Treating hepatocellular carcinoma (HCC) remains challenging due to the drug resistance of HCC cells, which limits the clinical efficacy of sorafenib. This study elucidates the role of nuclear factor activated T cells 2 (NFAT2) in sorafenib resistance in HCC cells and reveals the underlying mechanism. Sorafenib-resistant cell lines were constructed, with NFAT2 overexpressed and knocked down via genetic engineering. Fura-2 detected intracellular calcium ion concentration; transmission electron microscopy (TEM) assessed organelle damage; wound healing and transwell assays evaluated cell migration and invasion; clone formation and CCK8 assays measured cell proliferation. Flow cytometry detected apoptosis; Western blot analyzed protein expressions. Tumorigenesis was evaluated using a sorafenib-resistant HCC orthotopic xenograft mouse model. We found that NFAT2 was upregulated in MHCC97H-SR and HepG2-SR cells. Overexpression of NFAT2 inhibited Ca2+ influx in MHCC97H-SR, reduced the expression of Ca2+ regulation-related proteins (p-PLCγ, p-IP3R, p-CaMKII), ER-related proteins (CPR94, CPR78), and oxidative stress-related proteins (NOX2, NOX4). NFAT2 overexpression inhibited apoptosis and enhanced cell migration, invasion, and proliferation. NFAT2 knockdown reduced tumorigenesis. Our study uncovered a mechanism by which NFAT2 increases HCC cell resistance to sorafenib by altering intracellular calcium ion signals, highlighting NFAT2 as a promising target for HCC drug therapy.

Liver cancer remains one of the most lethal malignancies worldwide, primarily due to limited diagnostic and therapeutic strategies. Biological imaging agents capable of selective accumulation in cancerous liver tissue offer a promising route for earlier detection and improved patient outcomes. In this work, we synthesized and characterized alkaline phosphatase (ALP)-targeted, gadolinium-labeled gold nanoparticles (AuNPs) designed for simultaneous detection using magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence (Fl) microscopy. The synthesized AuNPs feature 13 nm gold cores functionalized with ALP-binding ligands and Gd(III)-macrocycles. Characterization by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDX) confirmed successful functionalization. During the functionalization process, variations in Gd(III) loading, surface packing density, and r1 relaxivity were observed; however, high reproducibility was achieved when including methanol during the AuNP labeling protocol. In vitro studies with HepG2 liver cancer and HEK293 kidney cells demonstrated selective cellular uptake in relation to cellular ALP expression levels. Optimized uptake conditions demonstrated 10-fold increase in Gd(III) internalization into HepG2 versus HEK293 cells. Further imaging by scanning electron microscopy (SEM) and TEM on thinly sliced cell samples verified the intracellular localization of these nanoparticles. Collectively, these findings underscore the potential of ALP-targeted, gadolinium-labeled AuNPs as a versatile multimodal imaging platform for the early detection of liver cancer.

This review provides an overview of research evidence focused on the microbial components essential to clinical cancer care, called the oncobiota (the interaction of human microbiota and cancer cells). It specifically examines the oncobiota in central nervous system cancer,breast cancer, pancreatic cancer, liver cancer, lung cancer, and cervical cancer. The literature review reveals insufficient knowledge about the oncobiota of organs once considered sterile. Many studies on oncobiota focus on small, geographically specific patient groups, and the absence of a reference (control) group complicates the development of microbial profiles for selected cancers. Consequently, this review aims to analyze the literature data and reports on the role of oncobiota in selected "sterile" organs and the resulting therapeutic or preventive implications. All relevant publications on oncobiota in patients with the selected cancers were considered to provide the most thorough analysis possible. Understanding the significance and role of oncobiota in the pathomechanisms of carcinogenesis may pave the way for targeted cancer prevention methods. Furthermore, therapeutic strategies based on oncobiota could represent a novel area of ​​personalized cancer treatment. Additionally, oncobiota may serve as an additional diagnostic tool in oncology.

Hinokitiol (HK), a monoterpenoid that naturally occurs in plants belonging to the Cupressaceae family, possesses important biological activities, including an anticancer effect. This review summarizes its anticancer potential and draws possible molecular interventions. In addition, it evaluates the biopharmaceutical, toxicological properties, and clinical application of HK to establish its viability for future advancement as a dependable anticancer medication. The assessment is based on the most recent information available from various databases. Findings demonstrate that HK possesses substantial therapeutic advantages against diverse types of cancer (colon, cervical, breast, bone, endometrial, liver, prostate, oral, and skin) through various molecular mechanisms. HK induces oxidative stress, cytotoxicity, apoptosis, cell-cycle arrest at the G and S phases, and autophagy through modulation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), p38/ERK/MAPK, nuclear factor kappa B, and c-Jun N-terminal kinase signaling pathways. Furthermore, this compound exhibits good oral bioavailability with excellent plasma clearance. Clinical uses of HK demonstrate therapeutic advantages without any significant negative effects. A thorough study of the pertinent data suggests that HK may serve as a viable candidate for developing novel cancer therapies. Consequently, more extensive studies are necessary to evaluate its cancer treatment efficacy, safety, and possible long-term hazards.

In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC50) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.

Hepatocellular carcinoma (HCC) accounts for 85%-90% of all primary liver cancers (PLCs). Owing to the occult nature of HCC, most patients present at an advanced stage at the time of initial diagnosis and have a poor prognosis. With regard to systemic therapy, targeted therapy and immunotherapy are currently the centers of clinical research. With regard to local treatment, surgical resection, radiofrequency ablation, hepatic artery chemoembolization, and radiotherapy are commonly used. Interstitial brachytherapy is commonly used for the treatment of cervical and genitourinary cancers. In this case, interstitial brachytherapy was used to treat gluteus medius muscle metastasis from PLC, with good local control and symptom relief.

Hepatocellular carcinoma (HCC), originating from hepatocytes, is the most common type of primary liver cancer. HCC imposes a significant global health burden with high morbidity and mortality, making it a critical public concern. Surgical interventions, including hepatectomy and liver transplantation, are pivotal in achieving long-term survival for patients with HCC. Additionally, ablation therapy, endovascular interventional therapy, radiotherapy, and systemic anti-tumor therapies are commonly employed. However, these treatment modalities are often associated with considerable challenges, including high postoperative recurrence rates and adverse effects. Traditional Chinese medicine (TCM) and natural products have been utilized for centuries as a complementary approach in managing HCC and its complications, demonstrating favorable clinical outcomes. Various bioactive compounds derived from TCM and natural products have been identified and purified, and their mechanisms of action have been extensively investigated. This review aims to provide a comprehensive and up-to-date evaluation of the clinical efficacy of TCM, natural products and their active constituents in the treatment and management of HCC. Particular emphasis is placed on elucidating the potential molecular mechanisms and therapeutic targets of these agents, including their roles in inhibiting HCC cell proliferation, inducing apoptosis and pyroptosis, suppressing tumor invasion and metastasis, and restraining angiogenesis within HCC tissues.

Selective internal radiation therapy (SIRT) is an effective, minimally invasive treatment for intermediate and advanced-stage liver malignancies, particularly when other curative options are not viable. As an alternative to commercially available Yittrium-90 (90Y) resin or glass microspheres, we have developed novel radiopharmaceutical, neutron-activated Samarium-153 oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres for SIRT. The therapeutic efficacy of the formulation has been assessed in our previous study. This extended study aimed to evaluate the biodistribution and long-term toxicity of [153Sm]Sm2O3-PS microspheres in a healthy Sprague-Dawley (SD) rat model.

Biodistribution was assessed in six healthy male SD rats following direct intrahepatic injection of radioactive [153Sm]Sm2O3-PS microspheres. Static whole-body gamma imaging was performed at 1, 24, and 48 hour post-injection. Radioactivity levels in major organs were measured after euthanasia. For long-term toxicity evaluation, eighteen healthy male SD rats were divided into three groups and tested with: (1) decayed [153Sm]Sm2O3-PS microspheres; (2) 4 % gelatin solution; and (3) untreated control. Over a 12-month period, body weight, body temperature and liver function biomarkers (ALT, AST, ALP and GGT) were monitored. Histopathological evaluations (HPE) of liver tissues were performed after the rats were sacrificed at the end of the study.

The highest radioactivity (25.15 ± 2.32 % injected dose (ID)/g) was observed at the injected site in the liver at 48 h post-injection, with minimal or undetectable radioactivity in other organs, including spleen, bladder, kidneys, lungs, heart, bone, muscle, and blood. No significant changes (p > 0.05) in body weight and body temperature were observed across groups, and no signs of systemic illness were noted in any of the rats. Liver function biomarkers remained within normal physiological ranges in all groups throughout the study. HPE revealed no lesions or severe inflammation in liver tissues across all groups.

[153Sm]Sm2O3-PS microspheres demonstrated favourable biodistribution and no evidence of systemic or hepatic toxicity over a 12-month period in healthy rats. These findings support the safety profile of the microspheres and their feasibility for further preclinical and clinical trials.

Hepatocellular carcinoma (HCC) is a common type of liver cancer that progresses quickly and has limited treatment options. Nutraceutical anacardic acid (AA), a bioactive compound derived from cashew nut shell, has emerged as a potential candidate for HCC treatment owing to its reported anti-inflammatory, anticancer and diverse pharmacological properties. In the present study, we investigate the potential of AA as an HCC inhibitor using molecular docking, gene ontology, and network pharmacology.

The pharmacokinetic and physicochemical properties of AA were assessed using Swiss ADME. SuperPred, Similarity Ensemble Approach, ChEMBL and Swiss Target Prediction online tools were used for determining molecular targets of AA. In addition, GeneCards, NCBI, DisGeNET and UniProt ID were used to search the targets of HCC and the top 25 hub genes were determined using Cytohubba plugin. A protein protein interaction (PPI) network was constructed through the STRING database. Gene Ontology (GO) biological process and Kyoto Encyclopaedia of Genes and Genes (KEGG) pathway enrichment analysis were performed through FunRich and ShinyGO 0.77. Moreover, molecular docking studies were performed on NF-κB and GSK-3β. The expression levels of the hub genes were also validated by western blotting.

Comprehensive data analysis identified 375 targets for AA and 11,333 for HCC, with 264 targets in common. Network analysis determined 25 key HCC targets, including caspase-3, and NF-κB. Gene ontology and topology analysis highlighted essential pathways implicated in HCC progression such as the renin-angiotensin system, VEGF signalling, and apoptosis. Molecular docking analysis revealed strong binding affinity of HCC proteins with NF-κB and GSK-3β. Upregulation of p-NRF2 and p-GSK-3β, and downregulation of p-NF-κB and caspase-1 expression were validated using western blotting.

Taken together, our study highlights the potential of AA as a promising chemopreventive agent for HCC because of its significant modulatory effects on important regulatory proteins linked to cell division, inflammation, apoptosis, and antioxidant response.

Primary liver cancer, predominantly hepatocellular carcinoma (HCC), is a major global health concern. Liver transplantation is a critical therapeutic option for HCC, offering potential tumor eradication and cure of underlying liver disease. Enhanced Recovery After Surgery (ERAS) protocols aim to improve patient outcomes by optimizing perioperative care. This study evaluates the efficacy of ERAS in elderly liver transplant recipients.

A retrospective study was conducted on elderly liver transplant patients treated from January 2016 to March 2023. Patients were divided into two groups: conventional care (n = 58) and ERAS-based care (n = 57). Propensity score matching controlled for confounding variables. Perioperative care interventions included preoperative education, intraoperative management, and postoperative strategies emphasizing early mobilization, pain management, and nutrition. Outcomes included postoperative recovery times, complication rates, and anxiety levels.

ERAS group patients showed significantly improved recovery metrics: reduced times to first oral intake (29.26 vs. 38.42 h, p = 0.011), first ambulation (3.93 vs. 5.46 days, p = 0.008), and first flatus (3.07 vs. 4.33 days, p = 0.003). ICU and total hospital stays were shorter (2.89 vs. 4.52 days, p = 0.007; 22.18 vs. 27.14 days, p = 0.014). The ERAS group had lower complication rates (31.6% vs. 56.9%, p = 0.009) and reduced anxiety levels.

ERAS protocols significantly enhance postoperative recovery and reduce complications in elderly liver transplant recipients. These findings support the integration of ERAS principles into liver transplantation care to improve patient outcomes.

Liver cancer is one of the major causes of cancer-related death in the world. As a breakthrough therapy, immunotherapy had significantly improved the prognosis of patients. However, the current research status and research hotspots in the field of liver cancer immunotherapy still lack systematic review. Based on the bibliometric analysis of highly cited papers, this study intended to reveal the current research status, research hotspots and future research trends in this field.

The purpose of this study was to analyze the national/regional contributions, authors and institutions cooperation network, keywords clustering and keywords burst analysis of highly cited papers on liver cancer immunotherapy through bibliometrics, so as to clarify the research frontier and development direction, and provide objective data support for future research direction and clinical practice.

The highly cited papers on liver cancer immunotherapy from the Web of Science core collection up to February 23, 2025 were retrieved, and 232 studies were included. CiteSpace was used to build a knowledge map, analyze the distribution of years, countries, authors, institutions and cooperation networks, and identify research hotspots and emerging trends through keyword clustering and burst detection.

The number of highly cited papers continued to increase from 2014 and reached a peak in 2022. China and the United States had the highest number of publications and the centrality of cooperation networks. The author with the highest number of papers was Llovet, Josep M, whose research direction mainly focused on immune checkpoint inhibitor combination therapy and molecular typing. The author with the highest cooperation network centrality was Duda, Dan G, whose research team focused on tumor microenvironment regulation. Harvard University and the University of Barcelona played an important central role in the institutional collaboration. Keywords analysis showed that immune checkpoint inhibitors, tumor microenvironment and combination therapy were the core of liver cancer immunotherapy. Burst keywords such as cell lung cancer, pembrolizumab, advanced melanoma, blockade, lymphocytes, etc. had revealed the research frontier of liver cancer immunotherapy research.

The research on liver cancer immunotherapy had made multi-dimensional progress, with China and the United States leading the global cooperation. The main research directions were the combination strategy of immunization, the regulation of tumor microenvironment and the exploration of novel targets. In the future, it is necessary to optimize treatment resistance solutions, integrate interdisciplinary resources, and promote the development of precision and personalized treatment.

Liver cancer is a leading cause of cancer-associated mortality and is often linked to preexisting liver conditions. Emerging research demonstrates FXR dysregulation, particularly its reduced expression, in the pathogenesis of liver diseases, including inflammation, fibrosis, cholestatic disorders, metabolic dysregulation, and liver cancer. Therefore, this review explores the role of FXR and its agonists in mitigating these conditions.

This article summarizes FXR's involvement in liver disorders, primarily emphasizing on hepatic neoplasms, and examines the potential of FXR agonists in restoring FXR activity in liver diseases, thereby preventing their progression to liver cancer. The information presented is drawn from existing preclinical and clinical studies specific to each liver disorder, sourced from PubMed.

It is well established that FXR expression is downregulated in liver disorders, contributing to disease progression. Notably, FXR agonists have demonstrated therapeutic potential in ameliorating liver diseases, including hepatocellular carcinoma. We believe that activating or restoring FXR expression with agonists offers significant promise for the treatment of liver cancer and other liver conditions. Therefore, FXR modulation by agonists, particularly in combination with other therapeutic agents, could lead to more targeted treatments, improving efficacy while reducing side effects.

RNA N6-methyladenosine (m6A) is a common RNA modification in eukaryotes, and its abnormal regulation is closely related to cancer progression. Aerobic glycolysis is a main way for cancer cells to obtain energy. It was found that beaded filament structural protein 1 (BFSP1) is a m6A related gene in liver cancer. However, the effect of m6A-modified BFSP1 on aerobic glycolysis and how it is regulated in liver cancer progression have not been explored. Here, we found that BFSP1 was upregulated in liver cancer cells and tissues. Overexpression of BFSP1 promoted the viability, invasion, and aerobic glycolysis of liver cancer cells, whereas knockdown of BFSP1 showed the opposite effects. Co-immunoprecipitation, immunofluorescence and GST pull down analyses showed that BFSP1 directly interacted with tropomodalin 4 (TMOD4), and knockdown of TMOD4 reversed BFSP1 overexpression-induced malignant phenotypes and aerobic glycolysis in liver cancer cells. Moreover, methyltransferase-like 3 (METTL3) enhanced BFSP1 stability by augmenting m6A modification of BFSP1 mRNA, which is achieved in a YTHDF1-dependent manner. In vivo experiments in mice confirmed that METTL3 increased BFSP1 stability by promoting m6A modification of BFSP1 mRNA, and knockdown of BFSP1 inhibited tumor growth and metastasis. In summary, METTL3-mediated m6A methylation of BFSP1 mRNA plays an important role in the aerobic glycolysis and progression of liver cancer, providing a potential therapeutic strategy for liver cancer.

The tumor microenvironment (TME) plays a critical role in the development, progression, and clinical outcomes of hepatocellular carcinoma (HCC). Despite the critical role of natural killer (NK) cells in tumor immunity, there is limited research on their status within the tumor microenvironment of HCC. In this study, single-cell RNA sequencing (scRNA-seq) analysis of HCC datasets was performed to identify potential biomarkers and investigate the involvement of natural killer (NK) cells in the TME.

Single-cell RNA sequencing (scRNA-seq) data were extracted from the GSE149614 dataset and processed for quality control using the "Seurat" package. HCC subtypes from the TCGA dataset were classified through consensus clustering based on differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was employed to construct co-expression networks. Furthermore, univariate and multivariate Cox regression analyses were conducted to identify variables linked to overall survival. The single-sample gene set enrichment analysis (ssGSEA) was used to analyze immune cells and the screened genes.

A total of 715 DEGs from GSE149614 and 864 DEGs from TCGA were identified, with 25 overlapping DEGs found between the two datasets. A prognostic risk score model based on two genes was then established. Significant differences in immune cell infiltration were observed between high-risk and low-risk groups. Immunohistochemistry showed that HRG expression was decreased in HCC compared to normal tissues, whereas TUBA1B expression was elevated in HCC.

Our study identified a two-gene prognostic signature based on NK cell markers and highlighted their role in the TME, which may offer novel insights in immunotherapy strategies. Additionally, we developed an accurate and reliable prognostic model, combining clinical factors to aid clinicians in decision-making.

Hepatocellular carcinoma (HCC) is one of the most common solid malignancies in the world. Due to the limited effectiveness of current drug treatments, further research on HCC is necessary. PANoptosis is defined as an inflammatory RCD whose main features combine pyroptosis, apoptosis and necroptosis which cannot be explained by any of these three RCDs alone. In HCC, risk stratification based on PANoptosis-associated lncRNAs has clinical application potential. In this study, we explored HCC related PANoptosis-related lncRNAs (PRLs) by analyzing significantly differentially expressed genes in HCC. HCC-associated PRL scores were established by WGCNA, LASSO analysis and multivariate Cox assessment. Subsequently, we verified the prognostic analysis ability of PRL score for HCC patients, and on this basis established a prognostic risk assessment model for HCC and verified its reliability. The relationship between PRL score and immune infiltration as well as drug sensitivity was further analyzed to evaluate the clinical reference value of this model. Western blot analysis and PCR further verified the reliability of bioinformatics results. The observed suppression of HCC progression and invasiveness following selected PRL knockdown further validated the reliability of our bioinformatics analysis results. Our results provide new evidence for the role of PANoptosis-associated lncRNAs in HCC.

Glycyrrhiza uralensis Fisch. (GC) is widely utilized in traditional Chinese medicine (TCM) for its properties in Qi tonification, heat clearing, and detoxification. Within TCM theory, Qi is also implicated in tumor development. Numerous TCM formulas containing GC are used for their anti-tumor effects, and contemporary pharmacological research has demonstrated that ethyl acetate extracts (EAe) of GC, along with potential bioactive compounds like glabridin (Gla), possess anti-tumor properties. Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and a major challenge to global healthcare, with high incidence and poor prognosis. Nevertheless, the effects and mechanisms of action of Gla in inhibiting HCC have not been extensively studied.

This study aims to elucidate the effects and mechanisms of action of Gla against HCC by in vitro and in vivo experiments.

The inhibitory effects of ethyl acetate extract (EAe) of GC and its bioactive compounds on HCC were studied using a drug-cell interaction system equipped with UPLC-MS/MS and high-throughput screening methods in vitro. RNA sequencing (RNA-seq) and bioinformatics technologies were employed to detect the differentially expressed genes (DEGs) and pathways in HepG2 cells. The findings were further validated using quantitative real-time PCR (qPCR) and Western blot (WB) assays. Additionally, an in vivo tumor-bearing mouse model established with H22 cells was utilized to examine alterations in tumor tissues via hematoxylin-eosin (HE) staining. Immunohistochemistry was used to assess the protein expression levels of hub targets within each group.

Both in vitro and in vivo experiments demonstrated the effects of EAe against HCC, identifying Gla was one of its main bioactive compounds. Integration of RNA-seq data with clinical databases revealed that Gla inhibited HCC by up-regulating the expression levels of DUSP5, ZFP36, KLF10, and NR4A1, while down-regulating RMI2 expression. These findings were further validated by Gene Expression Omnibus (GEO), qPCR, WB and immunohistochemistry assays.

Gla regulates the expression levels of DUSP5, ZFP36, KLF10, NR4A1, and RMI2 to against HCC, providing valuable insights for the application of Gla in HCC treatment.

Hepatocellular carcinoma (HCC) has a poor prognosis, partly due to resistance to treatments like sorafenib. The 5-hydroxytryptamine receptor 1D (HTR1D) is involved in cancer progression through the PI3K/Akt pathway, but its role in HCC is not well understood. This study investigates HTR1D's expression, function, and potential as a prognostic marker in HCC.

First, the correlation between HTR1D and hepatocellular carcinoma was analyzed using the TCGA database, and the expression level of HTR1D in clinical samples was detected by qPCR. Then the siRNA was transfected into Huh-7 and Hep3B cells, and the cell proliferation ability, colony formation ability, migration and invasion ability were detected with or without sorafenib. And the expression of the PI3K/Akt pathway was detected by Western Blot. Finally, the potential of HTR1D as a predictive marker for patient prognosis was evaluated by immunohistochemistry.

Analysis of TCGA data showed that methylation of the HTR1D gene was associated with cancer status. Clinical samples confirmed significant differences in HTR1D expression between HCC and adjacent tissues, with higher expression correlating with poorer patient prognosis. Interference with HTR1D gene expression demonstrated its role in promoting HCC proliferation, migration, and drug resistance through the PI3K/Akt pathway. These findings were validated in a mouse model. Immunohistochemical analysis of clinicopathological samples suggested that HTR1D could be a valuable prognostic marker for HCC.

HTR1D is highly expressed in hepatocellular carcinoma tissues, and it can influence hepatocellular carcinoma development and resistance to sorafenib by regulating the PI3K/Akt signaling pathway. In addition, HTR1D has potential as a prognostic indicator.

Argemone mexicana, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of Argemone mexicana in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of Argemone mexicana.

A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of Argemone mexicana, specifically emphasizing its impact on liver health and cancer.

The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of Argemone mexicana, further well-designed trials are warranted to establish its clinical efficacy.

In conclusion, Argemone mexicana shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of Argemone mexicana in liver health and cancer management.

Among the many cancer treatment methods, there have been many reports on the use of nanoplatforms with single treatment methods such as photothermal, photodynamic or chemodynamic for cancer treatment. In this study, Ru(III) with photodynamic effect and Fe3O4 nanoparticles with photothermal and chemodynamic effects are connected through long DNA chains with efficient active targeting rolling circle amplification to construct Ru(III)/Fe3O4/DNA nano-platform realizes the combination of photothermal, photodynamic and chemodynamic treatment, which significantly improves the therapeutic effect of the nano-platform. Its multiple active targeting capabilities reduce the damage to normal cells. Ru(III) has excellent photodynamic effect and can catalyze the respiration product NADH (Nicotinamide adenine dinucleotide)to produce highly oxidizing H2O2. Fe3O4 NPs has weak absorption at 808 nm indicates that it can perform mild photothermal treatment, and the Fe2+ in it can react with H2O2 to produce ·OH and participate in chemodynamic treatment. Each repeating unit on the rolling circle amplified DNA long chain is connected to the AS1411 aptamer that can actively target cancer cells. Unlike the passive targeting of other nanomedicines, active and efficient targeting is achieved, and a small amount of drugs can achieve high efficacy. The therapeutic effect also reduces the damage to normal cells. The comprehensive killing effect of Ru(III)/Fe3O4/DNA can reach 85.1 %. Its high targeting of cancer cells can also be used for imaging detection of cancer cells. This new nanoplatform provides an idea for the synergy of multiple cancer treatments.

Liver cancer has become a major global health challenge due to its high incidence, high rate of late diagnosis and limited treatment options. Although there are many clinical treatments available for liver cancer, the cure rate is still very low, and now researchers have begun to explore new aspects of liver cancer treatment, and nanotechnology has shown great potential for improving diagnostic accuracy and therapeutic efficacy and is therefore a promising treatment option. In diagnosis, nanomaterials such as gold nanoparticles, magnetic nanoparticles, and silver nanoparticles can realize highly sensitive and specific detection of liver cancer biomarkers, supporting diagnosis and real-time monitoring of the disease process. In terms of treatment, nanocarriers can realize precise targeted delivery of drugs, improve the bioavailability of liver cancer therapeutic drugs and reduce systemic toxic side effects. In addition, advanced technologies such as nanoparticle-based photothermal therapy and photodynamic therapy provide innovative solutions to overcome drug resistance and local tumor ablation. Therefore, in this paper, we will introduce nanotechnology for hepatocellular carcinoma in terms of tumor marker detection, targeted drug delivery, and synergistic PDT/CDT therapy.

Young adults contribute substantially to the social economy. However, the number of young adults with liver cancer has increased recently. In addition, the mortality rate of these patients is high.

This retrospective study investigated the risk factors of young patients diagnosed with liver cancer over the past 12 years.

The risk factors of liver cancer, including male, HBV infection, and family history of diseases, were more common in young patients. Nearly 80% of young patients (198/253) were tested as positive HBsAg. However, most of these patients did not visit doctors regularly, as recommended. Thus, 55.7% of young patients were diagnosed with advanced liver cancer. The aspartate aminotransferase (AST) levels were independently associated with advanced liver cancer (OR = 4.262, 95% CI = 1.559-11.65, P = 0.005) in the multivariable logistic regression. The 1-year survival rate of these patients was 19.4%.

The high-risk factors of liver cancer are common in young patients. The poor adherence to regularly visited doctors in young patients might contribute to the high ratio of advanced liver cancer. The 1-year survival rate of these patients is low. Improving patient's adherence via mobile healthcare platform and monitoring serum AST levels might decrease the incidence and mortality of liver cancer in young adults.

Rhubarb has the effect of breaking blood stasis and abnormal mass, and was often used to treat various tumor diseases including liver cancer in ancient China. Recipes containing rhubarb have anti-liver cancer properties and are still used today. However, the main components and mechanism of action of rhubarb against liver cancer are still unclear.

To conduct a review of the anti-liver cancer effects and toxicity of rhubarb anthraquinones (AQs).

This article reviewed the effects of rhubarb AQs in the treatment of liver cancer and the signaling pathways involved, and discussed the toxicity and pharmacokinetics of rhubarb AQs by searching the Web of Science, PubMed and CNKI databases.

Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine that has been existed for thousands of years and is used as an anti-cancer drug. Modern pharmacological research shows that rhubarb AQs, as the main component of rhubarb, contains emodin, rhein, chrysophanol, physcione and aloe-emodin, which has anti-liver cancer effects and can be considered as a potential therapeutic drug for liver cancer. However, many modern studies have shown that rhubarb AQs have certain toxicity, which hinders in-depth research on rhubarb AQs.

Rhubarb AQs can be used as a potential anti-liver cancer drug, but its research still has many limitations. Strengthening research on related experiments and finding a balance between toxicity and efficacy are all directions worth studying in the future.

The development of cancer is accompanied by metabolic reprogramming, and the liver serves as a central hub for lipid transportation. Apigenin, a plant-derived flavonoid, demonstrates potent anticancer properties across various cancer types and exhibits promising potential as a therapeutic agent for cancer treatment. However, there are limited studies focusing on the downstream targets of apigenin. Moreover, there are few reports on the impact of apigenin in lipid metabolism within liver cancer cells.

The objective is to elucidate the metabolic mechanism underlying the inhibitory effect of apigenin on liver cancer progression, search for downstream targets and provide reliable data support for the clinical trials of apigenin.

Anticancer effects of apigenin were detected at cellular and molecular levels in vitro, and downstream targets of apigenin, especially metabolic pathway genes, were analyzed by transcriptome. Next, the downstream target of apigenin was verified and the biological function of the downstream target was examined. Finally, the downstream target of apigenin was further verified by restoring target gene expression.

Cellular molecular experiments showed that Apigenin inhibited the proliferation, migration, invasion and lipid metabolism of hepatocellular carcinoma (HCC) cells. Transcriptome analysis showed apigenin widely regulates histone demethylase, particularly histone H3K4 lysine demethylase 1A (KDM1A). Apigenin treatment inhibited the expression of KDM1A protein and mRNA levels in liver cancer cells, molecular docking predicted the interaction between apigenin and KDM1A. Furthermore, downregulation KDM1A inhibited the proliferation and lipid metabolism of HCC cells, in the same way, overexpressing KDM1A promoted proliferation of HCC cells. Finally, restoring KDM1A expression partially attenuated the effects of apigenin on lipid metabolism in HCC cells.

In conclusion, our study provides compelling evidence that apigenin inhibits liver cancer progression and elucidates its mechanism of action in regulating lipid metabolism. Specifically, we find that apigenin suppresses the progression of HCC cells by downregulating genes involved in lipid metabolism. Additionally, our results indicate that KDM1A acts as a downstream target of apigenin in the inhibition of lipid metabolism in HCC. These findings offer experimental support for the potential use of apigenin as a therapeutic agent for liver cancer, highlighting its relevance in future clinical applications.

Recent research has shown that Doublecortin-like kinase 1 (DCLK1) is overexpressed in different types of cancer. It has recently been described as a cancer stem cells (CSCs) marker, is associated with carcinogenesis, and positively correlates with infiltration of multiple immune cell types in some cancers. However, studies focused on assessing DCLK1 expression in HCC are limited, and the role of DCLK1 in HCC tumor immunity remains to be determined. In this study, we used a modified model of the resistant hepatocyte (MRHM) to evaluate DCLK1 expression in HCC. Furthermore, DCLK1 expression in HCC was analyzed using TIMER 2.0, UALCAN, GEPIA, GEO, and HPA web-based tools. Correlations between DCLK1 expression and clinicopathological factors in patients were analyzed using the UALCAN web-based tool. Finally, correlations between DCLK1 and immune infiltrates were investigated using the TIMER 2.0 and TISIDB web-based tools. The results showed that DCLK1 is significantly overexpressed during progression of the HCC carcinogenic process in the MRHM. DCLK1 is overexpressed in HCC according to multiple publics web-based tools, and its overexpression is associated with cancer stage. Furthermore, DCLK1 expression was correlated with infiltration levels of multiple immune cells, immunomodulatory factors, immunoinhibitors, MHC molecules, chemokines, receptors, and immune cell-specific markers. These results suggest that DCLK1 is a potential prognostic biomarker that determines cancer progression and correlates with immune cell infiltration in HCC.

Liver cancer stem cells (LCSCs) are thought to drive the metastasis and recurrence, however, the heterogeneity of molecular markers of LCSCs has hindered the development of effective methods to isolate them.

This study introduced an effective approach to isolate and culture LCSCs from human primary liver cancer (HPLC), leveraging mouse embryonic fibroblasts (MEFs) as feeder cells in conjunction with using defined medium. Isolated LCSCs were further characterized by multiple approaches. Transcriptome sequencing data analysis was conducted to identify highly expressed genes in LCSCs and classify different subtypes of liver cancers.

Total sixteen cell strains were directly isolated from 24 tissues of three types of HPLC without sorting, seven of which could be maintained long-term culture as colony growth on MEFs, which is unique characteristics of stem cells. Even 10 of cloned cells formed the tumors in immunodeficient mice, indicating that those cloned cells were tumorgenic. The histologies and gene expression pattern of human xenografts were very similar to those of HPLC where these cloned cells were isolated. Moreover, putative markers of LCSCs were further verified to all express in cloned cells, confirming that these cells were LCSCs. These cloned LCSCs could be cryopreserved, and still maintained the feature of colony growth on MEFs after the recovery. Compared to suspension culture as conventional approach to culture LCSCs, our approach much better maintained stemness of LCSCs for a long time. To date, these cloned cells could be cultured on MEFs over 12 passages. Moreover, bioinformatics analysis of sequencing data revealed the gene expression profiles in LCSCs, and liver cancers were classified into two subtypes C1 and C2 based on genes associated with the prognosis of LCSCs. Patients of the C2 subtype, which is closely related to the extracellular matrix, were found to be sensitive to treatments such as Cisplatin, Axitinib, JAK1 inhibitors, WNT-c59, Sorafenib, and RO-3306.

In summary, this effective approach offers new insights into the molecular landscape of human liver cancers, and the identification of the C2 subtype and its unique response to the treatment pave the way for the creation of more effective, personalized therapeutic strategies.

Since the discovery of Fe3O4 nanoparticles with enzyme-like activity in 2007, nanozymes have emerged as a promising class of catalysts, offering advantages such as high catalytic efficiency, low cost, mild reaction conditions, and excellent stability. These properties make nanozymes highly suitable for large-scale production. In recent years, the convergence of nanomedicine and nanocatalysis has highlighted the potential of nanozymes in diagnostic and therapeutic applications, particularly in tumor therapy. Despite these advancements, the clinical translation of nanozymes remains hindered by the lack of designs tailored to specific tumor characteristics, limiting their effectiveness in targeted therapy. This review addresses the mechanisms by which nanozymes induce cell death in various tumor types and emphasizes the key design considerations needed to enhance their therapeutic potential. By identifying the challenges and opportunities in the field, this study aims to provide a foundation for future nanozyme development, ultimately contributing to more precise and effective cancer treatments.

Hepatocellular Carcinoma (HCC) is commonly treated with surgery, liver transplantation, and chemotherapy, but recurrence and metastasis remain challenges. Natural complementary therapies like propolis, known for its hepatoprotective properties, are gaining interest due to limited efficacy and toxicity of conventional chemotherapy. This study aims to identify core targets for HCC, assess the therapeutic potential of East Kalimantan propolis (EKP) from stingless bees, and analyze the molecular interactions.

EKP compounds were analyzed using target prediction tools related to HCC, alongside clinical data from the Gene Expression Omnibus (GEO) database, to identify overlapping genes with clinical relevance. The selected genes were then subjected to protein-protein interaction (PPI), GO and KEGG enrichment, immunohistochemical comparison and survival analysis to identify potential core targets and related pathways for HCC therapy. Furthermore, molecular docking and dynamics were conducted to verify the molecular interactions and stability of EKP compounds with targets.

108 genes have been selected as HCC potential targets, which mostly associated with MicroRNAs in cancer, chemical carcinogenesis, and viral carcinogenesis pathways. These targets were obtained by overlapping genes from GEO clinical databases and target predictors. PPI network analysis revealed 4 main targets of propolis in HCC. Furthermore, differential expression genes, survival analysis, and Immunohistochemical analysis from databases suggested that AKR1C3 and MAPK1 promote HCC progression and shorten survival rate of HCC patients. Molecular docking and dynamic studies confirmed strong binding affinity and stability of Baicalein, Chrysin, Quercetin, and Myricetin with receptor targets within simulation time.

This study provides insight into the mechanism of action of EKP on HCC and identifies AKR1C3 and MAPK1 as candidate target treatments for future drug development.

Liver hepatocellular carcinoma (LIHC) is a major contributor to cancer-related mortality worldwide, posing substantial diagnostic and therapeutic challenges. Although zinc finger proteins (ZNFs) are known to play a role in LIHC, the specific function of ZNF248 remains poorly understood. In this study, we analyzed genomic and clinical data from The Cancer Genome Atlas (TCGA) to elucidate the role of ZNF248 through differential expression analysis, bioenrichment, immune response correlation, and drug sensitivity evaluation. Machine learning was employed to identify prognostic signatures derived from ZNF248, which were further validated using Receiver Operating Characteristic (ROC) analysis. Functional assays, including Western blot and rescue experiments, were performed to assess the impact of ZNF248 on the PI3K/AKT signaling pathway. Our results demonstrate that ZNF248 is significantly overexpressed in LIHC patients and is associated with poor prognosis. Bioenrichment analysis revealed activation of oncogenic pathways, and elevated ZNF248 expression correlated with increased immune cell infiltration and enhanced immune scores, thereby influencing both immunotherapy response and drug sensitivity. Functional assays further confirmed that ZNF248 promotes LIHC progression and invasion, while silencing ZNF248 inhibited the PI3K/AKT pathway - a phenomenon reversible by the AKT activator SC79. These findings suggest that ZNF248 contributes to LIHC progression through the PI3K/AKT pathway and may represent a novel immunotherapeutic target and prognostic biomarker for LIHC.

Primary liver cancer (PLC), comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a severe form of cancer associated with a high mortality and morbidity rate and increasing incidence worldwide. Current treatment options are limited and chemotherapeutics demonstrate strong side effects. New therapies are highly required. Lactobacilli represent the most diverse lactic acid-producing bacteria group and a prominent example of probiotics. Several studies have highlighted the anticancer efficacy of probiotics, especially of Lactiplantibacillus plantarum. However, there are limited studies on its activity on two PLC types, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). This study evaluated the inhibitory mechanism and properties of L. plantarum ONU 12 (Lp 12) and L. plantarum ONU 355 (Lp 355), isolated from grapes in Ukraine and France, in murine PLC cell lines, in vitro. Strain Lacticaseibacillus casei ATCC 393 (Lc 393) has been taken for a direct comparison, as the most studied probiotic strain. The three Lactobacillus species were used in three forms: as live and heat-killed suspensions, and as sonicated extracts, and tested either as a monotherapy or in combination with standard chemotherapeutics (sorafenib for HCC and gemcitabine for CCA). Cell proliferation and viability were assessed via crystal violet staining assay and cell counting kit-8 assay. The induction of senescence was investigated by senescence-associated β-galactosidase assay. Fluorescence-activated cell sorting analysis was used to determine the apoptotic mechanism behind the inhibitory property of lactobacilli. The results showed that the live suspensions and sonicated extracts of Lp 12, Lp 355, and Lc 393 demonstrated inhibitory properties in CCA and HCC cells after 48 h of incubation. In combinations with standard chemotherapeutics, lactobacilli treatments have shown strong synergistic effects. The combination therapy allowed to reduce the chemotherapeutic doses of gemcitabine from 50 μM to 0.1 and 0.05 μM and sorafenib from 13.8 μM to 6.9 and 3.45 μM. Successful treatment regimes induced early apoptosis and cellular senescence in PLC, as the mechanism of inhibition. Heat-killed suspensions showed no inhibitory effect in none of the cell lines. Both strains, Lp 12 and Lp 355, showed successful results and need further testing in vivo, using autochthonous HCC and CCA models.

Globally, liver cancer as one of the most frequent fatal malignancies, hits hard and fast. And the lack of effective treatments for liver hepatocellular carcinoma (LIHC), activates the researchers to promote promising precision medicine. Interestingly, emerging evidence proves that cellular senescence is involved in the progression of cancers and is recognized for its hallmark-promoting capabilities. Hence, efforts have been made to construct and validate the senescence risk score signature (SRSS) model as a novel prognostic biomarker for LIHC.

The existing databases were mined for the following bioinformatics analyses. GSE22405, GSE57957, and senescence-related genes (SRGs) from public databases were utilized as a training set and the validation set was constituted by LIHC and pancreatic adenocarcinoma (PAAD) from The Cancer Genome Atlas (TCGA). After overlapping differentially expressed genes (DEGs) with SRGs, differentially expressed SRGs were identified with the progression of liver cancer through univariate and multivariate Cox regression and enrichment analyses. The model that utilized three SRGs was constructed using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Next, to evaluate the predictive performance of the SRSS model, the overall survival (OS) and survival rates were assessed through Kaplan-Meier (KM) and the receiver operating characteristic (ROC) curves. The predictive value for LIHC prognosis was further evaluated by capitalizing on risk score, nomograms, decision curve analysis (DCA) curves, and clinical information including tumor stages, gender, age, and race.

DEGs were revealed as enriching in multiple tumor-related biological processes (BPs) and pathways. IGFBP3, SOCS2, and RACGAP1 were identified as the three considerable SRGs for the model. The high-risk group had a worse prognosis [both hazard ratio (HR) >1, P<0.001] and ROC curves showed a reliable predictive model with area under the curve (AUC) predictive values ranging from 0.673-0.816 for different-year survival rates respectively. The univariate and multivariate Cox regression analyses exhibited that risk score was the only credible prognostic predictor (HR >1, P<0.001) among clinical features such as tumor stage, age, etc., in LIHC. The nomograms, and DCA curves, combined with multiple clinical information, proved that the predictive ability of SRSS was strongest, followed by nomogram and traditional tumor node metastasis (TNM) stage was the weakest.

In summary, comprehensive analyses supported that the SRSS model can better predict survival and risk in LIHC patients. Promisingly, it may point out a brand-new direction for LIHC therapy.

MiR-105 exerts inhibitory effects on the development and progression of various cancers, including breast cancer, lung cancer, and gastric cancer. Through GEO data analysis, we observed decreased expression of miR-105 in liver cancer tissues compared to adjacent tissues. Furthermore, miR-105 downregulates KIFC1 expression levels by targeting its 3' UTR. KIFC1 (Kinesin Family Member C1), a Protein Coding gene, may play a role in mitotic metaphase plate polymerization and mitotic spindle assembly. However, our findings suggest that this gene could serve as a potential chemotherapeutic target for Liver hepatocellular carcinoma (LIHC). We obtained the LIHC dataset from the TCGA database and genotype Tissue Expression Project (GTEx) normal tissue data for differential analysis. Additionally, we utilized the cBioPortal database, tumor immune single-cell center (TISCH) database, gene set enrichment analysis (GSEA), and R software to investigate the possible functions and mechanisms of KIFC1. These findings were further validated through experiments such as immunohistochemistry and wound healing assays. Our results indicate that KIFC1 might be involved in DNA repair and cell cycle regulation in LIHC cells which subsequently impacts tumor cell proliferation; moreover, miR-105 influences hepatoma cell line proliferation via its interaction with KIFC1. Collectively, these results highlight the potential therapeutic significance of targeting KIFC1 for chemotherapy treatment in LIHC patients.

Hepatocellular carcinoma (HCC) is characterized by a lack of obvious clinical features in the early stages and is likely to progress to advanced HCC. Advanced HCC is a highly malignant tumor. However, there are few treatment options for advanced HCC. Therefore, screening for new drugs that target HCC will provide a new approach to the treatment of HCC. The CCK8 assay was performed to screen compounds inhibiting HCC cell proliferation and to evaluate the IC50 (half-maximal inhibitory concentration) of compounds on cell lines. Colony formation assay was used to determine HCC cell proliferation. The effect of compounds on HCC cell migration and invasion were analyzed using wound healing and transwell assays, respectively. Tumor growth and metastasis were assessed in vivo in a xenograft mouse model. Flow cytometry was carried out to measure apoptotic cells. Reverse transcription and quantitative real-time polymerase chain reaction (RT‒qPCR) and Western blot were performed to examine the expression of epithelial-mesenchymal transition (EMT)- and apoptosis-related genes. Through large-scale screening, we have discovered the anti-tumor activity of cetylpyridinium chloride (CPC) against HCC cells. CPC inhibited the proliferation, invasion and metastasis of HCC cells. Cancer cells are more sensitive to CPC than normal cells. CPC suppressed HCC tumor growth and metastasis in vivo. Mechanistically, CPC promoted apoptosis of HCC cells by affecting the expression of apoptosis-related genes, and inhibited HCC invasion and metastasis by suppressing EMT and expression of EMT markers. Our investigation showed that CPC significantly inhibited HCC cell proliferation, invasion and metastasis in vivo and in vitro, by inducing the expression of apoptosis-related genes and inhibiting expression of EMT markers, suggesting that CPC is a potential agent for HCC treatment.

Hepatopancreatobiliary (HPB) cancers encompassing malignancies of the liver, pancreas, gall bladder, and bile ducts pose a significant health burden in Africa. While the association of certain occupational carcinogens in cancer is well established globally, their potential role in HPB cancers remains understudied, especially in an African context.

This systematic review delves into the association between occupational carcinogens and HPB cancer in Africa. It examines the current state of research on occupational carcinogens and HPB cancers in Africa, identifying key challenges and knowledge gaps.

This systematic review examined publications (published between 01 January 2012 and 31 May 2023) that highlight occupational carcinogens and HBP cancers in Africa. The search was conducted on electronic databases namely PubMed, Web of Science, and Africa Wide Information.

Due to the lack of information on the association between occupational carcinogens and HPB cancers in Africa, as a result of the paucity of published studies, only four articles were included in this study. Hepatocellular carcinoma (HCC) was the predominant cancer associated with the occupational carcinogen, aflatoxin. Agricultural workers, especially those involved in the production and processing of maize and peanuts, appear to be the most exposed to aflatoxin.

Despite the sample size limitations due to the paucity of research studies on occupational carcinogens and HPB cancers in Africa, this study provides a reasonable tool for subsequent epidemiological studies. There is a need for more research on the association of occupational carcinogens and HPB cancers in Africa, especially with the growing industrialization.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.

Hepatocellular carcinoma (HCC) remains the most prevalent form of primary liver cancer, characterized by late detection and suboptimal response to current therapies. The tumour microenvironment, especially the role of M2 macrophages, is pivotal in the progression and prognosis of HCC. We applied the machine learning algorithm-CIBERSORT, to quantify cellular compositions within the HCC TME, focusing on M2 macrophages. Gene expression profiles were analysed to identify key molecules, with ATP6V1E1 as a primary focus. We employed Gene Set Enrichment Analysis (GSEA) and Kaplan-Meier survival analysis to investigate the molecular pathways and prognostic significance of ATP6V1E1. A prognostic model was developed using multivariate Cox regression analysis based on ATP6V1E1-related molecules, and functional impacts were assessed through cell proliferation assays. M2 macrophages were the dominant cell type in the HCC TME, significantly correlating with adverse survival outcomes. ATP6V1E1 was robustly associated with advanced disease stages and poor prognostic features such as vascular invasion and elevated alpha-fetoprotein levels. GSEA linked high ATP6V1E1 expression to critical oncogenic pathways, including immunosuppression and angiogenesis, and reduced activity in metabolic processes like bile acid and fatty acid metabolism. The prognostic model stratified HCC patients into distinct risk categories, showing high predictive accuracy (1-year AUC = 0.775, 3-year AUC = 0.709 and 5-year AUC = 0.791). In vitro assays demonstrated that ATP6V1E1 knockdown markedly inhibited the proliferation of HCC cells. The study underscores the significance of M2 macrophages and ATP6V1E1 in HCC, highlighting their potential as therapeutic and prognostic targets.

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

Integrating conventional ultrasound features with 2D shear wave elastography (2D-SWE) can potentially enhance preoperative hepatocellular carcinoma (HCC) predictions.

To develop a 2D-SWE-based predictive model for preoperative identification of HCC.

A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital. The patients were divided into the modeling group (n = 720) and the control group (n = 164). The study included conventional ultrasound, 2D-SWE, and preoperative laboratory tests. Multiple logistic regression was used to identify independent predictive factors for malignant liver lesions, which were then depicted as nomograms.

In the modeling group analysis, maximal elasticity (Emax) of tumors and their peripheries, platelet count, cirrhosis, and blood flow were independent risk indicators for malignancies. These factors yielded an area under the curve of 0.77 (95% confidence interval: 0.73-0.81) with 84% sensitivity and 61% specificity. The model demonstrated good calibration in both the construction and validation cohorts, as shown by the calibration graph and Hosmer-Lemeshow test (P = 0.683 and P = 0.658, respectively). Additionally, the mean elasticity (Emean) of the tumor periphery was identified as a risk factor for microvascular invasion (MVI) in malignant liver tumors (P = 0.003). Patients receiving antiviral treatment differed significantly in platelet count (P = 0.002), Emax of tumors (P = 0.033), Emean of tumors (P = 0.042), Emax at tumor periphery (P < 0.001), and Emean at tumor periphery (P = 0.003).

2D-SWE's hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions, correlating significantly with MVI and antiviral treatment efficacy.