Infrared spectroscopy analysis determining secondary structure change in albumin by cerium oxide nanoparticles

Cerium oxide (CeO2) nanoparticles are expected to have applications in the biomedical field because of their antioxidative properties. Inorganic nanoparticles interact with proteins at the nanoparticle surface and change their conformation when administered; however, the principle underlying this interaction is still unclear. This study aimed to investigate the secondary structural changes occurring in bovine serum albumin (BSA) mixed with CeO2 nanoparticles having different surface modifications using Fourier transform infrared spectroscopy. CeO2 nanoparticles (diameter: 240 nm) were synthesized from an aqueous cerium (III) nitrate solution using a homogeneous precipitation method. The surfaces of the nanoparticles were modified by the catechol compounds dopamine and 3,4-dihydroxyhydrocinnamic acid (DHCA). In the presence of these CeO2 nanoparticles (0.11–0.43 mg/mL), β-sheet formation of BSA (30 mg/mL) was promoted especially on the amine-modified (positively charged) nanoparticles. The local concentration of BSA on the surface of the positively charged nanoparticles may have resulted in structural changes due to electrostatic and other interactions with BSA. Further investigations of the interaction mechanism between nanoparticles and proteins are expected to lead to the safe biomedical applications of inorganic nanoparticles

CHANGES IN THE SECONDARY STRUCTURE AND ASSEMBLY OF PROTEINS ON FLUORIDE CERAMIC (CEF3) NANOPARTICLE SURFACES

Fluoride nanoparticles (NPs) are materials utilized in the biomedical field for applications including imaging of the brain. Their interactions with biological systems and molecules are being investigated, but the mechanism underlying these interactions remains unclear. We focused on possible changes in the secondary structure and aggregation state of proteins on the surface of NPs and investigated the principle underlying the changes using the amyloid β peptide (Aβ16−20) based on infrared spectrometry. CeF3 NPs (diameter 80 nm) were synthesized via thermal decomposition. Infrared spectrometry showed that the presence of CeF3 NPs promotes the formation of the β-sheet structure of Aβ16−20. This phenomenon was attributed to the hydrophobic interaction between NPs and Aβ peptides in aqueous environments, which causes the Aβ peptides to approach each other on the NP surface and form ordered hydrogen bonds. Because of the coexisting salts on the secondary structure and assembly of Aβ peptides, the formation of the β-sheet structure of Aβ peptides on the NP surface was suppressed in the presence of NH4 + and NO3 − ions, suggesting the possibility that Aβ peptides were adsorbed and bound to the NP surface. The formation of the β-sheet structure of Aβ peptides was promoted in the presence of NH4 + , whereas it was suppressed in the presence of NO3 − because of the electrostatic interaction between the lysine residue of the Aβ peptide and the ions. Our findings will contribute to comparative studies on the effect of different NPs with different physicochemical properties on the molecular state of proteins

Japanese subpopulation analysis of MONARCH 2: phase 3 study of abemaciclib plus fulvestrant for treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that progressed on endocrine therapy

BACKGROUND: This was a Japanese subpopulation analysis of MONARCH 2, a double-blind, randomized, placebo-controlled, phase 3 study of abemaciclib plus fulvestrant in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). METHODS: Eligible women had progressed on (neo)adjuvant endocrine therapy (ET),  ≤ 12 months from end of adjuvant ET, or on first-line ET for ABC, and had not received chemotherapy for ABC. Patients were randomized 2:1 to receive abemaciclib or placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), pharmacokinetics (PK), health-related quality of life (HRQoL), and safety. RESULTS: In Japan, 95 patients were randomized (abemaciclib, n = 64; placebo, n = 31). At final PFS analysis (February 14, 2017), median PFS was 21.2 and 14.3 months, respectively, in the abemaciclib and placebo groups (hazard ratio: 0.672; 95% confidence interval: 0.380-1.189). Abemaciclib had a higher objective response rate (37.5%) than placebo (12.9%). PK and safety profiles for Japanese patients were consistent with those of the overall population, without clinically meaningful differences across most HRQoL dimensions evaluated. The most frequent adverse events in the abemaciclib versus placebo groups were diarrhea (95.2 versus 25.8%), neutropenia (79.4 versus 0%), and leukopenia (66.7 versus 0%). At a second data cutoff (June 20, 2019), median OS was not reached with abemaciclib and 47.3 months with placebo (hazard ratio: 0.755; 95% confidence interval: 0.390-1.463). CONCLUSIONS: Results of the Japanese subpopulation were consistent with the improved clinical outcomes and manageable safety profile observed in the overall population. CLINICAL TRIAL REGISTRATION: NCT02107703; U.S. National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT02107703

Combined insulin B:9-23 self-peptide and polyinosinic-polycytidylic acid accelerate insulitis but inhibit development of diabetes by increasing the proportion of CD4+Foxp3+ regulatory T cells in the islets in non-obese diabetic mice.

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes. Combined treatment with B:9-23 peptide and polyinosinic-polycytidylic acid (poly I:C), but neither alone, induce insulitis in normal BALB/c mice. In contrast, the combined treatment accelerated insulitis, but prevented diabetes in NOD mice. Our immunofluorescence study with anti-CD4/anti-Foxp3 revealed that the proportion of Foxp3 positive CD4(+)CD25(+) regulatory T cells (Tregs) was elevated in the islets of NOD mice treated with B:9-23 peptide and poly I:C, as compared to non-treated mice. Depletion of Tregs by anti-CD25 antibody hastened spontaneous development of diabetes in non-treated NOD mice, and abolished the protective effect of the combined treatment and conversely accelerated the onset of diabetes in the treated mice. These results indicate that poly I:C combined with B:9-23 peptide promotes infiltration of both pathogenic T cells and predominantly Tregs into the islets, thereby inhibiting progression from insulitis to overt diabetes in NOD mice

Gasification of bio-oil and bio-oil/char slurry

Economic utilization of biomass as a fuel has been limited by transportation cost. One suggested remedy to address the problems of processing biomass on a large scale is to pyrolyze solid biomass at numerous local sites and transport the resulting liquid or liquid/char slurry to a large centralized conversion plant. This research involves the gasification of biomass fast pyrolysis oil, so called bio-oil, and a slurry mixture of bio-oil and fast pyrolysis char into synthesis gas. Kinetics of the reaction of steam with chars was studied using a thermo-gravimetric analyzer. Slurry Char was produced by pyrolysis of an 80 wt% bio-oil/20 wt% char mixture at nominal heating rates of 100–10,000°C/s. The resulting Slurry Char was subjected to steam gasification with 10–50 mol% steam at 800–1200°C. Reactivity of the Slurry Chars increased with the pyrolysis heating rate, but was lower than that of Original Chars. Kinetic parameters were established for a power-law rate model. Some measurements were initially done of gasification in CO₂. A fluidized bed reactor, equipped with an atomization system, was constructed for gasification of bio-oil and slurry. The reactor contained either sand, or Ni-based catalyst. Experiments included gasification with pure steam and air. Effects of bed temperatures in the range 720–850°C, steam-to-carbon molar ratios of 2.0–7.5, and air ratios of 0–0.5 on gas composition and yields were tested. The carbon conversion of bio-oil to gas was found to be greater than that of slurry. The product gas composition was affected significantly by catalysis of the water-gas shift and the steam gasification. Greater yields of hydrogen and lesser yields of CO and hydrocarbons were found when catalyst was used. On a dry, inert-free basis, gases of up to 61% H₂ were obtained. The data were compared with a thermodynamic equilibrium model. The product gas yield was reasonably predictable by the model. A mass and energy balance model of steam gasification in a dual-bed gasifier-combustor revealed that energy requirements are sensitive to the steam/carbon ratio and to the recovery of latent heat in the produced gas.Applied Science, Faculty ofChemical and Biological Engineering, Department ofGraduat