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Pharmacology Research & Perspectives · 2020 ·Vol. 8 ·期 5 ·e00660 · IF 2.052

Arctigenin protects mice from thioglycollate-induced acute peritonitis

Jingyi Zhao,Ying Chen,Lijun Dong,Xin Li,Ruijie Dong,Dongmei Zhou,Chengzhi Wang,Xiangdong Guo,Jieyou Zhang,Zhenyi Xue,Qing Xi,Lijuan Zhang,Guangze Yang,Yan Li,Rongxin Zhang

Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa . In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b + Ly6G + neutrophils and F4/80 + macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice.

CAS / MDL: 7770-78-7
研究领域: 药理学 · 免疫学 · 炎症性疾病
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BIOLOGICAL TRACE ELEMENT RESEARCH · 2023 · IF 3.9

Arsenic Exposure Induces Neuro-immune Toxicity in the Cerebral Cortex and the Hippocampus via Neuroglia and NLRP3 Inflammasome Activation in C57BL/6 Mice

Yan Nan,Wang Zhengdong,Li Zhou,Zheng Yang,Chang Nan,Xu Kangjie,Wang Qian,Duan Xiaoxu

This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights ( p  < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform ( p  < 0.05). Hematoxylin–eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group ( p  < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus ( p  < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups ( p  < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic. Graphical abstract

CAS / MDL: 47165-04-8
研究领域: 神经毒理学 · 免疫毒理学 · 神经科学
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PLoS One · 2024 ·Vol. 19 ·期 8 ·e0308132 · IF 2.9

Oligodendroglia-to-pericyte conversion after lipopolysaccharide exposure is gender-dependent

Qingting Yu,Linyuan Zhang,Ting Xu,Jiapeng Shao,Falei Yuan,Zuisu Yang,Yuncheng Wu,Haiyan Lyu

To investigate the sex-dependent differentiation of Sox10 cells and their response to pathological conditions such as lipopolysaccharide (LPS) exposure or ischemia, we utilized Sox10 Cre-ER T2 , tdTomato mice. Tamoxifen administration induced the expression of red fluorescent protein (RFP) in these cells, facilitating their subsequent tracking and analysis after LPS injection and ischemia via immunofluorescence staining. Propidium iodide (PI) was injected to label necrotic cells following LPS administration. We found that the conversion of Sox10 cells to pericytes in female mice was significantly higher than in male mice, especially in those exposed to LPS. After LPS injection, the number of PI + necrotic cells were significantly greater in females than in males. Moreover, RFP + cells did not co-localize with glial fibrillary acidic protein (GFAP) or cluster of differentiation 11b (CD11b). Similarly, after brain ischemia, RFP + cells did not express cluster of differentiation 13 (CD13), neuronal nuclei (NeuN), GFAP, or ionised calcium binding adaptor molecule 1 (Iba-1). These findings indicate that the conversion of Sox10 cells to pericytes following LPS exposure is sex-dependent, with neither male nor female groups showing differentiation into other cell types after LPS exposure or under ischemic conditions. The differences in LPS-induced necrosis of pericytes between sexes may explain the variations in the conversion of Sox10 cells to pericytes in both sexes.

研究领域: 神经科学 · 免疫学 · 细胞生物学
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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY · 2019 · IF 4.315

High-glucose/high-cholesterol diet in zebrafish evokes diabetic and affective pathogenesis: The role of peripheral and central inflammation, microglia and apoptosis

JiaJia Wang,YanJun Li,Ke Lai,QiMei Zhong,Konstantin A. Demin,Allan V. Kalueff,Cai Song

Neuroinflammation and metabolic deficits contribute to the etiology of human affective disorders, such as anxiety and depression. The zebrafish ( Danio rerio ) has recently emerged as a powerful new model organism in CNS disease modeling. Here, we exposed zebrafish to 2% glucose and 10% cholesterol for 19 days to experimentally induce type 2 diabetes (DM) and to assess stress responses, microglia , inflammation and apoptosis . We analyzed zebrafish anxiety-like behavior in the novel tank and light-dark box (Days 15–16) tests, as well as examined their biochemical and genomic biomarkers (Day 19). Confirming DM-like state in zebrafish, we found higher whole-body glucose, triglyceride , total cholesterol, low-density lipoprotein levels and glucagon mRNA expression, and lower high-density lipoprotein levels. DM zebrafish also showed anxiety-like behavior, elevated whole-body cortisol and cytokines IFN-γ and IL-4, as well as higher brain mRNA expression of the glucocorticoid receptor , CD11b (a microglial biomarker), pro-inflammatory cytokines IL-6 and TNF-α (but not IL-1β or anti-inflammatory cytokines IL-4 and IL-10), GFAP (an astrocytal biomarker), neurotrophin BDNF , its receptors p75 and TrkB, as well as apoptotic Bax and Caspase-3 (but not BCl-2 ) genes. Collectively, this supports the overlapping nature of DM-related affective pathogenesis and emphasizes the role of peripheral and central inflammation and apoptosis in DM-related affective and neuroendocrine deficits in zebrafish.

研究领域: 神经科学 · 代谢紊乱 · 行为科学 · 炎症研究 · 分子生物学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Positively Charged-Amylose-Entangled Au-Nanoparticles Acting as Protein Carriers and Potential Adjuvants to SARS-CoV-2 Subunit Vaccines

Baochao Fan,Jun Gu,Bin Deng,Weilu Guo,Shuaifeng Zhang,Li Li,Bin Li

The COVID-19 pandemic continues to spread worldwide. To protect and control the spread of SARS-CoV-2, varieties of subunit vaccines based on spike (S) proteins have been approved for human applications. Here, we report a new subunit vaccine design strategy that functions as both an antigen carrier and an adjuvant in immunization to elicit high-level immune responses. The complex of 2-hydroxypropyl-trimethylammonium chloride chitosan and amylose entangles Au nanoparticles (HTCC/amylose/AuNPs) forming 40 nm nanocarriers with a positive charge. The obtained positively charged nanoparticles reveal many merits, including the larger S protein loading capacity in PBS buffer, higher cellular uptake ability, and lower cell cytotoxicity, supporting their potential as safe vaccine nanocarriers. Two functionalized nanoparticle subunit vaccines are prepared via loading full-length S proteins derived from SARS-CoV-2 variants. In mice, both prepared vaccines elicit high specific IgG antibodies, neutralize antibodies, and immunoglobulin IgG1 and IgG2a. The prepared vaccines also elicit robust T- and B-cell immune responses and increase CD19+ B cells, CD11C+ dendritic cells, and CD11B+ macrophages at the alveoli and bronchi of the immunized mice. Furthermore, the results of skin safety tests and histological observation of organs indicated in vivo safety of HTCC/amylose/AuNP-based vaccines. Summarily, our prepared HTCC/amylose/AuNP have significant potential as general vaccine carriers for the delivery of different antigens with potent immune stimulation.

研究领域: 纳米技术 · 免疫学 · 病毒学 · 药学 · 生物医学工程
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