INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 16
·8878
·
IF 4.9
Lanfei Wang,Nianfeng Qiu,Suyuan Tong,Yan Yu,Shuhua Xi,Fei Wang
Arsenic (As) has been classified as a carcinogen for humans. There is abundant evidence indicating that arsenic increases the risk of bladder cancer among human populations. However, the underlying mechanisms have yet to be fully understood and elucidated. NADPH oxidases (NOXs) are the main enzymes for ROS production in the body. NADPH Oxidase 2 (NOX2), which is the most distinctive and ubiquitously expressed subunit of NOXs, can promote the formation and development of tumors. The utilization of NOX2 as a therapeutic target has been proposed to modulate diseases resulting from the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Matrine has been reported to exhibit various pharmacological effects, including anti-inflammatory, antifibrotic, antitumor, and analgesic properties. However, it has not been reported whether matrine can inhibit malignant transformation induced by arsenic in uroepithelial cells through NOX2. We have conducted a series of experiments using both a sub-chronic NaAsO2exposure rat model and a long-term NaAsO2exposure cell model. Our findings indicate that arsenic significantly increases cell proliferation, migration, and angiogenesis in vivo and in vitro. Arsenic exposure resulted in an upregulation of reactive oxygen species (ROS), NOX2, and NLRP3 inflammasome expression. Remarkably, both in vivo and in vitro, the administration of matrine demonstrated a significant improvement in the detrimental impact of arsenic on bladder epithelial cells. This was evidenced by the downregulation of proliferation, migration, and angiogenesis, as well as the expression of the NOX2 and NLRP3 inflammasomes. Collectively, these findings indicate that matrine possesses the ability to reduce NOX2 levels and inhibit the transformation of bladder epithelial cells.
研究领域:
毒理学
·
癌症研究
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Mengli Han,Zhao Chen,Genlou Sun,Yuxi Feng,Yuxia Guo,Shiqie Bai,Xuebing Yan
Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe 3 O 4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe 3 O 4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe 3 O 4 , and co-treatment with nano-Fe 3 O 4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe 3 O 4 . The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans . The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe 3 O 4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe 3 O 4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans . This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe 3 O 4 .
研究领域:
环境科学
·
植物生理学
·
农学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BREAST CANCER RESEARCH
·
2025
·Vol. 27
·期 1
·1-19
·
IF 5.6
Kong Linghui,Hu Song,Zhao Ying,Huang Yan,Xiang Xiaobing,Yu Yang,Mao Xiaochun,Xie Kangjie,Zhu Xiaoyan,Xu Pingbo
Background The mechanisms underpinning neoadjuvant chemotherapy-induced vascular endothelial injury in breast cancer remain elusive. Our study aims to demonstrate that Neutrophil Extracellular Traps (NETs) play a pivotal role in neoadjuvant chemotherapy-induced vascular endothelial injury in breast cancer, elucidating that chemotherapy-induced upregulation of Solute Carrier 11a1 (Slc11a1) modulates Reactive Oxygen Species (ROS) generation, which may be critical for NETs formation.Methods We investigated the impact of neoadjuvant chemotherapy for breast cancer on NETs formation and vascular endothelial injury by analyzing NETs dsDNA and serum markers in patients, cells, and chemotherapy mouse models. RNA sequencing of neutrophils from chemotherapy mouse models was performed to identify the potential NETs formation-associated gene Slc11a1, which was further validated through cellular and animal experiments by assessing Slc11a1 expression, intracellular ferrous ion content, and ROS levels. Knockdown of Slc11a1 in human neutrophils and mouse models were also performed to further confirm the phenotypic results.Results Our study revealed that plasma NETs formation and endothelial injury markers were significantly elevated in breast cancer patients undergoing docetaxel & carboplatin (TCb) neoadjuvant chemotherapy, compared to controls. In these patients, NETs formation was associated with the augmentation of endothelial injury markers. Chemotherapy mouse models demonstrated that TCb treatment markedly elevated NETs formation and endothelial injury, which can be mitigated by CI-amidine, a protein-arginine deiminase inhibitor. In human neutrophils, we demonstrated that the TCb chemotherapeutic agents (combination of docetaxel and carboplatin) induced the formation of NETs, which subsequently facilitated damage to human umbilical vein endothelial cells in vitro. RNA sequencing of mouse neutrophils identified Slc11a1 as a key NETs formation-related gene, which was upregulated by TCb chemotherapy in neutrophils, leading to increased intracellular ferrous ion content and ROS generation. Knockdown of Slc11a1 in human neutrophils and mouse models demonstrated its reversal effect on TCb-induced ferrous ion upregulation, ROS generation, and NETs formation.Conclusion sOur research underscores the capacity of TCb neoadjuvant chemotherapy in breast cancer to augment NETs formation in neutrophils through Slc11a1-mediated ROS generation, which is linked to vascular endothelial injury. Our study elucidates the potential mechanisms underlying perioperative vascular endothelial injury in breast cancer patients undergoing neoadjuvant chemotherapy, offering novel insights into perioperative therapeutic management strategies for these patients.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED ORGANOMETALLIC CHEMISTRY
·
2025
·Vol. 39
·期 8
·e70305
·
IF 0
Yimei Wang,Xuechao Shi,Shuxian Hou,Guoqiang Yang,Xinxin Liu,Weiwei Zhang,Wanzhen Li,Ping Song,Longbao Zhu,Chaldi Kaoutar,Lin Gui,Jun Wang,Fei Ge
Antibiotic abuse has led to the emergence of drug-resistant bacteria, which have become the leading cause of death worldwide. Therefore, the search for effective antimicrobial reagents has become particularly important. In this study, gallium oxide nanoparticles (Ga 2 O 3 NPs) with controllable morphologies were successfully synthesized using a high-temperature thermal decomposition method. The synthesized Ga 2 O 3 NPs with different modifications exhibited good biocompatibility and photocatalytic antimicrobial activity. Notably, small-sized spherical Ga 2 O 3 NPs exhibited the best photocatalytic antibacterial properties, achieving over 99% bacterial inhibition at a 200 μg/mL concentration. Moreover, the antimicrobial mechanism of Ga 2 O 3 nanoparticles has been systematically studied. Ga 2 O 3 nanoparticles with a positive charge have strong absorption with bacteria, and they can impede biofilm formation, disrupt the bacterial cell membrane, induce nucleic acid leakage, and provoke an elevation in reactive oxygen species (ROS) under a xenon lamp light. The antibacterial process was related to protein binding, RNA degradation, and biofilm formation pathways. Ga 2 O 3 NPs combined with PCAT were first used as an effective antibacterial method, overcoming the low catalytic efficiency of traditional photocatalysts under visible light and demonstrating broader application potential, which will provide an essential reference for developing novel photocatalytic antimicrobial agents.
研究领域:
纳米技术
·
材料科学
·
抗菌剂
·
光催化
·
生物医学工程
✓ 已验证
产品关联
DOI
FREE RADICAL RESEARCH
·
2024
·
IF 3.6
Xue Peng,Xi Tan,Li Dai,Wei Xia,Zhao Wu
This research investigates the interplay between Reactive Oxygen Species (ROS) and Apelin (APLN) in regulating autophagy, with implications for placental cell senescence and apoptosis in pre-eclampsia (PE). We manipulated APLN expression using sgRNA to study its effects on ROS levels and subsequent cellular responses. Our findings reveal that APLN overexpression elevates ROS production, accelerating cellular senescence and apoptosis. In contrast, silencing APLN enhances autophagy, thereby diminishing cellular aging and apoptosis. These outcomes were confirmed in vitro and in vivo experiments, establishing a causative relationship between ROS-mediated APLN modulation and altered placental cell dynamics in PE. The results suggest potential therapeutic targets within the ROS and APLN pathways to alleviate detrimental changes in the placenta, offering new strategies for the clinical management of PE. This study emphasizes the crucial role of autophagy in placental health and sets the stage for future investigations into therapeutic interventions for pregnancy-related complications.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xilin Li,Junjiang Pan,Mingjie Liu,Enning Zhang,Yan Li,Yang He,Guang Yang,Shaobing Zhou
Frostbite is a prevalent form of acute cold injury that can cause extensive tissue damage, often requiring amputation. However, most clinical interventions face the challenge of preventing or mitigating reperfusion injury while restoring the blood supply. In this study, a fiber patch is developed with reperfusion injury prevention and thermal stimulation capabilities for frostbite treatment. Encapsulating itaconic acid (ITA) within the surface knots of the fabricated necklace-like polymer fibers optimizes its release kinetics, effectively inhibiting the generation of reactive oxygen species (ROS) through metabolic pathways. Localized thermal stimulation from the fiber matrix modulates cytokine secretion and promotes microcirculation remodeling in frostbitten tissues. In a study involving a third-degree frostbite model, the fiber patch demonstrates superior therapeutic efficacy in accelerating tissue repair, outperforming conventional pharmaceutical treatments. Hence, this study provides a portable, effective, and preventive solution for frostbite management.
研究领域:
生物医学工程
·
材料科学
·
急诊医学
·
热疗
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Hongjie Zhang,Jing Wang,Ruiying Wu,Benyan Zheng,Yanxiang Sang,Bibo Wang,Lei Song,Yuan Hu,Xiaopeng Ma
Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME-responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self-supply ROS-responsive cascade polyprodrug (PMTO) was designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO was degraded by endogenous ROS of the TME, another part of the polyprodrug backbone became cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy was further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrated remarkable antitumor efficacy, effectively addressing the limitations associated with MTO. This article is protected by copyright. All rights reserved
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Fan Xu,Jie Chen,Wei Wang,Lizhong Zhu
Polybrominated diphenyl ethers (PBDEs) in soils posed potential risks to crop growth and food safety due to their prevalence and persistence. PBDEs were capable of being absorbed and accumulated into crops, impacting their growth, whereas the interference on metabolic components and nutritional composition deserves further elucidation. This study integrated a combined non-targeted and targeted metabolomics method to explore the influences of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) and decabromodiphenyl ether (BDE-209) on the metabolic responses of rice ( Oryza sativa ). Metabolic pathways, which were associated with sugars, organic acids, and amino acids, were significantly disturbed under PBDE stresses. Particularly, 75% of the marked altered pathways belonged to amino acid metabolism, with alanine / aspartate / glutamate metabolism being commonly enhanced. The degradation of aspartic acid promoted the formation of downstream amino acids, among which the levels of lysine, methionine, isoleucine, and asparagine were increased by 1.31–3.15 folds compared to the control. Thus, the antioxidant capacity in rice plants was enhanced, particularly through the significant promotion of ascorbic acid-glutathione (AsA-GSH) cycle in rice leaves. The amino acids were promoted to resist reactive oxygen species (ROS) efficiently, thus were deficient for nutrient storage. When exposed to 4 μmol/kg PBDEs, the contents of amino acids and proteins in grains decreased by 9.1–32.1% and 8.6–34.8%, respectively. In particular, glutelin level was decreased by 5.6–41.2%, resulting in a decline in nutritional quality. This study demonstrated that PBDEs deteriorated the protein nutrition in rice grains by affecting amino acid metabolism, providing a new perspective for evaluating the ecological risks of PBDEs and securing agricultural products.
研究领域:
环境科学
·
农业
·
植物科学
·
食品安全
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 10
·1-15
·
IF 8.1
Zhao Rong,Guo Zizhen,Lu Kaikai,Chen Qian,Riaz Farooq,Zhou Yimeng,Yang Luyun,Cheng Xiaona,Wu Litao,Cheng Kexin,Feng Lina,Liu Sitong,Wu Xiaodan,Zheng Minghua,Yin Chunyan,Li Dongmin
Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2 HKO ) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2 HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1.
研究领域:
肝病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2024
·
IF 4.1
Hongming Huang,Huang Yang,Shunhang Feng,Xiaoyan Zhang,Chu Chen,Hongyu Yan,Rui Li,Mengxin Liu,Juan Lin,Yancheng Wen,Feifei She
The burgeoning emergence of drug-resistant Helicobacter pylori strains poses a significant challenge to the clinical success of eradication therapies and is primarily attributed to mutations within drug-targeting genes that lead to antibiotic resistance. This study investigated the effect of high salt conditions on the occurrence of drug-resistance mutations in H. pylori. We found that high salt condition significantly amplifies the frequency of drug resistance mutations in H. pylori. This can be chiefly attributed to our discovery indicating that high salt concentration results in elevated reactive oxygen species (ROS) levels, initiating DNA damage within H. pylori. Mechanistically, high salt condition suppresses lipopolysaccharide (LPS) synthesis gene expression, inducing alterations in the LPS structure and escalating outer membrane permeability. This disruption of LPS synthesis attenuates the expression and activity of SodB, facilitates increased ROS levels, and consequently increases the drug resistance mutation frequency. Impairing LPS synthesis engenders a reduction in intracellular iron levels, leading to diminished holo-Fur activity and increased apo-Fur activity, which represses the expression of SodB directly. Our findings suggest a correlation between high salt intake and the emergence of drug resistance in the human pathogen H. pylori, implying that dietary choices affect the risk of emergence of antimicrobial resistance.
研究领域:
微生物学
·
分子生物学
·
传染病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Shuyue Zheng,Jihong Dong,Quan Chen,Min Wu,Dong Zhu,Li Cui,Philippe Frangois-Xavier Corvini,Hong-Zhe Li,Bo Pan
Polycyclic aromatic hydrocarbons (PAHs) are widespread contaminants that can accumulate in microorganisms, posing significant ecological risks. While previous studies primarily focused on PAH concentrations, the impacts of PAH self-clustering have been largely overlooked, which will lead to inaccurate assessments of their ecological risks. This study evaluates the toxic effects of four prevalent PAH clusters on microbes with an emphasis on comparing the cluster sizes. Results revealed that over 95% of PAHs can form clusters in the aquatic environment, with smaller clusters more likely to form at lower concentrations and with fewer benzene rings. To quantify the toxic effects and understand underlying mechanisms, single-cell Raman-D2O was employed to link bacterial phenotypes with transcriptomic profiles. Bacteria exposed to smaller PAH clusters showed a 1%–10% reduction in metabolic activity, which was associated with a 1.8–2.9-fold increase in intracellular reactive oxygen species (ROS). Furthermore, when exposed to smaller PAH clusters, the expression of genes related to the ROS response and efflux pumps was upregulated by up to 6.33-fold and 4.97-fold, respectively, suggesting that smaller PAH clusters pose greater toxicity to microbes. These findings underscore the potentially overlooked risks of PAH clusters in environmental systems and deepen our understanding of the environmental fate and ecological risks of these contaminants.
研究领域:
环境科学
·
微生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 7
·786
·
IF 6
Tiantian Liu,Bin Jiang,Baoqiang Fu,Changyi Shang,Haobin Feng,Tao Chen,Yan Jiang
Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular senescence in H9c2 cardiomyoblast cells, as characterized by an increase in the percentage of β-galactosidase-positive cells, elevated expression levels of p16 and p21, and enhanced H3K9me3 foci. EOM also induced cell cycle arrest at the G1/S stage, accompanied by downregulation of CDK4 and Cyclin D1. Furthermore, EOM exposure led to a significant elevation in intracellular reactive oxygen species (ROS), mitochondrial ROS, and DNA damage. Supplementation with the antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings also revealed that exposure to EOM activated the aryl hydrocarbon receptor (AhR) signaling pathway, as evidenced by AhR translocation to the nucleus and upregulation of Cyp1a1 and Cyp1b1. Importantly, the AhR antagonist CH223191 effectively mitigated EOM-induced oxidative stress and cellular senescence. In conclusion, our results indicate that PM2.5-induced AhR activation leads to oxidative stress, DNA damage, and cell cycle arrest, leading to cardiac senescence. Targeting the AhR/ROS axis might be a promising therapeutic strategy for combating PM2.5-induced cardiac aging.
研究领域:
心血管疾病
·
毒理学
·
细胞生物学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）