Background Ubiquitination plays a significant role in biological processes and regulates the tumor microenvironment (TME). Tripartite Motif Containing 54 (TRIM54) is an E3 ubiquitin ligase that, in recent years, has been shown to control the development of certain malignancies. However, the expression and function of TRIM54 across pan-cancer and its role in the TME remain unclear. Methods Data from the public databases were utilized to explore the expression, prognostic value, clinical features, enrichment analysis, and genetic alterations of TRIM54 in tumors. Associations between TRIM54 expression and immune cell infiltration (ICI), immunotherapy response, and targeted drugs were analyzed using bioinformatics. Results Compared with normal tissues, TRIM54 is aberrantly expressed across a diverse range of malignancies. The expression of TRIM54 could predict diagnosis and prognosis across most cancer types. The enrichment analysis showed that TRIM54 and its related proteins were closely associated with ubiquitination modification and tumor-associated pathways. In addition, TRIM54 was tightly associated with ICI and immunotherapy. Finally, we screened out several targeted drugs that could regulate TRIM54 expression during immunotherapeutic responses. Conclusion TRIM54 plays a vital part in pan-cancer development, and its aberrant expression in tumors may be associated with ICI in TME. At the same time, TRIM54 has strong prognostic predictive ability and is a promising predictive biomarker for immunotherapy.

Background Current treatments for ulcerative colitis (UC) are unsatisfactory. JiangFuZhiXie pill (JFZX) is an in-hospital traditional Chinese medicine widely used in clinical practice for the treatment of UC, with excellent therapeutic effects. Purpose To explore the specific effects and underlying mechanisms of JFZX in the treatment of UC and further search for new therapeutic targets. Methods The UC mice model was established by free access to a 3% dextran sulfate sodium aqueous solution and intervention with JFZX via intragastric administration. Mouse serum was used to detect inflammatory factor levels. Mouse colon tissues were used for pathological, immunohistochemical, and immunofluorescence staining. Mouse colon tissues and intestinal contents were used for transcriptomic analysis and metagenomic testing, respectively. Gene expression was detected using reverse transcription polymerase chain reaction (RT-PCR) and western blot. Results The intervention with JFZX significantly increased body weight and colonic tight junctions in UC mice, and decreased disease score, pathological score, and inflammatory level. Metagenomic analysis results showed that JFZX modulates the abundance of key bacterial populations and improves intestinal flora disorders in UC mice. The transcriptomic and RT-PCR analysis indicated that the key pathway regulated by JFZX in the treatment of UC is the IL6/STAT3 pathway. JFZX intervention significantly downregulated the expression of key targets, including Stat3, Il6, Lif, Il10, Il19, and Csf3. Conclusion JFZX has therapeutic effects in UC and effectively inhibits intestinal inflammation. Its mechanism of action involves rebalancing the intestinal flora and inhibiting the IL6/STAT3 signaling pathway, thus reducing intestinal inflammation damage.

Background Current treatments for ulcerative colitis (UC) are unsatisfactory. JiangFuZhiXie pill (JFZX) is widely used in hospitals as a traditional Chinese medicine for treating UC and has excellent therapeutic effects. Purpose To explore the specific effects and underlying mechanisms of JFZX in the treatment of UC and further search for new therapeutic targets. Methods The UC mouse model was established by providing free access to a 3% dextran sulfate sodium aqueous solution and by intragastric administration of JFZX. Mouse serum was used to measure inflammatory factor levels, including IL-6, IL-1β, and TNF-α. Mouse colon tissues were used for hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), immunohistochemical (IHC), and immunofluorescence (IF) staining. Mouse intestinal contents and colon tissues were used for metagenomic and transcriptomic analyses, respectively. Gene expression was detected using reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB). Results Compared with the DSS group, the JFZX intervention significantly increased body weight and colonic tight junction integrity and decreased disease score, pathological score, and inflammatory levels in UC mice. Metagenomic analysis showed that JFZX modulates the abundance of key bacterial populations and improves intestinal flora disorders in UC mice. Transcriptomic analysis indicated that the key pathway regulated by JFZX in UC treatment is the IL6/STAT3 pathway. RT-PCR, WB, and IF staining showed that JFZX intervention significantly downregulated key targets, including STAT3, IL6, LIF, IL10, IL19, and CSF3, and inhibited STAT3 phosphorylation and nuclear translocation. Conclusion JFZX has ameliorative effects in UC and effectively inhibits intestinal inflammation. Its mechanism of action involves rebalancing the gut microbiota and inhibiting the IL-6/STAT3 signaling pathway, thereby reducing intestinal inflammation-related damage.

INTRODUCTION:Acute Hepatitis B (AHB) remains a significant global health challenge, with complex interactions between metabolic and immune responses influencing disease progression. This study aimed to investigate the causal relationships between immune cell-mediated plasma metabolites and acute hepatitis B using Mendelian Randomization (MR) analysis. METHODS:A two-sample MR analysis was conducted using genome-wide association study data from the FinnGen consortium (133 AHB cases and 451,214 controls) to examine relationships between 1,400 plasma metabolites and 731 immune cell phenotypes. Inverse variance weighting, MR-Egger regression, and weighted median analyses were employed to assess causal relationships. Mediation analysis was performed to explore the role of immune cells in metabolite-AHB associations. RESULTS:A total of 49 circulating metabolites were identified as being significantly associated with AHB risk, including 32 risk factors (e.g., 4-methylguaiacol sulfate, N-formylmethionine) and 17 protective factors (e.g., indoleacetylglutamine, beta-hydroxyisovalerate). Mediation analysis revealed 12 pairs of immune cell-metabolite relationships significantly associated with AHB. Notably, phenyllactate levels negatively regulated AHB through CD39+ secreting Treg AC (MP=- 4.83%) and B cell AC (MP=-12.1%), while 4-methylguaiacol sulfate levels positively mediated AHB through CD38 on IgD+ CD24- (MP=6.41%) and naive-mature B cells (MP=7.37%). DISCUSSION:The study's findings provide genetic evidence for causal relationships between specific plasma metabolites and acute hepatitis B risk through immune cell-mediated pathways. The identification of phenyllactate as a protective factor via CD39+ regulatory T cells and 4-methylguaiacol sulfate as a risk factor through CD38+ B cells offers insights into the immunometabolic mechanisms underlying AHB pathogenesis. CONCLUSION:This Mendelian randomization study reveals novel causal associations between plasma metabolites and acute hepatitis B mediated by specific immune cell phenotypes, providing potential biomarkers and therapeutic targets for future hepatitis B management strategies.

A recent study identified taurine as a potential drug for suppressing gastric intestinal metaplasia (GIM) in patient-derived organoids and Atp4a-/- mice. Gastric cancer is one of the leading causes of cancer-related deaths worldwide. GIM is a reversible stage in the Correa cascade of gastric carcinogenesis, which is a research hotspot. Previous research models, which included animals and cells, to some extent limited the progress of GIM. Currently, the rapid development of organoid technology has significantly overcome the limitations of the research models in GIM. Organoid technology provides a novel research model for GIM studies that can preserve molecular characteristics of GIM patients with high similarity, thereby offering experimental evidence to support individualized diagnosis and treatment in the clinic. Here, we discuss research models, current therapeutic drugs, and treatment prospects for GIM. Our view is that future research should focus on patient-derived organoids to conduct more accurate studies of GIM pathogenesis and to advance drug development.

Chronic liver disease represents a major global public health challenge, and its malignant progression to hepatocellular carcinoma is the leading cause of death among affected patients. Gut microbiota dysbiosis is a critical driver of this process. As the central hub of the "gut-liver axis," the gut microbiota, when disrupted, compromises the integrity of the intestinal mucosal barrier, promoting the translocation of microbial metabolites, such as lipopolysaccharides and aberrant secondary bile acids, to the liver. In turn, key signaling pathways become activated, including TLR4/NF-κB, Wnt/β-catenin, and PI3K/Akt, sustaining persistent hepatic inflammation and oxidative stress. These pathological processes accelerate the progression from liver fibrosis to cirrhosis, promote genomic instability, and suppress tumor suppressor gene expression, paving the way for the malignant transformation of hepatocytes. Leveraging its holistic regulatory properties, characterized by multi-component, multi-target, and multi-pathway actions, Chinese medicine can intervene at multiple stages of this inflammation-to-cancer cascade by modulating both the structure and function of the gut microbiota. It does so first by enriching beneficial short-chain fatty acid-producing bacteria, such as Lactobacillus and members of the phylum Firmicutes, which helps restore the intestinal mucosal barrier, limit endotoxin translocation, and alleviate hepatic inflammation and fibrosis. In parallel, by normalizing bile acid metabolism and reestablishing gut microbial homeostasis, Chinese medicine counteracts the development of a tumor-permissive microenvironment marked by immune suppression and DNA damage in hepatocytes induced by microbial metabolites. At the same time, it enhances anti-tumor immune responses mediated by CD8+ T cells and other immune effectors. Drawing on evidence from multi-omics analyses and clinical studies, this review examines the core mechanisms and recent advances regarding how Chinese medicine monomers and formulations modulate the gut microbiota to impede the progression of chronic liver disease to HCC. It highlights gut microbiota dysbiosis as a key driver of hepatocarcinogenesis and highlights the therapeutic potential of targeted microbiota regulation by Chinese medicine, providing a conceptual foundation and strategic approaches for the precision prevention and treatment of hepatocellular carcinoma.

Background: As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of action has not yet been clarified. Aim: This study reviews the current status and characteristics of network pharmacology research in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese medicine treatment of the disease. Methods: This study was searched on the Web of Science and PubMed using keywords, such as "traditional Chinese medicine", "liver cancer," and "network pharmacology." The citation dates of the literature cited in this review are from 2000 to 2024. Results: The discovery of the key molecular mechanisms of traditional Chinese medicine in the treatment of liver cancer through the network pharmacology approach and the in-depth study of the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese medicine. Conclusion: Network pharmacology research plays a key role in the treatment and prevention of liver cancer and deserves deeper exploration in the future.

UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism and a key mediator in several cancer developmental signaling pathways. However, the expression and function of UGDH in colorectal cancer (CRC) are unclear. Bioinformatics analysis was conducted to research the expression, diagnosis, prognosis, functional enrichment, genetic alterations, and immune characteristics of UGDH in CRC. Hematoxylin-Eosin staining, KI67 immunohistochemistry staining, and UGDH immunohistochemistry staining of clinical colon tissues were performed. The UGDH gene was knocked down in HCT-8 cells. CCK8 and cell wound scratch assays were further performed in UGDH wild-type and UGDH-knockdown HCT-8 cells. UGDH is markedly downregulated in CRC tissues compared to normal tissues, which predicts a poor prognosis. The lower expression of UGDH is associated with a high gene promoter methylation level and genome deletion. UGDH expression is proportional to immune cell infiltration and immune-related genes. UGDH expression is correlated with the p53 signaling pathway. Knockdown of UGDH in HCT-8 cells promoted their proliferation and migration ability. UGDH could be useful as a valuable prognostic biomarker and potential therapeutic target in CRC. UGDH could inhibit the proliferation and migration of CRC cells.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatocellular injury, inflammation and fibrosis, which result from the accumulation of hepatic lipids. As one of the most prevalent chronic liver diseases globally, its pathogenesis remains complex. With the improvement in living standards, the incidence of NAFLD is expected to rise, drawing increasing attention to its development, prevention, and treatment from researchers worldwide. Currently, the therapeutic progress achieved by Western medicine in treating NAFLD remains limited, and its clinical efficacy is unsatisfactory. In contrast, Chinese medicine has a long history in the treatment of NAFLD, and possesses such advantages as fewer side effects, and multi-component, multi-target, and multi-pathway therapeutic actions. In recent years, several studies have demonstrated that Chinese medicine can modulate the progression of NAFLD by regulating relevant signaling pathways both in vivo and in vitro. However, comprehensive reviews on this topic remain scarce. Therefore, in this paper, a literature search was conducted using PubMed and Web of Science to summarize key signaling pathways implicated in Chinese medicine-mediated interventions in NAFLD, including AMPK, mTOR, PI3K/Akt, Toll-like receptor, NF-[Formula: see text]B, and MAPK pathways. Furthermore, the specific anti-NAFLD mechanisms of these pathways were elaborated. The objective of this paper is to provide an overview of the effective therapeutic pathways and mechanisms associated with Chinese medicine in the treatment of NAFLD, and to thereby offer a theoretical foundation and innovative perspectives for future research and clinical applications.

OBJECTIVE:To investigate the therapeutic effects of Chinese medicine Weifuchun (WFC, ) on gastric fundic gland polyps (FGPs). METHODS:FGPs organoids were constructed with patients-derived samples. The morphology and size of FGPs organoids were detected using bright-field imaging. Effective components and corresponding potential targets of WFC were screened using multiple open-source databases and research on Traditional Chinese Medicine or compound formulas. Core genes were identified through protein-protein interaction networks. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of the core genes were conducted. The interactions between main components and core targets were analyzed through the FerrDb database. The expressions of core targets were detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:After WFC treatment, the number and size of FGPs organoids were significantly reduced. Twenty nine active drug components and 162 candidate targets of WFC for treating FGPs were identified, including 37 targets related to ferroptosis. Quercetin, Glaucocalyxin B, Melissoidesin U, Melissoidesin O, Hesperetin, Glaucocalyxin A, Angustifolin, Melissoidesin M, Di-n-octyl phthalate, and beta-sitosterol were identified as the main active compounds. SRC proto-oncogene, non-receptor tyrosine kinase, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1 were identified as the primary targets. KEGG pathways related to carcinogenesis, cell proliferation and metabolism, and oxidative stress. WFC promoted FGPs organoids' death and could be reversed by ferroptosis inhibitor of Erastin. The qRT-PCR results showed that WFC treatment could regulate the mRNA expression levels of solute carrier family 7 member 11, acyl-CoA synthetase long chain family member 4, and arachidonate 15-lipoxygenase, type B. CONCLUSION:WFC may exert its therapeutic effects by inducing ferroptosis in FGPs cells.

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment.

Proangiogenic therapy offers a promising strategy for treating and preventing heart failure and cardiac remodeling following a myocardial infarction (MI). Although exosome-based proangiogenic therapy has significant potential in regenerative medicine and MI treatment, its application remains limited by suboptimal therapeutic efficacy. Here, we present exosomes (HXYQR-Exo) derived from the serum of mice treated with the Huoxue Yiqi Recipe (HXYQR) to promote angiogenesis and repair cardiac tissue post-MI, with a systematic elucidation of the underlying mechanisms. Our findings show that HXYQR-Exo incorporates pharmaceutically active components of HXYQR, enhancing the proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) under hypoxic conditions. In vivo studies demonstrate significant improvements in cardiac function and angiogenesis. Mechanistic investigations reveal that these effects are mediated through the activation of the HIF-1α/VEGF, Focal Adhesion Kinase (FAK), and p38/Mitogen-Activated Protein Kinase-Activated Protein Kinase (MAPKAPK)/Heat Shock Protein 27 (HSP27) pathways. This study introduces an exosome-based approach for MI treatment and cardiac repair, offering an effective strategy to enhance exosome biological activities and functions via traditional Chinese medicine preconditioning.

ETHNOPHARMACOLOGICAL RELEVANCE:Ethnopharmacological Significance: Artemisia annua L. (qinghao) is a traditional Chinese herbal medicine that has been used to treat malaria, bacterial infections, inflammation, various cancers, and parasites. This article focuses on the anticancer pharmacological components of Artemisia annua L. AIM OF THE STUDY:This review examines the chemical composition and anticancer mechanisms of Artemisia annua L., aiming to inform future research and clinical applications. MATERIALS AND METHODS:We conducted a bibliometric analysis of Artemisia annua L. anticancer research using Web of Science, VOSviewer, and CiteSpace. Then, we screened and studied its active components and targets via TCMSP, DAVID, and Cytoscape. Finally, we identified and summarized the main anticancer components and their mechanisms using PubMed, Web of Science, and Google databases. RESULTS:The main anticancer components of Artemisia annua L. are artemisinin and its derivatives, quercetin, and polyphenols (pKAL). These compounds inhibit cancer cell proliferation, invasion, and metastasis, and induce apoptosis by regulating pathways like PI3K/AKT, JAK-STAT, p53, and GPX4. They also modulate the immune and tumor microenvironment, enhancing chemotherapeutic drug efficacy. CONCLUSION:The active ingredients of Artemisia annua L. show great potential for cancer treatment, highlighting its broad applications and clinical value. This underscores the need for further exploration of its therapeutic potential.