Construction and analysis of protein-protein interaction network of non-alcoholic fatty liver disease

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

10.1101/2020.12.01.406215 ◽

2020 ◽

Author(s):

Athina I. Amanatidou ◽

George V. Dedoussis

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Protein Interaction ◽

Fatty Liver Disease ◽

Research Work ◽

Interaction Network ◽

Alcoholic Fatty Liver ◽

Protein Protein Interaction ◽

Human Proteins ◽

Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is a disease with multidimensional complexities. Many attempts have been made over the years to treat this disease but its incidence is rising. For this reason, the need to identify and study new candidate proteins that may be associated with NAFLD is of utmost importance. Systems-based approaches such as the analysis of protein-protein interaction (PPI) network could lead to the discovery of new proteins associated with a disease that can then be translated into clinical practice. The aim of this study is to analyze the interaction network of human proteins associated with NAFLD as well as their experimentally verified interactors and to identify novel associations with other human proteins that may be involved in this disease. Computational analysis made it feasible to detect 77 candidate proteins associated with NAFLD, having high network scores. Furthemore, clustering analysis was performed to identify densely connected regions with biological significance in this network. Additionally, gene expression analysis was conducted to validate part of the findings of this research work. We believe that our research will be helpful in extending experimental efforts to address the pathogenesis and progression of NAFLD.

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Network Pharmacology Exploration Reveals Anti-Apoptosis as a Common Therapeutic Mechanism for Non-Alcoholic Fatty Liver Disease Treated with Blueberry Leaf Polyphenols

Nutrients ◽

10.3390/nu13114060 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4060

Author(s):

Cai-Ren Wang ◽

Hong-Wei Chen ◽

Yan Li ◽

Ming-Yue Zhou ◽

Vincent Kam-Wai Wong ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Drug Targets ◽

Cell Model ◽

Interaction Network ◽

Network Pharmacology ◽

Alcoholic Fatty Liver ◽

Apoptosis Pathway ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by excessive fat accumulation in the liver. The aim of this study is to elucidate the multi-target mechanism of polyphenols in blueberry leaves (PBL) on NAFLD by network pharmacology and to validate its results via biological experiments. Twenty constituents in PBL were preliminarily determined by liquid chromatography-tandem mass spectrometry. Subsequently, 141 predicted drug targets and 1226 targets associated with NAFLD were retrieved from public databases, respectively. The herb-compound-target network and the target protein–protein interaction network (PPI) were established through Cytoscape software, and four compounds and 53 corresponding targets were identified. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to explore the biological processes of the predicted genes. The results of cell experiments demonstrated that PBL could significantly improve the viability of the NAFLD cell model, and the protein expressions of caspase-3 and Bcl-2 were consistent with the expected mechanism of action of PBL. Those results systematically revealed that the multi-target mechanism of PBL against NAFLD was related to the apoptosis pathway, which could bring deeper reflections into the hepatoprotective effect of PBL.

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Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000667 ◽

2020 ◽

pp. 1-8

Author(s):

Jeniffer Danielle M. Dutra ◽

Quelson Coelho Lisboa ◽

Silvia Marinho Ferolla ◽

Carolina Martinelli M. L. Carvalho ◽

Camila Costa M. Mendes ◽

...

Keyword(s):

Vitamin D ◽

Liver Disease ◽

Fatty Liver ◽

Disease Severity ◽

Fatty Liver Disease ◽

Hypovitaminosis D ◽

Alcoholic Fatty Liver ◽

Vitamin D Levels ◽

The Mean ◽

Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

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Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.78.1.27 ◽

2008 ◽

Vol 78 (1) ◽

pp. 27-32 ◽

Cited By ~ 15

Author(s):

Suano de Souza ◽

Silverio Amancio ◽

Saccardo Sarni ◽

Sacchi Pitta ◽

Fernandes ◽

...

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Lipid Profile ◽

Fatty Liver Disease ◽

Thiobarbituric Acid ◽

Serum Levels ◽

Control Group ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

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