The Effect of Advanced Glycation End Products (AGEs) on Human Umbilical Cord Mesenchymal Stem Cells (hUCMSCs) with regard to Osteogenesis and Calcification

2021 ◽  
pp. 4019-4024
Author(s):  
Mefina Kuntjoro ◽  
Bambang Agustono ◽  
Eric Priyo Prasetyo ◽  
Sherman Salim ◽  
Fedik Abdul Rantam ◽  
...  
Keyword(s):  
Treatment Group ◽  
Umbilical Cord ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Osteogenic Medium ◽  
Advanced Glycation ◽  
Alizarin Red ◽  
Runx2 Expression ◽  
Glycation End Products ◽  
End Products

Background: Diabetes Mellitus is a systemic disease characterized by an increase in blood glucose which, in the long term, enhances advanced glycation end product and leads to impaired osteogenesis. In prosthodontics, the osteogenic process plays an important role in successful treatment. Purpose: The purpose of this study is to determine the effect of Advanced Glycation End products (AGEs) present in Human Umbilical Cord Mesenchymal Stem Cells (hUCMSCs) on osteogenesis and calcification. Materials and Methods: MSCs isolated from human umbilical cord were cultured and underwent expansion up to passage 5. The research sample was divided into two sub-groups; a treatment group (osteogenic medium+AGE-BSA medium) and a control group (osteogenic medium) each of which underwent three replications. Samples were examined immunocytochemically on days 1, 3, 7, 8, 9, 12, 14 and 21 to quantify the level of RUNX2 expression. Alizarin red staining was performed on day 21. Results: In the treatment group, RUNX2 expression increased on day 3, reaching a peak on days 7 and 14. That expression decreased on day 8. In the control group, the expression of RUNX2 reached its peak on day 8 before decreasing on day 9. The presence of alizarin red indicated calcification in the control medium, but less mineralization in the treatment group. Conclusion: The research indicated that AGE-BSA enhances the production of RUNX2 expression in hUCMSCs at both the initial and maturation stages. This finding was supported by the results of alizarin red staining which indicated that increased levels of RUNX2 produced less mineralization.

scholarly journals ANTIDIABETIC EFFECTS OF INDONESIAN BAY LEAVES (SYZYGIUM POLYANTHUM) EXTRACTS THROUGH DECREASING ADVANCED GLYCATION END PRODUCTS AND BLOOD GLUCOSE LEVEL ON ALLOXAN-INDUCED HYPERGLYCEMIC WISTAR RATS

2018 ◽  
Vol 11 (4) ◽  
pp. 340 ◽  
Author(s):  
Sri Wahjuni ◽  
Aaia Mayun Laksmiwati ◽  
Ida Bagus Putra Manuaba
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Treatment Group ◽  
Wistar Rats ◽  
Control Group ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Post Test ◽  
Ages Level

 Objective: Increased production of reactive oxygen species is one of the causes of hyperglycemia. This study aims to determine the effectiveness of Indonesian bay leaves (Syzygium polyanthum) extracts as an antidiabetic agent in decreasing blood glucose and advanced glycation end products (AGEs) level of alloxan-induced hyperglycemic Wistar rats.Methods: This research is a real experimental study with pre- and post-test control group design. The study begins with the induction of hyperglycemia in 40 Wistar rats using alloxan. Subsequently, hyperglycemic rats were divided into 6 groups, namely, the positive control group (P0); the treatment group by not giving the intake of Indonesian bay leaf (P1); the treatment group was given the extract of Indonesian bay leaves (S. polyanthum) 0.5 mg/kg body weight/day (P2); treatment group given Indonesian bay leaves extract 2.0 mg/kg body weight/day (P3); treatment group given Indonesian bay leaves 5.0 mg/kg body weight/day (P4), and P5 was treatment group with glibenclamide (hyperglycemia-lowering medication).Results: In the treatment of P1, P2, P3, P4, and P5 groups, it can be seen that there are decreases of blood glucose and AGEs level between pre- and post-test comparison. However, the most significant drop in mean plasma glucose level was observed at the dosage 5.0 mg kg-1 (P4).Conclusion: The administration of Indonesian bay leaf extracts at a dose of 5.0 mg/kg body weight/day have an antidiabetic effect through decreasing blood glucose and AGEs level in alloxan-induced hyperglycemic Wistar rats.

scholarly journals MiR-92b-3p is Induced by Advanced Glycation End Products and Involved in the Pathogenesis of Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Wang ◽  
Jia-nan Geng ◽  
Bo Sun ◽  
Cheng-bo Sun ◽  
Yan Shi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Rat Kidney ◽  
Luciferase Reporter ◽  
Control Group ◽  
Age Group ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

Purpose. The current study aims to examine the effects of advanced glycation end products (AGEs) on the microRNA (miRNA) expression profile in the kidney tissues of rats. Methods. Wistar rats were randomly divided into three equal experiment groups: the AGE group, the RSA group, and the control group. The rats in the AGE group and the RSA group were administered with advanced glycation end products (AGEs) and rat serum albumin (RSA) via the tail vein, respectively, whereas the control group received PBS. Total RNA was prepared from the rat kidney tissues, and the miRNA expression profiles in different experiment groups were compared by microarray analysis. The expression levels of selected differential miRNAs were verified by RT-qPCR. Target gene prediction was conducted using algorithms such as TargetScan, miRanda, and PICTar. Functional analysis was performed to determine the putative biological roles of the validated miRNAs. Results. The microarray study revealed 451 upregulated and 320 downregulated miRNAs in the AGE group compared with the RSA group (p<0.05). Seven miRNAs, including miR-21-5p, miR-92b-3p, miR-140-3p, miR-196a-5p, miR-181b-5p, miR-186-5p, and miR-192-5p, were screened and verified using RT-qPCR, of which, the change of miR-92b-3p was the most obvious according to the miRNA expression different multiple and p value. Furthermore, the expression trend of miR-92b-3p measured by RT-qPCR was shown to be consistent with the microarray results. Bioinformatics analysis and luciferase reporter assay identified Smad7 was a direct target of miR-92b-3p. Both immunohistochemical and western blotting showed that Smad7 expression was significantly suppressed in the kidney tissues from the AGE group compared with the control and RSA groups. Conclusion. The results of the current study suggested that miR-92b-3p could mediate AGE-induced development of renal abnormalities through targeting Smad7 in rats with DN.

scholarly journals The Role and Mechanism of Exosomes from Umbilical Cord Mesenchymal Stem Cells in Inducing Osteogenesis and Preventing Osteoporosis

2021 ◽  
Vol 30 ◽  
pp. 096368972110574
Author(s):  
Ge Yahao ◽  
Wang Xinjia
Keyword(s):  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Umbilical Cord ◽  
Cell Counting ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Promoting Effect ◽  
Alizarin Red ◽  
Osteogenic Induction

Mesenchymal stem cell (MSC) exosomes promote tissue regeneration and repair, and thus might be used to treat many diseases; however, the influence of microenvironmental conditions on exosomes remains unclear. The present study aimed to analyze the effect of osteogenic induction on the functions of human umbilical cord MSC (HucMSC)-derived exosomes. Exosomes from standardized stem cell culture (Exo1) and osteogenic differentiation-exosomes (Exo2) were co-cultured with osteoblasts, separately. Cell counting kit-8 assays, alkaline phosphatase and alizarin red staining were used to observe the exosomes’ effects on osteoblast proliferation and differentiation. The levels of osteogenic differentiation-related proteins were analyzed using western blotting. Estrogen-deficient osteoporosis model mice were established, and treated with the two exosome preparations. Micro-computed tomography and hematoxylin and eosin staining were performed after 6 weeks. MicroRNAs in Exo1 and Exo2 were sequenced and analyzed using bioinformatic analyses. Compared with Exo1 group, Exo2 had a stronger osteogenic differentiation promoting effect, but a weaker proliferation promoting effect. In ovariectomy-induced osteoporosis mice, both Exo1 and Exo2 improved the tibial density and reversed osteoporosis in vivo. High-throughput microRNA sequencing identified 221 differentially expressed microRNAs in HucMSC-derived exosomes upon osteogenic induction as compared with the untreated control group. Importantly, we found that 41 of these microRNAs are potentially critical for MSC-secreted exosomes during osteogenic induction. Mechanistically, exosomal miRNAs derived from osteogenic induced-HucMSCs are involved in bone development and differentiation, such as osteoclast differentiation and the MAPK signaling pathway. The expression of hsa-mir-2110 and hsa-mir-328-3p gradually increased with prolonged osteogenic differentiation and regulated target genes associated with bone differentiation, suggesting that they are probably the most important osteogenesis regulatory microRNAs in exosomes. In conclusion, we examined the contribution of osteogenic induction to the function of exosomes secreted by HucMSCs following osteogenic differentiation in vitro and in vivo, and reveal the underlying molecular mechanisms of exosome action during osteoporosis.

scholarly journals Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm

2020 ◽  
Vol 9 (4) ◽  
pp. 927
Author(s):  
Willy Hauzer ◽  
Wojciech Witkiewicz ◽  
Jan Gnus
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Advanced Glycation End Products ◽  
Endovascular Aneurysm Repair ◽  
Control Group ◽  
Advanced Glycation ◽  
Abdominal Aortic ◽  
Potential Biomarker ◽  
Glycation End Products ◽  
End Products

Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm.

scholarly journals Cardioprotective effect of Volvariella volvacea in streptozotocin administered rats

2016 ◽  
Vol 11 (4) ◽  
pp. 903 ◽  
Author(s):  
Soosaimanickam Carmel Punitha ◽  
Muthu Rajasekaran
Keyword(s):  
Advanced Glycation End Products ◽  
Glycosylated Hemoglobin ◽  
Lipid Peroxides ◽  
Protein Carbonyls ◽  
Control Group ◽  
Volvariella Volvacea ◽  
Advanced Glycation ◽  
Group I ◽  
Glycation End Products ◽  
End Products

<p class="Abstract">The present study examined the cardioprotective role of methanol extract of the edible mushroom <em>Volvariella volvacea</em> against oxidative stress in hyperglycemic rats. Rats divided into 6 groups were administered with nicotinamide and streptozotocin intraperitoneally, except Group I (control). Group II served as diabetic control. Group III was given glibenclamide. Two groups (IV and V) of rats received (200 and 400 mg/kg) mushroom extracts orally for 30 days and Group VI received vitamin E (40 mg/kg). After the treatment period, lipid peroxides, carbonyl end products, advanced glycation end products, reduced glutathione, glutathione peroxidase, glutathione-S transferase, catalase, superoxide dismutase and non-enzymatic anti-oxidants (vitamin C and E) were assessed in the heart tissues of experimental animals. Glycosylated hemoglobin was estimated in blood. Electrocardiography recordings of the treated groups were also done. The results showed that mushroom extract treatment reduced the lipid peroxides, advanced glycation end products and protein carbonyls significantly and reversed the altered anti-oxidant enzymes, and the vitamins.</p><p class="Abstract"><strong>Video Clips</strong>:</p><p><a href="https://www.youtube.com/v/wn01m31-XhY">Hemolysate preparation</a>: 2 min 50 sec</p><p><a href="https://www.youtube.com/v/B0OLbU-NdEM">Mixing, glycosylated hemoglobin separation and reading absorbance</a>: 3 min 10 sec</p><p> </p>

scholarly journals Effect of allithiamine on the level of hyperglycaemia-induced advanced glycation end products

2019 ◽  
pp. 41-44
Author(s):  
Attila Bíró ◽  
Judit Remenyik
Keyword(s):  
Diabetes Mellitus ◽  
Advanced Glycation End Products ◽  
Tissue Injury ◽  
Enzymatic Digestion ◽  
Human Umbilical Cord ◽  
Advanced Glycation ◽  
Public Health Burden ◽  
Glycation End Products ◽  
End Products ◽  
Isolated Compound

Diabetes mellitus is a rapidly growing public health burden in both developed and developing countries. Diabetes mellitus is accompanied by hyperglycaemia, which can cause tissue injury by several mechanisms. One of these is the formation of advanced glycation end-products (AGEs). In this study, the effect of allithaimine, a fat-soluble thiamine derivative, was investigated on hyperglycaemia-induced AGEs levels using human umbilical cord vein endothelial cells (HUVECs) as a hyperglycaemic model. HUVECs were isolated by enzymatic digestion, characterized by flow cytometer and treated 30 mM glucose plus allithaimine or thiamine or cell maintenance medium as control.  Allithiamine was synthesized and purified. The structure of the synthesized and isolated compound was verified by reverse phase HPLC and MALDI-TOF. AGEs were evaluated by ELISA. Collectively, our results indicate that allithiamine can reduce level of the hyperglycaemia-induced AGEs similar to thiamine.

scholarly journals Role of Advanced Glycation End Products in Assessment of Diabetes Mellitus as a Risk Factor for Retinal Vein Occlusion

2021 ◽  
Vol 11 (17) ◽  
pp. 7934
Author(s):  
Karolina Kaźmierczak ◽  
Paweł Żuchowski ◽  
Katarzyna Łapińska-Duczmal ◽  
Katarzyna Zabel ◽  
Zofia Sikorska ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Retinal Vein Occlusion ◽  
Advanced Glycation End Products ◽  
Systemic Hypertension ◽  
Control Group ◽  
Skin Autofluorescence ◽  
Advanced Glycation ◽  
Vein Occlusion ◽  
Glycation End Products ◽  
End Products

Aim: In this study, we aimed to assess the correlation between diabetes mellitus (DM) and the retinal vein occlusion (RVO) based on skin autofluorescence (SAF) measurement, which reflects the accumulation of advanced glycation end products (AGE) in patients who have undergone an episode of central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Material and methods: In total, 23 patients (16 males, 7 females) with RVO were included in this study. Among these 23 participants, 12 (52%) had been diagnosed with CRVO and 11 (48%) with BRVO. The control group consisted of 14 healthy volunteers (11 females, 3 males). To calculate the risk of cardiovascular diseases (CVD) and DM, we conducted SAF examinations. We compared the SAF levels in three groups of patients: (1) with CRVO, (2) with BRVO, and (3) the control group. Basic demographic and clinical information and detailed history of the concurrent diagnoses of systemic diseases, such as systemic hypertension (HTN), DM, hyperlipidemia (HL), and heart diseases, were obtained. Results: In total, 10 (43.5%) patients were diagnosed with DM, 6 (55%) in the BRVO group and 4 (33%) in the CRVO group. The mean SAF value was significantly higher in the BRVO group than in the control group (2.64 a.u. and 2.35 a.u., respectively) (p = 0.023). More patients with risk of DM were identified in the CRVO group than in the BRVO group (p = 0.024). Conclusions: The advanced glycation end products (AGE) in the skin autofluorescence (SAF) is a viable method of evaluating the risk of DM in patients with RVO. We confirmed a correlation between RVO and DM, which was significantly pronounced in the CRVO form, although further carefully devised studies on the relationship between RVO and DM with a larger number of responders should be conducted in the future.

Influence of Icodextrin on Plasma and Dialysate Levels of N∊-(Carboxymethyl)Lysine and N∊-(Carboxyethyl)Lysine

2005 ◽  
Vol 25 (6) ◽  
pp. 591-595 ◽  
Author(s):  
Constantijn J. Konings ◽  
Casper G. Schalkwijk ◽  
Frank M. van der Sande ◽  
Karel M. Leunissen ◽  
Jeroen P. Kooman
Keyword(s):  
Mass Spectrometry ◽  
Stable Isotope ◽  
Tandem Mass Spectrometry ◽  
Control Group ◽  
Tandem Mass ◽  
Advanced Glycation ◽  
Stable Isotope Dilution ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

Rationale Standard peritoneal glucose solutions may induce the formation of advanced glycation end products (AGEs). Preliminary data suggest that AGE formation may be less with the use of polyglucose solutions (icodextrin). Therefore, we investigated whether the use of icodextrin for the long dwell would result in a reduction in plasma and dialysate levels of the AGE products N∊-(carboxymethyl) lysine (CML) and N∊-(carboxyethyl)lysine (CEL). Patients and Methods 40 patients were randomized to treatment with standard glucose solutions (1.36%) and icodextrin for the long dwell during a 4-month study period; 32 patients completed the study. CML was assessed by stable isotope dilution/tandem mass spectrometry. Results CML levels in plasma increased significantly in patients treated with icodextrin (0.146 ± 0.056 at start vs 0.188 ± 0.069 μmol/mmol Lys at the end of the study, p < 0.0001) but did not change in the control group (0.183 ± 0.090 vs 0.188 ± 0.085 μmol/mmol Lys). The same held true for CML levels in dialysate (0.28 ± 0.09 at start vs 0.33 ± 0.11 μmol/mmol Lys at the end of the study, p < 0.025). No change was observed in patients treated with the control solutions (0.31 ± 0.11 at start vs 0.31 ± 0.07 μmol/mmol Lys). Conclusion Contrary to the hypothesis, plasma and dialysate levels of CML increased in patients treated using icodextrin for the long dwell.

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