The energy for tumor cells mainly derives from the aerobic glycolysis,that is,the Warburg effect,which also provides a large amount of precursor substances for the growth of tumor cells.Hexokinase-Ⅱ (HK-Ⅱ),highly expressed in tumor tissue,is the rate-limiting enzyme of glycolysis and closely related to the energy metabolism of tumor.Recent studies have showed that HK-Ⅱ not only mediates Warburg effect,but also promotes tumor proliferation by inhibiting tumor cell apoptosis and regulating autophagy.It has been confirmed that blocking HK-Ⅱ gene expression and inhibiting HK-Ⅱ with small molecule inhibitor can kill tumor cells in many kinds of cancer.Agent targeting HK-Ⅱ may become a new generation of targeted drugs.

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence