The present investigation focused on the transepithelial flux of liquiritigenin (LG), davidigenin (DG), liquiritin (LQ), and liquiritin apioside (LA) using the human colonic cell line Caco-2 as a model of human intestinal absorption. Apparent permeability coefficients (Papp) for the apical to basolateral flux of LG and DG were (16.0 +/- 0.727) x 10(-6) cm/s and (18.2 +/- 1.67) x 10(-6) cm/s, respectively. These Papp were higher than that of the transcellular transport marker propranolol (13.5 +/- 0.34) x 10(-6) cm/s (P < 0.01). Papp for the apical to basolateral flux of LQ and LA were (0.26 +/- 0.12) x 10(-6) cm/s and (0.075 +/- 0.005) x 10(-6) cm/s, respectively. These Papp were lower than that of the paracellular transport marker mannitol (0.64 +/- 0.04) x 10(-6) cm/s (LG, P < 0.01; LA, P < 0.001). These data suggested excellent absorption of LG and DG through the human intestinal epithelial cell line. On the contrary, poor absorption of LQ and LA was expected due to the little transepithelial flux of these compounds in the human colonic cell line Caco-2.
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http://dx.doi.org/10.1016/j.jep.2003.09.009 | DOI Listing |
J Med Chem
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Warren Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37067, Unites States.
Herein, we report progress toward a metabotropic glutamate receptor subtype 1 (mGlu) positive allosteric modulator (PAM) clinical candidate and the discovery of VU6024578/BI02982816. From a weak high-throughput screening hit (VU0538160, EC > 10 μM, 71% Glu), optimization efforts improved functional potency over 185-fold to deliver the selective (inactive on mGlu) and CNS penetrant (rat K = 0.99, K = 0.
View Article and Find Full Text PDFMaterials (Basel)
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School of Transportation Engineering, Shandong Jianzhu University, Jinan 250101, China.
Sci Rep
October 2024
Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 44bis, 10126, Turin, Italy.
P. aeruginosa employs specific quorum sensing (QS) mechanisms to orchestrate biofilm formation, enhancing resistance to host defences. In physiological conditions, QS molecules permeate the lung environment and cellular membrane to reach the cytoplasmic Aryl Hydrocarbon Receptor (AhR) that is pivotal for activating the immune response against infection.
View Article and Find Full Text PDFNanoscale
November 2024
School of Electronic Science and Engineering, Nanjing University, Nanjing 210093, China.
Two-dimensional (2D) transition metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS), hold great promise for next-generation nanoelectronic and nanophotonic devices. While high photoresponsivity and broad spectral coverage (UV-IR) have been reported, the slow response time of MoS photodetectors caused by their unfavorable RC characteristics is still a major limit in current devices. Once the RC limit issue is resolved, the intrinsic saturation drift velocity of electrons in TMDs (∼10 cm s) may enable GHz opto-electronic operations.
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October 2024
Artois University, Blood-Brain Barrier Laboratory, UR 2465, Lens, France.
Several studies emphasized on the preventive and therapeutic potential of Docosahexaenoic Acid (DHA, 22:6n-3) supplementation in chronic and age-related disorders including neurodegenerative diseases. Researchers principally studied the cerebral accretion of Lysophosphatidylcholine (LysoPC-DHA), the furthermost vital Lysophospholipid-DHA (LysoPL-DHA) in blood plasma. Nevertheless, the cerebral bioavailability of other LysoPL-DHA forms including Lysophosphatidylethanolamine (LysoPE-DHA), and Lysophosphatidylserine (LysoPS-DHA) were not extensively examined even though their vital biological functions in the brain.
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