Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8 T cells in hepatocellular carcinoma.

Background & Aims: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear.

Methods: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens.

Efficacy and safety comparison between Lenvatinib and Sorafenib in hepatocellular carcinoma treatment: a systematic review and meta-analysis of real-world study.

Objective: Our study aimed to evaluate the efficacy and safety of Lenvatinib compared with Sorafenib for treating hepatocellular carcinoma (HCC) patients under real-world setting.

Methods: We retrieved relevant literature through the PubMed, Embase, Web of Science, and Cochrane Library databases from 1 January 2000 to 25 June 2022. The differences in overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) as well as treatment adverse related events were evaluated between HCC patients treated with Lenvatinib and Sorafenib using fixed or random-effects models.

Integrated Network Pharmacology and Metabolomics to Dissect the Mechanisms of Naringin for Treating Cervical Cancer.

Introduction: Cervical cancer is one of the malignant cancers with high mortality among women worldwide. Although vaccines and early detection have reduced cervical cancer mortality, it remains a malignancy with a high mortality rate in women.

Objectives: We aimed to develop a novel integrated strategy that combines metabolomics with network pharmacology to explore the therapeutic mechanisms of naringin in cervical cancer.

Identification of prognostic immune cells and potential immune-related markers in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadly tumors worldwide. Immunotherapy has emerged as a promising strategy for HCC treatment, and understanding the immune microenvironment of HCC provides a theoretical basis for identifying new immune targets. However, the roles of immune components and their regulatory mechanisms in HCC require further clarified.

LncRNA THEMIS2-211, a tumor-originated circulating exosomal biomarker, promotes the growth and metastasis of hepatocellular carcinoma by functioning as a competing endogenous RNA.

Hepatocellular carcinoma (HCC) is a major challenge for human health. Finding reliable diagnostic biomarkers and therapeutic targets for HCC is highly desired in the clinic. Currently, circulating exosomal lncRNA is a promising biomarker for the diagnosis of cancer and lncRNA is also a potential target in cancer therapy.

CircRNA-Mediated Regulation of Angiogenesis: A New Chapter in Cancer Biology.

Angiogenesis is necessary for carcinoma progression and is regulated by a variety of pro- and anti-angiogenesis factors. CircRNAs are RNA molecules that do not have a 5'-cap or a 3'-polyA tail and are involved in a variety of biological functions. While circRNA-mediated regulation of tumor angiogenesis has received much attention, the detailed biological regulatory mechanism remains unclear.

The Outcome of Primary Hepatic Carcinoid Tumor: A Retrospective Study Based on Propensity Score Matched Survival Analysis.

Background: Primary hepatic carcinoid tumor (PHCT) is rare and has unclear clinical characteristics and prognosis.

Methods: A retrospective study using data from the SEER database for patients diagnosed with PHCT used univariate and multivariate Cox models to screen for independent prognostic factors. The outcomes of patients in the surgical and nonsurgical groups were compared, and Propensity Score Matching (PSM) analysis was used to reduce confounder bias.

Cleavage and polyadenylation-specific factor 3 induces cell cycle arrest via PI3K/Akt/GSK-3β signaling pathways and predicts a negative prognosis in hepatocellular carcinoma.

Recent studies have shown that cleavage and polyadenylation-specific factor 3 (CPSF3) is a promising antitumor therapeutic target, but its potential role in hepatocellular carcinoma (HCC) has not been reported. We explored the expression pattern of CPSF3 in HCC through bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and western blot. The potential role of CPSF3 as a biomarker for HCC was evaluated by Kaplan-Meier analysis.

Donation after brain death followed by circulatory death, a novel donation pattern, confers comparable renal allograft outcomes with donation after brain death.

Background: Organ donation after brain death (DBD) is the standard strategy for organ transplantation; however, the concept of brain death is not universally accepted due to cultural beliefs and barriers amongst billions of people worldwide. Hence, a novel donation pattern has been established in China which outlines the concept of donation after brain death followed by circulatory death (DBCD). Differently from any current donation classification, this new concept is formulated based on combination of recognizing brain death and circulatory death.

New Factors Predicting Delayed Graft Function: a Multi-Center Cohort Study of Kidney Donation After Brain Death Followed by Circulatory Death.

Background/aims: Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD.

Allogeneic mesenchymal stem cell as induction therapy to prevent both delayed graft function and acute rejection in deceased donor renal transplantation: study protocol for a randomized controlled trial.

Background: Using kidneys from deceased donors is an available strategy to meet the growing need of grafts. However, higher incidences of delayed graft function (DGF) and acute rejection exert adverse effects on graft outcomes. Since ischemia-reperfusion injury (IRI) and ongoing process of immune response to grafts are the major causes of DGF and acute rejection, the optimal induction intervention should possess capacities of both repairing renal structure injury and suppressing immune response simultaneously.

Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis.

Background: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive.

Methods: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University.

Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity.

Substantial evidence indicates that cancer-associated fibroblasts (CAFs) are critical components in the process of cancer progression. However, the role of CAFs in the immunopathogenesis of human cancer remains elusive. In this study, we demonstrate that purified colorectal carcinoma-derived fibroblasts exhibit activated phenotypes characterized by substantial α-smooth muscle actin expression.

Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion.

Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression.

Comparative proteomic analysis of human donor tissues during orthotopic liver transplantation: ischemia versus reperfusion.

Purpose: To explore the specific alterations in protein profiles that occur during ischemia/reperfusion injury (I/RI) and find novel therapeutic strategies to reduce I/RI during orthotopic liver transplantation (OLT).

Method: We used the comparative proteomic approach of two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to compare the proteomic profiles of the same donor liver at three different time points: T1, immediately after cardiac arrest of donors (normal control); T2, before portal vein anastomosis (ischemia); and T3, 2 h after hepatic artery anastomosis (reperfusion).

Result: We identified 34 proteins that were significantly altered during I/RI.

βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway.

βKlotho is a regulator in multiple metabolic processes, while its role in cancer remains unclear. We found the expression of βKlotho was down-regulated in human hepatocellular carcinoma tissues compared with that in paired adjacent non-tumourous liver tissues. Hepatoma cells also showed decreased expression of βKlotho compared with normal hepatocyte cells.

Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO.

Defects in natural killer (NK) cell function are necessary for tumor immune escape, but the underlying regulatory mechanisms in human cancers remain largely unknown. Here we show that fibroblasts derived from hepatocellular carcinoma (HCC) were significantly superior to foreskin-derived fibroblasts at inducing NK cell dysfunction, which is characterized by low expression of cytotoxic molecules and surface markers for cell activation, impaired production of cytokines, and decreased cytotoxicity against K562 cells in vitro. Our results also indicate that PGE2 and IDO, derived from activated fibroblasts, suppress the activation of NK cells and thereby create favorable conditions for tumor progression.

Effect of pre-transplantation hemoglobin concentration on prognosis of renal transplant recipients.

Background: For the renal transplant recipients, anemia is one of the common complications and becomes a major medical issue before transplantation. Haemoglobin (Hb) is used as a prognostic indicator, although the optimal pre-transplantation Hb concentration associated with positive prognosis is still controversial. The aim of this study was to detect the optimal Hb concentration on predicting the graft survival and function.