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  1. AU="Levens, Cassandra"
  2. AU=Gerdes Hans-Hermann
  3. AU="Johnson, Abigail N"
  4. AU="Zheng, Yuanyuan"
  5. AU="Xia, Fan"
  6. AU="Wilson, Louis G"
  7. AU="Aubertin, Perrine"
  8. AU=Remmel Ariana
  9. AU="Tabbo, Agnese"
  10. AU="Chen, Linyi"
  11. AU="Milovanovic, Marija"
  12. AU="Vaught, Emma K"
  13. AU="Chapelle, Caroline"
  14. AU="Schmelzeisen, R"
  15. AU=Sillanaukee P AU=Sillanaukee P
  16. AU="Meyler, Shanique"

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  1. Artikel ; Online: Oral Cannabis consumption and intraperitoneal THC:CBD dosing results in changes in brain and plasma neurochemicals and endocannabinoids in mice.

    Reisdorph, Nichole / Doenges, Katrina / Levens, Cassandra / Manke, Jon / Armstrong, Michael / Smith, Harry / Quinn, Kevin / Radcliffe, Richard / Reisdorph, Richard / Saba, Laura / Kuhn, Kristine A

    Journal of cannabis research

    2024  Band 6, Heft 1, Seite(n) 10

    Abstract: Background: While the use of orally consumed Cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC) containing products, i.e. "edibles", has expanded, the health consequences are still largely unknown. This study examines the effects of oral ... ...

    Abstract Background: While the use of orally consumed Cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC) containing products, i.e. "edibles", has expanded, the health consequences are still largely unknown. This study examines the effects of oral consumption of whole Cannabis and a complex Cannabis extract on neurochemicals, endocannabinoids (eCB), and physiological parameters (body temperature, heart rate) in mice.
    Methods: In this pilot study, C57BL/6 J mice were treated with one of the following every other day for 2 weeks: a complex Cannabis extract by gavage, whole Cannabis mixed with nutritional gel through free feeding, or purified THC/CBD by intraperitoneal (i.p.) injection. Treatments were conducted at 4 doses ranging from 0-100 mg/kg/day of CBD with THC levels of ≤ 1.2 mg/kg/day for free feeding and gavage and 10 mg/kg/day for i.p. Body temperature and heart rate were monitored using surgically implanted telemetry devices. Levels of neurochemicals, eCB, THC, CBD, and 11-OH-THC were measured using mass spectrometry 48 h after the final treatment. Statistical comparisons were conducted using ANOVA and t-tests.
    Results: Differences were found between neurochemicals in the brains and plasma of mice treated by i.p. (e.g. dopamine, p < 0.01), gavage (e.g., phenylalanine, p < 0.05) and in mice receiving whole Cannabis (e.g., 3,4-dihydroxyphenylacetic DOPAC p < 0.05). Tryptophan trended downward or was significantly decreased in the brain and/or plasma of all mice receiving Cannabis or purified CBD/THC, regardless of dose, compared to controls. Levels of the eCB, arachidonoyl glycerol (2-AG) were decreased in mice receiving lowest doses of a complex Cannabis extract by gavage, but were higher in mice receiving highest doses compared to controls (p < 0.05). Plasma and brain levels of THC and 11-OH-THC were higher in mice receiving 1:1 THC:CBD by i.p. compared to those receiving 1:5 or 1:10 THC:CBD. Nominal changes in body temperature and heart rate following acute and repeated exposures were seen to some degree in all treatments.
    Conclusions: Changes to neurochemicals and eCBs were apparent at all doses regardless of treatment type. Levels of neurochemicals seemed to vary based on the presence of a complex Cannabis extract, suggesting a non-linear response between THC and neurochemicals following repeated oral dosing.
    Sprache Englisch
    Erscheinungsdatum 2024-03-02
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2522-5782
    ISSN (online) 2522-5782
    DOI 10.1186/s42238-024-00219-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Interplay of gut microbiota and host epithelial mitochondrial dysfunction is necessary for the development of spontaneous intestinal inflammation in mice.

    Alula, Kibrom M / Dowdell, Alexander S / LeBere, Brittany / Lee, J Scott / Levens, Cassandra L / Kuhn, Kristine A / Kaipparettu, Benny A / Thompson, Winston E / Blumberg, Richard S / Colgan, Sean P / Theiss, Arianne L

    Microbiome

    2023  Band 11, Heft 1, Seite(n) 256

    Abstract: Background: Intestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn's disease affecting the small intestine, is emerging in recent studies. As the interface between the self and the ... ...

    Abstract Background: Intestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn's disease affecting the small intestine, is emerging in recent studies. As the interface between the self and the gut microbiota, IECs serve as hubs of bidirectional cross-talk between host and luminal microbiota. However, the role of mitochondrial-microbiota interaction in the ileum is largely unexplored. Prohibitin 1 (PHB1), a chaperone protein of the inner mitochondrial membrane required for optimal electron transport chain function, is decreased during IBD. We previously demonstrated that mice deficient in PHB1 specifically in IECs (Phb1
    Results: Depletion of gut microbiota by broad-spectrum antibiotic treatment in Phb1
    Conclusions: These results suggest a mutual and essential reinforcing interplay of gut microbiota and host IEC, including Paneth cell, mitochondrial health in influencing ileitis. Restoration of butyrate is a potential therapeutic option in Crohn's disease patients harboring epithelial cell mitochondrial dysfunction. Video Abstract.
    Mesh-Begriff(e) Humans ; Animals ; Mice ; Crohn Disease ; Gastrointestinal Microbiome ; Ileitis/metabolism ; Inflammation/metabolism ; Inflammatory Bowel Diseases/metabolism ; Paneth Cells ; Butyrates/metabolism ; Mitochondria/metabolism ; Intestinal Mucosa/metabolism
    Chemische Substanzen Butyrates
    Sprache Englisch
    Erscheinungsdatum 2023-11-17
    Erscheinungsland England
    Dokumenttyp Video-Audio Media ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2697425-3
    ISSN 2049-2618 ; 2049-2618
    ISSN (online) 2049-2618
    ISSN 2049-2618
    DOI 10.1186/s40168-023-01686-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: MAIT cells drive chronic inflammation in a genetically diverse murine model of spontaneous colitis.

    Loh, Liyen / Orlicky, David / Spengler, Andrea / Levens, Cassandra / Celli, Sofia / Domenico, Joanne / Klarquist, Jared / Onyiah, Joseph / Matsuda, Jennifer / Kuhn, Kristine / Gapin, Laurent

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background & aims: Lymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting in tissue ...

    Abstract Background & aims: Lymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting in tissue damage, they are also capable of contributing directly or indirectly to tissue repair, thus necessitating more detailed investigation. Mucosal-Associated-Invariant-T (MAIT) cells are innate-like T cells, acquiring a type III phenotype in the thymus. Here, we dissected the role of MAIT cells
    Methods: Multiparameter spectral flow cytometry and scRNAseq were used to characterize MAIT and immune cell dynamics and transcriptomic signatures respectively, in the collaborative-cross strain, CC011/Unc and CC011/Unc-
    Results: In contrast to many conventional mouse laboratory strains, the CC011 strain harbors a high baseline population of MAIT cells. We observed an age-related increase in colonic MAIT cells, Th17 cells, regulatory T cells, and neutrophils, which paralleled the development of spontaneous colitis. This progression manifested histological traits reminiscent of human IBD. The transcriptomic analysis of colonic MAIT cells from CC011 revealed an activation profile consistent with an inflammatory milieu, marked by an enhanced type-III response. Notably, IL-17A was abundantly secreted by MAIT cells in the colons of afflicted mice. Conversely, in the MAIT cell-deficient CC011-Traj33-/- mice, there was a notable absence of significant colonic histopathology. Furthermore, myeloperoxidase staining indicated a substantial decrease in colonic neutrophils.
    Conclusions: Our findings suggest that MAIT cells play a pivotal role in modulating the severity of intestinal pathology, potentially orchestrating the inflammatory process by driving the accumulation of neutrophils within the colonic environment.
    Sprache Englisch
    Erscheinungsdatum 2023-12-01
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.11.29.569225
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: A dysbiotic microbiome promotes head and neck squamous cell carcinoma.

    Frank, Daniel N / Qiu, Yue / Cao, Yu / Zhang, Shuguang / Lu, Ling / Kofonow, Jennifer M / Robertson, Charles E / Liu, Yanqiu / Wang, Haibo / Levens, Cassandra L / Kuhn, Kristine A / Song, John / Ramakrishnan, Vijay R / Lu, Shi-Long

    Oncogene

    2022  Band 41, Heft 9, Seite(n) 1269–1280

    Abstract: Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy ...

    Abstract Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.
    Mesh-Begriff(e) Squamous Cell Carcinoma of Head and Neck
    Sprache Englisch
    Erscheinungsdatum 2022-01-28
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-021-02137-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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