
Amelia Chiara Trombetta, Carmen Pizzorni, Barbara Ruaro, Sabrina Paolino, Alberto Sulli, Vanessa Smith, Maurizio Cutolo
OBJECTIVE: To quantify in patients with systemic sclerosis (SSc) the absolute nailfold capillary number/mm (the absolute number of capillaries, observable in the first row, in 1 mm per field) and fingertip blood perfusion (FBP) during longterm therapy with the endothelin receptor antagonist bosentan (BOSE) and the synthetic analog of prostacyclin PGI2 iloprost (ILO) by multiple diagnostic tools. Observed values were correlated with clinical outcomes. METHODS: Thirty patients with SSc already receiving intravenous ILO (80 μg/day) for 5 continuous days (every 3 mos) were recruited in the clinic...
October 1, 2016: Journal of Rheumatology
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