Dihydromyricetin(DMY),a flavonoid compound extracted from Ampelopsis grossedentata,exhibits diverse pharmacological activities,including anti-inflammatory,antioxidant,antitumor,neuroprotective,and immuno-modulatory effects.Recent studies have demonstrated that DMY can suppress inflammatory responses and oxidative stress through multiple molecular pathways,as well as regulate bile acid metabolism and maintain intestinal microbiota balance.These actions help reduce histopathological damage,improve gastrointestinal barrier function,and alleviate the symptoms of digestive system diseases.DMY has shown significant therapeutic effects in the treatment of gastrointestinal inflamma-tion,liver diseases,and digestive tract tumors.This review systematically summarizes the mechanisms of action and thera-peutic potential of DMY in digestive system diseases,providing a scientific basis and theoretical support for its clinical ap-plication and the development of new drugs.

Dihydromyricetin(DMY),a flavonoid compound extracted from Ampelopsis grossedentata,exhibits diverse pharmacological activities,including anti-inflammatory,antioxidant,antitumor,neuroprotective,and immuno-modulatory effects.Recent studies have demonstrated that DMY can suppress inflammatory responses and oxidative stress through multiple molecular pathways,as well as regulate bile acid metabolism and maintain intestinal microbiota balance.These actions help reduce histopathological damage,improve gastrointestinal barrier function,and alleviate the symptoms of digestive system diseases.DMY has shown significant therapeutic effects in the treatment of gastrointestinal inflamma-tion,liver diseases,and digestive tract tumors.This review systematically summarizes the mechanisms of action and thera-peutic potential of DMY in digestive system diseases,providing a scientific basis and theoretical support for its clinical ap-plication and the development of new drugs.

Background/Aims: Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression. Methods: We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo. Results: Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice. Conclusions KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.

Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.