Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis.

Background: Colorectal cancer (CRC) exhibits a high incidence globally, with the liver being the most common site of distant metastasis. At the time of diagnosis, 20-30% of CRC patients already present with liver metastases. Colorectal liver metastasis (CRLM) is a major cause of mortality among CRC patients.

Establishment of two novel organoid lines from patients with combined hepatocellular cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a unique subtype of primary liver cancer displaying both hepatocytic and cholangiocytic differentiation. The development of effective treatments for cHCC-CCA remains challenging because of its high heterogeneity and lack of a suitable model system. Using a three-dimensional culture system, we successfully established two novel cHCC-CCA organoid lines from patients undergoing surgical resection for primary liver cancer.

Myeloid Trem2 ameliorates the progression of metabolic dysfunction-associated steatotic liver disease by regulating macrophage pyroptosis and inflammation resolution.

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing year by year and has become one of the leading causes of end-stage liver disease worldwide. Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) has been confirmed to play an essential role in the progression of MASLD, but its specific mechanism still needs to be clarified. This study aims to explore the role and mechanism of Trem2 in MASLD.

Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The tumor microenvironment (TME) contributes to the poor response of patients with HCC to current therapies, while tumor vascular endothelial cells (ECs) are fundamental TME components that significantly contribute to tumor progression. However, the specific functions and mechanisms of tumor vascular ECs in HCC remain unclear.

Blockade of Hepatocyte PCSK9 Ameliorates Hepatic Ischemia-Reperfusion Injury by Promoting Pink1-Parkin-Mediated Mitophagy.

Background & Aims: Hepatic ischemia-reperfusion injury is a significant complication of partial hepatic resection and liver transplantation, impacting the prognosis of patients undergoing liver surgery. The protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily synthesized by hepatocytes and has been implicated in myocardial ischemic diseases. However, the role of PCSK9 in hepatic ischemia-reperfusion injury remains unclear.

Correction: miR-146a Ameliorates Liver Ischemia/Reperfusion Injury by Suppressing IRAK1 and TRAF6.

[This corrects the article DOI: 10.1371/journal.pone.

Thymidine kinase 1 drives hepatocellular carcinoma in enzyme-dependent and -independent manners.

Metabolic reprogramming plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the key drivers of metabolic reprogramming underlying HCC progression remain unclear. Using a large-scale transcriptomic database and survival correlation screening, we identify thymidine kinase 1 (TK1) as a key driver.

Myeloid Trem2 Dynamically Regulates the Induction and Resolution of Hepatic Ischemia-Reperfusion Injury Inflammation.

Trem2, a transmembrane protein that is simultaneously expressed in both bone marrow-derived and embryonic-derived liver-resident macrophages, plays a complex role in liver inflammation. The unique role of myeloid Trem2 in hepatic ischemia-reperfusion (IR) injury is not precisely understood. Our study showed that in the early stage of inflammation induction after IR, Deletion of myeloid Trem2 inhibited the induction of iNOS, MCP-1, and CXCL1/2, alleviated the accumulation of neutrophils and mitochondrial damage, and simultaneously decreased ROS formation.

Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3.

Background: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Surgical resection of the liver metastases increases the incidence of long-term survival in patients with colorectal liver metastasis (CRLM). However, many patients experience CRLM recurrence after the initial liver resection.

Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble's proteins 1 mediated macrophage polarization.

Aggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the inflammatory response in the liver after ischemia/reperfusion injury. In the present study, we determined that aging promoted macrophage-mediated liver injury and that inflammation was mainly responsible for lower M2 polarization in liver transplantation-exposed humans post I/R.

Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial.

Objective: This study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy.

Methods: Initially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery.

Targeting SYK of monocyte-derived macrophages regulates liver fibrosis via crosstalking with Erk/Hif1α and remodeling liver inflammatory environment.

Liver fibrosis is a danger signal indicating a huge risk of liver cancer occurrence, but there is still no effective clinical means to regulate the progress of liver fibrosis. Although a variety of drugs targeting SYK have been developed for tumors and autoimmune diseases, the mechanism and specific efficacy of SYK's role in liver fibrosis are not yet clear. Our studies based on chronic CCL4, bile duct ligation, and subacute TAA mouse models show that SYK in monocyte-derived macrophages (MoMFs) is fully dependent on phosphorylation of Erk to up-regulate the expression of Hif1α, thereby forming the crosstalk with SYK to drive liver fibrosis progress.

Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1.

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro.

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation.

N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC).

Eva1a inhibits NLRP3 activation to reduce liver ischemia-reperfusion injury via inducing autophagy in kupffer cells.

Ischemia-reperfusion(IR) injury is one of the main complications of liver transplantation and partial hepatectomy. Innate immunity mediated by kupffer cells plays an important role in it. In this study, we focused on evaluating the intrinsic relationship between the autophagy induction of kupffer cells and the activation of NLRP3 inflammasomes caused by liver ischemia-reperfusion.

Hypomethylation-mediated activation of cancer/testis antigen KK-LC-1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling.

Objectives: Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen reactivated in several human malignancies. So far, the major focus of studies on KK-LC-1 has been on its potential as diagnostic biomarker and immunotherapy target. However, its biological functions and molecular mechanisms in cancer progression remain unknown.

5-Hydroxytryptamine Receptor 1D Aggravates Hepatocellular Carcinoma Progression Through FoxO6 in AKT-Dependent and Independent Manners.

Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5-HT1D expression level was significantly up-regulated in HCC tissues and cell lines.

circLARP4 induces cellular senescence through regulating miR-761/RUNX3/p53/p21 signaling in hepatocellular carcinoma.

Circular RNAs (circRNAs), a novel class of non-coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumors is yet to determined.

Precoagulation with microwave ablation for hepatic parenchymal transection during liver partial resection.

Purpose: To evaluate the feasibility of precoagulation with microwave ablation (MWA) for hepatic parenchymal transection during liver partial resection.

Methods: A total of 66 eligible patients were enrolled in this double-blind, randomized, controlled study. Patients were randomized to receive either the traditional clamp-crushing method (Control group) or the MWA precoagulation method (MWA group) for hepatic parenchymal transection during liver partial resection.

Immune Responsive Release of Tacrolimus to Overcome Organ Transplant Rejection.

Transplant rejection is the key problem in organ transplantation and, in clinic, immunosuppressive agents such as tacrolimus are directly administered to the recipients after surgery for T-cell inhibition. However, direct administration of tacrolimus may bring severe side effects to the recipients. Herein, by rational design of two hydrogelators NapPhePheGluTyrOH (1) and Nap d-Phe dPheGluTyrOH (2), a facile method of immune responsive release of tacrolimus is developed from their hydrogels to overcome organ transplantation rejection.

ATRA Regulates Innate Immunity in Liver Ischemia/Reperfusion Injury via RARα/Akt/Foxo1 Signaling.

All-trans retinoic acid (ATRA) has been proved to protect liver from ischemia/reperfusion (IR) injury, however, its mechanism is still unclear. This study is to investigate the mechanism of effect of ATRA on innate immunity in mice liver IR injury. Before operation, mice were gavaged by ATRA at 15 mg/kg/d for two weeks, and then the liver was underwent 70% ischemia (90 min) and reperfusion (6 h).

PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting NAP1L1.

Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. PRDI-BF1 and RIZ homology domain containing 8 (PRDM8) is a key regulator in neural development and testis steroidogenesis; however, its role in liver carcinogenesis remains to be investigated. In this study, PRDM8 was found to be down-regulated in HCC, which was linked with shorter recurrence-free survival.