PHYTOMEDICINE
·
2023
·
IF 7.9
Yuhong Li,Shuying Hu,Yueqi Chen,Xing Zhang,Hanchi Gao,Jing Tian,Jian Chen
Background Triple-negative breast cancer (TNBC) is a heterogeneous carcinoma characterized by the most aggressive phenotype among all breast cancer subtypes. However, therapeutic options for TNBC patients have limited clinical efficacy due to lack of specific target and efficient targeted therapeutics. Aim To investigate the biological characteristics of a novel estrogen receptor (ER)-α splice variant ER-α30 in breast cancer cells , and its possible role in the anticancer effects of calycosin , a typical phytoestrogen derived from the herbal plant Astragalus membranaceus , against TNBC. This may also provide a better understanding of the inhibitory activity of calycosin on TNBC progression. Methods Breast cancer tissues and para-cancer tissues were collected and analyzed for the expression levels of ER-α30 using immunohistochemistry (IHC), and its expression in two TNBC cell lines (MDA-MB-231 and BT-549) was detected by western blot and qRT-PCR assays. Then the alteration of cell viability , apoptosis , migration, invasion and epithelial-mesenchymal transition (EMT) in response to overexpression or knockdown of ER-α30 was separately determined by CCK-8, Hoechst 33258 , wound healing, transwell and western blot assays in two TNBC cell lines. Next, the anticancer effects of calycosin on MDA-MB-231 cells were evaluated through CCK-8, colony formation, flow cytometry, Hoechst 33258 and western blot assays, along with the role of ER-α30 in these effects and the possible downstream targets of ER-α30. In addition, the in vivo experiments were carried out using MDA-MB-231 xenograft model intraperitoneally treated with calycosin. The volume and weight of xenograft tumor were measured to evaluate the in vivo anticancer activities of calycosin, while the corresponding changes of ER-α30 expression in tumor tissues were detected by IHC. Results It was demonstrated that the novel ER-α splice variant ER-α30 was primarily distributed in the nucleus of TNBC cells. Compared with normal breast tissues, ER-α30 expression was found in significantly higher levels in breast cancer tissues of ER- and progesterone receptor (PR)-negative subtype, so did in TNBC cell lines (MDA-MB-231 and BT-549) when compared to normal breast cell line MCF10A. Moreover, ER-α30 overexpression strikingly enhanced cell viability, migration, invasion and EMT progression and reduced apoptosis in TNBC cells, whereas shRNA-mediated knockdown of ER-α30 revealed the opposite results. Notably, calycosin suppressed the expression of ER-α30 in a dose-dependent manner, accompanied with the inhibition of TNBC growth and metastasis . A similar finding was observed for the xenografts generated from MDA-MB-231 cells. The treatment with calycosin suppressed the tumor growth and decreased ER-α30 expression in tumor tissues. Furthermore, this inhibition by calycosin was more pronounced in ER-α30 knockdown cells. Meanwhile, we found a positive relationship between ER-α30 and the activity of PI3K and AKT, which could also be inactivated by calycosin treatment. Conclusion For the first time, it is demonstrated that the novel estrogen receptor-α splice variant ER-α30 could function as pro-tumorigenic factor in the context of TNBC by participating in cell proliferation , apoptosis, invasion and metastasis, thus it may serve as a potential therapeutic target for TNBC therapy. Calycosin could reduce the activation of ER-α30-mediated PI3K/AKT pathway, thereby inhibited TNBC development and progression, suggesting that calycosin may be a potential therapeutic option for TNBC.
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高影响因子
APPLIED SURFACE SCIENCE
·
2016
·
IF 3.15
Zhenli Qin,Sinan Du,Yang Luo,Zhijian Liao,Fang Zuo,Jianbin Luo,Dong Liu
We report the use of an efficient hydrothermal method to synthesize superparamagnetic and red luminescent bifunctional Fe 3 O 4 @Mn 2+ -doped NaYF 4 :Yb/Er nanoparticles (NPs) with core@shell structures via a seed-growth procedure. Oleic acid coated Fe 3 O 4 (OA-Fe 3 O 4 ) NPs were initially synthesized using a coprecipitation method. The as-synthesized OA-Fe 3 O 4 NPs were then used as seeds, on which the red upconversion luminescent shell (Mn 2+ -doped NaYF 4 :Yb/Er) was formed. Furthermore, hydrophobic to hydrophilic surface modification of the Fe 3 O 4 @Mn 2+ -doped NaYF 4 :Yb/Er NPs was achieved via a ligand exchange method where oleic acid was displaced by a PEG phosphate ligand [PEG = poly(ethylene glycol)]. These materials were characterized by means of transmission electron microscopy (TEM), X-ray diffraction (XRD), photoluminescence (PL) spectroscopy, and vibrating sample magnetometry (VSM). The Fe 3 O 4 cores were uniformly coated with a Mn 2+ -doped NaYF 4 :Yb/Er shell, and the bifunctional Fe 3 O 4 @Mn 2+ -doped NaYF 4 :Yb/Er NPs were monodispersed. Furthermore, the Fe 3 O 4 @Mn 2+ -doped NaYF 4 :Yb/Er NPs exhibited a saturated magnetization value of 6.2 emu/g and emitted red luminescence under a 980 nm laser. The obtained bifunctional Fe 3 O 4 @Mn 2+ -doped NaYF 4 :Yb/Er NPs may find potential applications in drug targeting, bioseparation, and diagnostic analysis. The synthetic method may be employed for the preparation of other bifunctional nanomaterials.
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高影响因子
TALANTA
·
2017
·
IF 4.162
Ling-Feng Jiang,Bo-Cheng Chen,Ben Chen,Xue-Jian Li,Hai-Lin Liao,Hong-Miao Huang,Zhan-Jing Guo,Wen-Yan Zhang,Lin Wu
A sensitive and stable bioassay for the detection of Aβ oligomer (Aβo), a potentially promising candidate biomarker for Alzheimer's disease (AD) diagnosis, was developed using Fe 3 O 4 magnetic nanoparticles (MNPs) as the recognition and concentration elements and BaYF 5 :Yb,Er upconversion nanoparticles (UCNPs) as highly sensitive labels, conjugated with the Aβo aptamer (DNA1) and the complementary oligonucleotide of the Aβo aptamer (DNA2), respectively. The DNA1 hybridized with DNA2 to form the duplex structure on the surface of the MNPs/UCNPs nanocomposites probe. When the target Aβo was introduced, the aptamer DNA1 preferentially bound with Aβo and caused the dissociation of some complementary DNA2, liberating some UCNP-labeled complementary DNA2 and leading to a decreased upconversion fluorescent intensity on the surface of MNPs. The decreased fluorescence intensity of UCNPs was related to the concentration of Aβo in the range of 0.2–15 nM with a detection limit of 36 pM. The developed method then was successfully applied to measure Aβo in artificial cerebrospinal fluid. Benefiting from the magnetic separation and concentration effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and stability of the aptamer, the present strategy offered valuable information related to early diagnosis of AD process.
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高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 9
·3469-3475
·
IF 4.58
Tang Yiwei,Li Min,Gao Xue,Liu Xiuying,Gao Jinwen,Ma Tao,Li Jianrong
The paper describes the preparation of a fluorescent probe based on the use of up-conversion particles (UCPs) of the type NaYF 4 : Er, Yb and shelled with a molecularly imprinted polymer (MIP) that is specific for the antibiotic enrofloxacin. The upconverted green luminescence emitted by the UCPs upon photoexcitation at 980 nm was used to locally generate a thin MIP shell around the UCPs via photopolymerization. Enrofloxacin is used as the template, and ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. It is found that enrofloxacin is well captured by the MIP and then quenches the fluorescence of the UCPs. Fluorescence decreases linearly in the 63 ng·L −1 to 60 μg·L −1 enrofloxacin concentration range, with a 8 ng·L −1 limit of detection. The method was applied to the determination of enrofloxacin in spiked fish samples. Recoveries ranged from 83.7 to 87.7%, with relative standard deviations between 2.0 and 5.5% (for n = 3).
Schematic of an NIR-responsive up-conversion nanoparticle probe of the NaYF 4 :Er,Yb type and coated with a MIP for fluorometric determination of enrofloxacin. The upconverted luminescence emitted by the UCPs was used to locally generate a thin MIP shell around the UCPs via photopolymerization.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Junxian Hu,Zeyu Pang,Xiaoxiao Li,Chen Zhao,Yibo Zhu,Xiangwei Li,Huilin Zhang,Mingjie Chen,Yiyang Wang,Pei Li,Qiang Zhou
Oxidative stress-induced endoplasmic reticulum stress (ERS) plays a pivotal role in the senescence and degeneration of nucleus pulposus cells, and currently, no effective therapeutic options exist for intervertebral disc degeneration. The limited self-repair capacity of nucleus pulposus cells hampers their ability to recover, even after the removal of oxidative stressors. Consequently, the identification of cytokines capable of effectively mitigating ERS induced by cellular oxidative stress is of paramount importance for the repair of intervertebral discs. Calreticulin (CRT), an endoplasmic reticulum-resident protein, has been shown in recent studies to promote cell proliferation and collagen secretion; however, its role in intervertebral disc repair remains underexplored. This study demonstrated that CRT can repair damaged nucleus pulposus cells through two independent pathways: 1. Reducing the cell ERS condition to alleviate the rate of cell senescence; 2. Activating the FPR1/PI3K/AKT pathway to promote cell proliferation. Furthermore, a targeted endoplasmic reticulum lipid nanoparticle encapsulating CRT was successfully developed for material-based repair of damaged intervertebral discs. This novel approach provides a promising strategy for the repair of intervertebral disc degeneration.
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高影响因子
JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
·
2024
·
IF 5.8
Xinwen Liu,Bingchu Mei,Guolong Tan
Lanthanide-ion-doped red upconversion (UC) fluorescent materials with excellent signal-to-noise ratio, stability, and red-green luminous intensity ratio have proven of tremendous research importance for biomedical, three-dimensional (3D) displays, sensors, and other sectors. In this study, xYb, 1Er: Sr 5 (PO 4 ) 3 F (S-FAP) (x=0–5 at%) transparent ceramics with outstanding optical quality were fabricated by hot pressing the co-precipitation powder with high sintering activity. The energy dispersive X-ray (EDX) results showed that the trivalent lanthanide ions were evenly doped into the S-FAP ceramic lattice. Increased Yb 3+ doping considerably restricted the growth of ceramic grain size, which should be attributable to a decrease in sintering activity under high Yb doping conditions. The co-doping of Yb 3+ successfully resulted in a significant improvement in up/down conversion efficiency via effective energy transfer mechanisms and the optimization of the electron population at the energy level of red-green emission. Furthermore, single-band red upconversion luminescence with the greatest red-green upconversion luminescence integral intensity ratio of 125.74 was discovered under 980 nm laser pumping at room temperature. The energy transition process involved in the phenomenon of the up-conversion luminescence intensity shift of red-green emission has been thoroughly examined. Finally, the noncontact optical thermometric ability based on fluorescence intensity ratio (FIR) technology showed that the maximum absolute sensitivity (Sa) of the 5Yb1Er sample in the temperature range of 320–556 K is 1.1×10 −3 K −1 , implying the possible use of Yb/Er-doped S-FAP transparent ceramics in the field of optical thermometers.
研究领域:
材料科学
·
光学
·
生物医学工程
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JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Teng Wang,Weilin Liu,Chunyi Lyu,Yunxiao Luo,Xinyu Tang,Chen Han,Ruirong Xu
Ethnopharmacological relevance Realgar is an arsenic-containing mineral medicine and a key component of Realgar-Indigo naturalis formula, an oral traditional Chinese medicine preparation clinically used in China for acute promyelocytic leukemia (APL), a biologically distinct subtype of acute myeloid leukemia (AML). Realgar Transforming Solution (RTS) is a microbially processed realgar preparation. Its activity in AML stem cell-like contexts outside APL remains insufficiently defined, particularly in cell-line-derived CD34 + CD38 − LSC-like models. Aim of the study: To evaluate whether RTS suppresses stemness-associated phenotypic features in KG-1a-derived CD34 + CD38 − LSC-like cells and to explore its association with endoplasmic reticulum stress (ERS), mitochondrial injury, and mitophagy-related alterations. Materials and methods CD34 + CD38 − LSC-like cells were enriched from KG-1a cells and used as a cell-line-derived in vitro model. Cell viability, apoptosis, cell cycle, CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression were assessed after RTS treatment. RNA sequencing, Ca 2+ measurement, ROS detection, mitochondrial membrane potential assay, MDC staining, western blotting, RT-qPCR, immunofluorescence, and transmission electron microscopy were performed. 4-phenylbutyric acid and Mdivi-1 were used as pharmacological rescue agents. Results RTS reduced the CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression, while inducing apoptosis in KG-1a-derived LSC-like cells. Transcriptomics implicated ER protein processing, unfolded protein response, apoptosis, autophagy, and mitophagy-related pathways. RTS increased Ca 2+ levels, ROS accumulation, mitochondrial depolarization, PERK-eIF2α-ATF4-CHOP signaling, and PINK1/Parkin-associated mitophagy-like marker changes. 4-phenylbutyric acid and Mdivi-1 partially rescued RTS-impaired LSC-like phenotypic features, supporting pathway involvement. Conclusions RTS suppressed stemness-associated phenotypic features in a KG-1a-derived CD34 + CD38 − LSC-like model. These effects were associated with ERS, mitochondrial injury, and PINK1/Parkin-related mitophagy-like alterations.
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高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2022
·
IF 5.756
Tao Wei,Zhiwei Zheng,Xiaoyan Wei,Yugang Liu,Wentao Li,Bingqing Fang,Di Yun,Zhaojun Dong,Baozhu Yi,Wulan Li,Xiaoping Wu,Dezhi Chen,Liping Chen,Jianzhang Wu
Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to β-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Yuanyuan Zhai,Jia Xu,Li Feng,Qinan Liu,Weifeng Yao,Hui Li,Yudan Cao,Fangfang Cheng,Beihua Bao,Li Zhang
Ethnopharmacological relevance Er-Zhi-Wan (EZW), a famous traditional Chinese formulation, is used to prevent, or to treat, various liver and kidney diseases for its actions of replenishing liver and kidney. However, the mechanisms of treating Liver-kidney Yin deficiency syndrome (LKYDS) of EZW have not been comprehensively investigated. Aim of the study In this study, a broad range metabolomics strategy coupled with network analysis was established to investigate possible mechanisms of EZW in treating LKYDS. Materials and method The rat models of LKYDS were established using the mixture of thyroxine and reserpine , and the changes of biochemical indices in serum and histopathology were detected to explore the effects of EZW. Next, a broad range metabolomics strategy based on RPLC-Q-TOF/MS and HILIC-Q-TOF/MS has been developed to find the possible significant metabolites in the serum and urine of LKYDS rats. Then, network analysis was applied to visualize the relationships between identified serum and urine metabolites and in detail to find hub metabolites, which might be responsible for the effect of EZW on rats of LKYDS. Furthermore, the shortest path of “disease gene-pathway protein-metabolite” was built to investigate the possible intervention path of EZW from the systematic perspective. Results Five hub metabolites, namely, arachidonic acid , L -arginine, testosterone, taurine and oxoglutaric acid, were screened out and could be adjusted to recover by EZW. After that, the shortest path starting from disease genes and ending in metabolites were identified and disclosed, and the genes of aging such as CAV1 and ACO1 were selected to explain the pathological mechanism of LKYDS. Conclusion Broad range metabolomics coupled with network analysis could provide another perspective on systematically investigating the molecular mechanism of EZW in treating LKYDS at metabolomics level. In addition, EZW might prevent the pathological process of LKYDS through regulating the disturbed metabolic pathway and the aging genes such as CAV1 and ACO1, which may be potential targets for EZW in the treatment of LKYDS.
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高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 4
·1-8
·
IF 5.705
Shao Hong,Xu Dan,Ding Yadan,Hong Xia,Liu Yichun
The authors describe an “off-on” colorimetric and fluorometric assay for the determination of Cu(II). It is based on the use of upconversion nanoparticles (UCNPs) of type NaYF 4 :Yb(III),Er(III) that were functionalized with branched polyethylenimine (BPEI). A color change from colorless to blue occurs within 2 s after addition of Cu(II) to a solution of the modified UCNPs. The color change can be visually detected at Cu(II) concentrations down to 80 μM. The upconversion fluorescence of the modified UCNPs, measured at excitation wavelength of 980 nm, is reduced due to the predominant inner filter effect caused by the formation of the BPEI-Cu(II) complex. Normalized fluorescence intensity drops linearly in the 50 nM to 10 μM Cu(II) concentration range, and the fluorometric detection limit is 45 nM. Both the color and the fluorescence are recovered on addition of EDTA. Excellent selectivity over other metal ions and anions is achieved.
Upconversion nanoparticles of type NaYF4:Yb,Er were functionalized with branched polyethylenimine (UCNP/BPEI) and used in an “off-on” colorimetric and fluorometric assay for Cu(II). The upconversion fluorescence is selectively quenched on addition of Cu(II), and this is accompanied by a rapid colorless-to-blue color switch. The colorimetric changes and quenched fluorescence can be reversed by adding EDTA.
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高影响因子
JOURNAL OF STRUCTURAL CHEMISTRY
·
2017
·Vol. 58
·期 7
·1472-1476
·
IF 0.472
Li L.,Yuan F.
The reaction of LnCl3 with Na3salmp/H3salmp (H3salmp = 2-bis(salicylidieneamino)methyl-phenol) affords [LnNa(salmp)(sal)]2 (Ln = Sm(I), Er(II); sal = salicylaldehydato) complexes being different from the known Ln-salmp complex of [Sm(salmp)(THF)]2. In the reaction, the cleavage of C=N bonds happens in H3salmp, and the regenerated salicylaldehydato anion arises and takes part in the coordination. Both complexes are characterized by elemental analysis, IR spectroscopy, and X-ray crystallography.
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wen-lin Li,Ke Li,Wen-guang Chang,Hui Shi,Wen-xuan Zhang,Zi Wang,Wei Li
Background Although our previous work confirmed 20(R)-ginsenoside Rg3 (R-Rg3), which is an active ingredient in the Panax Ginseng C.A. Meyer, to have good anti-diabetic activity, its beneficial effect on diabetic retinal injury was found to be limited. Purpose This study aims to investigate the protective effects of R-Rg3 on diabetes-induced retinal injury and the associated molecular mechanisms of action. Methods Diabetic retinal injury was induced in mice using a combination of a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). R-Rg3 (10 and 20 mg/kg) was subsequently administered for 6 weeks. The human retinal endothelial cells (HRECs) were subjected to high glucose (HG)-induced injury for the in vitro analysis and treated with R-Rg3 (4, 8, 16 μM), antioxidant N-Acetylcysteine (NAC, 1 mM) and Nrf2 inhibitor ML385 (5 μM). The mice retinas then underwent functional and histopathological analysis. Expression levels of proteins related to the Nrf2/HO-1 axis, tight junction proteins, endoplasmic reticulum (ER) stress and the apoptosis in retinal tissue and HRECs were determined by western blot. Expressions of ZO-1 and Nrf2 in the retina and HRECs were assessed by immunofluorescence. Additional evaluations included measuring body weights, fasting blood glucose (FBG), lipid levels and oxidative markers. Results The results showed 6 weeks of R-Rg3 treatment significantly restored the functional changes and redox system imbalance that was induced by HFD/STZ in mice. R-Rg3 was also found to significantly reduce retinal barrier damage and thickness changes resulting from hyperglycaemia exposure. At the same time, R-Rg3 also protected HRECs from HG-induced damage. R-Rg3 could also activate Nrf2/HO-1 axis and inhibit endoplasmic reticulum stress as a means of alleviating retinal endothelial cells apoptosis. The molecular docking results also demonstrated that R-Rg3 had a good binding ability with Nrf2. Conclusion Our study suggested Nrf2/HO-1 axis might be crucial for the ability of R-Rg3 to prevent diabetic retinal injury.
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高影响因子
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