Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy

Shimazaki, Toshiharu; Noro, Nobuhiro; Hagikura, Kazuhiro; Matsumoto, Tarô; Yoshida-Noro, Chikako

doi:10.3390/biology10111212

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…After 24 h, the culture medium was removed and cells were treated for 1 h with a DMSO solution of resveratrol (10, 30, and 100 µM), compound 3d (10, 30, and 100 µM), or vehicle (DMSO 0.01%). Such concentrations have been selected based on previous experiments evaluating the potential effects of resveratrol against oxidative stress and angiogenesis in HUVECs [ 55 , 72 , 73 ].…”

Section: Methodsmentioning

confidence: 99%

Resveratrol-like Compounds as SIRT1 Activators

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Brogi

et al. 2022

IJMS

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The sirtuin 1 (SIRT1) activator resveratrol has emerged as a promising candidate for the prevention of vascular oxidative stress, which is a trigger for endothelial dysfunction. However, its clinical use is limited by low oral bioavailability. In this work, we have applied a previously developed computational protocol to identify the most promising derivatives from our in-house chemical library of resveratrol derivatives. The most promising compounds in terms of SIRT1 activation and oral bioavailability, predicted in silico, were evaluated for their ability to activate the isolated SIRT1 enzyme. Then, we assessed the antioxidant effects of the most effective derivative, compound 3d, in human umbilical vein endothelial cells (HUVECs) injured with H2O2 100 µM. The SIRT1 activator 3d significantly preserved cell viability and prevented an intracellular reactive oxygen species increase in HUVECs exposed to the oxidative stimulus. Such effects were partially reduced in the presence of a sirtuin inhibitor, sirtinol, confirming the potential role of sirtuins in the activity of resveratrol and its derivatives. Although 3d appeared less effective than resveratrol in activating the isolated enzyme, the effects exhibited by both compounds in HUVECs were almost superimposable, suggesting a higher ability of 3d to cross cell membranes and activate the intracellular target SIRT1.

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Section: Methodsmentioning

confidence: 99%

Resveratrol-like Compounds as SIRT1 Activators

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Piragine

Brogi

et al. 2022

IJMS

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Constructing a novel gene signature derived from oxidative stress specific subtypes for predicting survival in stomach adenocarcinoma

Zhou¹,

Peng

2022

Front. Immunol.

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Oxidative stress (OS) response is crucial in oncogenesis and progression of tumor. But the potential prognostic importance of OS-related genes (OSRGs) in stomach adenocarcinoma (STAD) lacked comprehensive study. STAD clinical information and transcriptome data were retrieved from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The prognostic OSRGs were filtered via the univariate Cox analysis and OSRG-based molecular subtypes of STAD were developed using consensus clustering. Weighted gene co-expression network analysis (WGCNA) was subsequently conducted to filter molecular subtype-associated gene modules. The prognosis-related genes were screened via univariate and least absolute shrinkage and selection operator Cox regression analysis were used to construct a prognostic risk signature. Finally, a decision tree model and nomogram were developed by integrating risk signature and clinicopathological characteristics to analyze individual STAD patient’s survival. Four OSRG-based molecular subtypes with significant diversity were developed based on 36 prognostic OSRGs for STAD, and an OSRGs-based subtype-specific risk signature with eight genes for prognostic prediction of STAD was built. Survival analysis revealed a strong prognostic performance of the risk signature exhibited in predicting STAD survival. There were significant differences in mutation patterns, chemotherapy sensitivity, clinicopathological characteristics, response to immunotherapy, biological functions, immune microenvironment, immune cell infiltration among different molecular subtypes and risk groups. The risk score and age were verified as independent risk factors for STAD, and a nomogram integrating risk score and age was established, which showed superior predictive performance for STAD prognosis. We developed an OSRG-based molecular subtype and identified a novel risk signature for prognosis prediction, providing a useful tool to facilitate individual treatment for patients with STAD.

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Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches

Pagano¹,

Longhi

Molinari³

et al. 2022

IJMS

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NMR-based approaches play a pivotal role in providing insight into molecular recognition mechanisms, affording the required atomic-level description and enabling the identification of promising inhibitors of protein–protein interactions. The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signaling pathway drives several pathologies, including cancer development, metastasis formation, resistance to therapy, angiogenesis-driven pathologies, vascular diseases, and viral infections. Most FGFR inhibitors targeting the intracellular ATP binding pocket of FGFR have adverse effects, such as limited specificity and relevant toxicity. A viable alternative is represented by targeting the FGF/FGFR extracellular interactions. We previously identified a few small-molecule inhibitors acting extracellularly, targeting FGFR or FGF. We have now built a small library of natural and synthetic molecules that potentially act as inhibitors of FGF2/FGFR interactions to improve our understanding of the molecular mechanisms of inhibitory activity. Here, we provide a comparative analysis of the interaction mode of small molecules with the FGF2/FGFR complex and the single protein domains. DOSY and residue-level NMR analysis afforded insights into the capability of the potential inhibitors to destabilize complex formation, highlighting different mechanisms of inhibition of FGF2-induced cell proliferation.

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Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy

Cited by 3 publications

References 45 publications

Resveratrol-like Compounds as SIRT1 Activators

Resveratrol-like Compounds as SIRT1 Activators

Constructing a novel gene signature derived from oxidative stress specific subtypes for predicting survival in stomach adenocarcinoma

Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches

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