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| 1 | Exogenous phosphatidic acid reduces acetaminophen-induced liver injury in mice by activating hepatic interleukin-6 signaling through inter-organ crosstalk显示文摘We previously demonstrated that endogenous phosphatidic acid(PA)promotes liver regeneration after acetaminophen(APAP)hepatotoxicity.Here,we hypothesized that exogenous PA is also beneficial.To test that,we treated mice with a toxic APAP dose at 0 h,followed by PA or vehicle(Veh)posttreatment.We then collected blood and liver at 6,24,and 52 h.Post-treatment with PA 2 h after APAP protected against liver injury at 6 h,and the combination of PA and N-acetyl-L-cysteine(NAC)reduced injury more than NAC alone.Interestingly,PA did not affect canonical mechanisms of APAP toxicity.Instead,transcriptomics revealed that PA activated interleukin-6(IL-6)signaling in the liver.Consistent with that,serum IL-6 and hepatic signal transducer and activator of transcription 3(Stat3)phosphorylation increased in PA-treated mice.Furthermore,PA failed to protect against APAP in IL-6-deficient animals.Interestingly,IL-6 expression increased 18-fold in adipose tissue after PA,indicating that adipose is a source of PA-induced circulating IL-6.Surprisingly,however,exogenous PA did not alter regeneration,despite the importance of endogenous PA in liver repair,possibly due to its short half-life.These data demonstrate that exogenous PA is also beneficial in APAP toxicity and reinforce the protective effects of IL-6 in this model. | Melissa M.Clemens Stefanie Kennon-McGill Joel H.Vazquez Owen W.Stephens Erich A.Peterson Donald J.Johann Felicia D.Allard Eric U.Yee Sandra SMcCullough Laura P.James Brian N.Finck Mitchell R.McGill | 2021 | Acta Pharmaceutica Sinica B2021，11，12： | 5 |
| 2 | Evaluating the Environmental Health Effect of Bamboo-Derived Volatile Organic Compounds through Analysis the Metabolic Indices of the Disorder Animal Model显示文摘Objective To identify the bamboo VOCs(volatile organic compounds) effect on animal physiological indices, which associated with human health. Methods GC/MS was used to analyze the volatile organic compounds from Moso bamboo(Phyllostachys heterocyla cv. pubescens). The effect of VOCs on environmental health was evaluated by analyzing the metabolic indices of the type 2 diabetic mouse model. Results Spectra of VOC generated by GC/MS were blasted against an in-house MS library confirming the identification of 33 major components that were manually validated. The relative constituent compounds as a percentage of total VOCs determined were alcohols(34.63%), followed by ether(22.02%), aldehyde(15.84%), ketone(11.47%), ester(4.98%), terpenoid(4.38%), and acids(3.83%). Further experimentation established that the metabolic incidence of the disease can be improved if treated with vanillin, leaf alcohol, β-ionone and methyl salicylate. The effects of these VOCs on type 2 diabetes were evident in the blood lipid and blood glucose levels. Conclusion Our model suggests that VOCs can potentially control the metabolic indices in type 2 diabetes mice. This experiment data also provides the scientific basis for the comprehensive utilization of ornamental bamboos and some reference for other similar study of environmental plants. | GUO Ming HU Zheng Qing STRONG P.James SMIT Anne-Marie XU Jian Wei FAN Jun WANG Hai Long | 2015 | Biomedical and Environmental Sciences2015，28，8： | 2 |
| 3 | Pre-treatment twice with liposomal clodronate protects against acetaminophen hepatotoxicity through a pre-conditioning effect显示文摘Background and aim:Acetaminophen(APAP)overdose is a major cause of acute liver injury,but the role of macrophages in the propagation of the hepatotoxicity is controversial.Early research revealed that macrophage inhibitors protect against APAP injury.However,later work demonstrated that macrophage ablation by acute pre-treatment with liposomal clodronate(LC)exacerbates the toxicity.To our surprise,during other studies,we observed that pre-treatment twice with LC seemed to protect against APAP hepatotoxicity,in contrast to acute pre-treatment.The aim of this study was to confirm that observation and to explore the mechanisms.Methods:We treated mice with empty liposomes(LE)or LC twice per week for 1 week before APAP overdose and collected blood and liver tissue at 0,2,and 6 h post-APAP.We then measured liver injury(serum alanine aminotransferase activity,histology),APAP bioactivation(total glutathione,APAP-protein adducts),oxidative stress(oxidized glutathione(GSSG)),glutamate-cysteine ligase subunit c(Gclc)mRNA,and nuclear factor erythroid 2-related factor(Nrf2)immunofluorescence.We also confirmed the ablation of macrophages by F4/80 immunohistochemistry.Results:Pre-treatment twice with LC dramatically reduced F4/80 staining,protected against liver injury,and reduced oxidative stress at 6 h post-APAP,without affecting APAP bioactivation.Importantly,Gclc mRNA was higher in the LC group at 0 h and total glutathione was higher at 2 h,indicating accelerated glutathione re-synthesis after APAP overdose due to greater basal glutamate-cysteine ligase.Oxidative stress was lower in the LC groups at both time points.Finally,total Nrf2 immunofluorescence was higher in the LC group.Conclusions:We conclude that multiple pre-treatments with LC protect against APAP by accelerating glutathione re-synthesis through glutamate-cysteine ligase.Investigators using twice or possibly more LC pre-treatments to deplete macrophages,including peritoneal macrophages,should be aware of this possible confounder. | Melissa M.Clemens Joel H.Vazquez Stefanie Kennon-McGill Sandra S.McCullough Laura P.James Mitchell R.McGill | 2020 | Liver Research2020，4，3： | 1 |
| 4 | ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders显示文摘 | F.RODEGHIERO A.TOSETTO T.ABSHIRE D. M.ARNOLD B.COLLER P.JAMES C.NEUNERT D.LILLICRAP | 2010 | Journal of Thrombosis and Haemostasis2010，，9： | 1 |
| 5 | PVC – as flooring material – and its association with incident asthma in a Swedish child cohort study显示文摘 | M.Larsson L.H?gerhed‐Engman B.Kolarik P.James F.Lundin S.Janson J.Sundell C. G.Bornehag | 2010 | Indoor Air2010，，6： | 1 |
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