Hepatic stellate cells (HSCs) and cancer-associated fibroblasts (CAFs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). MyD88 controls the expression of several key modifier genes in liver tumorigenesis; however, whether and how MyD88 in myofibroblasts contributes to the development of fibrosis-associated liver cancer remain elusive. Here, we used an established hepatocarcinogenesis mouse model involving apparent liver fibrogenesis, in which MyD88 was selectively depleted in myofibroblasts. Myofibroblast MyD88-deficient (Fib-MyD88 KO) mice developed significantly fewer and smaller liver tumor nodules. MyD88 deficiency in myofibroblasts attenuated liver fibrosis and aerobic glycolysis in hepatocellular carcinoma tissues. Mechanistically, MyD88 signaling in myofibroblasts increased the secretion of CCL20, which promoted aerobic glycolysis in cancer cells. This process was dependent on the CCR6 receptor and ERK/PKM2 signaling. Furthermore, liver tumor growth was greatly relieved when the mice were treated with a CCR6 inhibitor. Our data revealed a critical role for MyD88 in myofibroblasts in the promotion of hepatocellular carcinoma by affecting aerobic glycolysis in cancer cells and might provide a potential molecular therapeutic target for HCC.
Citation Format: Qi Yuan, Jinhua Zhang. MyD88 in myofibroblasts regulates aerobic glycolysis-driven hepatocarcinogenesis via ERK-dependent PKM2 nuclear relocalization and activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5666.
The COVID-19 pandemic has continued to result in severe disruptions to food supply chains. In this research, we present a simulation study on the impact of the COVID-19 pandemic on food supply chains and their sustainability using the lobster industry in Nova Scotia, Canada, as an example. The main contributions of this paper are twofold. First, it analyzes how the pandemic has negatively disrupted lobster supply chains and their sustainability. Second, it demonstrates how a simulation-based methodology based on the software AnyLogistix can be applied to examine the effects of a pandemic on food supply chains. We show the impacts of the COVID-19 pandemic from four perspectives: production-inventory dynamics, customer performance, financial performance, and lead-time performance. Our findings include the following. First, the pandemic has created a backlog problem for the live lobster industry. Second, it has significantly increased the lead time of the lobster supply chain. Overall, this research can help the government and trade organizations to devise appropriate policies to reduce the negative impacts of the pandemic on food supply chains and their sustainability.
Technological innovation and competition has forced some farms and granges to adopt supply chain mode to manage their supply, production and sale. Obviously, the operation of agriculture supply chain can not be separated from simultaneous, accurate information about purchase, production, demand, supply, sale and other operational activities. However, there are few scholars who have ever specially discussed on agriculture product supply chain information sharing system both in domestic and foreign literature. This paper attempts to sum up information and Web Service standard in agriculture product supply chain and establishes an information sharing system based on Web Service. By analyzing four information sharing system modules, the authors introduce the visiting principle of the information sharing system and explain how they are used and implemented in our platform. The authors hold that this kind of information sharing system can help the users view their interests visually in the client and the system can display what specify users interests in the platform.
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