NEUROTOXICITY RESEARCH
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2022
·Vol. 40
·期 1
·78-88
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IF 3.978
Ji Na,Wu Lirong,Shi Hui,Li Qianlu,Yu Anyong,Yang Zhao
Intracerebral hemorrhage (ICH) is a fatal cerebrovascular disease. Neuroinflammation plays an important pathological role in brain injury after ICH. NLRP3 contributes to the pathogenesis of ICH, but the underlying mechanisms regulating of NLRP3 remain elusive. V-set and immunoglobulin domain containing 4 (VSIG4), specifically expressed in resting tissue-resident macrophages, can deliver anti-inflammatory signals into various inflammatory diseases. However, the interaction between VSIG4 and NLRP3, as well as the underlying mechanisms after ICH have not been reported. C57BL/6 mice were subjected to the autologous blood injection ICH model. VSIG4 and NLRP3 levels of macrophages were detected following ICH. Ad-VSIG4 or controls were administered via intracerebroventricular (i.c.v) injection before ICH induction. STAT3 inhibitor (S31-201), JAK2 inhibitor (TG101348), or Ad-A20 RNAi was administered to investigate the role of JAK2-STAT3-A20 pathway in VSIG4-mediated neuroinflammation after ICH. Pro-inflammatory cytokine production, BBB disruption, brain water content, and neurological test were examined in ICH mice. VSIG4 levels were significantly decreased, and NLRP3 levels were significantly increased in the perihematomal brain tissues after ICH. Ad-VSIG4 attenuated NLRP3 levels and inhibited inflammation, as well as improved neurological function and reduced BBB disruption and brain water content. Furthermore, Ad-VSIG4 increased the protein levels of phosphorylated JAK2 and STAT3, and A20 levels at 24 h after ICH. STAT3 inhibitor, JAK2 inhibitor, and A20 RNAi abolished the beneficial effects of Ad-VSIG4 after ICH. In summary, these data suggested that VSIG4 attenuated NLRP3 and ameliorated neuroinflammation via JAK2-STAT3-A20 pathway after intracerebral hemorrhage in mice. VSIG4 might be an ideal therapeutic target for ICH patients.
研究领域:
神经科学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.8
Wei Wei,Heng Yan-Yan,Wu Fei-Fei,Dong Hao-Yu,Zhang Peng-Fei,Li Jing-Xia,Liu Chun-Yan,Yang Bing-Jie,Fu Jia-Ning,Liang Xin-Yue
Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence β-Galactosidase Staining (SA-β-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-β-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.
研究领域:
药理学
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心血管疾病
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分子生物学
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糖尿病
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炎症
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氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL AND EXPERIMENTAL BOTANY
·
2018
·
IF 3.666
Yan-E Cheng,Ming-You Dong,Xian-Wei Fan,Li-Li Nong,You-Zhi Li
Soil salinity, commonly dominated by NaCl, is a major constraint to the production of food crops. Cassava ( Manihot esculenta ) is the most important tropical starch-producing crop. Reportedly, this crop is moderately sensitive to salt stress, and the A20/AN1-type zinc finger genes can confer abiotic stress tolerance to plants as the emerging target genes. However, neither cassava tolerance to salt nor the response of A20/AN1-type zinc finger genes from cassava to salt has yet to be characterized in detail. South China 124 (SC124), Fuxuan 01, South China 205, Kasetsart 50 and Argentina 7 (C4), somewhat differ in salt tolerance and starch content in storage roots under pre-established NaCl concentrations of 0, 10, 20, 30, 40, 50, 100, and 200 mM. In this study, we investigated responses of in vitro-grown plantlets of these five cultivars, focusing on plantlet growth, phytohormones, antioxidant enzymes, soluble protein and sugar, H 2 O 2 content, and expression of A20/AN1-type zinc finger genes. The major results were as follows: the growth of cassava was obviously inhibited, starting at 20 mM NaCl depending on the cultivars. All five cultivars could not grow at 100 mM NaCl; 10 mM NaCl caused promoted growth by increasing number, volume, surface area, viability, length of fibrous rootlets, and elongated root cells; 20 mM NaCl facilitated both accumulation of total starch in fibrous rootlets and increase in total protein content in shoots; increased growth and starch accumulation did not correlate with phytohormone levels, antioxidant enzyme activities between shoots and rootlets, or, consequently, in the whole plantlets; and the A20/AN1 gene family was composed of at least 11 members and their expression was induced or suppressed in rootlets of plantlets of pot-grown SC124 under 200 mM NaCl, depending on gene members. In conclusion, low salt (NaCl) can not only promote the cassava growth but also lead to accumulation of total starch in the fibrous rootlets and increase in total protein content in shoots instead of rootlets. Low salt promoting growth effects are likely associated with lower levels of abscisic acid and higher levels of gibberellin and indole-3-acetic acid under salt stress. Such antagonistic relationship among these three phytohormones maybe involves expression of A20/AN1 genes under salt stress. The demand for H 2 O 2 levels, osmoprotectants, and antioxidant enzyme activities in salt stress responses is cassava cultivar-dependent.
研究领域:
植物科学
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分子生物学
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农学
✓ 已验证
产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Shufeng Yin,Bingrui Guo,Wenqing Wang,Wei Ji,Siqi Zhang,Changlei Ji,Chaofan Ji,Yiwei Dai,Sufang Zhang,Xinping Lin
This study evaluated the effects of co-inoculation with Latilactobacillus sakei A20 and Lactiplantibacillus plantarum LJ1–1 at different ratios on the quality and safety of fermented mandarin fish ( Siniperca chuatsi ). Compared with the C group without starter culture, the inoculated groups effectively delayed lipid oxidation and decreased TVB-N content by 14.00%. Notably, the accumulation of biogenic amines was markedly inhibited, with tyramine and cadaverine levels decreasing by over 30.00%. It also reshaped the microbial community by suppressing spoilage bacteria such as Shewanella baltica and Aeromonas sobria , while promoting the accumulation of esters and aldehydes. Sensory evaluation confirmed a 15.44% increase in overall acceptability. Furthermore, a fermentation period of 7 days is recommended to ensure product safety and quality. These results indicate that Lat. sakei A20 and Lpb. plantarum LJ1–1 have great potential as mixed starter cultures for improving the safety, flavor, and sensory acceptability of fermented mandarin fish.
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2021
·
IF 2.649
Cuizhen Long,Na Xie,Yuanhui Shu,Yafeng Wu,Ping He,Yan Zhou,Yining Xiang,Junying Gu,Lei Yang,Yuping Wang
Background This study aimed to investigate the effect of deleting the cannabinoid receptor 2 (CB2) gene on the development of hepatic fibrosis induced by carbon tetrachloride (CCl 4 ) in mice via regulating inflammation. Material/Methods The DNA was extracted from the tails of mice to identify whether the cannabinoid receptor 2 gene was successfully knocked out. A liver fibrosis model was established by an intraperitoneal injection of CCl 4 into mice. Hepatic damage and hepatic fibrosis were evaluated by detecting serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and staining paraffin sections of liver tissue with hematoxylin-eosin (HE). The secretion and distribution of collagen in liver tissue were observed by Masson staining. Western blot analysis was performed to detect the expression of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), tumor necrosis factor alpha-induced protein 3 (A20), phosphorylated nuclear factor-κB p65 (p-NF-κB p65), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in liver tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-6 and TNF-α mRNA in liver tissue. Results Compared with the control mice, the mice with CB2 knockout that were exposed to CCl 4 exhibited increased liver damage, liver fibrosis, and upregulated α-SMA, TGF-β1, A20, and p-NF-κB p65 protein levels. IL-6 and TNF-α protein levels and mRNA levels were upregulated. Conclusions The deletion of the CB2 gene promoted the activation of hepatic stellate cells in mice with liver fibrosis and aggravated liver fibrosis by up-regulating the protein expression of A20 and p-NF-κB p65 and inducing inflammatory response, potentially providing new insight into the treatment of liver fibrosis.
研究领域:
分子生物学
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药理学
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肝病学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
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