TALANTA
·
2018
·
IF 4.244
Kailun Deng,Lei Wang,Qi Xia,Ruiyuan Liu,Jinqing Qu
Nucleus imaging is of great importance for understanding cellular processes of genetic expression, proliferation and growth, etc. Although many nucleic-acid selective dyes for nucleus staining are available, few of them meet multiple standards. Herein, we report a cationic fluorescence dye FTI that possesses visible light excitation (436 nm), orange emission (571 nm) and a large Stokes shift (~135 nm) for nucleic-acid staining. FTI displays an obvious and sensitive fluorescent response to DNA in vitro with a 6.4-fold quantum yield increasing. Co-staining and nucleic acid digest experiments in live cells demonstrate that FTI exhibits an unexpected selectivity for the nucleolus of the cells due to the stronger affinity to RNA than DNA. Because of good photostability and low cytotoxicity, FTI can accomplish a promising stain for DNA recognition in vitro and nucleolus-specific imaging in cancer cells.
研究领域:
细胞生物学
·
分子生物学
·
生物成像
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产品关联
DOI
PubMed
高影响因子
Animals
·
2025
·Vol. 15
·期 2
·140
·
IF 2.7
Kexin Ma,Yueyao Yang,Yifan Li,Chuan Li,Taicheng Li,Haiyan Ma,Zibin Jiang,He Zhou,Wei Wang
Simple SummaryOur study investigates the karyotype of a vital polyploid fish,Carassius auratus gibelio. We found 150 chromosomes with 6 nucleolar organizer regions, suggesting complex chromosomal interactions. Male and femaleC. gibelioshow different chromosome pairings, indicating asynchronous evolution. The formation of two trivalents or two bivalents and two univalents from six NOR bearing chromosomes in maleC. gibeliois considered evidence of being in the process of rediploidization. The presence of only univalents and bivalents in the oocytes of femaleC. gibelioindicates that their cytogenetics are more stable, suggesting that they have completed rediploidization. Our findings contribute to the understanding of the underlying mechanisms and evolutionary outcomes of this species’ genome. They provide relevant insights for further exploration of the reproductive modes of polyploid organisms and breeding strategies.Carassius auratus gibelio, a significant polyploid fish in Chinese aquaculture, can reproduce through both unisexual gynogenesis and sexual reproduction. WhileC. gibeliois known to exhibit polyploidy throughout its lifecycle, whether the homologous pairing of chromosomes is associated with the mode of reproduction remains unclear. Our study determined its karyotype as 2n = 150, comprising 42 metacentric, 24 submetacentric, 6 subtelocentric, and 78 telocentric chromosomes. Using AgNORs, CMA3/DAPI double fluorescence staining, and FISH, we identified six nucleolar organizer regions inC. gibeliochromosomes. FemaleC. gibelioexhibited only univalent and bivalent configurations, while males showed a range of chromosome configurations from univalent to hexavalent. CMA3-positive sites and FISH signals in trivalents spermatocytes hint at homologous triploidization. The formation of two trivalents or two bivalents and two univalents from six NORs bearing chromosomes in maleC. gibeliois considered evidence of being in the process of rediploidization. The presence of only univalents and bivalents in the oocytes of femaleC. gibelioindicates that their cytogenetics are more stable, suggesting that they have completed rediploidization. Asynchronous progression of polyploidization may lead to differences in reproductive patterns between male and femaleC. gibelio. Our results offer cytogenetic insights into the polyploidy and evolution ofC. gibelio, providing foundational cytogenomics data. This study provides relevant references for revealing the distinct reproductive strategies of male and femaleC. gibelio: under stable conditions, gynogenesis enables rapid clonal reproduction and swift population growth, while sexual reproduction enhances the genetic diversity within the population.
研究领域:
细胞遗传学
·
进化生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Shuo Guo,Yuanqiang Sun,Jinquan Li,Xin Geng,Ran Yang,Xiaoge Zhang,Lingbo Qu,Zhaohui Li
Monitoring cell viability plays a vital role in fundamental aspects of pathology, medicine, and biology. Mitochondria and the nucleolus are involved in regulating cell viability in many biological processes, such as mitochondrial autophagy, apoptosis, and cell growth. Thus, exploring the variational cell viability reflecting with mitochondria and the nucleolus is very significant and highly required. Herein, in this work, a kind of fluorescent carbon dots (CDs) capable of shuttling between mitochondria and the nucleolus was synthesized through a simple microwave-assisted strategy and utilized for in situ visualization of cell viability. Meanwhile, hydrogen peroxide (H2O2)-induced cell damage and ascorbic acid-mediated cell protective effects were successfully visualized. Moreover, these CDs demonstrate an intrinsic character of wash-free imaging that makes them preferable for the monitoring of cell viability. We believe that the developed CDs have a great potential to be used as a robust tool to facilitate the progress in cell viability-related medicine, biology, and pathology studies.
研究领域:
细胞生物学
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医学
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病理学
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产品关联
DOI
RSC Advances
·
2017
·Vol. 7
·期 27
·16730-16736
·
IF 3.108
Ruiqing Feng,Longlong Li,Bing Li,Jinhui Li,Dan Peng,Yitao Yu,Qiuhong Mu,Ning Zhao,Xiaoqiang Yu,Zhenhua Wang
We have synthesized two-photon organic molecule probes (IMT-E and IMT-M), which selectively stain endogenous RNA in the nucleolus and cytoplasm of living cells in a short incubation time. Using these probes, bright two-photon excitation fluorescence (TPEF) images of living cells have been developed. Titrations and digest tests of ribonuclease indicate the markedly higher affinity of these probes for RNA, especially when using IMT-E. Upon binding to RNA, the fluorescence intensity of IMT-E increases by about 15-fold, showing that IMT-E is a turn-on probe for the detection of RNAs. MTT assays demonstrate that the mitochondria of cells maintain their electron mediating ability after being stained with the probes. These results demonstrate that IMT-E is an attractive two-photon turn-on fluorescent probe for visualizing RNA in living cells.
研究领域:
生物化学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Shaofang Ma,Yan Zhang,Zihan Zhu,Deping Wang,Xin Zhou,Jing Wang,Wei Bian,Xinjing Tang
The low cure rate and high mortality associated with cancer pose significant threats to human health. Photodynamic and photothermal therapies have emerged as promising treatment strategies for various types of cancers. In this study, we successfully synthesized a novel type of carbon dot (CD) using 1,2,4-aminobenzene and ethylenediamine as precursors. Surprisingly, these CDs exhibited outstanding nucleolus-targeting capabilities coupled with a remarkable photothermal effect. Through the integration of these nucleolus-targeting CDs with indocyanine green (ICG) and folic acid (FA), we created CDs-ICG-FA nanocomplexes suitable for combined photodynamic and photothermal therapy. In vitro experiments demonstrated that CDs-ICG-FA maintained a robust photothermal ability, achieving a conversion efficiency of up to 34.3%. Furthermore, CDs-ICG-FA generated abundant reactive oxygen species, effectively inducing cancer cell death and demonstrating its potential for photodynamic therapy. In MCF-7 cancer cells, CDs-ICG-FA exhibited a pronounced synergistic photothermal/photodynamic anticancer effect. Subsequent in vivo experiments in mice revealed that CDs-ICG-FA could selectively accumulate at tumor sites, significantly inhibiting tumor growth upon exposure to an 808 nm laser. These findings suggest that the developed nucleolus-targeting CDs-ICG-FA hold promising potential for cancer targeting and the application of combined photothermal/photodynamic therapy.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2015
·
IF 5.636
Yan-Ran Li,Qian Liu,Zhangyong Hong,He-Fang Wang
For the widely used “off-on” fluorescence (or phosphorescence) resonance energy transfer (FRET or PRET) system, the separation of donors and acceptors species was vital for enhancing the sensitivity. To date, separation of free donors from FRET/PRET inhibition systems was somewhat not convenient, whereas separation of the target-induced far-between acceptors has hardly been reported yet. We presented here a novel magnetic separation-assistant fluorescence resonance energy transfer (MS-FRET) inhibition strategy for highly sensitive detection of nucleolin using Cy5.5-AS1411 as the donor and Fe3O4-polypyrrole core–shell (Fe3O4@PPY) nanoparticles as the NIR quenching acceptor. Due to hydrophobic interaction and π–π stacking of AS1411 and PPY, Cy5.5-AS1411 was bound onto the surface of Fe3O4@PPY, resulting in 90% of fluorescence quenching of Cy5.5-AS1411. Owing to the much stronger specific interaction of AS1411 and nucleolin, the presence of nucleolin could take Cy5.5-AS1411 apart from Fe3O4@PPY and restore the fluorescence of Cy5.5-AS1411. The superparamagnetism of Fe3O4@PPY enabled all separations and fluorescence measurements complete in the same quartz cell, and thus allowed the convenient but accurate comparison of the sensitivity and fluorescence recovery in the cases of separation or nonseparation. Compared to nonseparation FRET inhibition, the separation of free Cy5.5-AS1411 from Cy5.5-AS1411-Fe3O4@PPY solution (the first magnetic separation, MS-1) had as high as 25-fold enhancement of the sensitivity, whereas further separation of the nucleolin-inducing far-between Fe3O4@PPY from the FRET inhibition solution (the second magnetic separation, MS-2) could further enhance the sensitivity to 35-fold. Finally, the MS-FRET inhibition assay displayed the linear range of 0.625–27.5 μg L–1 (8.1–359 pM) and detection limit of 0.04 μg L–1 (0.05 pM) of nucleolin. The fluorescence intensity recovery (the percentage ratio of the final restoring fluorescence intensity to the quenched fluorescence intensity of Cy5.5-AS1411 solution by 0.09 g L–1 Fe3O4@PPY) was enhanced from 36% (for nonseparation) to 56% (for two magnetic separations). This is the first accurate evaluation for the effect of separating donor/acceptor species on the FRET inhibition assay.
研究领域:
生物化学
·
分析化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2025
·
IF 2.8
Minglu Zhang,Jianbo He,Rao Fu,Guojian Bao,Yijun Lu,Zechuan Zhang,Jiawu Yan,Jialu Ding,Fei Yang,Beicheng Sun
Introduction: Small nucleolar RNA (snoRNA) mediates RNA modifications, including 2′-O-methylation (Nm) and pseudouridine (Ψ), which has been proven to impact tumor progression. However, the role of snoRNA in the epigenetics of tumors remains poorly understood due to the lack of sufficiently effective experimental methods to identify snoRNA targets. Here, we identified SNORD13H, a C/D box snoRNA, as being downregulated in hepatocellular carcinoma (HCC), and its low expression was associated with HCC development.Methods: To elucidate specific roles of SNORD13H in HCC, we used a comprehensive array of methodologies, including flow cytometry, xenograft mouse model, reverse transcription at low dNTP concentration followed by PCR (RTL-P) assay, and surface sensing of translation (SUnSET) assay.Results: In this study, we first demonstrated that reduced SNORD13H serves as a biomarker for HCC, facilitating cellular proliferation. SNORD13H mediates 2′-O-methylations of 18S rRNA and RAS mRNA, thereby enhancing translation efficiency and regulating RAS protein levels in HCC. The diminution of SNORD13H activates the RAS pathway, contributing to the progression of HCC.Discussion: Our study establishes SNORD13H as a dual-function regulator in HCC progression. Furthermore, our findings indicate that SNORD13H is detectable in plasma, highlighting its potential utility in tumor screening.
研究领域:
分子生物学
·
癌症研究
·
遗传学
·
表观遗传学
·
RNA修饰
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产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
·Vol. 8
·期 8
·13240
·
IF 5.168
Zhixiong Dong,Changjun Zhu,Qimin Zhan,Wei Jiang
The nucleolus controls ribosome biogenesis and its perturbation induces nucleolar stress that inhibits cell cycle progression and activates checkpoint responses. Here, we investigate the roles of ribosomal RNA processing protein, RRP15, in nucleolar formation, ribosome biogenesis, cell cycle progression and checkpoint control in human cells. RRP15 is localized in the nucleolus and required for nucleolar formation. In contrast to the budding yeast Rrp15p that was reported as a component of pre-60S subunits, RRP15 is found in both pre-40S and pre-60S subunits and involved in regulating rRNA transcription and ribosome biogenesis. Perturbation of RRP15 induces nucleolar stress that activates RPL5/RPL11/5S rRNA (RP)-Mdm2-p53 axis checkpoint response and arrests cells at G1-G1/S in p53-proficient non-transformed RPE1 cells but not in p53-deficient HeLa and MCF7 tumor cells. Instead, p53-deficient HeLa and MCF7 cells with RRP15-dependent nucleolar stress enter S-phase with S-phase perturbation that activates ATR-Chk1- γH2AX axis DNA replication/damage checkpoint response, delaying S-G2/M progression and, ultimately, causing cell death. The selective checkpoint response, cell cycle inhibition and/or cytotoxicity induced by RRP15-dependent nucleolar stress in p53-proficient non-transformed cells and p53-deficient tumor cells suggest that RRP15 might be a potential target for cancer therapy.
研究领域:
分子生物学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Yan-Wen Bao,Xian-Wu Hua,Yan-Hong Li,Hao-Ran Jia,Fu-Gen Wu
Lysosomal entrapment and liver accumulation are the two main obstacles faced by many anticancer drugs for achieving satisfactory therapeutic outcomes. Here, we develop a facile one-step hydrothermal synthetic route to prepare trace metal (M)-, N-, and O-doped carbon-dominated nanoparticles (termed as MNOCNPs, M = Ni, Pd, or Cu, metal content: <0.1 mol%) with exceptional photothermal properties (e.g., the ultrahigh extinction coefficient of 32.7 L g −1 cm −1 ), which can simultaneously realize preferable endoplasmic reticulum (ER) targeting and specific tumor enrichment without noticeable liver accumulation after poly(ethylene glycol) (PEG) conjugation. More interestingly, the PEG-modified MNOCNPs with nanoscale lengths exhibit considerable nucleolar delivery and increased tumor accumulation upon laser irradiation. After fluorescence labeling, these PEG-modified MNOCNPs are suitable for fluorescence/photoacoustic/thermal triple-modal imaging-guided photothermal cancer treatment. Additionally, the ultralow metal content ensures the exceptional biosafety of the nanoagents. The present work provides a novel, facile, and general synthetic method of carbon-dominated nanoparticles with superior photothermal properties for highly efficient tumor ablation, and the large-organelle (ER and nucleus)-targeted cancer therapeutic strategy may represent an alternative solution for optimizing the anticancer efficacy of nanomaterials . Statement of Significance Limited wire-like nanomaterials have been used for biomedical applications due to their lack of intrinsic photothermal properties, poor cellular uptake and tumor accumulation, and potential biotoxicity arising from their micrometer lengths and/or massive heavy metal doping. Besides, the clinical applications of many nanoagents are hindered by their tendency to accumulate in liver, which may cause severe liver toxicity. Herein, we develop for the first time a one-step hydrothermal method to prepare wire-like trace metal-, N-, and O-doped carbon-dominated nanoparticles with excellent photothermal properties, massive cellular uptake, preferable ER localization, selective tumor targeting with negligible liver deposition, laser irradiation-enhanced nucleolar delivery and tumor accumulation, and multimodal imaging-guided cancer therapy. This work opens a new window for simultaneously overcoming lysosomal entrapment and liver accumulation in cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 5
·期 4
·655-660
·
IF 4.872
Hengchang Ma,Zengming Yang,Haiying Cao,Lei Lei,Lu Chang,Yucheng Ma,Manyi Yang,Xiaoqiang Yao,Shaobo Sun,Ziqiang Lei
Specific organelle imaging and long-term cellular tracking are of paramount importance in monitoring biological processes, pathological pathways, and therapeutic effects, etc. Herein, we report a novel macromolecule fluorescent probe (TPPA–DBO), which is synthesized from tris(4-(pyridin-4-yl)phenyl)amine (TPPA) and 1,8-dibromononane (DBO) with a gram scale by a simple method. TPPA–DBO demonstrates a highly specific nucleolus-targeting ability, which is very challenging in the bioimaging research field. We have shown that the green nucleolus-specificity probe TPPA–DBO has advantages over the commercially available nucleolus-staining probes such as DAPI, Hoechst dyes and SYTOs in terms of its AIE-performance, large Stokes shift (175 nm), excellent photostability, and promising usefulness in live cell imaging experiments. Surprisingly, after internalizing TPPA–DBO into the nucleus region for a period of time, some TPPA–DBO are reversely diffused from nucleolus into the cytoplasm, thus resulting in the staining of mitochondria with a redder emission color. This research result may provide a new concept of cellular tracker design and provide insight into biological questions, understanding disease mechanismss, and designing new therapeutic strategies.
研究领域:
生物成像
·
细胞生物学
·
分子医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Yubo Wang,Yong Zhou,Jinling Wang,Lu Zhang,Chen Liu,Ding Guo,Yanlin Yu,Roumei Ye,Yun Wang,Bing Xu,Yiming Luo,Dengyue Chen
The limited selectivity and high systemic toxicity of traditional chemotherapy hinder its efficacy in treating diffuse large B-cell lymphoma (DLBCL). The combination of sonodynamic therapy (SDT) with chemotherapy has emerged as a novel strategy for cancer treatment, aiming to improve therapeutic outcomes and reduce systemic toxicity. However, challenges such as elevated drug clearance rates and non-selecitivity remain to be resolved. This study has developed a biocompatible nanomedicine delivery system, PA-HM@DOX/ICG, employing hollow mesoporous silica nanoparticles (HMSNs) as the nanocarrier. The nanomedicine incorporates the chemotherapeutic agent doxorubicin (DOX) along with the sonosensitizer indocyanine green (ICG) within its encapsulation, and undergoes additional surface modification using lipid-nucleic acid conjugates (DSPE-PEG-AS1411) to facilitate active targeted delivery. In vitro cellular experiments have validated that PA-HM@DOX/ICG can specifically recognize and be internalized by SU-DHL-4 lymphoma cells due to the overexpression of nucleolin on their surface. The synergistic effects of DOX-induced DNA damage and reactive oxygen species (ROS) generated by ultrasound-activated ICG induce apoptosis in these cells. Furthermore, PA-HM@DOX/ICG displays minimal toxicity towards LO2 normal hepatocytes, indicating a favorable biosafety profile. In vivo animal studies have shown that PA-HM@DOX/ICG effectively accumulates in tumor sites in mice through both the enhanced permeability and retention (EPR) effect and nucleolin-mediated targeting. Under ultrasound irradiation, PA-HM@DOX/ICG significantly inhibits tumor growth. This study introduces a nanoplatform that integrates chemotherapy with sonodynamic therapy, offering a novel approach for the efficient treatment of DLBCL.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 6
·1-10
·
IF 5.833
Zhang Li,Wang Zihan,Wang Huiping,Dong Wenjuan,Liu Yang,Hu Qin,Shuang Shaomin,Dong Chuan,Gong Xiaojuan
Carbon dots (CDs) are a rising star in the field of cellular imaging, especially cytoplasmic imaging, attributing to the super-stable optical performance and ultra-low biological toxicity. Nucleolus can accurately reflect the expression state of a cell and is strongly linked to the occurrence and development of many diseases, so exploring bran-new CDs for nucleolus-orientation imaging with no-wash technology has important theoretical value and practical significance. Herein, nitrogen-doped carbon dots (N-CDs) with green fluorescence (the relative fluorescence quantum yield of 24.4%) was fabricated by the hydrothermal treatment of m -phenylenediamine and p -aminobenzoic acid. The N-CDs possess small size, bright green fluorescence, abundant surface functional groups, excellent fluorescence stability and good biocompatibility, facilitating that the N-CDs are an excellent imaging reagent for cellular imaging. N-CDs can particularly bind to RNA in nucleoli to enhance their fluorescence, which ensures that the N-CDs can be used in nucleolus-orientation imaging with high specificity and wash-free technique. This study demonstrates that the N-CDs have a significant feasibility to be used for nucleolus-orientation imaging in biomedical analysis and clinical diagnostic applications. Graphical abstract
研究领域:
生物化学
·
分子生物学
·
生物医学工程
✓ 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）