Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Ramai, Daryl; Facciorusso, Antonio; Vigandt, Erika; Schaf, Bryan; Saadedeen, Waleed; Chauhan, Aditya; Nunzio, Sara di; Shah, Aashni; Giacomelli, Luca; Sacco, Rodolfo

doi:10.3390/cells10123401

Cited by 21 publications

(16 citation statements)

References 100 publications

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“…Viral hepatitis and NASH are important causes of liver cancer development. Liver fibrosis due to viral hepatitis and NASH has been shown to be a risk factor for the development of hepatocellular carcinoma 49 – 51 . It has been suggested that ADAM12 is significantly associated with liver fibrosis 52 .…”

Section: Discussionmentioning

confidence: 99%

ADAM12 is an independent predictor of poor prognosis in liver cancer

Sun

Wang

et al. 2022

Sci Rep

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Disintegrin and metalloproteinase 12 (ADAM12) is thought to trigger the occurrence and development of numerous tumours, including colorectal, breast, and pancreatic cancers. On the basis of The Cancer Genome Atlas (TCGA) datasets, in this study, the relationship between ADAM12 gene expression and hepatocellular carcinoma (HCC), the prognostic value of this relationship, and the potential mechanisms influencing HCC development were evaluated. The results showed that the ADAM12 gene was significantly and highly expressed in liver cancer tissue. The high expression of the ADAM12 gene in liver cancer tissue significantly and positively correlated with T stage, pathological stage, and residual tumour. Kaplan–Meier and Cox regression analyses revealed that ADAM12 gene expression is an independent risk factor influencing the prognosis of patients with liver cancer. Pathway analyses of ADAM12 in HCC revealed ADAM12-correlated signalling pathways, and the expression level of ADAM12 was associated with immune cell infiltration. In vitro experiments demonstrated that the expression level of ADAM12 in Huh-7 and Hep3B cells was significantly higher than that in other HCC cells. ShRNA transfection experiments confirmed that the expression levels of TGF-β and Notch pathway-related proteins were significantly decreased. An EdU cell proliferation assay showed that a low level of ADAM12 gene expression significantly inhibited the proliferative activity of HCC cells. Cell cycle experiments showed that low ADAM12 expression blocked the G1/S phase transition. Overall, this research revealed that high ADAM12 gene expression implies a poor prognosis for patients with primary liver cancer. In addition, it is a potential indicator for the diagnosis of liver cancer.

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Section: Discussionmentioning

confidence: 99%

ADAM12 is an independent predictor of poor prognosis in liver cancer

Sun

Wang

et al. 2022

Sci Rep

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“…Early detection of NAFLD is essential for preventing progression of this condition to more advanced stages [31]. The process of fat accumulation in the liver is generally reversible before the onset of fibrosis by adjusting the daily diet and following a healthy lifestyle [32].…”

Section: Discussionmentioning

confidence: 99%

Multimodal Assessment of Non-Alcoholic Fatty Liver Disease with Transmission-Reflection Optoacoustic Ultrasound

Lafci

Hadjihambi

Konstantinou

et al. 2022

Preprint

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Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. We exploited the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS), which combines the advantages of optical and acoustic contrasts, for an early-stage multi-parametric assessment of NAFLD in mice. The multispectral optoacoustic imaging allowed for spectroscopic differentiation of lipid content, as well as the bio-distributions of oxygenated and deoxygenated hemoglobin in liver tissues in vivo. The pulse-echo (reflection) ultrasound (US) imaging further provided a valuable anatomical reference whilst transmission US facilitated the mapping of speed of sound changes in lipid-rich regions, which was consistent with the presence of macrovesicular hepatic steatosis in the NAFLD livers examined with ex vivo histological staining. The proposed multimodal approach facilitates quantification of liver abnormalities at early stages using a variety of optical and acoustic contrasts, laying the ground for translating the TROPUS approach toward diagnosis and monitoring NAFLD in patients.

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“…These animals had increased levels of lipid peroxidation markers, such as malondialdehyde ( 120 ). Noteworthy, oxidative damage on lipids is a common feature of metabolic diseases that predisposes to the development of other conditions such as atherosclerosis and NAFLD ( 121 , 122 ). Sodium arsenite treatment (100 ppb) in utero and until postnatal week 13 exacerbated the effects of a Western diet on the development of NAFLD, induced the overexpression of genes involved in free fatty acid synthesis, triacylglycerol packaging, ketogenesis and beta-oxidation in Swiss Webster male mice ( 37 ).…”

Section: Effects Of Arsenic Exposure On Lipid Metabolismmentioning

confidence: 99%

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

et al. 2022

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Exposure to arsenic in drinking water is a worldwide health problem. This pollutant is associated with increased risk of developing chronic diseases, including metabolic diseases. Metabolic syndrome (MS) is a complex pathology that results from the interaction between environmental and genetic factors. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, and cancer. The MS includes at least three of the following signs, central obesity, impaired fasting glucose, insulin resistance, dyslipidemias, and hypertension. Here, we summarize the existing evidence of the multiple mechanisms triggered by arsenic to developing the cardinal signs of MS, showing that this pollutant could contribute to the multifactorial origin of this pathology.

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Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Cited by 21 publications

References 100 publications

ADAM12 is an independent predictor of poor prognosis in liver cancer

ADAM12 is an independent predictor of poor prognosis in liver cancer

Multimodal Assessment of Non-Alcoholic Fatty Liver Disease with Transmission-Reflection Optoacoustic Ultrasound

Is Arsenic Exposure a Risk Factor for Metabolic Syndrome? A Review of the Potential Mechanisms

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