SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Mengzhu Lv,Xiaoyu Mao,Zheng Lu,Yanzhu Yang,Jiangtao Huang,Yuqin Cheng,Chuan Ye,Zhixu He,Liping Shu,Dashuang Mo
N -(1,3-dimethylbutyl)- N′ -phenyl- p -phenylenediamine (6PPD), which is widely used as an antiozonant in rubber tires, has recently got much attention for its acute aquatic toxicity. However, the developmental toxicity of 6PPD in cerebrovascular network remains unknown. Here, we investigated the effects of 6PPD exposure in cerebral vascular using zebrafish. 6PPD would not affect the body length and shape of zebrafish larvae at the concentrations ranging from 20 μg/L to 1000 μg/L. 6PPD induced developmental defects in the brain in a concentration-dependent manner. The trunk vascular development would not be affected while the cerebrovascular network was disrupted upon 6PPD exposure. 6PPD would trigger excessive Reactive Oxygen Species (ROS) in the brain, indicating abnormal oxidative stress. Mechanistically, brain-specific transcriptome analysis showed that 6PPD could potentially cause the blockage of arachidonic acid (AA) metabolism-related genes and the upregulation of ferroptosis-related genes. Besides, treatment with ferroptosis inhibitor N -Acetyl-L-cysteine (NAC) attenuated oxidative damage and improved the construction of cerebrovascular network upon 6PPD exposure. Moreover, using a human vascular endothelial cell line, we further confirmed that 6PPD could trigger abnormal oxidative stress and defective expansion capacity, implying the conserved toxicity cross species. These findings are useful for the elucidation of toxicity underlying 6PPD in cerebrovascular systems of both zebrafish and humans.
研究领域:
毒理学
·
发育生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2018
·
IF 8.537
Chao Zhang,Wei Feng,Yanjie Zhao,Tingting Yu,Pengcheng Li,Tonghui Xu,Qingming Luo,Dan Zhu
Rationale: Intravital optical imaging is a significant method for investigating cerebrovascular structure and function. However, its imaging contrast and depth are limited by the turbid skull. Tissue optical clearing has a great potential for solving this problem. Our goal was to develop a transparent skull window, without performing a craniotomy, for use in assessing cerebrovascular structure and function. Methods: Skull optical clearing agents were topically applied to the skulls of mice to create a transparent window within 15 min. The clearing efficacy, repeatability, and safety of the skull window were then investigated. Results: Imaging through the optical clearing skull window enhanced both the contrast and the depth of intravital imaging. The skull window could be used on 2-8-month-old mice and could be expanded from regional to bi-hemispheric. In addition, the window could be repeatedly established without inducing observable inflammation and metabolic toxicity. Conclusion: We successfully developed an easy-to-handle, large, switchable, and safe optical clearing skull window. Combined with various optical imaging techniques, cerebrovascular structure and function can be observed through this optical clearing skull window. Thus, it has the potential for use in basic research on the physiopathologic processes of cortical vessels.
研究领域:
神经科学
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生物医学工程
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显微成像技术
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
·
IF 8.063
Zhe Feng,Xiaoming Yu,Minxiao Jiang,Liang Zhu,Yi Zhang,Wei Yang,Wang Xi,Gonghui Li,Jun Qian
Rationale: Cerebrovascular diseases, together with malignancies, still pose a huge threat to human health nowadays. With the advantages of its high spatial resolution and large penetration depth, fluorescence bioimaging in the second near-infrared spectral region (NIR-II, 900-1700 nm) and its related imaging-guided therapy based on biocompatible fluorescence dyes have become a promising theranostics method. Methods: The biocompatibility of IR-820 we used in NIR-II fluorescence bioimaging was verified by long-term observation. The model of the mouse with a cranial window, the mouse model of middle cerebral artery occlusion (MCAO) and a subcutaneous xenograft mouse model of bladder tumor were established. NIR-II fluorescence cerebrovascular functional imaging was carried out by IR-820 assisted NIR-II fluorescence microscopy. Bladder tumor was treated by NIR-II fluorescence imaging-guided photothermal therapy. Results: We have found that IR-820 has considerable NIR-II fluorescence intensity, and shows increased brightness in serum than in water. Herein, we achieved real time and in vivo cerebrovascular functional imaging of mice with high spatial resolution and large penetration depth, based on IR-820 assisted NIR-II fluorescence microscopy. In addition, IR-820 was successfully employed for NIR-II fluorescence imaging and photothermal therapy of tumor in vivo , and the subcutaneous tumors were inhibited obviously or eradicated completely. Conclusion: Due to the considerable fluorescence intensity in NIR-II spectral region and the good photothermal effect, biocompatible and excretable IR-820 holds great potentials for functional angiography and cancer theranostics in clinical practice.
研究领域:
生物医学工程
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神经科学
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肿瘤学
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DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2020
·Vol. 4
·期 6
·1634-1642
·
IF 6.788
Haiyan Tian,Dongyu Li,Xi Tang,Yubo Zhang,Zhiyong Yang,Jun Qian,Yong Qiang Dong,Mei Han
Nanoparticle-assisted deep-tissue fluorescence imaging is of great significance to bioimaging and disease diagnosis. Through the combination of the electron donor triphenylamine and electron acceptor cyan, the compound 1,1-dicyano-2-phenyl-2-(4-diphenylamino)phenylethylene (DCPE-TPA, 1) was synthesized and exhibited an aggregation-induced emission (AIE) effect. Compound 1 can form three kinds of aggregation states: orange crystals (1OC, 578 nm, ΦF = 50.6%), red crystals (1RC, 613 nm, ΦF = 78.4%) and deep-red emissive amorphous solids (1Am, 667 nm, ΦF = 30.4%) with notable differences in their emission wavelengths and quantum yields. The DCPE-TPA molecules are encapsulated with a polymeric matrix of Pluronic F-127 to form nanoparticles (NPs) that exhibit intense three-photon fluorescence (3PF) in the deep-red region as well as high stability, good photostability and good biocompatibility. Under a 1560 nm fs laser, the DCPE-TPA NPs are further utilized for in vivo 3PF imaging of the vasculature in the brain of a mouse at various vertical depths, producing a penetration depth of 300 μm with a high spatial resolution of 1.8 μm and a high signal-to-background ratio (SBR) of 14. A high-resolution three-dimensional (3D) model of the vasculature beneath the skull could be reconstructed. It is worth mentioning that such a high quantum yield for the deep-red emission of a purely organic material has rarely been reported.
研究领域:
生物成像
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疾病诊断
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材料科学
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光学
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DOI
高影响因子
AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 7
·1-19
·
IF 3.4
Long Yanqiu,Lei Fang,Hu Jie,Zheng Zhiyun,Gui Shuangying,He Ning
The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses. Graphical Abstract
研究领域:
药剂学
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生物医学工程
·
眼科药物递送
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产品关联
DOI
PubMed
高影响因子
Open Life Sciences
·
2020
·Vol. 15
·期 1
·1042-1048
·
IF 0.69
Tao Jin,Lu Wang,Dongbo Li,Tao Yang,Yuefei Zhou
Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. In vitro studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.
研究领域:
神经科学
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药理学
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血管生物学
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DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
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2021
·Vol. 39
·期 6
·1937-1945
·
IF 3.911
Wang Guijie,Tian Fang,Li Yu,Liu Yang,Liu Chunfeng
Acute ischemic stroke is a challenging disease that threatens the life of older people. Dysfunction of brain endothelial cells is reported to be involved in the pathogenesis of acute ischemic stroke. Ramelteon is a novel agonist of melatonin receptor developed for the treatment of insomnia. Recently, the promising protective effect of Ramelteon on brain injury has been widely reported. The present study aims to investigate the protective effect of Ramelteon against free fatty acid (FFA)–induced damages in brain vascular endothelial cells and the underlying mechanism. Firstly, we discovered that Ramelteon administration remarkably reversed the decreased cell viability, increased LDH release, activated oxidative stress, and excessive released inflammatory factors caused by FFAs. Secondly, Ramelteon extensively suppressed the attachment of U937 monocytes to bEnd.3 brain endothelial cells induced by FFAs. In addition, the elevated expression of E-selectin and the reduced expression of KLF2 induced by FFAs were pronouncedly alleviated by Ramelteon. Lastly, silencing of KLF2 abolished the protective effects of Ramelteon against FFA-induced expression of E-selectin and the attachment of U937 monocytes to bEnd.3 brain endothelial cells. In conclusion, Ramelteon mitigated FFA-induced attachment of monocytes to brain vascular endothelial cells by increasing the expression of KLF2 and reducing the expression of E-selectin.
研究领域:
神经科学
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药理学
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心血管疾病
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2018
·
IF 1.652
Yanbin Wang,Yao Liu,Yuchen Li,Binbing Liu,Pei Wu,Shancai Xu,Huaizhang Shi
The purpose of this study was to evaluate the neuroprotective effects of astaxanthin on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) in rats and to explore possible molecular mechanisms. Experimental SAH model was introduced in adult male SD rats by injecting autologous arterial blood into the prechiasmatic cistern. Astaxanthin (75 mg/kg bodyweight) or olive oil was administered by oral gavage at 3 h after SAH. Our results showed that astaxanthin attenuated SAH-induced cerebral vasospasm and reduced neuronal apoptosis. Astaxanthin inhibited mitochondria-associated neuron apoptosis in the prefrontal cortex after SAH: increased mitochondrial membrane potential, decreased Bax/Bcl-2 ratio, inhibited cytochrome C release in cytoplasm, and suppressed caspase-3 enzyme activity. Furthermore, the cerebral expression levels of synaptic proteins (Synapsin-1, postsynaptic density-95 and growth-associated protein-43) and nerve growth and neuronal differentiation factors (brain-derived neurotropic factor and purine-rich binding protein-alpha) were reduced following SAH. Astaxanthin partly restored their expression. In conclusion, our current work demonstrates that astaxanthin attenuates SAH-induced EBI, possibly by improving neuronal survival and mitochondrial function.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Jinxia Hou,Lanping Zhong,Jianming Liu,Fanglan Liu,Chunhua Xia
Ethnopharmacological relevance Shengmai formula (SMF) is a classical traditional Chinese medicine prescription, which is widely used in the treatment of cardiovascular and cerebrovascular diseases . Our previous studies have demonstrated that some components in SMF can interact with each other through breast cancer resistance protein , sodium taurocholate co-transporting polypeptide , organic anion transporting polypeptide 1B1 and 1B3. Organic anion transporter 1 (OAT1) is highly expressed in kidney, mediating the elimination of many endogenous and exogenous substances. However, the interaction between the main active components in SMF and OAT1 is not clear. Aim of the study This study aimed to investigate the interactions of the major bioactive components in SMF mediated by OAT1. Materials and methods Four main fractions, namely, ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), fructus schisandrae total lignans (STL), and 12 active components, namely, ginsenoside Rg1, Re, Rd and Rb1, ophiopogonin D and Dˊ, methylophiopogonanone A and B, schizandrol A and B, schizandrin A and B, were selected to explore the interactions of SMF with OAT1 using cell and rat models. Results The above four main fractions in SMF all exhibited inhibitory effects on the uptake of 6-carboxyfluorescein (6-CF), a classic substrate of OAT1. Among the 12 main effective components, only ginsenoside Re , Rd, and methylophiopogonanone A showed inhibition of 6-CF uptake. Additionally, we found that schizandrin B was transported by HEK293-OAT1 cells, and schizandrin B uptake was markedly inhibited by GTS, OTS, OTF, ginsenoside Re, Rd, and methylophiopogonanone A. In rats, ginsenoside Re, Rd, and methylophiopogonanone A jointly increased the AUC (0-t) , AUC (0-∞) , and C max of schizandrin B, but they decreased its clearance in plasma and excretion in urine. Conclusions Ginsenoside Re, Rd, and methylophiopogonanone A were the potential inhibitors of OAT1, and may interact with some drugs serving as OAT1 substrates clinically. Schizandrin B was a potential OAT1 substrate, and its OAT1-mediated transport was inhibited by ginsenoside Re, Rd, and methylophiopogonanone A. OAT1-mediated interactions of the main active components in SMF can be regarded as one of the important compatibility mechanisms of traditional Chinese medicine preparations.
研究领域:
药理学
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中药学
·
分子生物学
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
npj Regenerative Medicine
·
2023
·Vol. 8
·期 1
·1-14
·
IF 7.2
Wang Deping,Li Bowen,Wang Shuchao,Hao Yingjian,Wang Hua,Sun Wei,Cao Jimin,Zhou Xin,Zheng Bin
Mitochondrial dysfunction and subsequent accumulation of reactive oxygen species (ROS) are key contributors to the pathology of ischemic cerebrovascular disease. Therefore, elimination of ROS and damaged mitochondria is crucial for the effective treatment of this disease. For this purpose, we designed an inhalation nanotherapeutic agent, P/D@Mn/Co 3 O 4 , to treat ischemic cerebrovascular disease. Mn/Co 3 O 4 effectively removed excess ROS from cells, reduced acute cellular oxidative stress, and protected neural cells from apoptosis. Furthermore, it depleted the H + surrounding mitochondria and depolarized the mitochondrial membrane potential, inducing mitophagy and eliminating abnormal mitochondria, thereby avoiding the continuous overproduction of ROS by eliminating the source of ROS regeneration. On intranasal administration, Mn/Co 3 O 4 encapsulated by platelet membranes and 2,3-(dioxy propyl)-trimethylammonium chloride can bypass the blood–brain barrier, enter the brain through the trigeminal and olfactory pathways, and target inflammatory regions to remove ROS and damaged mitochondria from the lesion area. In rat models of stroke and vascular dementia, P/D@Mn/Co 3 O 4 effectively inhibited the symptoms of acute and chronic cerebral ischemia by scavenging ROS and damaged mitochondria in the affected area. Our findings indicate that the nanotherapeutic agent developed in this study can be used for the effective treatment of ischemic cerebrovascular disease.
研究领域:
神经科学
·
药理学
·
纳米技术
·
治疗学
·
脑血管疾病
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Jingxin Hou,Jun Zhou,Meiqi Chang,Guangcheng Bao,Jie Xu,Man Ye,Yixin Zhong,Shuling Liu,Junrui Wang,Wei Zhang,Haitao Ran,Zhigang Wang,Yu Chen,Dajing Guo
Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive [email protected] nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and Fe 3 O 4 endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered [email protected] nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.
研究领域:
纳米技术
·
生物医学工程
·
心脏病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Shuai Hong,Changxiu Lin,Junsheng Hu,Jingshu Piao,Ming Guan Piao
Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 μg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0–∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 μg·mL–1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 μg·mL–1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.
研究领域:
药学
·
神经学
·
药物递送系统
·
药理学
·
生物技术
✓ 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）