Serum netrin and VCAM-1 as biomarker for Egyptian patients with type IΙ diabetes mellitus

Fadel, Maher M.; Ghaffar, Faten R. Abdel; Zwain, Shimaa K.; Ibrahim, Hany M.; Badr, Eman

doi:10.1016/j.bbrep.2021.101045

Cited by 11 publications

(11 citation statements)

References 44 publications

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“…In addition, VCAM1 protein level was significantly correlated with T2DM complications. The enhanced induction of VCAM1 expression in endothelial cells by circulating factors may play a role in the development of atherosclerosis in diabetes [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Network Pharmacology and Molecular Docking to Verify the Treatment of Type 2 Diabetes with Pueraria Lobata Radix and Salviae Miltiorrhizae Radix

Mao

Wang

Yang

et al. 2023

Computational and Mathematical Methods in Medicine

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Objective. To explore the potential molecular mechanism of Pueraria Lobata Radix (RP) and Salviae Miltiorrhizae Radix (RS) in the treatment of type 2 diabetes mellitus (T2DM) based on network pharmacology and molecular docking. Methods. The chemical constituents and core targets of RP and RS were searched by Traditional Chinese Medicine System Pharmacology (TCMSP); target genes related to T2DM were obtained through GeneCards database, component target network diagram was constructed, intersection genes of active compounds and T2DM were synthesized, protein-protein interaction (PPI) relationship was obtained, and core targets were screened by using Cytoscape 3.7.2. Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed utilizing R studio 4.0.4 according to David database. Based on molecular docking, the screened active components of RP and RS were verified by molecular docking with the core target using Discovery Studio 2019. Results. There were totally 92 components and 29 corresponding targets in the component target network of RP and RS drug pair, of which 6 were the core targets of RP and RS in the treatment of T2DM. Molecular docking results showed that the active compounds of puerarin, formononetin, tanshinone iia, and luteolin had better binding activity with AKT1, VEGFA, NOS3, PPARG, MMP9, and VCAM1, respectively. Among them, puerarin showed significant effects in activating NOS3 pathway and luteolin exhibited significant effects in activating MMP9 pathway, respectively. The main biological processes mainly including xenobiotic stimulus, response to peptide, gland development, response to radiation, cellular response to chemical stress, response to oxygen levels, and the main signal pathways include response to xenobiotic stimulus, cellular response to chemical stress, response to peptide, gland development, and response to oxygen levels. Conclusion. Network pharmacology is an effective tool to explain the action mechanism of Traditional Chinese Medicine (TCM) from the overall perspective. RP and RS pair could alleviate T2DM via the molecular mechanism predicted by the network pharmacology, which provided new ideas and further research on the molecular mechanism of T2DM.

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Section: Discussionmentioning

confidence: 99%

Combined Network Pharmacology and Molecular Docking to Verify the Treatment of Type 2 Diabetes with Pueraria Lobata Radix and Salviae Miltiorrhizae Radix

Mao

Wang

Yang

et al. 2023

Computational and Mathematical Methods in Medicine

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“…[209], FLNA (filamin A) [444] and ACTA2 [422] plays an important role in the hypertension. Altered expression of HSPA8 [600], VCAM1 [618] and MYH9 [647] are associated with type 2 diabetes mellitus. HSPA5 [488] and VCAM1 [515] might play an important role in regulating the genetic network related to the occurrence, development of obesity.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Diabetic patients are prone to diabetic kidney disease (DKD), which may cause cardiovascular damage, hypertension and obesity, and reduce quality of life. As a result, the life quality of patients was seriously reduced. However, the pathogenesis of diabetic kidney disease (DKD) has not been fully elucidated, and current treatments remain inadequate. Therefore, it is essential to explore the molecular mechanism of DKD and its complications. Next Generation Sequancing (GSE217709) dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were picked out by R software. Then Gene ontology (GO) and REACTOME pathway enrichment analysis were performed by g:Profiler database, protein-protein interaction (PPI) of DEGs was constructed by Human Integrated Protein-Protein Interaction rEference (HIPPIE) database . Module analysis was carried out by Cytoscape plug-in PEWCC. Subsequently, miRNA-hub gene regulatory network and TF- hub gene regulatory network were performed by miRNet database and NetworkAnalyst database. Finally, validation of hub genes was performed by receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. In total, 958 DEGs, including 479 up regulated and 479 down regulated genes, were identified. The GO and pathway enrichment changes of DEGs were mainly enriched in biological regulation, multicellular organismal process, signaling by GPCR and extracellular matrix organization. Ten hub genes (HSPA8, HSP90AA1, HSPA5, SDCBP, HSP90B1, VCAM1, MYH9, FLNA, MDFI and PML) associated with DKD and its complications were identified. Bioinformatics analysis is a useful tool to explore the molecular mechanism and pathogenesis of DKD and its complications. The identified hub genes may participate in the onset and development of DKD and its complications and serve as therapeutic targets.

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“…Further cell trajectory studies revealed that Vcam1 may play important roles in dysregulation of biological functions of EC_EndMT via cell-cell communication. Other studies have suggested that Vcam1 could be a marker for transitional obesity and diabetic nephropathy ( Fadel et al, 2021 ). In the presence of hyperinsulinemia in type 2 diabetes, it activates the MAPK signaling pathway, which in turn activates the expressions VCAM1 and E-selectin and induces the production of ROS, involved in vascular damage in diabetes, including the neurodegenerative diseases ( Potenza et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

Huang

Lin

Sun

et al. 2022

Front. Aging Neurosci.

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IntroductionEndothelial cells play important roles in neurodegenerative diseases caused by diabetes, therefore, we aimed at investigating the mechanisms through which endothelial cells are involved in diabetes development.MethodsSingle cell analysis was performed to identify the major endothelial cell subtypes in cardiovascular tissues that are involved in diabetes development. A cell-cell communication approach was then used to identify ligand-receptor interaction pairs between these cell types. Differential expression analysis between the two experimental groups [standard chow diet group and diabetogenic diet with cholesterol (DDC) group] was used to identify diabetes-related differentially expressed genes (DEGs). The upregulated genes were used to identify candidate ligands or receptors, as well as the corresponding cell types. Cell trajectory inference was performed to identify the stage of cell development and changes in expression of candidate ligands or receptors during cell development. Gene set enrichment analysis (GSEA) was conducted to investigate the biological functions of genes of purpose. Finally, molecular dynamics simulations (MDSs) were used to predict potential drugs with the ability to target the proteins of purpose.ResultsSeven cell types, including five endothelial cell subtypes (EC_1, EC_2, EC_3, EC_4, and EC_EndMT), were identified from endothelial cell-enriched single cell samples from the heart and aorta of mice. Cell-cell communication analysis revealed the potential ligand-receptor interactions between these cell types while five important ligand-receptor-associated genes, including Fn1, Vcam1, Fbn1, Col4a1, and Col4a2, were established by differential expression analysis. Among them, Vcam1 is mainly expressed in EC_EndMT and is involved in interactions between EC_EndMT and other cells. Cell trajectory extrapolation analysis revealed a shift from EC_2/EC_4 to EC_EndMT and a shift from EC_EndMT to EC_3/EC_1 during the progression of diabetes. GSEA analysis revealed that upregulation of VCAM1 may have inhibitory effects on cell growth and energy metabolism.ConclusionEC_EndMT subtypes have a complex role in neurodegenerative diseases caused by diabetes. Through mechanisms involved in cell-cell communication, Vcam1 may play an important role in dysregulation of biological functions of EC_ EndMT. Molecular docking results of the quercetin-VCAM1 complex suggest that quercetin may be an effective drug for targeting this protein.

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Serum netrin and VCAM-1 as biomarker for Egyptian patients with type IΙ diabetes mellitus

Cited by 11 publications

References 44 publications

Combined Network Pharmacology and Molecular Docking to Verify the Treatment of Type 2 Diabetes with Pueraria Lobata Radix and Salviae Miltiorrhizae Radix

Combined Network Pharmacology and Molecular Docking to Verify the Treatment of Type 2 Diabetes with Pueraria Lobata Radix and Salviae Miltiorrhizae Radix

Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis

Quercetin targets VCAM1 to prevent diabetic cerebrovascular endothelial cell injury

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