FXR inhibition functions as a checkpoint blockade of the pathogenic Tfh cell response in lupus.

T follicular helper (Tfh) cells specialize in facilitating germinal center B-cell activation and high-affinity antibody generation, which are crucial in humoral immune responses. However, aberrant control of Tfh cells also contributes to the generation of self-reactive autoantibodies and promotes autoimmune diseases such as systemic lupus erythematosus (SLE). The mechanisms that control proper Tfh expansion remain unclear.

Research landscape and trends of human umbilical cord mesenchymal stem cell-derived exosomes.

Background: Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) have gained significant attention for their potential in cellular regeneration and functional rehabilitation. Nevertheless, the rapid expansion of research in this field makes it challenging for emerging trends and strategic priorities, potentially impeding scientific advancement. This study employs bibliometric analysis to systematically evaluate the research landscape and highlight pivotal research trajectories of hUCMSC-Exos.

Explainable machine learning for the assessment of donor grafts in liver transplantation.

Background And Aim: The shortage of liver grafts compared to recipients necessitates precise organ assessment. This study aimed to develop a Machine learning (ML) model to predict postoperative delayed graft function (DGF) and visualize the decision-making process for clinical application.

Method: Data from 5242 donor-recipient pairs who underwent liver transplantation (LT) at the top 10 liver transplant centers in China (January 2017 to December 2022) were collected.

Lactate accumulation drives hepatocellular carcinoma metastasis through facilitating tumor-derived exosome biogenesis by Rab7A lactylation.

Previous studies have demonstrated that lactate accumulation, a common hallmark for metabolic deprivation in solid tumors, could actively drive tumor invasion and metastasis. However, whether lactate influences the biogenesis of tumor-derived exosomes (TDEs), the prerequisite for distant metastasis formation, remains unknown. Here, we demonstrated that extracellular lactate, after taken up by tumor cells via lactate transporter MCT1, drove the release of TDE mainly through facilitating multivesicular body (MVB) trafficking towards plasma membrane instead of lysosome.

METTL3 knockout accelerates hepatocarcinogenesis via inhibiting endoplasmic reticulum stress response.

Hepatocellular carcinoma (HCC) is among the most common causes of cancer-related deaths worldwide. Previous studies showed that N6-methyladenosine (mA), the most abundant chemical modification in eukaryotic RNAs, is implicated in HCC progression. Using liver-specific conditional knockout mice, we found that the loss of METTL3, the core catalytic subunit of mA methyltransferase, significantly promoted hepatic tumor initiation under various oncogenic challenges, contrary to the previously reported oncogenic role of METTL3 in liver cancer cell lines or xenograft models.

Tissue-resident peripheral helper T cells foster hepatocellular carcinoma immune evasion by promoting regulatory B-cell expansion.

Background: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown.

Methods: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used.

Tumor derived exosomal ENTPD2 impair CD8 T cell function in colon cancer through ATP-adenosine metabolism reprogramming.

Background: Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is primarily catalysed by Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39), a widely studied ATPase, which is expressed in tumor-associated immune cells. However, the function of ATPases derived from tumor cells themselves remains poorly understood.

Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma.

Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC.

Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8 exhausted-like T cells.

Atezolizumab (anti-PD-L1) combined with bevacizumab (anti-VEGFA) is the first-line immunotherapy for advanced hepatocellular carcinoma (HCC), but the number of patients who benefit from this regimen remains limited. Here, we combine dual PD-L1 and VEGFA blockade (DPVB) with low-dose radiotherapy (LDRT), which rapidly inflames tumors, rendering them vulnerable to immunotherapy. The combinatorial therapy exhibits superior antitumor efficacy mediated by CD8 T cells in various preclinical HCC models.

Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma.

Background & Aims: Integrin αv (ITGAV, CD51) is regarded as a key component in multiple stages of tumor progression. However, the clinical failure of cilengitide, a specific inhibitor targeting surface CD51, suggests the importance of yet-unknown mechanisms by which CD51 promotes tumor progression.

Methods: In this study, we used several hepatocellular carcinoma (HCC) cell lines and murine hepatoma cell lines.

Angiogenesis and immune checkpoint dual blockade: Opportunities and challenges for hepatocellular carcinoma therapy.

The disease burden related to hepatocellular carcinoma (HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors (ICIs) has provided a new therapeutic strategy for HCC.

Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma.

Background And Aims: TMCO3, a member of the monovalent cation:proton antiporter-2 family, has been annotated as a Na/H antiporter, but its pathophysiological role is still unclear. We aimed to investigate the expression profile, prognostic significance, and oncogenic role of TMCO3 in hepatocellular carcinoma (HCC).

Methods: Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression, prognosis, and functional enrichment of TMCO3 in HCC.

Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC.

Background: Emerging evidence indicates that the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis plays a pivotal role in intrinsic antitumor immunity. Previous studies demonstrate that the conventional chemotherapy agent, teniposide, effectively promotes the therapeutic efficacy of programmed cell death protein-1 antibody (PD-1 Ab) through robust cGAS-STING activation. Unfortunately, the cGAS expression of tumor cells is reported to be severely suppressed by the hypoxic status in solid tumor.

Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma.

Background And Aims: Numerous studies have explored the important role of N6-methyladenosine (mA) in cancer. Nonetheless, the interaction between mA and long noncoding RNAs (lncRNAs) is poorly investigated. Herein, we systematically analyzed the role and prognostic value of mA-related lncRNAs in hepatocellular carcinoma (HCC).

NTF3 Correlates With Prognosis and Immune Infiltration in Hepatocellular Carcinoma.

The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC). We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics.

Norcholic Acid Promotes Tumor Progression and Immune Escape by Regulating Farnesoid X Receptor in Hepatocellular Carcinoma.

Accumulating evidence shows a close association between various types of bile acids (BAs) and hepatocellular carcinoma (HCC), and they have been revealed to affect tumor immune response and progression mainly by regulating Farnesoid X receptor (FXR). Nevertheless, the roles of Norcholic acid(NorCA) in HCC progression remain unknown yet. In this study, herein we demonstrate that NorCA can promote HCC cell proliferation, migration and invasion through negatively regulating FXR.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity.

Regulation Network and Prognostic Significance of Aldo-Keto Reductase (AKR) Superfamily Genes in Hepatocellular Carcinoma.

Purpose: The aldo-keto reductase (AKR) superfamily members have been proposed with multiple roles in various tumors. Here, a comprehensive analysis on the integral role of AKR genes was conducted to evaluate the expression profile, regulation network, and prognostic significance in hepatocellular carcinoma (HCC).

Materials And Methods: Transcriptome datasets of HCC were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus.

ABL1 Is a Prognostic Marker and Associated with Immune Infiltration in Hepatocellular Carcinoma.

Background: The role of ABL1 in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the potential role of ABL1 in the progression of HCC using bioinformatics methods.

Methods: We analyzed the expression, prognostic potential, and immune cell effect of ABL1 in HCC by using a variety of datasets.

Association of phenotypic transformation of circulating tumor cells and early recurrence in patients with hepatocellular carcinoma following liver transplantation.

Background: CTCs play a critical role in the diagnosis and prognosis of liver cancer. However, there are few studies on whether different types of CTCs can predict the prognosis in patients with HCC following LT.

Methods: Retrospective data including CTCs detected by the CanPatrolTM platform combined with RNA-ISH were collected and analyzed on 56 patients from December 2016 to December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Prognostic Role and Potential Mechanisms of the Ferroptosis-Related Metabolic Gene Signature in Hepatocellular Carcinoma.

Purpose: Ferroptosis, as a novel regulated cell death form, has a close interaction with metabolism, which is largely unknown in cancer. In the present study, we conducted a comprehensive analysis of ferroptosis-related metabolic genes to delineate the metabolic signatures induced by ferroptosis and evaluate its prognostic significance in hepatocellular carcinoma (HCC).

Methods: The ferroptosis-related metabolic genes (Fer-MRGs) were identified by correlation analyses with transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus.