Decellularization of Human Pancreatic Fragments with Pronounced Signs of Structural Changes

A significant lack of donor organs restricts the opportunity to obtain tissue-specific scaffolds for tissue-engineering technologies. One of the acceptable solutions is the development of decellularization protocols for a human donor pancreas unsuitable for transplantation. A protocol of obtaining a biocompatible tissue-specific scaffold from decellularized fragments with pronounced human pancreas lipomatosis signs with preserved basic fibrillary proteins of a pancreatic tissue extracellular matrix was developed. The scaffold supports the adhesion and proliferation of human adipose derived stem cell (hADSCs) and prolongs the viability and insulin-producing function of pancreatic islets. Experiments conducted allow for the reliance on the prospects of using the donor pancreas unsuitable for transplantation in the technologies of tissue engineering and regenerative medicine, including the development of a tissue equivalent of a pancreas.     

Effect of Betaine and Arginine on Interaction of αB-Crystallin with Glycogen Phosphorylase b

Protein–protein interactions (PPIs) play an important role in many biological processes in a living cell. Among them chaperone–client interactions are the most important. In this work PPIs of αB-crystallin and glycogen phosphorylase b (Phb) in the presence of betaine (Bet) and arginine (Arg) at 48 °C and ionic strength of 0.15 M were studied using methods of dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation. It was shown that Bet enhanced, while Arg reduced both the stability of αB-crystallin and its adsorption capacity (AC₀) to the target protein at the stage of aggregate growth. Thus, the anti-aggregation activity of αB-crystallin increased in the presence of Bet and decreased under the influence of Arg, which resulted in inhibition or acceleration of Phb aggregation, respectively. Our data show that chemical chaperones can influence the tertiary and quaternary structure of both the target protein and the protein chaperone. The presence of the substrate protein also affects the quaternary structure of αB-crystallin, causing its disassembly. This is inextricably linked to the anti-aggregation activity of αB-crystallin, which in turn affects its PPI with the target protein. Thus, our studies contribute to understanding the mechanism of interaction between chaperones and proteins.     

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2–F3–F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

Carotenoids from Marine Sources as a New Approach in Neuroplasticity Enhancement

An increasing number of people experience disorders related to the central nervous system (CNS). Thus, new forms of therapy, which may be helpful in repairing processes’ enhancement and restoring declined brain functions, are constantly being sought. One of the most relevant physiological processes occurring in the brain for its entire life is neuroplasticity. It has tremendous significance concerning CNS disorders since neurological recovery mainly depends on restoring its structural and functional organization. The main factors contributing to nerve tissue damage are oxidative stress and inflammation. Hence, marine carotenoids, abundantly occurring in the aquatic environment, being potent antioxidant compounds, may play a pivotal role in nerve cell protection. Furthermore, recent results revealed another valuable characteristic of these compounds in CNS therapy. By inhibiting oxidative stress and neuroinflammation, carotenoids promote synaptogenesis and neurogenesis, consequently presenting neuroprotective activity. Therefore, this paper focuses on the carotenoids obtained from marine sources and their impact on neuroplasticity enhancement.     

Ether alcohol sulfates. The effect of oxypropylation and oxybutylation on surface active properties

The reaction of 1,2-butylene oxide with fatty alcohols of 12 to 18 carbon atoms was investigated and products were compared with those from the propylene oxide reaction. A 60% yield of the first derivative was obtained for the butylene oxide reaction compared with a maximum yield of 50% for the propylene oxide reaction. First and second derivatives were fractionally distilled from the reaction mixtures and characterized as pure ether alcohols and their acetates. Sulfation of the pure ether alcohols permitted some interesting comparisons of the effect of structural change on surface active properties. Oxybutylation gave slightly greater solubility increases than oxypropylation and both reactions were more effective than oxyethylation. Dioxyalkylated products had lower Krafft points than monooxyalkylated products. A low degree of oxyalkylation had only minor effects on the detergency of alcohol sulfates but polyoxybutylation caused significant reductions in foam height for the 16 and 18 carbon alcohol sulfates. Critical micelle concentration was reduced both by increasing degree of oxyalkylation and molecular weight of epoxide. All of the ether alcohol sulfates were effective lime soap dispersing agents. Presented at the AOCS Meeting in Philadelphia, October 1966. E. Utiliz. Res. Dev. Div., ARS, USDA.     

Comparative Characteristics of the Structure and Physicochemical Properties of Silica Synthesized by Pyrogenic and Fluoride Methods

Silicon - This paper presents the comparative analysis of the properties of highly dispersed silicas synthesized by pyrogenic and fluoride methods. Raw materials and synthesis conditions differ...     

Field Comparison of P-Trak and Condensation Particle Counters

The P-trak ultrafine particle counter is a portable version of a condensation particle counter (CPC). Both instruments detect particle number concentrations in real time but have different detection limits. The P-trak has been widely used for indoor air quality evaluation and aerosol research. However, there is very limited information about the reliability and precision of this instrument and its comparability with other similar instruments. The purpose of this study was to compare a P-trak ultrafine particle counter with a standard CPC and evaluate its applicability to ambient air monitoring.

This study was carried out near the Interstate 405 freeway (I-405) in Los Angeles. Measurements were made at increasing distances from the freeway on both sides at night as well as inside and outside of two 2-bedroom apartments located near the freeway. A CPC and a Scanning Mobility Particle Sizer (SMPS) were collocated with two P-traks and measurement results compared.

In general, higher correlations were observed between P-trak and CPC data for indoor measurements than outdoor. The highest P-trak and CPC correlation ( r ² = 0.9385) was detected inside Apartment 2, which is located farther away from the freeway than Apartment 1. The poorest correlation occurred at 30 m downwind from the freeway. In that case, the P-trak reported about 25% of ultrafine particle concentration that CPC did. A sigmoid (S-shape) function was fitted to observed P-trak to CPC ratios and geometric mean diameters of the corresponding ultrafine particle size distributions. Overall, we concluded the P-trak worked reasonably well when sampled indoor air. However, it has significant limitations in detecting freshly emitted ultrafine particles from vehicles. The P-trak underestimated ultrafine particles especially for particles smaller than its activation size which was found to be approximately 25–30 nm. Caution must be given in interpreting data collected by P-trak monitors near combustion sources.     

A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.     

Effect of temperature on hot-air drying rate and on retention of antioxidant capacity in apple leathers

Fruit leathers are pectic gels, eaten as snack or dessert, obtained by dehydrating fruit purees. In this work, apple leathers were prepared by a hot-air drying process which allows the formation of a gel, following the “saccharide–acid–high methoxyl pectin” gelation mechanism. Leathers were produced at 50, 60 and 70 °C, from two formulations: control and added with potassium metabisulphite (KM) as antioxidant. The drying process was studied applying a diffusive model, while antioxidant capacity (AC) losses were represented by a first-order model. Activation energy for drying (20.6 kJ/mol) was lower than those estimated for AC losses in control (31.5 kJ/mol) and KM-added (37.9 kJ/mol) leathers. Therefore, the drying time reduction achieved by increasing air temperature is not sufficient to decrease AC losses in the range covered. AC retention decreased in both formulations at increasing air temperature. KM-added samples showed higher AC retention than the controls, except for those dried at 70 °C. Kinetic constants were lower for KM-added samples, suggesting a protective effect of the additive, especially at moderate air temperatures. In the most favorable situation, AC retention was of only 16%. Therefore, the functional character of these products may not be preserved if dried with hot air and the research on economically viable, less-severe drying technologies should be intensified.