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Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.

Eur J Pharm Sci

January 2025

Preclinical Sciences & Translational Safety, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address:

The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.

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Apatinib, a commonly used tyrosine kinase inhibitor in cancer treatment, can cause adverse reactions such as hypertension. Hypertension, in turn, can increase the risk of certain cancers. The coexistence of these diseases makes the use of combination drugs more common in clinical practice, but the potential interactions and regulatory mechanisms in these drug combinations are poorly understood.

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Peripheral nerves promote mouse bone marrow regeneration by activating b2 and b3 adrenergic receptor signaling, raising the possibility that non-selective b blockers could inhibit engraftment after hematopoietic cell transplants (HCTs). We observed no effect of b blockers on steady-state mouse hematopoiesis. However, mice treated with a non-selective b blocker (carvedilol), but not a b1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs.

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Background: Historically, β-blockers have been associated with erectile dysfunction (ED). Nebivolol, a third-generation β-blocker, may have had no negative effect on erectile function because of its vasodilating properties. However, the evidence level was considered either as low or very low.

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In recent years, due to large-scale production and widespread use, drugs have posed a potential threat to biological and human health and have received increasing attention. The occurrence and distribution of drugs in urban rivers are influenced by various factors, such as urbanization level, population density, regional geographical and climatic characteristics, and drug consumption habits. In October 2022, the Yongjiang River Basin was divided into four sub-basins: upstream, midstream, tributaries, and downstream.

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