Xiaojing Song

Post-hepatectomy liver failure (PHLF) is a serious complication after partial hepatectomy without approved therapies to safely enhance liver regeneration. This study investigated whether exosomes derived from human umbilical cord mesenchymal stem cells promote liver regeneration by regulating a macrophage-transforming growth factor-beta (TGF-β)-ZBP1-PANoptosis axis. Using a 70% partial hepatectomy mouse model and a macrophage-hepatocyte co-culture system, we found that exosome treatment preserved liver structure, reduced serum injury markers (ALT/AST), increased liver-to-body weight ratio by 32.4%, and elevated proliferating hepatocytes (Ki67-positive cells) by 2.8-fold. Exosomes shifted hepatic macrophages towards a reparative (CD206-positive) phenotype, increased anti-inflammatory cytokines (interleukin-10 and TGF-β), suppressed ZBP1 expression, and inhibited PANoptosis markers. Overexpression of ZBP1 in macrophages reversed the exosome-induced polarization and cytokine changes. Neutralizing TGF-β blocked the ability of exosome-exposed macrophages to suppress hepatocyte ZBP1 expression and PANoptosis. These results identify a key mechanism by which mesenchymal stem cell-derived exosomes enhance liver regeneration after partial hepatectomy by at least partially promoting TGF-β-dependent reparative macrophage polarization, which inhibits ZBP1-mediated PANoptosis in hepatocytes, suggesting a potential therapeutic strategy for preventing PHLF.

We report a case of patient with Stage IIIa Hepatocellular Carcinoma Complicated by Early Gastric Cancer. Although Stage IIIa liver cancer can be treated with surgery, the overall prognosis of surgery is not ideal. Alternatively, conversion therapy is reported with different effectiveness towards stage IIIa liver cancer. Herein, this study shared the successful conversion of a patient with stage IIIa liver cancer and with early gastric cancer at Lanzhou University First Hospital, which is hoped to engage clinicians in evaluation and discussion.

Few studies have explored the biological mechanism by which probiotics alleviate adverse reactions to chemotherapy drugs after local hepatic chemotherapy perfusion by regulating the intestinal flora. This study investigates the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the intestinal microbial structure and intestinal barrier function, as well as the potential mechanism in rabbits after local hepatic chemotherapy infusion. Eighteen New Zealand White rabbits were randomly divided into a control group, a hepatic local chemotherapy perfusion group, and a hepatic local chemotherapy perfusion + Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets group to assess the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the adverse reactions. The administration of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets alleviated the intestinal flora disorder caused by local hepatic perfusion chemotherapy, promoted the growth of beneficial bacteria, and inhibited the growth of harmful bacteria. The Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets also reduced the levels of serum pro-inflammatory cytokines and liver injury factors induced by local hepatic perfusion chemotherapy. Our findings indicate that Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets can ameliorate the toxicity and side effects of chemotherapy by regulating intestinal flora, blocking pro-inflammatory cytokines, reducing liver injury factors, and repairing the intestinal barrier. Probiotics may be used as a potential alternative therapeutic strategy to prevent the adverse reactions caused by chemotherapy with local hepatic perfusion.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host’s GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut–liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

Umbilical cord mesenchymal stem cell (UC-MSC) therapy improves liver function in liver cirrhosis patients. This study aimed to elucidate the therapeutic mechanism underlying cell therapy by analyzing changes in the modification and expression of proteins 1 month post-treatment with UC-MSCs. This prospective study included 11 cirrhosis patients who received MSC injection. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of UC-MSCs, and the protein expression and lactylation modification in the liver were comprehensively revealed. Meanwhile, weighted gene co-expression network analysis was used to analyze the co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving UC-MSC treatment; specifically, the liver protein synthesis function was significantly improved and the coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 lysine lactylation (Kla) sites of 119 proteins. Functional analysis showed that the lactylation-modified proteins were enriched in the pathway of glucose and other substances’ metabolism, and many key enzymes of glycolysis and gluconeogenesis were lactated. UC-MSC therapy has a certain clinical effect in the treatment of liver cirrhosis and may act by regulating material metabolism, because the lactylation protein points to energy metabolism.

Biliary pancreatic malignancy has an occultic onset, a high degree of malignancy, and a poor prognosis. Most clinical patients miss the opportunity for surgical resection of the tumor. Systemic chemotherapy is still one of the important methods for the treatment of biliary pancreatic malignancies. Many chemotherapy regimens are available, but their efficacy is not satisfactory, and the occurrence of chemotherapy resistance is a major reason leading to poor prognosis. With the advancement of studies on intestinal flora, it has been found that intestinal flora is correlated with and plays an important role in chemotherapy resistance. The application of probiotics and other ways to regulate intestinal flora can improve this problem. This paper aims to review and analyze the research progress of intestinal flora in the chemotherapy resistance of biliary pancreatic malignancies to provide new ideas for treatment.

The intestinal flora plays an important role in the occurrence and development of liver cancer, affecting the efficacy and side effects of conventional antitumor therapy. Recently, immunotherapy for liver cancer has been a palliative treatment for patients with advanced liver cancer lacking surgical indications. Representative drugs include immune checkpoint inhibitors, regulators, tumor vaccines, and cellular immunotherapies. The effects of immunotherapy on liver cancer vary because of the heterogeneity of the tumors. Intestinal flora can affect the efficacy and side effects of immunotherapy for liver cancer by regulating host immunity. Therefore, applying probiotics, prebiotics, antibiotics, and fecal transplantation to interfere with the intestinal flora is expected to become an important means of assisting immunotherapy for liver cancer. This article reviews publications that discuss the relationship between intestinal flora and immunotherapy for liver cancer and further clarifies the potential relationship between intestinal flora and immunotherapy for liver cancer.

Hepatocellular carcinoma (HCC) has high mortality and incidence worldwide. The molecular mechanism associated with HCC is largely unexplored. Objective: To investigate the impact of CD44 knock-down on the proliferation, migration, and invasiveness in HCC cells. Methods: Colony formation and MTT assay were used to observe cellular proliferation and viability. In addition, cellular invasion and migration were studied by Transwell and wound healing assays respectively. Finally, western blotting was utilized to check the protein expression levels. Results: The cellular proliferation, invasion and metastasis in Huh7 cells were inhibited after the silencing of CD44. Furthermore, expression levels of MMP-2, MMP-9, CXCR4, GSK-3β and β-catenin was significantly decreased. However, opposite results were demonstrated when CD44 was overexpressed. Conclusions: Interference with the expression of CD44 significantly inhibits the invasion and metastasis in the HCC cell line, Huh7. Furthermore, CD44 was found to regulate the expression of MMP-2, MMP-9, CXCL12, CXCR4 and Wnt/β-catenin signal pathway.