► Veronica montana had protocatechuic acid as the main phenolic molecule. ► Extract of V. montana and protocatechuic acid successively inhibited the growth of bacteria in vitro and in vivo. ► ...Protocatechuic acid killed bacteria by affecting its cytoplasmic membrane.
This study was designed to evaluate the antibacterial activity of the Veronica montana L. water extract and its main phenolic compound, protocatechuic acid. The antibacterial activity was determined by microdilution assay against six strains of Gram-positive and Gram-negative bacteria. Listeria monocytogenes was the most sensitive of the tested bacterial species. Antibacterial preserving properties of protocatechuic acid were also evaluated after its incorporation in cream cheese, using L. monocytogenes as commonly cheese contaminant. The compound successfully inhibited L. monocytogenes development in cream cheese, at room temperature and in refrigerator (25°C and 4°C, respectively), after 3days of inoculation. Sensory evaluation was carried out in order to validate the mentioned food system. A possible mode of action of the tested compound towards bacterial cells was assessed and appears to be direct lysis of pathogenic cytoplasmic membrane. Prediction of pharmacokinetic properties was also performed using computational analyzes. The obtained results can serve as an important platform for the development of effective natural preservatives.
Understanding the effects of global climate change on the algae that form the basis of most aquatic food chains is of paramount importance in our ability to make informed decisions about the future ...of production systems, marine ecosystems, and the global carbon cycle. Despite the Montreal Protocol to restrict the release of harmful chlorofluorocarbons into the atmosphere, ozone levels have not recovered at all latitudes, and in some regions levels of UVB are still rising due to interactions with phenomena related to climate change. However, the effects of UV radiation may be modulated by other environmental changes. In this review, we discuss how factors such as elevated CO sub(2) and ocean acidification, increasing temperature, and reduced nutrient supply associated with enhanced stratification can interact with UV radiation to affect algal physiological performance and growth. For instance, nutrient limitation enhances UV-induced inhibition due to the reduced capacity of algae to screen out UVB and/or impairment of their capacity to repair damage. Higher temperatures tend to promote repair more than photochemical damage so result in a net reduction of UV inhibition. Elevated CO sub(2) and ocean acidification has complex interactions with UV radiation, with mixed net outcomes for algal productivity. Differential effects of UVA and UVB have been shown to depend on their irradiance levels; while moderate levels of UVA stimulate growth and photosynthesis of some algae, UVB almost always results in harm to marine primary producers.
Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is ...characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics.
Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens.
Serum NGAL median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001 and MMP-9/NGAL 41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017 were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics 128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2 and 101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL 60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001 and MMP-9/NGAL 20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007 in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.
Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective Neutrophil gelatinase-associated lipocalin (NGAL), a protein found in activated neutrophils, is expressed in kidney tubule cells in response to noxious stimuli, and is thus recognized as a ...marker of acute kidney injury. Recent studies have suggested that NGAL could also have pathophysiological importance in cardiovascular diseases. The aim of the present study was to examine NGAL expression in human carotid endarterectomy tissues ex vivo as well as the effects of NGAL in the main cell types involved in atherogenesis, namely in human macrophages, endothelial cells, and smooth muscle cells in vitro. Methods NGAL protein was analyzed in human endarterectomy samples from patients with asymptomatic and symptomatic carotid stenosis by immunofluorescence, and NGAL mRNA expression was detected using RealTime-PCR. Human monocyte derived macrophages (MDM), human coronary artery smooth muscle cells (HCASMC), and human umbilical vein endothelial cells (HUVEC) were treated with recombinant human (rh) NGAL at different concentrations. Interleukin (IL)-6, IL-8, and monocyte chemo-attractant protein-1 (MCP-1) were determined by specific enzyme linked immunosorbent assays (ELISAs) in culture supernatants of such treated cells. Results Expression of NGAL protein was demonstrated by macrophages, smooth muscle cells, and endothelial cells in human carotid atherosclerotic tissue. NGAL mRNA expression was detected at a higher rate in atherosclerotic tissue of patients with symptomatic carotid stenosis (in 70%; n = 19) compared with asymptomatic patients (in 37%; n = 20, p < .001). Treatment of MDM, HCASMC, and HUVEC with rhNGAL led to a significant ( p < 0.05) and concentration dependent increase of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in all cell types analyzed. Conclusion By induction of pro-inflammatory mediators in human macrophages, smooth muscle cells and endothelial cells, NGAL, which is predominantly expressed in atherosclerotic plaques of symptomatic patients, could be involved in creating the local and systemic pro-inflammatory environment characteristic for atherosclerosis.
The design of a single-molecule machine consisting of functional components requires a detailed understanding of its mechanical motion. The scanning tunnelling microscope (STM) is the only available ...tool for driving and imaging such a nanoscale machine on a surface. Both lateral hopping motions and conformational changes of single molecules can be induced using the STM tip. However, no rolling of a wheel has been demonstrated so far at the nanoscale, even though this is a very useful motion at the macroscopic scale. Here we show how the rolling of a single molecule equipped with two wheels (0.8 nm in diameter) can be induced by the STM tip. The characteristics of the rolling are recorded in the STM feedback loop manipulation signal and in real time. We capture unambiguous signatures of the conformational change happening during the rolling. Our approach of controlling the intramolecular mechanics provides a path towards the bottom-up assembly of more complex molecular machines.
Summary
Background
Urokinase‐type plasminogen activator (u‐PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. ...Interleukin (IL)‐33 is a member of the IL‐1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL‐33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells.
Objective
We investigated the impact of IL‐33 on u‐PA in endothelial cells as a new possible function for IL‐33.
Methods and results
We could demonstrate that IL‐33 upregulated u‐PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time‐ and concentration‐dependent manner via interaction with its receptor ST2 and activation of the nuclear factor–κB pathway but independent of autocrine IL‐1–induced effects. The hydroxymethylglutaryl–coenzyme A reductase inhibitor simvastatin abrogated the IL‐33–induced increase in u‐PA, thus providing further evidence for pleiotropic effects of statins. IL‐33 induced u‐PA–dependent capillary‐like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u‐PA mRNA positively correlated with IL‐33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL‐33 and u‐PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry.
Conclusions
We hypothesize that IL‐33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u‐PA–driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies.
Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 ...(CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.
Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).
Results: A total of 61 patients died during the median follow-up of 7.0 5.2-8.4 years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, 95%CI: 1.08-1.85, p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 0.98-1.17, p = 0.113) and MR-proADM (HR = 1.80 0.92-3.55, p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 1.07-1.22, p < 0.001), MR-proANP (HR = 1.64 1.29-2.08, p < 0.001) and MR-pro ADM (HR = 2.06 1.12-3.77, p = 0.020) were associated with a higher risk for overall mortality.
Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.
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