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- Godoy, Patricio, et al.
(författare)
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Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
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Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
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| 2. |
- Chen, Tao, et al.
(författare)
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Update on Novel Non-Operative Treatment for Osteoarthritis : Current Status and Future Trends
- 2021
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Osteoarthritis (OA) is a leading cause of pain and disability which results in a reduced quality of life. Due to the avascular nature of cartilage, damaged cartilage has a finite capacity for healing or regeneration. To date, conservative management, including physical measures and pharmacological therapy are still the principal choices offered for OA patients. Joint arthroplasties or total replacement surgeries are served as the ultimate therapeutic option to rehabilitate the joint function of patients who withstand severe OA. However, these approaches are mainly to relieve the symptoms of OA, instead of decelerating or reversing the progress of cartilage damage. Disease-modifying osteoarthritis drugs (DMOADs) aiming to modify key structures within the OA joints are in development. Tissue engineering is a promising strategy for repairing cartilage, in which cells, genes, and biomaterials are encompassed. Here, we review the current status of preclinical investigations and clinical translations of tissue engineering in the non-operative treatment of OA. Furthermore, this review provides our perspective on the challenges and future directions of tissue engineering in cartilage regeneration.
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| 4. |
- Tan, Jun, et al.
(författare)
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The Effectiveness of Metagenomic Next-Generation Sequencing in the Diagnosis of Prosthetic Joint Infection : A Systematic Review and Meta-Analysis
- 2022
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Background: A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI. Methods: We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as “prosthetic joint infection”, “PJI”, and “metagenomic sequencing”. Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis. Results: We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97). Conclusion: Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
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