Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ–Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while lutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.

Erratum: Correction of Figure. Influence of Gas Pain, Post-operative Resilience, and Body Temperature Discomfort in Laparoscopic Myomectomy Patients after Thermotherapy / 여성건강간호학회지

The authors found a language error in the published article. The authors replace the Figure 1.

Influence of Gas Pain, Post-operative Resilience, and Body Temperature Discomfort in Laparoscopic Myomectomy Patients after Thermotherapy / 여성건강간호학회지

PURPOSE: The purpose of this study was to investigate the effects of thermotherapy on gas pain, post-operative resilience, and body temperature discomfort among patients who received laparoscopic myomectomies. METHODS: The experimental group consisted of 62 patients with thermotherapy and the control group consisted of 60 patients. Thermotherapy was applied individually to the experimental group four hours after surgery. The collected data was analyzed using descriptive statistics, t-tests, χ²-tests, and repeated measures of analysis of variance, using IBM SPSS Statistics version 18. RESULTS: The results showed no significant interaction effect between the group and time of measurement in gas-related pain in the experimental group. For gas-related pain, there was significant difference in right shoulder pain at 24 hours (t=-4.222, p=.000), 48 hours (t=-3.688, p=.000), 72 hours (t=-2.250, p=.028), and left at 24 hours (t=-3.727, p=.000), 48 hours (t=-4.150, p=.000), and 72 hours (t=-2.482, p=.016) and both shoulders at 24 hours (t=-2.722, p=.009) and 48 hours (t=-2.525, p=.014). There was no significant difference in epigastric pain, excluding both epigastric pain at 48 hours (t=2.908, p=.005), 72 hours (t=3.010, p=.004), but there was a significant difference in objective body temperature discomfort (t=2.895, p=.008). CONCLUSION: Thermotherapy relieved shoulder gas-related pain and objective body temperature discomfort. It needs to be developed and applied to improve post-operative discomfort in patients with laparoscopic hysterectomies.

Targeting the epitope spreader Pep19 by naïve human CD45RA⁺ regulatory T cells dictates a distinct suppressive T cell fate in a novel form of immunotherapy

PURPOSE: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. METHODS: Human polyclonal CD4⁺CD25⁺CD127(lo−) Tregs (127-Tregs) and naïve CD4⁺CD25⁺CD45RA⁺ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an NOD/scid/IL-2Rγ(−/−) mouse model of collagen-induced arthritis. RESULTS: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of CD4⁺CD25⁺ Tregs at the articular joints in a mechanistic and orchestrated way. CONCLUSIONS: We propose human naïve CD4⁺CD25⁺CD45RA⁺ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

The Effects of Wearing Protective Devices among Residents and Volunteers Participating in the Cleanup of the Hebei Spirit Oil Spill / 예방의학회지

OBJECTIVES: To assess the protective effects of wearing protective devices among the residents and volunteers who participated in the cleanup of the Hebei Spirit oil spill. METHODS: A total of 288 residents and 724 volunteers were surveyed about symptoms, whether they were wearing protective devices and potential confounding variables. The questionnaires were administered from the second to the sixth week following the accident. Spot urine samples were collected and analyzed for metabolites of 4 volatile organic compounds (VOCs), 2 polycyclic aromatic hydrocarbons (PAHs), and 6 heavy metals. The association between the wearing of protective devices and various symptoms was assessed using a multiple logistic regression adjusted for confounding variables. A multiple generalized linear regression model adjusted for the covariates was used to test for a difference in least-square mean concentration of urinary biomarkers between residents who wore protective devices and those who did not. RESULTS: Thirty nine to 98% of the residents and 62-98% of volunteers wore protective devices. Levels of fatigue and fever were higher among residents not wearing masks than among those who did wear masks (odds ratio 4.5; 95% confidence interval 1.23-19.86). Urinary mercury levels were found to be significantly higher among residents not wearing work clothes or boots (p<0.05). CONCLUSIONS: Because the survey was not performed during the initial high-exposure period, no significant difference was found in metabolite levels between people who wore protective devices and those who did not, except for mercury, whose biological half-life is more than 6 weeks.