Clinical features and management issues of NAFLD-related HCC: what we know so far

Pugliese, Nicola Riccardo; Alfarone, Ludovico; Arcari, Ivan; Giugliano, Silvia; Parigi, Tommaso Lorenzo; Rescigno, María; Aghemo, Alessio

doi:10.1080/17474124.2023.2162503

Cited by 4 publications

(3 citation statements)

References 122 publications

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“…Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world and affects 30% of the general population . NAFLD is also one of the most common causes of hepatocellular carcinoma. − A high-fat diet causes an increased incidence of metabolic disorders, and NAFLD is one of the markers of high-fat diet-induced metabolic syndrome . Although its disease burden continues to increase, diagnosis and treatment options are still very limited.…”

Section: Introductionmentioning

confidence: 99%

Molecular Drug Simulation and Experimental Validation of the CD36 Receptor Competitively Binding to Long-Chain Fatty Acids by 7-Ketocholesteryl-9-carboxynonanoate

Xiang

Chen

et al. 2023

ACS Omega

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Long-chain fatty acids (LCFAs) are one of the main energy-supplying substances in the body. LCFAs with different lengths and saturations may have contrasting biological effects that exacerbate or alleviate progress against a variety of systemic disorders of lipid metabolism in organisms. Nonalcoholic fatty liver disease is characterized by chronic inflammation and steatosis, mainly caused by the ectopic accumulation of lipids in the liver, especially LCFAs. CD36 is a scavenger receptor that recognizes and mediates the transmembrane absorption of LCFAs and is expressed in a variety of cells throughout the body. In previous studies, our group found that 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) has the biological effect of targeting CD36 to inhibit oxidized low-density lipoprotein lipotoxicity-induced lipid metabolism disorder; it has an ω-carboxyl physiologically active center and is structurally similar to LCFAs. However, the biological mechanism of oxLig-1 binding to CD36 and competing for binding to different types of LCFAs is still not clear. In this study, molecular docking and molecular dynamics simulation were utilized to simulate and analyze the binding activity between oxLig-1 and different types of LCFAs to CD36 and confirmed by the enzyme-linked immunosorbent assay (ELISA) method. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) platform was applied to predict the drug-forming properties of oxLig-1, and HepG2 cells model of oleic acid and nonalcoholic fatty liver disease (NAFLD) model mice were validated to verify the biological protection of oxLig-1 on lipid lowering. The results showed that there was a co-binding site of LCFAs and oxLig-1 on CD36, and the binding driving forces were mainly hydrogen bonding and hydrophobic interactions. The binding abilities of polyunsaturated LCFAs, oxLig-1, monounsaturated LCFAs, and saturated LCFAs to CD36 showed a decreasing trend in this order. There was a similar decreasing trend in the stability of the molecular dynamics simulation. ELISA results similarly confirmed that the binding activity of oxLig-1 to CD36 was significantly higher than that of typical monounsaturated and saturated LCFAs. ADMET prediction results indicated that oxLig-1 had a good drug-forming property. HepG2 cells model of oleic acid and NAFLD model mice study results demonstrated the favorable lipid-lowering biological effects of oxLig-1. Therefore, oxLig-1 may have a protective effect by targeting CD36 to inhibit the excessive influx and deposition of lipotoxicity monounsaturated LCFAs and saturated LCFAs in hepatocytes.

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Section: Introductionmentioning

confidence: 99%

Molecular Drug Simulation and Experimental Validation of the CD36 Receptor Competitively Binding to Long-Chain Fatty Acids by 7-Ketocholesteryl-9-carboxynonanoate

Xiang

Chen

et al. 2023

ACS Omega

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“…Interestingly, HCC is the sixth most commonly occurring cancer worldwide and, due to its constantly increasing incidence, has become the third leading cause of cancer-related death among general populations and the most common cause of death in patients with cirrhosis [1,2]. The incidence of HCC is rapidly growing despite the decreased incidence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) falling, mainly because of the new metabolic pandemic affecting our Westernized societies, re-assembled by metabolically associated fatty liver disease (MAFLD) that comprised the definition of nonalcoholic fatty liver disease (NAFLD) [3,4].…”

Section: Introductionmentioning

confidence: 99%

Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors

Abenavoli

Montori²,

Baroni

et al. 2023

Medicina

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Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI’s treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.

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“…Liver cancer, specifically hepatocellular carcinoma (HCC), is a major global health concern due to its high prevalence in many countries [1]. It is frequently linked to risk factors such as viral infections (hepatitis B and C) [2], alcohol consumption [3], smoking [4], and non-alcoholic fatty liver disease [5]. Notably, studies have demonstrated that aflatoxin exposure leads to liver cancer by forming adducts in DNA sequences and inducing mutations [6,7].…”

mentioning

confidence: 99%

Liver Cancer 2.0

Taniguchi

2023

IJMS

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Clinical features and management issues of NAFLD-related HCC: what we know so far

Cited by 4 publications

References 122 publications

Molecular Drug Simulation and Experimental Validation of the CD36 Receptor Competitively Binding to Long-Chain Fatty Acids by 7-Ketocholesteryl-9-carboxynonanoate

Molecular Drug Simulation and Experimental Validation of the CD36 Receptor Competitively Binding to Long-Chain Fatty Acids by 7-Ketocholesteryl-9-carboxynonanoate

Perspective on the Role of Gut Microbiome in the Treatment of Hepatocellular Carcinoma with Immune Checkpoint Inhibitors

Liver Cancer 2.0

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