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  1. Article ; Online: Reduction of daily-use parabens and phthalates reverses accumulation of cancer-associated phenotypes within disease-free breast tissue of study subjects

    Dairkee, Shanaz H. / Moore, Dan H. / Luciani, M. Gloria / Anderle, Nicole / Gerona, Roy / Ky, Karina / Torres, Samantha M. / Marshall, Polly V. / Goodson, William H.

    Chemosphere. 2023 Feb. 04, p.138014-

    2023  , Page(s) 138014–

    Abstract: Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly ... ...

    Abstract Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly within human estrogen responsive breast tissue of subjects enrolled in a regimen of reduced XE use (REDUXE). Pre- and post-intervention fine needle aspirates (FNAs) of the breast were collected from healthy volunteers who discontinued the use of paraben and phthalate containing PCPs over a 28 d period. Based on high-dimensional gene expression data of matched FNA pairs of study subjects, we demonstrate a striking reversal of cancer-associated phenotypes, including the PI3K-AKT/mTOR pathway, autophagy, and apoptotic signaling networks within breast cells of REDUXE compliant subjects. These, and other altered phenotypes were detected together with a significant reduction in urinary parabens and phthalate metabolites. Moreover, in vitro treatment of paired FNAs with 17β-estradiol (E2), displayed a ‘normalizing’ impact of REDUXE on gene expression within known E2-modulated pathways, and on functional endpoints, including estrogen receptor alpha: beta ratio, and S-phase fraction of the cell cycle. In a paradigm shifting approach facilitated by community-based participatory research, REDUXE reveals unfavorable consequences from exposure to XEs from daily-use PCPs. Our findings illustrate the potential for REDUXE to suppress pro-carcinogenic phenotypes at the cellular level towards the goal of breast cancer prevention.
    Keywords apoptosis ; autophagy ; breast neoplasms ; breasts ; carcinogenicity ; cell cycle ; cooperative research ; estrogen receptors ; estrogens ; gene expression ; humans ; metabolites ; phthalates ; xenoestrogens ; Endocrine disruption ; Biomarkers ; Nonmalignant breast tissue ; Paired human samples ; Pan-cancer pathways ; PCP ; XE ; REDUXE ; FNA ; E2 ; Pg ; SHBG ; REDUXExE2 ; DEG
    Language English
    Dates of publication 2023-0204
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 120089-6
    ISSN 1879-1298 ; 0045-6535 ; 0366-7111
    ISSN (online) 1879-1298
    ISSN 0045-6535 ; 0366-7111
    DOI 10.1016/j.chemosphere.2023.138014
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2540: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Reduction of daily-use parabens and phthalates reverses accumulation of cancer-associated phenotypes within disease-free breast tissue of study subjects.

    Dairkee, Shanaz H / Moore, Dan H / Luciani, M Gloria / Anderle, Nicole / Gerona, Roy / Ky, Karina / Torres, Samantha M / Marshall, Polly V / Goodson Iii, William H

    Chemosphere

    2023  Volume 322, Page(s) 138014

    Abstract: Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly ... ...

    Abstract Estrogenic overstimulation is carcinogenic to the human breast. Personal care products (PCPs) commonly contain xenoestrogens (XE), such as parabens and phthalates. Here, we identified the adverse effects of persistent exposure to such PCPs directly within human estrogen responsive breast tissue of subjects enrolled in a regimen of reduced XE use (REDUXE). Pre- and post-intervention fine needle aspirates (FNAs) of the breast were collected from healthy volunteers who discontinued the use of paraben and phthalate containing PCPs over a 28 d period. Based on high-dimensional gene expression data of matched FNA pairs of study subjects, we demonstrate a striking reversal of cancer-associated phenotypes, including the PI3K-AKT/mTOR pathway, autophagy, and apoptotic signaling networks within breast cells of REDUXE compliant subjects. These, and other altered phenotypes were detected together with a significant reduction in urinary parabens and phthalate metabolites. Moreover, in vitro treatment of paired FNAs with 17β-estradiol (E2), displayed a 'normalizing' impact of REDUXE on gene expression within known E2-modulated pathways, and on functional endpoints, including estrogen receptor alpha: beta ratio, and S-phase fraction of the cell cycle. In a paradigm shifting approach facilitated by community-based participatory research, REDUXE reveals unfavorable consequences from exposure to XEs from daily-use PCPs. Our findings illustrate the potential for REDUXE to suppress pro-carcinogenic phenotypes at the cellular level towards the goal of breast cancer prevention.
    MeSH term(s) Humans ; Parabens ; Phosphatidylinositol 3-Kinases ; Phthalic Acids ; Neoplasms ; Phenotype
    Chemical Substances Parabens ; phthalic acid (6O7F7IX66E) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Phthalic Acids
    Language English
    Publishing date 2023-02-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 120089-6
    ISSN 1879-1298 ; 0045-6535 ; 0366-7111
    ISSN (online) 1879-1298
    ISSN 0045-6535 ; 0366-7111
    DOI 10.1016/j.chemosphere.2023.138014
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2540: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus.

    Rubinstein, Linda / Kiffer, Frederico / Puukila, Stephanie / Lowe, Moniece G / Goo, Brie / Luthens, Amalia / Schreurs, Ann-Sofie / Torres, Samantha M / Steczina, Sonette / Tahimic, Candice G T / Allen, Antiño R

    Life (Basel, Switzerland)

    2022  Volume 12, Issue 11

    Abstract: Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical ... ...

    Abstract Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth.
    Language English
    Publishing date 2022-11-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life12111838
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Overexpression of catalase in mitochondria mitigates changes in hippocampal cytokine expression following simulated microgravity and isolation.

    Rubinstein, Linda / Schreurs, Ann-Sofie / Torres, Samantha M / Steczina, Sonette / Lowe, Moniece G / Kiffer, Frederico / Allen, Antiño R / Ronca, April E / Sowa, Marianne B / Globus, Ruth K / Tahimic, Candice G T

    NPJ microgravity

    2021  Volume 7, Issue 1, Page(s) 24

    Abstract: Isolation on Earth can alter physiology and signaling of organs systems, including the central nervous system. Although not in complete solitude, astronauts operate in an isolated environment during spaceflight. In this study, we determined the effects ... ...

    Abstract Isolation on Earth can alter physiology and signaling of organs systems, including the central nervous system. Although not in complete solitude, astronauts operate in an isolated environment during spaceflight. In this study, we determined the effects of isolation and simulated microgravity solely or combined, on the inflammatory cytokine milieu of the hippocampus. Adult female wild-type mice underwent simulated microgravity by hindlimb unloading for 30 days in single or social (paired) housing. In hippocampus, simulated microgravity and isolation each regulate a discrete repertoire of cytokines associated with inflammation. Their combined effects are not additive. A model for mitochondrial reactive oxygen species (ROS) quenching via targeted overexpression of the human catalase gene to the mitochondria (MCAT mice), are protected from isolation- and/or simulated microgravity-induced changes in cytokine expression. These findings suggest a key role for mitochondrial ROS signaling in neuroinflammatory responses to spaceflight and prolonged bedrest, isolation, and confinement on Earth.
    Language English
    Publishing date 2021-07-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2823626-9
    ISSN 2373-8065
    ISSN 2373-8065
    DOI 10.1038/s41526-021-00152-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Influence of Social Isolation During Prolonged Simulated Weightlessness by Hindlimb Unloading.

    Tahimic, Candice G T / Paul, Amber M / Schreurs, Ann-Sofie / Torres, Samantha M / Rubinstein, Linda / Steczina, Sonette / Lowe, Moniece / Bhattacharya, Sharmila / Alwood, Joshua S / Ronca, April E / Globus, Ruth K

    Frontiers in physiology

    2019  Volume 10, Page(s) 1147

    Abstract: The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among ...

    Abstract The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation to tissue responses to HU. To accomplish this, we developed a refinement to the traditional NASA Ames single housing HU system to accommodate social housing in pairs, retaining desirable features of the original design. We conducted a 30-day HU experiment with adult, female mice that were either singly or socially housed. HU animals in both single and social housing displayed expected musculoskeletal deficits versus housing matched, normally loaded (NL) controls. However, select immune and hypothalamic-pituitary-adrenal (HPA) axis responses were differentially impacted by the HU social environment relative to matched NL controls. HU led to a reduction in % CD4
    Language English
    Publishing date 2019-09-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2019.01147
    Database MEDical Literature Analysis and Retrieval System OnLINE

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