Advanced glycation end products enhance M1 macrophage polarization by activating the MAPK pathway

He, Sunyue; Hu, Qiuyue; Xu, Xiaoyuan; Niu, Yixin; Chen, Youming; Lu, Yao; Su, Qing; Qin, Li

doi:10.1016/j.bbrc.2020.02.053

Cited by 48 publications

(38 citation statements)

References 35 publications

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“…M1-type MAs are considered to be beneficial for tumor suppression, while M2-type MAs are associated with the progression of solid tumors. CD16/32 and CD11c are highly expressed on M1 cell surface, while CD206 tends to be overexpressed on the M2-type MA surface 44 , 45 . Herein, M1-phenotype MAs stimulated by LPS (1 μg/mL) and M2-type MAs induced by IL-4 (10 ng/mL) were used as controls.…”

Section: Resultsmentioning

confidence: 99%

Macrophage-mediated tumor homing of hyaluronic acid nanogels loaded with polypyrrole and anticancer drug for targeted combinational photothermo-chemotherapy

Xiao

Fan

et al. 2021

Theranostics

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Rationale: Development of nanosystems that can be integrated with macrophages (MAs), an emerging carrier system, for effective tumor therapy remains to be challenging. We report here the development of MAs specifically loaded with hyaluronic acid (HA) nanogels (NGs) encapsulated with a photothermal agent of polypyrrole (PPy) and anticancer drug doxorubicin (DOX) (HA/DOX@PPy NGs) for tumor homing and combination photothermo-chemotherapy. Methods: Cystamine dihydrochloride-crosslinked HA NGs were first prepared through a double emulsification method, then loaded with PPy via an in-situ oxidization polymerization and physically encapsulated with DOX. The created HA/DOX@PPy NGs were well characterized and subjected to be endocytosed by MAs (MAs-NGs). The MAs-mediated tumor-homing property, phenotype changes and photothermal performance of MAs-NGs were investigated in vitro , and a subcutaneous tumor model was also established to confirm their targeting capability and enhanced antitumor therapy effect in vivo . Results: The generated hybrid NGs possess a size around 77 nm and good colloidal stability, and can be specifically endocytosed by MAs without appreciably affecting their normal biofunctionalities. In particular, NG-loaded MAs display excellent in-vitro cancer cell and in-vivo tumor homing property. Systemic administration of the MAs-NGs leads to the significant inhibition of a subcutaneous tumor model through combination photothermo-chemotherapy under laser irradiation. Conclusions: The developed hybrid HA-based NG nanosystem incorporated with PPy and DOX fully integrates the coordination and heating property of PPy to regulate the optimized DOX release in the tumor region with the assistance of MA-mediated tumor homing, providing a promising cell therapy strategy for enhanced antitumor therapy.

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Section: Resultsmentioning

confidence: 99%

Macrophage-mediated tumor homing of hyaluronic acid nanogels loaded with polypyrrole and anticancer drug for targeted combinational photothermo-chemotherapy

Xiao

Fan

et al. 2021

Theranostics

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“…We found that paraquat exposure increased citric acid levels; citric acid is an intermediate product of the TCA cycle, indicating that paraquat poisoning blocks the TCA cycle to affect energy supply [ 49 ]. Galactose is a reducing monosaccharide that can be metabolized to glucose under normal conditions, but an excess leads to formation of reactive oxygen species and advanced glycation end-products, which can result in oxidative stress, mitochondrial dysfunction, cell damage, and inflammation [ 50 – 52 ]. Paraquat has been reported to interfere with glucose metabolism and the TCA cycle in dopaminergic neurons [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fluorofenidone Against Paraquat-Induced Pulmonary Fibrosis Based on Metabolomics and Network Pharmacology

Jiang

Wang

et al. 2021

Med Sci Monit

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Background Fluorofenidone (AKF-PD) is an anti-fibrotic small-molecule compound. Its mechanism of action on paraquat (PQ)-induced pulmonary fibrosis is still unclear. Material/Methods Forty-eight SD rats were divided into 4 groups: control group, PQ group, PQ+AKF-PD group, and AKF-PD group. The pathological changes of lung tissues were observed by Masson and HE staining. The UPLC-QTOF-MS analysis was performed to detect the differences in metabolites among groups, then the possible mechanisms of the anti-pulmonary fibrosis effects of fluorofenidone were further revealed by network pharmacology analysis. Biological methods were used to verify the results of the network pharmacology analysis. Results The results showed that fluorofenidone treatment significantly alleviated paraquat-induced pulmonary fibrosis. Metabolomics analysis showed that 18 metabolites were disordered in the serum of paraquat-poisoned rats, of which 13 were restored following fluorofenidone treatment. Network pharmacology analysis showed that the drug screened a total of 12 targets and mainly involved multiple signaling pathways and metabolic pathways to jointly exert anti-pulmonary fibrosis effects. Autophagy is the main pathway of fluorofenidone in treatment pulmonary fibrosis. The western blot results showed that fluorofenidone upregulated the expression of LC3-II/I and E-cadherin, and downregulated the expression of p62, α-SMA, and TGF-β1, which validated that fluorofenidone could inhibit the development of paraquat-induced pulmonary fibrosis by increasing autophagy. Conclusions In conclusion, metabolomics combined with network pharmacology research strategy revealed that fluorofenidone has a multi-target and multi-path mechanism of action in the treatment of pulmonary fibrosis.

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“…Long-term deleterious effects of MG on β-cell lines (Ins-1 and RIN-m5F) have been shown in vitro, namely, redox-independent inhibition of insulin receptor substrate (IRS) 1 and PI3K/Akt pathway, generation of oxidative stress, mitochondrial damage through decreased membrane potential and ATP, and mitochondria-induced apoptosis [32,[35][36][37][38][39][40][41]. Moreover, He et al (2020) have demonstrated β-cell dysfunction and impaired glucose-stimulated insulin secretion after co-culture with AGE-pretreated macrophages, which was attributed to increased expression of proinflammatory cytokines [42]. Altogether, such mechanisms were demonstrated to be involved in MG-induced decrease of cell viability and insulin secretion.…”

Section: Regulation Of Insulin Secretion By Glycotoxinsmentioning

confidence: 99%

Another Player in the Field: Involvement of Glycotoxins and Glycosative Stress in Insulin Secretion and Resistance

Matafome

2020

Diabetology

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The term glycotoxins includes the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds, such as methylglyoxal (MG). Glycotoxins were initially thought to participate in the development of diabetic complications because of their increased formation from glucose. However, they also form and accumulate in tissues since the early stages of disease, such as metabolically unhealthy obesity and prediabetes. Such accumulation has been suggested to result from dysregulated activity of detoxification systems, such as the glyoxalase system, as well as increased dietary consumption, namely from high-glucose and high-fructose foods processed at high temperatures. Although some studies may have used supraphysiological doses, in vitro systems and animal models have shown glycotoxin-induced insulin resistance. Moreover, dietary glycotoxin restriction was shown to improve insulin resistance in humans and glyoxalase (GLO)-1 upregulation improved insulin sensitivity and metabolic function. This review summarizes the current knowledge about glycotoxin involvement in the development of insulin resistance, the mechanisms involved and the usefulness of GLO-1 modulation, and a possible therapeutic strategy to improve insulin sensitivity.

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Advanced glycation end products enhance M1 macrophage polarization by activating the MAPK pathway

Cited by 48 publications

References 35 publications

Macrophage-mediated tumor homing of hyaluronic acid nanogels loaded with polypyrrole and anticancer drug for targeted combinational photothermo-chemotherapy

Macrophage-mediated tumor homing of hyaluronic acid nanogels loaded with polypyrrole and anticancer drug for targeted combinational photothermo-chemotherapy

Effect of Fluorofenidone Against Paraquat-Induced Pulmonary Fibrosis Based on Metabolomics and Network Pharmacology

Another Player in the Field: Involvement of Glycotoxins and Glycosative Stress in Insulin Secretion and Resistance

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