The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis.

Evidence for the involvement of N6-Methyladenosine (m6A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m6A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m6A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m6A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis.

A rare case of gallbladder cystic echinococcosis disease in western China.

Hydatid disease, also known as echinococcosis, is an endemic zoonotic parasitic disease caused by larvae of the Echinococcus tapeworm.Humans as accidental intermediate hosts in the parasite life cycle, echinococcus usually parasitizes the liver, solitary cystic echinococcosis in the gallbladder is very rare. Here we report a rare case of cystic echinococcosis in the gallbladder without liver involvement. A female patient was admitted to the hospital primarily for "right upper abdominal pain with radiating pain in the back of the shoulder for 20 days", initially suspected to be gallbladder stones, and underwent laparoscopic cholecystectomy after completing the relevant investigations, and was diagnosed with primary cystic echinococcosis of the gallbladder based on the pathologic findings in the postoperative period. The patient recovered well after surgery and remained well without complications during the 6-month follow-up period. This case illustrates that echinococcus granulosus can also parasitize in the gallbladder only, although it is quite uncommon. In addition, it is difficult to distinguish it from gallbladder stones by conventional imaging. The diagnosis of some cases of gallbladder cystic echinococcosis is completed during surgery and confirmed by postoperative pathological results.