Exploring the anticancer potential of Eleutherine bulbosa: A systematic network pharmacology study on lung cancer.

Chemotherapy application in lung cancer patients has several side effects and shows lower effectiveness due to chemoresistance. Although Eleutherine bulbosa (Mill.) Urb. (EBE) elicit anticancer properties, yet the exact profile of its active compounds and lung cancer inhibition mechanisms were not fully understood. This study aimed to identify suggestive compounds from EBE extract and explain the molecular mechanisms of EBE against lung cancer. Identification of the compound from the EBE extract was confirmed using liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). The bioavailability profile of three major metabolites was identified using absorption, distribution, metabolism, excretion, toxicity software. The anticancer molecular mechanism prediction of the drugs was ascertained by network pharmacology using Cytoscape 3.9.1 and the protein-protein interaction network technique with STRING 11.0. Interaction between resveratrol and extracellular growth factor receptor (EGFR) was analyzed using site-specific molecular docking with erlotinib as the control using PyRx Autodock Vina 9.0 and BIOVIA Discovery Studio. A total of 16 active compounds were identified from LC-MS/MS. Only resveratrol showed anticancer properties by its interaction with 13 genes and 6 signaling pathways related to lung cancer. The molecular docking result supports the network pharmacology finding. The binding affinity of resveratrol with EGFR, important receptor in lung cancer, was more negative (-6.9 kcal/mol) than erlotinib (-6.2 kcal/mol) as the control. Evidence suggested that resveratrol in EBE exhibits anticancer effects by modulating lung cancer cell proliferation and apoptosis through EGFR binding.

Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract.

Although positive association between fermented vegetables intake with the risk of coronary heart disease (CHD) has increased attention nowadays, the metabolite profiling and the mechanism of action are still elusive. This study designed to investigate the secondary metabolites, hypolipidemic, and anti-atherogenic effect of mixed vegetable fermentation extract (MVFE). The metabolite screening of the MVFE was assessed using the Liquid Chromatography Tandem Mass Spectrophotometer (LC-MS/MS) method. The result of LC-MS/MS was used as ligands to inhibit the binding of oxidized LDL (oxLDL) and Cluster Differentiation 36 (CD36), Scavenger Receptor A1 (SRA1), Lectin-type oxidized LDL receptor 1 (LOX1). This work was performed with molecular docking using Discovery Studio 2021, PyRx 0.9, and Autodock Vina 4.2 followed by analyzing Network Pharmacology, Protein Protein Interaction (PPI) using Cytoscape 3.9.1 and String 2.0.0. Finally, the clinical effect of MVFE was evaluated using in vivo study. Twenty rabbits were assigned to normal, negative control, and MVFE group that were fed with standard diet, high fat diet (HFD), HFD supplemented with MVFE 100, 200 mg/kg BW, respectively. The serum level of Total Cholesterol (TC) and Low-Density Lipoprotein (LDL-c) were detected at the end of week 4. The LC-MS/MS analysis identified 17 compounds categorized as peptides, fatty acids, polysaccharides, nucleoside, flavonoids, flavanols, and phenolic compounds. Based on the docking study, more negative binding affinity was observed in the interaction between metabolites with the scavenger receptors (SR) than simvastatin. The number of nodes and edges based on Network Pharmacology analysis were 268 and 482, respectively. The PPI network showed that MVFE metabolites exerts its athero-protective effect by modulating various cellular processes including inflammation, improvement of endothelial function, and modulation of lipid metabolism. Blood TC and LDL-c concentrations in the negative control (458.82 ± 82.03; 191.87 ± 92.16 mg/dL) were higher significantly compared to the normal group (87.03 ± 29.27; 43.33 ± 5.75 mg/dL). The MVFE administration decreased the TC (100, 200 mg/kg BW MVFE: 269.96 ± 85.34; 130.17 ± 45.02 mg/dL) and LDL-c level (100, 200 mg/kg BW MVFE = 87.24 ± 22.85; 41.82 ± 11.08 mg/dL) dose-dependently (p < 0,001). The secondary metabolites derived from fermented mixed vegetables extract might be developed as a potential strategy to prevent CHD by targeting the multiple pathways in atherosclerosis.

Serum IL-6/IL-10 ratio as a biomarker for the diagnosis and severity assessment of primary-open angle glaucoma.

OBJECTIVE: To assess the performance of serum cytokine IL-6 and IL-6/IL-10 ratio as biomarkers for the diagnosis of primary open-angle glaucoma (POAG) and for determining its progression. METHODS: In this study, 20 POAG patients and 21 healthy individuals from the Indonesian population were enrolled. The serum concentration of IL-6 and IL-10 were quantified. Comparative analysis was performed in addition to assessment of the diagnostic performance of cytokines using receiver-operating-curve (ROC) analysis. RESULTS: POAG patients had a higher IL-6 (p < 0.0001) and IL-6/IL-10 ratio (p < 0.0001) than controls. Among the POAG subjects, advanced-stage patients exhibited a higher IL-6/IL-10 ratio than those in the early-moderate stage (p = 0.001; p = 0.006). The ROC curve analysis showed that both IL-6 level and IL-6/IL-10 ratio exhibited an excellent capability of diagnosing POAG (cut-off of 20.5 pg/mL (100% sensitivity and 94% specificity) and 4.4 (88% sensitivity and 94% specificity), respectively). Serum IL-6/IL-10 ratio displayed a better performance than IL-6 in discriminating POAG severity with cut-off of at least 6.6 (sensitivity of 86% and specificity of 90%) and 9.1 (sensitivity of 89% and specificity of 78%) classified according to C/D ratio and MD of VF, respectively. CONCLUSION: The balance between IL-6 and IL-10 serum levels is potentially useful in discriminating POAG severity.

miR-155-5p predictive role to decelerate foam cell atherosclerosis through CD36, VAV3, and SOCS1 pathway.

MicroRNAs (miRNAs) are noncoding RNA molecules that play a significant role in atherosclerosis pathogenesis through post-transcriptional regulation. In the present work, a bioinformatic analysis using TargetScan and miRdB databases was performed to identify the miRNAs targeting three genes involved in foam cell atherosclerosis (CD36, Vav3, and SOCS1). A total number of three hundred and sixty-seven miRNAs were recognized and only miR-155-5p was selected for further evaluation based on Venn analysis. Another objective of this study was to evaluate the biological process and regulatory network of miR-155-5p associated with foam cell atherosclerosis using DIANA, DAVID, Cytoscape, and STRING tools. Additionally, the comprehensive literature review was performed to prove the miR-155-5p function in foam cell atherosclerosis. miR-155-5p might be related with ox-LDL uptake and endocytosis in macrophage cell by targeting CD36 and Vav3 genes which was showed from the KEGG pathways hsa04979, hsa04666, hsa04145 H, hsa04810, and GO:0099632, GO:0060100, GO:0010743, GO:001745. Furthermore, miR-155-5p was also predicted to increase the cholesterol efflux from macrophage by inhibit SOCS1 expression based on KEGG pathway hsa04120. Eleven original studies were included in the review and strongly suggest the role of miR-155-5p in foam cell atherosclerosis inhibition.