SCIENCE OF THE TOTAL ENVIRONMENT
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2025
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IF 8
Bin Li,Chenglong Sun,Yanan Yang,Chenqinyao Li,Te Zheng,Jiashuo Zhou,Yun Zhang
This study focuses on the potential hazards of borneol (BO) to aquatic organisms and human health. BO has antibacterial, anti-inflammatory and antioxidant activities, and is widely used in medicine, cosmetics, and detergents. In this study, zebrafish was used as a model organism to systematically evaluate the effects of BO on the heart, liver, kidney, and nervous system. The effects of BO on metabolites of zebrafish were studied using MALDI-MSI. The results showed that a high concentration of BO (500 μM) could induce morphological abnormalities (swim-bladder loss, spinal curvature, body-length shortening), cardiotoxicity (decreased heart rate, increased SV-BA distance), hepatotoxicity (reduced liver area index), and neurotoxicity (impaired behavioral ability, and dopamine neuron development deficits), but there was no renal toxicity observed in zebrafish. Additionally, MALDI-MSI analysis showed that BO exposure significantly altered the levels of metabolites, including phospholipids, fatty acids, choline, and amino acids. The contents of PC-34:1, PC-34:2, PI-36:4, PE-36:1, LysoPE-22:5, LysoPC-18:1, FA-18:2, phenylalanine, lysine and glutathione were significantly increased, while the contents of PC-38:6 and PC-40:6 were significantly decreased. Notably, BO elicited a significant alteration in the mRNA expression levels of genes associated with phospholipid metabolism, fatty acid metabolism, choline metabolism, and amino acid metabolism (such as elovl5 , chpt1 , chka , setd7 , hgd ). This study revealed that BO exerted toxicity on multiple organs and demonstrated that BO causes metabolic dysregulation in zebrafish. These findings provide a novel insight into the toxicity of BO.
研究领域:
毒理学
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环境科学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Jiajin Xu,Zeyi Zhang,Hongtao Hu,Yaqin Yang,Chenghong Xiao,Luyi Xi,Jiahui Lu,Shasha Tian,Huajun Zhao
Peiminine, the primary biologically active compound from Fritillaria thunbergii Miq., has demonstrated significant pharmacological activities. Doxorubicin is one of the most potent chemotherapeutic agents for breast cancer (BC). This study was designed to investigate the efficacy and underlying mechanisms of Peiminine combined with Doxorubicin in treating BC. Our results demonstrated that the combination of Peiminine and 1 mg/kg Doxorubicin exhibited more significant suppression of tumor growth compared with the monotherapy in MDA-MB-231 xenograft nude mice model, which is comparable to the effect of 3 mg/kg Doxorubicin in vivo. Notably, the 3 mg/kg Doxorubicin monotherapy resulted in organ toxicity, specifically in the liver and heart, whereas no toxicity was observed in the combination group. In vitro , this combined treatment exhibited a synergistic reduction on the viability of BC cells. Peiminine enhanced the cell cycle arrest and DNA damage induced by Doxorubicin. Furthermore, the combination treatment effectively blocked DNA repair by inhibiting the MAPKs signaling pathways. And ZEB1 knockdown attenuated the combined effect of Peiminine and Doxorubicin on cell viability and DNA damage. In conclusion, our study found that the combination of Peiminine and Doxorubicin showed synergistic inhibitory effects on BC both in vivo and in vitro through enhancing Doxorubicin-induced DNA damage. These findings support that their combination is a novel and promising therapeutic strategy for treating BC .
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Particle and Fibre Toxicology
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2016
·Vol. 13
·期 1
·1-13
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IF 8.649
Guo Hua,Zhang Jing,Boudreau Mary,Meng Jie,Yin Jun-jie,Liu Jian,Xu Haiyan
Background Administration of silver nanoparticles (AgNPs) to mice could result in their distribution and accumulation in multiple organs, with notable prominence in liver, lungs, and kidneys. However, how AgNPs transport through blood vesicular system to reach the target organs is unclear, and the precise differences in the mechanisms of toxicity between AgNPs and silver ions still remain elusive. In the present research, the pathological changes on these target organs with a focus on inter-endothelial junction was investigated to gain a new insight of AgNPs toxicity by comparing the mechanisms of action of AgNPs and AgNO3.Methods We investigated the in vitro cytotoxicity of either citrated-coated AgNPs (10, 75, and 110 nm) or silver nitrate (AgNO3) following 24 h incubations (1–40 μg/mL) in the presence of primary human umbilical vein endothelial cells (HUVEC). Meanwhile, we detected the effects of AgNPs on intercellular conjunction and intracellular ROS by VE-cadherin staining and 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, respectively. To assess in vivo toxicity, we administered single or multiple intravenous injections (25 μg Ag for AgNPs and 2.5 μg Ag for AgNO3 per dose) to mice.Results In the in vitro study, the TEM observation showed that AgNPs were taken up by endothelial cells while AgNO3 was taken up little. Meanwhile AgNPs incubation induced the elevation of intracellular ROS and down-regulation of VE-cadherin between the endothelial cells and affected the cytoskeleton actin reorganization, which could be rescued by antioxidant N-acetylcysteine. In contrast, AgNO3 caused direct cell death when the concentration was higher than 20 μg/mL and without ROS induction at lower concentration. The release of AgNPs from leaking vessels induced peripheral inflammation in the liver, lungs, and kidneys, and the severity increased in proportion to the diameter of the AgNPs used.Conclusion It is AgNPs but not AgNO3 that were taken up by vascular endothelial cells and induced intracellular ROS elevated, which was closely related to disruption of the integrity of endothelial layer. The AgNPs-induced leakiness of endothelial cells could mediate the common peripheral inflammation in liver, kidney and lung through intravenous exposure.
研究领域:
毒理学
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纳米技术
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2024
·Vol. 14
·期 1
·1-16
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IF 3.8
Li Siyao,Chen Quanlong,Zhang Yanglin,Wang Di,Hu Huiling,Li Jingjing,Zhang Chen,Zhang Jinming
Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F, has been shown excellent pharmacological effects on rheumatoid arthritis. However, TP is prone to causing severe organ toxicity, which limits its clinical application. In recent years, microneedle technology has provided a new option for the treatment of arthritis due to its advantages of efficient local transdermal drug delivery. In this study, we constructed a microneedle platform to deliver TP locally to the joints, thereby enhancing TP penetration and reducing systemic toxicity. Additionally, we investigated whether acupoint drug delivery can produce a synergistic effect of needles and drugs. First, TP was loaded into microneedles using polyvinylpyrrolidone and hyaluronic acid as matrix materials. Next, we established a rat adjuvant-induced arthritis (AIA) model to evaluate the therapeutic effect of TP-loaded microneedles. The experiments showed that TP-loaded microneedles alleviated the AIA rats’ inflammatory response, joint swelling, and bone erosion. However, there was no significant difference in the therapeutic effect observed in the acupoint and non-acupoint administration groups. In conclusion, TP-loaded microneedles have the advantages of safety, convenience, and high efficacy over conventional administration routes, laying a foundation for the transdermal drug delivery system-based treatment of rheumatoid arthritis.
研究领域:
药学
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生物医学工程
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中医
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风湿病学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Haiting Liu,Guangqing Cai,Shuai Yuan,Xionghui Zhou,Rong Gui,Rong Huang
Triple-negative breast cancer (TNBC) is characterized by high malignancy and limited treatment options. Given the pressing need for more effective treatments for TNBC, this study aimed to develop platelet membrane (PM)-camouflaged silver metal–organic framework nanoparticles (PM@MOF-Ag NPs), a biomimetic nanodrug. PM@MOF-Ag NP construction involved the utilization of 2-methylimidazole and silver nitrate to prepare silver metal–organic framework (MOF-Ag) NPs. The PM@MOF-Ag NPs, due to their camouflage, possess excellent blood compatibility, immune escape ability, and a strong affinity for 4T1 tumor cells. This enhances their circulation time in vivo and promotes the aggregation of PM@MOF-Ag NPs at the 4T1 tumor site. Importantly, PM@MOF-Ag NPs demonstrated promising antitumor activity in vitro and in vivo. We further revealed that PM@MOF-Ag NPs induced tumor cell death by overproducing reactive oxygen species and promoting cell apoptosis. Moreover, PM@MOF-Ag NPs enhanced apoptosis by upregulating the ratios of Bax/Bcl-2 and cleaved caspase3/pro-caspase3. Notably, PM@MOF-Ag NPs exhibited no significant organ toxicity, whereas the administration of MOF-Ag NPs resulted in liver inflammation compared to the control group.
研究领域:
肿瘤学
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纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2015
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IF 7.705
HongYan Zhu,ShengYu Zhang,Yong Ling,GuoLiang Meng,Yu Yang,Wei Zhang
Hypoxia is a characteristic of cancer and plays a key role in tumorigenesis, angiogenesis and resistance to cancer therapies. SiRNA treatment is effective against hypoxic tumors by gene silencing. However, siRNA delivery to the hypoxic regions of solid tumors still presents a challenge due to the distance from blood vessels and the increased presence of efflux transporters. Therefore, tumor therapies would be improved through the immediate development of an effective siRNA delivery system to hypoxic regions. To this end, we synthesized a system to deliver HIF-1α siRNA into hypoxic tumor cells. The system consists of a functional shell composed of 2-deoxyglucose (DG)-polyethylene glycol (PEG) connected with the compound of lipoic acid , lysine and 9-poly- d -arginine (LA–Lys–9R) by a hydrazone bond and a core of CdTe quantum dots (QDs). The molecular structure of DG–PEG–LA–Lys–9R was confirmed by liquid chromatography–mass spectrometry (LC–MS), nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The multifunctional CdTe QDs measured approximately 200 nm and showed excellent biocompatibility , perfect siRNA binding capability and enhanced hypoxic tumor targeting. Importantly, the system described here is pH-responsive with a hydrazone bond; therefore, it avoids GLUT1 receptor-mediated endocytic recycling, resulting in irreversible delivery of the siRNA. We used Western blots to confirm the superior gene silencing efficiency induced by the DG–PEG–LA–Lys–9R with hydrazone modified CdTe QDs. Here, we demonstrate high efficacy of the siRNA tumor delivery system using in vitro and in vivo experiments. In addition, these studies demonstrate that pH-responsive hybrid quantum dots show improved antitumor efficacy with decreased organ toxicity , indicating a promising siRNA delivery system for hypoxic cancer therapy.
研究领域:
癌症治疗
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纳米技术
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Jihui Lu,Zhijia Wang,Desheng Cai,Xiaoyu Lin,Xuemei Huang,Zhihua Yuan,Yaozhi Zhang,Haimin Lei,Penglong Wang
Background Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed.Methods Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and “one-pot” preparation process.Results The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant S. aureus (MRSA) by downregulating mRNA expression of rpsF, rplC, rplN, rplX, rpsC, rpmC and rpsH to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity.Conclusion GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.
研究领域:
药学
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纳米技术
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微生物学
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伤口愈合
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中医药
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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
危险品化学品经营许可证（带存储）