scholarly journals Angiogenic properties of human endothelial colony-forming cells in Granulomatosis with Polyangiitis

2020 ◽  
Author(s):  
Ana Paula Toledo Del Rio ◽  
Stephanie Ospina Prieto ◽  
Jessica Oliveira Frade ◽  
Bruno Lino Kosa Duarte ◽  
Manoel Barros Bertolo ◽  
...  

Abstract BACKGROUND Endothelial progenitor cells are essential for vascular homeostasis. Considering the recurrent nature of granulomatosis with polyangiitis (GPA) the aim of the study was to evaluate the angiogenic capacity of endothelial colony-forming cells (ECFC), which have the capacity for neovasculogenesis in vitro, of the patients with GPA, before and after plasma stimulation. METHODS Thirteen GPA PR3-positive patients and 15 healthy controls were included. ECFC were isolated from periferic blood and characterized by flow cytometry (FACS). Capillary tube formation (Matrigel assay) and scratching assay were measured during 24 hours. The migration assay was also performed after overnight incubation with healthy control plasma and active GPA patient plasma. Three patients with active disease where submitted to recollection of ECFC after treatment for longitudinal evaluation. RESULTS The culture was successful in 62% of GPA patients and 57% of controls. In the matrigel assay the ECFC from patients and controls showed similar capillary structures formation, however ECFC from inactive GPA alone showed early loss of angiogenic capacity between 15 and 24 hours. In scratching assay, there was an impairment in the proliferative capacity of the ECFC between GPA patients and controls without significant difference (12th hour, p = 0.05). When incubated with control plasma, ECFC of remission GPA patients showed a significant lower migration capacity after the 4th hour (p = 0.0001). In longitudinal analysis, ECFC isolated after treatment showed significantly lower migration rates. CONCLUSIONS PR3-positive remission GPA ECFC demonstrated early loss of tube formation and less proliferative capacity compared to those of healthy controls, suggesting impairment of endothelial function.

2018 ◽  
Vol 129 (5) ◽  
pp. 1151-1159 ◽  
Author(s):  
Jung Won Choi ◽  
Sung Min Son ◽  
Inhee Mook-Jung ◽  
Youn Joo Moon ◽  
Ji Yeoun Lee ◽  
...  

OBJECTIVEMoyamoya disease (MMD) is a unique cerebrovascular disorder characterized by the progressive occlusion of the bilateral internal carotid arteries. Endothelial colony-forming cells (ECFCs), previously termed “endothelial progenitor cells,” play an important role in the pathogenesis of MMD. In this study, the authors performed morphological and functional studies of the mitochondria of ECFCs from patients with MMD to present new insights into the pathogenesis of the disease.METHODSThe morphology of ECFCs from 5 MMD patients and 5 healthy controls was examined under both a transmission electron microscope and a confocal laser scanning microscope. The oxygen consumption rates (OCRs), mitochondrial membrane potentials (MMPs), intracellular Ca2+ concentrations, mitochondrial enzyme activities, and reactive oxygen species (ROS) levels were measured. Functional activity of the ECFCs was evaluated using a capillary tube formation assay.RESULTSThe ECFCs from the MMD patients displayed a disrupted mitochondrial morphology, including a shorter and more circular shape. The ECFC mitochondria from the MMD patients exhibited functional abnormalities, which were assessed as a decreased OCR and an increased intracellular Ca2+ concentration. Moreover, the ECFCs from MMD patients showed increased ROS levels. Interestingly, treatment with an ROS scavenger not only reversed the mitochondrial abnormalities but also restored the angiogenic activity of the ECFCs from the MMD patients.CONCLUSIONSThe mitochondria of ECFCs from MMD patients, as compared with those from healthy patients, exhibited morphological and functional abnormalities. This finding suggests that the mitochondrial abnormalities may have a role in the pathogenesis of MMD.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared


Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pasquale Loiudice ◽  
Marco Pellegrini ◽  
Michele Marinò ◽  
Barbara Mazzi ◽  
Ilaria Ionni ◽  
...  

Abstract Background Hemodynamic changes have been observed in patients with Graves’ disease. The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index (CVI) in patients with thyroid-associated ophthalmopathy (TAO). Methods In this cross-sectional observational study, 40 patients affected by TAO were recruited. Forty healthy individuals, matched for age and sex, served as controls. Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants. Images were binarized using the ImageJ software and luminal area (LA) and total choroidal area (TCA) were measured. CVI was calculated as the proportion of LA to TCA. The relation between CVI or subfoveal choroidal thickness (SFCT) and clinical activity score, exophthalmometric value, diplopia status, gender, and age was evaluated. Results CVI was significantly higher in patients with TAO (P = 0.004). No significant difference was observed in SFCT (P = 0.200) and TCA (P = 0.153) comparing TAO patients and healthy controls. LA was significantly higher in TAO group (P = 0.045). On multiple regression analysis, CVI was associated with TCA (P = 0.043). No association was found between SFCT or CVI and TCA, clinical activity score, exophthalmometric value, Inami value, diplopia status, gender or age (P > 0.05). Conclusions This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.


2021 ◽  
pp. 1-5
Author(s):  
Mahdi Ramezani ◽  
Alireza Komaki ◽  
Mohammad Mahdi Eftekharian ◽  
Mehrdokht Mazdeh ◽  
Soudeh Ghafouri-Fard

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.


Author(s):  
Mahir Tıraş ◽  
Emrah Can ◽  
Şahin Hamilçıkan

Objective This study aimed to assess whether cord blood carboxyhemoglobin (COHb) levels in jaundiced term neonates with and without a positive direct Coombs test (DCT) and in healthy controls could be used as a predictor of severe hyperbilirubinemia. The percentage of cord blood COHb should be higher among neonates with Coombs-positive ABO hemolytic disease than among those with Coombs-negative ABO incompatibility and higher than that of ABO-compatible control neonates. Study Design This cross-sectional descriptive study of 198 term neonates comprised three subgroups: group I featured 68 DCT-positive ABO-incompatible neonates (ABO + DCT), group II featured 60 DCT-negative ABO-incompatible neonates with hyperbilirubinemia (ABO–DCT), and group III featured 70 healthy controls. COHb was determined by an OSM3 hemoximeter. Results Group I differed from groups II and III for cord blood bilirubin, cord blood hemoglobin, and cord blood hematocrit. Groups I and II had higher mean total serum bilirubin (TSB) levels than group III, while there was no difference in the mean TSB levels between groups I and II. There was no significant difference between the COHb group means for groups I, II, and III (p = 0.98). The area under the receiver operating characteristic curve calculated for group I/group III and group II/group III were found to be 0.62 and 0.54, respectively. Conclusion COHb levels did not prove to be superior to the DCT for predicting the risk of developing severe hyperbilirubinemia in term neonates. Key Points


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Li ◽  
Fengyan Zhang ◽  
Lu Wang ◽  
Yifan Zhang ◽  
Tingting Yang ◽  
...  

Abstract Objective Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. Methods We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson’s correlation revealed the relationship among total score of DM and clinical and neuropsychological data. Results Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. Conclusions Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Sasikarn Looprasertkul ◽  
Amornpun Sereemaspun ◽  
Nakarin Kitkumthorn ◽  
Kanidta Sooklert ◽  
Tewarit Sarachana ◽  
...  

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-β (PDGFR-β) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-β mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-β mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.


2020 ◽  
Vol 36 (1) ◽  
Author(s):  
Doaa Elmoazen ◽  
Hesham Kozou ◽  
Jaidaa Mekky ◽  
Dalia Ghanem

Abstract Background Patients suffering from vestibular migraine (VM) are known to have various vestibular test abnormalities interictally and ictally. Recently, vestibular evoked myogenic potentials (VEMPs) have become accepted as a valid method for otolith function assessment. Many studies have identified various vestibular symptoms and laboratory abnormalities in migraineurs. Since migraineurs with no accompanying vestibular symptoms might exhibit subclinical vestibular dysfunction, we investigated vestibular function using ocular and cervical VEMPs in migraine patients. The aim was to study cervical VEMP and occular VEMP in migraineurs with and without vestibular symptoms interictally. Results Migraine and VM patients showed significantly longer P13 latency of cVEMP compared to controls. A statistically significant cVEMP interaural P13 latency difference was found in VM compared to healthy controls. Cervical VEMP N23 latency, peak-to-peak amplitude, interaural N23 latency, and amplitude asymmetric ratio did not show any significant difference in migraine and VM patients compared to healthy controls as well as no significant difference across the three groups regarding oVEMP parameters. Conclusions Abnormal interictal cVEMP results in migraineurs might indicate subclinical vestibulo-collic pathway dysfunction.


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