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  1. Article ; Online: Dietary Supplementation with 23-Hydroxy Ursolic Acid Reduces the Severity and Incidence of Acute Experimental Autoimmune Encephalomyelitis (EAE) in a Murine Model of Multiple Sclerosis.

    Asmis, Reto / Medrano, Megan T / Chase Huizar, Carol / Griffith, Wendell P / Forsthuber, Thomas G

    Nutrients

    2024  Volume 16, Issue 3

    Abstract: 23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and ...

    Abstract 23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation-resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2% wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between the groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN-γ between 23-OH UA-fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T cell responses. In summary, our findings in EAE mice strongly suggest that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.
    MeSH term(s) Female ; Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Multiple Sclerosis/drug therapy ; Ursolic Acid ; Disease Models, Animal ; Incidence ; Mice, Inbred C57BL ; Dietary Supplements
    Chemical Substances Ursolic Acid (P3M2575F3F)
    Language English
    Publishing date 2024-01-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu16030348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Genomic, proteomic, and systems biology approaches in biomarker discovery for multiple sclerosis.

    Chase Huizar, Carol / Raphael, Itay / Forsthuber, Thomas G

    Cellular immunology

    2020  Volume 358, Page(s) 104219

    Abstract: Multiple sclerosis (MS) is a neuroinflammatory disorder characterized by autoimmune-mediated inflammatory lesions in CNS leading to myelin damage and axonal loss. MS is a heterogenous disease with variable and unpredictable disease course. Due to its ... ...

    Abstract Multiple sclerosis (MS) is a neuroinflammatory disorder characterized by autoimmune-mediated inflammatory lesions in CNS leading to myelin damage and axonal loss. MS is a heterogenous disease with variable and unpredictable disease course. Due to its complex nature, MS is difficult to diagnose and responses to specific treatments may vary between individuals. Therefore, there is an indisputable need for biomarkers for early diagnosis, prediction of disease exacerbations, monitoring the progression of disease, and for measuring responses to therapy. Genomic and proteomic studies have sought to understand the molecular basis of MS and find biomarker candidates. Advances in next-generation sequencing and mass-spectrometry techniques have yielded an unprecedented amount of genomic and proteomic data; yet, translation of the results into the clinic has been underwhelming. This has prompted the development of novel data science techniques for exploring these large datasets to identify biologically relevant relationships and ultimately point towards useful biomarkers. Herein we discuss optimization of omics study designs, advances in the generation of omics data, and systems biology approaches aimed at improving biomarker discovery and translation to the clinic for MS.
    MeSH term(s) Biomarkers/analysis ; Genomics/methods ; Humans ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Proteomics/methods ; Systems Biology/methods
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-09-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2020.104219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glucan particles as a novel adjuvant for the induction of experimental autoimmune encephalomyelitis.

    Chase Huizar, Carol / Ji, Niannian / Reddick, Robert / Ostroff, Gary R / Forsthuber, Thomas G

    Cellular immunology

    2021  Volume 366, Page(s) 104383

    Abstract: For over 70 years experimental autoimmune encephalomyelitis (EAE) has been induced with myelin autoantigens emulsified in complete Freund's adjuvant (CFA) which has significant side effects such as pain, inflammation, and tissue necrosis at the injection ...

    Abstract For over 70 years experimental autoimmune encephalomyelitis (EAE) has been induced with myelin autoantigens emulsified in complete Freund's adjuvant (CFA) which has significant side effects such as pain, inflammation, and tissue necrosis at the injection site. β-1,3-d-glucan particles (GPs) are hollow microcapsules prepared from Saccharomyces cerevisiae cell walls that induce potent Th17 cell responses without causing strong injection site tissue reactions. We evaluated the potential of GPs complexed with neuroantigens to induce EAE while avoiding undesirable side effects. GPs loaded with myelin oligodendrocyte glycoprotein 35-55 (MOG
    MeSH term(s) Adjuvants, Immunologic/metabolism ; Animals ; Capsules/metabolism ; Cell Wall/metabolism ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Female ; Freund's Adjuvant ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/immunology ; Myelin Proteolipid Protein/immunology ; Myelin-Oligodendrocyte Glycoprotein/immunology ; Peptide Fragments/immunology ; Proteoglycans/immunology ; Proteoglycans/metabolism ; Saccharomyces cerevisiae/metabolism ; Th17 Cells/immunology
    Chemical Substances Adjuvants, Immunologic ; Capsules ; Myelin Proteolipid Protein ; Myelin-Oligodendrocyte Glycoprotein ; Peptide Fragments ; Proteoglycans ; myelin oligodendrocyte glycoprotein (35-55) ; myelin proteolipid protein (139-151) ; polysaccharide-K (3X48A86C8K) ; Freund's Adjuvant (9007-81-2)
    Language English
    Publishing date 2021-05-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2021.104383
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis.

    Porritt, Rebecca A / Chase Huizar, Carol / Dick, Edward J / Kumar, Shyamesh / Escalona, Renee / Gomez, Angela C / Marek-Iannucci, Stefani / Noval Rivas, Magali / Patterson, Jean / Forsthuber, Thomas G / Arditi, Moshe / Gorelik, Mark

    Frontiers in immunology

    2021  Volume 12, Page(s) 630196

    Abstract: Objective: Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in the developed world. 10% of KD patients are resistant to front-line therapy, and no interventions exist to address secondary complications such as ... ...

    Abstract Objective: Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in the developed world. 10% of KD patients are resistant to front-line therapy, and no interventions exist to address secondary complications such as myocardial fibrosis. We sought to identify proteins and pathways associated with disease and anti-IL-1 treatment in a mouse model of KD.
    Methods: Vasculitis was induced
    Results: STAT3 was highly expressed and phosphorylated in cardiac tissue of LCWE-injected mice, and reduced following anakinra treatment.
    Conclusion: Proteomic analysis of cardiac tissues demonstrates differential protein expression between KD-like, control and anakinra treated cardiac tissue. STAT3 and IL-6 were highly upregulated with LCWE and normalized by anakinra treatment. However, both STAT3 and IL-6 were dispensable for disease development indicating they may be bystanders of inflammation.
    MeSH term(s) Animals ; Cell Wall ; Disease Models, Animal ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/blood ; Interleukin-6/physiology ; Lactobacillus casei ; Male ; Mice ; Mice, Inbred C57BL ; Mucocutaneous Lymph Node Syndrome/drug therapy ; Mucocutaneous Lymph Node Syndrome/etiology ; Myocardium/metabolism ; Proteomics ; STAT3 Transcription Factor/analysis ; STAT3 Transcription Factor/antagonists & inhibitors ; STAT3 Transcription Factor/physiology ; Serum Amyloid A Protein/antagonists & inhibitors
    Chemical Substances Interleukin 1 Receptor Antagonist Protein ; Interleukin-6 ; STAT3 Transcription Factor ; Serum Amyloid A Protein ; Stat3 protein, mouse
    Language English
    Publishing date 2021-04-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.630196
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis.

    Raphael, Itay / Webb, Johanna / Gomez-Rivera, Francisco / Chase Huizar, Carol A / Gupta, Rishein / Arulanandam, Bernard P / Wang, Yufeng / Haskins, William E / Forsthuber, Thomas G

    Frontiers in immunology

    2017  Volume 8, Page(s) 812

    Abstract: There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the ... ...

    Abstract There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood-brain barrier (BBB) is tightly regulated, whereas, in MS, central nervous system (CNS) inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here, we sought to determine if changes in serum NDICPs are detectable prior to clinical onset of experimental autoimmune encephalomyelitis (EAE) and, therefore, enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE that pre-onset expression waves of synapsin-2, glutamine synthetase, enolase-2, and synaptotagmin-1 enable the prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggesting hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.
    Language English
    Publishing date 2017-07-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.00812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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