Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease

Background: Coronary artery disease (CAD) affects milions of people and can result in myocardialinfarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity,however as regulators of the local inflammatory response they can potentially contribute toCAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases:carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI.Methods: The 44 patients with angiographically confirmed CAD (23 subjects with non-ST-segmentelevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as wellserum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured.Results: Patients with single vessel CAD had higher serum concentration of carboxypeptidase thanthose with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). Therewere no significant differences in levels of any protease between patients with stable CAD and those withNSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensiveindividuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreasedin sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL,p = 0.02).Conclusions: Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. Lowerserum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damagesuggesting a protective role of these enzymes in CAD

Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti-Angiogenic Factors

<div><p>Objective</p><p>Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors.</p><p>Materials and Methods</p><p>82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF).</p><p>Results</p><p>Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation.</p><p>Conclusions</p><p>Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation.</p></div

Active Disturbance Rejection Control of Linear Induction Motor

This paper proposes the theoretical framework and the experimental application of the active disturbance rejection control to linear induction motors. Such a nonlinear control (ADRC) technique can be viewed as a particular kind of input-output linearization control, where the nonlinear transformation of the state is not computed by means of the model, but it is estimated online. Such an approach permits to cope with unmodeling dynamics, as well as uncertainty in the knowledge of the model parameters and exogenous disturbances. The effectiveness of the proposed ADRC control law has been verified both by numerical simulations and experimentally on a suitably developed test setup. Moreover, the results have been compared with those achievable with the model-based feedback linearization control

Statin treatment and serum levels of VEGF.

<p>Healthy and hypertensive individuals treated with statins had increased serum levels of VEGF when compared with not treated subjects (Mann- Whitney U test; p = 0.04). The data are presented as medians (symbols inside the boxes), 25–75% percentiles (boundaries of the boxes) and minimum-maximum (error bars outside the boxes). Statistical significance (p<0.05) is marked with “*”.</p

IL-8 concentration in hypertension.

<p>Hypertension was associated with increased serum levels of IL = 8 (Mann- Whitney U test; p = 0.02). The data are presented as medians (symbols inside the boxes), 25–75% percentiles (boundaries of the boxes) and minimum—maximum (error bars outside the boxes). Statistical significance (p<0.05) is marked with “*” (A). Concentration of IL = 8 was in positive correlation (Spearman’s rank correlation) with systolic blood pressure (B; R = 0,326, p = 1x10^-3) and in negative correlation with glomerular filtration rate (GFR) (C; R = -0.26, p = 0.01). Correlations were calculated for both- hypertensive and healthy individuals together.</p

Endostatin concentration in hypertension.

<p>Hypertension was associated with increased serum levels of endostatin (Mann- Whitney U test; p = 8x10^-4). The data are presented as medians (symbols inside the boxes), 25–75% percentiles (boundaries of the boxes) and minimum—maximum (error bars outside the boxes). Statistical significance (p<0.05) is marked with “*” (A). Endostatin concentration was in positive correlation (Spearman’s rank correlation) with systolic blood pressure (B; R = 0.287, p = 1x10^-3), CRP (C; R = 0,326,p = 4x10^-4), triglycerides (D; R = 0.260, p = 4x10^-3), serum creatinine (E; R = 0,313 p = 8x10^-4) and in negative correlation with glomerular filtration rate (GFR) (F; R = -0.42, p = 1x10^-5). Correlations were calculated for both- hypertensive and healthy individuals together.</p

Angiogenin concentration in hypertension.

<p>Patients with hypertension were characterized by lower serum concentration of angiogenin than healthy individuals (Mann- Whitney U test; p = 0.01). The data are presented as medians (symbols inside the boxes), 25–75% percentiles (boundaries of the boxes) and minimum—maximum (error bars outside the boxes). Statistical significance (p<0.05) is marked with “*”.</p

Taxonomic Position and Phylogeny of the Genus <i>Vargasiella</i> (Orchidaceae, Vandoideae) Based on Molecular and Morphological Evidence

<div><p>Since the description of the Neotropical genus <i>Vargasiella</i> in 1952, its taxonomic position has remained unclear, mainly due to a lack of sufficient data. In this study, the taxonomic position of <i>Vargasiella</i> was revised based on the outcomes of macro- and micromorphological studies, analyses of selected molecular markers and ecological methods of niche distribution modeling. The phylogenetic relationships were inferred using three DNA markers: <i>mat</i>K, <i>trn</i>L-F and ITS sequences. The morphological studies included the analysis of macromorphological features of herbarium specimens as well as micromorphological examination of preserved flowers. The ecological niche modeling was applied to identify the distribution of the suitable niches of the studied taxa. The relationships between <i>Vargasiella</i> and most similar taxa remain unresolved based on the molecular analysis. The outcomes from the morphological studies indicated significant differences between <i>Vargasiella, Warrea</i> and <i>Warreopsis</i>. Moreover, a niche shift in response to changing climate after the last glacial maximum is observed in <i>Vargasiella</i>, while no substantial changes in the occupied habitats were identified in the other related taxa. The clocktree of the Zygopetaleae estimated from the <i>mat</i>K gene indicated that the most recent common ancestors of <i>Vargasiella</i>, <i>Warrea</i> and <i>Warreopsis</i> originated in the Miocene, while the divergence time for <i>Vargasiella</i> and <i>Warrea</i> was assessed at approximately 5.4 Ma ago. <i>Vargasiella</i> seems to be an outshoot of the main branch of evolution of the Zygopetaleae. It is noteworthy that the <i>Vargasiella-Warrea</i> dichotomy could have taken place later than the divergence of <i>Warreopsis</i> from the mutual lineage. The molecular analysis and morphological data suggest that <i>Vargasiella</i> and <i>Warrea</i> could have evolved from a common ancestor. Accumulation of morphological differences and acceleration of the evolution of <i>Vargasiella</i> were more intensive than in other Warreinae and this could probably be synchronized with adaptation to different climatic conditions.</p></div

Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1&ndash;16 &micro;g/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8&ndash;1.6 &micro;g/mL and was confirmed as the leading structure with MICs 1 &micro;g/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14&ndash;1.11 while the mentioned three ranged 1.9&ndash;3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency

<i>Vargasiella venezuelana</i> C.Schweinf.

<p>(A) Lip with central fleshy disc divided into two thickenings. (B) Lip base. (C) Details of (B): the irregularly sized rounded cells to obpyriform and conical papillae, visible cuticle swellings on the cells. (D) Lip middle part and apex. (E) Detail of (D). Surface between thickenings built by the obpyriform to slightly conical papillae (F). (G) Conical papillae present on the thickenings; Visible cuticle swellings on the cells (F-G). (H) The involute undulate margins built by groups of elongated conical papillae. (I) Papillae (detail of H) covered by undulated cuticle, cuticle swellings also present.</p