Integrative analysis reveals that SLC38A1 promotes hepatocellular carcinoma development via PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism.

Although hepatocellular carcinoma (HCC) is rather frequent, little is known about the molecular pathways underlying its development, progression, and prognosis. In the current study, we comprehensively analyzed the deferentially expressed metabolism-related genes (MRGs) in HCC based on TCGA datasets attempting to discover the potentially prognostic genes in HCC. The up-regulated MRGs were further subjected to analyze their prognostic values and protein expressions.

Kupffer cells depletion alters cytokine expression and delays liver regeneration after Radio-frequency-assisted Liver Partition with Portal Vein Ligation.

Radio-frequency-assisted Liver Partition with Portal Vein Ligation (RALPP) induces comparable hypertrophy of the liver remnant compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) in humans. However, whether it is significantly improved compared to ALPPS is unclear, and the underlying mechanisms of liver regeneration after RALPP need to further investigate. The present study was to develop an animal model mimicking RALPP and explore mechanisms of liver regeneration.

Effectiveness and safety of focused ultrasound ablation surgery compared with radiofrequency ablation in primary hepatocellular carcinoma treatment: a meta-analysis.

Background: The effectiveness and safety of focused ultrasound ablation surgery (FUAS) for primary hepatocellular carcinoma (HCC) treatment has not been fully evaluated. This study analyzed the effectiveness and safety of FUAS compared to radiofrequency ablation (RFA).

Methods: Studies published before November 1, 2020, in the following databases were analyzed: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CqVip, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) database.

Activator-Mediated Pyruvate Kinase M2 Activation Contributes to Endotoxin Tolerance by Promoting Mitochondrial Biogenesis.

Pyruvate kinase M2 (PKM2) is a key glycolysis enzyme, and its effect on macrophages has not been entirely elucidated. Here, we identified that the PKM2 small-molecule agonist TEPP-46 mediated PKM2 activation by inducing the formation of PKM2 tetramer and promoted macrophage endotoxin tolerance. Lipopolysaccharide (LPS)-tolerant mice had higher expression of the PKM2 tetramer, which was associated with a reduced immune response to LPS.

Kupffer Cell-Derived TNF- Triggers the Apoptosis of Hepatic Stellate Cells through TNF-R1/Caspase 8 due to ER Stress.

Purpose: To investigate the roles of ER stress in Kupffer cells (KCs) and KC-derived TNF- in the apoptosis of hepatic stellate cells (HSCs).

Methods: A rat model of liver fibrosis was established. Liver and blood serum samples were collected.

Macrophage Membrane-Coated Nanoparticles Alleviate Hepatic Ischemia-Reperfusion Injury Caused by Orthotopic Liver Transplantation by Neutralizing Endotoxin.

Purpose: To investigate the effect and mechanism of macrophage membrane-coated nanoparticles (M-NPs) on hepatic ischemia-reperfusion injury (I/RI) caused by orthotopic liver transplantation. In addition, the advantages of TLR4/M-NPs compared to M-NPs are discussed.

Materials And Methods: We prepared biomimetic M-NPs and identified their characteristics.

The on-off action of Forkhead protein O3a in endotoxin tolerance of Kupffer cells depends on the PI3K/AKT pathway.

Background: The endotoxin tolerance (ET) of Kupffer cells (KCs) is an important protective mechanism for limiting endotoxin shock. As a key anti-inflammatory molecule, the roles and mechanism of Forkhead protein O3a (Foxo3a) in ET of KCs are not yet well understood.

Methods: ET and nonendotoxin tolerance (NET) KCs models were established in vitro and in vivo.

Activation of PPARγ by Curcumin protects mice from ischemia/reperfusion injury induced by orthotopic liver transplantation via modulating polarization of Kupffer cells.

Curcumin shows protective effects on various diseases due to its anti-inflammatory and anti-oxidative functions; however, its effect on organ transplantation has not been fully elucidated. To understand its role in liver ischemia/reperfusion (I/R) injury, we studied its impact on orthotopic liver transplantation (OLT) and Kupffer cells (KCs) polarization and its underlying mechanisms. We first investigated the reactive oxygen species (ROS) accumulation and cytokines profile of KCs, intracellular ROS and the mRNA level of pro-inflammatory cytokines were downregulated while the mRNA level of anti-inflammatory cytokine was upregulated by the pretreatment of Curcumin; Then the liver injury was detected by histopathological examination and liver function.

Retroperitoneal versus open intraperitoneal necrosectomy in step-up therapy for infected necrotizing pancreatitis: A meta-analysis.

Background: Step-up therapy is the recommended therapy for infected necrotizing pancreatitis (INP). However, the most appropriate secondary therapy for use after initial drainage has not been fully determined. This meta-analysis was designed to evaluate the efficacy and safety of retroperitoneal versus open intraperitoneal necrosectomy as part of a step-up strategy for INP.

Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development.

NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear.

Investigation for role of tissue factor and blood coagulation system in severe acute pancreatitis and associated liver injury.

This study aims to investigate the molecular mechanisms underlying the pathogenesis of severe acute pancreatitis (SAP) and SAP-associated liver injury, we performed an association analysis of the functions of tissue factor (TF) and blood coagulation system in both SAP patients and mouse SAP model. Our results showed that serum TF and tissue factor-microparticle (TF-MP) levels were highly up-regulated in both SAP patients and SAP mouse model, which was accompanied by the dysfunction of blood coagulation system. Besides, TF expression was also highly up-regulated in the Kupffer cells (KCs) of SAP mouse model.

Bone marrow stromal cells attenuate LPS-induced mouse acute liver injury via the prostaglandin E 2-dependent repression of the NLRP3 inflammasome in Kupffer cells.

The nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome participates in the pathogenesis of acute liver injury during sepsis. Bone marrow mesenchymal stem cells (BMSCs) attenuate sepsis through prostaglandin E 2 (PGE2) by increasing the interleukin-10 (IL-10) production of macrophages; moreover, NLRP3 inflammasome assembly is effectively regulated by IL-10 during infection. Whether BMSCs have an effect on the activation of the NLRP3 inflammasome and its underlying mechanism is unclear.

LXRα represses LPS-induced inflammatory responses by competing with IRF3 for GRIP1 in Kupffer cells.

Liver X receptors (LXRs) in the nucleus play important roles in lipid metabolism and inflammation. The mechanism of LXR regulation of the LPS-induced Toll-like receptor 4 (TLR4) inflammatory signaling pathway remains to be elucidated. C57/BL6 mice were randomly divided into four groups: control, T0901317 (a LXRs agonist), LPS and T0901317+LPS.

[Effect of the liver X receptor agonist on LPS-induced inflammatory response associated factor IRAK-4 and NF-kappaB].

Aim: To investigate the effect of the activated LXR on the expression of IRAK-4 and NF-kappaB in the inflammatory response which was induced by LPS in Kupffer cells.

Methods: The Kuppfer cells were isolated from male Kunming mice by collagen perfusion in situ. These cells were divided into four groups: normal control group, LPS treatment group, LXR agonist T0901317 treatment group, LPS and T0901317 combined treatment group.

[Influence of continuous high-volume hemofiltration on IRAK-4 protein expression in severe acute pancreatitis].

Objective: To investigate the influence of continuous high-volume hemofiltration (CHVHF) on interleukin 1 receptor-associated kinase-4 (IRAK-4) and tumor necrosis factor-alpha (TNF-alpha) levels in patients with severe acute pancreatitis (SAP).

Methods: Forty-one patients with SAP were randomly divided into two groups to receive treatment with CHVHF plus conventional therapy (21 patients) and conventional therapy only (20 patients). Venous blood samples were taken before and 12, 24, and 72 h after the treatment for evaluation of APACHE II scores.