Jove-Journal of Visualized Experiments
·
2021
·
IF 1.355
Qixiao Jiang,Xiaohui Xu,Jamie C. DeWitt,Yuxin Zheng
Chicken embryos are a classical model in developmental studies. During the development of chicken embryos, the time window of heart development is well-defined, and it is relatively easy to achieve precise and timely exposure via multiple methods. Moreover, the process of heart development in chicken embryos is similar to mammals, also resulting in a four-chambered heart, making it a valuable alternative model in the assessment of developmental cardiotoxicities. In our lab, the chicken embryo model is routinely used in the assessment of developmental cardiotoxicities following exposure to various environmental pollutants, including per- and polyfluoroalkyl substances (PFAS), particulate matter (PMs), diesel exhaust (DE) and nano materials. The exposure time can be freely selected based on the need, from the beginning of development (embryonic day 0, ED0) all the way to the day prior to hatch. The major exposure methods include air-cell injection, direct microinjection, and air-cell inhalation (originally developed in our lab), and the currently available endpoints include cardiac function (electrocardiography), morphology (histological assessments) and molecular biological assessments (immunohistochemistry, qRT-PCR, western blotting, etc.). Of course, the chicken embryo model has its own limitations, such as limited availability of antibodies. Nevertheless, with more laboratories starting to utilize this model, it can be used to make significant contributions to the study of developmental cardiotoxicities.
研究领域:
毒理学
·
发育生物学
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Hong-Yu Fu,Yue Li,Han Cui,Jiu-Zhi Li,Wan-Xue Xu,Xi Wang,Rui-Feng Fan
Mercuric chloride (HgCl 2 ), a widespread environmental pollutant, induces ferroptosis in chicken embryonic kidney (CEK) cells. Whereas activating transcription factor 4 (ATF4), a critical mediator of oxidative homeostasis, plays a dual role in ferroptosis, but its precise mechanisms in HgCl 2 -induced ferroptosis remain elusive. This study aims to investigate the function and molecular mechanism of ATF4 in HgCl 2 -induced ferroptosis. Our results revealed that ATF4 was downregulated during HgCl 2 -induced ferroptosis in CEK cells. Surprisingly, HgCl 2 exposure has no significant impact on ATF4 mRNA level. Further investigation indicated that HgCl 2 enhanced the expression of the E3 ligase beta-transducin repeat-containing protein (β-TrCP) and increased ATF4 ubiquitination. Subsequent findings identified that miR-15b-5p as an upstream modulator of β-TrCP, with miR-15b-5p downregulation observed in HgCl 2 -exposed CEK cells. Importantly, miR-15b-5p mimics suppressed β-TrCP expression and reversed HgCl 2 -induced cellular ferroptosis. Mechanistically, HgCl 2 inhibited miR-15b-5p, and promoted β-TrCP-mediated ubiquitin degradation of ATF4, thereby inhibited the expression of antioxidant-related target genes and promoted ferroptosis. In conclusion, our study highlighted the crucial role of the miR-15b-5p/β-TrCP/ATF4 axis in HgCl 2 -induced nephrotoxicity, offering a new therapeutic target for understanding the mechanism of HgCl 2 nephrotoxicity.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Hui Wang,Weili Wang,Qianqian Xie,Di Wu,Jiayu Cao,Huilin Chen,Meng Gao,Huizhen Zheng,Xi Liu,Jie Jiang,Wenjie Li,Xiaoming Cai,Sergey V. Gudkov,Ruibin Li
Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air–blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air–blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air–blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.
研究领域:
环境科学
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毒理学
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纳米生物学
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DOI
PubMed
高影响因子
HUMAN & EXPERIMENTAL TOXICOLOGY
·
2013
·
IF 1.453
Y Bai,X Zhao,C Qi,L Wang,Z Cheng,M Liu,J Liu,D Yang,S Wang,T Chai
Chromium picolinate (CrPic), which is used as a nutritional supplement and to treat type 2 diabetes, has gained much attention because of its cytotoxicity. This study evaluated the effects of CrPic on the viability of the chick embryo fibroblast (CEF) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, morphological detection, and flow cytometry. The results show that lower concentrations of CrPic (8 and 16 μM) did not damage CEF viability (p > 0.05). However, higher CrPic concentrations (400 and 600 μM) indicated a highly significant effect on the production of intracellular reactive oxygen species, alteration of mitochondrial membrane potential, intracellular calcium ion concentration, and the apoptosis rate (p < 0.01), contrary to lower CrPic concentrations (8 and 16 μM) and control group. Moreover, apoptotic morphological changes induced by these processes in CEF were confirmed using Hoechst 33258 staining. Cell death induced by higher concentrations of CrPic was caused by an apoptotic and a necrotic mechanism, whereas the main mechanism of oxidative stress-induced mitochondrial dysfunction was apoptotic death.
研究领域:
毒理学
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细胞生物学
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营养学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Chanjuan Yue,Jin Chen,Ranran Hou,Weijun Tian,Kuanhui Liu,Deyun Wang,Yu Lu,Jiaguo Liu,Yi Wu,Yuanliang Hu
The antioxidant action and mechanism of selenizing schisandra chinensis polysaccharide (sSCP) were investigated in chicken embryo hepatocyte (CEH) taking schisandra chinensis polysaccharide (SCP) and N-acetyl-L-cysteine (NAC) as control. The CEH was cultured and treated with sSCP, then exposed to H 2 O 2 . The CEHs’ viability, apoptosis, ROS and antioxidase contents and the protein expression in MAPKs pathway and mitochondrion-dependence apoptotic signal pathway were assayed. The results showed that sSCP could significantly raise the cell viability and the activities of SOD, CAT and GSH-Px, decrease the cell apoptosis and the content of LDH, AST, ALT and MDA, down-regulate the protein expression of p-JNK 1 , p-ERK 1/2 , p-p38, Bax, Caspase 3 and cytochrome C, and up-regulate the protein expression of Bcl-2 in comparison with H 2 O 2 control group. The action of sSCP were stronger than those of SCP and NAC. These results indicated that selenylation modification could significantly enhance the antioxidant activity of SCP, sSCP could significantly protect hepatocyte from oxidative damage induced by H 2 O 2 , and its mechanism was by regulating the protein expression in MAPKs and mitochondrion-dependence apoptotic signaling pathways.
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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产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Chang-Yu Yan,Jie Sun,Gui-Yuan Yu,Jiang-Han-Zi Liu,Rong-Ping Huang,Shao-Cong Han,Qiong-Yi Zhang,Xiao-Min Li,Jian-Gang Yan,Hiroshi Kurihara,Wei-Xi Li,Yi-Fang Li,Rong-Rong He
Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.
研究领域:
营养学
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胚胎学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Xi-you Li,Xiao-yuan Gu,Xiao-min Li,Jian-gang Yan,Xin-liang Mao,Qin Yu,Yu-lan Du,Hiroshi Kurihara,Chang-Yu Yan,Wei-xi Li
BACKGROUND Carnosine, a natural bioactive dipeptide derived from meat muscle, possesses strong antioxidant properties. Dexamethasone, widely employed for treating various inflammatory diseases, raises concerns regarding its detrimental effects on bone health. This study aimed to investigate the protective effects of carnosine against dexamethasone-induced oxidative stress and bone impairment, along with its underlying mechanisms, utilizing chick embryos and a zebrafish model in vivo , as well as MC3T3-E1 cells in vitro . RESULTS Our findings revealed that carnosine effectively mitigated bone injury in dexamethasone-exposed chick embryos, accompanied by reduced oxidative stress. Further investigation demonstrated that carnosine alleviated impaired osteoblastic differentiation in MC3T3-E1 cells and zebrafish by suppressing the excessive production of reactive oxygen species (ROS) and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPX). Moreover, mechanistic studies elucidated that carnosine promoted the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby facilitating the transcription of its downstream antioxidant response elements, including heme oxyense-1 (HO-1), glutamate cysteine ligase modifier (GCLM), and glutamate cysteine ligase catalytic (GCLC) to counteract dexamethasone-induced oxidative stress. CONCLUSION Overall, this study underscores the potential therapeutic efficacy of carnosine in mitigating oxidative stress and bone damage induced by dexamethasone exposure, shedding light on its underlying mechanism of action by activating the NRF2 signaling pathway. © 2024 Society of Chemical Industry.
研究领域:
药理学
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生物化学
·
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
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 39
·9110-9120
·
IF 5.344
Zhiyang Xu,Yulong Xu,Papia Basuthakur,Chitta Ranjan Patra,Seeram Ramakrishna,Yong Liu,Vinoy Thomas,Himansu Sekhar Nanda
Functionalized cerium oxide nanoparticle (CeNP)-loaded fibro-porous poly-L-lactic acid (PLLA)/gelatin composite membranes were prepared via an electrospinning technology. Considering the importance of such membrane scaffolds for promoting angiogenesis in tissue engineering and drug screening, a series of PLLA/gelatin composite fiber membranes loaded with different doses of CeNPs was prepared. The prepared composite membranes demonstrated hydrophilicity, water absorption, and improved mechanical properties compared to a PLLA and PLLA/gelatin membrane. Also, cell viability assay using somatic hybrid endothelial cells (EA.hy926) proved the biocompatible nature of the scaffolds. The biocompatibility was further supported by in vivo chick embryo angiogenesis assay using fertilized eggs. Our initial results support that these membrane scaffolds could be useful for angiogenesis-related disease treatment after further investigations.
研究领域:
组织工程
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材料科学
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生物材料
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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
Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
·
2016
·Vol. 299
·期 4
·450-460
·
IF 1.507
Fuyin Hou,Min Xiao,Jian Li,Devin W. Cook,Weidong Zeng,Caiqiao Zhang,Yuling Mi
Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers ( Stra8 , Spo11 , Scp3 , and Dmc1 ) together with those of Raldh2 , a retinoic acid (RA) synthetase, and of the receptors ( RARα and RARβ ). In addition, exposure to Cd increased the production of H 2 O 2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. Anat Rec, 299:450–460, 2016. © 2016 Wiley Periodicals, Inc.
研究领域:
毒理学
·
生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
·
2024
·
IF 1.2
Miao Cui,Lijuan Jiang,Wei Yang,Wenfeng Zhang
The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development.Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67.The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.
研究领域:
肿瘤学
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药理学
·
中医药
·
动物模型
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分子生物学
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组织病理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Xi-you Li,Xiao-yuan Gu,Bai-ling Zhou,Bun Tsoi,Wei-xi Li
Eye deformity, a noteworthy embryopathy, is intricately linked with maternal diabetes, frequently resulting in embryonic malformation or even death. In this investigation, a hyperglycemic chick embryo model was established to delve into the protective potential of tamarind shell extract (TSE) on eye development. Chick embryos were administered with TSE (at dosages of 1, 2, and 4 µg/egg) through air sac injection on embryo development day 0 (EDD0) and later exposed to D-glucose (0.4 mmol/egg) on EDD1. To validate our findings, we replicated hyperglycemic environment using D-glucose in ARPE-19 cell model. Our research unveiled that TSE proficiently counters O-GlcNAcylation of proteins in the presence of D-glucose, thereby reinstating levels of key proteins involved in eye development, including Pax6, Daam1, mTOR, and Cdc42. Furthermore, TSE was pinpointed to curtail the D-glucose concentration within the embryo eye, considerably decreasing the accumulation of reactive oxygen species and malondialdehyde accumulation in both the ARPE-19 cells and chick embryos. Beyond its fundamental role in boosting the cellular antioxidative activity, the improved expression of apoptosis-related proteins like Caspase-3, BAX, BCL-2 and other like PI3K and AKT were observed. This suggests a probable activation of the PI3K-AKT-mTOR pathway on ARPE-19 cells by TSE, thereby downregulating apoptotic proteins in ARPE-19 cells during oxidative stress. TSE may become a potent natural countermeasure against D-glucose-induced eye malformation.
研究领域:
发育生物学
·
药理学
·
细胞生物学
·
胚胎学
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产品关联
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 107
·105442-105448
·
IF 3.289
Yue Cao,Yan Li,Yin Wu,Wenliang Li,Chunlei Yu,Yanxin Huang,Luguo Sun,Yongli Bao,Yuxin Li
Co-Encapsulated angiostatin (AS) and curcumin (Cur) in poly(ethylene glycol)-b-poly(ε-caprolactone) polymersomes (PEG–PCL-PMs) were prepared by film hydration method. The size and zeta potential of the prepared PEG–PCL-PMs were about 153 nm and −0.22 mV, respectively. Transmission electron microscopy was employed to confirm the polymersomal structure of PEG–PCL-PMs. In vitro drug release profiles showed a sustained release of angiostatin and curcumin from the dual-drug loaded polymersomes under physiological conditions (pH 7.4). In addition, confocal laser scanning microscopy and flow cytometry showed that drug-loaded polymersomes were delivered efficiently into the cytoplasm and nuclei of human microvascular endothelial cell line (HMEC-1) and then released active drugs in cells. Dual drug-loaded polymersomes (AS–Cur-PMs) remarkably inhibited proliferation and migration of HMEC-1 cells compared to those treated with the single drug. The chick chorioallantoic membrane assay showed that AS–Cur-PMs inhibited vessel sprouting in the chicken chorioallantoic membrane. Our data demonstrates a synergistic effect of angiostatin and curcumin in inhibiting angiogenesis, both in vitro and in vivo.
研究领域:
药学
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生物医学工程
·
细胞生物学
·
药物递送系统
·
血管生成研究
✓ 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）