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1.
Cell Rep ; 29(10): 3223-3234.e6, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801085

RESUMO

Major depression is a serious global health concern; however, the pathophysiology underlying this condition remains unclear. While numerous studies have focused on brain-specific mechanisms, few have evaluated the role of peripheral organs in depression. Here, we show that the liver activates an intrinsic metabolic pathway that can modulate depressive-like behavior. We find that chronic stress specifically increases the protein levels of monomeric and oligomeric soluble epoxide hydrolase (sEH), a key enzyme in epoxyeicosatrienoic acid (EET) signaling, in the liver. Hepatic deletion of Ephx2 (which encodes sEH) results in antidepressant-like effects, while the hepatic overexpression of sEH induces depressive phenotypes. The activity of sEH in hepatocytes modulates the plasma levels of 14,15-EET, which then interacts with astrocytes in the medial prefrontal cortex to mediate the effects of hepatic Ephx2 deletion. These results suggest that targeting mechanisms underlying the hepatic response to stress would increase our therapeutic options for the treatment of depression.

2.
Nat Chem Biol ; 15(12): 1214-1222, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31591566

RESUMO

Iron is essential for a broad range of biochemical processes in the brain, but the mechanisms of iron metabolism in the brain remain elusive. Here we show that iron functionally translocates among brain regions along specific axonal projections. We identified two pathways for iron transport in the brain: a pathway from ventral hippocampus (vHip) to medial prefrontal cortex (mPFC) to substantia nigra; and a pathway from thalamus (Tha) to amygdala (AMG) to mPFC. While vHip-mPFC transport modulates anxiety-related behaviors, impairment of Tha-AMG-mPFC transport did not. Moreover, vHip-mPFC iron transport is necessary for the behavioral effects of diazepam, a well-known anxiolytic drug. By contrast, genetic or pharmacological promotion of vHip-mPFC transport produced anxiolytic-like effects and restored anxiety-like behaviors induced by repeated restraint stress. Taken together, these findings provide key insights into iron metabolism in the brain and identify the mechanisms underlying iron transport in the brain as a potential target for development of novel anxiety treatments.

3.
J Chromatogr A ; 1563: 144-153, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-29887336

RESUMO

This study aims to develop a straightforward, sensitive UHPLC-MS/MS method to quantify 15 eicosanoids derived from arachidonic acid in human plasma. Tert-Butyl methyl ether was used on the liquid-liquid extraction method and significantly reduced the expense and time. The method showed excellent linearity for all analytes, with regression coefficients higher than 0.99 over a wide range of concentrations from 0.01 ng mL-1 to 100 ng mL-1. The recovery rates were over 65.00%, and the matrix effects ranged from 8.42% to 40.00%. The limits of detection ranged from 6 pg mL-1 to 10 pg mL-1, and all of the limits of quantification were 20 - 33 pg mL-1. For the broad concentration range, the RE% for accuracy and precision were less than ±â€¯15%. Moreover, trans-4-{4-[3-(4-Trifluoromethoxyphenyl)-ureido] cyclohexyloxy} benzoic acid (t-TUCB) pretreatment extended the window of detection for as much as 30 days. Eicosanoid signaling is altered in various neurological diseases, including pain, Alzheimer's disease and major depressive disorder. Therefore, this rapid, robust quantitative profiling of 15 eicosanoids in plasma could provide a distinct eicosanoid fingerprint for precision medicine in these patients.


Assuntos
Ácido Araquidônico/sangue , Sistema Enzimático do Citocromo P-450/metabolismo , Ácido Araquidônico/isolamento & purificação , Ácido Araquidônico/metabolismo , Cromatografia Líquida de Alta Pressão , Transtorno Depressivo Maior , Eicosanoides/sangue , Eicosanoides/química , Eicosanoides/isolamento & purificação , Humanos , Limite de Detecção , Extração Líquido-Líquido , Espectrometria de Massas em Tandem
4.
Int J STD AIDS ; 17(5): 324-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16643683

RESUMO

China is facing a major crisis because of the increasing epidemic of HIV/AIDS, especially in the western areas. The purpose of this paper is to enhance understanding of the crisis by analysing the published literature on the epidemiology, demographic features, routes of infection, and risk factors of HIV/AIDS infection in the 12 provinces in the west of China. HIV/AIDS has increased rapidly in recent years. The situation is urgent and requires comprehensive action. China's health care system is decentralized and under-funded, and access to treatment by the poor is seriously limited. There is a lack of knowledge about HIV/AIDS in the general public and health care workers. The HIV/AIDS epidemic emerged initially in western areas of the country by means of intravenous drug use, but sexual risk behaviour and mother-to-child transmissions in the west of China are becoming important for HIV transmission.


Assuntos
Síndrome de Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Saúde Pública , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Adulto , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Masculino , Pobreza , Gravidez , Prevalência , Fatores de Risco , Comportamento Sexual , Doenças Virais Sexualmente Transmissíveis/transmissão
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