Acute liver failure (ALF) is an acute inflammatory liver disease with high mortality. Previous preclinical and clinical trials have confirmed that mesenchymal stem cell (MSC) is a promising therapeutic approach; however, the effect is not satisfied as the underlying molecular mechanisms of MSC in treating ALF remain unclear.

Animal bile is an important component of natural medicine and is widely used in clinical treatment. However, it is easy to cause mixed applications during processing, resulting in uneven quality, which seriously affects and harms the interests and health of consumers. Bile acids are the major bioactive constituents of bile and contain a variety of isomeric constituents. Although the components are structurally similar, they exhibit different pharmacological activities. Identifying the characteristics of each animal bile is particularly important for processing and reuse. It is necessary to establish an accurate analysis method to distinguish different types of animal bile. We evaluated the biological activity of key feature markers from various animal bile samples. In this study, a strategy combining metabolomics and machine learning was used to compare the bile of three different animals, and four key markers were screened. Quantitative analysis of the key markers showed that the levels of Glycochenodeoxycholic acid (GCDCA) and Taurodeoxycholic acid (TDCA) were highest in pig bile; Glycocholic acid (GCA) and Cholic acid (CA) were the most abundant in bovine and sheep bile, respectively. In addition, four key feature markers significantly inhibited the production of NO in LPS-stimulated RAW264.7 macrophage cells. These findings will contribute to the targeted development of bile in various animals and provide a basis for its rational application.

Transplantation of mesenchymal stem cells (MSCs) derived from bone marrow (BM) is an alternative treatment of acute liver failure (ALF) mainly because of the resulting anti-inflammatory activity. It is not known how MSCs regulate local immune responses and liver regeneration. This study explored the effects of MSCs on hepatic macrophages and the Wnt signaling pathway in ALF.

The interaction between small-molecule compounds of traditional Chinese medicine and their direct targets is the molecular initiation event, which is the key factor for toxicity efficacy. Psoralen, an active component of Fructus Psoraleae, is toxic to the liver and has various pharmacological properties. Although the mechanism of psoralen-induced hepatotoxicity has been studied, the direct target of psoralen remains unclear. Thus, the aim of this study was to discover direct targets of psoralen. To this end, we initially used proteomics based on drug affinity responsive target stability (DARTS) technology to identify the direct targets of psoralen. Next, we used surface plasmon resonance (SPR) analysis and verified the affinity effect of the 'component-target protein'. This method combines molecular docking technology to explore binding sites between small molecules and proteins. SPR and molecular docking confirmed that psoralen and tyrosine-protein kinase ABL1 could be stably combined. Based on the above experimental results, ABL1 is a potential direct target of psoralen-induced hepatotoxicity. Finally, the targets Nrf2 and mTOR, which are closely related to the hepatotoxicity caused by psoralen, were predicted by integrating proteomics and network pharmacology. The direct target ABL1 is located upstream of Nrf2 and mTOR, Nrf2 can influence the expression of mTOR by affecting the level of reactive oxygen species. Immunofluorescence experiments and western blot results showed that psoralen could affect ROS levels and downstream Nrf2 and mTOR protein changes, whereas the ABL1 inhibitor imatinib and ABL1 agonist DPH could enhance or inhibit this effect. In summary, we speculated that when psoralen causes hepatotoxicity, it acts on the direct target ABL1, resulting in a decrease in Nrf2 expression, an increase in ROS levels and a reduction in mTOR expression, which may cause cell death. We developed a new strategy for predicting and validating the direct targets of psoralen. This strategy identified the toxic target, ABL1, and the potential toxic mechanism of psoralen.

Donors with fatty livers are considered to address the shortage of livers for transplantation, but those livers are particularly sensitive to ischemia-reperfusion injury (IRI), and an increased incidence of graft failure is observed. Kupffer cells account for 20-35% of liver nonparenchymal cells, and have been shown to participate in the process of IRI and inflammatory reactions of hepatic steatosis. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is an intracellular sensor activated by Kupffer cells to promote generation and participates in IRI. Dynamics-associated protein 1 (Drp1) is one of the main proteins regulating mitochondrial division and exacerbates IRI by affecting mitochondrial dynamics. The mechanism of interaction of Kupffer cells with Drp1 and NLRP3 to aggravate IRI has not been clarified.

Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive.