ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2025
·
IF 11.3
Jinxiu Lou,Feilong Dong,Huijie Lu,Shuangxi Fang,Xiangliang Pan
Disinfection byproducts (DBPs), such as haloacetamides (HAMs), have been associated with adverse health outcomes, including bladder cancer. The potential for DBPs to exacerbate cellular senescence, thereby linking exposure to health impacts, remains underexplored. In this study, MRC-5 cells were exposed to HAMs at concentrations of 2, 5, and 8 μg/L for 30 days to simulate long-term exposure to levels found in drinking water. All six tested HAMs significantly increased the cellular senescence degree and enriched the cellular senescence pathway at the proteomic-wide level. Specifically, HAMs upregulated microRNA-24 expression, which increased p16 mRNA levels and decreased p16 protein levels, thereby activating oncogene-induced senescence pathways. Additionally, HAMs were found to covalently bind to TNRC6A, activating the p53/p21 pathway. Principal component analysis highlighted the critical role of functional groups in activating senescence, and the interaction between HAMs and TNRC6A could extend to at least 27 other amide-containing DBPs. Prolonged exposure to HAMs at environmentally relevant levels notably exacerbates cellular senescence, shedding light on a commonly overlooked phenomenon. Given the widespread presence of DBPs in drinking water and their continuous exposure in humans, their role in cellular senescence represents an ongoing public health concern.
研究领域:
环境科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kang wei,Lu He,Xuan Li,Meng Wu,Haijie Wang,Liangcong Hu,Huanhuan Xu,Yixuan Zhang,Ling Zhou,Xiaojuan Xu,Liang Guo
Excessive exposure to ultraviolet (UV) radiation results in premature aging of the skin. Lentinan polysaccharide (LNT), has been reported in the literature to exhibit a variety of biological functions, such as anti-inflammatory, antioxidant, and anticancer activities. In this research, the function and underlying mechanisms of LNT in UVB-induced photoaging were evaluated in vivo and in vitro . Initially, we developed a UVB-induced photoaging model in HDFs. The results indicated that following UVB irradiation, the positive rate of β-galactosidase, the proportion of dead cells, the generation of ROS, the expression of the senescence-associated secretory phenotype (SASP), the mRNA levels of inflammatory factors, as well as the activity of matrix metalloproteinases (MMPs) were upregulated in HDFs. In contrast, the components of the extracellular matrix (ECM), were decreased. Simultaneously, the impact of UVB exposure on the dorsal skin of mice exhibited a similar pattern. LNT was demonstrated to effectively mitigate the aforementioned changes and inhibit UVB-induced skin photoaging and damage in mice. Mechanistically, our findings revealed that LNT inhibited UVB-activated nuclear factor kappa B (NF-κB), the mitogen-activated protein kinase (MAPK) pathways and the P21/P16 axis. This property of LNT presents considerable potential for the development of therapeutic strategies aimed at delaying skin photoaging.
研究领域:
皮肤生物学
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分子生物学
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药理学
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光老化研究
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天然产物药理
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细胞衰老机制
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信号转导
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 144
·期 10
·3282-3288
·
IF 4.019
Bobo Huang,Lin Ji,Bo Liang,Qingpeng Cao,Tingting Tu,Xuesong Ye
There is a great demand for robust diagnostic and prognostic approaches for Hepatocellular Carcinoma (HCC). DNA methylation, a common epigenetic modification, has been found in many promoter regions of tumor suppressor genes. Hypermethylation of these gene promoters will repress the gene transcription and lead to the occurrence of cancers. The abnormal methyation level of the p16 gene promoter could be a promising marker for the detection of HCC. The adsorption affinities between different DNA bases and AuNPs are not the same. After bisulfite treatment and asymmetric PCR, methylation and unmethylation sequences can be changed into guanine-enriched and adenine-enriched sequences, respectively. A home-made gold nanoparticle modified screen printed carbon electrode (AuNP-SPCE) was employed to distinguish the adsorption affinities between guanine-enriched and adenine-enriched sequences, which could be used to analyze the level of DNA methylation. Several key experimental factors were investigated and optimized. The results had shown that the optimal AuNP electrodeposition time was 100 s and 15 min of adsorption could distinguish guanine-enriched and adenine-enriched sequences with a concentration of 100 nM at 25 °C. The detection limit of our AuNP-SPCE was 1.1 ng, and the assay had a good sensitivity of 10% methylation change and was able to distinguish only one methylated CpG site. What's more, the RSD over three assays with a disposable AuNP-SPCE was ≤7.2%. The assay was applied to real samples including cell lines and clinical tissues. Compared with normal hepatic cell lines and normal tissues, lower signals of HCC cell lines and cancer tissues were observed, respectively. It had shown a good discrimination of the abnormal methylation level of the p16 gene promoter.
研究领域:
癌症诊断
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分子生物学
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电化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Jiaxin Dong,Qi Wang,Tingting Gu,Guanxiong Liu,Yuri V. Petrov,Vladimir E. Baulin,Aslan Yu Tsivadze,Dechang Jia,Yu Zhou,Huiping Yuan,Baoqiang Li
Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 10 4 times higher than that of Rapa (2.6 × 10 -4 g). The half maximal inhibitory concentration (IC 50 ) of Rapa-CDs toward hydroxyl radical ( • OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P 21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.
研究领域:
药理学
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纳米技术
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心血管疾病
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2023
·
IF 11.4
Chen-Yu Zhang,Wen-Jing Zhong,Yu-Biao Liu,Jia-Xi Duan,Nan Jiang,Hui-Hui Yang,Sheng-Chao Ma,Ling Jin,Jie-Ru Hong,Yong Zhou,Cha-Xiang Guan
Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro , we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and γH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
研究领域:
药理学
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细胞生物学
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分子生物学
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呼吸医学
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DOI
PubMed
高影响因子
JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2020
·Vol. 167
·期 6
·067501
·
IF 3.721
Xiaoying Wang,Miao Gong,Linyu Li,Liangrui Lv,Xin Jin,Yijie Wang
An enzyme electrocatalytic p16 protein (AGp16INK4a) immunosensor based on polymethylene blue (PMB) decorated on functional composite modified glassy carbon electrode (PG-GR-CS/GCE) is constructed successfully. The PG-GR-CS having good conductivity and large specific surface area is composed of graphene (GR) doped polycaprolactam 6 (PA6) electrospun nanofibers (PG), GR and chitosan (CS), which could serve as a stable electropolymerization substrate for increasing the amount of PMB. The active catalytic electrode (PG-GR-CS-PMB/GCE) was used as the platform for the construction of an electrocatalytic immunosensor, it can greatly increase the immobilization capacity of AGp16INK4a capture antibody (Ab1), and further catch the AGp16INK4a and horseradish peroxidase-labeled detection antibody (HRP@Ab2) through the sandwich immunoreaction. The PMB decorated on PG-GR-CS/GCE exhibited good electron transfer and electrochemical properties, which could apply as electrocatalytically nanomaterials. Thus, the amplified electrocatalytic response were produced by the reduction of enzymatically oxidized PMB in the presence of hydrogen peroxide via HRP. It was observed that the change of the differential pulse voltammetry of the PMB was proportional to the AGp16INK4a ranging from of 1.0 pg ml−1 to 1.0 ng ml−1. The detection limit was down to 0.5 pg ml−1. The successful immunosensor provides a promising alternative to the electrocatalytic detection of various tumor markers.
研究领域:
生物化学
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生物技术
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电化学
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纳米技术
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癌症研究
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产品关联
DOI
高影响因子
Oncotarget
·
2016
·
IF 5.008
Jingnan Chen,Yan Wei,Xinyu Chen,Jingjing Jiao,Yu Zhang
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F 2 -isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc -mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.
研究领域:
营养学
·
衰老研究
·
分子生物学
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生物化学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Min Cai,Xiaojun Li,Meng Xu,Shiqi Zhou,Lei Fan,Jingyan Huang,Cairong Xiao,Yichen Lee,Bo Yang,Le Wang,Ross William Crawford,Yin Xiao,Lei Zhou,Chengyun Ning,Yan Wang
Patients with postoperative tumor-associated bone defects need both chemotherapy and bone repair in the shifted disease states, but chemotherapy resistance, severe side-effects, and poor bone regeneration result in tumor recurrence and therapy failure. Herein, we develop an injectable and tumor microenvironment (TME)-modulated hydrogel composed of bio-responsive drug-loaded mesoporous bioactive glass nanoparticles (MBGN), gelatin (Gel), and oxidized chondroitin sulfate (OCS) for tumor-associated bone defects closed-loop management. The TME-modulated hydrogels can deplete protons and glutathione (GSH) within residual tumor tissues with sustained drug responsive-release capability, therefore interfering TME and overcoming cancer resistance, and also reducing off-target effects. Mechanistically, in the early state of treatment, acidic environment of TME will break the Schiff’s base bond network of hydrogels, thus deliver drug-loaded nanoparticles into tumor cells. Subsequently, the pH-responsive amide bonds, GSH-responsive disulfide bonds and acidity-degradable nanocarriers of drug-loaded nanoparticles can induce ROS stress and mitochondrial-related damage, activating the p16-CYLD tumor suppressor pathway to induce apoptosis and inhibit metastasis. In the late state of treatment, the hydrogels shifted into regenerative scaffolds to exert long-lasting osteogenesis effects. Overall, the TME-modulated hydrogels can orchestrate steady bone repair and avoid tumor recurrence, achieving closed-loop management of postoperative tumor-associated bone defects.
研究领域:
生物材料
·
癌症治疗
·
再生医学
·
纳米技术
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药学
·
生物医学工程
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产品关联
DOI
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Peidong You,Anning Yang,Yue Sun,Hongwen Zhang,Yaling Zeng,Yinju Hao,Jiantuan Xiong,Shengchao Ma,Huiping Zhang,Bin Liu,Yideng Jiang
Atherosclerosis is chronic inflammatory disease tightly related with defective efferocytosis of apoptotic cells (ACs) in the plaques. The strategy of efferocytosis reactivation using Atorvastatin (AT) and Metformin (Met) has attracted increasing attention for atherosclerosis treatment. Although these drug-based therapies could stimulate the phagocytic clearance of ACs, the rapid drug clearance and poor bioavailability limited their efficacy. In this study, by co-loading AT and Met into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs), we developed a biomimetic nanocomplexes for targeted atherosclerosis treatment. Macrophages membrane-coated nanocomplexes efficiently avoided the clearance of NPs from immune system and achieved targeting ability to the atherosclerotic plaques. Moreover, modified hyaluronic acid (HA) delivered NPs into the dysfunctional efferocytic cells of plaques, and achieved the plaques-macrophages-targeted therapy. In vitro results indicated that the biomimetic nanocomplexes reactivated efferocytosis by facilitating macrophages polarization from M1 to M2 phenotype through enhancing ERK5/MerTK pathway and inhibiting cellular senescence through inhibiting p53-p16/pRB pathway. In vivo study indicated that this biomimetic nanocomplexes accumulated in the atherosclerotic plaques, resulting in reduction of necrotic core area and protection against plaque rupture by reactivating efferocytosis. These findings indicated that reactivation of efferocytosis by AT and Met co-delivered nanocomplexes provided a novel promising strategy for targeted atherosclerosis treatment.
研究领域:
心血管疾病
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）