INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 4
·1925-1934
·
IF 2.784
Yunfei Ma,Tuo Tang,Lili Sheng,Ziqian Wang,Hong Tao,Qing Zhang,Yao Zhang,Zhilin Qi
The anti‑inflammatory effects of aloin, a bioactive ingredient extracted from Aloe vera, have been described previously. The present study aimed to assess these effects and explore the underlying molecular mechanisms. RAW264.7 cells were incubated with different doses of aloin (100, 150 and 200 µg/ml) and lipopolysaccharide (LPS; 100 ng/ml) for the indicated times. Then, inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 expression levels were detected by western blot analysis and reverse transcription polymerase chain reaction (RT‑PCR).The concentrations of inflammatory cytokines in the cell culture supernatant were determined by ELISA. Total nitric oxide (NO) assay and reactive oxygen species (ROS) kits were used to detect NO and ROS levels, respectively. Mitogen‑activated protein kinase, nuclear factor κB and Janus kinase‑signal transducer and activator of transcription (JAK‑STAT) pathway activation were verified by western blot analysis. Confocal and nucleocytoplasmic separation experiments were used to detect STAT nuclear translocation. It was identified that aloin decreased the level of LPS‑induced iNOS expression, inhibiting the release of interleukin (IL)‑1β, IL‑6, tumour necrosis factor‑α and NO dose‑dependently. Mechanistically, aloin suppressed LPS‑induced JAK1‑STAT1/3 activation and STAT1/3 nuclear translocation. Additionally, LPS‑induced ROS production was inhibited by aloin. Collectively, these data suggest that aloin attenuated LPS‑induced inflammation by inhibiting ROS‑mediated activation of the JAK1‑STAT1/3 signalling pathway, thereby inhibiting the nuclear translocation of STAT1/3 in RAW264.7 cells. The present study provides an experimental basis for the clinical application of aloin in inflammatory‑associated diseases.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Mengxing Cui,Qianmei He,Ziwei Wang,Yongjiang Yu,Huan Gao,Ziqi Liu,Honghao Peng,Han Wang,Xue Zhang,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Qing Wang
Micro/nano-plastics (MPs/NPs) are a newly discovered environmental pollutant that can be ingested by humans through food and drinking water. In this study we evaluated the impact of MPs/NPs on the intestinal barrier and its mechanism. Doses of MPs/NPs were used to treat Caco-2/HT29-MTX in-vitro model and in-vivo model. In in-vitro model, 20 nm polystyrene nanoplastics (PS-NPs) had higher cytotoxicity than larger particles (200 nm and 2000 nm), and led to the increase of the permeability along with the decreased expression of tight junction proteins. Intriguingly, 20 nm PS-NPs elevated the expression of MUC2 simultaneously. Further studies revealed that PS-NPs increased the expression of HO1 through ROS generation, and then activated p38 to elevate IL-10 secretion in Caco-2 cell. The IL-10 secreted by Caco-2 cell promoted the expression of MUC2 in HT29-MTX cell through STAT1/3. Elevated MUC2 expression alleviates the cytotoxicity of PS-NPs. Besides, increased intestinal permeability and up-regulation of MUC2 through Ho1/p38/IL-10 pathway was also observed in 20 nm PS-NPs treated mouse model. In conclusion, PS-NPs can induce the intestinal toxicity and result in the increased adaptive expression of MUC2 to resist this adverse effect. People with inadequate mucin expression need to pay more attention to the toxicity of PS-NPs. This study provided a valuable insight for clarifying the mechanism and potential risk of intestinal toxicity induced by nanoplastics.
研究领域:
环境科学
·
毒理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2023
·Vol. 14
·期 2
·1-13
·
IF 9
Liu Nian,Zhang Jianglin,Yan Mingjie,Chen Lihui,Wu Jie,Tao Qian,Yan Bei,Chen Xiang,Peng Cong
Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG’s function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.
研究领域:
肿瘤学
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免疫学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Famin Zhang,Yaoyao Yan,Xu Han,Jun Cheng Du,Rende Zhu,Xin Hua Liu
On basis of Quercetin moiety, two series of 20 new compounds were designed and synthesized accordingly in this study, and their anti-inflammatory activities in vitro and in vivo were evaluated. At last, compound 8A2 : 3- (1- (2- (4- (5-bromo-2-chlorobenzoyl) piperazin-1-yl) ethyl)-1 H -1,2,3-triazol-4-yl) methoxy)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4 H -chromen-4-one with low toxicity was found the best one for inhibiting of NO. Meanwhile, this compound could significantly inhibit the expression of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α) and IL-17 (Interleukin-17), and also significantly down-regulate IL-17 mRNA psoriasis model in vitro . Further studies were performed to establish mouse psoriasis model induced by Imiquimod (IMQ), and the preliminary mechanism indicated that compound 8A2 may alleviate mouse psoriasis through obstructed the JAK1/2-STAT1/3 pathway. This study should be provide a basis for further study of effective treatment of psoriasis.
研究领域:
药理学
·
化学
·
免疫学
·
皮肤病学
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DOI
PubMed
高影响因子
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