ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Dongxu Wang,Kai Yin,Yue Zhang,Hongmin Lu,Lulu Hou,Hongjing Zhao,Mingwei Xing
Endemic fluorosis (EF) has been listed as one of the serious public health problems in many countries. Long-term exposure to high fluoride can lead to severe neuropathological damage to the brain. Although long-term research has revealed the mechanism of some brain inflammation caused by excessive fluoride, the role of intercellular interactions, especially immune cells, in brain damage is still unclear. Fluoride can induce ferroptosis and inflammation in the brain in our study. A co-culture system of neutrophil extranets and primary neuronal cells showed that fluoride can aggravate neuronal cell inflammation by causing neutrophil extranets (NETs). In terms of the mechanism of action, we found that fluoride leads to the opening of calcium ion channels by causing neutrophil calcium imbalance, which in turn leads to the opening of L-type calcium ion channels (LTCC). Extracellular free iron enters the cell from the open LTCC, leading to neutrophil ferroptosis, which releases NETs. Blocking LTCC (nifedipine) rescued neutrophil ferroptosis and reduced the generation of NETs. Inhibition of ferroptosis (Fer-1) did not block cellular calcium imbalance. In summary, our study explores the role of NETs in fluoride-induced brain inflammation and suggests that blocking calcium channels may be one of the possibilities to rescue fluoride-induced ferroptosis.
研究领域:
神经科学
·
免疫学
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毒理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Public Health
·
2024
·
IF 3
Ma Tianbao,Li Kexian,Sang Wenjuan,Liu Xingyu,Luo Qun,Peng Ye,Wang Mingxing,Luo Xiu,Fang Jingjing,Wang Haijun,Wang Tao,Zuo Changjing
Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR).Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood–brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus.Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K–Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group.Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.
研究领域:
放射生物学
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神经科学
·
认知科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-17
·
IF 12.6
Li Li,Wang Wang,Li Rong,Guo Jiayue,Hu Xulin,Pan Yu,Zhang Taoyuan,Chi Sensen,Gu Zili,Zhu Gaohui,Liu Qi,Tan Shuai
Gut microbiota is increasingly recognized for its profound influence on host metabolism. However, the mechanisms underlying the distinct metabolic phenotype observed in germ-free (GF) mice are not fully understood. Here, the serum levels of metabolic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were shown with significant elevation in GF than the conventionally-raised (CONV-R) mice. Single-cell transcriptome analysis revealed that Secretogranin II ( Scg2 ), with a known function in secretion control, was exclusively expressed in enteroendocrine cells (EECs). Scg2 transcript levels were significantly up-regulated in GF mice, positively correlated with enhanced GLP-1 and peptide PYY secretion. To examine the functional significance of Scg2 in hormone regulation, cross-linked nanoparticles capable of long-term adhesion to intestinal epithelium were designed, with AAV adsorbed within the cross-linked structure. This innovative design enhances its stability and retention in vivo, providing a robust platform for continuous and efficient gene delivery. We evidenced that over-expression of Scg2 via AAV-loaded nanocarriers in the colons of mice on high-fat diet or with the ob/ob genotype not only enhanced the secretion of GLP-1 and PYY but also mitigated weight gain in these mice by reducing their appetite. A multi-omics analysis reveals that Scg2 overexpression in the colon decreased hypothalamic inflammation and activated tryptophan metabolic pathways. Collectively, our findings suggest a potential therapeutic approach for treating metabolic disorders by enhancing Scg2 expression in colonic EECs. Graphical
研究领域:
分子生物学
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遗传学
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生物化学
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药理学
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纳米技术
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微生物学
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内分泌学
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代谢组学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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