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  1. Article ; Online: Physiology of the tongue with emphasis on taste transduction.

    Doyle, Máire E / Premathilake, Hasitha U / Yao, Qin / Mazucanti, Caio H / Egan, Josephine M

    Physiological reviews

    2022  Volume 103, Issue 2, Page(s) 1193–1246

    Abstract: The tongue is a complex multifunctional organ that interacts and senses both interoceptively and exteroceptively. Although it is easily visible to almost all of us, it is relatively understudied and what is in the literature is often contradictory or is ... ...

    Abstract The tongue is a complex multifunctional organ that interacts and senses both interoceptively and exteroceptively. Although it is easily visible to almost all of us, it is relatively understudied and what is in the literature is often contradictory or is not comprehensively reported. The tongue is both a motor and a sensory organ: motor in that it is required for speech and mastication, and sensory in that it receives information to be relayed to the central nervous system pertaining to the safety and quality of the contents of the oral cavity. Additionally, the tongue and its taste apparatus form part of an innate immune surveillance system. For example, loss or alteration in taste perception can be an early indication of infection as became evident during the present global SARS-CoV-2 pandemic. Here, we particularly emphasize the latest updates in the mechanisms of taste perception, taste bud formation and adult taste bud renewal, and the presence and effects of hormones on taste perception, review the understudied lingual immune system with specific reference to SARS-CoV-2, discuss nascent work on tongue microbiome, as well as address the effect of systemic disease on tongue structure and function, especially in relation to taste.
    MeSH term(s) Humans ; Taste Perception ; Taste/physiology ; SARS-CoV-2 ; COVID-19 ; Population Health ; Tongue ; Taste Buds/physiology
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Intramural
    ZDB-ID 209902-0
    ISSN 1522-1210 ; 0031-9333
    ISSN (online) 1522-1210
    ISSN 0031-9333
    DOI 10.1152/physrev.00012.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Corrigendum to "Beta cell specific cannabinoid 1 receptor deletion counteracts progression to hyperglycemia in non-obese diabetic mice" [Mol Metab 82 (2024 April) 101906].

    Aseer, Kanikkai Raja / Mazucanti, Caio Henrique / O'Connell, Jennifer F / González-Mariscal, Isabel / Verma, Anjali / Yao, Qin / Dunn, Christopher / Liu, Qing-Rong / Egan, Josephine M / Doyle, Máire E

    Molecular metabolism

    2024  Volume 82, Page(s) 101917

    Language English
    Publishing date 2024-03-16
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2024.101917
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Long-Term Dysfunction of Taste Papillae in SARS-CoV-2.

    Yao, Qin / Doyle, Máire E / Liu, Qing-Rong / Appleton, Ashley / O'Connell, Jennifer F / Weng, Nan-Ping / Egan, Josephine M

    NEJM evidence

    2023  Volume 2, Issue 9

    Abstract: Background: We sought to determine whether ongoing taste disturbance in the postacute sequelae of coronavirus disease 2019 period is associated with persistent virus in primary taste tissue.: Methods: We performed fungiform papillae biopsies on 16 ... ...

    Abstract Background: We sought to determine whether ongoing taste disturbance in the postacute sequelae of coronavirus disease 2019 period is associated with persistent virus in primary taste tissue.
    Methods: We performed fungiform papillae biopsies on 16 patients who reported taste disturbance lasting more than 6 weeks after molecularly determined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Then, on multiple occasions, we rebiopsied 10 of those patients who still had taste complaints for at least 6 months postinfection. Fungiform papillae obtained from other patients before March 2020 served as negative controls. We performed hematoxylin and eosin staining to examine fungiform papillae morphology and immunofluorescence and fluorescence in situ hybridization to look for evidence of persistent viral infection and immune response.
    Results: In all patients, we found evidence of SARS-CoV-2, accompanying immune response and misshapen or absent taste buds with loss of intergemmal neurite fibers. Six patients reported normal taste perception by 6 months postinfection and were not further biopsied. In the remaining 10, the virus was eliminated in a seemingly random fashion from their fungiform papillae, but four patients still, by history, reported incomplete return to preinfection taste perception by the time we wrote this report.
    Conclusions: Our data show a temporal association in patients between functional taste, taste papillae morphology, and the presence of SARS-CoV-2 and its associated immunological changes. (Funded by Intramural Research Program/National Institute on Aging/National Institute of Allergy and Infectious Diseases/National Institutes of Health; ClinicalTrials.gov numbers NCT03366168 and NCT04565067.).
    MeSH term(s) Humans ; COVID-19/complications ; In Situ Hybridization, Fluorescence ; SARS-CoV-2/genetics ; Taste ; Taste Buds/anatomy & histology ; Taste Buds/pathology ; Taste Perception ; Tongue/anatomy & histology ; Tongue/pathology ; United States ; Dysgeusia/etiology ; Dysgeusia/pathology
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Clinical Study ; Journal Article
    ISSN 2766-5526
    ISSN (online) 2766-5526
    DOI 10.1056/evidoa2300046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Beta cell specific cannabinoid 1 receptor deletion counteracts progression to hyperglycemia in non-obese diabetic mice.

    Aseer, Kanikkai Raja / Mazucanti, Caio Henrique / O'Connell, Jennifer F / González-Mariscal, Isabel / Verma, Anjali / Yao, Qin / Dunn, Christopher / Liu, Qing-Rong / Egan, Josephine M / Doyle, Máire E

    Molecular metabolism

    2024  Volume 82, Page(s) 101906

    Abstract: Objective: Type 1 diabetes (T1D) occurs because of islet infiltration by autoreactive immune cells leading to destruction of beta cells and it is becoming evident that beta cell dysfunction partakes in this process. We previously reported that genetic ... ...

    Abstract Objective: Type 1 diabetes (T1D) occurs because of islet infiltration by autoreactive immune cells leading to destruction of beta cells and it is becoming evident that beta cell dysfunction partakes in this process. We previously reported that genetic deletion and pharmacological antagonism of the cannabinoid 1 receptor (CB1) in mice improves insulin synthesis and secretion, upregulates glucose sensing machinery, favors beta cell survival by reducing apoptosis, and enhances beta cell proliferation. Moreover, beta cell specific deletion of CB1 protected mice fed a high fat high sugar diet against islet inflammation and beta cell dysfunction. Therefore, we hypothesized that it would mitigate the dysfunction of beta cells in the precipitating events leading to T1D.
    Methods: We genetically deleted CB1 specifically from beta cells in non-obese diabetic (NOD; NOD RIP Cre
    Results: Beta cell specific deletion of CB1 in NOD mice significantly reduced the incidence of hyperglycemia by preserving beta cell function and mass. Deletion also prevented beta cell apoptosis and aggressive insulitis in NOD RIP Cre
    Conclusions: Collectively these data demonstrate how protection of beta cells from metabolic stress during the active phase of T1D can ameliorate destructive insulitis and provides evidence for CB1 as a potential pharmacologic target in T1D.
    MeSH term(s) Mice ; Female ; Animals ; Mice, Inbred NOD ; Diabetes Mellitus, Type 1/metabolism ; Islets of Langerhans/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Cannabinoids/metabolism ; Hyperglycemia/genetics ; Hyperglycemia/metabolism
    Chemical Substances Cannabinoids
    Language English
    Publishing date 2024-02-28
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2024.101906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Human Taste Cells Express ACE2: a Portal for SARS-CoV-2 Infection.

    Doyle, Máire E / Appleton, Ashley / Liu, Qing-Rong / Yao, Qin / Mazucanti, Caio Henrique / Egan, Josephine M

    bioRxiv : the preprint server for biology

    2021  

    Abstract: Loss and changes in taste and smell are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by high affinity binding of its spike protein to cell-surface angiotensin-converting enzyme- 2 (ACE2). It was not known whether ACE2 ...

    Abstract Loss and changes in taste and smell are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by high affinity binding of its spike protein to cell-surface angiotensin-converting enzyme- 2 (ACE2). It was not known whether ACE2 is expressed on taste receptor cells (TRCs) nor if TRCs are infected directly. Using an
    Language English
    Publishing date 2021-04-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.04.21.440680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The role of the endocannabinoid system in islet biology.

    Doyle, Máire E

    Current opinion in endocrinology, diabetes, and obesity

    2011  Volume 18, Issue 2, Page(s) 153–158

    Abstract: Purpose of review: The endogenous cannabinoids (endocannabinoids) are long-chain polyunsaturated fatty acids synthesized on demand in situ by catabolism of phospholipid precursors in the cell membrane. Here we discuss the emerging role of the ... ...

    Abstract Purpose of review: The endogenous cannabinoids (endocannabinoids) are long-chain polyunsaturated fatty acids synthesized on demand in situ by catabolism of phospholipid precursors in the cell membrane. Here we discuss the emerging role of the endocannabinoids in the function of the pancreatic islet of Langerhans in particular on the secretion of insulin from the islet beta cell.
    Recent findings: It is now established that there is a functional endocannabinoid system in the pancreatic islet of Langerhans and that endocannabinoids are released concurrently with glucose-induced insulin secretion. The majority of the published papers show evidence of negative effects of the endocannabinoids on insulin secretion with antagonism of the cannabinoid 1 receptor improving beta cell function. This indicates that there is a tonic inhibition of insulin secretion by endocannabinoids. Here we examine these reports and recent papers showing that endocannabinoids increase insulin secretion and discuss the discrepancies in these observations.
    Summary: Conclusions on the exact nature of the effects of endocannabinoids on insulin secretion require rigorous study examining both acute and long-term effects at physiologically relevant doses employing both whole animal and clinically relevant models such as human islets in vitro and explanted in vivo, in rodent models of diabetes.
    MeSH term(s) Animals ; Cannabinoid Receptor Modulators/metabolism ; Endocannabinoids ; Humans ; Hypoglycemic Agents/pharmacology ; Insulin/metabolism ; Insulin Resistance ; Insulin Secretion ; Islets of Langerhans/drug effects ; Islets of Langerhans/metabolism ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Receptor, Cannabinoid, CB1/metabolism ; Signal Transduction/drug effects
    Chemical Substances Cannabinoid Receptor Modulators ; Endocannabinoids ; Hypoglycemic Agents ; Insulin ; Receptor, Cannabinoid, CB1
    Language English
    Publishing date 2011-02-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2272017-0
    ISSN 1752-2978 ; 1752-296X
    ISSN (online) 1752-2978
    ISSN 1752-296X
    DOI 10.1097/MED.0b013e32834455a8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

    Doyle, Máire E / Appleton, Ashley / Liu, Qing-Rong / Yao, Qin / Mazucanti, Caio H / Egan, Josephine M

    The American journal of pathology

    2021  Volume 191, Issue 9, Page(s) 1511–1519

    Abstract: Chemosensory changes are well-reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme 2 (ACE2). It is not ...

    Abstract Chemosensory changes are well-reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme 2 (ACE2). It is not known whether ACE2 is expressed on taste receptor cells (TRCs), or whether TRCs are infected directly. in situ hybridization probe and an antibody specific to ACE2 indicated presence of ACE2 on a subpopulation of TRCs (namely, type II cells in taste buds in taste papillae). Fungiform papillae of a SARS-CoV-2
    MeSH term(s) Angiotensin-Converting Enzyme 2/biosynthesis ; COVID-19/enzymology ; COVID-19/pathology ; COVID-19/virology ; Female ; Gene Expression Regulation, Enzymologic ; Humans ; Male ; SARS-CoV-2/metabolism ; Stem Cells/enzymology ; Stem Cells/pathology ; Stem Cells/virology ; Taste Buds/enzymology ; Taste Buds/pathology ; Taste Buds/virology
    Chemical Substances ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2021.05.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: AAV5-mediated manipulation of insulin expression in choroid plexus has long-term metabolic and behavioral consequences.

    Mazucanti, Caio Henrique / Kennedy, Vernon / Premathilake, Hasitha U / Doyle, Maire E / Tian, Jane / Liu, Qing-Rong / O'Connell, Jennifer / Camandola, Simonetta / Egan, Josephine M

    Cell reports

    2023  Volume 42, Issue 8, Page(s) 112903

    Abstract: The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs ... ...

    Abstract The choroid plexus (CP) is a source of trophic factors for the developing and mature brain. Insulin is produced in epithelial cells of the CP (EChPs), and its secretion is stimulated by Htr2c-mediated signaling. We modulated insulin expression in EChPs with intracerebroventricular injections of AAV5. Insulin overexpression in CP decelerates food intake, whereas its knockdown has the opposite effect. Insulin overexpression also results in reduced anxious behavior. Transcriptomic changes in the hypothalamus, especially in synapse-related processes, are also seen in mice overexpressing insulin in CP. Last, activation of Gq signaling in CP leads to acute Akt phosphorylation in neurons of the arcuate nucleus, indicating a direct action of CP-derived insulin on the hypothalamus. Taken together, our findings signify that CP is a relevant source of insulin in the central nervous system and that CP-derived insulin should be taken into consideration in future work pertaining to insulin actions in the brain.
    MeSH term(s) Mice ; Animals ; Insulin/metabolism ; Choroid Plexus/metabolism ; Brain ; Hypothalamus/metabolism ; Arcuate Nucleus of Hypothalamus
    Chemical Substances Insulin
    Language English
    Publishing date 2023-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112903
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Diabetic serum from older women increases adipogenic differentiation in mesenchymal stem cells.

    Moseley, Kendall F / Doyle, Máire E / Jan De Beur, Suzanne M

    Endocrine research

    2018  Volume 43, Issue 3, Page(s) 155–165

    Abstract: Background: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local effects on the skeleton. One such ... ...

    Abstract Background: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local effects on the skeleton. One such factor could be by altering the microenvironment of the mesenchymal stem cells (MSCs), multipotent progenitors capable of differentiating into adipocytes or osteoblasts.
    Methods: Sera were obtained from four participant groups (n = 40 total, 10 per group): (1) young women with normal glucose tolerance (NGTY), (2) postmenopausal women with NGT), (3) postmenopausal women with impaired glucose tolerance (IGT), and (4) postmenopausal women with T2DM. Sera were incubated with human MSCs for 14 days. Cell proliferation and apoptosis were measured using EdU and TUNEL labeling assays, respectively. MSC differentiation for each group was determined using osteogenic and adipogenic gene expression markers quantified by qRT-PCR, as well as Alizarin Red and Oil Red O staining.
    Results: Expression of adipogenic genes was greater than twofold higher (P < 0.05) in MSCs cultured with T2DM sera compared to those incubated with NGTY, NGT, or IGT sera. The increase in adipogenic gene expression corresponded with increased Oil Red O staining. Despite the increased adipogenic differentiation of MSCs exposed to T2DM sera, cell proliferation and apoptosis rates as well as osteoblastic activity were not significantly different among the four conditions.
    Conclusions: Systemic, circulating factors in the serum of older women with T2DM may promote MSC differentiation into adipocytes versus osteoblasts. Increased differentiation of MSCs into adipocytes is one possible mechanism by which T2DM increases fracture risk.
    MeSH term(s) Adipogenesis/physiology ; Aged ; Apoptosis/physiology ; Cell Line ; Cell Proliferation/physiology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood ; Female ; Glucose Intolerance/blood ; Humans ; Mesenchymal Stem Cells/metabolism ; Middle Aged ; Osteogenesis/physiology ; Postmenopause/blood
    Language English
    Publishing date 2018-03-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 605823-1
    ISSN 1532-4206 ; 0743-5800
    ISSN (online) 1532-4206
    ISSN 0743-5800
    DOI 10.1080/07435800.2018.1441868
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: A hyper-quiescent chromatin state formed during aging is reversed by regeneration.

    Yang, Na / Occean, James R / Melters, Daniël P / Shi, Changyou / Wang, Lin / Stransky, Stephanie / Doyle, Maire E / Cui, Chang-Yi / Delannoy, Michael / Fan, Jinshui / Slama, Eliza / Egan, Josephine M / De, Supriyo / Cunningham, Steven C / de Cabo, Rafael / Sidoli, Simone / Dalal, Yamini / Sen, Payel

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations ... ...

    Abstract Epigenetic alterations are a key hallmark of aging but have been limitedly explored in tissues. Here, using naturally aged murine liver as a model and extending to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach, and the first direct visualization of aged chromatin we find that globally, old cells show H3K27me3-driven broad heterochromatinization and transcription suppression. At the local level, site-specific loss of H3K27me3 over promoters of genes encoding developmental transcription factors leads to expression of otherwise non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.14.528512
    Database MEDical Literature Analysis and Retrieval System OnLINE

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