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  1. Article: The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review.

    McCord, Joe M / Gao, Bifeng / Hybertson, Brooks M

    Antioxidants (Basel, Switzerland)

    2023  Volume 12, Issue 2

    Abstract: Nrf2 is a major transcription factor that significantly regulates-directly or indirectly-more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that ... ...

    Abstract Nrf2 is a major transcription factor that significantly regulates-directly or indirectly-more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that are seemingly unrelated to oxidative stress. In the past 25 years, the number of factors involved in the activation, nuclear translocation, and deactivation of Nrf2 has continued to expand. The purpose of this review is to provide an overview of the remarkable complexity of the tortuous sequence of stop-and-go signals that not only regulate expression or repression, but may also modify transcriptional intensity as well as the specificity of promoter recognition, allowing fluidity of its gene expression profile depending on the various structural modifications the transcription factor encounters on its journey to the DNA. At present, more than 45 control points have been identified, many of which represent sites of action of the so-called Nrf2 activators. The complexity of the pathway and the synergistic interplay among combinations of control points help to explain the potential advantages seen with phytochemical compositions that simultaneously target multiple control points, compared to the traditional pharmaceutical paradigm of "one-drug, one-target".
    Language English
    Publishing date 2023-02-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12020366
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of the Phytochemical Combination PB123 on Nrf2 Activation, Gene Expression, and the Cholesterol Pathway in HepG2 Cells.

    Hybertson, Brooks M / Gao, Bifeng / McCord, Joe M

    OBM integrative and complimentary medicine

    2022  Volume 7, Issue 1

    Abstract: There has been a long history of human usage of the biologically-active phytochemicals ... ...

    Abstract There has been a long history of human usage of the biologically-active phytochemicals in
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article
    ISSN 2573-4393
    ISSN (online) 2573-4393
    DOI 10.21926/obm.icm.2201002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Oxyradicals in medical biology

    Mccord, Joe M.

    (Advances in molecular and cell biology ; 25)

    1998  

    Author's details guest ed. Joe M. McCord
    Series title Advances in molecular and cell biology ; 25
    Collection
    Language English
    Size X, 189 S. : Ill., graph. Darst.
    Publisher JAI Press
    Publishing place Greenwich, Conn. u.a.
    Publishing country Netherlands
    Document type Book
    HBZ-ID HT015192488
    ISBN 0-7623-0379-4 ; 978-0-7623-0379-3
    Database Catalogue ZB MED Medicine, Health

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  4. Article ; Online: The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review

    McCord, Joe M. / Gao, Bifeng / Hybertson, Brooks M.

    Antioxidants. 2023 Feb. 03, v. 12, no. 2

    2023  

    Abstract: Nrf2 is a major transcription factor that significantly regulates—directly or indirectly—more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that ... ...

    Abstract Nrf2 is a major transcription factor that significantly regulates—directly or indirectly—more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that are seemingly unrelated to oxidative stress. In the past 25 years, the number of factors involved in the activation, nuclear translocation, and deactivation of Nrf2 has continued to expand. The purpose of this review is to provide an overview of the remarkable complexity of the tortuous sequence of stop-and-go signals that not only regulate expression or repression, but may also modify transcriptional intensity as well as the specificity of promoter recognition, allowing fluidity of its gene expression profile depending on the various structural modifications the transcription factor encounters on its journey to the DNA. At present, more than 45 control points have been identified, many of which represent sites of action of the so-called Nrf2 activators. The complexity of the pathway and the synergistic interplay among combinations of control points help to explain the potential advantages seen with phytochemical compositions that simultaneously target multiple control points, compared to the traditional pharmaceutical paradigm of “one-drug, one-target”.
    Keywords DNA ; epigenetics ; gene expression ; oxidative stress ; phytochemicals ; transcription (genetics) ; transcription factors
    Language English
    Dates of publication 2023-0203
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12020366
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Phytochemical Combination PB125 Activates the Nrf2 Pathway and Induces Cellular Protection against Oxidative Injury.

    Hybertson, Brooks M / Gao, Bifeng / Bose, Swapan / McCord, Joe M

    Antioxidants (Basel, Switzerland)

    2019  Volume 8, Issue 5

    Abstract: Bioactive phytochemicals ... ...

    Abstract Bioactive phytochemicals in
    Language English
    Publishing date 2019-05-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox8050119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19.

    McCord, Joe M / Hybertson, Brooks M / Cota-Gomez, Adela / Gao, Bifeng

    Free radical biology & medicine

    2021  Volume 175, Page(s) 56–64

    Abstract: PB125® is a phytochemical composition providing potent Nrf2 activation as well as a number of direct actions that do not involve Nrf2. Nrf2 is a transcription actor that helps maintain metabolic balance by providing redox-sensitive expression of numerous ...

    Abstract PB125® is a phytochemical composition providing potent Nrf2 activation as well as a number of direct actions that do not involve Nrf2. Nrf2 is a transcription actor that helps maintain metabolic balance by providing redox-sensitive expression of numerous genes controlling normal day-to-day metabolic pathways. When ordinary metabolism is upset by extraordinary events such as injury, pathogenic infection, air or water pollution, ingestion of toxins, or simply by the slow but incessant changes brought about by aging and genetic variations, Nrf2 may also be called into action by the redox changes resulting from these events, whether acute or chronic. A complicating factor in all of this is that Nrf2 levels decline with aging, leaving the elderly less able to maintain proper redox balance. The dysregulated gene expression that results can cause or exacerbate a wide variety of pathological conditions, including susceptibility to viral infections. This review examines the characteristics desirable in Nrf2 activators that have therapeutic potential, as well as some of the patterns of dysregulated gene expression commonly observed during pulmonary infections and the normalizing effects possible by judicious use of phytochemicals to increase the activation level of available Nrf2.
    MeSH term(s) Abietanes/pharmacology ; Aged ; COVID-19 ; Humans ; NF-E2-Related Factor 2/genetics ; SARS-CoV-2
    Chemical Substances Abietanes ; NF-E2-Related Factor 2 ; salvin (LI791SXT24)
    Language English
    Publishing date 2021-05-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 807032-5
    ISSN 1873-4596 ; 0891-5849
    ISSN (online) 1873-4596
    ISSN 0891-5849
    DOI 10.1016/j.freeradbiomed.2021.05.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Nrf2 Activator PB125

    McCord, Joe M / Hybertson, Brooks M / Cota-Gomez, Adela / Geraci, Kara P / Gao, Bifeng

    Antioxidants (Basel, Switzerland)

    2020  Volume 9, Issue 6

    Abstract: Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to ... ...

    Abstract Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2-activating composition PB125
    Keywords covid19
    Language English
    Publishing date 2020-06-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox9060518
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Nrf2 Activator PB125® as a Potential Therapeutic Agent Against COVID-19.

    McCord, Joe M / Hybertson, Brooks M / Cota-Gomez, Adela / Gao, Bifeng

    bioRxiv : the preprint server for biology

    2020  

    Abstract: Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to ... ...

    Abstract Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-α the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the "cytokine storm" observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm.
    Keywords covid19
    Language English
    Publishing date 2020-06-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.05.16.099788
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Nrf2 Activator PB125® as a Potential Therapeutic Agent against COVID-19

    McCord, Joe M / Hybertson, Brooks M / Cota-Gomez, Adela / Geraci, Kara P / Gao, Bifeng

    Antioxidants. 2020 June 12, v. 9, no. 6

    2020  

    Abstract: Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to ... ...

    Abstract Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2-activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-CoV-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells, we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL-1-beta, IL-6, TNF-α, the cell adhesion molecules ICAM-1, VCAM-1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the “cytokine storm” observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; elderly ; endothelial cells ; gene expression ; gene expression regulation ; genes ; human cell lines ; immunity ; inflammation ; intercellular adhesion molecule-1 ; interleukin-1beta ; interleukin-6 ; messenger RNA ; microarray technology ; noninsulin-dependent diabetes mellitus ; pulmonary artery ; sequence analysis ; storms ; therapeutics ; transcription factors ; tumor necrosis factor-alpha ; vascular cell adhesion molecules
    Language English
    Dates of publication 2020-0612
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox9060518
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Biodriven investigation of the wild edible mushroom Pleurotus eryngii revealing unique properties as functional food

    Teniou, Soumia / Bensegueni, Abderrahmane / Hybertson, Brooks M. / Gao, Bifeng / Bose, Swapan K. / McCord, Joe M. / Chovelon, Benoît / Bensouici, Chawki / Boumendjel, Ahcène / Hininger-Favier, Isabelle

    Journal of functional foods. 2022 Feb., v. 89

    2022  

    Abstract: Pleurotus eryngii (P. eryngii) is largely represented among consumed mushrooms. We conducted an investigation dealing with its antioxidant potential, the presence of essential trace elements and its contribution to the management of brain-related ... ...

    Abstract Pleurotus eryngii (P. eryngii) is largely represented among consumed mushrooms. We conducted an investigation dealing with its antioxidant potential, the presence of essential trace elements and its contribution to the management of brain-related disorders. A bio-guided extraction revealed that one extract was highly effective on activation of the nuclear factor Nrf2, the regulator of the cellular resistance to oxidants. Its analysis revealed the presence of N-acetyltryptamine (NAT), a precursor of the neurotransmitters, melatonin and serotonin. Both extract and NAT, were found as competitive inhibitors of acetylcholinesterase. The essential trace elements analyses showed the presence of high amounts of zinc. RNA-seq technology confirmed upregulates expression of Nrf2 on HepG2 cells and revealed key genes involved in anticholesterolemic, antioxidant effects, cancer and brain disorders. Our study achieved a comprehensive strengthening of the nutritional health-benefit properties of P. eryngii largely used in folk medicines and open perspectives for investigation in food and medicine.
    Keywords Pleurotus eryngii ; acetylcholinesterase ; antioxidant activity ; antioxidants ; brain ; functional foods ; melatonin ; mushrooms ; neurotransmitters ; sequence analysis ; serotonin ; zinc
    Language English
    Dates of publication 2022-02
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2511964-3
    ISSN 1756-4646
    ISSN 1756-4646
    DOI 10.1016/j.jff.2022.104965
    Database NAL-Catalogue (AGRICOLA)

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