Search Results (11)

There is growing interest in the non-invasive identification and monitoring of the outcome of liver damage in obese patients. Plasma cytokeratin-18 (CK-18) fragment levels correlate with the magnitude of hepatocyte apoptosis and have recently been proposed to independently predict the presence of non-alcoholic steatohepatitis (NASH). The aim of the study was to analyze the associations of CK-18 with obesity and related complications: insulin resistance, impaired lipid metabolism and the secretion of hepatokines, adipokines and pro-inflammatory cytokines. The study involved 151 overweight and obese patients (BMI 25–40), without diabetes, dyslipidemia or apparent liver disease. Liver function was assessed based on alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and the fatty liver index (FLI). CK-18 M30 plasma levels, FGF-21, FGF-19 and cytokines were determined by ELISA. CK-18 values >150 U/l were accompanied by high ALT, GGT and FLI, insulin resistance, postprandial hypertriglyceridemia, elevated FGF-21 and MCP-1 and decreased adiponectin. ALT activity was the strongest independent factor influencing high CK-18 plasma levels, even after an adjustment for age, sex and BMI [β coefficient (95%CI): 0.40 (0.19–0.61)]. In conclusion, the applied CK-18 cut-off point at 150 U/l allows to distinguish between two metabolic phenotypes in obesity. Full article

Elevated glucose-dependent insulinotropic peptide (GIP) levels in obesity may predict the metabolic benefits of n-3 PUFA supplementation. This placebo-controlled trial aimed to analyze fasting and postprandial GIP response to 3-month n-3 PUFA supplementation (1.8 g/d; DHA:EPA, 5:1) along with caloric restriction (1200–1500 kcal/d) in obese subjects. Compliance was confirmed by the incorporation of DHA and EPA into red blood cells (RBCs). Blood analyses of glucose, insulin, non-esterified fatty acids (NEFAs), GIP and triglycerides were performed at fasting, and during an oral glucose tolerance test and a high fat mixed-meal tolerance test. Fatty acid composition of RBC was assessed by gas chromatography and total plasma fatty acid content and composition was measured by gas–liquid chromatography. The DHA and EPA content in RBCs significantly increased due to n-3 PUFA supplementation vs. placebo (77% vs. −3%, respectively). N-3 PUFA supplementation improved glucose tolerance and decreased circulating NEFA levels (0.750 vs. 0.615 mmol/L), as well as decreasing plasma saturated (1390 vs. 1001 µg/mL) and monounsaturated (1135 vs. 790 µg/mL) fatty acids in patients with relatively high GIP levels. The effects of n-3 PUFAs were associated with the normalization of fasting (47 vs. 36 pg/mL) and postprandial GIP levels. Obese patients with elevated endogenous GIP could be a target group for n-3 PUFA supplementation in order to achieve effects that obese patients without GIP disturbances can achieve with only caloric restriction. Full article

Total transferrin concentration changes in acute-phase reactions. Additionally, the alteration of transferrin glycosylation in inflammations can occur. The aim of this study is to evaluate the effect of pancreatitis on the serum profile of transferrin isoforms. The tested groups consisted of 84 patients with acute pancreatitis and 42 patients with chronic hepatitis. Transferrin isoforms were analyzed by capillary electrophoresis on a MINICAP electrophoretic system (Sebia, France). There was a significant decrease in the concentration of pentasialotransferrin in both acute and chronic pancreatitis, and a significant increase in tetrasialotransferrin in the acute pancreatitis group when compared to the control group. There were no significant changes in transferrin isoforms between the acute and chronic pancreatitis groups, and between the edematous and necrotizing forms of the disease. Considering the etiology of acute pancreatitis, we noticed higher values of bile acids and γ-glutamyltransferase in acute pancreatitis of alcoholic etiology than that in pancreatitis of other etiologies. In conclusion, the alterations in transferrin isoform profile in acute and chronic pancreatitis are not organ specific. Because similar changes were observed in hepatitis, we can conclude that the serum profile of transferrin isoforms is involved in the pathogenesis of the disease. Full article

It is not easy to find data in the scientific literature on the quantitative content of individual phytochemicals. It is possible to find groups of compounds and even individual compounds rather easily, but it is not known what their concentration is in cultivated or wild plants. Therefore, the subject of this study was to determine the content of individual compounds in the new Paulownia species, Oxytree, developed in a biotechnology laboratory in 2008 at La Mancha University in Spain. Six secondary metabolites were isolated, and their chemical structure was confirmed by spectral methods. An analytical method was developed, which was then used to determine the content of individual compounds in leaves, twigs, flowers and fruits of Paulownia Clon in Vitro 112^®. No flavonoids were found in twigs and fruits of Oxytree, while the highest phenylethanoid glycosides were found in twigs. In this study, we also focused on biological properties (anticoagulant or procoagulant) of extract and four fractions (A–D) of different chemical composition from Paulownia Clon in Vitro 112 leaves using whole human blood. These properties were determined based on the thrombus-formation analysis system (T-TAS), which imitates in vivo conditions to assess whole blood thrombogenecity. We observed that three fractions (A, C and D) from leaves decrease AUC₁₀ measured by T-TAS. In addition, fraction D rich in triterpenoids showed the strongest anticoagulant activity. However, in order to clarify the exact mechanism of action of the active substances present in this plant, studies closer to physiological conditions, i.e., in vivo studies, should be performed, which will also allow to determine the effects of their long-term effects. Full article

The difference from 4 to 6 $\sigma$ in the Hubble constant ($H_0$) between the values observed with the local (Cepheids and Supernovae Ia, SNe Ia) and the high-z probes (Cosmic Microwave Background obtained by the Planck data) still challenges the astrophysics and cosmology community. Previous analysis has shown that there is an evolution in the Hubble constant that scales as $f\left(z\right)={\mathcal{H}}_0/{(1+z)}^{\eta }$, where ${\mathcal{H}}_0$ is $H_0(z=0)$ and $\eta$ is the evolutionary parameter. Here, we investigate if this evolution still holds by using the SNe Ia gathered in the Pantheon sample and the Baryon Acoustic Oscillations. We assume $H_0=70{\mathrm{km}\mathrm{s}}^{-1}{\mathrm{Mpc}}^{-1}$ as the local value and divide the Pantheon into three bins ordered in increasing values of redshift. Similar to our previous analysis but varying two cosmological parameters contemporaneously ($H_0$, ${\Omega }_{0m}$ in the $\Lambda$CDM model and $H_0$, $w_a$ in the $w_0{w}_a$CDM model), for each bin we implement a Markov-Chain Monte Carlo analysis (MCMC) obtaining the value of $H_0$ assuming Gaussian priors to restrict the parameters spaces to values we expect from our prior knowledge of the current cosmological models and to avoid phantom Dark Energy models with $w<-1$. Subsequently, the values of $H_0$ are fitted with the model $f\left(z\right)$. Our results show that a decreasing trend with $\eta \sim {10}^{-2}$ is still visible in this sample. The $\eta$ coefficient reaches zero in 2.0 $\sigma$ for the $\Lambda$CDM model up to 5.8 $\sigma$ for $w_0{w}_a$CDM model. This trend, if not due to statistical fluctuations, could be explained through a hidden astrophysical bias, such as the effect of stretch evolution, or it requires new theoretical models, a possible proposition is the modified gravity theories, $f\left(R\right)$. This analysis is meant to further cast light on the evolution of $H_0$ and it does not specifically focus on constraining the other parameters. This work is also a preparatory to understand how the combined probes still show an evolution of the $H_0$ by redshift and what is the current status of simulations on GRB cosmology to obtain the uncertainties on the ${\Omega }_{0m}$ comparable with the ones achieved through SNe Ia. Full article

The Poland-AOD aerosol research network was established in 2011 to improve aerosol–climate interaction knowledge and provide a real-time and historical, comprehensive, and quantitative database for the aerosol optical properties distribution over Poland. The network consists of research institutions and private owners operating 10 measurement stations and an organization responsible for aerosol model transport simulations. Poland-AOD collaboration provides observations of spectral aerosol optical depth (AOD), Ångstrom Exponent (AE), incoming shortwave (SW) and longwave (LW) radiation fluxes, vertical profiles of aerosol optical properties and surface aerosol scattering and absorption coefficient, as well as microphysical particle properties. Based on the radiative transfer model (RTM), the aerosol radiative forcing (ARF) and the heating rate are simulated. In addition, results from GEM-AQ and WRF-Chem models (e.g., aerosol mass mixing ratio and optical properties for several particle chemical components), and HYSPLIT back-trajectories are used to interpret the results of observation and to describe the 3D aerosol optical properties distribution. Results of Poland-AOD research indicate progressive improvement of air quality and at mospheric turbidity during the last decade. The AOD was reduced by about 0.02/10 yr (at 550 nm), which corresponds to positive trends in ARF. The estimated clear-sky ARF trend is 0.34 W/m²/10 yr and 0.68 W/m²/10 yr, respectively, at TOA and at Earth’s surface. Therefore, reduction in aerosol load observed in Poland can significantly contribute to climate warming. Full article

Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25–40 kg/m²) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300–2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect. Full article

In this paper, we propose a new estimation procedure for discovering the structure of Gaussian Markov random fields (MRFs) with false discovery rate (FDR) control, making use of the sorted ${\ell }_1$ -norm (SL1) regularization. A Gaussian MRF is an acyclic graph representing a multivariate Gaussian distribution, where nodes are random variables and edges represent the conditional dependence between the connected nodes. Since it is possible to learn the edge structure of Gaussian MRFs directly from data, Gaussian MRFs provide an excellent way to understand complex data by revealing the dependence structure among many inputs features, such as genes, sensors, users, documents, etc. In learning the graphical structure of Gaussian MRFs, it is desired to discover the actual edges of the underlying but unknown probabilistic graphical model—it becomes more complicated when the number of random variables (features) p increases, compared to the number of data points n. In particular, when $p\gg n$ , it is statistically unavoidable for any estimation procedure to include false edges. Therefore, there have been many trials to reduce the false detection of edges, in particular, using different types of regularization on the learning parameters. Our method makes use of the SL1 regularization, introduced recently for model selection in linear regression. We focus on the benefit of SL1 regularization that it can be used to control the FDR of detecting important random variables. Adapting SL1 for probabilistic graphical models, we show that SL1 can be used for the structure learning of Gaussian MRFs using our suggested procedure nsSLOPE (neighborhood selection Sorted L-One Penalized Estimation), controlling the FDR of detecting edges. Full article

CA-170 is currently the only small-molecule modulator in clinical trials targeting PD-L1 and VISTA proteins – important negative checkpoint regulators of immune activation. The reported therapeutic results to some extent mimic those of FDA-approved monoclonal antibodies overcoming the limitations of the high production costs and adverse effects of the latter. However, no conclusive biophysical evidence proving the binding to hPD-L1 has ever been presented. Using well-known in vitro methods: NMR binding assay, HTRF and cell-based activation assays, we clearly show that there is no direct binding between CA-170 and PD-L1. To strengthen our reasoning, we performed control experiments on AUNP-12 – a 29-mer peptide, which is a precursor of CA-170. Positive controls consisted of the well-documented small-molecule PD-L1 inhibitors: BMS-1166 and peptide-57. Full article

Nutrients influence bone turnover. Carboxylated osteocalcin (Gla-OC) participates in bone formation whereas its undercarboxylated form (Glu-OC) acts as a hormone in glucose metabolism. The aim of the study was to determine the responses of Gla-OC, Glu-OC, and total-OC (calculated as the sum of Gla-OC and Glu-OC) to a high fat mixed meal tolerance test (HFMTT) in non-obese (body mass index (BMI) < 30 kg/m², n = 24) and obese subjects (30 < BMI < 40 kg/m², n = 70) (both sexes, aged 25–65 years). Serum Gla-OC and Glu-OC were measured at baseline as well as at 2 and 6 h during a HFMTT by enzyme-linked immunosorbent assay (ELISA). Baseline Gla-OC, Glu-OC, and total-OC levels were lower in obese individuals compared to non-obese participants (p = 0.037, p = 0.016 and p = 0.005, respectively). The decrease in Gla-OC and total-OC, but not in Glu-OC, concentrations during the HFMTT was suppressed in obese, but not in non-obese controls (p < 0.05, p < 0.01, p = 0.08, respectively). Subjects with the highest homeostatic model assessment for insulin resistance (HOMA-IR) index values had a less pronounced decrease in total-OC compared to patients with values of HOMA-IR index in the 1st quartile (p < 0.05). Net incremental area under Gla-OC inversely correlated with adiponectin (rho = −0.35, p = 0.001). Increase in insulin sensitivity and adiponectin level in obese subjects could beneficially influence postprandial bone turnover expressed by osteocalcin concentration. Full article