Properties and chemical modifications of lignin : Towards lignin-based nanomaterials for biomedical applications

Biorenewable polymers have emerged as an attractive alternative to conventional metallic and organic materials for a variety of different applications. This is mainly because of their biocompatibility, biodegradability and low cost of production. Lignocellulosic biomass is the most promising renewable carbon-containing source on Earth. Depending on the origin and species of the biomass, lignin consists of 20-35% of the lignocellulosic biomass. After it has been extracted, lignin can be modified through diverse chemical reactions. There are different categories of chemical modifications, such as lignin depolymerization or fragmentation, modification by synthesizing new chemically active sites, chemical modification of the hydroxyl groups, and the production of lignin graft copolymers. Lignin can be used for different industrial and biomedical applications, including biofuels, chemicals and polymers, and the development of nanomaterials for drug delivery but these uses depend on the source, chemical modifications and physicochemical properties. We provide an overview on the composition and properties, extraction methods and chemical modifications of lignin in this review. Furthermore, we describe different preparation methods for lignin-based nanomaterials with antioxidant UV-absorbing and antimicrobial properties that can be used as reinforcing agents in nanocomposites, in drug delivery and gene delivery vehicles for biomedical applications. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Permeation of Dopamine Sulfate through the Blood-Brain Barrier

Dopamine sulfate (DA-3- and DA-4-S) have been determined in the human brain, but it is unclear whether they are locally formed in the central nervous system (CNS), or transported into the CNS from peripheral sources. In the current study, permeation of the blood-brain barrier (BBB) by DA-S was studied by injecting C-13(6)-labelled regioisomers of DA-S ((13)DA-3-S and (13)DA-4-S) and dopamine (DA) subcutaneously (s.c.) in anesthetized rats, then analyzing brain microdialysis and plasma samples by UPLC-MS/MS. The results in the microdialysis samples demonstrated that brain concentrations of (13)DA-S regioisomers clearly increased after the s.c. injections. The concentration of DA did not change, indicating the permeation of DA-S through an intact BBB. The analysis of plasma samples, however, showed that DA-S only permeates the BBB to a small extent, as the concentrations in plasma were substantially higher than in the microdialysis samples. The results also showed that the concentrations of DA-3-S were around three times higher than the concentrations of DA-4-S in rat brain, as well as in the plasma samples after the s.c. injections, indicating that DA-3-S and DA-4-S permeate the BBB with similar efficiency. The fate of (13)DA-S in brain was followed by monitoring C-13(6)-labelled DA-S hydrolysis products, i.e. (13)DA and its common metabolites; however, no C-13(6)-labelled products were detected. This suggests that DA-S either permeates through the BBB back to the peripheral circulation or is dissociated or metabolized by unexpected mechanisms.Peer reviewe

Knoevenagel condensation for modifying the reducing endgroups of cellulose nanocrystals

Peer reviewe

Superhydrophobic Paper from Nanostructured Fluorinated Cellulose Esters

The development of economically and ecologically viable strategies for sup erhydrophobization offers a vast variety of interesting applications in self-cleaning surfaces. Examples include packaging materials, textiles, outdoor clothing, and microfluidic devices. In this work, we produced superhydrophobic paper by spin-coating a dispersion of nanostructured fluorinated cellulose esters. Modification of cellulose nanocrystals was accomplished using 2H,2H,3H,3H-perfluorononanoyl chloride and 2H,2H,3H,3H-perfluoroundecanoyl chloride, which are well-known for their ability to reduce surface energy. A stable dispersion of nanospherical fluorinated cellulose ester was obtained by using the nanoprecipitation technique. The hydrophobized fluorinated cellulose esters were characterized by both solid- and liquid-state nuclear magnetic resonance, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and contact angle measurements. Further, we investigated the size, shape, and structure morphology of nanostructured fluorinated cellulose esters by dynamic light scattering, scanning electron microscopy, and X-ray diffraction measurements.Peer reviewe

Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients

Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R-2), and intra- and inter-day repeatability of each metabolite. The method's performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic

DNA-origami-directed virus capsid polymorphism

Viral capsids can adopt various geometries, most iconically characterized by icosahedral or helical symmetries. Importantly, precise control over the size and shape of virus capsids would have advantages in the development of new vaccines and delivery systems. However, current tools to direct the assembly process in a programmable manner are exceedingly elusive. Here we introduce a modular approach by demonstrating DNA-origami-directed polymorphism of single-protein subunit capsids. We achieve control over the capsid shape, size and topology by employing user-defined DNA origami nanostructures as binding and assembly platforms, which are efficiently encapsulated within the capsid. Furthermore, the obtained viral capsid coatings can shield the encapsulated DNA origami from degradation. Our approach is, moreover, not limited to a single type of capsomers and can also be applied to RNA–DNA origami structures to pave way for next-generation cargo protection and targeting strategies.</p

Work-family life courses and BMI trajectories in three British birth cohorts.

BACKGROUND/OBJECTIVES: Combining work and family responsibilities has previously been associated with improved health in mid-life, yet little is known about how these associations change over time (both biographical and historical) and whether this extends to body mass index (BMI) trajectories for British men and women. The purpose of this study was to investigate relationships between work-family life courses and BMI trajectories across adulthood (16-42 years) for men and women in three British birth cohorts. SUBJECTS/METHODS: Multiply imputed data from three nationally representative British birth cohorts were used-the MRC National Survey of Health and Development (NSHD; 1946 birth cohort, n=3012), the National Child Development Study (NCDS; 1958 birth cohort, n=9614) and the British Cohort Study (BCS; 1970 birth cohort, n=8140). A typology of work-family life course types was developed using multi-channel sequence analysis, linking annual information on work, partnerships and parenthood from 16 to 42 years. Work-family life courses were related to BMI trajectories using multi-level growth models. Analyses adjusted for indicators of prior health, birthweight, child BMI, educational attainment and socioeconomic position across the life course, and were stratified by gender and cohort. RESULTS: Work-family life courses characterised by earlier transitions to parenthood and weaker long-term links to employment were associated with greater increases in BMI across adulthood. Some of these differences, particularly for work-family groups, which are becoming increasingly non-normative, became more pronounced across cohorts (for example, increases in BMI between 16 and 42 years in long-term homemaking women: NSHD: 4.35 kg m-2, 95% confidence interval (CI): 3.44, 5.26; NCDS: 5.53 kg m-2, 95% CI: 5.18, 5.88; BCS: 6.69 kg m-2, 95% CI: 6.36, 7.02). CONCLUSIONS: Becoming a parent earlier and weaker long-term ties to employment are associated with greater increases in BMI across adulthood in British men and women.Rebecca Lacey, Anne McMunn, Amanda Sacker and Meena Kumari received funding from the European Research Council (grant number: ERC-2011-StG_20101124, PI: Anne McMunn). Steven Bell also received funding from the European Research Council (grant number: ERCStG-2012-309337_Alcohol-Lifecourse, PI: Annie Britton) and UK Medical Research Council/Alcohol Research UK (MR/M006638/1). Amanda Sacker, Anne McMunn and Meena Kumari additionally received support from the Economic and Social Research Council’s International Centre for Life Course Studies in Society and Health (grant number: ES/J019119/1). DK is supported by the UK Medical Research Council (MC_UU_12019/1). The MRC National Survey of Health and Development is funded by the UK Medical Research Council. Peggy McDonough and Diana Worts were supported by the Canadian Institutes of Health Research grant MOP 119526 and the Social Sciences and Humanities Research Council grant 43512-1267

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well