Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Ανδρουτσάκος, Θεόδωρος; Bakasis, Athanasios‐Dimitrios; Pouliakis, Abraham; Gazouli, Maria; Vallilas, Christos; Hatzis, Gregorios

doi:10.3390/ijms23169430

Cited by 7 publications

(5 citation statements)

References 60 publications

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“…HCC is one of the most common malignant tumours, with a low survival rate globally. The specific mechanism of HCC occurrence has not been fully elucidated, due to its complexity and diversity of the pathogenesis, 23 – 26 and clinical treatments still lack effective therapeutic strategies. Metformin is currently used as a first-line drug treatment for T2D.…”

Section: Discussionmentioning

confidence: 99%

Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway

Zhao,

Zheng,

et al. 2024

Int J Immunopathol Pharmacol

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Background and objectives Metformin, an oral hypoglycemic drug, has been suggested to possess antitumour activity in several types of cancers. Additionally, interleukin-8 (IL-8) has been reported to be involved in the development and metastasis of many cancers. However, the effect of metformin on IL-8 expression in hepatocellular carcinoma (HCC) remains unclear. Therefore, this study aimed to investigate whether metformin could inhibit IL-8 expression to exert an inhibitory effect on HCC progression. Materials and methods The IL-8 levels were measured in the plasma of 159 HCC patients (86 men, 73 women; average age 56 years) and in the culture supernatant of HCC cells (Hep3B and HuH7) using flow cytometry. In addition, the protein expression levels of IL-8 were also validated by the Human Protein Atlas (HPA) database. The prognostic value of IL-8 was evaluated using the Kaplan–Meier Plotter database. The association between IL-8 expression and immune checkpoints was estimated using the TIMER and The Cancer Genome Atlas (TCGA) databases. What’s more, bioinformatics analysis, western blotting, and transwell assays were conducted to illustrate the molecular mechanism of metformin (≤1 mM) on IL-8 in HCC. Results IL-8 expression was found to be increased in the plasma of HCC patients, which is consistent with the expression of IL-8 in HCC cells and tissues. High expression of IL-8 was significantly related to poor prognosis. In addition, IL-8 was positively correlated with immune checkpoints in HCC. Notably, we found that low-dose metformin could inhibit the secretion of IL-8 by HCC cells and the migration of HCC cells. Mechanistically, low-dose metformin significantly suppresses HCC metastasis mainly through the AMPK/JNK/IL-8/MMP9 pathway. Conclusion The results indicate that low-dose metformin can inhibit HCC metastasis by suppressing IL-8 expression. Targeting the AMPK/JNK/IL-8 axis may be a promising treatment strategy for patients with HCC metastasis.

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Section: Discussionmentioning

confidence: 99%

Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway

Zhao,

Zheng,

et al. 2024

Int J Immunopathol Pharmacol

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“…Previous studies showed disparities in HCC among females compared to males in terms of undergoing HCC surveillance, tumor size at diagnosis, and vascular involvement [ 13 , 14 ]. Previous studies showed that older age, male sex, the severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Comorbidities and Outcomes among Females with Non-Alcoholic Fatty Liver Disease Compared to Males

et al. 2022

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Sex-based medicine is an important emerging discipline within medicine. We investigated the clinical characteristics, complications, and outcomes of Nonalcoholic Fatty Liver Disease (NAFLD) in females compared to males. Demographics, comorbidities, malignancy, complications, outcomes, and all-cause mortality of NAFLD patients older than 18 years were analyzed. The data were extracted using the MDClone platform from “Clalit” in Israel. A total of 111,993 (52.8%) of the study subjects were females with an average age of 44.4 ± 14.7 years compared to 39.62 ± 14.9 years in males, p < 0.001. Significantly higher rates of hypertension, diabetes mellitus, obesity, dementia, and thyroid cancer and lower rates of ischemic heart disease (22.3% vs. 27.3%, p < 0.001) were found among females. Females had a higher rate of cirrhosis, 2.3% vs. 1.9%, p < 0.001, and a lower rate of hepatocellular carcinoma, 0.4% vs. 0.5%, p < 0.001. In the multivariate analysis, a relationship between age, diabetes mellitus, and cirrhosis development were found among males and females. A lower age-adjusted mortality rate was found among females, 94.5/1000 vs. 116/1000 among males. In conclusion, older age at diagnosis, higher rates of hypertension, diabetes mellitus, obesity, cirrhosis, and a lower age-adjusted all-cause mortality rate were found among females with NAFLD.

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“…However, Mousa et al [ 280 ] did not find any link between rs4986791 C/T and POAG in a study on the Saudi population with a much smaller sample size. Evidence suggests that these functional polymorphisms promote apoptosis in hepatic stellate cells by decreasing Bcl-2 [ 284 , 285 ], although the roles of these mutations are controversially discussed for various diseases. The polymorphisms rs4986790 A/G and rs4986791 C/T were therefore proposed to promote RGC apoptosis [ 277 ].…”

Section: Microbiome Dysbiosis At the Intersection Of Obesity And Glau...mentioning

confidence: 99%

Microbiome Dysbiosis: A Pathological Mechanism at the Intersection of Obesity and Glaucoma

Pezzino

Sofia

Greco

et al. 2023

IJMS

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The rate at which obesity is becoming an epidemic in many countries is alarming. Obese individuals have a high risk of developing elevated intraocular pressure and glaucoma. Additionally, glaucoma is a disease of epidemic proportions. It is characterized by neurodegeneration and neuroinflammation with optic neuropathy and the death of retinal ganglion cells (RGC). On the other hand, there is growing interest in microbiome dysbiosis, particularly in the gut, which has been widely acknowledged to play a prominent role in the etiology of metabolic illnesses such as obesity. Recently, studies have begun to highlight the fact that microbiome dysbiosis could play a critical role in the onset and progression of several neurodegenerative diseases, as well as in the development and progression of several ocular disorders. In obese individuals, gut microbiome dysbiosis can induce endotoxemia and systemic inflammation by causing intestinal barrier malfunction. As a result, bacteria and their metabolites could be delivered via the bloodstream or mesenteric lymphatic vessels to ocular regions at the level of the retina and optic nerve, causing tissue degeneration and neuroinflammation. Nowadays, there is preliminary evidence for the existence of brain and intraocular microbiomes. The altered microbiome of the gut could perturb the resident brain–ocular microbiome ecosystem which, in turn, could exacerbate the local inflammation. All these processes, finally, could lead to the death of RGC and neurodegeneration. The purpose of this literature review is to explore the recent evidence on the role of gut microbiome dysbiosis and related inflammation as common mechanisms underlying obesity and glaucoma.

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Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma—A Single-Center Study

Cited by 7 publications

References 60 publications

Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway

Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway

Comorbidities and Outcomes among Females with Non-Alcoholic Fatty Liver Disease Compared to Males

Microbiome Dysbiosis: A Pathological Mechanism at the Intersection of Obesity and Glaucoma

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