Analytical Strategy for Oxylipin Annotation by Combining Chemical Derivatization-Based Retention Index Algorithm and Feature Tandem Mass Spectrometric Fragmentation as a Biomarker Discovery Tool.

Accurate oxylipin annotation is crucial for advancing our understanding of physiological processes in health and disease and identifying biomarkers. However, a full view of oxylipins for early diagnosis needs further attention due to the lack of proper analytical methods, which may be attributed to the wide dynamic range, poor sensitivity, extreme molecular complexity, and limited commercially available standards of oxylipins. Here, we devised a novel method by combining a chemical derivatization (CD)-based retention index (RI) algorithm and feature tandem mass spectrometric fragmentation annotation (CD-RI-LC-MS/MS) for identification and quantification of oxylipins. To this end, N,N-diethyl-1,3-diaminopropane (DEPA) was used for fast labeling of oxylipin (within 0.5 min at room temperature) to improve separation resolution and detection sensitivity. The RI algorithm was established to calibrate the retention time variances and assist the identification of oxylipins during liquid chromatography-tandem mass spectrometry (LC-MS) analysis. MS/MS analysis of in total 58 DEPA derivatives of authentic oxylipin standards was subsequently employed to obtain the tandem mass spectrometric feature fragmentation rules for further structure elucidation of the unknown regio-isomers. Finally, a method based upon CD-RI-LC-MS/MS was established for profiling oxylipins from Standard Reference Material (SRM) 1950 human plasma and nonalcoholic fatty liver disease (NAFLD) mouse liver tissue samples. A total of 87 and 96 potential oxylipins including 12 and 14 unreported oxylipins were detected and identified from human plasma and mouse liver tissues, respectively. The results showed that compared to the control group, in the liver samples of the NAFLD mouse, the content levels of prostaglandin (PG) E2, PGF2a, 8-hydroxy-eicosatrienoic acid (8-HETrE), and the newly discovered 2-hydroxy-octadecatrienoic acid (2-HOTrE) were remarkably increased, while the oxidation product of n-3 PUFA (p < 0.05) and all hydroperoxy oxylipins significantly decreased. On balance, this method contributes to future studies on oxylipin screening and application in other biological samples for facilitating the understanding of oxylipin roles in metabolic regulation of numerous diseases.

Volume-Corrected Free Energy as a New Criterion for Structural Elucidation in Chemical-Tagging-Based Metabolomics.

Chemical tagging via possible derivatization reagents alters metabolites' retention times, leading to different retention behavior during liquid chromatography-mass spectrometry (LC-MS) analysis. Incorporation of the retention time dimension can dramatically reduce false-positive structural elucidation in chemical-tagging-based metabolomics. However, few studies predict the retention times of chemically labeled metabolites, especially requiring a simple, easy-to-access, accurate, and universal predictor or descriptor. This pilot study demonstrates the application of volume-corrected free energy (VFE) calculation and region mapping as a new criterion to describe the retention time for structure elucidation in chemical-tagging-based metabolomics. The universality of VFE calculation is first evaluated with four different types of submetabolomes including hydroxyl-group-, carbonyl-group-, carboxylic-group-, and amino-group-containing compounds and oxylipins with similar chemical structures and complex isomers on reverse-phase LC. Results indicate a good correlation (r > 0.85) between VFE values and their corresponding retention times using different technicians, instruments, and chromatographic columns, describing retention behavior in reverse-phase LC. Finally, the VFE region mapping is described for identifying 1-pentadecanol from aged camellia seed oil using three proposed steps, including public database searching, VFE region mapping for its 12 isomers, and chemical standard matching. The possibility of VFE calculation of nonderivatized compounds in retention time prediction is also investigated, demonstrating its effectiveness on retention times with different influence factors.

Comparison of Flap Fixation to Its Bed and Conventional Wound Closure with Drainage in Preventing Seroma Formation Following Mastectomy for Breast Cancer: Systematic Review and Meta-analysis.

BACKGROUND: Seroma formation is a common complication following mastectomy. The objective of this systematic review and meta-analysis is to evaluate the impact of flap fixation techniques that omit drainage versus conventional closed drainage on seroma formation and related complications after mastectomy. METHODS: Clinical studies of flap fixation techniques versus the conventional closure technique in patients undergoing mastectomy with or without axillary clearance were retrieved from the PubMed, Embase and Cochrane databases. Papers were eligible for inclusion if the outcome was described in terms of seroma formation. Studies older than 20 years, animal studies and studies involving patients undergoing direct breast reconstruction were excluded. RESULTS: Four randomized controlled trials (RCTs) and four cohort studies were included in our examination. Compared with the conventional drainage group, the flap fixation group had a similar incidence of seroma formation (OR 0.76, 95% CI 0.30-1.93, p = 0.57). CONCLUSION: Based on current evidence, mechanical flap fixation can replace conventional drainage without increasing seroma formation after mastectomy. Further well-designed RCTs are warranted to evaluate the effects of flap fixation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Two-channel near-infrared fluorescence Ag+ ion sensing of a new star-shaped dendrimer.

A new near-infrared fluorescence sensor PDI-PD for Ag+ ions was successfully prepared and its structure characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR and high-resolution mass spectrometry; matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (HRMS MALDI-TOF). The probe exhibited rapid, sensitive, and selective two-channel fluorescence responses towards Ag+ ions and protons. The probe has a marked high binding affinity and high sensitivity for Ag+ , with a detection limit of 1.4 × 10-6  M. An approximately five-fold enhanced core emission at 784 nm was attributed to fluorescence resonance energy transfer (FRET). The enhanced core emission of the probe with Ag+ ions based on photo-induced electron transfer and FRET is discussed. In addition, the probe presented a visible colour change. All experimental results demonstrated that PDI-PD is an efficient tool for the selective, sensitive and rapid detection of Ag+ ions and protons using two-channel fluorescence responses.

Effects of Cholinergic Lesions and Cholinesterase Inhibitors on Aromatase and Estrogen Receptor Expression in Different Regions of the Rat Brain.

Cholinergic projections have been shown to interact with estrogens in ways that influence synaptic plasticity and cognitive performance. The mechanisms are not well understood. The goal of this study was to investigate whether cholinergic projections influence brain estrogen production by affecting aromatase (ARO), or influence estrogen signaling by affecting estrogen receptor expression. In the first experiment, ovariectomized rats received intraseptal injection of the selective immunotoxin 192IgG-saporin to destroy cholinergic inputs to the hippocampus. In the second experiment ovariectomized rats received daily intraperitoneal injections of the cholinesterase inhibitors donepezil or galantamine for 1 week. ARO activity and relative levels of ARO, ERα, ERß, and GPR30 mRNAs were quantified in the hippocampus, frontal cortex, amygdala and preoptic area. Results show that the cholinergic lesions effectively removed cholinergic inputs to the hippocampus, but had no significant effect on ARO or on relative levels of ER mRNAs. Likewise, injections of the cholinesterase inhibitors had no effect on ARO or ER expression in most regions of the brain. This suggests that effects of cholinergic inputs on synaptic plasticity and neuronal function are not mediated by effects on local estrogen production or ER expression. One exception was the amygdala where treating with galantamine was associated with a significant increase in ARO activity. The amygdala is a key structure involved in registering fear and anxiety. Hence this finding may be clinically relevant to elderly patients who are treated for memory impairment and who also struggle with fear and anxiety disorders.