- Metabolic syndrome components are associated with oxidative stress in overweight and obese patients. [Journal Article]
- AEArch Endocrinol Metab 2018 May 17
- CONCLUSIONS: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.
- Elastin-like Polypeptide (ELP) Charge Influences Self-Assembly of ELP-mCherry Fusion Proteins. [Journal Article]
- BBiomacromolecules 2018 May 23
- Self-assembly of protein-polymer bioconjugates presents an elegant strategy for controlling nanostructure and orientation of globular proteins in functional materials. Recent work has shown that gene...
Self-assembly of protein-polymer bioconjugates presents an elegant strategy for controlling nanostructure and orientation of globular proteins in functional materials. Recent work has shown that genetic fusion of globular protein mCherry to an elastin-like polypeptide (ELP) yields similar self-assembly behavior to these protein-polymer bioconjugates. In the context of studying protein-polymer bioconjugate self-assembly, the mutability of the ELP sequence allows several different properties of the ELP block to be tuned orthogonally while maintaining consistent polypeptide backbone chemistry. This work uses this ELP sequence tunability in combination with the precise control offered by genetic engineering of an amino acid sequence to generate a library of four novel ELP sequences that are used to study the combined effect of charge and hydrophobicity on ELP-mCherry fusion protein self-assembly. Concentrated solution self-assembly is studied by small-angle X-ray scattering (SAXS) and depolarized light scattering (DPLS). These experiments show that fusions containing a negatively charged ELP block do not assemble at all, and fusions with a charge balanced ELP block exhibit a weak propensity for assembly. By comparison, the fusion containing an uncharged ELP block starts to order at 40 wt % in solution and at all concentrations measured has sharper, more intense SAXS peaks than other fusion proteins. These experiments show that charge character of the ELP block is a stronger predictor of self-assembly behavior than the hydrophobicity of the ELP block. Dilute solution small-angle neutron scattering (SANS) on the ELPs alone suggests that all ELPs used in this study (including the uncharged ELP) adopt dilute solution conformations similar to those of traditional polymers, including polyampholytes and polyelectrolytes. Finally, dynamic light scattering studies on ELP-mCherry blends shows that there is no significant complexation between the charged ELPs and mCherry. Therefore, it is proposed that the superior self-assembly of fusion proteins containing uncharged ELP block is due to effective repulsions between charged and uncharged blocks due to local charge correlation effects and, in the case of anionic ELPs, repulsion between like charges within the ELP block.
- Risk Factors of Valproic Acid-Induced Hyperammonaemia in Chinese Paediatric Patients with Epilepsy. [Journal Article]
- BCBasic Clin Pharmacol Toxicol 2018 May 23
- The present study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic ...
The present study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic patients, treated with VPA as monotherapy, were enrolled and classified into hyperammonaemia and control groups according to their blood ammonia level (cut-off value 50 μmol/L). Serum concentrations of VPA and its major metabolites were simultaneously determined by ultra-high performance liquid chromatography-tandem mass spectrometry. Six single nucleotide polymorphisms in the candidate genes, CYP2C9, CYP2A6, CYP2B6 and CPS1, were analysed by a matrix-assisted laser desorption ionization-time of flight mass spectrometry method or nested-PCR. Significant differences in age, aspartate transaminase level and the incidence of liver injury were observed between patients of hyperammonaemia and control groups. Genotype distributions of CYP2C9*3, CYP2A6*4 and CPS1 4217C>A allelic variants were also significantly different between the two groups. According to multiple regression analysis, a significant negative correlation was detected between age and the blood ammonia level, while liver injury, the concentration-dose ratio (CDR) of VPA and 2-propyl-4-pentenoic acid (4-ene VPA), and the presence of CYP2C9*3, CYP2A6*4 or CPS1 4217C>A showed positive correlations with the blood ammonia level. In addition, the risk factors for hyperammonaemia identified by logistic regression analysis were: a younger age (odds ratio [OR] = 0.85; 95% confidence interval [CI] = 0.76 - 0.96; p = 0.007), occurrence of liver injury (OR = 4.60; 95% CI = 1.27 - 16.74; p = 0.021), higher CDR of 4-ene VPA (OR = 1.08; 95% CI = 1.03 - 1.14; p = 0.001), and carrying mutant alleles of CYP2C9*3 (OR = 3.42; 95% CI = 1.15 - 10.19; p = 0.028), CYP2A6*4 (OR = 3.23; 95% CI = 1.40 - 7.48; p = 0.006) and CPS1 4217C>A (OR = 3.25; 95% CI = 1.52 - 6.94; p = 0.002). Our findings indicated that multiple genetic and non-genetic risk factors that were identified can be used to predict the development of VPA-induced hyperammonaemia in Chinese paediatric patients with epilepsy. This article is protected by copyright. All rights reserved.
- The effect of elevated α1-acid glycoprotein on the pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, in rats. [Journal Article]
- XXenobiotica 2018 May 23; :1-32
- 1. The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. 2. Follow...
1. The pharmacokinetics of TAK-272 (SCO-272), an orally active renin inhibitor, was investigated in rats with subcutaneously injected turpentine oil, which was an inflammation animal model. 2. Following intravenous administration of TAK-272 to the turpentine-treated rats, the systemic clearance and volume of distribution decreased with the elevated plasma α1-acid glycoprotein (AGP) levels. The elevated plasma AGP levels were negatively correlated with the plasma unbound fraction of TAK-272 in the rats. Although the AUCs of total TAK-272 in the turpentine-treated rats were higher than those in the control rats after intravenous and oral administration, those of unbound TAK-272, which seem to directly contribute to the pharmacological effect and safety, were nearly equal between the turpentine-treated and control rats in the respective dose routes. TAK-272 has been shown to primarily bind to AGP in the human plasma. 3. These results strongly suggested that the pharmacokinetic of TAK-272 in humans would also be affected by the variation in the plasma AGP levels and should be discussed with not only the total concentrations but also the unbound concentrations in the clinical trial for patients with elevated plasma AGP levels.
- Development and characterization of polymeric microparticle of poly(D,L-lactic acid) loaded with holmium acetylacetonate. [Journal Article]
- JMJ Microencapsul 2018 May 23; :1-31
- Biodegradable polymers containing radioactive isotopes such as Holmium 166 (166Ho) have potential applications as beta particle emitters in tumor tissues. It is also a gamma ray emitter, allowing nuc...
Biodegradable polymers containing radioactive isotopes such as Holmium 166 (166Ho) have potential applications as beta particle emitters in tumor tissues. It is also a gamma ray emitter, allowing nuclear imaging of any tissue to be acquired. It is frequently used in the form of complexes such as holmium acetylacetonate (HoAcAc), which may cause damages in tissues next to the targets cancer cells, as it is difficult to control its linkage or healthy tissues radiotherapy effects. Poly(D,L-lactic acid), PDLLA, was used to encapsulate holmium acetylacetonate (HoAcAc) using an emulsion solvent extraction/evaporation technique. Microspheres with sizes between 20-53 µm were extensively characterized. HoAcAc release from the microspheres was assessed through studies using Inductively Coupled Plasma - Optical Emission Spectroscopy, and the microspheres showed no holmium leakage after a period of 10 half-lives and following gamma irradiation. Thus, HoAcAc loaded microspheres are here presented as a potential system for brachytherapy and imaging purposes.
- Amino Acid-Assisted Incorporation of Dye Molecules within Calcite Crystals. [Journal Article]
- ACAngew Chem Int Ed Engl 2018 May 23
- Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic...
Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic studies have investigated the cooperative effectives of soluble additives. This work addresses this challenge and focuses on the combined effects of amino acids and coloured dye molecules. The experiments demonstrate that strongly coloured calcite crystals only form in the presence of Brilliant Blue R (BBR) and four of the seventeen soluble amino acids, as compared with almost colourless crystals using the dye alone. The active amino acids are identified as those which themselves effectively occluded in calcite, suggesting a mechanism where they can act as chaperones for individual molecules or even aggregates of dyes molecules. These results provide new insight into crystal-additive interactions and suggest a novel strategy for generating materials with target properties.
- Rapid and non-invasive quality control of anhydrous milk fat by PTR-MS: the effect of storage time and packaging. [Journal Article]
- JMJ Mass Spectrom 2018 May 23
- In this study, Proton Transfer Reaction - Mass Spectrometry (PTR-MS), coupled with a time-of-flight mass analyzer and a multipurpose automatic sampler, was evaluated as a rapid and non-destructive to...
In this study, Proton Transfer Reaction - Mass Spectrometry (PTR-MS), coupled with a time-of-flight mass analyzer and a multipurpose automatic sampler, was evaluated as a rapid and non-destructive tool for the quality control (QC) of anhydrous milk fat (AMF). AMFs packed in cardboard and bag-in-box were compared during refrigerated shelf-life at 4°C for 9 months. AMF samples were taken at 120, 180 and 240 days and measured by PTR-MS during storage at 50°C for 11 days. Univariate and multivariate data analysis were performed in order to classify samples according to the packaging type and compare aromatic profiles. Markers related to both packaging and storage duration were identified and all stored samples were clearly distinguishable from reference fresh samples. Significant differences in some key butter aroma compounds such as 2-pentanone, 2-heptanone, 2/3-methylbutanal, acetoin, and butanoic acid were observed between different types of packaging. During the refrigerated storage, differences related to packaging are more evident, while during the storage at 50°C, the fat oxidation induced by the high temperature becomes the most relevant phenomenon independently of the packaging type. These results indicates the importance of avoiding AMF storage at 50°C for long times during industrial production processes. All together data demonstrated the viability of PTR-MS as a rapid and high sensitivity tool in agroindustry quality control program.
- Effects of rearing system on meat quality, fatty acid and amino acid profiles of Hu lambs. [Journal Article]
- ASAnim Sci J 2018 May 23
- To determine the effects of early rearing system on meat quality traits, fatty acid and amino acid profiles of meat, 48 Hu lambs were selected and randomly divided into four treatments: control lambs...
To determine the effects of early rearing system on meat quality traits, fatty acid and amino acid profiles of meat, 48 Hu lambs were selected and randomly divided into four treatments: control lambs were ewe-reared from birth to 60 days of age (ER), while treatment lambs were segregated from their dams at 10, 20 and 30 days of age, then artificially reared with milk replacer until 60 days of age (EW10, EW20 and EW30, respectively). All lambs had no access to the milk replacer or their dams from 61 to 90 days. Creep feed was supplied ad libitum to all lambs from 15 to 90 days of age. Artificially reared lambs (EW10, EW20 and EW30) had higher (p < .05) creep feed intake, average daily gain, slaughter weight, hot carcass weight, meat ether extract content, bright meat color (lightness and yellowness) than ewe-reared lambs. The content of unsaturated fatty acids and monounsaturated fatty acids in EW10 and EW20 were greater (p < .05) than that in ER, whereas the proportions of saturated fatty acids in EW10 and EW20 were lower than that in ER (p < .05). The percentages of C18:0, C18:2, C18:3 and the ratio of polyunsaturated fatty acids and saturated fatty acids of artificially reared lambs were greater than ewe-reared lambs (p < .05). The meat proportions of leucine, alanine and proline were higher (p < .05) in artificially reared lambs than ewe-reared ones. Finally, the artificially reared system increased meat production and changed the fatty acid and amino acid profiles of meat, and it would be appropriate to rear Hu lambs artificially from 10 days with milk replacer.
- Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents. [Journal Article]
- HepHepatology 2018 May 23
- Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of...
Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet (HFSD)-induced hepatic steatosis, PKCε activation and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (∼30 to 130%, depending on length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to a ∼15% increase in hepatic VLDL production and ∼20% reduction in triglyceride clearance by lipoprotein lipase (LPL) (P ≤ 0.05). At the molecular level, these changes were associated with increases in LXR/SREBP1 and decreases in PPARα target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. This article is protected by copyright. All rights reserved.
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- Is gestational diabetes mellitus in obese women predicted by oxidative damage in red blood cells? [Journal Article]
- GEGynecol Endocrinol 2018 May 23; :1-6
- Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To e...
Obesity in pregnant women has been associated with an increased risk of maternal complications, including gestational diabetes mellitus (GDM), a process that is related to oxidative stress (OS). To evaluate the biomarkers of OS in red blood cells (RBCs), we assigned 80 pregnant women to one of three groups: control (n = 28), overweight (n = 26) and obese (n = 26). Then, we measured in plasma, the levels of glucose, triacylglycerol (TAG), insulin, free fatty acids (FFAs), leptin and cytokines (e.g. interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]) and OS biomarkers, such as lipohydroperoxides (LHP), malondialdehyde (MDA) and protein carbonylation (PC) in RBCs. We found significant positive correlations between OS biomarkers, body mass index (BMI) and pregnancy progression. Seven (26.9%) obese women who were diagnosed with GDM at 24-28 weeks of pregnancy showed significantly increased concentrations of FFAs, insulin, leptin, TNF-alpha and biomarkers of OS measured at 12-13 weeks of gestation. We propose to quantify LHP, MDA and PC in membranes of erythrocytes as possible markers to diagnose GDM from weeks 12-14.