A Strategy based on Bioinformatics and Machine Learning Algorithms Reveals Potential Mechanisms of Shelian Capsule against Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and life-threatening form of cancer, with Shelian Capsule (SLC), a traditional Chinese medicine (TCM) formulation, being recommended for clinical treatment. However, the mechanisms underlying its efficacy remain elusive. This study sought to uncover the potential mechanisms of SLC in HCC treatment using bioinformatics methods. METHODS: Bioactive components of SLC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and HCC-related microarray chip data were sourced from the Gene Expression Omnibus (GEO) database. The selection criteria for components included OB ≧ 30% and DL ≧ 0.18. By integrating the results of differential expression analysis and weighted gene co-expression network analysis (WGCNA), disease-related genes were identified. Therapeutic targets were determined as shared items between candidate targets and disease genes. Protein-protein interaction (PPI) network analysis was conducted for concatenated genes, with core protein clusters identified using the MCODE plugin. Machine learning algorithms were applied to identify signature genes within therapeutic targets. Subsequently, immune cell infiltration analysis, single-cell RNA sequencing (sc-RNA seq) analysis, molecular docking, and ADME analysis were performed for the screened genes. RESULTS: A total of 153 SLC ingredients and 170 candidate targets were identified, along with 494 HCCrelated disease genes. Overlapping items between disease genes and drug candidates represented therapeutic genes, and PPI network analysis was conducted using concatenated genes. MCODE1 and MCODE2 cluster genes underwent Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Four signature genes (TOP2A, CYP1A2, CYP2B6, and IGFBP3) were identified from 28 therapeutic genes using 3 machine learning algorithms, with ROC curves plotted. Molecular docking validated the interaction modes and binding abilities between signature genes and corresponding compounds, with free binding energy all <-7 kcal/mol. Finally, ADME analysis revealed similarities between certain SLC components and the clinical drugs Sorafenib and Lenvatinib. CONCLUSION: In summary, our study revealed that the mechanism underlying the anti-HCC effects of SLC involves interactions at three levels: components (quercetin, beta-sitosterol, kaempferol, baicalein, stigmasterol, and luteolin), pathways (PI3K-Akt signaling pathway, TNF signaling pathway, and IL-17 signaling pathway), and targets (TOP2A, CYP1A2, CYP2B6, and IGFBP3). This study provides preliminary insights into the potential pharmacological mechanisms of SLC in HCC treatment, aiming to support its clinical application and serve as a reference for future laboratory investigations.

Low-level laser therapy induces human umbilical vascular endothelial cell proliferation, migration and tube formation through activating the PI3K/Akt signaling pathway.

Low-level laser therapy (LLLT) has been recognized as a light therapy that may be used for tissue regeneration, inflammation reduction, and pain relief. We intended to evaluate the effects of LLLT on the proliferation, migration, and tube formation of HUVECs as well as their related mechanisms. HUVECs were exposed to laser irradiation under different laser parameters (irradiation dose, interval and power intensity) in order to choose the optimal parameters, which were determined by the increase in proliferation of HUVECs as follows: irradiation dose of 4.0 J/m2, interval time of 12 h and 6 times in total. The HUVEC proliferation, migration, and tube formation, and levels of angiogenesis-related genes (HIF-1α, eNOS and VEGFA) were examined following LLLT. As suggested by the obtained data, LLLT (1.0, 2.0 and 4.0 J/m2) increased the HUVEC proliferation, migration, and tube formation in dose-and time-dependent manner, accompanied with increases in the levels of HIF-1α, eNOS, and VEGFA. Furthermore, the regulatory mechanism regarding the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was explored, phosphorylation levels of PI3K and Akt proteins were assessed by Western blot assay, which showed the enhancement of phosphorylation of PI3K, Akt, and mTOR by LLLT. The inhibitor for the PI3K/Akt axis was used to verify the involvement of PI3K/Akt signaling pathway. The obtained results suggested that the inhibition of the PI3K/Akt signaling pathway attenuated the effects of LLLT on proliferation, migration, and angiogenesis of HUVECs. In conclusion, LLLT promotes the proliferation, migration, and angiogenesis of HUVECs via activation of the PI3K/Akt signaling pathway.

Effects of dimethylglycine sodium salt supplementation on growth performance, hepatic antioxidant capacity, and mitochondria-related gene expression in weanling piglets born with low birth weight1.

Dimethylglycine sodium salt (DMG-Na) has exhibited excellent advantages in animal experiments and human health. The present study aimed to investigate the effects of dietary supplementation with 0.1% DMG-Na on the growth performance, hepatic antioxidant capacity, and mRNA expression of mitochondria-related genes in low birth weight (LBW) piglets during weaning period. Sixteen piglets with normal birth weight (NBW) and 16 LBW piglets were fed either a basal diet or a 0.1% DMG-Na supplemented diet from age of 21 to 49 d. Blood and liver samples were collected at the end of the study. The results showed that compared with NBW piglets, LBW piglets exhibited greater (P < 0.05) alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase activities in the serum. LBW decreased (P < 0.05) the activity of glutathione peroxidase and increased (P < 0.05) the contents of malondialdehyde and H2O2 in liver. DMG-Na supplementation increased (P < 0.05) body weight gain, feed intake, and feed efficiency, decreased (P < 0.05) ALT and AST activities, and reduced the content of H2O2 in LBW piglets. LBW piglets had downregulated (P < 0.05) mRNA expression of thioredoxin 2, thioredoxin reductases 2, and nuclear respiratory factor-1 (Nrf1) in the liver. However, DMG-Na supplementation increased (P < 0.05) mRNA expression of Nrf1 in the liver. In conclusion, DMG-Na supplementation has beneficial effects in alleviating LBW-induced hepatic oxidative damage and changed mitochondrial genes expression levels, which is associated with increased antioxidant enzyme activities and up-regulating mRNA gene abundance.