Drug hepatotoxicity testing requires in vitro hepatocyte culture to maintain the long-term and stable liver specific functions. We developed a drug testing platform based on laminar-flow immediate-overlay hepatocyte sandwich perfusion culture. The immediate-overlay sandwich (collagen-coated porous polymeric membrane as top overlay) protects the cells and integrity of the top collagen matrix from the impact of flow. A bioreactor was designed that allowed proper control of shear stress and mass transfer. The culture parameters such as the optimal perfusion initiation time and flow rate were systematically and mechanistically determined. The optimized system could re-establish hepatocyte polarity to support biliary excretion and to maintain other liver specific functions, such as the biotransformation enzyme activities, for two weeks that extended the usable in vitro hepatocyte-based drug testing window. When the perfusion cultured hepatocytes from days 7 or 14 were used for drug testing, the APAP-induced hepatotoxicity measurements were more sensitive and consistent over time than the static culture control, enabling further exploitations in large-scale drug testing applications.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biomaterials.2009.07.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Finding potential inhibitors from phytochemicals against nucleoprotein of crimean congo fever virus using in silico approach.
Sci Rep
December 2024
Department of Chemical and Biological Engineering, Gachon University, Seongnam, 13120, Republic of Korea.
The Crimean Congo virus has been reported to be a part of the spherical RNA-enveloped viruses from the Bunyaviridae family. Crimean Congo fever (CCHF) is a fatal disease with having fatality rate of up to 40%. It is declared endemic by the World Health Organization.
View Article and Find Full Text PDFBAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.
View Article and Find Full Text PDFThe current landscape of 1,2,3-triazole-(fused) six-membered nitrogen-containing heteroaromatic ring hybrids with anticancer therapeutic potential.
Arch Pharm (Weinheim)
January 2025
School of Chemistry and Pharmaceutical Engineering, Huanghuai University, Zhumadian, Henan, China.
Cancer, characterized by uncontrolled growth and spread of abnormal cells potentially influencing almost all tissues in the body, is one of the most devastating and lethal diseases throughout the world. Chemotherapy is one of the principal approaches for cancer treatment, but multidrug resistance and severe side effects represent the main barriers to the success of therapy, creating a vital need to develop novel chemotherapeutic agents. The 1,2,3-triazole moiety can be conveniently constructed by "click chemistry" and could exert diverse noncovalent interactions with various enzymes in cancer cells.
View Article and Find Full Text PDFRNA-ModX: a multilabel prediction and interpretation framework for RNA modifications.
Brief Bioinform
November 2024
In-Service Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, 110, Taipei, Taiwan.
Accurate prediction of RNA modifications holds profound implications for elucidating RNA function and mechanism, with potential applications in drug development. Here, the RNA-ModX presents a highly precise predictive model designed to forecast post-transcriptional RNA modifications, complemented by a user-friendly web application tailored for seamless utilization by future researchers. To achieve exceptional accuracy, the RNA-ModX systematically explored a range of machine learning models, including Long Short-Term Memory (LSTM), Gated Recurrent Unit, and Transformer-based architectures.
View Article and Find Full Text PDFPrecise identification of somatic and germline variants in the absence of matched normal samples.
Brief Bioinform
November 2024
The Department of Medical Oncology, Jilin Cancer Hospital, No. 1066, Jinhu Road, Changchun, 130012, China.
Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!