The application of bacteria-derived dehydrogenases and oxidases in the synthesis of gold nanoparticles.

In this work the green synthesis of gold nanoparticles (Au-NPs) using the oxidoreductive enzymes Myriococcum thermophilum cellobiose dehydrogenase (Mt CDH), Glomerella cingulata glucose dehydrogenase (Gc GDH), and Aspergillus niger glucose oxidase (An GOX)) as bioreductants was investigated. The influence of reaction conditions on the synthesis of Au-NPs was examined and optimised. The reaction kinetics and the influence of Au ions on the reaction rate were determined. Based on the kinetic study, the mechanism of Au-NP synthesis was proposed. The Au-NPs were characterized by UV-Vis spectroscopy and transmission electron microscopy (TEM). The surface plasmon resonance (SPR) absorption peaks of the Au-NPs synthesised with Mt CDH and Gc GDH were observed at 535 nm, indicating an average size of around 50 nm. According to the image analysis performed on a TEM micrograph, the Au-NPs synthesized with Gc GDH have a spherical shape with an average size of 2.83 and 6.63 nm after 24 and 48 h of the reaction, respectively. KEY POINTS: • The Au NPs were synthesised by the action of enzymes CDH and GDH. • The synthesis of Au-NPs by CDH is related to the oxidation of cellobiose. • The synthesis of Au-NPs by GDH was not driven by the reaction kinetic.

Mesocellular Silica Foam as Immobilization Carrier for Production of Statin Precursors.

The employment of 2-deoxyribose-5-phosphate aldolase (DERA) stands as a prevalent biocatalytic route for synthesizing statin side chains. The main problem with this pathway is the low stability of the enzyme. In this study, mesocellular silica foam (MCF) with different pore sizes was used as a carrier for the covalent immobilization of DERA. Different functionalizing and activating agents were tested and kinetic modeling was subsequently performed. The use of succinic anhydride as an activating agent resulted in an enzyme hyperactivation of approx. 140%, and the stability almost doubled compared to that of the free enzyme. It was also shown that the pore size of MCF has a decisive influence on the stability of the DERA enzyme.

ADMISSION CARDIAC TROPONINS PREDICT HOSPITAL MORTALITY IN TYPE A ACUTE AORTIC DISSECTION: A META-ANALYSIS OF ADJUSTED RISK ESTIMATES.

Acute aortic dissection (AAD) is a serious medical emergency that requires early diagnosis and rapid treatment. Whether cardiac troponin could be an independent prognostic marker in patients with type A AAD is still unknown. We systematically searched Medline and Scopus to identify all observational cohort studies published before January 2020 that compared outcome (in-hospital mortality) in patients with type A AAD with and without troponin elevation on admission. Four studies with 412 patients were included in final analysis (median age 59 years, 65% of males). A total of 124 (30%) patients died during in-hospital stay, and 73% underwent surgery. Elevated troponins (39.6% of patients) were associated with an increased risk of short-term mortality (adjusted odds ratio 1.26; 95% confidence interval 1.08-1.47), with low heterogeneity among studies (I2 =29.81%). Elevated troponins on admission are independently associated with increased in-hospital mortality in type A AAD.

Admission C-reactive protein and outcomes in acute aortic dissection: a systematic review.

AIM: To assess the prognostic role of admission C-reactive protein (CRP) in patients with acute aortic dissection (AAD). METHODS: We searched Medline and Scopus for studies published before January 2019 that evaluated the prognostic impact of CRP on all-cause mortality during short- and mid-term follow-up period in patients with AAD. Additional studies were identified by manual search of the references from the original studies. Receiver-operating characteristic curves were used to determine the optimal cut-off values of admission CRP for the prediction of mortality, and patients were categorized into two groups based on the CRP cut-off levels. RESULTS: Medline, Scopus, and manual literature search yielded 138 citations. Based on the title and abstract analysis and review of potentially relevant studies, five studies, involving 711 patients, were included in the final analysis. Multivariate statistical analysis was performed in all the studies. The median admission CRP value across the studies was 13 mg/L (range 4-21 mg/L). Two out of three studies that evaluated in-hospital outcome and all of the studies that evaluated medium-term outcome reported a significant association between elevated CRP values and mortality. The studies that included treatment strategy (surgery vs conservative treatment) as a confounding variable confirmed a significant effect of elevated CRP values on both in-hospital and mid-term unfavorable outcomes. CONCLUSION: This systematic review demonstrated a clear association between elevated admission serum CRP levels and increased in-hospital and mid-term mortality risk in AAD.

C-reactive protein, renal function, and cardiovascular outcome in patients with symptomatic peripheral artery disease and preserved left ventricular systolic function.

AIM: To investigate the prognostic role of C-reactive protein (CRP) and renal function for the occurrence of major adverse cardiovascular events (MACE) in patients with symptomatic peripheral artery disease (PAD) and preserved left ventricular ejection fraction (LVEF). METHODS: The occurrence of MACE, defined as composite endpoint of acute myocardial infarction, urgent coronary revascularization, stroke, and death was assessed in 319 consecutive PAD patients admitted to the University Hospital between January 2010 and January 2014 (66.5% men, mean [±standard deviation] age 70±10 years, mean ankle brachial index 0.58±0.14) with normal LVEF (>50%). Multivariate Cox regression analysis adjusted for age, sex, traditional cardiovascular risk factors, anemia, polyvascular disease, critical limb ischemia (CLI), statin treatment, CRP (>5 mg/L), and impaired renal function (estimated glomerular filtration rate <60 mL/min) was applied to assess the independent predictors of MACE. RESULTS: During median follow-up period of 24 months (interquartile range, 16-34 months), 77 patients (24%) experienced MACE. Compared to patients without MACE, these patients were older, more likely to have CLI, polyvascular disease, anemia, elevated CRP, and impaired renal function. In multivariate regression analysis, age (HR 1.04, 95% CI 1.01-1.07), polyvascular disease (HR 1.95, 95% CI 1.23-3.09), elevated CRP (HR 1.89, 95% CI 1.18-3.02), and impaired renal function (HR 1.68, 95% C 1.01-2.78) remained independent predictors of MACE. Patients with both impaired renal function and high CRP values on admission were 3.59 times more likely to experience MACE than patients with normal CRP and preserved renal function. CONCLUSION: Elevated admission CRP and renal impairment are independent predictors of MACE in symptomatic PAD patients with preserved LVEF.

Cardiac troponins predict mortality and cardiovascular outcomes in patients with peripheral artery disease: A systematic review and meta-analysis of adjusted observational studies.

BACKGROUND: A significant proportion of patients (pts) with peripheral artery disease (PAD) have concomitant coronary artery disease and polyvascular involvement contributes to increased risk of death and unfavorable cardiovascular events. HYPOTHESIS: Cardiac troponins are associated with adverse cardiovascular outcomes in PAD pts. METHODS: We systematically searched Medline and Scopus to identify all observational cohort studies published before June 2021 (combining terms "troponin," "peripheral artery disease," "peripheral arterial disease," "intermittent claudication," and "critical limb ischemia") that evaluated the prognostic impact of troponin rise on admission on all-cause mortality and/or major cardiovascular events (MACEs; composite of myocardial infarction, stroke, and cardiovascular death) in PAD pts followed up at least 6 months. A meta-analysis was conducted using the generic inverse variance method. Heterogeneity between studies was investigated using Cochrane's Q test and I2 statistic. RESULTS: Eight studies were included in the final analysis (5313 pts) with a median follow-up of 27 months (interquartile range: 12-59 months). The prevalence of troponin positivity was 5.3% (range: 4.4%-8.7%) in pts with intermittent claudication, and 62.6% (range: 33.6%-85%) in critical limb ischemia. Elevated troponins were significantly associated with an increased risk of all-cause mortality (hazard ratio [HR]: 2.85, 95% confidence interval [CI]: 2.28-3.57; I2 = 50.97%), and MACE (HR: 2.58, 95% CI: 2.04-3.26; I2 = 4.00%) without publication bias (p = .24 and p = .10, respectively). CONCLUSION: Troponin rise on admission is associated with adverse long-term cardiovascular outcomes in symptomatic PAD.

Modelling as a tool of enzyme reaction engineering for enzyme reactor development.

Strategy of the development of model for enzyme reactor at laboratory scale with respect to the modelling of kinetics is presented. The recent literature on the mathematic modelling on enzyme reaction rate is emphasized.

New approach to the evaluation of lignocellulose derived by-products impact on lytic-polysaccharide monooxygenase activity by using molecular descriptor structural causality model.

Lytic-polysaccharide monooxygenase (LPMO) is one of the most important enzyme involved in biocatalytic lignocellulose degradation, and therefore inhibition of LPMO has significant effects on all related processes. Structural causality model (SCM) were established to evaluate impact of phenolic by-products in lignocellulose hydrolysates on LPMO activity. The molecular descriptors GATS4c, ATS2m, BIC3 and VR2_Dzs were found to be significant in describing inhibition. The causalities of the molecular descriptors and LPMO activity are determined by evaluating the directed acyclic graph (DAG) and the d-separation algorithm. The maximum causality for LPMO activation is ß = 0.79 by BIC3 and the maximum causality of inhibition is ß = -0.56 for the GATS4c descriptor. The model has the potential to predict the inhibition of LPMO and its application could be useful in selecting an appropriate lignocellulose pretreatment method to minimise the production of a potent inhibitor. This will subsequently lead to more efficient lignocellulose degradation process.

N-terminal pro-brain natriuretic peptide and short-term mortality in acute aortic dissection: A meta-analysis.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening medical emergency that requires immediate diagnosis and rapid treatment. There is a paucity of data on the role of biomarkers in risk stratification of patients with AAD. HYPOTHESIS: N-terminal pro-brain natriuretic peptide (NT-proBNP) is associated with short-term mortality in AAD patients. METHODS: We systematically searched Medline and Scopus to identify all observational cohort studies published before January 2020 that compared outcome (short-term mortality) in patients with AAD with high vs low levels of baseline NT-proBNP combining terms "brain natriuretic peptide" and "aortic dissection." A meta-analysis was conducted using the generic inverse variance method. Heterogeneity between studies was investigated using the Cochrane's Q test and I2 statistic. RESULTS: Four studies were included in final analysis including a total of 950 patients, and 105 (11%) patients died. Baseline NT-proBNP concentrations were significantly higher in nonsurvivors (median 2240 pg/mL, range 1678-16 347 pg/mL) when compared to survivors (665 pg/mL, 328-1252 pg/mL). Elevated NT-proBNP values were significantly associated with an increased risk of short-term mortality (odds ratio 4.13, 95% CI [confidence interval] 2.33-7.33), with low heterogeneity (I2 = 8.77%, Cochran Q = 2.19, P = .33), and no publication bias. The pooled standardized mean difference between groups was 1.28 (95% CI 0.99-1.56), with low heterogeneity (I2 = 38.73%, Cochran Q = 3.26, P = .19). CONCLUSION: Elevated NT-proBNP levels on admission are associated with an increased risk of short-term mortality in AAD.

Mathematical modelling of NADH oxidation catalyzed by new NADH oxidase from Lactobacillus brevis in continuously operated enzyme membrane reactor.

NADH oxidase from Lactobacillus brevis was kinetically characterized in two different buffers: Tris-HCl and glycine-sodium pyrophosphate (pH 9.0). Reaction kinetics was described using the Michaelis-Menten model with product (NAD(+)) inhibition. It was found that this type of inhibition is uncompetitive. Experiments in the continuously operated enzyme membrane reactor revealed a strong enzyme deactivation at two different residence times: 12 and 60 min. A stronger deactivation was observed at the lower residence time in the glycine-sodium pyrophosphate buffer. Enzyme deactivation was assumed to be of the first order. The developed mathematical model for the continuously operated enzyme membrane reactor described these experiments very well. The mathematical model simulations revealed that a high enzyme concentration (up to 30 g cm(-3)) is necessary to obtain and maintain the stationary NADH conversion near 100% for a longer period of time.

Impact of diabetes on mortality in peripheral artery disease: a meta-analysis.

BACKGROUND: There are accumulating studies showing the association between diabetes and all-cause mortality in peripheral vascular disease. However, the results in these studies are conflicting regarding the impact of diabetes on outcome. HYPOTHESIS: Diabetes is associated with increased risk of mortality in peripheral artery disease. METHODS: Using MEDLINE and Scopus, we searched for studies published before January 2016. Additionally, studies were identified by manual search of references of original articles or review studies on this topic. Of the 1072 initially identified records, 21 studies with 15,857 patients were included in the final analysis. RESULTS: Diabetes was associated with a statistically significant increased risk of all-cause mortality (odds ratio: 1.89, 95% confidence interval: 1.51-2.35, P < 0.001), without detected publication bias (Egger bias = 0.75, P = 0.631). The stronger effect on outcome was obtained in patients with critical limb ischemia (odds ratio: 2.38, 95% confidence interval: 1.22-4.63, P < 0.001) as the most severe form of peripheral vascular disease. CONCLUSIONS: Diabetes is associated with an increased risk of mortality in peripheral vascular disease, and the effect is even more pronounced in patients with critical limb ischemia.

Coenzyme regeneration in hexanol oxidation catalyzed by alcohol dehydrogenase.

The enzymatic ways of coenzyme regeneration include the addition of a second enzyme to the system or the addition of the co-substrate. In the present study, both methods of enzymatic coenzyme (NAD(+)) regeneration were studied and compared in the reaction of hexanol oxidation catalyzed by alcohol dehydrogenase (ADH). As a source of ADH, commercial isolated enzyme and the whole baker's yeast cells were used. First, coenzyme regeneration was employed in the reaction of acetaldehyde reduction catalyzed by the same enzyme that catalyzed the main reaction, and then NAD(+) regeneration was applied in the reaction of pyruvate reduction catalyzed by L-lactate dehydrogenase (L-LDH). Hexanal was obtained as the product of hexanol oxidation catalyzed by isolated ADH while hexaonic acid was detected as a product of the same reaction catalyzed by baker's yeast cells. All of the used biocatalysts were kinetically characterized. The mass reactions were described by the mathematical models. All models were validated in the batch reactor. One hundred percent hexanol conversion was obtained using permeabilized yeast cells using both methods of cofactor regeneration. By using isolated enzyme ADH, the higher conversion was achieved in a system with cofactor regeneration catalyzed by L-LDH.

Impact of admission anemia, C-reactive protein and mean platelet volume on short term mortality in patients with acute ST-elevation myocardial infarction treated with primary angioplasty.

OBJECTIVES: To investigate admission anemia, C-reactive protein (CRP) and mean platelet volume (MPV) together as prognostic markers in ST-elevation myocardial infarction (STEMI). DESIGN AND METHODS: Baseline hemoglobin, CRP and MPV were determined in 543 patients with acute STEMI to whom primary angioplasty was performed and evaluated for short term mortality (30 days). RESULTS: After multivariate analysis anemia (odds ratio 2.69, 95% confidence interval 1.24-5.86) and CRP (odds ratio 3.40, 95% confidence interval 1.13-10.22) remained significant independent predictors of short-term mortality. Addition of anemia and CRP to PAMI risk score improved prediction of short-term outcome; area under ROC curve rose from 0.76 to 0.87 (p<0.001). CONCLUSION: Better ability to determine 30-day mortality was obtained when anemia and CRP were incorporated into the PAMI risk score.