Evaluation of the usefulness of determining the level of selected inflammatory biomarkers and resistin concentration in perivascular adipose tissue and plasma for predicting postoperative atrial fibrillation in patients who underwent myocardial revascularisation.

BACKGROUND: The development of coronary artery disease (CAD) is related to the impaired quantity and composition of inflammatory proteins found in plasma and tissue, such as interleukin 6 (IL-6), adipokines, and resistin. Therefore, the level of plasma resistin in patients with advanced CAD could be indicative of the condition of epicardial adipose tissue and thus have an impact on the frequency and severity of postoperative complications in the form of paroxysmal atrial fibrillation. METHODS: The study included 108 patients who qualified for elective coronary artery bypass grafting (CABG) surgery from 2017 to 2020 and were categorized into two groups. The first group consisted of patients who developed atrial fibrillation in the postoperative period - the AF group, and the second group included patients who did not have arrhythmia - the non-AF group. The analysis incorporates the history, course of treatment, anthropometric characteristics of the test subjects, biochemical laboratory tests, and echocardiography. Perivascular adipose tissue (PVAT) sections were surgically harvested from the area of the left coronary trunk. RESULTS: The resistin levels in the PVAT were significantly higher in the AF group than in the non-AF group (P = 0.000015). Similarly, plasma resistin levels increased significantly in the AF group compared to the non-AF group (P = 0.044). The values of other analyzed variables were not significantly different (analysis performed using the Mann-Whitney U test). Spearman's rank-order correlation technique found a correlation between resistin in PVAT and plasma (r = 0.5933; P < 0.0001) in the whole study group, as well as in the AF group (r = 0.4782; P = 0.021) and the non-AF group (r = 0.4938; P < 0.0001). A correlation arose between the level of resistin in PVAT and the level of hsCRP (r = 0.3463; P = 0.005) in the whole study group and the non-AF group (r = 0.4448; P = 0.0011); however, no such correlation appeared in the AF group (r = 0.3076; P = 0.306). CONCLUSIONS: Elevated levels of plasma resistin, which reflect PVAT resistin levels in patients qualified for myocardial revascularisation, may be associated with postoperative atrial fibrillation complications.

Resistin levels in perivascular adipose tissue and mid-term mortality in patients undergoing coronary artery bypass grafting.

Higher serum resistin levels were reported to be associated with increased mortality risk. We aimed to assess the predictive value of resistin levels in perivascular adipose tissue (PVAT) around the left main coronary artery (LMCA) for mid-term survival of patients with advanced coronary artery disease (CAD).This was a prospective study including patients referred for elective coronary artery grafting in 2016 and 2017, performed using a standard approach. A sample of PVAT was harvested and resistin levels were measured using an enzyme-linked immunosorbent assay. Patients were followed from the day of the procedure until March 2021. In each patient, the SYNTAX score and EuroSCORE II were calculated. The study included 108 patients aged 68.1 ±7.9 years, including 83 men (76.9%). The duration of follow-up was 731 (range, 275-1020) for nonsurvivors and 1418 median (range, 1174-1559) for survivors (p <0.001). Patients who died had a higher SYNTAX score, higher EuroSCORE II, and lower resistin levels in PVAT than survivors (p <0.001, p = 0.004, and p = 0.041, respectively). A stepwise regression analysis revealed that survival was related to resistin concentrations above the median value (hazard ratio [HR], 4.67; 95% CI, 1.02-21.4; p = 0.048) and EuroSCORE II (used as continuous variable; HR, 1.55; 95% CI, 1.16-2.07; p = 0.003). The mid-term mortality in patients with advanced CAD is associated with low resistin concentrations in PVAT surrounding the LMCA.

On the spectral properties of methyl and methoxy derivatives of 1,3-diphenyl-1H-pyrazolo[3,4-b]quinoxalines: Experiment and DFT/TDDFT calculations.

Paper reports the synthesis and spectroscopic studies of two novel 1,3-diphenyl pyrazoloquinoxaline (PQX) derivatives with 6-substituted methyl (MePQX) or methoxy (MeOPQX) side groups. The optical absorption and fluorescence emission spectra are recorded in solvents of different polarity. Other photophysical constants, such as the fluorescence lifetime and quantum yield, radiationless and radiative rate constants, electronic transition dipole moments, give complete characterization of MePQX and MeOPQX dyes as materials for potential luminescence or electroluminescence applications. Measured optical absorption and fluorescence emission spectra are compared with the results of quantum-chemical analysis using density functional theory (DFT/TDDFT) methods based on hybrid and long range corrected (LRC) exchange-correlation (xc) functionals in combination with solvation self consistent reaction field model. Comparing to conventional hybrid xc-functionals, the DFT/TDDFT calculations using LRC xc-functionals yield considerably more accurate description of optical absorption and fluorescence emission spectra. The best description of the absorption-emission circle provides the model assuming that optical absorption takes place from preferably flat or weakly twisted molecular conformations in the ground state, as particularly is suggested by the geometrical DFT optimization, whereas the fluorescence emission would be expected from more twisted molecular conformations in the excited state.

DFT/TDDFT study on the electronic structure and spectral properties of diphenyl azafluoranthene derivative.

Paper reports the DFT/TDDFT study on the electronic structure and spectral properties of the five-membered annulated diphenyl azafluoranthene derivative 1,3-diphenyl-3H-indeno[1,2,3-de]pyrazolo[3,4-b]quinoline (DPIPQ) by means of polarizable continuum model (PCM) and Onsager reaction field approaches at the B3LYP/6-31+G(d,p) level of theory. The results of calculations are compared with the optical absorption and fluorescence spectra as well as with the cyclic voltammetry data. The DFT/TDDFT/PCM approaches exhibit rather good quantitative agreement regarding the spectral position of the first absorption band; the discrepancy between the experiment and theory is less than 0.06 eV (linear response approach) or 0.25 eV (state specific approach). As for the fluorescence emission the TDDFT/PCM calculations underestimate the transition energy on about of 0.7-0.8 eV. Such discrepancy should be attributed to insufficient quality of the TDDFT/PCM optimization in the excited state. Ignoring the geometrical relaxation in the excited state provides considerably better agreement between the experiment and theory; discrepancy is less than 0.1-0.22 eV depending on a solvent polarity. The dominant influence on the fluorescence emission results mainly from the solvent reorganization in the excited state whereas the solute relaxation is indeed weak and may be ignored.

Increase in serum platelet-derived growth factor (PDGF)-BB reflects lymph node involvement in esophageal cancer patients independently from platelet count.

AIM: To evaluate clinical significance and diagnostic utility of increase in serum PDGF-BB (sPDGF-BB) in esophageal cancer, which have not been addressed yet despite the relevance of PDGF axis in this cancer type. METHODS: Immunoenzymatically assessed sPDGFBB was related to clinicopathological features, and inflammatory, angiogenic, and lymphangiogenic indices in 84 patients with esophageal cancer and 47 controls. Its diagnostic utility was evaluated by receiver operating characteristics (ROC) curve analysis. RESULTS: sPDGF-BB was significantly higher in esophageal cancer patients than controls (3.76 vs. 2.66 µg/l, p = 0.0001) and corresponded with the disease advancement. Of evaluated clinicopathological features, lymph node metastases and distant metastases were independently associated with an increase in sPDGF-BB; however, only the association with lymph node metastases persist adjustment to platelets. In univariate analysis, sPDGF positively correlated with platelets (r=0.70, p < 0.0001), vascular endothelial growth factor (VEGF)-A (r=0.50, p < 0.0001), VEGF-C (r=0.57, p < 0.0001), white blood cells (r=0.32, p = 0.004), C-reactive protein (r=0.34, p = 0.004), IL-6 (r=0.35, p = 0.003), and IL-8 (r=0.45, p < 0.0001). In multivariate analysis, VEGF-C and platelets were independently associated with sPDGF-BB explaining 61% in its variability. With >2.845 µg/l cut-off, over 76% of patients had elevated sPDGF-BB. Its accuracy as lymph node metastases marker was 75%, sensitivity and specificity corresponding with >3.029 µg/l cut-off were 84 and 61%, respectively. CONCLUSIONS: sPDGF-BB owns potential as a possible lymph node metastases marker and might be considered as a diagnostic tool in preliminary evaluation of esophageal cancer patients identifying those likely to be burdened with lymph node metastases, the disease recurrence monitoring, and/or preselecting patients for PDGF-directed cancer therapies.

Synthesis and spectroscopic study of several novel annulated azulene and azafluoranthene based derivatives.

A series of cyclized five-membered annulated azafluoranthene (AAF) and seven-membered annulated azulene (AA) derivatives have been synthesized and characterized by spectroscopic methods. The optical absorption and fluorescence spectra have been recorded in organic solvents of different polarity and analyzed within the semiempirical quantum chemical model PM3. In combination with the molecular dynamics simulations it properly reproduces the overall shape of the measured absorption spectra of both AA and AAF dyes including the strongest band in the region of 250-300 nm and the broad first absorption band above 400 nm. While the solvent polarity rises all the dyes exhibit the hypsochromic shift of the first absorption band and the bathochromic shift of the fluorescence band. Such opposite solvatochromic trends appear to be consistent with the Lippert-Mataga solvatochromic model. Compared to AA compounds, both AAF dyes reveal much stronger solvatochromic shift and broadening of the fluorescence band likewise the relative decrease in quantum yield on rising solvent polarity what may be an evidence for the intramolecular charge transfer mechanism being involved into the fluorescence emission. Depending on solvent polarity AA and AAF dyes emit light in the green-yellow range of the visible spectra what may be of interest for potential luminescent or electroluminescent applications.

UV-vis spectroscopy and semiempirical quantum chemical studies on methyl derivatives of annulated analogues of azafluoranthene and azulene dyes.

Paper reports the measured optical absorption and fluorescence spectra of 4-(2-chlorophenyl)-7-methyl-1,3-diphenyl-1H-pyrazolo[3,4-b]quinoline (MCPDPPQ), as well as 6-methyl-1,3-diphenyl-3H-indeno[1,2,3-de]pyrazolo[3,4-b]quinoline (MDPIPQ) and 9-methyl-6-phenyl-6H-5,6,7-triazadibenzo[f,h]naphtho[3,2,1-cd]azulene (MPTNA) representing cyclized five- or seven-membered regioisomeric products of MCPDPPQ, respectively. The spectra has been recorded in solvents of different polarity and compared with the results of quantum chemical calculations performed by means of the semiempirical method PM3 in combination with molecular dynamics (MD) simulations. Cyclization of MCPDPPQ into MDPIPQ or MPTNA is accompanied by a significant red shift of the first optical absorption and fluorescence bands. While the solvent polarity rises all the dyes exhibit the blue shift of the first absorption band and the red shift of the fluorescence band. These trends have been reproduced within the semiempirical calculations in combination with the Lippert-Mataga dielectric polarization model and explained by specific orientations of the dipole moments in the ground and excited states. All dyes may be considered as candidates for the luminescent or electroluminescent applications. Depending on solvent polarity they emit light in the green-yellow range of the visible spectra.

Even a mild anemia is related to tumor aggressiveness mediated by angiogenic factors.

UNLABELLED: Esophagogastric cancers have high recurrence rates with lymph nodes being a common pattern. Pre-treatment anemia has been reported an independent prognostic factor of treatment failure regardless of treatment strategy, particularly associated with poor locoregional control. A causative relationship between anemia - tumor hypoxia - tumor aggressiveness mediated by angiogenesis up-regulation is advocated, yet remains controversial. AIM: To determine whether and how the pre-treatment anemia is associa-ted with various aspects of disease aggressiveness and to evaluate the possible involvement of angiogenesis mediators. METHODS: In 111 esophagogastric cancer patients we investigated the association of pre-treatment hemoglobin concentration and anemia presence with cancer-related, patients-related features and laboratory parameters including angiogenic factors: vascular endothelial growth factors A and C, interleukin-8 and midkine. Serum levels of angiogenic factors were assessed with immunoenzymatic tests. RESULTS: Histology, disease stage, regional metastasis and dissemination in general, malnutrition and angiogenesis represented by midkine were found to correlate with anemia presence and hemoglobin concentration, while tumor extension, patient's age and sex accounted only for anemia presence. A tendency towards hemoglobin correlation with VEGF-A and Il-8 was also observed. Midkine, tumor histology and malnutrition were found to exert an independent effect on pre-treatment hemoglobin concentration and anemia presence in esophagogastric cancer patients. Hemoglobin level of 12 g/dL was found an optimal cut-off value for discrimination between localized and disseminated cancers. CONCLUSIONS: Even a mild pre-treatment anemia is associated with cancers metastasizing especially to regional lymph nodes, which seems to be mediated by some of studied angiogenic factors.

Respiratory insufficiency related to COPD accelerates systemic inflammation, under-nutrition, and angiogenesis in esophageal malignancies.

UNLABELLED: A number of esophageal cancer patients suffer from respiratory insufficiency due to the coexistence of chronic obstructive pulmonary disease (COPD). AIM: To test the hypothesis that COPD-related systemic hypoxemia may result in accelerated inflammation, malnutrition, and angiogenesis in esophageal cancer patients. METHODS: Serum levels of C-reactive protein (CRP), albumin, transferrin, interleukin-1, interleukin-6, interleukin-8, TNF-alpha, platelet-derived growth factor (PDGF-BB), and midkine and patient BMI and weight-loss rate were determined and compared with blood oxygenation status (pO(2), SaO(2)) in 35 esophageal cancer patients and 42 controls. RESULTS: The incidence of cachexia tended to be higher in patients with systemic hypoxemia (67% vs 40%, p = 0.169). Mean SaO(2) level was also significantly decreased in cachectic patients (90.3 vs 93.3%, p = 0.026) and pO(2) exhibited a similar trend (58.0 vs 63.4 mmHg, p = 0.120). Transferrin (234 vs 316 mg/dl, p = 0.005) and albumin (31.9 vs 37.1 mg/dl, p= 0.002) concentrations were reduced and CRP was elevated (129.9 vs 54.7 mg/l, p = 0.004) in hypoxemic patients and correlated with pO(2) (r = 0.47, p = 0.016; r= 0.48, p = 0.012; r = -0.37, p = 0.064) and SaO(2) (r = 0.52, p = 0.006; r = 0.53, p = 0.006; r = -0.40, p= 0.042). Interleukin-6 (9.97 vs 2.21 pg/ml, p = 0.005) and midkine (2101 vs 944 pg/ml, p < 0.001) were elevated and PDGF-BB was decreased (12.2 vs 17.3 pg x 10(-6)/PLT, p = 0.014) in hypoxemic compared with normoxemic patients. Interleukin-6 and midkine negatively correlated with pO(2) (r = -0.44, p = 0.016; r = -0.42, p = 0.011) and SaO(2) (r = -0.54, p = 0.003; r = -0.57, p < 0.0001) and PDGF-BB correlated positively (r = 0.53, p = 0.003; r = 0.44, p = 0.020). Interleukin-8 level was affected by pO(2) (r = -0.55, p = 0.015) and SaO(2) (r= -0.55, p = 0.018) only in hypoxemic patients. CONCLUSIONS: COPD-related systemic hypoxemia negatively affects the status of esophageal cancer patients by accelerating inflammation, under-nutrition, and angiogenesis.

Impact of systemic hypoxemia on cancer aggressiveness and circulating vascular endothelial growth factors A and C in gastroesophageal cancer patients with chronic respiratory insufficiency.

AIM: Due to the common etiologic factor, a considerable number of esophagogastric cancer patients suffer from respiratory insufficiency in course of chronic obstructive pulmonary disease, primary to cancer. Systemic hypoxemia may account for poor oxygenation of tumor tissue-a main driving force of tumor neoangiogenesis. We hypothesized that in cancer patients with respiratory insufficiency, systemic hypoxemia may be related to enhanced aggressiveness of cancer on one side and to the elevation of angiogenic factors on the other. METHODS: The levels of vascular endothelial growth factors A and C were determined with immunoenzymatic methods in patients diagnosed with esophagogastric cancer with or without co-existing respiratory insufficiency in course of chronic obstructive pulmonary disease and in healthy controls. Blood gasometry and hemoglobin levels of cancer patients were related to cancer histology and TNM status, and to circulating vascular endothelial growth factors A and C. RESULTS: Patients with systemic hypoxemia had higher incidence rates of locally advanced tumors. Partial oxygen pressure and blood oxygen saturation were significantly lowered in patients with T4 cancers as compared to less advanced ones. Circulating vascular endothelial growth factor A, but not C, was more elevated in esophagogastric cancer patients with co-existing respiratory insufficiency, as compared to those without respiratory insufficiency. Vascular endothelial growth factor A was also strongly related to the extension of primary tumor. CONCLUSION: Our results show that systemic hypoxemia in esophagogastric cancer patients is associated with the extension of primary tumor and that this effect might be mediated by the up-regulation of circulating vascular endothelial growth factor A.

Serum midkine depends on lymph node involvement and correlates with circulating VEGF-C in oesophageal squamous cell carcinoma.

Lymph node metastasis (LNM) is a key factor for selection of treatment method and patients' prognosis in oesophageal squamous cell carcinoma (ESCC). However, no biomarkers able to support the clinical detection of LNM have been reported. Recently, vascular endothelial growth factor C (VEGF-C) was found to be a more accurate marker of LNM in lung cancer than computed tomography. Midkine is a multifunctional cytokine involved in cancer development. We investigated circulating midkine levels in ESCC patients (n=73) compared with those in healthy subjects (n=42) with double-antibody-sandwich indirect enzyme-linked immunosorbent assay (DASI-ELISA). We found that midkine was elevated in ESCC and involved in metastatic disease. Serum midkine (sMK) was a good marker of LNM, evaluated both clinically and pathologically, as revealed by ROC analysis. It also correlated with serum levels of VEGF-C. The increase of sMK was related to cancer cells, although a weak correlation was observed between sMK and platelet and leucocyte counts.

Perspectives of clinical application of bone morphogenetic proteins in children.

UNLABELLED: The purpose of the study was to modify the method of Bone Morphogenetic Protein (BMP) extraction from bovine bones, estimate the osteoinductive potential of the extracted protein fractions in relation to the degree of protein purity and to test collagen formed in porous discs as a carrier. It was required before BMP application in reconstructive surgery in children. MATERIAL AND METHOD: BMP preparation from bovine bones was conducted according to a modification of Luyten's method. Three fractions of different degree of purity - demineralised bone matrix "M", extract "E", and fraction after hydroxyapatite column "HP" - were tested for their osteoinductive potential. They were implanted on a collagen carrier into the right rat femoral muscle pouch. Controls were implanted in the same way in the left muscle pouch. The discs were removed after 3 and 6 weeks and tested for alkaline phosphatase activity, a marker of new bone formation. RESULTS: Out of the 10 animals used for testing the osteoinductive potential of matrix fraction, 7 results were positive and 3 negative. In the case of the extract fraction, the analysis was conducted for 3 weeks on 9 rats and 6 weeks on 13 rats. Six and 11 positive results were obtained, respectively. In the HP group 5 animals were observed for 3 weeks (3 positive, 2 negative) and 10 animals for 6 weeks (7 positive, 3 negative). In the case of the extract, the differences in alkaline phosphatase activity after 6 weeks were statistically significant (p

Utilization of the bone/liver alkaline phosphatase activity ratio in blood plasma as an indicator of ascorbate deficiency in salmonid fish.

The goal of this study was to test the hypothesis that the ratio of liver to bone alkaline phosphatase in blood plasma reflects the ascorbate status in scurvy-prone teleost fish (rainbow trout [Oncorhynchus mykiss]). The studies focused on finding a method for distinguishing bone alkaline phosphatase present in blood plasma from other alkaline phosphatase isoforms. We tested temperature optima and thermostability of liver, kidney, gill cartilage, and intestinal alkaline phosphatases. We did not observe differences among liver, bone, and kidney enzymes with respect to temperature optima and thermostability. We partially purified alkaline phosphatase from juvenile rainbow trout vertebrae and liver using n-butanol solubilization and ammonium sulfate fractionation. We found a difference between bone alkaline phosphatase, which precipitated in 0%-20% ammonium sulfate saturation, and liver enzyme, which required 40%-50% ammonium sulfate saturation to precipitation. We conducted a series of urea inactivation studies on partially purified enzymes from liver and vertebrae. Urea differentially inhibited the enzymes with t 1/2 = 1.1 and 0.4 min, for bone and liver, respectively. Subsequently, we subjected blood plasma alkaline phosphatase to urea inhibition, and using regression analysis we calculated the ratio of liver to bone alkaline phosphatase. We found that thus obtained ratios of bone enzyme in blood plasma correlated with liver ascorbate concentration. Bone alkaline phosphatase declined in ascorbate deficiency 10-fold, whereas low ascorbate status resulted in a 3.5-fold decrease. In order to draw a general conclusion on the linearity of the response of blood plasma/bone alkaline phosphatase as an indicator of ascorbate deficiency in fish, further studies must include analysis of individual fish followed in the process of developing avitaminosis.

Ascorbate polyphosphate is a bioavailable vitamin C source in juvenile rainbow trout: tissue saturation and compartmentalization model.

We studied the bioavailability of ascorbic acid ester, ascorbate polyphosphate, to juvenile rainbow trout (Oncorhynchus mykiss). Fish were fed molar equivalents of 0, 20, 40, 80, 160, 320 and 1280 mg ascorbic acid/kg diet in the form of ascorbate polyphosphate. During the 18 wk of the experiment, when body weight increase averaged 3.5-fold, we did not observe any deficiency symptoms in any group. Liver and kidney ascorbate concentrations differed significantly among groups after wk 9. The ascorbic acid concentrations in liver were significantly different in fish fed for 9 wk an equivalent of 0, 40 and 160 mg ascorbic acid/kg as ascorbate polyphosphate, values were 22.7 +/- 3.4, 93.7 +/- 17.0 and 368.0 +/- 60.8 nmol ascorbic acid/g. The ascorbic acid concentrations in kidney were significantly different in fish fed for 18 wk an equivalent of 0,20 and 40 mg ascorbic acid/kg as ascorbic polyphosphate (23.9 +/- 4.0, 72.1 +/- 13.6 and 254.4 +/- 22.7 nmol ascorbic acid/g, respectively). After wk 18, fish from groups fed 0, 20, 320 and 1280 mg ascorbic polyphosphate/kg were intraperitoneally injected with 25 mg/ascorbic acid/kg body wt. We observed differences in the profiles of tissue ascorbate concentration during the 96 h following the injection between groups with high and low tissue ascorbate concentration, i.e., fish fed 320 and 0 ascorbic acid/kg, respectively. We conclude that ascorbic acid metabolism in rainbow trout after intraperitoneal injection followed the three-compartmental model, with the intraperitoneal cavity as the first compartment, blood as the second, and tissues as the third.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of proteases on the activity of enolase from muscle of carp (Cyprinus carpio) and pig.

The treatment of enolase from pig and carp (Cyprinus carpio) with proteases resulted in a decrease of enzymatic activity, which depended on the kind of protease used. The most active were trypsin and subtilisin. Substrate and magnesium ions protected enolase against inactivation. The enolase from pig muscle was much more resistant to protease action than this enzyme from carp muscle. Some differences in the structure between the two enolases are suggested.