ADVANCED MATERIALS
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2023
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IF 29.4
Mingyuan Wang,Qiong Huang,Min Liu,Tianjiao Zhao,Xiangping Song,Qiaohui Chen,Yongqi Yang,Yayun Nan,Zerun Liu,Yuntao Zhang,Wei Wu,Kelong Ai
The increased incidence of inflammatory bowel disease (IBD) has seriously affected the life quality of patients. IBD develops due to excessive intestinal epithelial cell (IEC) apoptosis, disrupting the gut barrier, colonizing harmful bacteria, and initiating persistent inflammation. The current therapeutic approaches that reduce inflammation are limited. Although IBD can be treated significantly by directly preventing IEC apoptosis, achieving this therapeutic approach remains challenging. Accordingly, we are the first to develop an oral pifithrin-α (PFTα, a highly specific p53 inhibitor) embedded nanomedicine (OPEN) to effectively treat IBD by inhibiting excessive IEC apoptosis. As a major hub for various stressors, p53 is a central determinant of cell fate, and its inhibition can effectively reduce excessive IEC apoptosis. The tailored OPEN can precisely inhibit the off-target and inactivation resulting from PFTα entry into the bloodstream. Subsequently, it persistently targets IBD lesions with high specificity to inhibit the pathological events caused by excessive IEC apoptosis. Eventually, OPEN exerts a significant curative effect compared with the clinical first-line drugs 5-aminosalicylic acid (5-ASA) and dexamethasone (DEX). Consequently, the OPEN therapeutic strategy provides new insights into comprehensive IBD therapy. This article is protected by copyright. All rights reserved
研究领域:
药理学
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胃肠病学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Science Advances
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2025
·Vol. 11
·期 33
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IF 12.5
Wenjing Liang,Sha Huang,Xinran Chen,Kai Jiang,Xin Gong,Hongwei Guo,Lin Li
Shade avoidance syndrome (SAS) commonly occurs in plants sensing shading and the proximity of neighbors, leading to morphological and physiological changes that are detrimental to plant health and consequently crop yield. Controlling SAS could be beneficial for sustainable agriculture. Here, we performed a phenotype-based chemical screening in Arabidopsis and identified pifithrin-α (PFT-α) as a compound that suppresses shade-induced hypocotyl elongation and gene expression. Through genetic, biochemical, and molecular approaches, we demonstrated that PFT-α mimics ethylene by deactivating the ethylene receptor 1 (ETR1). Accumulated ethylene-insensitive 3 (EIN3) influences the expression of phytochrome-interacting factors ( PIF4 and PIF7 ) and subsequently inhibits shade-induced hypocotyl elongation. Our findings not only provide molecular insights into SAS but also suggest that PFT-α, acting as a potent ethylene mimic, plays a crucial role in hormone-regulated plant development and holds potential for modulating SAS in agricultural practices.
研究领域:
植物生物学
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分子生物学
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生物化学
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遗传学
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农业科学
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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2021
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IF 6.543
Yanzhuo Zhang,Zhe Lv,Yudong Liu,Huan Cao,Jianwang Yang,Baoshan Wang
A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.
研究领域:
衰老
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听力科学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2016
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IF 2.326
Qin Tang,Fangling Ji,Jianli Guo,Jingyun Wang,Yachen Li,Yongming Bao
Chrysin , one of natural flavonoid compounds, has recently been found to possess anti-inflammatory, antiallergic and anticancer properties. To increase its anticancer effects, 5 chrysin derivates were synthesized on the base of DNA intercalator structure. The inhibiting effects of chrysin and its derivatives on cancer cells Hela, BGC823, MCF-7, HepG2, and normal cells HEK-293, were evaluated by MTT assays . 5-(2′-amino) phenyl-7-cyclohexanemethylchrysin (Ch-1), a unique chrysin derivate, killed all the cancer cells but kept above 60% survival rate in normal cells HEK-293 at 62.5 μM. Treated with chrysin from 250 μM to 500 μM, those cells were still maintained above 60% survival rate. The result of circular dichroism spectra showed that Ch-1 could intercalate DNA while chrysin had no effects on DNA. Interestingly, Hela cells survival rates were 95% and 10%, after treated with 20 μM and 30 μM of Ch-1, respectively. Both intrinsic and extrinsic apoptotic pathway were identified in regulating the cell death caused by Ch-1 in Hela cells. p53, the upstream regulator of apoptotic pathway were extremely significantly up-regulated in Hela cells treated with 25 μM Ch-1. Moreover, the inhibiting effects and apoptotic related proteins responses to Ch-1 on Hela cells were abolished after pre-treated with Pifithrin-α (Pft-α), a p53 inhibitor. So, p53-depedent apoptosis is the crucial factor governing the inhibiting effects of Ch-1 in Hela cells. Amazingly, Ch-1 at non-toxic concentration (2.5–10 μM) enhanced significantly anti-cancer effect of 10-hydroxy camptothecin (HCPT) on Hela, BGC823, and MCF-7 cells.
研究领域:
癌症研究
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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