Atherosclerosis is a chronic inflammatory disease that is promoted, among others, by pro-inflammatory cytokines such as IL-1β and IL-18 produced by NLRP 3 inflammasome. Development of atherosclerotic ...lesions is also affected by leptin. Furthermore, inflammasome's action is interfered with other inflammatory diseases, like diabetes. On the other hand, colchicine is reported to act as anti-inflammatory agent inhibiting inflammasome's action and stabilizing atherosclerotic lesions. The purpose of this study is to investigate the effect of per os colchicine on the de novo formation of atherosclerotic lesions and on the levels of IL-18, leptin and insulin in cholesterol-fed rabbits.
Twenty-three male, 2 months old New Zealand White rabbits, were seperated in 3 groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w and cholesterol 1% w/w plus colchicine 2 mg/kg body weight. Blood was collected for biochemical measurements and conduction of ELISA for leptin, IL-18 and insulin. Histologic examination of stained with eosin and hematoxylin aorta specimens was performed. Aortic intimal thickness was evaluated using image analysis. The statistical analysis included non-parametric tests: a) paired-sample Wilcoxon test, b) Spearman correlation coefficient and c) Kruscal-Wallis test.
Triglerycide levels were decreased in cholesterol plus colchicine group in the end of the experiment (p < 0.05), whereas the cholesterol group had increased levels. No statistical differences were observed in the levels of IL-18, leptin and insulin between groups. Likewise, there was neither any correlation between IL-18, leptin and intima thickness nor between IL-18 and glucose and between leptin and weight. In cholesterol and colchicine group there was a strong positive correlation between IL-18 and insulin levels in the 4th week (r
= .66, n = 10, p < 0.05), whereas in the 7th week this correlation became strong negative (r
= -.86, n = 10, p < 0.05). Finally, intima thickness in the ascending and thoracic aorta of the cholesterol and colchicine group was significantly greater than that of the other groups (p < 0.05).
Per os administration of colchicine did not influence atherosclerosis progression in cholesterol-fed rabbits, levels of IL-18, insulin and leptin. We encountered the attenuating role of colchicine on TG levels.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abdominal aortic aneurysm (AAA) formation is associated with by inflammation and matrix degradation. This study tested the hypothesis that calprotectin, a novel biomarker for inflammation, as well as ...established biomarkers such as C-reactive protein (CRP) and matrix metalloproteinase- 9 (MMP-9) could also be indicative inflammatory biomarkers during AAA pathogenesis and progression. We also evaluated the correlation of serum soluble Receptor for Advanced Glycation End Products (sRAGE) with AAA diameter and serum calprotectin levels.
Rat abdominal aortas were perfused with porcine pancreatic elastase (AAA Group) or saline (Control Group) and studied on post-perfusion days 7 and 14 (n=11 per treatment group). Aneurysm was defined as a dilatation of the aorta above 150% of its original diameter. Laparotomy was performed on days 0 (T0), 7 (T7) and 14 (T14) for aortic diameter measurement. At the same time intervals, we measured the serum levels of calprotectin, CRP, sRAGE and MMP-9.
All animals developed AAA and no rupture occurred. MMP-9 in AAA group at T14 (p<0.05 compared with T7 and p<0.005 compared with T0) and calprotectin in AAA group at T14 (p<0.001 compared with T7 and T0) continued to significantly increase at all times. Serum sRAGE was significantly lower in the AAA group compared with the control group and within AAA group at all time points (p<0.001). On the other hand, the highest levels of CRP were identified at T7 in both groups. Calprotectin concentrations in AAA group were significantly higher compared with controls at T7 and T14 (p<0.001 and p<0.001, respectively). Aortic diameter was significantly correlated with MMP-9 and calprotectin serum concentrations at all time points (r=0.51, p<0.001; r=0.728, p<0.001 respectively). Serum sRAGE levels were significantly correlated with aortic diameter at all time points (r=-0.48, p<0.001) and serum calprotectin levels (r=-0.22, p<0.001).
This is the first evaluation of calprotectin as an AAA inflammation biomarker. It seems to be a promising marker related to AAA natural history. Further experimental and large human studies are needed to fully elucidate the role of calprotectin in the development and progression of AAAs.
MicroRNAs (miRNAs) are key regulators of diverse biological processes and their functional analysis has been deemed central in many research pipelines. The new version of DIANA-miRPath web server was ...redesigned from the ground-up. The user of DNA Intelligent Analysis (DIANA) DIANA-miRPath v2.0 can now utilize miRNA targets predicted with high accuracy based on DIANA-microT-CDS and/or experimentally verified targets from TarBase v6; combine results with merging and meta-analysis algorithms; perform hierarchical clustering of miRNAs and pathways based on their interaction levels; as well as elaborate sophisticated visualizations, such as dendrograms or miRNA versus pathway heat maps, from an intuitive and easy to use web interface. New modules enable DIANA-miRPath server to provide information regarding pathogenic single nucleotide polymorphisms (SNPs) in miRNA target sites (SNPs module) or to annotate all the predicted and experimentally validated miRNA targets in a selected molecular pathway (Reverse Search module). DIANA-miRPath v2.0 is an efficient and yet easy to use tool that can be incorporated successfully into miRNA-related analysis pipelines. It provides for the first time a series of highly specific tools for miRNA-targeted pathway analysis via a web interface and can be accessed at http://www.microrna.gr/miRPathv2.
A numerical study is presented of unsteady two-dimensional natural convection of an electrically conducting fluid in a laterally and volumetrically heated square cavity under the influence of a ...magnetic field. The flow is characterized by the external Rayleigh number,
Ra
E, determined from the temperature difference of the side walls, the internal Rayleigh number,
Ra
I, determined from the volumetric heat rate, and the Hartmann number,
Ha, determined from the strength of the imposed magnetic field. Starting from given values of
Ra
E and
Ha, for which the flow has a steady unicellular pattern, and gradually increasing the ratio
S
=
Ra
I/
Ra
E, oscillatory convective flow may occur. The initial steady unicellular flow for
S
=
0 may undergo transition to steady or unsteady multicellular flow up to a threshold value,
Ra
I,cr, of the internal Rayleigh number depending on
Ha. Oscillatory multicellular flow fields were observed for
S values up to 100 for the range 10
5–10
6 of
Ra
E studied. The increase of the ratio
S results usually in a transition from steady to unsteady flow but there have also been cases where the increase of
S results in an inverse transition from unsteady to steady flow. Moreover, the usual damping effect of increasing Hartmann number is not found to be straightforward connected with the resulting flow patterns in the present flow configuration.
A series of numerical simulations were performed in order to study liquid metal MHD natural convection in a vertical cylindrical container with a sinusoidal temperature distribution at the upper wall ...and the other surfaces being adiabatic. Starting from the basic hydrodynamic case, the effect of vertical (axial) and horizontal magnetic fields is assessed. Depending on the magnitude of the Rayleigh and Hartmann numbers, both turbulent and laminar (azimuthally symmetric or not) flows are observed. The results show that the increase of Rayleigh number promotes heat transfer by convection while the increase of Hartmann number favors heat conduction. The vertical magnetic field reduces the Nusselt number more than the horizontal. The circulation patterns for the most convective cases are confined close to the top corner of the container with the simultaneous formation of a secondary flow pattern at the bottom corner, while for the more conductive cases only one circulation pattern exists covering the entire domain.
To investigate the efficacy and safety of supplementation with a fixed combination of magnesium, vitamin B2, feverfew, andrographis paniculata and coenzyme Q10 in episodic migraine (EM) prevention.
A ...pilot, single-arm, open-label study was conducted. After a one-month baseline period, the above-described supplementation was introduced in 113 EM Greek patients, who were prospectively followed-up for three months. The primary endpoint was the change in monthly migraine days between baseline period (BSL) and the third month of supplementation (T3). Secondary endpoints included changes in mean intensity of migraine and in days with use of acute migraine medications. Changes in scores of Migraine Disability Assessment questionnaire (MIDAS), Headache Impact Test-6 (HIT-6), Migraine Therapy Assessment questionnaire (MTAQ), Migraine-Specific Quality-of-life questionnaire (MSQ-QOL), Hospital Anxiety and Depression Scale (HADS) were also evaluated. Those with ≥50% reduction in monthly migraine days at T3, compared to BSL were considered supplementation-responders.
The mean number of migraine days was significantly decreased between BSL and T3 (9.4 ± 3.7 vs. 6.1 ± 3.5;
< 0.001). Likewise, days with peak headache intensity of >4/10 (5.7 ± 3.4 vs. 4.9 ± 3.1;
< 0.001) as well as days using acute headache medications per month (8.9 ± 3.6 vs. 5.7 ± 3.4;
< 0.001) were significantly reduced. At T3, 64 patients (56.6%) were classified as responders. The beneficial effect of supplementation was also associated with significant changes in HIT-6, MIDAS, MTAQ and MSQ-QOL scores. There were no safety concerns.
The supplementation we have tested appears to be an effective and well-tolerated preventive approach against EM. A randomized, placebo-controlled study is needed to confirm our results.
OBJECTIVE:Sympathetic fibers connect sphenopalatine ganglion (SPG) area with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients ...with stage I-II essential hypertension.
DESIGN AND METHOD:We performed bilateral SPG block with lidocaine 2% in 34 hypertensive patients (mean age 48+12 years, 25 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51+12 years, 8 men). All patients have been subjected to 24 hour ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24 h SBP decrease > 5 mmHg
RESULTS:We found that 24 h (p = 0.01) and daytime DBP (p = 0.005) as well as daytime DBP load (p = 0.008) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/34 responders (35%) regardinga. SBP and DBP during overall 24 h and daytime (p < 0.001) and night-time periods (p = 0.001 and p = 0.01, respectively), b. pre-awake SBP and DBP (p = 0.01 and p = 0.03, respectively) and c. SBP (daytime and night-time) and DBP (daytime) load (p < 0.001). No differences regarding BP were found in the sham operation group.
CONCLUSIONS:SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure.
Diabetic foot ulceration is a major diabetic complication with unmet needs. We investigated the efficacy of epidermal stem cells and epidermal stem cells–derived exosomes (ESCs-Exo) in improving ...impaired diabetic wound healing and their mechanisms of action. In vitro experiments showed that ESCs-Exo enhanced the proliferation and migration of diabetic fibroblasts and macrophages and promoted alternative or M2 macrophage polarization. In wounds of db/db mice, treatment with both epidermal stem cells and ESCs-Exo, when compared with fibroblast exosomes and PBS control, accelerated wound healing by decreasing inflammation, augmenting wound cell proliferation, stimulating angiogenesis, and inducing M2 macrophage polarization. Multiplex protein quantification of wound lysates revealed TGFβ signaling influenced by ESCs-Exo. High-throughput sequencing of small RNAs contained in the ESCs-Exo showed higher proportions of microRNAs than those contained in fibroblast exosomes. In silico functional analysis showed that the ESCs-Exo microRNAs‒target genes were primarily involved in homeostatic processes and cell differentiation and highlighted regulatory control of phosphatidylinositol-3 kinase/protein kinase B and TGFβ signaling pathways. This was also validated in vitro. Collectively, our results indicate that epidermal stem cells and ESCs-Exo are equally effective in promoting impaired diabetic wound healing and that ESCs-Exo treatment may be a promising and technically advantageous alternative to stem cell therapies.
Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed at a late stage and are locally advanced or with concurrent metastases. The aggressive phenotype and relative chemo- ...and radiotherapeutic resistance of PDAC is thought to be mediated largely by its prominent stroma, which is supported by an extracellular matrix (ECM). Therefore, we investigated the impact of tissue-matched human ECM in driving PDAC and the role of the ECM in promoting chemotherapy resistance. Decellularized human pancreata and livers were recellularized with PANC-1 and MIA PaCa-2 (PDAC cell lines), as well as PK-1 cells (liver-derived metastatic PDAC cell line). PANC-1 cells migrated into the pancreatic scaffolds, MIA PaCa-2 cells were able to migrate into both scaffolds, whereas PK-1 cells were able to migrate into the liver scaffolds only. These differences were supported by significant deregulations in gene and protein expression between the pancreas scaffolds, liver scaffolds, and 2D culture. Moreover, these cell lines were significantly more resistant to gemcitabine and doxorubicin chemotherapy treatments in the 3D models compared to 2D cultures, even after confirmed uptake by confocal microscopy. These results suggest that tissue-specific ECM provides the preserved native cues for primary and metastatic PDAC cells necessary for a more reliable in vitro cell culture.
OBJECTIVE:Target organ damage (TOD) evaluation in patients with arterial hypertension is necessary in order to estimate cardiovascular risk (CVR) and plan treatment. Increased carotid intima-media ...thickness (IMT), an index of TOD, represents the diffuse vascular atheromatosis. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity and finally to cardiovascular disease. Sideview Darkfield imaging allows for non-invasive automated estimation of EG dimensions based on the erythrocyte column distribution. We aimed to investigate any differences in EG levels in untreated patients with essential hypertension.
DESIGN AND METHOD:We studied 86 patients with newly diagnosed and never treated essential hypertension (mean age 53 + 7 years, 53 males). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. We estimated carotid intima-media thickness using carotid ultrasonography (normal levels IMT < 0.8 mm).
RESULTS:The whole population was divided in two groups regarding IMT levels, group A (IMT < 0.8 mm, n = 30, mean age 52 + 7 years, 17 males) and group B (IMT > 0.8 mm, n = 56, mean age 54 + 7 years, 36 males). Group A and B were also matched for age and sex. No differences were found within groups regarding 24 h systolic and diastolic ABPM as well as PBR 5–25, PBR 10–19 and PBR 20–25. We found that PBR 5–9 was increased in group B (1.19 + 0.1 vs. 1.13 + 0.1, p = 0.04) compared with group A.
CONCLUSIONS:EG dimensions are reduced in hypertensive patients with augmented cardiovascular risk. Further studies are needed to confirm our results in a larger population and possibly establish EG measurement as a new cardiovascular risk marker.
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