作者：
Zhao, Yun;Magana, Laura C.;Cui, Haiyan;Huang, Jiawei;McHale, Cliona M.;...
期刊：
Archives of Toxicology,2021年95(2):693-701 ISSN：0340-5761
通讯作者：
Zhang, Luoping;Li, Rui
作者机构：
[Zhang, Luoping; McHale, Cliona M.; Zhao, Yun; Magana, Laura C.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.;[Li, Rui; Yang, Xu; Zhao, Yun; Huang, Jiawei; Cui, Haiyan] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan, Peoples R China.;[Looney, Mark R.] Univ Calif San Francisco UCSF, Dept Med, San Francisco, CA USA.;[Looney, Mark R.] Univ Calif San Francisco UCSF, Dept Lab Med, San Francisco, CA USA.
通讯机构：
[Zhang, Luoping] U;[Li, Rui] C;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan, Peoples R China.
作者机构：
[Shen, Zhuping; Liu, Guozhen; Wei, Hui] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;[Li, Rui; Huang, Jiawei] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.;[Niu, Huan; Li, Bitong; Liu, Guozhen] Univ New South Wales, Fac Engn, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.;[Liu, Guozhen] Univ New South Wales, Australian Ctr NanoMed, Sydney, NSW 2052, Australia.;[Liu, Guozhen] Univ New South Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia.
通讯机构：
[Liu, Guozhen] U;Univ New South Wales, Grad Sch Biomed Engn, Sydney, NSW, Australia.
关键词：
Cytokines;Electrochemical immunosensors;Multiplex sensing;In vivo detection;Parkinson's disease;Mouse brain
摘要：
Parkinson's Disease (PD) is a neurodegenerative chronic disorder which destroys brain tissue and result in impaired movement. Early diagnosis of PD before the appearance of clinical symptom is vital for effective treatment. High levels of proinflammatory cytokines found in PD patient's brains, as natural inflammation response product, are potential biomarkers for PD detection in the early stage. Herein, we developed an in vivo electrochemical immunosensing device based on glassy carbon rod to simultaneously detect three proinflammatory cytokines (IL-1 beta, IL-6 and TNF-alpha). The levels of IL-1 beta, IL-6 and TNF-alpha secreted by N2a cells significantly increased within 24 h after lipopolysaccharide (LPS) stimulation. Under in vivo conditions, the concentrations of IL-1 beta, IL-6 and TNF-alpha in PD model group achieved by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally, were significantly higher than those in the control mouse group. The concentrations of three cytokines in vivo/vitro detected by this immunosensing device was comparable to that obtained by ELISA. Furthermore, this deployable immunosensing device was proved to be highly sensitive with the limits of detection (LODs) of 5 pg mL(-1) for each cytokine, specific and reliable, suggesting its potential to be a universal immunosensing platform for early identification and diagnosis of PD in vivo in the future. (C) 2020 Elsevier B.V. All rights reserved.
摘要：
The toxicity of formaldehyde (FA) has always been of great concern, particularly since its use is unavoidable. On the other hand, epigallocatechin-3-gallate (EGCG), an active substance in tea polyphenols, has been shown to demonstrate physiological protective functions by in both epidemiological and zoological studies, particularly in the nervous system. The study described here, aims to explore whether EGCG can alleviate the neurotoxic effects induced by formaldehyde. After 14 days of exposure to 3 mg/m(3) formaldehyde, mice exhibited significant cognitive impairment. In the FA group, a significant increase in iNOS level compared with the control group was observed. The reduced GSH level was significantly decreased. The levels of IL-1beta, TNF-alpha and Caspase-3 were obviously raised, while H&E and Nissl staining illustrated significant neuronal damage. After administering EGCG as a protective agent, all the above observed changes were reversed, and the protective effect of EGCG became gradually evident in the 20-500 mg/kg range. Immunohistochemistry results showed that EGCG could activate the Nrf2 signaling pathway, thus alleviating the oxidative damage caused by formaldehyde.
摘要：
Formaldehyde (FA), a well-known toxic gas molecule similar to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), is widely produced endogenously via numerous biochemical pathways, and has a number of physiological roles in the biosystem. We attempted to investigate the vasorelaxant effects of FA and their underlying mechanisms. We found that FA induced vasorelaxant effects on rat aortic rings in a concentration-dependent manner. The NO/cyclic guanosine 5' monophosphate (cGMP) pathway was up-regulated when the rat aortas were treated with FA. The expression of large-conductance Ca(2+)-activated K(+) (BKCa) channel subunits alpha and beta of the rat aortas was increased by FA. Similarly, the levels of ATP-sensitive K(+) (KATP) channel subunits Kir6.1 and Kir6.2 were also up-regulated when the rat aortas were incubated with FA. In contrast, levels of the L-type Ca(2+) channel (LTCC) subunits, Cav1.2 and Cav1.3, decreased dramatically with increasing concentrations of FA. We demonstrated that the regulation of FA on vascular contractility may be via the up-regulation of the NO/cGMP pathway and the modulation of ion channels, including the upregulated expression of the KATP and BKCa channels and the inhibited expression of LTCCs. Further study is needed to explore the in-depth mechanisms of FA induced vasorelaxation.
通讯机构：
Key Laboratory of Genetic Regulation and Integrated Biology of Hubei Province, School of Life Sciences, Central China Normal University, Wuhan, China
期刊：
Alzheimer's & Dementia: Translational Research & Clinical Interventions,2019年5(1):671-684 ISSN：2352-8737
通讯作者：
Tong, Z.
作者机构：
[Chunli Duan; Ge Gao; Hui Yang] Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China;[Dehua Cui; Jun Yang; Aibo Wang; Rui Wang] Department of Radiology, Peking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and Technique, Beijing, China;Corresponding author. Tel: +86-010-83950362;Fax: +86-010-83950363.;∗Corresponding author. Tel: 604-822-8019
通讯机构：
[Weihong Song; Hongbin Han] D;[Zhiqian Tong] L;Department of Radiology, Peking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and Technique, Beijing, China<&wdkj&>Corresponding author. Tel: +86-010-83950362;Fax: +86-010-83950363.<&wdkj&>∗Corresponding author. Tel: 604-822-8019;Fax: 604-822-7981.<&wdkj&>∗∗Corresponding author. Tel: +86-010-82266972
关键词：
Red light (RL);Alzheimer's disease (AD);Amyloid β (Aβ);Formaldehyde (FA);Formaldehyde dehydrogenase (FDH);Extracellular space (ECS);Interstitial fluid (ISF)
摘要：
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Pharmacological therapies to treat Alzheimer's disease (AD) targeting “Aβ” have failed for over 100 years. Low levels of laser light can disassemble Aβ. In this study, we investigated the mechanisms that Aβ‐blocked extracellular space (ECS) induces memory disorders in APP/PS1 transgenic mice and addressed whether red light (RL) at 630 nm rescues cognitive decline by reducing Aβ‐disturbed flow of interstitial fluid (ISF).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compared the heating effects on the brains of rats illuminated with laser light at 630, 680, and 810 nm for 40 minutes, respectively. Then, a light‐emitting diode with red light at 630 nm (LED‐RL) was selected to illuminate AD mice. The changes in the structure of ECS in the cortex were examined by fluorescent double labeling. The volumes of ECS and flow speed of ISF were quantified by magnetic resonance imaging. Spatial memory behaviors in mice were evaluated by the Morris water maze. Then, the brains were sampled for biochemical analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>RL at 630 nm had the least heating effects than other wavelengths associated with ~49% penetration ratio into the brains. For the molecular mechanisms, Aβ could induce formaldehyde (FA) accumulation by inactivating FA dehydrogenase. Unexpectedly, in turn, FA accelerated Aβ deposition in the ECS. However, LED‐RL treatment not only directly destroyed Aβ assembly <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> but also activated FA dehydrogenase to degrade FA and attenuated FA‐facilitated Aβ aggregation. Subsequently, LED‐RL markedly smashed Aβ deposition in the ECS, recovered the flow of ISF, and rescued cognitive functions in AD mice.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Aβ‐obstructed ISF flow is the direct reason for the failure of the developed medicine delivery from superficial into the deep brain in the treatment of AD. The phototherapy of LED‐RL improves memory by reducing Aβ‐blocked ECS and suggests that it is a promising noninvasive approach to treat AD.</jats:p></jats:sec>
作者机构：
[Xie, Bo; Ge, Leixin; Li, Rui; Yang, Xu; Zhao, Yun; Guo, Junhui] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Zhang, Luoping; Guo, Junhui] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.;[Xie, Hao; Guo, Junhui] Wuhan Univ Technol, Sch Chem Chem Engn & Life Sci, Wuhan 430070, Hubei, Peoples R China.;[Jiang, Xingpeng] Cent China Normal Univ, Sch Comp, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Yang, Xu] C;[Zhang, Luoping] U;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
关键词：
16s rRNA gene;Formaldehyde (FA);Gut microbiome;High-throughput;Murine model
摘要：
Exposure to Formaldehyde (FA) results in many pathophysiological symptoms, however the underlying mechanisms are not well understood. Given the complicated modulatory role of intestinal microbiota on human health, we hypothesized that interactions between FA and the gut microbiome may account for FA's toxicity. Balb/c mice were allocated randomly to three groups: a control group, a methanol group (0.1 and 0.3 ng/mL MeOH subgroups), and an FA group (1 and 3 ng/mL FA subgroups). Groups of either three or six mice were used for the control or experiment. We applied high-throughput sequencing of 16S ribosomal RNA (rRNA) gene approaches and investigated possible alterations in the composition of mouse gut microbiota induced by FA. Changes in bacterial genera induced by FA exposure were identified. By analyzing KEGG metabolic pathways predicted by PICRUSt software, we also explored the potential metabolic changes, such as alpha-Linolenic acid metabolism and pathways in cancer, associated with FA exposure in mice. To the best of our knowledge, this preliminary study is the first to identify changes in the mouse gut microbiome after FA exposure, and to analyze the relevant potential metabolisms. The limitation of this study: this study is relatively small and needs to be further confirmed through a larger study.
摘要：
Diisodecyl phthalate (DIDP) is extensively used as an environmentally friendly plasticizer. However, little is known about the adverse effects and the underlying mechanisms of DIDP exposure on immunological diseases. We aimed to determine the role and mechanisms of DIDP exposure in allergic contact dermatitis-like skin lesions. We show that oral DIDP exposure can aggravate allergic dermatitis in mice. Moreover, an increase of ROS, total serum IgE and IL-4 levels were concomitant with this deterioration. We detected the expression of Thymic stromal lymphopoietin (TSLP) and the activation of STATs and NF-kappa B signal pathways. The data indicated that DIDP in combination with FITC triggers TSLP production. Our results also suggested that DIDP exacerbated the activation of NF-kappa B signal pathways, with an enhancement in TSLP expression, which potentiated the activation of STATs and the degranulation of mast cells in the skin, and finally exacerbated allergic dermatitis. The study also suggested that melatonin enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic dermatitis. The results demonstrated that DIDP exacerbated allergic dermatitis through oxidative stress and enhanced TSLP production. (C) 2016 Elsevier Ltd. All rights reserved.
