Key Points• Platelets stimulate proliferation of HepG2 cells, which requires uptake of platelets by the HepG2 cell.• Platelets stimulate HepG2 cell proliferation in part by transfer of RNA from the anucleate platelet to the nucleated HepG2 cell.Liver regeneration is stimulated by blood platelets, but the molecular mechanisms involved are largely unexplored. Although platelets are anucleate, they do contain coding or regulatory RNAs that can be functional within the platelet or, after transfer, in other cell types. Here, we show that platelets and platelet-like particles (PLPs) derived from the megakaryoblastic cell line MEG-01 stimulate proliferation of HepG2 cells. Platelets or PLPs were internalized within 1 hour by HepG2 cells and accumulated in the perinuclear region of the hepatocyte. Platelet internalization also occurred following a partial hepatectomy in mice. Annexin A5 blocked platelet internalization and HepG2 proliferation. We labeled total RNA of MEG-01 cells by incorporation of 5-ethynyluridine (EU) and added EU-labeled PLPs to HepG2 cells. PLP-derived RNA was detected in the cytoplasm of the HepG2 cell. We next generated PLPs containing green fluorescent protein (GFP)-tagged actin messenger RNA. PLPs did not synthesize GFP, but in coculture with HepG2 cells, significant GFP protein synthesis was demonstrated. RNA-degrading enzymes partly blocked the stimulating effect of platelets on hepatocyte proliferation. Thus, platelets stimulate hepatocyte proliferation via a mechanism that is dependent on platelet internalization by hepatocytes followed by functional transfer of RNA stored in the anucleate platelet. This mechanism may contribute to platelet-mediated liver regeneration. (Blood. 2015;126(6):798-806) IntroductionBlood platelets have essential roles in hemostasis and thrombosis, inflammation, host defense, and wound healing. [1][2][3][4] Emerging evidence from recent in vitro and in vivo studies suggests that platelets have a pivotal role in liver regeneration. [5][6][7][8] In experimental animal models in which platelets were depleted or functionally impaired, liver regeneration after a partial liver resection was substantially delayed. 6 Conversely, following a partial liver resection in animals with a drug-induced thrombocytosis, liver regeneration was accelerated. 9,10 In a clinical study, we showed that a low platelet count is an independent predictor of delayed postoperative liver function recovery following a partial liver resection, suggesting that platelets stimulate liver regeneration also in humans. 11The molecular mechanisms of platelet-mediated stimulation of liver regeneration are largely unexplored. Platelets contain 2 distinct types of storage organelles: a granules and dense granules. The a granules contain, among many proteins, a number of growth factors that have an established role in liver regeneration (platelet-derived growth factor [PDGF], hepatocyte growth factor [HGF], insulin-like growth factor [IGF], and vascular endothelial growth factor [VEGF]). 8,12 In addition...
Valve ablation with bladder neck incision may result in better bladder urodynamic function in comparison to simple valve ablation. However, long-term studies with followup through puberty are required to evaluate the final effects on renal function.
Artificial intelligence (AI) is being increasingly applied in healthcare. The expansion of AI in healthcare necessitates AI-related ethical issues to be studied and addressed. This systematic scoping review was conducted to identify the ethical issues of AI application in healthcare, to highlight gaps, and to propose steps to move towards an evidence-informed approach for addressing them. A systematic search was conducted to retrieve all articles examining the ethical aspects of AI application in healthcare from Medline (PubMed) and Embase (OVID), published between 2010 and July 21, 2020. The search terms were “artificial intelligence” or “machine learning” or “deep learning” in combination with “ethics” or “bioethics”. The studies were selected utilizing a PRISMA flowchart and predefined inclusion criteria. Ethical principles of respect for human autonomy, prevention of harm, fairness, explicability, and privacy were charted. The search yielded 2166 articles, of which 18 articles were selected for data charting on the basis of the predefined inclusion criteria. The focus of many articles was a general discussion about ethics and AI. Nevertheless, there was limited examination of ethical principles in terms of consideration for design or deployment of AI in most retrieved studies. In the few instances where ethical principles were considered, fairness, preservation of human autonomy, explicability and privacy were equally discussed. The principle of prevention of harm was the least explored topic. Practical tools for testing and upholding ethical requirements across the lifecycle of AI-based technologies are largely absent from the body of reported evidence. In addition, the perspective of different stakeholders is largely missing.
BackgroundA real-time objective evaluation for the extent of liver steatosis during liver transplantation is currently not available. Diffuse reflectance spectroscopy (DRS) rapidly and accurately assesses the extent of steatosis in human livers with mild steatosis. However, it is yet unknown whether DRS accurately quantifies moderate/severe steatosis and is able to distinguish between micro- and macrovesicular steatosis.MethodsC57BL/6JolaHsd mice were fed wit a choline-deficient l-amino acid-defined diet (CD-AA) or a choline-sufficient l-amino acid-defined control diet (CS-AA) for 3, 8, and 20 weeks. In addition B6.V-Lepob/OlaHsd (ob/ob) mice and their lean controls were studied. A total of 104 DRS measurements were performed in liver tissue ex vivo. The degree of steatosis was quantified from the DRS data and compared with histopathological analysis.ResultsWhen assessed by histology, livers of mice fed with a CD-AA and CS-AA diet displayed macrovesicular steatosis (range 0–74 %), ob/ob mice revealed only microvesicular steatosis (range 75–80 %), and their lean controls showed no steatosis. The quantification of steatosis by DRS correlated well with pathology (correlation of 0.76 in CD-AA/CS-AA fed mice and a correlation of 0.75 in ob/ob mice). DRS spectra did not distinguish between micro- and macrovesicular steatosis. In samples from CD-AA/CS-AA fed mice, the DRS was able to distinguish between mild and moderate/severe steatosis with a sensitivity and specificity of 86 and 81 %, respectively.ConclusionDRS can quantify steatosis with good agreement to histopathological analysis. DRS may be useful for real-time objective evaluation of liver steatosis during liver transplantation, especially to differentiate between mild and moderate/severe steatosis.
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