INFLAMMATION
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2020
·Vol. 43
·期 5
·1751-1758
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IF 3.212
Zhaohui Chen,Shuihua Wu
Accumulating evidence supports that Sirtuin 6 (SIRT6) may play a vital role in the pathogenesis of spinal cord injury. The current study was designed to investigate the specific effects of SIRT6 on spinal cord injury (SCI). HE and Nissl staining were performed for pathological analysis in SCI rats. SIRT6 expression was detected by RT-qPCR. CCK8 assay was applied for the detection of cell viability of LPS-injured PC12 cells. TNF-a, IL-1β, IL-6, MCP-1 levels and ROS, MPO, SOD levels were assessed to evaluate inflammation and oxidative stress in spinal cord injury. Cell apoptosis were evaluated by morphological examination using AO/EB fluorescent staining methods and key proteins related to apoptosis were explored via western blot. HE staining revealed increased cavity involving the dorsal white matter and central gray matter, and Nissl staining discovered the loss of motor neurons in the ventral horn in SCI rats. SIRT6 had lower expression in SCI rats. Lipopolysaccharide (LPS) exposure induced cell apoptosis and reduced the expression of SIRT6. Mechanistically, we revealed that up-regulation of SIRT6 alleviated inflammation and oxidative stress and inhibited cell apoptosis in spinal cord injury. Together, our findings indicated that SIRT6 attenuated spinal cord injury by suppressing inflammation, oxidative stress, and cell apoptosis. This study demonstrates that SIRT6 may represent a protective effect against spinal cord injury.
研究领域:
神经科学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2019
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IF 5.589
Shuang Liang,Yueyue Chen,Shiming Zhang,Yuanyuan Cao,Junchao Duan,Yapei Wang,Zhiwei Sun
Silica nanoparticles (SiNPs) have been widely used in human health related products, such as food additives, cosmetics and even drug delivery, gene therapy or bioimaging. Recently, a first-in-human clinical trial based on polyethylene glycol (PEG)-modified SiNPs had been approved by US FDA to trace melanoma. However, as a nano-based drug delivery system, its biocompatibility and vascular toxicity are still largely unknown. Thus, we synthesized the fluorescent SiNPs to explore the biocompatibility and vascular endothelial function, and compare different biological effects caused by PEG-modified and unmodified SiNPs in cells and zebrafish model. The characterizations of SiNPs and PEG-modified SiNPs were analyzed by TEM, SEM, AFM and DLS, which exhibited relatively good stable and dispersive. Compared with SiNPs, PEG-modified SiNPs had markedly reduced the inflammatory response and vascular damage in Tg (fli-1: EGFP) and Tg (mpo: GFP) transgenic zebrafish lines, respectively. Consistent with the in vivo results, the PEG-modified SiNPs had been found to significantly decline the levels of ROS, inflammatory cytokines and mitochondrial-mediated apoptosis in vascular endothelial cells compared to SiNPs, and the ROS scavenger NAC could effectively alleviate the above adverse effects induced by nanoparticles. Our results suggested that the PEG-modified SiNPs could become more safety via increasing the biocompatibility and decreasing cellular toxicities in living organisms.
研究领域:
纳米技术
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生物医学工程
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药理学
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毒理学
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DOI
PubMed
高影响因子
Food Science and Human Wellness
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2022
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IF 8.022
Menglin Chen,Hong Yao,Huizi Tan,Wenqi Huang,Quanyong Wu,Shaoping Nie
Most scientific investigations regarding inflammatory bowel disease (IBD) pathogenesis or therapeutic strategies use dextran sulfate sodium (DSS)-induced models performed on mice. However, differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials. In this study, the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota. Disorders in disease activity index (DAI), morphology and histology of colon tissue, intestinal permeability, and secretion of MPO, TNF-α and IL-6 were ameliorated by daily intake of live B. longum NSP001 cells in both conventional and humanised colitis mice. But the abnormal thymus index, and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B. longum NSP001 and humanised microbiome. The accumulation of acetic acid and propionic acid in colon microbiome, and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B. longum NSP001. These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.
研究领域:
炎症性肠病
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微生物组
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益生菌
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治疗策略
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动物模型
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人源化模型
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Yao Hua,Limei Zhou,Weidong Yang,Wenji An,Xiaolin Kou,Jian Ren,Hailang Su,Rong Chen,Zhengping Zhang,Jianjun Zou,Zhihong Zhao
Intracerebral hemorrhage (ICH) is a devastating disease, and there is currently no specific pharmacological treatment that can improve clinical outcomes. Y-2 sublingual tablets, each containing 30 mg edaravone and 6 mg (+) - borneol , is undergoing a phase III clinical trial for treatment of ischemic stroke in China. The purpose of the present study is to investigate the efficacy and potential mechanism of Y-2 in a rat model of collagenase IV injection induced ICH. Sublingual administration of Y-2 at the dose of 1, 3 and 6 mg/kg improved ICH-induced sensorimotor dysfunction, alleviated cell death and histopathological change, restored the hippocampal long-term potentiation (LTP), reduced brain edema and maintained blood-brain barrier (BBB) integrality in ICH rats. Further study demonstrated that Y-2 could reduce inflammatory response and oxidative stress by decreasing the levels of myeloperoxidase (MPO), ionized calcium-binding adaptor protein-1 (Iba-1), inflammatory cytokines and oxidative products, inhibit transcription factor nuclear factor-κB (NF-κB) activation, cyclooxygenase-2 (COX-2) and matrix metallopeptidase 9 (MMP-9) expression in brain tissue around in the core regions of hematoma . Importantly, the protective efficacy of Y-2 from ICH-induced injury was superior to edaravone. In conclusion, Y-2 sublingual tablets might be a promising therapeutic agent for the treatment of ICH.
研究领域:
神经病学
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药理学
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实验性卒中研究
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Wang Kaiping,Yang Linlin,Zhou Jing,Pan Xianglin,He Zihao,Liu Junxi,Zhang Yu
The alleviation of oxidative stress is considered an effective treatment for acetaminophen (APAP)-induced acute liver injury (AILI). However, it remains unknow whether the potential antioxidant Smilax china L. polysaccharide (SCLP) protects against AILI. In this study, in vitro and in vivo experiments were conducted to verify the hepatoprotective effect of SCLP against AILI and explore the potential mechanism. We found that SCLP relieved liver histopathological changes; reversed the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and reactive oxygen species (ROS); reversed the change in liver myeloperoxidase (MPO) activity; and enhanced liver antioxidant (GSH, GSH-Px, and t-SOD) levels in APAP-treated mice, thereby significantly reducing APAP-induced liver toxicity. SCLP rescued the cell viability and alleviated oxidative stress in H2O2-treated mouse AML12 (Alpha mouse liver 12) hepatocytes. The results of the mechanistic studies showed that SCLP upregulated nuclear factor E2 related factor (Nrf2) expression, promoted Nrf2 nuclear translocation, and enhanced the ability of Nrf2 to bind antioxidant response elements (AREs). Furthermore, SCLP activated Nrf2-ARE pathway, thus upregulating the expression of oxidative stress-related proteins heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1(NQO-1) and glutamic acid cysteine ligase catalytic subunit (GCLC). In conclusion, this study confirmed the close correlation between liver protection by SCLP upon exposure to APAP and activated of the Nrf2-ARE pathway. These findings suggest that SCLP is an attractive therapeutic candidate drug for the treatment of AILI.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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