NEUROCHEMICAL RESEARCH
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2022
·Vol. 47
·期 10
·3178-3191
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IF 4.414
Wang Lei,Li Min,Zhu Cuiping,Qin Aiping,Wang Jinchun,Wei Xianni
The purpose of the present study was to evaluate the protective effect of Palmatine on LPS-induced depressive like behavior and explore its potential mechanism. The mice were intragastrically treated with Fluoxetine or Palmatine once daily for 1 week. After the last drug administration, the mice were intraperitoneally challenged with LPS and suffered for Sucrose preference test, Tail suspension test, Forced swimming test and Open field test. The pro-inflammatory biomarkers were measured by ELISA, qPCR, WB and immunofluorescence. As a result, the administration of Palmatine effectively lessened depressive-like behavior. Palmatine could decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, the expressions of CD68, iNOS mRNA, as well as increase the levels of anti-inflammatory cytokines IL-4, IL-10, the expressions of CD206, Arg1 mRNA, Ym1 mRNA both in LPS-induced mice and in LPS-induced BV2 cells. The beneficial effect of Palmatine might be attributed to the suppression of M1 microglia polarization and the promotion of M2 microglia polarization via PDE4B/KLF4 signaling. The similar results were observed in CUMS-induced depressive mice. The transfection with PDE4B SiRNA or KLF4 SiRNA indicated that PDE4B and KLF4 were both involved in the Palmatine-mediated microglia polarization. Molecular docking indicated that Palmatine could interact with PDE4B. In conclusion, this research demonstrated that Palmatine attenuated depressive like behavior by modulating microglia polarization via PDE4B/KLF4 signaling.
研究领域:
神经科学
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药理学
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免疫学
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行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
You Xiao,Yuanyuan He,Chongsi Xu,Mei Li,Fan Hu,Wei Wang,Zhenquan Wang,Yi Cao
MoS 2 nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS 2 NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS 2 NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS 2 NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS 2 materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
研究领域:
纳米技术
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分子生物学
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毒理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Dacheng Yang,Yanhong Ran,Xusheng Li,Xinwei Jiang,Jiali Chen,Jianxia Sun,Lingmin Tian,Katia Teerds,Weibin Bai
Cadmium (Cd) is an environmental pollutant and endocrine disrupter , abundantly present in water, food, and soil. Accumulation of Cd in the body can negatively affect female reproduction; especially the uterus is exceptionally sensitive to the toxic actions of Cd. The anthocyanin cyanidin-3- O -glucoside (C3G) is a naturally occurring phenolic compound in fruits and plants that can antagonize the toxic effects of Cd. This capacity makes C3G a possible candidate to prevent Cd-induced female infertility. The present study aimed to investigate: 1) whether C3G intake could prevent Cd-induced female reproductive toxicity, and 2) the underlying mechanisms responsible for this protective effect. The results of our study indicated that Cd exposure did not affect ovarian function, but induced hypertrophy of the uterine endometrium. Oral intake of C3G markedly reduced the effects of Cd exposure on the thickness of the uterine epithelium cells. Transcriptomic analysis of the endometrium revealed that C3G intake had anti-estrogenic effects, attenuating Cd-induced endometrial epithelial cell proliferation by inhibiting estrogen-responsive genes, enhancing epithelial progesterone receptor expression, and regulating Klf4 expression. The current findings implicate that C3G has the potential to be used as a dietary supplement based on its capacity to intervene in Cd-induced female reproductive toxicity.
研究领域:
毒理学
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生殖生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）