scholarly journals A Novel Microfluidic Device for the Neutrophil Functional Phenotype Analysis: Effects of Glucose and Its Derivatives AGEs

Micromachines ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 944
Author(s):  
Ke Yang ◽  
Xiao Yang ◽  
Chaoru Gao ◽  
Changyi Hua ◽  
Chenggang Hong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Microfluidic Device ◽  
Normal Serum ◽  
Neutrophil Chemotaxis ◽  
Negative Effects ◽  
Patients With Diabetes ◽  
Phenotype Analysis ◽  
High Concentrations ◽  
Functional Phenotype

Neutrophil dysfunction is closely related to the pathophysiology of patients with diabetes mellitus, but existing immunoassays are difficult to implement in clinical applications, and neutrophil’s chemotaxis as a functional biomarker for diabetes mellitus prognostic remains largely unexplored. Herein, a novel microfluidic device consisted of four independent test units with four cell docking structures was developed to study the neutrophil chemotaxis, which allowed multiple cell migration observations under a single field of view (FOV) and guaranteed more reliable results. In vitro studies, the chemotaxis of healthy neutrophils to N-Formyl-Met-Leu-Phe (fMLP) gradient (0, 10, 100, and 1000 nM) was concentration-dependent. The distinct promotion or suppression in the chemotaxis of metformin or pravastatin pretreated cells were observed after exposure to 100 nM fMLP gradient, indicating the feasibility and efficiency of this novel microfluidic device for clinically relevant evaluation of neutrophil functional phenotype. Further, the chemotaxis of neutrophils pretreated with 25, 50, or 70 mM of glucose was quantitatively lower than that of the control groups (i.e., 5 mM normal serum level). Neutrophils exposed to highly concentrated advanced glycation end products (AGEs) (0.2, 0.5, or 1.0 μM; 0.13 μM normal serum AGEs level), a product of prolonged hyperglycemia, showed that the higher the AGEs concentration was, the weaker the migration speed became. Specifically, neutrophils exposed to high concentrations of glucose or AGEs also showed a stronger drifting along with the flow, further demonstrating the change of neutrophil chemotaxis. Interestingly, adding the N-benzyl-4-chloro-N-cyclohexylbenzamide (FPS-ZM1) (i.e., high-affinity RAGE inhibitor) into the migration medium with AGEs could hinder the binding between AGEs and AGE receptor (RAGE) located on the neutrophil, thereby keeping the normal chemotaxis of neutrophils than the ones incubated with AGEs alone. These results revealed the negative effects of high concentrations of glucose and AGEs on the neutrophil chemotaxis, suggesting that patients with diabetes should manage serum AGEs and also pay attention to blood glucose indexes. Overall, this novel microfluidic device could significantly characterize the chemotaxis of neutrophils and have the potential to be further improved into a tool for risk stratification of diabetes mellitus.

INTERRELATION OF HEMORHEOLOGICAL PARAMETERS WITH GLUCOSE AND GLYCATED HEMOGLOBIN IN PATIENTS WITH DIABETES MELLITUS TYPE2

2018 ◽  
Author(s):  
А.В. Муравьев ◽  
И.А. Тихомирова ◽  
С.В. Булаева ◽  
Ю.В. Малышева ◽  
А.В. Замышляев
Keyword(s):  
Diabetes Mellitus ◽  
Glycated Hemoglobin ◽  
Healthy Individuals ◽  
Glucose Content ◽  
Metabolic Hormones ◽  
Metabolism Regulation ◽  
Patients With Diabetes ◽  
Glycated Hemoglobin Level ◽  
Blood Transport

Введение. Нарушения реологических свойств крови при сахарном диабете 2 типа (СД-2) может приводить к снижению микрососудистой перфузии. Основной механизм, вероятно, связан с ухудшением микрореологии эритроцитов, в том числе из-за высокого содержания глюкозы и гликозилирования белков мембран клеток. Цель исследования: провести анализ связи гемореологических характеристик цельной крови и эритроцитов с содержанием глюкозы и гликированного гемоглобина и выявить влияние ряда метаболических гормонов на микрореологию эритроцитов у больных СД-2. Материалы и методы. У 30 больных СД-2 регистрировали параметры гемореологического профиля. Наряду с измерениями вязкости, деформируемости эритроцитов (ДЭ) и их агрегации (АЭ) определяли содержание глюкозы, гликированного гемоглобина и белков плазмы (альбуминов, глобулинов, фибриногена). В in vitro исследованиях регистрировали микрореологические характеристики эритроцитов после их инкубации с глюкозой и рядом метаболических гормонов (инсулином, глюкагоном, адреналином). Результаты. Наиболее существенные отличия гемореологических профилей у больных СД-2 от данных здоровых лиц были в их микрореологической части. Значения глюкозы и гликированного гемоглобина более выражено коррелировали с показателями гемореологического профиля у больных СД-2, чем у здоровых лиц: коэффициент корреляции между АЭ и концентраций глюкозы у больных СД-2 составил 0,660, в контрольной группе — 0,480. Под влиянием инсулина ДЭ достоверно повышалась, а АЭ, напротив, снижалась (p < 0,05). При инкубации эритроцитов с глюкагоном у больных СД-2 и у здоровых лиц АЭ была снижена на сходную величину. Адреналин в трех концентрациях умеренно повышал ДЭ (p < 0,05), а наблюдавшийся прирост АЭ был наибольшим при низкой концентрации гормона (0,01 мкМ). Заключение. Анализ параметров гемореологического профиля у больных СД-2 свидетельствует о нарушениях текучести крови и снижении ее транспортных возможностей. Также было показано, что гормоны, участвующие в регуляции метаболизма, оказывают прямое воздействие на микрореологию эритроцитов. Introduction. Disorders of blood rheological properties in diabetes mellitus type 2 (DM-2) can lead to reduction of microvascular perfusion. The main mechanism is probably associated with impairment of erythrocytes microrheology and also due to high glucose content and glycosylation of cell membrane proteins. Aim: to analyze the relationship between hemorheological characteristics of whole blood and erythrocytes with glucose content and glycated hemoglobin level, and to reveal the infl uence of metabolic hormones on erythrocytes microrheology in patients with DM-2. Materials and methods. In 30 patients with DM-2 we determined hemorheological parameters, blood viscosity, erythrocytes deformability (ED), erythrocytes aggregation (EA), glucose and glycated hemoglobin content, plasma proteins (albumins, globulins, fibrinogen) levels. In in vitro studies we recorded the microrheological characteristics of erythrocytes after their incubation with glucose and with some metabolic hormones (insulin, glucagon, adrenaline). Results. Microrheological parameters in patients with DM-2 diff ered signifi cantly from the parameters in healthy individuals. Glucose and glycated hemoglobin values more evidently correlated with hemorheological parameters in patients with DM-2 than in healthy individuals: the correlation coeffi cient between EA and glucose concentration in patients with DM-2 was 0.660, in healthy individuals — 0.480. Under insulin stimulus ED signifi cantly increased and AE, on contrary, decreased (p < 0.05). During erythrocytes incubation with glucagon EA similar reduced in patients with DM-2 and in healthy individuals. Adrenaline in three concentrations moderately increased ED (p < 0.05), and the observed EA increasing was greatest at low hormone concentration (0.01 μM). Conclusion. Analysis of hemorheological parameters in patients with DM-2 showed disorders of blood fl uidity and decreasing of blood transport capacity. It was also shown that hormones involved in metabolism regulation had a direct effect on erythrocytes microrheology.

scholarly journals The Functionality of Endothelial-Colony-Forming Cells from Patients with Diabetes Mellitus

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1731
Author(s):  
Caomhán J. Lyons ◽  
Timothy O'Brien
Keyword(s):  
Diabetes Mellitus ◽  
Cell Therapy ◽  
Diabetic Patients ◽  
Angiogenic Potential ◽  
Endothelial Colony Forming Cells ◽  
Allogeneic Cell Therapy ◽  
Patients With Diabetes ◽  
Pre Treatment

Endothelial-colony-forming cells (ECFCs) are a population of progenitor cells which have demonstrated promising angiogenic potential both in vitro and in vivo. However, ECFCs from diabetic patients have been shown to be dysfunctional compared to ECFCs from healthy donors. Diabetes mellitus itself presents with many vascular co-morbidities and it has been hypothesized that ECFCs may be a potential cell therapy option to promote revascularisation in these disorders. While an allogeneic cell therapy approach would offer the potential of an ‘off the shelf’ therapeutic product, to date little research has been carried out on umbilical cord-ECFCs in diabetic models. Alternatively, autologous cell therapy using peripheral blood-ECFCs allows the development of a personalised therapeutic approach to medicine; however, autologous diabetic ECFCs are dysfunctional and need to be repaired so they can effectively treat diabetic co-morbidities. Many different groups have modified autologous diabetic ECFCs to improve their function using a variety of methods including pre-treatment with different factors or with genetic modification. While the in vitro and in vivo data from the literature is promising, no ECFC therapy has proceeded to clinical trials to date, indicating that more research is needed for a potential ECFC therapy in the future to treat diabetic complications.

scholarly journals Health Properties and Composition of Honeysuckle Berry Lonicera caerulea L. An Update on Recent Studies

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 749 ◽  
Author(s):  
Gołba ◽  
Sokół-Łętowska ◽  
Kucharska
Keyword(s):  
Diabetes Mellitus ◽  
European Union ◽  
Antioxidant Activity ◽  
Eastern Europe ◽  
Traditional Food ◽  
Negative Effects ◽  
Lonicera Caerulea ◽  
Potential Benefits ◽  
Hydroxybenzoic Acids ◽  
High Concentrations

Lonicera caerulea L., also known as haskap or honeysuckle berry, is a fruit commonly planted in eastern Europe, Canada and Asia. The fruit was registered as a traditional food from a third country under European Union regulations only on December 2018. It is resistant to cold, pests, various soil acidities and diseases. However, its attractiveness is associated mostly with its health properties. The fruit shows anticancer, anti-inflammatory, and antioxidant activity—important factors in improving health. These features result from the diverse content of phytochemicals in honeysuckle berries with high concentrations of phytocompounds, mainly hydroxycinnamic acids, hydroxybenzoic acids, flavanols, flavones, isoflavones, flavonols, flavanones and anthocyanins but also iridoids, present in the fruit in exceptional amounts. The content and health properties of the fruit were identified to be dependent on cultivar, genotype and the place of harvesting. Great potential benefits of this nutritious food are its ability to minimize the negative effects of UV radiation, diabetes mellitus and neurodegenerative diseases, and to exert hepato- and cardioprotective activity.

scholarly journals Analysis of protein glycation in human fingernail clippings with near-infrared (NIR) spectroscopy as an alternative technique for the diagnosis of diabetes mellitus

2018 ◽  
Vol 56 (9) ◽  
pp. 1551-1558 ◽  
Author(s):  
Tinne Monteyne ◽  
Renaat Coopman ◽  
Antoine S. Kishabongo ◽  
Jonas Himpe ◽  
Bruno Lapauw ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Healthy Subjects ◽  
Near Infrared ◽  
Nir Spectroscopy ◽  
Partial Least Square ◽  
Least Square ◽  
Protein Glycation ◽  
Patients With Diabetes ◽  
Diagnosis Of Diabetes Mellitus

Abstract Background: Glycated keratin allows the monitoring of average tissue glucose exposure over previous weeks. In the present study, we wanted to explore if near-infrared (NIR) spectroscopy could be used as a non-invasive diagnostic tool for assessing glycation in diabetes mellitus. Methods: A total of 52 patients with diabetes mellitus and 107 healthy subjects were enrolled in this study. A limited number (n=21) of nails of healthy subjects were glycated in vitro with 0.278 mol/L, 0.556 mol/L and 0.833 mol/L glucose solution to study the effect of glucose on the nail spectrum. Consequently, the nail clippings of the patients were analyzed using a Thermo Fisher Antaris II Near-IR Analyzer Spectrometer and near infrared (NIR) chemical imaging. Spectral classification (patients with diabetes mellitus vs. healthy subjects) was performed using partial least square discriminant analysis (PLS-DA). Results: In vitro glycation resulted in peak sharpening between 4300 and 4400 cm−1 and spectral variations at 5270 cm−1 and between 6600 and 7500 cm−1. Similar regions encountered spectral deviations during analysis of the patients’ nails. Optimization of the spectral collection parameters was necessary in order to distinguish a large dataset. Spectra had to be collected at 16 cm−1, 128 scans, region 4000–7500 cm−1. Using standard normal variate, Savitsky-Golay smoothing (7 points) and first derivative preprocessing allowed for the prediction of the test set with 100% correct assignments utilizing a PLS-DA model. Conclusions: Analysis of protein glycation in human fingernail clippings with NIR spectroscopy could be an alternative affordable technique for the diagnosis of diabetes mellitus.

scholarly journals Assessment of Absorption of Glycated Nail Proteins in Patients with Diabetes Mellitus and Diabetic Retinopathy

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 658
Author(s):  
Ieva Jurgeleviciene ◽  
Daiva Stanislovaitiene ◽  
Vacis Tatarunas ◽  
Marius Jurgelevicius ◽  
Dalia Zaliuniene
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Ftir Spectroscopy ◽  
Region Of Interest ◽  
Control Group ◽  
Before And After ◽  
Patients With Diabetes ◽  
Long Term Observation

Background and objectives: Glycation occurs in a variety of human tissues and organs. Knowledge about the relationship between predictive biochemical factors such as absorption of glycated nail proteins and severity of type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) remains limited. Materials and Methods: The study group consisted of patients with type 2 DM and DR (n = 32) and a control group (n = 28). Each patient underwent a comprehensive ophthalmic examination. The glycation process in nail clippings was evaluated in stages of in vitro glycation and deglycation stages. ATR–FTIR spectroscopy was used to calculate the infrared absorption in the region of interest. The absorption of solutions with nail clippings was evaluated by NanoDrop spectrophotometry. Absorption spectra differences before and after the exposure to fructosamine 3-kinase were compared between DM patients with DR and the control group. Results: The absorption of glycated nail protein greater than 83.00% increased the chance of developing DM and DR (OR = 15.909, 95% CI 3.914–64.660, p < 0.001). Absorption of glycated nail protein by ATR–FTIR spectroscopy in patients with DM and DR in vitro glycation was statistically significantly higher than in the control group; also absorption of solution with nails by NanoDrop spectroscopy was statistically significantly higher than in controls in vitro glycation and in vitro deglycation. After exposure to fructosamine 3-kinase, absorption of nail protein in DM + severe/proliferative DR group was statistically significantly lower in comparison with DM + mild/moderate group DR. Conclusions: Evaluation of glycated nail protein could be applied to evaluate the risk of having DM and for long-term observation of DM control.

scholarly journals Cost and Scalability Analysis of Porcine Islet Isolation for Islet Transplantation: Comparison of Juvenile, Neonatal and Adult Pigs

2019 ◽  
Vol 28 (7) ◽  
pp. 967-972 ◽  
Author(s):  
Rachel Vanderschelden ◽  
Mayilone Sathialingam ◽  
Michael Alexander ◽  
Jonathan R. T. Lakey
Keyword(s):  
Diabetes Mellitus ◽  
Cost Effective ◽  
Human Islets ◽  
High Price ◽  
Porcine Islets ◽  
In Vivo Experiments ◽  
Porcine Islet ◽  
Patients With Diabetes

The limited availability of human islets has led to the examination of porcine islets as a source of clinically suitable tissue for transplantation in patients with diabetes mellitus. Islets from porcine donors are commonly used in both in vitro and in vivo experiments studying diabetes mellitus. However, there are significant differences in quality and quantity of islet yield depending on donor pig age, as well as substantial differences in the costs of pancreas procurement in adult versus neonatal and juvenile pigs. In this study, we compared the total cost per islet of juvenile pig pancreata with that of neonatal and adult pigs. Although adult porcine pancreata yield, on average, more than five times the amount of islets than do juvenile and neonatal pancreata, we found that the high price of adult pigs led to the cost per islet being more than twice that of juvenile and neonatal islets (US $0.09 vs $0.04 and $0.02, respectively). In addition, neonatal and juvenile islets are advantageous in their scalability and retention of viability after culture. Our findings indicate that isolating neonatal and juvenile porcine islets is more cost-effective and scalable than isolating adult porcine islets.

scholarly journals Function Analysis of Choline Binding Domains of LytA, LytC and CbpD in The Biofilm Formation Process of Streptococcus Pneumoniae

2021 ◽  
Author(s):  
Hongsheng Ji ◽  
Yingshun Zhou ◽  
Luhua Zhang ◽  
Ying Wang ◽  
Feiyang Zhang ◽  
...  
Keyword(s):  
Membrane Transport ◽  
Biofilm Formation ◽  
Function Analysis ◽  
Amino Sugar ◽  
Extracellular Dna ◽  
Transport Pathways ◽  
Binding Domains ◽  
Phenotype Analysis ◽  
High Concentrations

Abstract Background: Choline binding proteins (CBPs) are a family of proteins that can interact with pneumococcal cell wall by choline binding domains (CBDs). In this study, we found a modified choline binding repeat (ChBp-I) with a pI of 7.66 can promote the development of biofilm in vitro. Thus, we aim to characterize the function of CBDs of LytA, LytC and CbpD in biofilm formation.Results: By transcriptome analysis, 81 genes were identified as down regulated and 138 genes were up regulated (|log2 fold change|≥1.5) under ChBp-I of 50mg/L. The up regulated genes are well clustered in membrane transport (carbohydrate, lipid, protein, cation and phosphate) and carbohydrate metabolism (fructose, mannose, galactose, starch, sucrose, amino sugar and nucleotide) related pathways. The up-regulated genes are mostly regulated the same under CBD-A, CBD-C and CBD-D. Phenotype analysis reveal high concentrations of CBD-C and CBD-D (>100μg/mL) but not CBD-A (negative charged) can promote the biofilm formation. Meanwhile, the existence of CBD-C and CBD-D promote the growth rate and both CBDs inhibit the autolysis of pneumococcal cell. By component analysis, these three CBDs were proved involved in the regulation of extracellular DNA, protein, cation and phosphate, and promote the forming of insoluble precipitates.Conclusions: The binding of CBPs can influence the membrane transport pathways and react with extracellular DNA and protein to promote biofilm formation in S. pneumoniae.

scholarly journals Are Supplements Safe? Effects of Gallic and Ferulic Acids on In Vitro Cell Models

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1591 ◽  
Author(s):  
Francesca Truzzi ◽  
Maria Chiara Valerii ◽  
Camilla Tibaldi ◽  
Yanxin Zhang ◽  
Veronika Abduazizova ◽  
...  
Keyword(s):  
Biological Activities ◽  
Intestinal Wall ◽  
Cell Models ◽  
Negative Effects ◽  
Mucosal Layer ◽  
Health Promoting ◽  
High Concentrations ◽  
And Migration ◽  
Ferulic Acids

Polyphenols display health-promoting properties linked to their biological activities. They are initially absorbed in the small intestine, then they are largely metabolized in the colon, whereupon they are able to exert systemic effects. The health-promoting properties of polyphenols have led to the development of food supplements, which are also largely consumed by healthy people, even if data on their safety are still yet lacking. In the present paper, the content of gallic acid and ferulic acid was analyzed in two supplements, and shown to be higher than the relative contents found in fruit and flour. To evaluate the effects of these phenolic compounds on epithelial intestinal tissue, gallic and ferulic acids were added to a new in vitro model of the intestinal wall at different concentrations. The effects on viability, proliferation and migration of these compounds were respectively tested on three different cell lines (Caco2, L929 and U937), as well as on a tridimensional intestinal model, composed of a mucosal layer and a submucosa with fibroblasts and monocytes. Results indicated that gallic and ferulic acids can exert toxic effects on in vitro cell models at high concentrations, suggesting that an excessive and uncontrolled consumption of polyphenols may induce negative effects on the intestinal wall.

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