Tumor cells (TCs) produce exosomes (EXOs), nanovesicles formed in endosomes. Tumor-derived exosomes (TDEs) are tiny, bubble-shaped structures formed by TCs that include microRNAs (miRNA), proteins, enzymes, and copies of DNA and RNA. Many different kinds of cancer rely on TDEs. For instance, TDEs play a large role in the tumor microenvironment (TME) and promote tumor spread via many pathways. Furthermore, TDEs impact the efficacy of cancer treatments. Additionally, because of their low immunogenicity, high biocompatibility, and low toxicity, TDEs have been extensively used as drug delivery vehicles for cancer immunotherapy. Consequently, future cancer treatments may benefit from focusing on both the therapeutic function and the tumorigenic pathways of TDEs. Consequently, in this work, we have examined the roles of TDEs in cancer development, such as tumor angiogenesis, immune system evasion, and tumor metastasis. Then, we reviewed TDEs used to transport anticancer medicines, including chemotherapeutic medications, therapeutic compounds (including miRNA), and anticancer nanoparticles. We have concluded by outlining the challenges of clinical translation, including carcinogenicity and medication resistance, and by offering some suggestions for addressing these issues.

Liver cancer, a malignant tumor of the digestive system, is a leading cause of cancer‑related mortality globally. Numerous genetic mutations associated with tumorigenesis have been identified, stemming from genomic instability. However, the clinical implications and therapeutic relevance of these mutations remain poorly understood. The present study evaluated the prognostic significance of titin (TTN) mutations in liver cancer by analyzing the mutation landscape of liver cancer tissues from The Cancer Genome Atlas (TCGA) database. The association between TTN mutations and drug susceptibility was subsequently examined using the OncoPredict algorithm and Cell Counting Kit‑8 (CCK‑8) assays. Furthermore, the impact of TTN mutations on hepatoma cell biology both in vivo and in vitro were assessed by reverse transcription‑quantitative PCR, protein stability assays, colony formation assays, tumor spheroid formation assays and subcutaneous tumor transplantation in BALB/c nude mice. Genetic analysis of the TCGA database revealed that TTN mutations are among the most frequent mutations in liver cancer. Patients with TTN mutations exhibited worse prognoses compared with those with the wild‑type allele. The OncoPredict algorithm and CCK‑8 assays revealed that TTN mutations are associated with altered drug sensitivity, particularly to GSK1904529A, nilotinib, 5‑fluorouracil (5‑FU) and sapitinib. Additionally, TTN mutations were shown to enhance TTN protein stability, decrease intracellular ferrous ion levels and significantly decrease liver cancer sensitivity to 5‑FU both in vitro and in vivo. The findings indicated that TTN mutations increase protein stability and lower intracellular ferrous ion levels, thereby suppressing ferroptosis and contributing to resistance to 5‑FU in hepatoma cells. These results suggest that TTN mutations are associated with poor prognosis in liver cancer and could serve as a predictive biomarker for liver cancer progression, prognosis and drug resistance.

Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.

Cancers of the gastrointestinal (GI) tract, including colorectal, pancreatic, and hepatocellular carcinomas, represent a significant global health burden due to their high incidence and mortality rates. Doublecortin-like kinase 1 (DCLK1), initially identified for its role in neurogenesis, has emerged as a crucial player in GI cancer progression. This review comprehensively examines the multifaceted roles of DCLK1 in GI cancers, focusing on its structural isoforms, functions in normal and inflammatory states, and contributions to cancer progression and metastasis. DCLK1 is overexpressed in various GI cancers and is associated with poor prognosis, enhanced tumorigenic potential, and increased metastatic capacity. The review discusses the molecular mechanisms through which DCLK1 influences cancer stem cell maintenance, epithelial-mesenchymal transition (EMT), and cell survival pathways, as well as its interactions with key signaling pathways such as Notch, WNT/β-catenin, and NF-κB. The potential of DCLK1 as a therapeutic target is also explored, highlighting preclinical and early clinical efforts to inhibit its function using small molecule inhibitors or monoclonal antibodies. Despite significant advancements, further research is needed to fully elucidate DCLK1's role in GI cancers and to develop effective therapeutic strategies targeting this protein.

Xihuang Pill (XHP) is a traditional Chinese medicine formula that was originally used to treat malignant ulcers. Recent studies revealed its therapeutic effects on various malignant tumors. However, its potential efficacy and mechanisms in primary liver cancer (PLC) were not thoroughly investigated.

This study aimed to elucidate the efficacy and potential mechanisms of XHP in the treatment of PLC.

An orthotopic PLC mice model was established adopting hydrodynamic tail vein injection method. Human liver cancer cell lines and organoids were utilized to assess the effect of XHP in vitro. The expressions of alpha-fetoprotein (AFP) and Yes-associated protein (YAP) were evaluated with western blotting. The mRNA expressions of YAP downstream targets were detected with qRT-PCR. Data from Liver Hepatocellular Carcinoma Collection of the Cancer Genome Atlas (TCGA-LIHC) were extracted to identify the potential targets of HCC. The major active components of XHP methanol extract and XHP medicated serum were detected by UHPLC-MS/MS. Human liver cancer cell lines were used to assess the efficacy and potential mechanisms of these active components in XHP in vitro. Finally, molecular docking was conducted to predict the binding affinities of XHP's active components with AFP and YAP.

XHP inhibited PLC tumor growth in the mice model with decreased AFP and Ki-67 index. In vitro, XHP suppressed the proliferation and migration of liver cancer cell lines in a time- and dose-dependent manner. Furthermore, even with a low concentration (5 mg/mL), XHP paralyzed the growth of PLC organoids derived from patients. Mechanistically, XHP downregulated the expression of AFP and YAP signaling in vitro and in vivo. UHPLC-MS/MS analysis identified 25 active components in XHP medicated serum. Among them, certain active compounds suppressed PLC cell proliferation and downregulated AFP and YAP signaling, suggesting their therapeutic potentials in PLC. Molecular docking indicated that several components in XHP exhibited strong binding affinities with both AFP and YAP.

XHP inhibited PLC growth by suppressing AFP and YAP signaling. This study provides an experimental basis for XHP application in PLC treatment.

Notch signaling is a widely preserved communication pathway that supports essential cellular functions by allowing adjacent cells to interact. The Notch signaling pathway consists of Notch ligands (DSL proteins), Notch receptors, DNA-binding proteins, and downstream target genes. Hepatocellular carcinoma (HCC) represents the predominant cause of cancer-related deaths globally and poses a significant threat to human health. For highly malignant HCC, current treatment options, including chemotherapy, radiotherapy, immunotherapy, targeted therapies, and surgical procedures, often have poor prognoses. Therefore, there is a need to explore additional therapeutic strategies. Many studies have found that abnormal activation of the Notch signaling pathway contributes to tumor initiation and progression by promoting HCC proliferation, metastasis, stem cell-like properties, and drug resistance. In this research, we reveal the composition and activation mechanisms of the Notch signaling pathway, as well as the molecular mechanism underlying its aberrant activation in HCC. Furthermore, we summarize recent advances in targeting Notch signaling for the treatment of HCC. This review aims to highlight the promising potential of investigating the Notch pathway as a therapeutic target in HCC.

Hepatocellular carcinoma (HCC) is a significant malignant tumor that is typically diagnosed late and has a poor prognosis. USP28 (Ubiquitin-specific protease 28), a deubiquitinating enzyme within the ubiquitin-specific proteases (USPs) family, plays a pivotal role in various biological processes, especially in cancer progression. However, its functions and molecular mechanisms in HCC are still unknown.

We first analyzed the expression level of USP28 in HCC tissues relative to normal tissues using TCGA database. This was further validated by qRT-PCR and Western Blot. To investigate the function of USP28 in HCC, CCK-8 assay, clone formation assay and Transwell assay were performed in control and USP28 knockdown or overexpressed HCC cells. To explore potential downstream targets of USP28, we used IP-MS analysis. The interaction between USP28 and KRT1 was confirmed by immunoprecipitation and immunofluorescence staining. Finally, we evaluated the in vivo effects of USP28 on HCC growth and metastasis using a ectopic tumor-bearing mouse model.

The expression of USP28 in HCC tissues was significantly higher than that in normal tissues, and its high expression was associated with poor prognosis. Functional experiments showed that down-regulation of USP28 expression effectively inhibited the proliferation, migration and invasion of HCC cells, while overexpression of USP28 produced the opposite effect. Mechanistic investigations demonstrated that USP28 interacted with KRT1 and exerted deubiquitination on KRT1, thereby maintaining the stability of KRT1. Further studies revealed that USP28 knockdown resulted in decreased IFITM3 expression, which inhibited HCC cell proliferation. In addition, USP28 knockdown combined with sorafenib inhibited tumor growth and metastasis in tumor xenograft mice model.

Our study confirmed the carcinogenic effects of USP28 by stabilizing KRT1 expression and promoting IFITM3. USP28 small molecule inhibitors can inhibit the proliferation of hepatocellular carcinoma cells and enhance the sensitivity of hepatocellular carcinoma cell lines to sorafenib. This provides a theoretical basis for USP28 to be a new clinical method to alleviate sorafenib resistance.

Liver cancer is challenging to detect in its early stages, and the global incidence rate and mortality associated with this disease have reached alarming levels. Currently, treatment options for liver cancer are limited, and there is a significant lack of safe and effective therapeutic agents. Esculetin is a natural product, exhibits almost non-toxic and inhibitory properties against various malignancies, making it a subject worthy of further investigation in liver cancer.

In this study, potential targets of esculetin in liver cancer were identified through transcriptomics, network pharmacology, and molecular docking technologies, and gene interference. Direct binding targets of esculetin were identified using surface plasmon resonance (SPR). The molecular mechanisms by which esculetin affects glucose metabolism in liver cancer were also explored. Finally, the activity against liver cancer and mechanisms of action of esculetin were validated in vivo using a mouse tumor model.

Glucose-6-phosphate isomerase (GPI) was shown to have a direct binding affinity for this compound. Esculetin inhibits glycolysis in liver cancer through its interaction with GPI and it was shown to exert a significant inhibitory effect on the genes and proteins associated with glycolysis such as ALDOA, ENO1, GAPDH, LDHA, PFKL, PGAM1, PGK1, and PKM2. Furthermore, esculetin not only suppresses the growth of liver cancer cells in vitro but also exhibits notable anti-tumor effects in vivo.

This study demonstrated the inhibitory effects of esculetin against liver cancer both in vitro and in vivo, demonstrating inhibition of glycolysis in liver cancer cells. In addition, the key glycolysis enzyme GPI was identified as a direct target of esculetin.

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 study investigated the role of MDK (Midkine) in hepatocellular carcinoma (HCC) through bioinformatics analysis and experimental validation, focusing on its relationship with tumor immune microenvironment and patient prognosis.

We employed the GEPIA database to analyze MDK expression patterns across cancer types and specifically in HCC versus normal tissues. MDK expression was validated through immunohistochemistry (IHC) in 100 paired HCC and adjacent tissue samples. Survival analyses were conducted using Kaplan-Meier and Cox regression methods. The relationship between MDK expression and immune cell infiltration was investigated using TIMER 2.0 database and verified through IHC staining of immune cell markers.

MDK expression was significantly elevated in HCC tissues compared to adjacent normal tissues. High MDK expression strongly correlated with tumor number, vascular invasion, advanced clinical stage and poor prognosis, serving as an independent prognostic factor. Notably, elevated MDK expression predicted poor outcomes in patients receiving immunotherapy. Database analysis and IHC analysis revealed that MDK expression positively correlated with regulatory T (Treg) cell infiltration while negatively correlating with natural killer (NK) cell presence, suggesting its role in shaping the tumor immune microenvironment.

High MDK expression in HCC correlates with unfavorable patient outcomes and impacts immune cell infiltration. MDK may serve as a novel prognostic biomarker and potential therapeutic target in HCC treatment.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related mortality globally. Current systemic therapies for HCC are limited and often exhibit unsatisfactory efficacy, underscoring the need for novel therapeutic approaches. Nuclear factor erythroid 2-related factor-2 (NRF2), a master transcription factor regulating cellular redox and metabolic homeostasis, is frequently overexpressed in HCC due to mutations in NFE2L2/NRF2 or its negative regulator Kelch-like ECH-associated protein 1 (KEAP1), contributing to tumor progression. In this study, we identify CYP4F11, a member of the Cytochrome P450 family, as a direct target gene of NRF2. CYP4F11, primarily expressed in the liver, is crucial in fatty acid oxidation and eicosanoid metabolism. We demonstrate that CYP4F11 expression is driven by NRF2 and is significantly elevated in HCC patients harboring NFE2L2 gain of function or KEAP1 loss of function mutations. Functionally, CYP4F11 promotes HCC cell growth, and reduced expression of CYP4F11 not only suppresses HCC cell proliferation but also enhances sorafenib-induced HCC cell death. Further, NRF2 inhibition sensitizes HCC to sorafenib through downregulation of CYP4F11. These findings position CYP4F11 as a novel contributor to HCC progression and highlight the potential of targeting the NRF2-CYP4F11 axis for HCC treatment.

Hepatocellular carcinoma (HCC) is one of the most lethal forms of cancer globally. HCC cells frequently undergo macroautophagy, also known as autophagy, which can lead to tumor progression and chemotherapy resistance. Annexin A2 (ANXA2) has been identified as a potential therapeutic target in HCC and is involved in the regulation of autophagic process. Here, we for the first time showed that ANXA2 deacetylation plays a crucial role in donafenib-induced autophagy. Mechanistically, donafenib increased SIRT2 activity via triggering both SIRT2 dephosphorylation and deacetylation by respectively downregulating cyclin E/CDK and p300. Moreover, elevation of SIRT2 activity by donafenib caused ANXA2 deacetylation at K81/K206 sites, leading to a reduction of the binding between ANXA2 and mTOR, which resulted in a decrease of mTOR phosphorylation and activity, and ultimately promoted protective autophagy and donafenib insensitivity in HCC cells. Additionally, ANXA2 deacetylation at K81/K206 sites was positively correlated with poor prognosis in HCC patients. Meanwhile, we found that selective inhibition of SIRT2 increased the sensitivity of donafenib in HCC cells by strengthening ANXA2 acetylation. In summary, this study reveals that donafenib induces protective autophagy and decreases its sensitivity in HCC cells through enhancing SIRT2-mediated ANXA2 deacetylation, which suggest that targeting ANXA2 acetylation/deacetylation may be a promising strategy for improving the sensitivity of donafenib in HCC treatment.

Primary gastric and liver cancers rank among the most prevalent malignant tumors of the digestive tract. Despite their serious implications for health, the global age-standardized incidence remains relatively low, at ~11.1 per 100,000 for primary gastric cancer and ~8.657 per 100,000 for primary liver cancer. Although the occurrence of multiple primary malignancies is not uncommon in clinical practice, reports of synchronous primary gastric and liver cancer are exceedingly rare. The present study describes a case involving a 60-year-old man diagnosed with synchronous primary gastric and liver cancer. The patient underwent endoscopic submucosal dissection for lesions located at the gastric angle, followed by laparoscopic resection of a small liver tumor. Pathological examinations revealed moderately differentiated intramucosal adenocarcinoma at the gastric angle and well-differentiated hepatocellular carcinoma in the liver. Following a 3-year follow-up, the patient remained in good health, with no evidence of disease recurrence. In conclusion, clinicians should exercise caution in patients presenting with distinct lesions to ensure that subtle malignancies are not overlooked, particularly in those with confirmed cancer. For patients with multiple cancers, it is crucial to ascertain whether the malignancies are primary, as this determination influences treatment strategies.

This study utilized GC-MS and NMR to characterize the detailed chain structure information of polysaccharide (HM0-1) from the Agelas aff. Nemoechinata sponge, and then explored its anti-liver cancer in vitro. Results showed that the HM0-1 was a homogeneous amino-polysaccharide with a molecular weight of 929 kDa, composed of mannose (Man), N-Acetyl-glucosamine (GlcNAc), N-Acetyl-galactosamine (GalNAc), galactose (Gal) and fucose (Fuc). The main chain of HM0-1 was composed of α-(1 → 2)-linked Man and α-(1 → 6)-linked GlcNAc, and the side chains were α-Galp (1→, α-Fucp-(1 → 3)-α-Galp-(1→, α-Manp-(1→) and a branch composed of GalNAc and Gal, which was connected to the main chain through the 3-O position of →2)-β-Manp-(1→and→6)-β-Manp-(1→. Additionally, HM0-1 exhibited anti-liver cancer effects by inhibiting cell proliferation, migration and invasion, and inducing cell apoptosis. We further investigated the potential mechanism of HM0-1-induced apoptosis by RNA-seq, which revealed 3679 significantly altered DEGs. GO enrichment analysis of the DEGs revealed significant enrichment of 2444 GO terms throughout the differentiation process (P < 0.05). KEGG analysis showed that the DEGs were successfully annotated as members of 347 pathways, with 42 significantly enriched KEGG pathways. In conclusion, these studies can provide valuable insights into the potential development and utilization of sponge polysaccharides as marine natural bio-active compounds.

The study aims to investigate the potential causal effects of lipids on liver cancer risk and to analyze the possible impact of lipid-lowering drug targets on liver cancer.

Genetic variants linked to lipid traits and drug targets were obtained from the Global Lipids Genetics Consortium and DrugBank. Liver cancer data were sourced from FinnGen. Mendelian randomization (MR) was used to assess causal relationships between lipid traits and liver cancer. Functional analyses included protein-protein interaction (PPI), KEGG pathway enrichment, transcription factor (TF) network analysis, and survival analysis. NPC1L1 expression, DNA methylation, and immune infiltration were analyzed using UALCAN, TCGA-LIHC, and TIMER, respectively.

MR analysis showed higher genetically predicted LDL-C levels reduced liver cancer risk (OR = 0.5981, p = 0.034). Drug target MR indicated that NPC1L1 inhibition (OR = 1.0638, p = 0.0311) and elevated PPARɑ levels (OR = 1.1339, p < 0.01) increased liver cancer risk. Functional analysis revealed NPC1L1 was highly expressed in liver cancer tissues due to hypomethylation and linked to immune cell infiltration, indicating its role in immune evasion and tumor progression.

The study demonstrates that elevated LDL-C levels are associated with a reduced risk of liver cancer and NPC1L1 plays a key role in regulating lipid metabolism and influencing immune evasion.

This study aimed to investigate the toxic effects of ellipticine on liver cancer cells and predict its anti-liver cancer mechanism through network pharmacology, especially by targeting FGFR3 to regulate the RAS/MAPK-P38 signaling pathway, thereby inducing apoptosis of liver cancer cells. The inhibitory effect of ellipticine on the proliferation of HepG2, Huh-7, SMMC7721, BEL-7402, SK-HEP-1, LX-2, and MHCC97H cells was detected by CCK-8 assay, and the IC50 value was calculated. The potential targets of ellipticine were predicted by the database, and the intersection analysis with liver cancer-related targets was performed to construct a protein interaction network (PPI), (KEGG) pathway enrichment analysis, and molecular docking verification. FGFR3 in HepG2 cells was knocked down by siRNA, and the effects on cell proliferation, apoptosis, and ROS levels were observed. The expression changes of FGFR3, RAS, P38, and their phosphorylated forms after ellipticine treatment, as well as the effects of RAS agonist ML-908 and P38 inhibitor PD169316 on cell proliferation, apoptosis, and migration, were detected by Western blotting. Ellipticine has an inhibitory effect on all tested liver cancer cell lines, among which HepG2 has the strongest inhibitory effect, with an IC50 of 5.15 ± 0.25 μM. Ellipticine is predicted to have 32 potential targets, and 5 common targets among the 225 targets related to liver cancer, including PDGFRA, KIT, FGFR3, ERBB2, and STAT3. KEGG analysis showed that these targets are mainly involved in cancer pathways. Molecular docking showed that Ellipticine can bind strongly to FGFR3. FGFR3 expression is highest in HepG2 cells. After knocking down FGFR3, the proliferation ability of HepG2 cells is further weakened, and the addition of apoptosis inhibitor ZVAD can partially restore the proliferation ability. ROS levels increase after Ellipticine treatment, and ROS levels further increase after knocking down FGFR3, and ZVAD treatment can reduce ROS levels. After Ellipticine treatment, the expression levels of FGFR3, RAS, and p-P38 decrease. Ellipticine-induced cell proliferation inhibition and apoptosis were reversed by RAS agonist ML-908, whereas P38 inhibitor PD169316 exacerbated cell apoptosis and migration inhibition. Ellipticine induces apoptosis of liver cancer cells by targeting FGFR3 and inhibiting the RAS/MAPK-P38 signaling pathway. This discovery provides new mechanistic insights into Ellipticine as a liver cancer treatment and may lay the foundation for the development of targeted therapeutic strategies.

Automated classification of liver lesions in multi-phase CT and MR scans is of clinical significance but challenging. This study proposes a novel Siamese Dual-Resolution Transformer (SDR-Former) framework, specifically designed for liver lesion classification in 3D multi-phase CT and MR imaging with varying phase counts. The proposed SDR-Former utilizes a streamlined Siamese Neural Network (SNN) to process multi-phase imaging inputs, possessing robust feature representations while maintaining computational efficiency. The weight-sharing feature of the SNN is further enriched by a hybrid Dual-Resolution Transformer (DR-Former), comprising a 3D Convolutional Neural Network (CNN) and a tailored 3D Transformer for processing high- and low-resolution images, respectively. This hybrid sub-architecture excels in capturing detailed local features and understanding global contextual information, thereby, boosting the SNN's feature extraction capabilities. Additionally, a novel Adaptive Phase Selection Module (APSM) is introduced, promoting phase-specific intercommunication and dynamically adjusting each phase's influence on the diagnostic outcome. The proposed SDR-Former framework has been validated through comprehensive experiments on two clinically collected datasets: a 3-phase CT dataset and an 8-phase MR dataset. The experimental results affirm the efficacy of the proposed framework. To support the scientific community, we are releasing our extensive multi-phase MR dataset for liver lesion analysis to the public. This pioneering dataset, being the first publicly available multi-phase MR dataset in this field, also underpins the MICCAI LLD-MMRI Challenge. The dataset is publicly available at: https://github.com/LMMMEng/LLD-MMRI-Dataset.

Hepatocellular carcinoma (HCC) is a type of highly heterogeneous tumor characterized by a high mortality rate and poor prognosis. Natural Killer cells (NK cells) are important immune cells that play an important role in anti-tumor activities, antiviral responses, and immune regulation. The relationship between NK cells and HCC remains unclear. It would be valuable to identify a NK-related prognostic signature for HCC. WGCNA and single-cell sequencing RNA were performed to identify NK cell related genes. Gene Enrichment Analysis were used to identify the potential signal pathway. After combing genes from WGCNA and scRNA, Unicox, LASSO + StepCox and Multicox analysis were used to filter prognostic-related gene and construct a prognostic model. Then we performed Proposed time analysis to identify the developmental trajectories of NK cells. Finally, ssGSEA and estimate methods were used to evaluate the immune microenvironment and sensitivity drugs. Using the scRNA-seq data, we identified 1396 genes with high NK cell scores. Based on the results of scRNA-seq, 250 NK-related genes were identified from WGCNA. We identified 223 intersecting genes between the scRNA-seq and WGCNA. After integrating clinical data with the bulk RNA-seq data of these intersecting genes, we constructed a prognostic model to accurately predict the prognosis of HCC patients. Eventually, we found that high-risk HCC patients exhibited worse survival outcomes and lower sensitivity to immunotherapy. We constructed a risk model based on NK cell-related genes that can predict the prognosis of HCC patients accurately. This model can also predict the immunotherapy response of HCC effectively.

TAT, a widely used treatment for HCC, can exacerbate the progression of residual HCC. The present study investigated the mechanism of action of PLK1 following ITA of HCC. The PLK1 levels in HCC were determined using qRT-PCR from clinical patient samples, IHC from tissue microarray, and data from globally high-throughput data and microarrays. The PLK1 levels and their effect on the biological phenotype of heat-stress HCC cells were evaluated through in vitro experiments. We detected PLK1 abnormal expression in HCC models of nude mice subjected to ITA. We detected the effects of different PLK1 expression levels on EMT pathway proteins. PLK1 exhibited an overexpression in HCC tissues with an SMD of 1.19 (3414 HCC and 3036 non-HCC tissues were included), distinguishing HCC from non-HCC effectively (AUC = 0.9). The qRT-PCR data from clinical HCC patient samples and IHC from HCC tissue microarray results also indicated an overexpressed level. In the incomplete ablation models, an increased PLK1 expression was found in both heat-stress cells and subcutaneous tumors. The upregulation of PLK1 following ITA was found to enhance the malignancy of HCC and exacerbate the proliferation, migration, and invasion of residual HCC cells, whereas PLK1 knockdown suppressed the biological malignancy of HCC cells. Meanwhile, PLK1 has different regulatory effects on various EMT pathway proteins. PLK1 promotes the progression of residual HCC by activating EMT pathway after ITA, which might provide a novel idea for the treatment and prognosis of residual HCC.

Disulfiram, a synthetic drug, has historically played a significant role in the treatment of alcoholic liver disease as the first medication approved by the U.S. Food and Drug Administration for alcohol use disorders. Beyond its efficacy in inhibiting alcohol addiction and treating alcoholic liver disease, disulfiram has also demonstrated potential in managing various liver conditions, including certain metabolic liver injuries and liver cancer. As an established, cost-effective drug with well-documented synthesis methods, disulfiram holds promise for broader application in liver disease treatment. However, its clinical use is hindered by the risk of inducing pharmacologic liver injury. This potential for liver toxicity necessitates careful patient selection, monitoring, and consultation with healthcare providers, which can limit its practicality in treating patients with existing liver conditions. This review aims to analyze the multifaceted role of disulfiram in liver diseases comprehensively. By exploring its therapeutic efficacy, potential benefits, and inherent limitations, we seek to provide a balanced perspective that maximizes disulfiram's therapeutic potential while ensuring the safety and well-being of patients. This thorough examination will also highlight areas for future research, paving the way for optimized treatment protocols that incorporate disulfiram in the context of liver disease management.

Among various cancers, primary liver cancer is the seventh most diagnosed malignancy and is the second most prevalent contributor to cancer-causing deaths. During conventional treatment, the recurrence of disease, low drug inefficacy, and severe side effects are the main limitations. Recently, natural anticancer medicines from the Middle East, Korea, China, Europe, North America, and India have attracted a lot of interest due to their low side effects and better remedial properties. The current study investigated the antioxidative and anticancer effects of ethanolic (BME) and n-hexane (BMH) extracts of B. monnieri (L.) Wettst.

In the current study, phytochemical profiling was done using gas chromatography-mass spectrometry (GC-MS) analysis. The antioxidant potential was measured using DPPH, nitric oxide, superoxide anion, and hydrogen peroxide assays, while the cell viability and apoptotic effect were measured by MTT, crystal violet, and annexin V/PI protocols, respectively.

Higher concentrations of total phenolic contents (274.92±3.52 mgGAE/g), total flavonoid contents (141.99±4.14 mgQE/g) and tannins (55.49±4.63 mgTAE/g) were observed in BME extract with strong antioxidant potential than BMH extract. Also, BME extract showed higher cytotoxicity with less IC50 value (24.70 μg/mL) and a lower percentage of cell viability, while the same extract exhibited 58.65% apoptosis against HepG2 cells in comparison to cisplatin and BMH extract. Furthermore, Spiro[(tricyclo[6.2.2.0(2,7)]dodeca-5,9-diene)-4,1'-cyclobutane]-11,2'-dione from BME extract showed the lead docking score of -8.8, -8.1 and -7.8 kcal/mol against TGF-βR1, TNF-α, and iNOS, respectively.

In conclusion, the ethanolic extract of B. monnieri has a significant potential for becoming a potent anticancer drug that effectively treats liver damage, including HCC.

Liver hepatocellular carcinoma (LIHC) often has a poor prognosis. Since the relationship between HRas proto-oncogene, GTPase (HRAS) and LIHC has not been elucidated, the aim of this study was to explore the mechanisms by which HRAS is involved in regulating the prognosis of LIHC.

We usedThe Cancer Genome Atlas (TCGA) database to characterize differences in HRAS gene expression between LIHC patients and healthy individuals. In addition, we analysed the relationships between HRAS gene expression levels and the clinicopathological characteristics of LIHC patients. Next, we used univariate and multivariate Cox regression analyses to identify prognostic factors. Differentially expressed genes were identified between the low- and high-expression groups, and KEGG and GO analyses and GSEA were performed to study the underlying mechanisms. The effects of high and low HRAS expression on the prognosis of LIHC patients was determined according to CIBERSORT. We subsequently assayed HRAS gene expression at the cellular level, and these data were validated in a tumour xenograft model.

We established and validated the HRAS gene as a prognostic signature and analysed the relationships between HRAS expression levels and clinicopathological features. Patients were categorized into high and low HRAS gene expression groups. We determined that high HRAS expression is associated with carbon metabolism, the PPAR signalling pathway, and small molecule catabolism in cancer. Furthermore, we conclude that the poor prognosis that results from elevated HRAS expression is associated with immune cell infiltration. We used LASSO + KNN to build an AI classification model that shows good performance in distinguishing liver cancer tissues form normal tissues. Finally, we verified that HRAS is highly expressed in hepatocellular carcinoma cells and promotes tumour growth.

We identified and validated the role of HRAS in hepatocellular carcinoma to assess hepatocellular carcinoma prognosis. The results of this study can be applied to predict survival, for personalized liver cancer treatment strategies, and provide information for the development of potential targeted therapies and new ideas for liver cancer patient treatment.

Minimally invasive needle-based interventions are commonly used in cancer diagnosis and treatment, including procedures, such as biopsy, brachytherapy, and microwave ablation. Although MR-guided needle placement offers several distinct advantages, such as high-resolution target visualization and accurate device tracking, one of the primary limitations that affect its widespread adoption is the ergonomic constraints of the closed-bore MRI environment, requiring the patients to be frequently moved in and out to perform the needle-based procedures. This paper introduces a low-profile, body-mounted, MR-guided robot designed to address this limitation by streamlining the operation workflow and enabling accurate needle placement within the MRI scanner.

The robot employs piezoelectric linear actuators and stacked Cartesian XY stages to precisely control the position and orientation of a needle guide. A kinematic model and control framework was developed to facilitate accurate targeting. Additionally, clinical workflow for the liver interventions was developed to demonstrate the robot's capability to replicate existing procedures. The proposed system was validated in benchtop environment and 3T MRI scanner to quantify the system performance.

Experimental validations conducted in free space demonstrated a position accuracy of 2.38 ± 0.94 mm and orientation error of 1.40 ± 2.89°. Additional tests to confirm MR-conditionality and MR-guided phantom placements were carried out to assess the system's performance and safety in MRI suite, yielding a position error of 2.01 ± 0.77 mm and an orientation error of 1.57 ± 1.31°.

The presented robot shows exceptional compatibility with a wide range of patients and bore sizes while maintaining clinically significant accuracy. Future work will focus on the validations in dynamic liver environments.

Astragaloside IV (C41H68O14, AS-IV) is a naturally occurring saponin isolated from the root of Astragalus membranaceus, a widely used traditional Chinese botanical drug in medicine. In recent years, AS-IV has attracted considerable attention for its hepatoprotective properties, which are attributed to its low toxicity as well as its anti-inflammatory, antioxidant and antitumour effects. Numerous preclinical studies have demonstrated its potential in the prevention and treatment of various liver diseases, including multifactorial liver injury, metabolic-associated fatty liver disease, liver fibrosis and liver cancer. Given the promising hepatoprotective potential of AS-IV and the growing interest in its research, this review provides a comprehensive summary of the current state of research on the hepatoprotective effects of AS-IV, based on literature available in databases such as CNKI, PubMed, ScienceDirect, Google Scholar and Web of Science. The hepatoprotective mechanisms of AS-IV are multifaceted, encompassing the inhibition of inflammatory responses, reduction of oxidative stress, improvement of insulin and leptin resistance, modulation of the gut microbiota, suppression of hepatocellular carcinoma cell proliferation and induction of tumour cell apoptosis. Notably, key molecular pathways involved in these effects include Nrf2/HO-1, NF-κB, NLRP3/Caspase-1, JNK/c-Jun/AP-1, PPARα/FSP1 and Akt/GSK-3β/β-catenin. Toxicity studies indicate that AS-IV has a high level of safety. In addition, this review discusses the sources, physicochemical properties, and current challenges in the development and clinical application of AS-IV, providing valuable insights into its potential as a hepatoprotective agent in the pharmaceutical and nutraceutical industries.

Hepatocellular carcinoma (HCC) is a prevalent form of primary liver cancer, and aberrant miRNAs expression significantly contributes to its progression. Although the abnormal expression of miR-6844 in HCC has been reported, its impact on the malignant phenotype of HCC cells and its potential mechanism remains unclear. In this study, we initially conducted a bioinformatics analysis to investigate the differential expression of miR-6844 in HCC tissues and its impact on patient prognosis. The association between miR-6844 expression levels and clinical characteristics of HCC patients was subsequently investigated by integrating data from clinical samples. Ultimately, the impact of miR-6844 on the malignant phenotype of HCC cells and the underlying mechanisms were examined through in vitro cellular experiments. The results showed that a high expression of miR-6844 in HCC, which was associated with poor prognosis and exhibited significant correlations with intrahepatic metastasis and clinical stage among patients. The upregulation of miR-6844 promoted the proliferation, migration, and invasion of HCC cells while suppressing apoptosis. Conversely, the downregulation of miR-6844 significantly attenuated the malignant phenotype of HCC cells. In addition, HSD17B13 was identified as a target gene of miR-6844, and the overexpression of HSD17B13 partially counteracted the oncogenic effects induced by miR-6844 in HCC cells, otherwise the opposite. Taken together, the above results suggest that miR-6844 plays a regulatory role in the malignant phenotype of HCC cells through its targeting of HSD17B13.

To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism.

Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.

Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1.

ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.

The formation of purinosomes, dynamic complexes involved in de novo purine biosynthesis, has been recognized as a critical process for cell growth. Although their upregulation in cancer cells suggests their potential as a therapeutic target, the specific role of purinosomes in hepatocellular carcinoma (HCC) remains uncertain. The purinosome score was found to have prognostic value. Enrichment analyses indicated a connection between purinosome-related genes and cell cycle regulation. Moreover, our research has demonstrated a correlation between the upregulation of genes associated with purinosomes and the enhanced formation of purinosomes in Huh-7 cells. Pyrimethamine has been identified as a promising therapeutic option for targeting purinosome to exert anti-cancer effects. Furthermore, the purinosome score exhibited an positive relationship with the response to immunotherapy. It may guide the stratification of liver cancer patients and screen for populations that may benefit from immunotherapy. This study examines the prognostic and predictive value of purinosome in liver cancer, suggesting that targeting purinosome formation with pyrimethamine or immunotherapy could benefit patients with high purinosome scores.

Liver puncture is an indispensable procedure in the diagnosis and treatment of liver diseases. However, traditional manual puncture typically relies on the extensive experience and judgment of physicians. Liver puncture robots, with their advantages of high stability, precision, and safety, can to some extent compensate for the shortcomings of traditional manual puncture. Based on the different imaging modalities, liver puncture robots are categorized into those guided by ultrasound, CT, and MRI, and the advantages and disadvantages of these three imaging guidance methods are analyzed. Spatial positioning methods play a crucial role in improving the accuracy of puncture during surgery. Therefore, the spatial positioning methods under image guidance are introduced. Finally, the current research status of image-guided liver puncture robots and positioning methods is summarized, and future research directions are discussed.

Hepatocellular carcinoma (HCC) is a particularly serious kind of liver cancer. Liver cancer ranks third in terms of mortality rate worldwide, putting it among the leading causes of deaths from cancer. HCC is the primary kind of liver cancer and makes up the vast majority of cases, accounting for approximately 90% of occurrences. Numerous research have verified this information. the progress of fatty liver, alcohol induced cirrhosis, smoking habits, obesity caused by overweight, and metabolic diseases such as diabetes. The treatment strategies for HCC can be divided into two categories: One is curative treatment, including liver transplantation, surgical resection, and ablation therapy or selective arterial radiation embolization, aimed at completely eliminating the lesion; Another type is non curative treatment options, including transarterial chemoembolization and systemic therapy, which focus on controlling disease progression and prolonging patient survival. The majority of HCC patients are found to be in an advanced stage and need systemic therapy. Sorafenib and lenvatinib are frequently used as first-line medications in traditional HCC treatment to slow the disease's progression. For second-line treatment, regorafenib, cabozantinib, or remdesizumab are used to inhibit tumors through different mechanisms and prolong survival. In recent years, with the in-depth exploration of the pathogenesis and progression mechanism of HCC, as well as the rapid progress within the domain of tumor immunotherapy, the treatment prospects for advanced HCC patients have shown a positive transformation. This transformation is reflected in the fact that more and more patients are gradually gaining significant and considerable therapeutic advantages from advanced immunotherapy regimens, bringing unprecedented improvements to their treatment outcomes. In order to enable activated T cells to attack tumor cells, immune checkpoint inhibitors interfere with the inhibitory.

To evaluate the effects of nivolumab in combination with cabozantinib on patient tumor markers and immune function, as well as the therapeutic efficacy of this combination in treating advanced HCC, a study was conducted.

In all, 100 patients with advanced HCC who were brought to our hospital between July 2022 and July 2023 and who did not match the requirements for surgical resection had their clinical data thoroughly analyzed retrospectively in this study. Among them, half of the patients (50 cases) only received oral cabozantinib as a single treatment regimen (set as the control group), while the other half of the patients (50 cases) received intravenous infusion of nivolumab in addition to oral cabozantinib (set as the observation group). The objective of the probe is to examine the variations in disease control rate (DCR) and objective response rate (ORR) between two groups; At the same time, changes in the levels of T lymphocyte subsets (CD3+, CD4+, CD8+) and tumor markers, including AFP, GP-73, and AFP-L3, were evaluated; In addition, changes in liver and kidney function indicators and adverse reactions during treatment were also monitored. For patients with advanced HCC, this research also calculated and analyzed the progression free survival of two patient groups throughout the course of a 12-month follow-up to assess the effectiveness and safety of this therapeutic approach.

Upon comparing baseline information for both groups of subjects before treatment, it was found that no statistically significant alterations had occurred (P > 0.05). After the therapeutic intervention, the observation group and control group's ORR and DCR differed statistically significantly (P < 0.05). The observation group's scores significantly improved. Subsequent examination revealed that the observation group's T lymphocyte subset levels had significantly changed, mostly exhibiting an increase in CD3+, CD4+, and CD4+/CD8+ levels while CD8+ levels had comparatively dropped. There was a significant difference (P < 0.05) between these changes and those in the control group. The observation group also showed positive improvements in tumor markers; AFP, GP-73, and AFP-L3 levels were considerably lower in the group under observation than in the control group, with statistically significant differences (P < 0.05). When liver function was assessed, total bilirubin and alanine aminotransferase were found to be considerably lower in the observation group than in the control group (P < 0.05). The incidence of adverse responses was not statistically significant (P > 0.05), indicating that the incidence of adverse responses did not differ significantly between the two groups.

When treating advanced HCC, nivolumab and cabozantinib together have the ability to increase T lymphocyte numbers, reduce tumor marker levels, effectively prolong survival time, and have better efficacy than simple control treatment, with good safety.

Liver cancer is a serious malignancy worldwide, and long noncoding RNAs (lncRNAs) have been implicated in its prognosis.It remains unclear how lncRNAs related to endoplasmic reticulum stress (ERS) influence liver cancer prognosis. Here, we analyzed RNA and clinical data from the Cancer Genome Atlas and sourced ERS-related genes from the Molecular Signatures Database. Co-expression analysis identified ERS-related lncRNAs, and Cox regression analysis as well as least absolute shrinkage and selection operator regression highlighted three lncRNAs for a prognostic model. Based on median risk scores, we classified patients into two risk groups. The high-risk group displayed poor prognosis, and this finding was validated in the test set. According to consistency clustering, the patients were assigned to two clusters, and tumor microenvironment scores were computed. Patients with a high mutation burden had worse outcomes. Furthermore, immune infiltration analysis indicated more immune cells and mutations in checkpoint molecules among high-risk individuals. Drug sensitivity varied between the risk groups. LINC01011 was selected for functional assays. Colony formation assay and CCK-8 assay revealed that silencing LINC01011 suppressed liver cancer cell proliferation. Transwell and scratch assays indicated that silencing LINC01011 inhibited liver cancer cell migration. Western blotting assay revealed that inhibiting LINC01011 induced apoptosis and simultaneously inhibited epithelial-mesenchymal transition. These findings confirm the validity of the prognostic model and indicate that LINC01011 could serve as a potential research target.

Hepatocellular carcinoma and cholangiocarcinoma, the two predominant histological subtypes of primary liver cancer, are characterized by a high global incidence and poor prognosis. Moreover, the therapeutic options are still limited, with surgical intervention being the predominant approach. Anchorage-Dependent Cell Death (Anoikis) is a form of regulated cell death triggered by the detachment of cells from their extracellular matrix, is crucial for maintaining tissue homeostasis. However, tumor cells often evade anoikis, a capability that is essential for their survival in the bloodstream and subsequent metastasis. Our study classified liver cancer into two distinct subtypes, C1 and C2, based on the differential expression of anoikis-related genes. Subtype C1 patients exhibited elevated expression of BRMS1, PTK2, and CASP8, which could serve as potential therapeutic targets for anoikis-based treatments. Conversely, subtype C2 patients showed higher expression of NTRK2, STAT3, SIK1, AKT1, and EGFR, suggesting these genes as promising therapeutic targets for C2 subtype liver cancer. Furthermore, employing Weighted Correlation Network analysis, machine learning models, and experimental validation, we identified NPY1R and HGF as potential biomarkers for the diagnosis and treatment of liver cancer.

Percutaneous thermal ablation is increasingly popular but still suffers from a complex preoperative planning, especially with multiple needles. Existing planning methods either use theoretical ablation shapes for faster estimates or are computationally intensive when incorporating realistic thermal propagation. This paper introduces a multi-resolution approach that accelerates thermal propagation simulation, enabling users to adjust ablation parameters and see the results in interactive time.

For static needle positions, a high-resolution simulation based on GPU-accelerated implementation of the Pennes bioheat equation is used. During user interaction, intermediate frames display a lower-resolution estimation of the ablated volume. Two methods are compared, based on GPU-accelerated reimplementations of finite difference and lattice Boltzmann approaches. A parameter study was conducted to identify the optimal balance between speed and accuracy for the low- and high-resolution frames. The chosen parameters are finally tested in multi-needle scenarios to validate the interactive capability in this context.

Tested with percutaneous radiofrequency data, our multi-resolution method significantly reduces computation time while maintaining good accuracy compared to the reference simulation. For high-resolution frames, we can reach up to 5.8 fps, while for intermediate low-resolution frames we can reach a frame rate of 32 fps with less than 20% loss of accuracy.

This multi-resolution approach allows for smooth interaction with multiple needles, with instant visualization of the predicted ablation volume, in the context of percutaneous radiofrequency treatments. It could also be applied to automated planning, reducing the time required for iterative adjustments.

Sorafenib (Sor), recognized as a frontline multi-kinase inhibitor, constitutes the primary targeted therapy for hepatocellular carcinoma (HCC). Despite its potential, many HCC patients exhibit reduced responsiveness to Sor, thereby undermining its therapeutic efficacy. Recent studies highlight the importance of nuclear factor erythroid-2-related factor 2 (Nrf2) activation in HCC, which contributes to Sor resistance. Brusatol (Bru), a plant-derived Nrf2 inhibitor, counteracts this resistance but faces challenges due to its poor solubility in aqueous media. In this study, we developed a glutathione (GSH)-responsive nanoplatform that effectively dispersed in water for the co-delivery of Bru and Sor (B/S NP). This approach enhanced Bru's therapeutic efficacy and increased Sor sensitivity in HCC. Our nanoplatform significantly reduced Nrf2 expression, thereby increasing Sor sensitivity both in vitro and in vivo, while presenting a favorable biosafety profile. These findings suggest that the nanoplatform-mediated co-delivery of Bru and Sor offers an innovative approach to enhance Sor's effectiveness in HCC treatment.

Epithelial-mesenchymal transition (EMT) is closely linked to liver cancer prognosis, invasiveness, and aggressiveness. One promising treatment for liver cancer is cell therapy, where stem cells are stimulated to develop into functional liver cells. This study aimed to investigate the effect of miR-122-5p on the differentiation of human induced pluripotent stem cells (hiPSCs) into hepatocyte-like cells and its impact on the EMT process in liver cancer cells. MiR-122-5p was overexpressed or silenced in hiPSCs to analyze the expression of liver-specific markers, including AFP, ALB and ASGPR, to confirm hepatocyte-like differentiation. A co-culture system with HepG2 liver cancer cells was also used to evaluate the effect of miR-122-5p-overexpressing hiPSCs or miR-122-5p-silencing hiPSCs on the expression of EMT markers. Results revealed that overexpression of miR-122-5p in hiPSCs induced hepatocyte-like characteristics, as evidenced by increased levels of AFP, ALB, and ASGPR. However, knockdown of miR-122-5p had the opposite effect. In the co-culture system, hiPSCs overexpressing miR-122-5p inhibited the EMT process of HepG2 cells, resulting in increased levels of mesenchymal markers and decreased levels of epithelial markers. Taken together, miR-122-5p promotes the differentiation of hiPSCs into hepatocyte-like cells and inhibits EMT process of liver cancer cells. Targeting miR-122-5p may be a novel approach to prevent liver cancer progression through cell therapy.

Nanotechnology has great potential and advantages in the treatment of hepatocellular carcinoma (HCC), but the research trends and future directions are not yet clear.

Analyze the development trajectory, research hotspots, and future trends of nanotechnology and HCC research globally in the past 20 years, providing a more comprehensive and intuitive reference for researchers in this field.

Retrieve relevant literature on nanotechnology and HCC research in the Web of Science (WOS) Core Collection database, and conduct bibliometric analysis using software such as CiteSpace, VOSviewer, and SCImago Graphica.

A total of 852 English publications meeting the criteria were retrieved from the WOS database, with an overall increasing trend in the number of publications and citation frequency over the years. China leads in the number of publications and international collaborations, followed by the USA and India. The most influential research institution is the Chinese Academy of Sciences, the most influential scholar/team is the Rahman, Mahfoozur team, and the journal with the most publications is the International Journal of Nanomedicine. A comprehensive analysis reveals that the current main research directions include new types of nanoparticles, targeted drug delivery systems, photothermal/photodynamic therapy, gene delivery systems, diagnostics, and imaging. It is anticipated that further collaboration among scholars, institutions, and countries will accelerate the development of nanotechnology in the field of HCC research.

This study provides an in-depth analysis of the research status and development trends of nanotechnology in treating HCC from a bibliometric perspective, offering possible guidance for researchers to explore hot topics and frontiers, select suitable journals, and partners in this field.

Hepatocellular carcinoma (HCC) exhibits a subtle onset, high incidence rates, and low survival rates, becoming a substantial threat to human health. Hence, it is crucial to discover fresh biomarkers and treatment targets for the early detection and management of HCC. CCK-8, scratch-wound, and transwell assays were used to evaluate the biological properties of HCC cell lines (Huh-7 and Hep3B). Bioinformatics analysis identified the downstream target mRNA of miR-145-5p as acyl-CoA synthetase long-chain family member 4 (ACSL4). RT-qPCR was used to test miR-145-5p and ACSL4 levels. Transwell chambers were used to co-incubate purified CD8+ T cells and HCC cells for 48 h, and the effect of CD8+ T cells on apoptosis in HCC cells was detected by flow cytometry. A subcutaneous graft tumor model was constructed, and ELISA kits were used to assess cytokine levels and CD8+ T cell activation markers. HCC cells showed a decline in miR-145-5p levels and a rise in ACSL4 levels. Overexpression of miR-145-5p hindered HCC cell proliferation, migration, and invasion, while stimulating CD8+ T cell activation. Conversely, overexpression of ACSL4 enhanced the malignant biological properties of HCC cells and reduced the effect of CD8+ T cells, while silencing ACSL4 had the opposite effect. miR-145-5p targeted and downregulated ACSL4, while overexpression of miR-145-5p weakened the promotion of HCC malignant progression caused by ACSL4 overexpression. Additionally, overexpression of miR-145-5p and silencing ACSL4 were effective in inhibiting tumor growth in vivo. In conclusion, miR-145-5p targets and downregulates ACSL4, leading to the inhibition of HCC malignant progression and preventing immune escape in HCC cells.

Programmed cell death (PCD) is a significant factor in the progression of hepatocellular carcinoma (HCC) and might serve as a crucial marker for predicting HCC prognosis and therapy response. However, the classification of HCC based on diverse PCD patterns requires further investigation. This study identified a novel molecular classification named PCD subtype (C1, C2, and C3) based on the genes associated with 19 PCD patterns, distinguished by clinical, biological functional pathways, mutations, immune characteristics, and drug sensitivity. Validated in 4 independent datasets, diverse cell death pathways were enriched in the C3 subtype, including apoptosis, pyroptosis, and autophagy, it also exhibited a highly infiltrative immunosuppressive microenvironment and demonstrated higher sensitivity to compounds such as Paclitaxel, Bortezomib, and YK-4-279, while C1 subtype was significantly enriched in cuproptosis and metabolism-related pathways, suggesting that it may be more suitable for cuproptosis-inducing agent therapy. Subsequently, utilizing the machine learning algorithms, we constructed a cell death-related index (CDRI) with 22 gene features and constructed prognostic nomograms with high predictive performance by combining CDRI with clinical features. Notably, we found that CDRI effectively predicted the response of HCC patients to therapeutic strategies, where patients with high CDRI were more suitable for sorafenib drug therapy and patients with low CDRI were more ideal for transarterial chemoembolization (TACE). In conclusion, the PCD subtype and CDRI demonstrate significant efficacy in predicting the prognosis and therapeutic outcomes for patients with HCC. These findings offer valuable insights for the development of precise, individualized treatment strategies.

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.

Identifying the mechanism by which lipid metabolism regulates cancer may offer a novel approach for therapeutic intervention. It has previously been identified that a lipid metabolism-related factor, namely fatty acid hydroxylase domain containing 2 (FAXDC2), is downregulated in various types of cancer, and inhibits the proliferation and migration of liver cancer cells through a mechanism associated with ERK. The liver is important for lipid metabolism, and FAXDC2 is involved in the synthesis of cholesterol and sphingomyelin. However, the functional mechanism by which FAXDC2 influences liver cancer cells through metabolic processes and ERK signaling remains unclear. Therefore, the present study induced the overexpression of FAXDC2 in HepG2 liver cancer cells and performed a metabolomics analysis. This identified guanosine diphosphate (GDP) as a significantly altered metabolite. Using AlphaFold3, a robust interaction was predicted between FAXDC2 and GDP, which lead to the hypothesis that GDP may mediate the inhibitory effects of FAXDC2 on liver cancer cells by directly modulating the functional properties of the cells, thereby influencing their behavior and progression. Cell Counting Kit-8 assays were used to study the impact of elevated GDP concentrations on HepG2 cell growth. The results revealed a gradual reduction in the viability of HepG2 cells as the GDP concentration increased. In addition, western blotting showed that GDP treatment was accompanied by a significant downregulation of cyclin dependent kinase 4 and cyclin D1 expression levels, and Transwell experiments revealed that GDP treatment significantly decreased the invasion of HepG2 cells. Treatment with GDP also significantly inhibited the expression of ERK. In summary, the present study is the first to indicate that GDP is a metabolic small molecule with inhibitory activity in cancer cells, which has previously been overlooked in tumor metabolic reprogramming. The study findings offer new insights and strategies for the diagnosis and treatment of liver cancer, and potentially other types of cancer.

Background: Methyltransferase-like 3 (METTL3) and HECT and RLD domain containing E3 ubiquitin protein ligase 4 (HERC4) have been studied in the field of oncology; however, their roles and interaction in hepatocellular carcinoma (HCC) await elucidation. Methods: Initially, METTL3 and HERC4 expressions in normal and HCC samples were predicted employing the UALCAN database, and the targeting relationship between these two was explored via coimmunoprecipitation assay. Following the quantification on N6-methyladenosine (m6A) enrichment, the localization of METTL3 and HERC4 on HCC cells was visualized via immunofluorescence assay. The effects of METTL3 and HERC4 on HCC cells proliferation and migration were determined in vitro assays. METTL3 and HERC4 expressions were quantified via quantitative polymerase chain reaction, and those of metastasis-related proteins N-cadherin and vimentin were calculated with immunoblotting assay. Furthermore, the levels of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor were measured by enzyme-linked immunosorbent assay. Results: METTL3 and HERC4 expressed highly in HCC and their expressions were positively correlated with tumor grade. METTL3 overexpression enhanced the expression of HERC4 and promoted the proliferation and migration abilities of HCC cells. Specifically, METTL3 overexpression increased vimentin and N-cadherin expressions, while its silencing did conversely. Besides, HERC4 overexpression reversed the effects of METTL3 silencing on the proliferation and migration as well as the levels of angiogenic factors in HCC cells. Conclusion: This study reveals the upregulation of METTL3 and HERC4 expression in HCC and their role in HCC by enhancing the proliferation, migration, and angiogenesis potential of HCC cells.