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  1. AU="Linden, David R"
  2. AU="Schaefer, Jan"
  3. AU="Sprent, Noah"
  4. AU="Dreyer, Benard P"
  5. AU=Borchman Douglas
  6. AU="Navarro-Garcia, Fernando"
  7. AU=Vandenbon Alexis
  8. AU="Alonso-Ventura, Vanesa"
  9. AU="Ganhewa, Aparna D"
  10. AU="Draggoo, V"
  11. AU="Natalia Skogberg"
  12. AU="Hiroaki Itoh" AU="Hiroaki Itoh"
  13. AU="Nicolette de Keizer"
  14. AU="Jamjoom, Dima"
  15. AU="Seeman, Tomas"
  16. AU="Popescu, S"
  17. AU="Kurtul, Irmak"
  18. AU="Christofferson, Scott"
  19. AU="Balghith, Mohammed A"
  20. AU="Banu, Qamar"
  21. AU="Giangregorio, Lora"
  22. AU="Stafiej, Patrycja"
  23. AU="Lau, Vincent W-H"
  24. AU="Francesca Storici"
  25. AU="Coulter-Mackie, Marion"
  26. AU="Mayank Goyal"
  27. AU="Lempke, Olga M"
  28. AU="Khan, Asad Majeed"
  29. AU=Ismail Mohd Iswadi
  30. AU="Jewel Park"
  31. AU="Hunter-Smith, David J"
  32. AU="Requião-Moura, Lúcio Roberto"
  33. AU=DesRochers Teresa M.
  34. AU="Kruschwitz, Sabine"
  35. AU=Sriwijiatalai Won
  36. AU="Bozzaro, Claudia"
  37. AU="Beckendorf, C"
  38. AU="Birge, N W"
  39. AU="Hoang, Oi Pui"
  40. AU="Saradha Baskaran"
  41. AU="Culotta, Lorenza"
  42. AU=Cleaver Ondine
  43. AU="Jordan A. Kreidberg"
  44. AU="Al-Marshoud, Majida"
  45. AU="David S Hui"
  46. AU="Manjappa, Shivaprasad"
  47. AU="Balkan, S"
  48. AU="Chen, Emma"
  49. AU="Delean, Ada"
  50. AU="Gurao, Ankita"
  51. AU="Lang, Zhen"
  52. AU="Mahnaz Mohammadpour"
  53. AU="Britta Grillitsch"
  54. AU=Hoeffner Ellen G
  55. AU="Al Harbi, Shmeylan"
  56. AU=Polevoda Bogdan
  57. AU="Raffaele Galiero"
  58. AU=Hruskova Z
  59. AU="Ayers, J"
  60. AU="Cohen, A D"
  61. AU="Brunetti, Gian Luca"
  62. AU=Andrade Daniel
  63. AU=Hay William W Jr

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  1. Artikel: Microbiota-dependent early life programming of gastrointestinal motility.

    Frith, Mary E / Kashyap, Purna C / Linden, David R / Theriault, Betty / Chang, Eugene B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli ... ...

    Abstract Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.
    Sprache Englisch
    Erscheinungsdatum 2023-11-13
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.11.08.566304
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Enhanced excitability of guinea pig ileum myenteric AH neurons during and following recovery from chemical colitis.

    Linden, David R

    Neuroscience letters

    2013  Band 545, Seite(n) 91–95

    Abstract: Inflammation of the colon changes motor function of more proximal regions of the gastrointestinal tract. Colitis alters the neurophysiology of enteric neurons within the region of inflammation, which may contribute to altered colonic motor and secretory ... ...

    Abstract Inflammation of the colon changes motor function of more proximal regions of the gastrointestinal tract. Colitis alters the neurophysiology of enteric neurons within the region of inflammation, which may contribute to altered colonic motor and secretory function. This study seeks to test the hypothesis that colitis alters the neurophysiology of myenteric neurons in the non-inflamed ileum, and that altered neurophysiology coincides with altered small bowel motor function. Trinitrobenzene sulfonic acid (TNBS)-induced colitis was associated with hyperexcitability of AH neurons in the ileum myenteric plexus, demonstrated by depolarized neurons and increased numbers of action potentials, but without changes in the action potential duration or afterhyperpolarization typical of plasticity in these cells. There were no changes in synaptic transmission of either AH neurons or S neurons observed in the current study. The onset of AH neuron hyperexcitability occurred 24 h following administration of TNBS, and persisted to eight weeks, a time point following the resolution of colitis. Small bowel transit was reduced as early as 12 h after TNBS and resolved by 48 h after TNBS. While AH neurons play a central role in coordinating motor function of the ileum, changes in excitability of these neurons did not coincide with changes in small bowel transit.
    Mesh-Begriff(e) Animals ; Colitis/chemically induced ; Colitis/physiopathology ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Gastrointestinal Motility/drug effects ; Gastrointestinal Motility/physiology ; Guinea Pigs ; Ileum/drug effects ; Ileum/physiology ; Motor Neurons/drug effects ; Motor Neurons/physiology ; Recovery of Function/physiology ; Trinitrobenzenesulfonic Acid
    Chemische Substanzen Trinitrobenzenesulfonic Acid (8T3HQG2ZC4)
    Sprache Englisch
    Erscheinungsdatum 2013-04-28
    Erscheinungsland Ireland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2013.04.021
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Hydrogen sulfide signaling in the gastrointestinal tract.

    Linden, David R

    Antioxidants & redox signaling

    2013  Band 20, Heft 5, Seite(n) 818–830

    Abstract: Significance: The current literature regarding the effects of the gaseous signal molecule hydrogen sulfide (H2S) in the gastrointestinal system is reviewed. Bacterial, host and pharmaceutical-derived H2S are all considered and presented according to the ...

    Abstract Significance: The current literature regarding the effects of the gaseous signal molecule hydrogen sulfide (H2S) in the gastrointestinal system is reviewed. Bacterial, host and pharmaceutical-derived H2S are all considered and presented according to the physiological or pathophysiological effects of the gaseous signal molecule. These subjects include the toxicology of intestinal H2S with emphasis on bacterial-derived H2S, especially from sulfate-reducing bacteria, the role of endogenous and exogenous H2S in intestinal inflammation, and the roles of H2S in gastrointestinal motility, secretion and nociception.
    Recent advances: While its pro- and anti-inflammatory, smooth muscle relaxant, prosecretory, and pro- and antinociceptive actions continue to remain the major effects of H2S in this system; recent findings have expanded the potential molecular targets for H2S in the gastrointestinal tract.
    Critical issues: Numerous discrepancies remain in the literature, and definitive molecular targets in this system have not been supported by the use of competitive antagonism.
    Future directions: Future work will hopefully resolve discrepancies in the literature and identify molecular targets and mechanisms of action for H2S. It is clear from the current literature that the long-appreciated relationship between H2S and the gastrointestinal tract continues to be strong as we endeavor to unravel its mysteries.
    Mesh-Begriff(e) Animals ; Bacteria/metabolism ; Gastrointestinal Motility ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Tract/metabolism ; Gastrointestinal Tract/microbiology ; Humans ; Hydrogen Sulfide/metabolism ; Inflammation/metabolism ; Intestinal Mucosa/metabolism ; Nociception ; Signal Transduction
    Chemische Substanzen Hydrogen Sulfide (YY9FVM7NSN)
    Sprache Englisch
    Erscheinungsdatum 2013-05-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1483836-9
    ISSN 1557-7716 ; 1523-0864
    ISSN (online) 1557-7716
    ISSN 1523-0864
    DOI 10.1089/ars.2013.5312
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation.

    Truong Thuy Nguyen, Vy / Taheri, Negar / Choi, Egan L / Kellogg, Todd A / Linden, David R / Hayashi, Yujiro

    Cellular and molecular gastroenterology and hepatology

    2023  Band 16, Heft 3, Seite(n) 369–383

    Abstract: Background & aims: Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of ... ...

    Abstract Background & aims: Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging.
    Methods: Klotho mice were treated with the stable IGF1 analog LONG R
    Results: LONG R
    Conclusions: IGF1 can mitigate age-related ICC/ICC-SC loss by activating ERK1/2 signaling, leading to improved gastric compliance and increased food intake in klotho mice.
    Mesh-Begriff(e) Aged ; Animals ; Humans ; Mice ; Aging ; Insulin/metabolism ; Interstitial Cells of Cajal/metabolism ; MAP Kinase Signaling System ; Stomach
    Chemische Substanzen Insulin ; insulin-like growth factor-1, mouse ; Mapk3 protein, mouse (EC 2.7.11.24) ; Mapk1 protein, mouse (EC 2.7.11.24)
    Sprache Englisch
    Erscheinungsdatum 2023-06-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2819778-1
    ISSN 2352-345X ; 2352-345X
    ISSN (online) 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2023.06.002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Colitis is associated with a loss of intestinofugal neurons.

    Linden, David R

    American journal of physiology. Gastrointestinal and liver physiology

    2012  Band 303, Heft 10, Seite(n) G1096–104

    Abstract: Intestinofugal neurons sense and receive information regarding mechanical distension of the bowel and transmit this information to postganglionic sympathetic neurons in the prevertebral ganglia. Previous studies have demonstrated that trinitrobenzene ... ...

    Abstract Intestinofugal neurons sense and receive information regarding mechanical distension of the bowel and transmit this information to postganglionic sympathetic neurons in the prevertebral ganglia. Previous studies have demonstrated that trinitrobenzene sulfonic acid (TNBS)-induced colitis is associated with a loss of myenteric neurons that occurs within the first 12 h following the inflammatory insult. The purpose of this study was to test the hypothesis that intestinofugal neurons are among the myenteric neurons lost during TNBS-induced colitis. The retrograde tracing dye Fast Blue was used to label intestinofugal neurons, and immunohistochemical staining for the RNA-binding proteins HuC/D was used to count all myenteric neurons. Ongoing synaptic input to neurons in the guinea pig inferior mesenteric ganglion (IMG) was recorded via conventional intracellular electrophysiology. In control preparations, intestinofugal neurons account for 0.25% of myenteric neurons. In the distal colon of TNBS-treated animals, the proportion of intestinofugal neurons was reduced to 0.05% (an 80% reduction) within the region of inflammation where 20-25% of myenteric neurons were lost. Neither intestinofugal neurons specifically nor myenteric neurons were reduced in more proximal uninflamed regions. There is a reduction in the frequency of ongoing synaptic potentials in visceromotor neurons of the IMG at 12 and 24 h and 6 and 56 days after TNBS. Collectively, the results of this study suggest that intestinofugal neurons are among the myenteric neurons lost during inflammation and may be selectively targeted. Because intestinofugal neurons are a major driver of sympathetic output to the gut, the loss of intestinofugal neurons may have a profound pathophysiological significance.
    Mesh-Begriff(e) Amidines ; Animals ; Colitis/chemically induced ; Colitis/pathology ; Colitis/physiopathology ; Female ; Ganglia, Sympathetic/physiology ; Guinea Pigs ; Intestines/physiopathology ; Male ; Myenteric Plexus/physiology ; Neurons/pathology ; Neurons/physiology ; Trinitrobenzenesulfonic Acid/adverse effects
    Chemische Substanzen Amidines ; diamidino compound 253-50 ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4)
    Sprache Englisch
    Erscheinungsdatum 2012-09-20
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00176.2012
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis.

    Linden, David R

    American journal of physiology. Gastrointestinal and liver physiology

    2012  Band 303, Heft 9, Seite(n) G1067–75

    Abstract: Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This ...

    Abstract Postganglionic sympathetic neurons in the prevertebral ganglia (PVG) provide ongoing inhibitory tone to the gastrointestinal tract and receive innervation from mechanosensory intestinofugal afferent neurons primarily located in the colon and rectum. This study tests the hypothesis that colitis alters the excitability of PVG neurons. Intracellular recording techniques were used to evaluate changes in the electrical properties of inferior mesenteric ganglion (IMG) neurons in the trinitrobenzene sulfonic acid (TNBS) and acetic acid models of guinea pig colitis. Visceromotor IMG neurons were hyperexcitable 12 and 24 h, but not 6 h, post-TNBS during "acute" inflammation. Hyperexcitability persisted at 6 days post-TNBS during "chronic" inflammation, as well as at 56 days post-TNBS when colitis had resolved. In contrast, there was only a modest decrease in the current required to elicit an action potential at 24 h after acetic acid administration. Vasomotor neurons from inflamed preparations exhibited normal excitability. The excitatory effects of XE-991, a blocker of the channel that contributes to the M-type potassium current, and heteropodatoxin-2, a blocker of the channel that contributes to the A-type potassium current, were unchanged in TNBS-inflamed preparations, suggesting that these currents did not contribute to hyperexcitability. Riluzole, an inhibitor of persistent sodium currents, caused tonic visceromotor neurons to accommodate to sustained current pulses, regardless of the inflammatory state of the preparation, and restored a normal rheobase in neurons from TNBS-inflamed preparations but did not alter the rheobase of control preparations, suggesting that enhanced activity of voltage-gated sodium channels may contribute to colitis-induced hyperexcitability. Collectively, these data indicate that enhanced sympathetic drive as a result of hyperexcitable visceromotor neurons may contribute to small bowel dysfunction during colitis.
    Mesh-Begriff(e) Acetic Acid/pharmacology ; Action Potentials/physiology ; Animals ; Anthracenes/pharmacology ; Colitis/chemically induced ; Colitis/physiopathology ; Disease Models, Animal ; Electrophysiology ; Excitatory Amino Acid Antagonists/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; Excitatory Postsynaptic Potentials/physiology ; Guinea Pigs ; Indicators and Reagents/pharmacology ; Intestines/innervation ; Intestines/physiopathology ; Myenteric Plexus/drug effects ; Myenteric Plexus/physiopathology ; Reaction Time ; Riluzole/pharmacology ; Trinitrobenzenesulfonic Acid/pharmacology
    Chemische Substanzen 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone ; Anthracenes ; Excitatory Amino Acid Antagonists ; Indicators and Reagents ; Riluzole (7LJ087RS6F) ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4) ; Acetic Acid (Q40Q9N063P)
    Sprache Englisch
    Erscheinungsdatum 2012-09-06
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00226.2012
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Circadian rhythm and whole gut transit in mice.

    Laible, Emma / Wegner, Andrew / Knutson, Kaitlyn / Kacmaz, Halil / Garramone, Gwyneth K / Gogineni, Kamalika / Matveyenko, Aleksey / Linden, David R / Farrugia, Gianrico / Beyder, Arthur

    Neurogastroenterology and motility

    2024  Band 36, Heft 4, Seite(n) e14771

    Abstract: Background: In preclinical studies whole gut transit (WGT) in mice is a gold-standard "leading-edge" approach that measures the time between orogastric gavage of carmine red and defecation of the first carmine red pellet. Transit studies in humans are ... ...

    Abstract Background: In preclinical studies whole gut transit (WGT) in mice is a gold-standard "leading-edge" approach that measures the time between orogastric gavage of carmine red and defecation of the first carmine red pellet. Transit studies in humans are performed during the active day because GI motility and transit are suppressed during the night. Since mice are nocturnal, WGT studies traditionally done during the day occur during their rest phase. How circadian rhythm affects WGT in mice is not known.
    Methods: We used an automated approach for high temporal resolution uninterrupted testing of mouse WGT and activity. We housed wild-type Bl6/C57 mice under the standard 12 h light-dark cycles. At 8 weeks, we performed carmine red orogastric gavage and assessed WGT during Light (rest) conditions. Then, we exposed mice to a reverse 12 h light-dark cycle for 2 weeks and tested them in the Dark (active) under red light conditions. Timelapse videos were analyzed to quantify activity and to timestamp all pellets, and multiple parameters were analyzed.
    Key result: When complementary light cycle reversal experiments were performed, we found a significant increase in mouse activity when mice were tested during their Dark (active) phase, compared to their Light (rest) phase. In mice tested in the Active phase compared to the Rest phase, we found a significant acceleration in WGT, increased rate and total number of pellets produced, and more pellet clustering. These data show that the mice tested in the Active phase have important differences in activity that correlate with multiple alterations in gastrointestinal transit.
    Conclusion & inferences: During the Active phase mice have faster WGT, produce more pellets, and cluster their output compared to testing in the Rest phase. Like in humans, circadian rhythm is an important consideration for transit studies in mice, and a simple reverse light cycle approach facilitates further studies on the role of circadian rhythm in GI motility.
    Mesh-Begriff(e) Humans ; Mice ; Animals ; Carmine ; Circadian Rhythm ; Photoperiod ; Gastrointestinal Transit ; Rest
    Chemische Substanzen Carmine (CID8Z8N95N)
    Sprache Englisch
    Erscheinungsdatum 2024-02-23
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 1186328-6
    ISSN 1365-2982 ; 1350-1925
    ISSN (online) 1365-2982
    ISSN 1350-1925
    DOI 10.1111/nmo.14771
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: Measurement of Gastrointestinal and Colonic Motor Functions in Humans and Animals.

    Camilleri, Michael / Linden, David R

    Cellular and molecular gastroenterology and hepatology

    2016  Band 2, Heft 4, Seite(n) 412–428

    Abstract: Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both ...

    Abstract Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both humans and animals. There remains further opportunity to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings.
    Sprache Englisch
    Erscheinungsdatum 2016-07
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2016.04.003
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Passive siRNA transfection method for gene knockdown in air-liquid interface airway epithelial cell cultures.

    Bartman, Colleen M / Stelzig, Kimberly E / Linden, David R / Prakash, Y S / Chiarella, Sergio E

    American journal of physiology. Lung cellular and molecular physiology

    2021  Band 321, Heft 1, Seite(n) L280–L286

    Abstract: Differentiation of human bronchial epithelial cells (HBEs) in air-liquid interface (ALI) cultures recapitulates organotypic modeling of the in vivo environment. Although ALI cultures are invaluable for studying the respiratory epithelial barrier, loss-of- ...

    Abstract Differentiation of human bronchial epithelial cells (HBEs) in air-liquid interface (ALI) cultures recapitulates organotypic modeling of the in vivo environment. Although ALI cultures are invaluable for studying the respiratory epithelial barrier, loss-of-function studies are limited by potentially cytotoxic reagents in classical transfection methods, the length of the differentiation protocol, and the number of primary epithelial cell passages. Here, we present the efficacy and use of a simple method for small interfering RNA (siRNA) transfection of normal HBEs (NHBEs) in ALI cultures that does not require potentially cytotoxic transfection reagents and does not detrimentally alter the physiology or morphology of NHBEs during the differentiation process. This transfection protocol introduces a reproducible and efficient method for loss-of-function studies in HBE ALI cultures that can be leveraged for modeling the respiratory system and airway diseases.
    Mesh-Begriff(e) Cell Culture Techniques/methods ; Cell Differentiation ; Cells, Cultured ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Humans ; RNA, Small Interfering/genetics ; Respiratory Mucosa/cytology ; Respiratory Mucosa/metabolism ; Transfection/methods
    Chemische Substanzen RNA, Small Interfering
    Sprache Englisch
    Erscheinungsdatum 2021-05-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00122.2021
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Modeling Gut Neuro-Epithelial Connections in a Novel Micro uidic Device.

    De Hoyos, Manolo / Yu, Xi / Gonzalez-Suarez, Alan / Mercado-Perez, Arnaldo / Krueger, Eugene / Hernandez, Jeric / Druliner, Brooke / Linden, David R / Beyder, Arthur / Chen, Sisi / Fedyshyn, Yaroslav / Revzin, Alexander

    Research square

    2023  

    Abstract: Organs that face external environments, such as skin and gut, are lined by epithelia, which have two functions - to provide a semi-permeable barrier and to sense stimuli. The intestinal lumen is filled with diverse chemical and physical stimuli. ... ...

    Abstract Organs that face external environments, such as skin and gut, are lined by epithelia, which have two functions - to provide a semi-permeable barrier and to sense stimuli. The intestinal lumen is filled with diverse chemical and physical stimuli. Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function. Yet, the neuro-epithelial connections between intestinal epithelial cells and enteric neurons remain poorly resolved, which leaves us with limited mechanistic understanding of their function. We describe the development of a two-compartment microfluidic device for modeling neuro-epithelial interactions, and apply it to form the gut's neuro-epithelial connections. The device contains epithelial and neuronal compartments connected by microgrooves. The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids. We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week. In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons (IPANs) from transgenic mice that expressed the fluorescent protein tdTomato. IPANs extended projections into microgrooves, surrounded and frequently made contacts with epithelial cells. The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment. Our microfluidic device represents a platform for dissecting structure and function of neuro-epithelial connections in the gut and other organs (skin, lung, bladder, and others) in health and disease.
    Sprache Englisch
    Erscheinungsdatum 2023-09-07
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-2972828/v1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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