scholarly journals Influences of advanced glycosylation end products on the inner blood–retinal barrier in a co-culture cell model in vitro

2020 ◽  
Vol 15 (1) ◽  
pp. 619-628
Author(s):  
Chen Yuan ◽  
Ya Mo ◽  
Jie Yang ◽  
Mei Zhang ◽  
Xuejun Xie
Keyword(s):  
Electrical Resistance ◽  
Cell Model ◽  
Polyclonal Antibodies ◽  
Time Dependent ◽  
Dependent Manner ◽  
Blood Retinal Barrier ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation

AbstractAdvanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood–retinal barrier (iBRB). Rat retinal microvascular endothelial cells (RMECs) were isolated and cultured, and identified by anti-CD31 and von Willebrand factor polyclonal antibodies. Similarly, rat retinal Müller glial cells (RMGCs) were identified by H&E staining and with antibodies of glial fibrillary acidic protein and glutamine synthetase. The transepithelial electrical resistance (TEER) value was measured with a Millicell electrical resistance system to observe the leakage of the barrier. Transwell cell plates for co-culturing RMECs with RMGCs were used to construct an iBRB model, which was then tested with the addition of AGEs at final concentrations of 50 and 100 mg/L for 24, 48, and 72 h. AGEs in the in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of the vascular endothelial growth factor (VEGF) and pigment epithelial derivative factor (PEDF), and the permeability of the RMEC layer increased because the TEER decreased in a dose- and time-dependent manner. AGEs increased VEGF but lowered PEDF in a dose- and time-dependent manner. The intervention with AGEs led to the change of the transendothelial resistance of the RMEC layer likely caused by the increased ratio of VEGF/PEDF.

scholarly journals Influences of advanced glycosylation end products on the inner blood-retinal barrier in a co-cultural cell model in vitro

2020 ◽  
Author(s):  
Chen Yuan ◽  
Ya Mo ◽  
Jie Yang ◽  
Mei Zhang ◽  
Xuejun Xie
Keyword(s):  
Electrical Resistance ◽  
Time Dependent ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Blood Retinal Barrier ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Culture Models ◽  
Advanced Glycosylation

Abstract Background: Advanced glycosylation end products (AGEs) are harmful factors that can damage the inner blood-retinal barrier (iBRB). However, their effects on iBRB co-culture models in vitro have not been reported. This study is to understand the interactive effects of different concentrations of AGEs at different time points on rat retinal microvascular endothelial cells (RMEC) and rat retinal Müller glial cell (RMGC) co-culture models. Methods: RMEC of Sprague-Dawley rat was isolated and cultured, identified by anti-CD31 flow cytometry and immunocytometry with von Willebrand factor polyclonal antibody. Similarly, RMGC of Sprague-Dawley rat was identified by H&E staining, and immunohistochemical method with antibodies of Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The transepithelial electrical resistance (TEER) value was measured with the Millicell electrical resistance system to observe the leakage of the barrier. The Transwell cell for co-cultured RMEC with RMGC were used to construct an iBRB model and tested with the addition of AGEs at final concentrations of 50 mg/L and 100 mg/L, respectively, for 24 hours, 48 hours, and 72 hours.Results: AGEs in vitro iBRB model constructed by RMEC and RMGC co-culture led to the imbalance of VEGF and PEDF, and the permeability of the RMEC layer increased because TEER decreased in a dose- and time-dependent manner. In the AGEs intervention the vascular endothelial growth factor (VEGF) was increased, while pigment epithelial derivative factor (PEDF) decreased, respectively, in a dose- and time-dependent manner by enzyme-linked immunosorbent assay.Conclusions: The intervention with AGEs led to change of the RMEC layer transendothelial resistance and ratio of VEGF/PEDF. The iBRB in vitro model is a good tool to study the pathogenesis of retinal vascular diseases such as diabetic retinopathy and to evaluate the candidate drugs on the diseases.

scholarly journals Hyperglycemia-induced accumulation of advanced glycosylation end products in fibroblast-like synoviocytes promotes knee osteoarthritis

2021 ◽  
Author(s):  
Qingxian Li ◽  
Yinxian Wen ◽  
Linlong Wang ◽  
Biao Chen ◽  
Jun Chen ◽  
...  
Keyword(s):  
High Glucose ◽  
Glucose Transporter ◽  
Critical Role ◽  
Inflammatory Factors ◽  
Glucose Transporter 1 ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation ◽  
Fibroblast Like Synoviocytes

AbstractOsteoarthritis (OA) is significantly associated with diabetes, but how hyperglycemia induces or aggravates OA has not been shown. The synovium plays a critical role in cartilage metabolism and substance exchange. Herein, we intended to investigate whether and how hyperglycemia affects the occurrence and progression of OA by influencing the synovium. In patients with knee OA and diabetes (DM OA), we found a more severe inflammatory response, higher endoplasmic reticulum stress (ERS) levels, and more advanced glycosylation end products (AGEs) accumulation in the synovium than in patients without diabetes. Subsequently, we found similar results in the DM OA group in a rat model. In the in vitro cocultivation system, high glucose-stimulated AGEs accumulation, ERS, and inflammation in rat fibroblast-like synoviocytes (FLSs), which resulted in chondrocyte degeneration due to inflammatory factors from FLSs. Furthermore, in the synovium of the DM OA group and FLSs treated with high glucose, the expression of glucose transporter 1 (GLUT1) and its regulatory factor hypoxia-inducible factor (HIF)-1α was increased significantly. Inhibitors of HIF-1α, GLUT1 or AGEs receptors attenuated the effect of high glucose on chondrocyte degradation in the FLS-chondrocyte coculture system. In summary, we demonstrated that hyperglycemia caused AGEs accumulation in FLSs via the HIF-1α-GLUT1 pathway, which increases the release of inflammatory factors from FLSs, subsequently inducing chondrocyte degradation and promoting OA progression.

scholarly journals How Does Glycation Affect Binding Parameters of the Albumin-Gliclazide System in the Presence of Drugs Commonly Used in Diabetes? In Vitro Spectroscopic Study

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3869
Author(s):  
Katarzyna Wiglusz ◽  
Ewa Żurawska-Płaksej ◽  
Anna Rorbach-Dolata ◽  
Agnieszka Piwowar
Keyword(s):  
Association Constants ◽  
Pharmacokinetic Parameters ◽  
Spectroscopic Methods ◽  
Binding Parameters ◽  
Advanced Glycosylation End Products ◽  
Investigational Drugs ◽  
End Products ◽  
Glycation Process ◽  
Advanced Glycosylation

In this research, the selected drugs commonly used in diabetes and its comorbidities (gliclazide, cilazapril, atorvastatin, and acetylsalicylic acid) were studied for their interactions with bovine serum albumin—native and glycated. Two different spectroscopic methods, fluorescence quenching and circular dichroism, were utilized to elucidate the binding interactions of the investigational drugs. The glycation process was induced in BSA by glucose and was confirmed by the presence of advanced glycosylation end products (AGEs). The interaction between albumin and gliclazide, with the presence of another drug, was confirmed by calculation of association constants (0.11–1.07 × 104 M−1). The nature of changes in the secondary structure of a protein depends on the drug used and the degree of glycation. Therefore, these interactions may have an influence on pharmacokinetic parameters.

scholarly journals Synthesis and Evaluation of the Antitumor Activity of Novel 1-(4-Substituted phenyl)-2-ethyl Imidazole Apoptosis Inducers In Vitro

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4293
Author(s):  
Zhen-Wang Li ◽  
Chun-Yan Zhong ◽  
Xiao-Ran Wang ◽  
Shi-Nian Li ◽  
Chun-Yuan Pan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Antiproliferative Activity ◽  
Antitumor Agent ◽  
Positive Control ◽  
Selectivity Index ◽  
Time Dependent ◽  
Potential Candidate ◽  
Dependent Manner

Novel imidazole derivatives were designed, prepared, and evaluated in vitro for antitumor activity. The majority of the tested derivatives showed improved antiproliferative activity compared to the positive control drugs 5-FU and MTX. Among them, compound 4f exhibited outstanding antiproliferative activity against three cancer cell lines and was considerably more potent than both 5-FU and MTX. In particular, the selectivity index indicated that the tolerance of normal L-02 cells to 4f was 23–46-fold higher than that of tumor cells. This selectivity was significantly higher than that exhibited by the positive control drugs. Furthermore, compound 4f induced cell apoptosis by increasing the protein expression levels of Bax and decreasing those of Bcl-2 in a time-dependent manner. Therefore, 4f could be a potential candidate for the development of a novel antitumor agent.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

Advanced Glycosylation End Products in Patients with Diabetic Nephropathy

1991 ◽  
Vol 325 (12) ◽  
pp. 836-842 ◽  
Author(s):  
Zenji Makita ◽  
Steven Radoff ◽  
Elliot J. Rayfield ◽  
Zhi Yang ◽  
Edward Skolnik ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation

scholarly journals PDGF and TGF-β mediate collagen production by mesangial cells exposed to advanced glycosylation end products

1995 ◽  
Vol 48 (1) ◽  
pp. 111-117 ◽  
Author(s):  
Douglas C. Throckmorton ◽  
Anne P. Brogden ◽  
Brian Min ◽  
Howard Rasmussen ◽  
Michael Kashgarian
Keyword(s):  
Mesangial Cells ◽  
Collagen Production ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation
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