BIOMATERIALS
·
2014
·
IF 8.312
Dong Ma,Qian-Ming Lin,Li-Ming Zhang,Yuan-Yuan Liang,Wei Xue
The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro , and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays , and also showed a good biocompatibility in vivo . Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy.
研究领域:
药学
·
生物医学工程
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2024
·
IF 2.1
Wang Rui,Liao Zhaoping,Liu Chunhua,Yu Shifang,Xiang Kaihua,Wu Ting,Feng Jie,Ding Senjuan,Yu Tingao,Cheng Gang,Li Sanlian
Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that Cellular Retinoic Acid Binding Protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility, and apoptosis in multiple cancers, yet the effect of CRABP2 on PCa is poorly reported. The CRABP2 expression in different PCa cell lines and its effect on different cellular functions were various. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Besides, CRABP2 had no influence on the cell cycle distribution of PCa cells. RNA-seq assay showed that overexpressing CRABP2 up-regulated Laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in PI3K/AKT and MAPK signaling pathway. The following WB experiments also confirmed the up-regulated LAMB3 protein level and the activation of PI3K/AKT and MAPK signaling pathways. Moreover, overexpressing CRABP2 inhibited tumor growth significantly in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signaling pathways through upregulating LAMB3 in PCa.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Xinlan Zhu,Ziyan Zhang,Ruiyang Ma,Huachu Chen,Yi Zheng,Su Zeng,Zheyong Li,Sheng Cai
A label-free detection technique for microRNA (miRNA) was developed based on target replacement cycling, polymerization and isomerization cyclic amplification (PICA), and G/Hemin DNAzyme signal output. The designed hairpin probe undergoes cyclic alternation of polymerization and isomerization catalyzed by Bst DNA polymerase, enabling target replacement cycling and continuous self-extension of single-stranded DNA (ssDNA) strands. This process generates abundant G-quadruplex sequences that bind to Hemin, achieving label-free detection of miRNA through catalytic reactions. Its key advantages include a specific primer self-extension mechanism that avoids spurious amplification, one step isothermal design simplifies workflow and enhances system robustness, adapting to diverse detection scenarios, and label-free detection strategy that substantially reduces cost. Therefore, it is poised to become a reliable tool for clinical miRNA analysis, offering potential guidance for the early diagnosis, treatment, and prognosis of tumor biomarkers.
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Xuehong Min,Mengshi Zhang,Fujian Huang,Xiaoding Lou,Fan Xia
Enzyme-assisted detection strategies of microRNAs (miRNAs) in vitro have accomplished both great sensitivity and specificity. However, low expression of miRNAs and a complex environment in cells induces big challenges for monitoring and tracking miRNAs in vivo. The work reports the attempt to carry miRNA imaging into live cells, by enzyme-aided recycling amplification. We utilize facile probes based yellow aggregation-induced emission luminogens (AIEgens) with super photostable property but without quencher, which are applied to monitor miRNAs not only from urine sample extracts (in vitro) but also in live cells (in vivo). The assay could distinguish the cancer patients’ urine samples from the healthy urine due to the good specificity. Moreover, the probe showed much higher fluorescence intensity in breast cancer cells (MCF-7) (miR-21 in high expression) than that in cervical cancer cells (HeLa) and human lung fibroblast cells (HLF) (miR-21 in low expression) in more than 60 min, which showed the good performance and super photostability for the probe in vivo. As controls, another two probes with FAM/Cy3 and corresponding quenchers, respectively, could perform miRNAs detections in vitro and parts of in vivo tests but were not suitable for the long-term cell tracking due to the photobleach phenomena, which also demonstrates that the probe with AIEgens is a potential candidate for the accurate identification of cancer biomarkers.
研究领域:
分子生物学
·
癌症研究
·
分析化学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2021
·
IF 5.537
Pengyu Zhao,Weidan Li,Chaoying Zhen,Ke Wang,Zhen Qin,Haiyan Gao
γ-Aminobutyric acid (GABA) has several physiological functions and broad application prospects. In this study, as a tool used for transcriptomics , RNA-seq sequencing was employed to determine the mechanism by which GABA slows browning and induces resistance against the growth of bacterial in fresh-cut apples. GABA altered the expression level of genes related to the synthesis of browning enzymes and phenolic substances in fresh-cut apples, which slowed the browning process during storage. Additionally, GABA promoted the gene expression of enzymes or proteins related to disease resistance, which resultantly induced disease resistance in fresh-cut apples. Notably, GABA maintained the integrity and stability of the cell wall composition and structure in apple tissues to reduce browning and induce disease resistance. Our findings revealed the mechanism by which GABA acts as a protective agent against browning and bacterial growth in for fresh-cut apples.
研究领域:
园艺学
·
分子生物学
·
食品科学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 11
·2694
·
IF 4.183
Wenqi Li,Yubing Yong,Yue Zhang,Yingmin Lyu
Background: The LA hybrid lily ‘Aladdin’ has both excellent traits of Longiflorum hybrids and Asiatic hybrids—such as big and vivid flower, strong stem, high self-propagation coefficient, and shorter low temperature time required to release bulb dormancy in contrast to Oriental hybrids. A genome-wide transcriptional analysis using transcriptome RNA-Seq was performed in order to explore whether there is a gibberellin floral induction pathway in the LA hybrid lily. Subsequently, gene co-expression network analysis was used to analyze the possible interactions of key candidate genes screened from transcriptome data. At the same time, a series of physiological, biochemical, and cultivation tests were carried out. Results: The content of five endogenous hormones changed sharply in the shoot apex during the treatment of 200 mg/L exogenous gibberellin and the ratio of ABA/GA3dropped and stayed at a lower level after 4 hours’ treatment from the higher levels initially, reaching a dynamic balance. In addition, the metabolism of carbohydrates in the bulbs increase during exogenous gibberellin treatment. A total of 124,041 unigenes were obtained by RNA-seq. With the transcriptome analysis, 48,927 unigenes and 48,725 unigenes respectively aligned to the NR database and the Uniprot database. 114,138 unigenes, 25,369 unigenes, and 19,704 unigenes respectively aligned to the COG, GO, and KEGG databases. 2148 differentially expression genes (DEGs) were selected with the indicators RPKM ≥ 0, FDR ≤ 0.05 and |log2(ratio)| ≥ 2. The number of the upregulated unigenes was significantly more than the number of the downregulated unigenes. Some MADS-box genes related to flowering transformation—such asAGL20,SOC1, andCO—were found to be upregulated. A large number of gibberellin biosynthesis related genes such asGA2ox,GA3ox,GA20ox,Cytochrome P450,CYP81, and gibberellin signal transduction genes such asDELLA,GASA, andGID1were significantly differentially expressed. The plant hormones related genes such asNCED3and sugar metabolism related genes such asα-amylase,sucrose synthase hexokinase, and so on were also found expressing differentially. In addition, stress resistance related genes such asLEA1,LEA2,LEA4,serine/threonine protein kinase,LRR receptor-like serine/threonine protein kinase,P34 kinase,histidine kinase 3and epigenetic related genes in DNA methylation, histone methylation, acetylation, ubiquitination of ribose were also found. Particularly, a large number of transcription factors responsive to the exogenous gibberellin signal includingWRKY40, WRKY33, WRKY27, WRKY21, WRKY7, MYB, AP2/EREBP, bHLH, NAC1, NAC2, andNAC11were found to be specially expressing. 30 gene sequences were selected from a large number of differentially expressed candidate genes for qRT-PCR expression verification (0, 2, 4, 8, and 16 h) and compared with the transcriptome expression levels. Conclusions: 200mg/L exogenous GA3can successfully break the bulb’s dormancy of the LA hybrid lily and significantly accelerated the flowering process, indicating that gibberellin floral induction pathway is present in the LA lily ‘Aladdin’. With the GCNs analysis, two second messenger G protein-coupled receptor related genes that respond to gibberellin signals in the cell were discovered. The downstream transport proteins such asAMT,calcium transport ATPase, andplasma membrane ATPasewere also discovered participating in GA signal transduction. Transcription factors includingWRKY7,NAC2,NAC11, andCBFspecially regulated phosphorylation and glycosylation during the ubiquitination degradation process ofDELLAproteins. These transcription factors also activated in abscisic acid metabolism. A large number of transcription factors such asWRKY21,WRKY22,NAC1,AP2,EREB1,P450, andCYP81that both regulate gibberellin signaling and low-temperature signals have also been found. Finally, the molecular mechanism of GA floral induction pathway in the LA hybrid lily ‘Aladdin’ was constructed.Keywords:GA floral induction pathway;LA hybrid lily;transcriptome RNA-Seq;GCN;qRT-PCR
研究领域:
植物学
·
遗传学
·
分子生物学
·
植物生理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Yanci Zhang,Yujin Fan,Jiyuan Zhang,Yanxi Hu,Lili Duan,Zhanhui Wang,Yihong Wang,Jiansheng Cui,Liang Tian
The imbalanced expression of microRNA is related to many diseases and tumors, which can be used as a noninvasive biomarker to assist in the diagnosis, prognosis, and monitoring of cancer. A target conversion strategy-based electrochemical biosensor was developed by DNAzyme-cleavage dual cyclic signal amplification and the strand displacement reaction (SDR) to produce high electrochemical signals for microRNA-155 (miRNA-155) analysis. Thereinto, VSe2/multi-walled carbon nanotubes (MWCNTs) with high conductivity were applied as the electrode surface material to provide more active sites and accelerate electron transportation. Then, the excellent immobilization efficiency and large specific surface area of the ZnO@CuS nanoprobes were applied as a recognition molecule carrier. Furthermore, hexaammineruthenium(III) chloride (RuHex), with superior electrochemical redox activity, acted as the electroactive indicator by intercalating into double-helix DNA through electrostatic interaction, which produced high current responses in the presence of the target. Therefore, this miRNA-155 biosensing platform exhibited a relatively low limit of detection of 0.11 fM, ranging from 0.5 fM to 5 nM, and demonstrated excellent repeatability and stability. Hence, this platform appeared to possess favorable human serum detection capacity and be suitable for early cancer diagnostics.
研究领域:
生物医学工程
·
分子诊断学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
TALANTA
·
2017
·
IF 4.162
Shiyu Li,Kui He,Rong Liao,Chunyan Chen,Xiaoming Chen,Changqun Cai
An interference-free and label-free sensing platform was developed for the highly sensitive detection of microRNA-21 (miRNA-21) in vitro by magnetic silicon microsphere (MNP)-reduced graphene oxide (rGO)-based sandwich probe. In this method, DNA capture probes (P 1 ) were connected with MNPs at the 5′ end and hybridized with completely complementary target miRNA. Subsequently, rGO was retained and induced the fluorescence quenching in the supernatant. Through the magnetic separation, the supernatant environment was simplified and the interference to analytical signal was eliminated. When DNA capture probe-modified magnetic silicon microspheres (MNP-P 1 ) were adsorbed through rGO in the absence of a target and formed a sandwich structure, the formed nanostructure was easily removed from the solution by a magnetic field and the fluorescence intensity was maximally recovered. This proposed strategy, which both overcame the expensive and cumbersome fluorescent labeling , and eliminated interference to analytical signal for guaranteeing high signal-to-background ratio, exhibited high sensitivity with a detection limit as low as 0.098 nM and special selectivity toward miRNA-21. The method was potentially applicable for not only detection of miRNA-21 but also various biomarker analyses just by changing capture probes.
研究领域:
生物传感器
·
纳米技术
·
分子诊断
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Xin-Jun Yu,Hong Chen,Chang-Yi Huang,Xiao-Yu Zhu,Zhi-Peng Wang,Dong-Sheng Wang,Xiao-Yan Liu,Jie Sun,Jian-Yong Zheng,Hui-Juan Li,Zhao Wang
The phytohormone 6-benzylaminopurine (6-BAP) significantly improves lipid synthesis of oleaginous microorganisms with the great potential applied in lipid production. In the current study, the lipid and DHA productions in oleaginous Aurantiochytrium sp. were found to be improved by 48.7% and 55.3%, respectively, induced by 6-BAP treatments. Then, using high-throughput RNA-seq technology, the overall de novo assembly of the cDNA sequence data generated 53871 unigenes, and 15902 of these were annotated in at least one database. The comparative transcriptomic profiles of cells with and without 6-BAP treatments revealed that a total of 717 were differently expressed genes (DE), with 472 upregulated and 245 downregulated. Further annotation and categorization indicated that some DE genes were involved in pathways crucial to lipid and DHA productions, such as fatty acid synthesis, central carbon metabolism, transcriptional factor, signal transduction, and mevalonate pathway. A regulation mode of 6-BAP, in turn, perception and transduction of 6-BAP signal, transcription factor, expression regulations of the downstream genes, and metabolic changes, respectively, was put forward for the first time in the present study. This research illuminates the transcriptomic mechanism of phytohormone stimulation of lipid and DHA production in an oleaginous microorganism and provides the potential targets modified using genetic engineering for improving lipid and DHA productivity.
研究领域:
微生物学
·
分子生物学
·
生物技术
·
转录组学
✓ 已验证
DOI
PubMed
高影响因子
CANCER RESEARCH
·
2024
·
IF 12.5
Fang Liang,Zhang Li,Wang Mengran,He Yuhao,Yang Jiao,Huang Zengjin,Tan Ying,Fang Ke,Li Jun,Sun Zhiyuan,Li Yanping,Tang Yisen,Liang Weizheng,Cui Huanhuan,Zhu Qionghua,Wu Zhe,Li Yiming,Hu Yuhui,Chen Wei
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, post-transcriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1547 RNA binding proteins (RBPs) on cell motility in colon cancer cells and identified multiple core components of P-bodies (PBs) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multi-omics analysis revealed that PBs could repress the translation of the EMT-driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum (ER) stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in regulation of EMT in cancer.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 10
·5911-5925
·
IF 4.486
Dafeng Yang,Zhousheng Yang,Lei Chen,Dabin Kuang,Yang Zou,Jie Li,Xu Deng,Songyuan Luo,Jianfang Luo,Jun He,Miao Yan,Guixia He,Yang Deng,Rong Li,Qiong Yuan,Yangzhao Zhou,Pei Jiang,Shenglan Tan
Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata , in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient ( Apoe − / − ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe − / − mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe − / − mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.
研究领域:
心血管疾病
·
药理学
·
分子生物学
·
传统中药
✓ 已验证
DOI
PubMed
高影响因子
ACS Sensors
·
2025
·
IF 9.1
Qiuhao Xu,Yanxin Wang,Yingyu Zhu,Tan Wang,Yuan Rao,Xiaoping Gan,Yingcui Bu
Real-time monitoring of the dynamics and heterogeneity of mitochondria and nucleoli is essential for a comprehensive understanding of cellular homeostasis and pathological mechanisms. However, current approaches mainly suffer from two major limitations: (1) Limited permeability through nuclear pore complexes (NPCs) in live cells and (2) vulnerability of intensity-based detection methods to interference from the cellular microenvironment. To overcome these challenges, a red-emissive fluorescent probe (DSM) with high photostability was developed by strategically tuning the π-conjugation between electron-donating and accepting moieties. Gratifyingly, DSM can selectively accumulate in both mitochondria and nucleoli with a distinguishable average fluorescence lifetime after binding with RNA and protein, which enables their dynamic visualization of morphological changes and interplay during oxidative stress by fluorescence lifetime imaging microscopy (FLIM). This research not only paves a new pathway for real-time imaging the physiology of mitochondria and nucleoli but also inspires to guide the pathological study of related diseases.
研究领域:
细胞生物学
·
生物成像
·
荧光显微镜
·
分子生物学
·
生物物理学
✓ 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）