Dual Template Molecularly Imprinted Polymers Targeting Blockade of CD47 for Enhanced Macrophage Phagocytosis and Synergistic Antimetabolic Therapy.

Glycinamide ribonucleotide formyltransferase (GARFT) is an important enzyme in the folate metabolism pathway, and chemical drugs targeting GARFT have been used in tumor treatments over the past few decades. The development of novel antimetabolism drugs that target GARFT with improved performance and superior activity remains an attractive strategy. Herein, we proposed a targeted double-template molecularly imprinted polymer (MIP) for enhancing macrophage phagocytosis and synergistic antimetabolic therapy.

Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma.

Background: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis. However, the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated.

Mitochondria-Targeted Thymidylate Synthase Inhibitor Based on Fluorescent Molecularly Imprinted Polymers for Tumor Antimetabolic Therapy.

Antimetabolites targeting thymidylate synthase (TS), such as 5-fluorouracil and capecitabine, have been widely used in tumor therapy in the past decades. Here, we present a strategy to construct mitochondria-targeted antimetabolic therapeutic nanomedicines based on fluorescent molecularly imprinted polymers (FMIP), and the nanomedicine was denoted as Mito-FMIP. Mito-FMIP, synthesized using fluorescent dye-doped silica as the carrier and amino acid sequence containing the active center of TS as the template peptide, could specifically recognize and bind to the active site of TS, thus inhibiting the catalytic activity of TS, and therefore hindering subsequent DNA biosynthesis, ultimately inhibiting tumor growth.

Multimode Sensing Platform Based on Turn-On Fluorescent Silicon Nanoparticles for Monitoring of Intracellular pH and GSH.

Various physiological activities and metabolic reactions of cells need to be carried out under the corresponding pH environment. Intracellular GSH as an acid tripeptide and an important reducing substance also plays an important role in maintaining cellular acid-base balance and redox balance. Therefore, developing a method to monitor pH and GSH and their changes in cells is necessary.

Successful Identification of a Novel Therapeutic Compound for Hepatocellular Carcinoma Through Screening of ADAM9 Inhibitors.

Background/aim: MHC-class I-related chain A (MICA) functions as a ligand for natural killer group D, an activating receptor on natural killer (NK) cells, and its expression correlates with the carcinogenesis and progression of hepatocellular carcinoma (HCC). Although membranous MICA (mMICA) activates NK cells, soluble forms of MICA (sMICA), shed by cleaving enzymes, such as A disintegrin and metalloprotease (ADAM) 9, suppress NK cells. Therefore, the prevention of MICA shedding through the inhibition of ADAM9 has the potential to activate cancer immunity.

Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-β/Smad pathway suppression in hepatic stellate cells.

Transforming growth factor (TGF)-β/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-β/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-β/Smad pathway activity.

Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus.

A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity.

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring Mutation in Early Clinical Experience.

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated.

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD.

Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase.

As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. In the past, it mainly relied on chemical drugs. Here, we propose a new strategy, (3-propanecarboxyl)triphenylphosphonium bromide (CTPB)-modified molecularly imprinted polymer nanomedicine (MIP-CTPB).

Serum Angiopoietin 2 acts as a diagnostic and prognostic biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is typically accompanied by abundant arterial blood flow. Although angiogenic growth factors such as Angiopoietin 2 (Ang2) play a central role in tumor angiogenesis in HCC, the role of serum Ang2 as a biomarker in HCC remains unclear. In this study, we aimed to investigate the potential of Ang2 as a diagnostic and prognostic biomarker in HCC using a sandwich enzyme-linked immunosorbent assay (ELISA).

Acquisition of mesenchymal-like phenotypes and overproduction of angiogenic factors in lenvatinib-resistant hepatocellular carcinoma cells.

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells.

Tumor-Sensitive Biodegradable Nanoparticles of Molecularly Imprinted Polymer-Stabilized Fluorescent Zeolitic Imidazolate Framework-8 for Targeted Imaging and Drug Delivery.

Targeting enrichment of nanocarriers at tumor sites and effective drug release are critical in cancer treatment. Accordingly, we used fluorescent zeolitic imidazolate framework-8 nanoparticles loaded with doxorubicin (FZIF-8/DOX) as the core and a molecularly imprinted polymer (MIP) as the shell to synthesize tumor-sensitive biodegradable FZIF-8/DOX-MIP nanoparticles (FZIF-8/DOX-MIPs). The MIP prepared with the epitope of CD59 cell membrane glycoprotein as the template allowed FZIF-8/DOX-MIPs to be enriched to tumor sites by actively targeting recognition of MCF-7 cancer cells (CD59-positive).