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Abstract Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

Inflammation responses have identified as a key mediator of in various liver diseases with high morbidity and mortality. cGAS-STING signalling is essential in innate immunity since it triggers release of type I interferons and various of proinflammatory cytokines. The potential connection between cGAS-STING pathway and liver inflammatory diseases has recently been reported widely. In our review, the impact of cGAS-STING on liver inflammation and regulatory mechanism are summarized. Furthermore, many inhibitors of cGAS-STING signalling as promising agents to cure liver inflammation are also explored in detail. A comprehensive knowledge of molecular mechanisms of cGAS-STING signalling in liver inflammation is vital for exploring novel treatments and providing recommendations and perspectives for future utilization.

N6-methyladenosine (m6A), the most abundant RNA modification within cells, participates in various biological and pathological processes, including self-renewal, invasion and proliferation, drug resistance, and stem cell characteristics. The m6A methylation plays a crucial role in tumors by regulating multiple RNA processes such as transcription, processing, and translation. Three protein types are primarily involved in m6A methylation: methyltransferases (such as METTL3, METTL14, ZC3H13, and KIAA1429), demethylases (such as FTO, ALKBH5), and RNA-binding proteins (such as the family of YTHDF, YTHDC1, YTHDC2, and IGF2BPs). Various metabolic pathways are reprogrammed in digestive tumors to meet the heightened growth demands and sustain cellular functionality. Recent studies have highlighted the extensive impact of m6A on the regulation of digestive tract tumor metabolism, further modulating tumor initiation and progression. Our review aims to provide a comprehensive understanding of the expression patterns, functional roles, and regulatory mechanisms of m6A in digestive tract tumor metabolism-related molecules and pathways. The characterization of expression profiles of m6A regulatory factors and in-depth studies on m6A methylation in digestive system tumors may provide new directions for clinical prediction and innovative therapeutic interventions.

BackgroundHepatocellular carcinoma remains the third most common cause of cancer-related deaths worldwide. Although great achievements have been made in resection, chemical therapies and immunotherapies, the pathogenesis and mechanism of HCC initiation and progression still need further exploration. Necroptosis genes have been reported to play an important role in HCC malignant activities, thus it is of great importance to comprehensively explore necroptosis-associated genes in HCC.MethodsWe chose the LIHC cohort from the TCGA, ICGC and GEO databases for this study. ConsensusClusterPlus was adopted to identify the necroptosis genes-based clusters, and LASSO cox regression was applied to construct the prognostic model based on necroptosis signatures. The GSEA and CIBERSORT algorithms were applied to evaluate the immune cell infiltration level. QPCR was also applied in this study to evaluate the expression level of genes in HCC.ResultsWe identified three clusters, C1, C2 and C3. Compared with C2 and C3, the C1 cluster had the shortest overall survival time and highest immune score. The C1 was samples were significantly enriched in cell cycle pathways, some tumor epithelial-mesenchymal transition related signaling pathways, among others. The DEGs between the 3 clusters showed that C1 was enriched in cell cycle, DNA replication, cellular senescence, and p53 signaling pathways. The LASSO cox regression identified KPNA2, SLC1A5 and RAMP3 as prognostic model hub genes. The high risk-score subgroup had an elevated expression level of immune checkpoint genes and a higher TIDE score, which suggested that the high risk-score subgroup had a lower efficiency of immunotherapies. We also validated that the necroptosis signatures-based risk-score model had powerful prognosis prediction ability.ConclusionBased on necroptosis-related genes, we classified patients into 3 clusters, among which C1 had significantly shorter overall survival times. The proposed necroptosis signatures-based prognosis prediction model provides a novel approach in HCC survival prediction and clinical evaluation.

Abstract Various hepatoxic factors, such as viruses, drugs, lipid deposition, and autoimmune responses, induce acute or chronic liver injury, and 3.5% of all worldwide deaths result from liver cirrhosis, liver failure, or hepatocellular carcinoma. Liver transplantation is currently limited by few liver donors, expensive surgical costs, and severe immune rejection. Cell therapy, including hepatocyte transplantation and stem cell transplantation, has recently become an attractive option to reduce the overall need for liver transplantation and reduce the wait time for patients. Recent studies showed that mesenchymal stem cell (MSC) administration was a promising therapeutic approach for promoting liver regeneration and repairing liver injury by the migration of cells into liver sites, hepatogenic differentiation, immunoregulation, and paracrine mechanisms. MSCs secrete a large number of molecules into the extracellular space, and soluble proteins, free nucleic acids, lipids, and extracellular vesicles (EVs) effectively repair tissue injury in response to fluctuations in physiological states or pathological conditions. Cell-free-based therapies avoid the potential tumorigenicity, rejection of cells, emboli formation, undesired differentiation, and infection transmission of MSC transplantation. In this review, we focus on the potential mechanisms of MSC-based cell-free strategies for attenuating liver injury in various liver diseases. Secretome-mediated paracrine effects participate in the regulation of the hepatic immune microenvironment and promotion of hepatic epithelial repair. We look forward to completely reversing liver injury through an MSC-based cell-free strategy in regenerative medicine in the near future.

A novel avian-origin influenza A (H7N9) virus emerged and spread among humans in Eastern China in 2013. Prophylactic treatment with antibiotics and probiotics for secondary infection is as important as antiviral treatment. This study aims to assess the ability of probiotic treatment to restore internal homeostasis under antibiotic pressure and to reduce/ameliorate the risk of secondary infections resulting from infection with the H7N9 virus.This is a retrospective study in archival samples. Between April 1 and May 10, 2013, 113 stool, sputum, and blood specimens were collected and analyzed by denaturing gradient gel electrophoresis (DGGE) to determine the composition of the patient microbiomes. Microbial diversity was calculated using Gel-Pro analyzer and Past software. Cluster analysis of DGGE pattern profiles was employed to create a phylogenetic tree for each patient, and multidimensional scaling (MDS) and principal component analysis (PCA) were performed to visualize relationships between individual lanes.Five patients had secondary infections, including Klebsiella pneumonia, Acinetobacter baumanii and Candida albicans infection. The DGGE profiles of fecal samples obtained at different time points from the same individual were clearly different, particularly for patients with secondary infections. Shannon's diversity index and evenness index were lower in all infected groups compared to the control group. After B. subtilis and E. faecium or C. butyricum administration, the fecal bacterial profiles of patients who had not been treated with antibiotics displayed a trend of increasing diversity and evenness. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients, but administration of B. subtilis and E. faecium appeared to reduce/ameliorate secondary infection in one patient.H7N9 infection might decrease intestinal microbial diversity and species richness in humans. C. butyricum failed to reduce/ameliorate secondary infection in H7N9-infected patients. B. subtilis and E. faecium may also play a role in reducing/ameliorating secondary infection in these patients.