INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yuan-Yuan Li,Jing-Wen Sun,Lei Chen,Yong-Ming Lu,Qing-Xi Wu,Chao Yan,Yan Chen,Mei Zhang,Wen-Na Zhang
A new polysaccharide fraction (ATP) was obtained from Armillariella tabescens mycelium. Structural analysis suggested that the backbone of ATP was →4)- α -D-Glc p (1 → 2)- α -D-Gal p (1 → 2)- α -D-Glc p (1 → 4)- α -D-Glc p (1→, which branched at O-3 of →2)- α -D-Glc p (1 → and terminated with T- α -D-Glc p or T- α -D-Man p . Besides, ATP significantly alleviated ulcerative colitis (UC) symptoms and inhibited the production of pro-inflammation cytokines (IL-1 β , IL-6). Meanwhile, ATP could improve colon tissue damage by elevating the expression of MUC2 and tight junction proteins (ZO-1, occludin and claudin-1) levels and enhance intestinal barrier function through inhibiting the activation of MMP12/MLCK/ p -MLC2 signaling pathway. Further studies exhibited that ATP could increase the relative abundance of beneficial bacteria such as f. Muribaculacese , g. Muribaculaceae , and g. Alistips , and decrease the relative abundance of g. Desulfovibrio , g. Colidextribacter , g. Ruminococcaceae and g .Oscillibacter , and regulate the level of short-chain fatty acids. Importantly, FMT intervention with ATP-derived microbiome certified that gut microbiota was involved in the protective effects of ATP on UC. The results indicated that ATP was potential to be further developed into promising therapeutic agent for UC.
研究领域:
药理学
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免疫学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2024
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IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
研究领域:
呼吸病学
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免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Redox Biology
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2023
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IF 11.4
Tianxiang Wang,Changmei Yang,Zhiqiang Li,Ting Li,Ran Zhang,Yujiao Zhao,Tianyi Cheng,Zhaoyun Zong,Yingying Ma,Dongyuan Zhang,Haiteng Deng
Flavonoids are bioactive natural polyphenolic compounds with health benefits, including anti-tumor, anti-inflammatory and anti-aging effects. Our previous studies revealed that a flavonoid 4,4′-dimethoxychalcone (DMC) induced ferroptosis via inhibiting ferrochelatase (FECH). However, the effect of DMC on cellular senescence is unknown. In the present study, we found that DMC treatment selectively eliminated senescent cells, and DMC alone or a combination of DMC and quercetin or dasatinib showed high efficiency in the clearance of senescent cells. We identified FECH was highly expressed in senescent cells compared to non-senescent cells. Mechanistically, we found that DMC inhibited FECH and induced ferritinophagy, which led to an increase of labile iron pool, triggering ferroptosis of senescent cells. Importantly, we found that DMC treatment prevented hair loss, improved motor coordination, and reduced the expression of several senescence-associated secretory phenotype factors ( IL-6 , IL-1β , CXCL-10 , and MMP12 ) in the liver of old mice. Collectively, we revealed that, through the induction of ferroptosis, DMC holds the promise as a new senolytics to prevent age-related pathologies.
研究领域:
细胞生物学
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衰老研究
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
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