Hepatic ischemia-reperfusion injury (IRI) is an intricate and inevitable physiological event occurred in the liver transplantation (LT) and it is of paramount importance to devise novel and efficient methods to ameliorate IRI. Herein, we report a "one stone for two birds" strategy for IRI therapy. In this study, we engineered CAR-ART nanoparticles (CANPs) utilizing carvacrol (CAR) and artesunate (ART) as precursor monomers and simulated IRI in an in vivo mouse model. Our research results indicate that CANPs proficiently surmount the constraints linked with the solitary components utilized in preceding studies such as water solubility, stability, and biocompatibility. Furthermore, they exhibit a distinctive accumulation in the liver. From an immunological standpoint, CANPs have been observed to significantly impede the accumulation and activation of various immune cells such as macrophages, neutrophils, and Kupffer cells. This results in the restoration of the hepatic immune cell distribution to a state akin to that of a normal liver. Furthermore, CANPs markedly inhibit the accumulation of a multitude of pro-inflammatory cytokines. Cellularly, it has been observed that CANPs significantly hinder the onset of ferroptosis in hepatocytes. This is accomplished by inhibiting the accumulation of crucial enzymes such as long-chain-fatty-acid-CoA ligase 4 (ACSL4), as well as associated lipid oxidation intermediates like malondialdehyde (MDA), which are relevant to the process of ferroptosis. Consequently, a solitary intravenous administration of CANPs has the potential to simultaneously inhibit ferroptosis of hepatocytes and normalize proinflammatory immune cells, one stone for two birds. In conclusion, CANPs may serve as a promising multi-bioactive nanotherapeutic agent and a bioresponsive targeting delivery nanocarrier, offering a potentially effective treatment strategy for hepatic IRI.

Liver diseases are worldwide problems closely associated with various stresses, such as endoplasmic reticulum stress. The exact interplay between stress and liver diseases remains unclear. Autophagy plays an essential role in maintaining homeostasis, and recent studies indicate tight crosstalk between stress and autophagy in liver diseases. Once the balance between damage and autophagy is broken, autophagy can no longer resist injury or maintain homeostasis. In recent years, FGF21 (fibroblast growth factor 21)-induced autophagy has attracted much attention. FGF21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to stress. Also, increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal role. This review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

The research of mesenchymal stem cells (MSCs) in the field of liver diseases has received more and more attention. This paper introduces the current situation, hot spots, and development trends in this field. Comprehensive searches were conducted using Web of Science Core Collection from January 1, 2000 to December 13, 2021 with the following keywords: TS(topic) = (liver^*OR hepatic^*OR hepatocyte) AND TS(topic) = (Mesenchymal stem cell^*). VOSviewer (version 1.6.16) and CiteSpace V are used as bibliometric tools to analyze and visualize the knowledge graph. A total of 4452 papers were included in this study, and the number of research papers on MSCs in the field of liver diseases increased from January 2000 to December 2020. Eighty-four countries and regions have published articles on research in this field, among which China and the United States are the main two countries of publication. Based on the keyword burst detection, we find that the research in this field has shifted from basic research to clinical application, from medical research to interdisciplinary research. Tissue engineering and regenerative medicine are the frontier fields of MSCs research in liver diseases. Multicountry, multi-author cooperation, and multi-disciplinary intersection are the research trends in this field. Exocrine body, obesity, and tissue engineering are the hotspots in this field.

Congenital biliary tract malformations are a series of rare but extremely serious diseases that mainly include biliary atresia and biliary hypoplasia (referred to as Alagille syndrome). The rapid progression of biliary atresia and Alagille syndrome results in jaundice, cholestatic liver disease, cirrhosis, and even liver failure. In most cases, supportive or clinically specific therapies cannot achieve satisfactory outcomes. Therefore, liver transplantation (especially living donor liver transplantation) may be required. As many studies have elucidated the role of genetic factors and the molecular mechanism of congenital biliary tract malformations, experimental therapies such as organoid transplantation, cell therapy, and immunotherapy have been proved to be feasible. These advanced methods have shown outstanding advantages, particularly in patients with end-stage biliary tract malformations, surgery failure, and other problems that cannot be solved by conventional therapies. This review article discusses the potential pathogenesis of and promising therapeutic strategies for biliary tract malformations.

The use of neural networks (NNs) as a cutting-edge technique in the medical field has drawn considerable attention. NN models "learn" from a large amount of data and then find corresponding clinical patterns that are challenging for clinicians to recognize. In this study, we focus on liver transplantation (LT), which is an effective treatment for end-stage liver diseases. The management before and after LT produces a massive quantity of medical data, which can be fully processed by NNs. We describe recent progress in the clinical application of NNs to LT in five respects: pre-transplantation evaluation of the donor and recipient, recipient outcome prediction, allocation system development, operation monitoring, and post-transplantation complication prediction. This review provides clinicians and researchers with a description of forefront applications of NNs in the field of LT and discusses prospects and pitfalls.

Hepatocellular carcinoma (HCC) is one of the most aggressive human malignancies with a dismal survival rate. Few strategies can effectively prevent the occurrence of HCC. Although immunotherapy has significantly improved HCC-related survival in recent years, this systemic therapy is very expensive and lays a heavy burden on most HCC patients. Aspirin, which is currently one of the most widely used medications in analgesic and cardiovascular diseases, is reported to have anti-tumor effects on HCC. Most importantly, long-term administration of low-dose aspirin does not significantly increase the risk of gastrointestinal bleeding. Owing to its cost-effectiveness and wide use, aspirin can be easily applied as an HCC treatment and is affordable for a wide range of patients. Therefore, deeper understanding and more attention are needed to extend the frontline of aspirin's preventive and therapeutic potential into cancer research and management. In this review, we discuss the preventive effect of aspirin on HCC in the context of different etiological factors, including hepatitis B or hepatitis C virus infection, non-alcoholic fatty liver disease, and alcohol-associated liver disease. The therapeutic role of aspirin in resectable or unresectable HCC management is also discussed. Furthermore, the mechanisms underlying the anti-cancer effects of aspirin on HCC are fully reviewed and discussed in the following two aspects: the effect of aspirin on multi-oncogenic signaling pathways in HCC (e.g., AMPK, Wnt/β-catenin, NF-κB) and aspirin-mediated immunometabolic responses in liver diseases. These findings indicate aspirin is a promising agent for populations at risk and HCC patients to prevent or treat HCC.