70 results on '"Liu, Yunjun"'
Search Results
2. Construction of fatty acid-ovalbumin binary complexes to improve the water dispersibility, thermal/digestive stability and bioaccessibility of lutein: A comparative study of different fatty acids.
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Liu, Yunjun, Ma, Liyuan, Zhang, Qian, Liu, Yixiang, and Li, Dan
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LUTEIN , *OVALBUMINS , *FATTY acids , *TRANSMISSION electron microscopy , *INTESTINAL absorption , *ELECTRON spectroscopy , *THERMAL stability - Abstract
Lipids are increasingly being incorporated into delivery systems due to their ability to facilitate intestinal absorption of lipid-soluble nutrients through molecular solubilization and micellization. In this work, self-assembled complexes of ovalbumin (OVA) and nine dietary fatty acids (FAs) were constructed to improve the processability and absorbability of lutein (LUT). Results showed that all FAs could form stable hydrophilic particles with OVA under the optimized ultrasound-coupled pH conditions. Fourier infrared spectroscopy and transmission electron microscopy analysis showed that these binary complexes effectively encapsulated LUT with an encapsulation rate > 90.0 %. Stability experiments showed that these complexes protected LUT well, which could improve thermal stability and in vitro digestive stability by 1.66–3.58-fold and 1.27–2.74-fold, respectively. Besides, the bioaccessibility of LUT was also enhanced by 7.16–24.99-fold. The chain length and saturation of FAs affected the stability and absorption of LUT. Therefore, these results provided some reference for the selection of FAs for efficient delivery of lipid-soluble nutrients. • FAs and OVA could form hydrophilic complexes through noncovalent interactions. • FAs-OVA complexes exhibited outstanding encapsulation efficiency for LUT. • The optimal conditions for different FAs to undergo self-assembly with OVA were different. • The selected FAs enhanced the thermal and digestive stability of LUT to varying degrees. • The introduction of FAs into protein-based vehicles enhanced the absorbability of LUT. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Ultrasound-mediated host–guest self-assembly between different dietary fatty acids and sodium caseinate and their complexes improving the water dispersibility, stability, and bioaccessibility of quercetin.
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Liu, Yunjun, Wang, Shengnan, and Liu, Yixiang
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SODIUM caseinate , *FATTY acids , *QUERCETIN , *DIETARY supplements industry , *INTERMOLECULAR forces , *THERMAL stability - Abstract
• FAs and NaCas could form hydrophilic complexes through host–guest recognition. • FAs-NaCas complexes exhibited outstanding encapsulation efficiency for QUE. • FA ligands did not affect the binding mode between QUE and NaCas. • FA ligands enhanced the binding affinity of NaCas to QUE. • FA ligands improved the processing adaptability and absorbability of QUE. Quercetin (QUE) sufferred from poor processing adaptability and absorbability, hindering its application as a dietary supplement in the food industry. In this study, fatty acids (FAs)-sodium caseinate (NaCas) ligand complexes carriers were fabricated to improve the aqueous dispersibility, storage/thermal stability, and bioaccessibility of QUE using an ultrasound method. The results indicated that all six selected common dietary FAs formed stable hydrophilic complexes with NaCas and the FAs-NaCas complexes achieved an encapsulation efficiency greater than 90 % for QUE. Furthermore, the introduction of FAs enhanced the binding affinity between NaCas and QUE, but did not change the binding mode (static bursting) and types of intermolecular forces (mainly hydrogen bonding). In addition, a distinct improvement was discovered in the storage stability (>2.37-fold), thermal processing stability (>32.54 %), and bioaccessibility (>2.37-fold) of QUE. Therefore, the FAs-NaCas ligand complexes could effectively protect QUE to minimize degradation as fat-soluble polyphenol delivery vehicles. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Fabricating oleic acid-ovalbumin complexes using an ultrasonic-coupled weakly alkaline pH technique: Improving the dispersibility, stability, and bioaccessibility of lutein in water.
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Liu, Yunjun, Ma, Liyuan, Guo, Yuanjie, Kuang, Huiying, and Liu, Yixiang
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OVALBUMINS , *LUTEIN , *OLEIC acid , *TRANSMISSION electron microscopy , *ELECTRON spectroscopy , *MICROENCAPSULATION , *THERMAL stability - Abstract
• The ultrasonic coupled weakly alkaline pH technique enables the self-assembly of oleic acid (OA) and ovalbumin (OVA) molecules. • OA promotes the encapsulation efficiency of lutein (LUT) by OVA through noncovalent interactions. • The prepared LUT-OA-OVA ternary complexes exhibit spherical particles with good aqueous dispersibility. • OA-OVA complexes as encapsulated carriers can effectively improve the thermal and storage stability of LUT. • OA-OVA-based encapsulation can effectively improve the digestive stability and bioaccessibility of LUT. This study constructed a self-assembly non-covalent oleic acid (OA) and ovalbumin (OVA) complex via an ultrasonic coupled pH-driven approach to simultaneously improve the water dispersibility, stability, and bioaccessibility of lutein (LUT). The results showed that homogeneous, stable hydrophilic OA-OVA particles were obtained in optimized conditions (an OVA concentration of 4.0 mg/mL, pH 9.0, ultrasonic conditions of 200 W for 2 min, and OA-OVA molar ratios of 2:1–20:1), with the LUT encapsulation efficiency (EE) exceeding 88.9%. Furthermore, Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) confirmed complete LUT encapsulation in the OA-OVA particles, displaying spherical particle formation with smooth surfaces. The OA-OVA complexes effectively improved the thermal and storage stability of LUT and significantly enhanced its bioaccessibility. These findings suggest that fatty acid-protein complexes may have potential application value as carotenoid delivery vectors. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Effects of different fatty acid ligands on the host-guest interaction of astaxanthin-bovine serum albumin: Thermodynamical analysis, binding site identification, and in vivo antioxidant evaluation.
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Li, Donghui, Liu, Yunjun, Liu, Yixiang, Wang, Shengnan, Guo, Zixin, Li, Jie, and Wang, Yanbo
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ASTAXANTHIN , *BINDING sites , *SERUM albumin , *FATTY acids , *VAN der Waals forces , *LIGANDS (Chemistry) - Abstract
The multi-ligand binding properties of proteins make the introduction of small-molecule ligands an effective approach through which to improve the biological functions of protein-based carriers. In this study, the effect of fatty acids (FAs) as functional ligands on the self-assembly of astaxanthin (ASTA) and bovine serum albumin (BSA) and the in vivo antioxidant properties of their ternary ligand complexes were investigated. As the seven common dietary FAs, lauric acid (LAA), palmitic acid (PA), stearic acid (SA), oleic acid (OA), linoleic acid (LA), arachidonic acid (AA) and docosahexaenoic acid (DHA) were selected. The results indicated that, with the exception of DHA, six of these FAs were able to change the conformation of BSA while simultaneously improving its hydrophilicity. The introduction of FA ligands did not affect the binding mode (static quenching) or the type of intermolecular forces (hydrogen bonding and van der Waals forces) between ASTA and BSA. However, the involvement of FA ligands could cause the dominant binding domain of ASTA in BSA to migrate from the initial subdomain IIIA (site II) to subdomain IIA (site I). Simultaneously, the altered binding affinity between ASTA and BSA was also observed, and the effect of unsaturated FAs (except DHA) was more pronounced than that of saturated ones. As expected, compared with the ASTA-BSA binary complexes, the ASTA-FA-BSA terpolymer performed an increased total antioxidant capacity in vivo as well as an improved antioxidant protein expression. This study provides a new strategy for the efficient delivery of carotenoids using proteins and function ligands. [Display omitted] • Different FA ligands altered the conformation of BSA to different degrees. • The effect of different FA ligands on the hydrophilicity of BSA was variable. • The FA ligands did not affect the binding mode between astaxanthin and BSA. • The FA ligands changed the dominant binding domain of astaxanthin in BSA. • The FA ligands improved the in vivo anti-oxidative activity of astaxanthin. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Encapsulation of fucoxanthin in fatty acid-bovine serum albumin micelles to improve the stability, bioavailability, and bioefficacy.
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Li, Donghui, Liu, Yunjun, Liu, Yixiang, and Wang, Shengnan
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MICELLES , *BIOAVAILABILITY , *INTESTINAL absorption , *SERUM albumin , *CAROTENOIDS , *FATTY acids , *METABOLITES , *THERMAL stability - Abstract
The poor processing adaptability and bioavailability of carotenoids tend to limit their application in the food industry. Dietary fatty acids (FAs) are, however, valuable agents for the intestinal absorption of carotenoids and, thus, were employed in this study to construct protein-based encapsulation systems that can improve the thermal and storage stability and intestinal absorption of fucoxanthin (FUCO). Results showed that all the non-covalently connected micelles fabricated via FAs and bovine serum albumin (BSA) obviously improved the thermostability of FUCO and increased its retention rate. Simultaneously, the half-life of FUCO was prolonged with the introduction of saturated FAs. The animal experiment revealed that the introduction of FAs enhanced the oral absorbability and in vivo antioxidation of FUCO, displaying distinguished metabolites of FUCO in vivo with the involvement of different FAs. These findings can contribute to the development of a promising strategy for synchronously enhancing the processing adaptability and bioefficiency of carotenoids. [Display omitted] • The FAs-BSA non-covalently connected micelles obviously improved the thermostability of FUCO. • Saturated fatty acids are more favorable to the delivery system to increase the half-life of FUCO. • The introduction of FAs enhanced the oral absorbability of FUCO. • The FAs-BSA non-covalently connected micelles improved the in vivo antioxidation of FUCO. • The involvement of different FAs leads to the distinguished metabolites of FUCO in vivo. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Improving effect of oleic acid-mediated sodium caseinate-based encapsulation in an ultrasound field on the thermal stability and bioaccessibility of quercetin.
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Wang, Shengnan, Liu, Yunjun, Liu, Yixiang, Guo, Zixin, and Li, Jie
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THERMAL stability , *OLEIC acid , *SODIUM caseinate , *ULTRASONIC imaging , *TRANSMISSION electron microscopy , *INDUCTIVE effect - Abstract
• Stable OA-NaCas complexes were obtained after ultrasonic treatment at 300 W for 5 min. • The embedding rate of OA-NaCas complex to QUE was over 90%. • The OA-NaCas-QUE particles showed regular, spherical at mass ratios or 1:15 and 1:8. • The heat stability of QUE was enhanced by the OA-NaCas complex. • The bioaccessibility of QUE was over 60% after encapsulation with OA-NaCas particles. The simultaneous improvement of quercetin (QUE) processing stability and bioavailability has always presented a technical challenge during food processing. This study constructed a water-soluble carrier consisting of oleic acid (OA) and sodium caseinate (NaCas) in an ultrasonic field and investigated the effect of its encapsulation on improving the thermal stability and bioaccessibility of QUE. The results showed that the OA and NaCas generated uniform, stable water-soluble particles with a poly dispersity index (PDI) below 0.3 and an absolute value of Zeta potential above 30 mV in optimized conditions (a protein concentration of 4 mg/mL, ultrasonic power of 300 W, and ultrasonic time of 5 min). OA-NaCas mass ratio of 1:40, 1:15, 1:8, and 1:4 was selected for QUE loading to compare its encapsulation effect at different mass ratios. Compared with the NaCas without OA, the QUE embedding rate reached 95 % at OA-NaCas mass ratios of 1:15 and 1:8. In addition, the transmission electron microscopy (TEM) images confirmed that QUE was embedded in OA-NaCas particles, forming regular, spherical OA-NaCas-QUE particles at mass ratios or 1:15 and 1:8. Next, when heated at 80 °C for 120 min, the OA-NaCas (OA:NaCas, 1:15, 1:8, and W/W) particles significantly improved the QUE retention rate. The simulated in vitro gastrointestinal digestion experiments showed that the QUE bioaccessibility increased from 25 % to more than 60 % when it was encapsulated in OA-NaCas (OA:NaCas, 1:15, 1:8, and W/W) particles. These results indicated that the OA-NaCas complex was suitable as a hydrophilic delivery carrier of fat-soluble polyphenols. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Fabricating hydrophilic fatty acid-protein particles to encapsulate fucoxanthin: Fatty acid screening, structural characterization, and thermal stability analysis.
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Li, Donghui, Liu, Yunjun, Ma, Yu, Liu, Yixiang, Wang, Shengnan, Guo, Zixin, Li, Jie, Wang, Yanbo, Tan, Bin, and Wei, Ying
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ZETA potential , *FATTY acids , *THERMAL stability , *THERMAL analysis , *FOURIER transform infrared spectroscopy , *DOCOSAHEXAENOIC acid , *FATTY acid analysis , *SERUM albumin - Abstract
[Display omitted] • Dietary fatty acids (FAs) showed different regulatory effects on the intestinal absorption of fucoxanthin (FUCO). • Myristic, palmitic, stearic, oleic, linoleic, and docosahexaenoic acid obviously promoted FUCO absorption. • The encapsulation efficiency of FAs-bovine serum albumin (BSA) particles to FUCO reached>98%. • The FUCO-loading particles exhibited a "core-shell" structure. • The FAs-BSA particles improved the thermal stability of FUCO by 2.16–4.06 times. Biomacromolecules are used to encapsulate carotenoids, but their poor absorption-enhancing ability restricts their application. This study integrated dietary fatty acids (FAs) into the protein-based encapsulation of fucoxanthin (FUCO) due to its positive role in carotenoid absorption. The results showed that of the 14 tested FAs, only myristic, palmitic, stearic, oleic, linoleic, and docosahexaenoic acid obviously promoted FUCO absorption. FAs were employed for FUCO encapsulation using bovine serum albumin (BSA) to fabricate FUCO-FA-BSA systems, with an encapsulation efficiency of > 98%, a particle size ranging from 113.1 nm to 193.5 nm, and a Zeta-potential between −32.8 mV and −38.3 mV. Electron microscopy and Fourier transform infrared spectroscopy revealed complete FUCO encapsulation, while the FUCO-loading particles exhibited a "core-shell" structure. The retention rate of the encapsulated FUCO increased 2.16–4.06 times when heated at 80.0 °C for 200 min. These results suggested that FA-BSA complexes might provide a promising strategy for embedding carotenoids. [ABSTRACT FROM AUTHOR]
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- 2022
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9. A genome‐wide association study uncovers a ZmRap2.7‐ZCN9/ZCN10 module to regulate ABA signalling and seed vigour in maize.
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Guo, Shasha, Ai, Junmin, Zheng, Nannan, Hu, Hairui, Xu, Zhuoyi, Chen, Quanquan, Li, Li, Liu, Yunjun, Zhang, Hongwei, Li, Jieping, Pan, Qingchun, Chen, Fanjun, Yuan, Lixing, Fu, Junjie, Gu, Riliang, Wang, Jianhua, and Du, Xuemei
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Summary Seed vigour, including rapid, uniform germination and robust seedling establishment under various field conditions, is becoming an increasingly essential agronomic trait for achieving high yield in crops. However, little is known about this important seed quality trait. In this study, we performed a genome‐wide association study to identify a key transcription factor ZmRap2.7, which regulates seed vigour through transcriptionally repressing expressions of three ABA signalling genes ZmPYL3, ZmPP2C and ZmABI5 and two phosphatidylethanolamine‐binding genes ZCN9 and ZCN10. In addition, ZCN9 and ZCN10 proteins could interact with ZmPYL3, ZmPP2C and ZmABI5 proteins, and loss‐of‐function of ZmRap2.7 and overexpression of ZCN9 and ZCN10 reduced ABA sensitivity and seed vigour, suggesting a complex regulatory network for regulation of ABA signalling mediated seed vigour. Finally, we showed that four SNPs in ZmRap2.7 coding region influenced its transcriptionally binding activity to the downstream gene promoters. Together with previously identified functional variants within and surrounding ZmRap2.7, we concluded that the distinct allelic variations of ZmRap2.7 were obtained independently during maize domestication and improvement, and responded separately for the diversities of seed vigour, flowering time and brace root development. These results provide novel genes, a new regulatory network and an evolutional mechanism for understanding the molecular mechanism of seed vigour. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Genome‐wide expression quantitative trait locus analysis reveals silk‐preferential gene regulatory network in maize.
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Wang, Xiaoli, Lu, Jiawen, Han, Mingfang, Wang, Zheyuan, Zhang, Hongwei, Liu, Yunjun, Zhou, Peng, Fu, Junjie, and Xie, Yuxin
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GENE regulatory networks , *LOCUS (Genetics) , *GENE expression , *GENETIC regulation , *METABOLIC regulation , *CORN - Abstract
Silk of maize (Zea mays L.) contains diverse metabolites with complicated structures and functions, making it a great challenge to explore the mechanisms of metabolic regulation. Genome‐wide identification of silk‐preferential genes and investigation of their expression regulation provide an opportunity to reveal the regulatory networks of metabolism. Here, we applied the expression quantitative trait locus (eQTL) mapping on a maize natural population to explore the regulation of gene expression in unpollinated silk of maize. We obtained 3,985 silk‐preferential genes that were specifically or preferentially expressed in silk using our population. Silk‐preferential genes showed more obvious expression variations compared with broadly expressed genes that were ubiquitously expressed in most tissues. We found that trans‐eQTL regulation played a more important role for silk‐preferential genes compared to the broadly expressed genes. The relationship between 38 transcription factors and 85 target genes, including silk‐preferential genes, were detected. Finally, we constructed a transcriptional regulatory network around the silk‐preferential gene Bx10, which was proposed to be associated with response to abiotic stress and biotic stress. Taken together, this study deepened our understanding of transcriptome variation in maize silk and the expression regulation of silk‐preferential genes, enhancing the investigation of regulatory networks on metabolic pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Synthesis, Characterization and Anticancer Efficacy Evaluation of Benzoxanthone Compounds toward Gastric Cancer SGC-7901.
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Fu, Yuan, Xu, Yunran, Liu, Yunjun, Wang, Yi, Chen, Ju, and Wang, Xiuzhen
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BCL-2 proteins , *POLY(ADP-ribose) polymerase , *STOMACH cancer , *ANTINEOPLASTIC agents , *POLY ADP ribose , *REACTIVE oxygen species , *ADP-ribosylation - Abstract
Three benzoxanthone derivatives were synthesized through a new photochemical strategy. The in vitro cytotoxic activity of these compounds was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and their partition coefficients (logP) were measured by shake flask method. The pKa values of the compounds were detected by potentionmetric titration. The interaction of the compounds with calf thymus DNA (CT-DNA) was investigated by electronic absorption, luminescence spectra and viscosity. A molecular docking analysis was performed. The antitumor efficacy of the compounds was evaluated by cell apoptosis, cell cycle arrest, intracellular Ca2+ concentrations and reactive oxygen species (ROS) levels. The mitochondrial membrane potential was assayed using JC-1 (5,5′,6,6′-tetrachloro-1,1,3′,3′-tetraethyl-imidacarbocyanine iodide) as the fluorescence probe. The expression of Bcl-2 family protein, caspase 3 and poly ADP-ribose polymerase (PARP) was explored by western blot. The results showed that the compounds induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. This work provides an efficient approach to synthesize benzoxanthone derivatives, and is helpful for understanding the apoptotic mechanism. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Comparisons of wild and cultivated American ginseng (Panax quinquefolius L.) genomes provide insights into changes in root growth and metabolism during domestication.
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Wang, Zhengpeng, Wang, Tengteng, Hu, Jin, Jiao, Honghong, Jin, Yan, Sun, Jiahui, Nan, Tiegui, Zhao, Yuyang, Liu, Yunjun, Huang, Luqi, and Yuan, Yuan
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AMERICAN ginseng , *DOMESTICATION of animals , *GENOMES , *ROOT growth , *PANAX , *RNA interference , *GENE expression , *GENE families - Abstract
This article explores the genetic basis for changes in root growth and metabolism during the domestication of American ginseng (Panax quinquefolius L.). The researchers sequenced and analyzed the genomes of wild and cultivated American ginseng varieties, finding that cultivated varieties had fewer lateral roots and lower levels of ginsenoside Rg1 compared to wild varieties. They identified gene families related to cell wall synthesis and structure that were expanded in cultivated ginseng. Additionally, they found that certain genes related to cell wall development and stress resistance were positively selected in wild ginseng. The study suggests that the regulation of cell wall composition and structure plays a role in the formation of specific root morphology in cultivated ginseng. [Extracted from the article]
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- 2024
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13. Bacterium-enabled transient gene activation by artificial transcription factors for resolving gene regulation in maize.
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Zhao, Mingxia, Peng, Zhao, Qin, Yang, Tamang, Tej Man, Zhang, Ling, Tian, Bin, Chen, Yueying, Liu, Yan, Zhang, Junli, Lin, Guifang, Zheng, Huakun, He, Cheng, Lv, Kaiwen, Klaus, Alina, Marcon, Caroline, Hochholdinger, Frank, Trick, Harold N, Liu, Yunjun, Cho, Myeong-Je, and Park, Sunghun
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GENETIC regulation , *TRANSCRIPTION factors , *SYNTHETIC genes , *GENE regulatory networks , *CORN diseases , *BACTERIAL proteins , *CORN - Abstract
A bacterial protein delivery system for transient gene induction was used to study gene regulation in the cuticular wax biosynthesis pathway in maize. Understanding gene regulatory networks is essential to elucidate developmental processes and environmental responses. Here, we studied regulation of a maize (Zea mays) transcription factor gene using designer transcription activator-like effectors (dTALes), which are synthetic Type III TALes of the bacterial genus Xanthomonas and serve as inducers of disease susceptibility gene transcription in host cells. The maize pathogen Xanthomonas vasicola pv. vasculorum was used to introduce 2 independent dTALes into maize cells to induced expression of the gene glossy3 (gl3), which encodes a MYB transcription factor involved in biosynthesis of cuticular wax. RNA-seq analysis of leaf samples identified, in addition to gl3, 146 genes altered in expression by the 2 dTALes. Nine of the 10 genes known to be involved in cuticular wax biosynthesis were upregulated by at least 1 of the 2 dTALes. A gene previously unknown to be associated with gl3, Zm00001d017418, which encodes aldehyde dehydrogenase, was also expressed in a dTALe-dependent manner. A chemically induced mutant and a CRISPR-Cas9 mutant of Zm00001d017418 both exhibited glossy leaf phenotypes, indicating that Zm00001d017418 is involved in biosynthesis of cuticular waxes. Bacterial protein delivery of dTALes proved to be a straightforward and practical approach for the analysis and discovery of pathway-specific genes in maize. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Synthesis, characterization, anticancer efficacy evaluation of ruthenium(II) and iridium(III) polypyridyl complexes toward A549 cells.
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Liang, Lijuan, Yang, Yan, Liu, Haimei, Yuan, Fang, Yuan, Yuhan, Li, Wenlong, Huang, Chunxia, Chen, Jing, and Liu, Yunjun
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RUTHENIUM compounds , *ANTINEOPLASTIC agents , *IRIDIUM , *RUTHENIUM , *CELL cycle , *CELL death , *ORGANIC light emitting diodes - Abstract
A new ligand DFIP (2-(dibenzo[b,d]furan-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline) and its two complexes iridium(III) [Ir(ppy)2(DFIP)](PF6) (ppy = 2-phenylpyridine, Ir1) and ruthenium(II) [Ru(bpy)2(DFIP)](PF6)2 (bpy = 2,2′-bipyridine, Ru1) were synthesized and characterized. The anticancer effects of the two complexes on A549, BEL-7402, HepG2, SGC-7901, HCT116 and normal LO2 cells were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complex Ir1 shows high cytotoxic activity on A549, BEL-7402, SGC-7901 and HepG2, Ru1 exhibits moderate anticancer activity toward A549, BEL-7402 and SGC-7901 cells. The IC50 values of Ir1 and Ru1 toward A549 are 7.2 ± 0.1 and 22.6 ± 1.4 μM, respectively. The localization of complexes Ir1 and Ru1 in the mitochondrial, intracellular accumulation of reactive oxygen species (ROS) levels, and the changes of mitochondrial membrane potential (MMP) and cytochrome c (cyto-c) were investigated. Apoptosis and cell cycle were detected by flow cytometry. Immunogenic cell death (ICD) was used to detect the effects of Ir1 and Ru1 on the A549 using a confocal laser scanning microscope. The expression of apoptosis-related proteins was detected by western blotting. Ir1 and Ru1 can increase the intracellular ROS levels and release cyto-c, reduce the MMP, leading to the apoptosis of A549 cells and blocking the A549 cells at the G0/G1 phase. Additionally, the complexes caused a decrease of the expression of polyADP-ribose polymerase (PARP), caspase 3, Bcl-2 (B-cell lymphoma-2), PI3K (phosphoinositide-3 kinase) and upregulated the expression of Bax. All these findings indicated that the complexes exert anticancer efficacy to induce cell death through immunogenic cell death, apoptosis, and autophagy. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Evaluation of the Anticancer Activity and Mechanism Studies of Glycyrrhetic Acid Derivatives toward HeLa Cells.
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Chen, Ju, Xu, Yunran, Yang, Yan, Yao, Xin, Fu, Yuan, Wang, Yi, Liu, Yunjun, and Wang, Xiuzhen
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HELA cells , *BCL-2 proteins , *FOCAL adhesion kinase , *ANTINEOPLASTIC agents , *GENE expression , *B cell receptors - Abstract
In this paper, a series of glycyrrhetic acid derivatives 3a–3f were synthesized via the esterification reaction. The cytotoxicity of these compounds against five tumor cells (SGC-7901, BEL-7402, A549, HeLa and B16) and normal LO2 cells was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results showed that compound 3a exhibited high antiproliferative activity against HeLa cells (IC50 = 11.4 ± 0.2 μM). The anticancer activity was studied through apoptosis, cloning, and scratching; the levels of the intracellular ROS, GSH, and Ca2+; and the change in the mitochondrial membrane potential, cell cycle arrest and RNA sequencing. Furthermore, the effects of compound 3a on gene expression levels and metabolic pathways in HeLa cells were investigated via transcriptomics. The experimental results showed that this compound can block the cell cycle in the S phase and inhibit cell migration by downregulating Focal adhesion kinase (FAK) expression. Moreover, the compound can reduce the intracellular glutathione (GSH) content, increase the Ca2+ level and the intracellular ROS content, and induce a decrease in the mitochondrial membrane potential, further leading to cell death. In addition, it was also found that the mechanism of compounds inducing apoptosis was related to the regulation of the expression of mitochondria-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax), and the activation of the caspase proteins. Taken together, this work provides a help for the development of glycyrrhetinic acid compounds as potential anticancer molecules. [ABSTRACT FROM AUTHOR]
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- 2023
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16. cis‐Regulatory variation affecting gene expression contributes to the improvement of maize kernel size.
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Li, Yong‐xiang, Lu, Jiawen, He, Cheng, Wu, Xun, Cui, Yu, Chen, Lin, Zhang, Jie, Xie, Yuxin, An, Yixin, Liu, Xuyang, Zhen, Sihan, Liu, Yunjun, Li, Chunhui, Zhang, Dengfeng, Shi, Yun‐Su, Song, Yanchun, Wang, Jianhua, Li, Yu, Wang, Guoying, and Fu, Junjie
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GENE expression , *LOCUS (Genetics) , *CORN , *CIS-regulatory elements (Genetics) , *GENOME-wide association studies , *REGULATOR genes , *CORN seeds , *SINGLE nucleotide polymorphisms - Abstract
SUMMARY: cis‐Regulatory variations contribute to trait evolution and adaptation during crop domestication and improvement. As the most important harvested organ in maize (Zea mays L.), kernel size has undergone intensive selection for size. However, the associations between maize kernel size and cis‐regulatory variations remain unclear. We chose two independent association populations to dissect the genetic architecture of maize kernel size together with transcriptomic and genotypic data. The resulting phenotypes reflected a strong influence of population structure on kernel size. Compared with genome‐wide association studies (GWASs), which accounted for population structure and relatedness, GWAS based on a naïve or simple linear model revealed additional associated single‐nucleotide polymorphisms significantly involved in the conserved pathways controlling seed size in plants. Regulation analyses through expression quantitative trait locus mapping revealed that cis‐regulatory variations likely control kernel size by fine‐tuning the expression of proximal genes, among which ZmKL1 (GRMZM2G098305) was transgenically validated. We also proved that the pyramiding of the favorable cis‐regulatory variations has contributed to the improvement of maize kernel size. Collectively, our results demonstrate that cis‐regulatory variations, together with their regulatory genes, provide excellent targets for future maize improvement. Significance Statement: GWAS associations confounded with population structure and relatedness were found to contribute to the genetic architecture of maize kernel size. Meanwhile, the favourable cis‐regulatory variations were found to involve in the improvement of maize kernel size. [ABSTRACT FROM AUTHOR]
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- 2022
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17. Epigenetic Mutation in a Tubulin-Folding Cofactor B (ZmTFCB) Gene Arrests Kernel Development in Maize.
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Guo, Yingmei, Chen, Yan, Zhang, Jie, Li, Jiankun, Fan, Kaijian, Chen, Rongrong, Liu, Yunjun, Zheng, Jun, Fu, Junjie, Gu, Riliang, Wang, Guoying, Cui, Yu, Du, Xuemei, and Wang, Jianhua
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EPIGENETICS , *CORN , *PLANT breeding , *TUBULINS , *GENETIC variation , *NUCLEOTIDE sequence , *HISTONES - Abstract
Epialleles, the heritable epigenetic variants that are not caused by changes in DNA sequences, can broaden genetic and phenotypic diversity and benefit to crop breeding, but very few epialleles related to agricultural traits have been identified in maize. Here, we cloned a small kernel mutant, smk-wl10 , from maize, which encoded a tubulin-folding cofactor B (ZmTFCB) protein. Expression of the ZmTFCB gene decreased in the smk-wl10 mutant, which arrested embryo, endosperm and basal endosperm transfer layer developments. Overexpression of ZmTFCB could complement the defective phenotype of smk-wl10. No nucleotide sequence variation in ZmTFCB could be found between smk-wl10 and wild type (WT). Instead, we detected hypermethylation of nucleotide CHG (where H is A, C or T nucleotide) sequence contexts and increased level of histone H3K9me2 methylation in the upstream sequence of ZmTFCB in smk-wl10 compared with WT, which might respond to the attenuating transcription of ZmTFCB. In addition, yeast two-hybrid and bimolecular fluorescence complementation assays identified a strong interaction between ZmTFCB and its homolog ZmTFCE. Thus, our work identifies a novel epiallele of the maize ZmTFCB gene, which might represent a common phenomenon in the epigenetic regulation of important traits such as kernel development in maize. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Induction of apoptosis in SGC-7901 cells by iridium(III) complexes via endoplasmic reticulum stress-mitochondrial dysfunction pathway.
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Wang, Jiawen, Liu, Haimei, Wu, Xiaoyun, Shi, Chuanling, Li, Wenlong, Yuan, Yuhan, Liu, Yunjun, and Xing, Degang
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ENDOPLASMIC reticulum , *IRIDIUM , *APOPTOSIS , *WESTERN immunoblotting , *CELL cycle , *MITOCHONDRIAL membranes , *MEMBRANE potential - Abstract
This study was intended to evaluate the anticancer activity of three newly synthesized iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = (E)-2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline). The cytotoxic activity in vitro against A549, SGC-7901, HepG2, HeLa and normal NIH3T3 cells was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. We found that the complexes 1, 2 and 3 significantly inhibited cell proliferation, in particular, complexes 2 and 3 show high cytotoxic effect on SGC-7901 cells with an IC50 value of 5.8 ± 0.7 and 4.4 ± 0.1 μM. Moreover, cell cycle assay revealed that the complexes could block G2/M phase of the cell cycle. Apoptotic evaluation by Annexin V/PI staining indicated that complexes 1–3 can induce apoptosis in SGC-7901 cells. In addition, microscopy detection suggested that disruption of mitochondrial functions, characterized by increased generation of intracellular ROS and Ca2+ as well as decrease of mitochondrial membrane potential. Western blot analysis shows that the complexes upregulate the expression of pro-apoptotic Bax and downregulate the expression of anti-apoptotic Bcl-2, which further activates caspase-3 and prompts the cleavage of PARP. Taken together, these results demonstrated that complexes 1–3 exert a potent anticancer effect on SGC-7901 cells via ROS-mediated endoplasmic reticulum stress-mitochondrial apoptotic pathway and have a potential to be developed as novel chemotherapeutic agents for human gastric cancer. Three new iridium(III) complexes [Ir(ppy)2(PEIP)](PF6) (1) (ppy = 2-phenylpyridine, PEIP = 2-phenethyl-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(SIP)](PF6) (2) (SIP = 2-styryl-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(PEYIP)](PF6) (3) (PEYIP = 2-phenethynyl-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The anticancer activity in vitro was investigated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results show that the complexes induce apoptosis via ROS-mediated endoplasmic reticulum stress-mitochondrial dysfunction pathway. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Synthesis, characterization and irradiation enhances anticancer activity of liposome-loaded iridium(III) complexes.
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Tian, Shuang, Nie, Qianying, Chen, Haomin, Liang, Lijuan, Hu, Huiyan, Tang, Shuanghui, Yang, Jiawan, Liu, Yunjun, and Yin, Hui
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LIPOSOMES , *BCL-2 proteins , *IRIDIUM , *ANTINEOPLASTIC agents , *MALONDIALDEHYDE , *MEMBRANE potential , *CELL cycle , *METAL complexes - Abstract
Herein, we synthesized and characterized two novel iridium (III) complexes: [Ir(bzq) 2 (PPD)](PF 6) (4a, with bzq = deprotonated benzo[ h ]quinoline and PPD = pteridino[6,7-f][1,10]phenanthroline-11,13-diamine) and [Ir(piq) 2 (PPD)](PF 6) (4b, with piq = deprotonated 1-phenylisoquinoline). The anticancer efficacy of these complexes, 4a and 4b, was investigated using 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT). Complex 4a exhibited no cytotoxic activity, while 4b demonstrated moderate efficacy against SGC-7901, A549, and HepG2 cancer cells. To enhance their anticancer potential, we explored two strategies: (I) light irradiation and (II) encapsulation of the complexes in liposomes, resulting in the formation of 4alip and 4blip. Both strategies significantly increased the ability of 4a, 4b to kill cancer cells. The cellular studies indicated that both the free complexes 4a, 4b and their liposomal forms 4alip and 4blip effectively inhibited cell proliferation. The cell cycle arrest analysis uncovered 4alip and 4blip arresting cell growth in the S period. Additionally, we investigated apoptosis and ferroptosis pathways, observing an increase in malondialdehyde (MDA) levels, a reduction of glutathione (GSH), a down-regulation of GPX4 (glutathione peroxidase) expression, and lipid peroxidation. The effects on mitochondrial membrane potential and intracellular Ca2+ concentrations were also examined, revealing that both light-activated and liposomal forms of 4alip and 4blip caused a decline in mitochondrial membrane potential and an enhancement in intracellular Ca2+ levels. In conclusion, these complexes and them encapsulated liposomes induce cell death through apoptosis and ferroptosis. Two iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes and them encapsulated liposomes toward SGC-7901 cells were studied upon irradiation. [Display omitted] • Two new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro of the complexes and them encapsulated liposomes was studied. • Apoptosis and cell cycle arrest were detected. • The ferroptosis was investigated. • The expression of B-cell lymphoma-2 family proteins was explored. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Synthesis, characterization and studies on the antitumor activity of novel dibenzoxanthene derivatives.
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Yao, Xin, Chen, Ju, Fu, Yuan, Wang, Yi, Liu, Yunjun, and Wang, Xiuzhen
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BCL-2 proteins , *CELL cycle , *CELL migration , *ANTINEOPLASTIC agents , *CELL death , *BCL genes , *MALONDIALDEHYDE - Abstract
• A new series of dibenzoxanthene analogues were synthesized using a newly photochemical strategy. • The cytotoxicity of synthesized compounds was evaluated by MTT method. • The apoptosis inducing by compounds was investigated by AO/EB staining. • The DNA damage, ROS and mitochondrial membrane potential were studied. • Investigation of the expression of proteins in apoptosis pathway was performed by western blotting. Three new dibenzoxanthenes were synthesized and their antitumor activity were investigated. Compounds 3a-3c showed significant cytotoxicity to HeLa cells. The 1,3-diphenylisobenzofuran (DBPF) assay demonstrated that compounds could produce singlet oxygen. Cell cloning and wound healing assays demonstrated that compounds 3a-3c effectively inhibited HeLa cell cloning and migration. After entering the mitochondria, the compounds caused a decrease in mitochondrial membrane potential, an increase in intracellular ROS and Ca2+levels, and blocked the cell cycle in the G2/M phase. Through protein immunoblotting, the apoptotic mechanism was studied, the results show that 3a-3c regulated Bcl-2 family protein, caused abnormal mitochondrial function, which led to mitochondrial apoptotic pathway. ROS, GPX4, GSH and MDA assay indicated that compounds 3a-3c caused intracellular lipid peroxidation in HeLa cells leading to ferroptosis. GSDME cleavage and elevation of LDH release induced the occurrence of pyroptosis. Therefore, we conclude that the compounds cause cell death through three pathways: apoptosis, ferroptosis and pyroptosis. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Synthesis and mitochondria-localized iridium (III) complexes induce cell death through pyroptosis and ferroptosis pathways.
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Hu, Huiyan, Zhang, Fan, Sheng, Zhujun, Tian, Shuang, Li, Gechang, Tang, Shuanghui, Niu, Yajie, Yang, Jiawan, and Liu, Yunjun
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CELL death , *PYROPTOSIS , *IRIDIUM , *CELL morphology , *CELL cycle , *LIGANDS (Biochemistry) - Abstract
This paper introduces a new ligand, 4,6-dichloro-5-(1 H -imidazo [4,5-f]phenanthroline-2-yl)pyrimidin-2-amine (DPPA), and its corresponding new iridium(III) complexes: [Ir(ppy) 2 (DPPA)](PF 6) (2a) (where ppy represents deprotonated 2-phenylpyridine), [Ir(bzq) 2 (DPPA)](PF 6) (2b) (with bzq indicating deprotonated benzo[h]quinoline), and [Ir(piq) 2 (DPPA)](PF 6) (2c) (piq denoting deprotonated 1-phenylisoquinoline). The cytotoxic effects of both DPPA and 2a, 2b, and 2c were evaluated against human lung carcinoma A549, melanoma B16, colorectal cancer HCT116, human hepatocellular carcinoma HepG2 cancer cell lines, as well as the non-cancerous LO2 cell line using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. While DPPA exhibited moderate anticancer activity toward A549, B16, HCT116 and HepG2 cells, complexes 2a, 2b, and 2c displayed remarkable efficacy against A549, B16, and HCT116 cells. The cell colonies and wound healing were investigated. Moreover, various aspects of the anticancer mechanisms were explored. The cell cycle analyses revealed that the complexes block cell proliferation of A549 cells during the S phase. Complex 2c induce an early apoptosis, while 2a and 2b cause a late apoptosis. The interaction of 2a, 2b and 2c with endoplasmic reticulum and mitochondria was identified, leading to elevated ROS and Ca2+ amounts. This resulted in a reduced mitochondrial membrane potential, mitochondrial permeability transition pore opening, and an increase of cytochrome c. Also, ferroptosis was investigated through measurements of intracellular glutathione (GSH), malondialdehyde (MDA), and recombinant glutathione peroxidase (GPX4) protein expression. The pyroptosis was explored via cell morphology, release of lactate dehydrogenase (LDH) and expression of pyroptosis-related proteins. RNA sequencing was applied to examine the signaling pathways. Western blot analyses illuminated that the complexes regulate the expression of Bcl-2 family proteins. Additionally, an in vivo antitumor study demonstrated that complex 2c exhibited a remarkable inhibitory rate of 58.58% in restraining tumor growth. In summary, the findings collectively suggest that the iridium(III) complexes induce cell death via ferroptosis, apoptosis by a ROS-mediated mitochondrial dysfunction pathway and GSDMD-mediated pyroptosis. Three new iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes against A549 cells were investigated, the complexes exhibit high antitumor efficacy in vivo. [Display omitted] • Three new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was studied. • Apoptosis, reactive oxygen species and cell cycle arrest were detected. • The RNA-sequence, pyroptosis and ferroptosis were performed. • The antitumor efficacy in vivo was explored. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Mitochondria-targeted iridium(III) complexes encapsulated in liposome induce cell death through ferroptosis and gasdermin-mediated pyroptosis.
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Huang, Chunxia, Yuan, Yuhan, Li, Gechang, Tian, Shuang, Hu, Huiyan, Chen, Jing, Liang, Lijuan, Wang, Yi, and Liu, Yunjun
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ANTIBODY-dependent cell cytotoxicity , *LIPOSOMES , *HIGH mobility group proteins , *CELL death , *PYROPTOSIS , *IRIDIUM , *CELL cycle - Abstract
This paper unveils a novel perspective on synthesis and characterization of the ligand 5-bromo-2-amino-2'-(phenyl-1H-imidazo[4,5-f][1,10]phenanthroline) (BAPIP), and its iridium(III) complexes [Ir(PPY−) 2 (BAPIP)](PF 6) (1a, with PPY− as deprotonated 2-phenylpyridine), [Ir(PIQ−) 2 (BAPIP)](PF 6) (1b, piq− denoting deprotonated 1-phenylisoquinoline), and [Ir(BZQ−) 2 (BAPIP)](PF 6) (1c, bzq− signifying deprotonated benzo[h]quinoline). Systematic evaluation of the cytotoxicity of 1a, 1b, and 1c across diverse cell lines encompassing B16, HCT116, HepG2, A549, HeLa, and LO2 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Unexpectedly, compounds 1b and 1c demonstrated no cytotoxicity against the above cell lines. Motivated by the pursuit of heightened anti-proliferative potential, a strategic encapsulation approach yielded liposomes 1alip, 1blip, and 1clip. As expectation, 1alip, 1blip, and 1clip displayed remarkable anti-proliferative efficacy, particularly noteworthy in A549 cells, exhibiting IC 50 values of 4.9 ± 1.0, 5.9 ± 0.1, and 7.6 ± 0.2 μM, respectively. Moreover, our investigation illuminated the mitochondrial accumulation of these liposomal entities, 1alip, 1blip, and 1clip, evoking apoptosis through the mitochondrial dysfunction mediated by reactive oxygen species (ROS). The ferroptosis was confirmed by decrease in glutathione (GSH) concentrations, the downregulation of glutathione peroxidase 4 (GPX4), increase of high mobility group protein 1 (HMGB1), and lipid peroxidation. Simultaneously, pyroptosis as another mode of cell death was undertaken. RNA-sequencing was employed to investigate intricate signalling pathways. In vivo examination provided tangible evidence of 1alip in effectively curbing tumor growth. Collectively, this study provides a multifaceted mode of cellular demise orchestrated by 1a, 1alip, 1blip, and 1clip, involving pathways encompassing apoptosis, ferroptosis, and pyroptosis. Three new iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes toward A549 cells were explored, the liposomes entrapped complexes exhibit high antitumor efficacy in vivo. [Display omitted] • Three new iridium(III) complexes and their liposomes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes and their liposomes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were examined. • The RNA-sequence were carried out. • The antitumor efficacy in vivo was studied. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Targeted liposomes encapsulated iridium(III) compound greatly enhance anticancer efficacy and induce cell death via ferroptosis on HepG2 cells.
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Chen, Jing, Li, Wenlong, Li, Gechang, Liu, Xiaoming, Huang, Chunxia, Nie, Hua, Liang, Lijuan, Wang, Yi, and Liu, Yunjun
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LIPOSOMES , *IRIDIUM , *CELL death , *ANTINEOPLASTIC agents , *MEMBRANE potential , *CELL cycle , *RAPAMYCIN - Abstract
In this study, ligands 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (PIP), 2-(2-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (NPIP), 2-(2-nitronaphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NNIP) and their iridium(III) metal compounds [Ir(ppy) 2 (PIP)](PF 6) (ppy = 2-phenylpyridine, 1a), [Ir(ppy) 2 (NPIP)](PF 6) (1b), [Ir(ppy) 2 (NNIP)](PF 6) (1c) were designed and synthesized. The anti-cancer activities of 1a, 1b and 1c on BEL-7402, HepG2, SK-Hep1 and non-cancer LO2 were detected using MTT method. 1a shows moderate, 1b and 1c display low or no anti-cancer activities. To elevate the anti-cancer effectiveness, encapsulating the compounds 1a, 1b and 1c into the ordinary or targeted liposomes to produce 1alip, 1blip, 1clip, or targeted 1aTlip, 1bTlip and 1cTlip. The IC 50 values of 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip against HepG2 cells are 7.9 ± 0.1, 8.6 ± 0.2, 16.9 ± 0.5, 5.9 ± 0.2, 7.3 ± 0.1 and 9.7 ± 0.7 μM, respectively. Specifically, the anti-tumor activity assays in vivo found that the inhibitory rates are 23.24 % for 1a, 61.27 % for 1alip, 76.06 % for 1aTlip. It is obvious that the targeted liposomes entrapped iridium(III) compound greatly enhance anti-cancer efficacy. Additionally, 1alip, 1blip and 1clip or targeted 1aTlip, 1bTlip and 1cTlip can effectively restrain the cell colony and proliferation in the G0/G1 period. 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip can increase reactive oxygen species (ROS) concentration, arouse a decline in the mitochondrial membrane potential and promote Ca2+ release. RNA-sequence was applied to examine the signaling pathways. Taken together, the liposomes or targeted liposomes encapsulated compounds trigger cell death by way of apoptosis, autophagy, ferroptosis, disruption of mitochondrial function and PI3K/AKT/mTOR signaling pathways. Three iridium(III) polypyridyl compounds 1a, 1b, 1c and compound-loaded ordinary 1alip, 1blip, 1clip and targeted liposomes 1aTlip, 1bTlip and 1cTlip were synthesized and characterized. The antiproliferative ability of 1a, 1b, 1c, 1alip, 1blip, 1clip, 1aTlip, 1bTlip and 1cTlip against BEL-7402, HepG2, SK-Hep1 and non-cancer LO2 cells was investigated. The inhibitory rate in vivo of 1a, 1alip and 1aTlip inhibiting HepG2 tumor growth attains 23.24, 61.27 and 76.06 %. [Display omitted] • Three new iridium(III) complexes, ordinary and targeted liposomes were synthesized and characterization. • The cytotoxicity in vitro and in vivo of the complexes and their liposomes was investigated. • Cell cycle arrest, apoptosis, ferroptosis, reactive oxygen species were examined. • The RNA-sequence was explored. • The antitumor efficacy in vivo was evaluated. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Liposome as drug delivery system enhance anticancer activity of iridium (III) complex.
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Gu, Yiying, Bai, Lan, Zhang, Yuanyuan, Zhang, Huiwen, Xing, Degang, Tian, Li, Zhou, Yi, Hao, Jing, and Liu, Yunjun
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ANTINEOPLASTIC agents , *DRUG delivery systems , *CELL cycle , *IRIDIUM , *MICROTUBULES , *LIPOSOMES , *CELL survival - Abstract
Herein an Ir(III) complex [Ir(Hppy)2(HMNPIP)](PF6) (Ir1, Hppy = 2-phenylpyridine, HMNPIP = 2-(1H-imidazo[4,5-f][1, 10]phenanthroline-3-yl)-6-methoxy-4-nitrophenol) was prepared and characterized. Due to the low anticancer activity of Ir1 when administered free drug, we prepared a liposome Ir1Lipo encapsulated form of Ir1 to improve the antitumor effect, furthermore, we explored the antitumor mechanism of both forms in vitro experiments on HepG2 cells. We investigated the inhibitory efficiency of Ir1 and Ir1Lipo on cell viability and proliferation using MTT (MTT = 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide) and colony-forming assay. Intracellular accumulation of reactive oxygen species (ROS) was examined using a fluorescence microscope (High Content Screening System, ImageXpress Micro XLS System, Molecular Devices LLC, Sunnyvale, CA), programmed cell death cells stained with acridine orange/ethidium bromide (AO/EB) using flow cytometry detection and western blot have been performed. An in vivo study where HepG2 cells were transplanted into nude nice as xenografts. Tumour volume and body weight were monitored during the 10 days of administration. After encapsulation in liposomes Ir1Lipo displayed high potency against a variety of tumour cells in vitro, especially against HepG2 (IC50 = 4.6 ± 0.5 μM). Mechanism studies indicated that Ir1Lipo initiated apoptosis by generating intracellular ROS that regulate lysosomal-mitochondrial dysfunction, followed by microtubule disruption that subsequently leads to a G0/G1 phase of cell cycle arrest. Additionally, Ir1Lipo significantly curbed tumour growth in nude mice. The tumour inhibitory rate was 51.2% (5.6 mg/kg). Therefore, liposome as a drug delivery system greatly enhances anticancer activity of Ir1 by a factor of relatively minor side effects. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. pentatricopeptide repeat protein EMP603 is required for the splicing of mitochondrial Nad1 intron 2 and seed development in maize.
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Fan, Kaijian, Ren, Zhenjing, Zhang, Xiaofeng, Liu, Yan, Fu, Junjie, Qi, Chunlai, Tatar, Wurinile, Rasmusson, Allan G, Wang, Guoying, and Liu, Yunjun
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SEED development , *PLANT mitochondria , *INTRONS , *RNA splicing , *RNA helicase , *MITOCHONDRIA , *SPLICEOSOMES , *CORN - Abstract
Intron splicing is an essential event in post-transcriptional RNA processing in plant mitochondria, which requires the participation of diverse nuclear-encoded splicing factors. However, it is presently unclear how these proteins cooperatively take part in the splicing of specific introns. In this study, we characterized a nuclear-encoded mitochondrial P-type pentatricopeptide repeat (PPR) protein named EMP603. This protein is essential for splicing of intron 2 in the Nad1 gene and interacts with the mitochondria-localized DEAD-box RNA helicase PMH2-5140, the RAD52-like proteins ODB1-0814 and ODB1-5061, and the CRM domain-containing protein Zm-mCSF1. Further study revealed that the N-terminal region of EMP603 interacts with the DEAD-box of PMH2-5140, the CRM domain of Zm-mCSF1, and OBD1-5061, but not with OBD1-0814, whereas the PPR domain of EMP603 can interact with ODB1-0814, ODB1-5061, and PMH2-5140, but not with Zm-mCSF1. Defects in EMP603 severely disrupt the assembly and activity of mitochondrial complex I, leading to impaired mitochondrial function, and delayed seed development. The interactions revealed between EMP603 and PMH2-5140, ODB1-0814, ODB1-5061, and Zm-mCSF1 indicate a possible involvement of a dynamic 'spliceosome-like' complex in intron splicing, and may accelerate the elucidation of the intron splicing mechanism in plant mitochondria. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Synthesis and evaluation of iridium(III) complexes on antineoplastic activity against human gastric carcinoma SGC-7901 cells.
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Tian, Li, Zhang, Yuanyuan, Zhang, Huiwen, Zhou, Yi, Li, Wenlong, Yuan, Yuhan, Hao, Jing, Yang, Linlin, and Liu, Yunjun
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STOMACH cancer , *IRIDIUM , *WESTERN immunoblotting , *INHIBITION of cellular proliferation , *CELL cycle , *MITOCHONDRIAL membranes , *LIGANDS (Biochemistry) - Abstract
The study was intended to determine the antineoplastic effects of two new iridium(III) complexes [Ir(ppy)2(PTTP)](PF6) (1) (ppy = 2-phenylpyridine) and [Ir(piq)2(PTTP)](PF6) (2) (piq = 1-phenylisoquinoline, PTTP = 2-phenoxy-1,4,8,9-tetraazatriphenylene). In MTT assay, the ligand PTTP displayed ineffective inhibition on cell growth in SGC-7901, BEL-7402, HepG2 as well as NIH3T3 cell lines, while complexes 1 and 2 showed high cytotoxic activity on SGC-7901 cells with an IC50 value of 0.5 ± 0.1 µM and 4.4 ± 0.6 µM, respectively. Cellular uptake, cell cloning experiments, wound healing assay and cell cycle arrest indicated that the two complexes can inhibit the cell proliferation in SGC-7901 and induce cell cycle arrest at G0/G1 phase. Additionally, reactive oxygen species (ROS) and mitochondrial membrane potential suggested that the two complexes induced cell apoptosis through disrupting mitochondrial functions. Further, western blot analysis illustrated that the two complexes caused apoptosis via regulating expression levels of Bcl-2 family proteins. Moreover, complex 1 could suppress tumor growth in vivo with an inhibitory rate of 49.41%. Altogether, these results demonstrated that complexes 1 and 2 exert a potent anticancer effect against SGC-7901 cells via mitochondrial apoptotic pathway and have a potential to be developed as antineoplastic drug candidates for human gastric cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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27. Small kernel 501 (smk501) encodes the RUBylation activating enzyme E1 subunit ECR1 (E1 C‐TERMINAL RELATED 1) and is essential for multiple aspects of cellular events during kernel development in maize.
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Chen, Quanquan, Zhang, Jie, Wang, Jie, Xie, Yuxin, Cui, Yu, Du, Xuemei, Li, Li, Fu, Junjie, Liu, Yunjun, Wang, Jianhua, Wang, Guoying, and Gu, Riliang
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CORN , *UBIQUITIN ligases , *CELL cycle , *CORN seeds , *PROTEOLYSIS , *CELLULAR signal transduction , *UBIQUITINATION - Abstract
Summary: RUBylation plays essential roles in plant growth and development through regulating Cullin‐RING ubiquitin E3 ligase (CRL) activities and the CRL‐mediated protein degradations. However, the function of RUBylation in regulating kernel development remains unclear.Through genetic and molecular analyses of a small kernel 501 (smk501) mutant in maize (Zea mays), we cloned the smk501 gene, revealed its molecular function, and defined its roles in RUBylation pathway and seed development.Smk501 encodes a RUBylation activating enzyme E1 subunit ZmECR1 (E1 C‐TERMINAL RELATED 1) protein. Destruction in RUBylation by smk501 mutation resulted in less embryo and endosperm cell number and smaller kernel size. The transcriptome and proteome profiling, hormone evaluation and cell proliferation observation revealed that disturbing ZmECR1 expression mainly affects pathways on hormone signal transduction, cell cycle progression and starch accumulation during kernel development. In addition, mutant in zmaxr1 (Auxin resistant 1), another RUB E1 subunit, also showed similar defects in kernel development. Double mutation of zmecr1 and zmaxr1 lead to empty pericarp kernel phenotype.RUBylation is a novel regulatory pathway affecting maize kernel development, majorly through its functions in modifying multiple cellular progresses. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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28. Nuclear-Encoded Maturase Protein 3 Is Required for the Splicing of Various Group II Introns in Mitochondria during Maize (Zea mays L.) Seed Development.
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Chen, Weiwei, Cui, Yu, Wang, Zheyuan, Chen, Rongrong, He, Cheng, Liu, Yan, Du, Xuemei, Liu, Yunjun, Fu, Junjie, Wang, Guoying, Wang, Jianhua, and Gu, Riliang
- Subjects
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RNA splicing , *CORN , *SEED development , *INTRONS , *SEED proteins - Abstract
Splicing of plant organellar group II introns from precursor-RNA transcripts requires the assistance of nuclear-encoded splicing factors. Maturase (nMAT) is one such factor, as its three homologs (nMAT1, 2 and 4) have been identified as being required for the splicing of various mitochondrial introns in Arabidopsis. However, the function of nMAT in maize (Zea mays L.) is unknown. In this study, we identified a seed development mutant, empty pericarp 2441 (emp2441) from maize, which showed severely arrested embryogenesis and endosperm development. Positional cloning and transgenic complementation assays revealed that Emp2441 encodes a maturase-related protein, ZmnMAT3. ZmnMAT3 is highly expressed during seed development and its protein locates to the mitochondria. The loss of function of ZmnMAT3 resulted in the reduced splicing efficiency of various mitochondrial group II introns, particularly of the trans -splicing of nad1 introns 1, 3 and 4, which consequently abolished the transcript of nad1 and severely impaired the assembly and activity of mitochondrial complex I. Moreover, the Zmnmat3 mutant showed defective mitochondrial structure and exhibited expression and activity of alternative oxidases. These results indicate that ZmnMAT3 is essential for mitochondrial complex I assembly during kernel development in maize. [ABSTRACT FROM AUTHOR]
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- 2021
- Full Text
- View/download PDF
29. Studies of anticancer activity in vivo and in vitro behaviors of liposomes encapsulated iridium(III) complex.
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Gu, Yiying, Wen, Haoyu, Zhang, Yuanyuan, Bai, Lan, Zhou, Yi, Zhang, Huiwen, Tian, Li, Hao, Jing, and Liu, Yunjun
- Subjects
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LIPOSOMES , *INTRACELLULAR calcium , *BCL-2 proteins , *IRIDIUM , *MITOCHONDRIAL membranes , *MEMBRANE potential , *CYTOCHROME c - Abstract
Iridium(III) complexes have gained great attention in cancer treatment in recent years. In this paper, we designed and synthesized a new iridium(III) complex [Ir(piq)2(DQTT)](PF6) Ir1 (piq = 1-phenylisoquinoline, DQTT = 12-(1,4-dihydroquinoxalin-6-yl)-4,5,9,14-tetraazabenzo[b]triphenylene). The Ir1-loaded PEGylated liposomes (Lipo-Ir1) were prepared using the ethanol injection method. The anticancer activity of the complex and Lipo-Ir1 against SGC-7901 (human gastric adenocarcinoma), A549 (human lung carcinoma), HeLa (human cervical carcinoma), HepG2 (human hepatocellular carcinoma), BEL-7402 (human hepatocellular carcinoma), and normal NIH3T3 (mouse embryonic fibroblasts) was tested by the MTT method. The complex Ir1 shows moderate or low cytotoxicity against the selected cancer cells, whereas the Lipo-Ir1 exhibits high anticancer activity toward the same cancer cells. The apoptosis induced by Lipo-Ir1 was assayed by flow cytometry and Lipo-Ir1 induced apoptosis through increasing intracellular reactive-oxygen species levels, decreasing mitochondrial membrane potential, further promoting cytochrome c release and causing the increase of level of intracellular Ca2+. Western blot was used to detect the changes in Bcl-2 family protein and PI3K/AKT pathway proteins. The cloning experiments demonstrated that the Lipo-Ir1 can effectively inhibit cell proliferation. In vivo experiments, Lipo-Ir1 inhibited tumor growth in xenograft nude mice, and the percentage of tumor growth inhibition in vivo was 75.70%. Overall, the liposomes Lipo-Ir1 exhibits higher anticancer activity than Ir1 under the same conditions. These results indicated that Lipo-Ir1 may be a valuable resource for cancer therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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30. Transcriptome analysis of leafy near‐isogenic lines provides molecular insights into floral transition in maize (Zea mays).
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Du, Xuemei, Wang, Xiaoli, Zhang, Jie, Zhen, Sihan, Liu, Yunjun, Fu, Junjie, Wang, Jianhua, Gu, Riliang, Wang, Guoying, and Tuberosa, Roberto
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CORN , *CLOCK genes , *CIRCADIAN rhythms , *FLOWERING time , *FUNCTIONAL analysis , *MOLECULAR clock , *INSIGHT , *PHENOTYPES - Abstract
Leafy (Lfy1) is a typical late‐flowering mutant with locus being fine‐mapped, but its underlying molecular mechanism is unknown. In this study, two near‐isogenic lines, with and without the Lfy1 locus, were developed for phenotypic and transcriptional analysis of Lfy1‐mediated floral transition. Phenotypic observation showed that wild‐type (WT) plants transited into the tassel primordium at the V6 (6 expanded leaves) stage, whereas the Lfy1 mutant maintained the vegetative stage up to the V9 stage. Transcriptome analysis of shoot tips of both lines revealed more differentially expressed genes (DEGs) at the V5 (394) than the V3 stage (227). Functional enrichment analysis showed that circadian clock pathway genes exhibited lower expression levels in the Lfy1 mutant than in the WT at the V5 stage. A few integrator genes that functioned as downstream regulators of circadian clock genes also showed a lower transcript abundance in mutant lines, suggesting that the Lfy1‐mediated late‐flowering phenotype was partially caused by inefficient expression of circadian clock pathway genes. These results provide molecular clues for the late‐flowering phenotype of the Lfy1 mutant. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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31. Global Profiling of Alternative Splicing in Callus Induction of Immature Maize Embryo.
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Du, Xuemei, Fang, Ting, Liu, Yan, Huang, Liying, Wang, Xiaoli, Zhang, Jie, Cui, Yangbo, Zang, Maosen, Wang, Guoying, Fu, Junjie, and Liu, Yunjun
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RNA splicing , *CALLUS , *SOMATIC embryogenesis , *PLURIPOTENT stem cells , *GREEN'S functions , *CORN , *NUCLEOTIDE sequence - Abstract
Callus induction in plants is similar to pluripotent stem cell induction in animals and can incite global changes in gene expression. Alternative splicing is considered a key factor underlying functional complexity and function in the induction of pluripotent stem cells in animals. However, the role of alternative splicing in plant callus induction remains unclear. We performed high-throughput RNA sequencing of maize callus induced on a callus induction medium (CIM) at different stages and recorded global alternative splicing changes. At every stage, over 20,000 alternative splicing events were detected, and the numbers slightly increased with callus induction. In total, 648 to 2580 genes were found to exhibit significant alternative splicing changes during callus induction—mainly those that belong to the spliceosome, metabolic pathways, and mRNA surveillance pathways. It was also found that alternative splicing can function alongside transcriptional regulation to contribute to callus induction. Especially, ZmWOX11, whose orthologous gene in Arabidopsis plays a vital role in the first-step cell fate transition of callus induction, was found to exhibit alternative splicing and expression level changes during callus induction. Our results establish a foundation from which researchers can further explore the molecular mechanism of callus induction in maize, especially at alternative splicing level. [ABSTRACT FROM AUTHOR]
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- 2020
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32. Maize Empty Pericarp602 Encodes a P-Type PPR Protein That Is Essential for Seed Development.
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Ren, Zhenjing, Fan, Kaijian, Fang, Ting, Zhang, Jiaojiao, Yang, Li, Wang, Jianhua, Wang, Guoying, and Liu, Yunjun
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RNA splicing , *SEED development , *CORN seeds , *PROTEINS , *CORN - Abstract
Pentatricopeptide repeat (PPR) proteins play crucial roles in intron splicing, which is important for RNA maturation. Identification of novel PPR protein with the function of intron splicing would help to understand the RNA splicing mechanism. In this study, we identified the maize empty pericarp602 (emp602) mutants, the mature kernels of which showed empty pericarp phenotype. We cloned the Emp602 gene from emp602 mutants and revealed that Emp602 encodes a mitochondrial-localized P-type PPR protein. We further revealed that Emp602 is specific for the cis -splicing of mitochondrial Nad4 intron 1 and intron 3, and mutation of Emp602 led to the loss of mature Nad4 transcripts. The loss of function of Emp602 nearly damaged the assembly and accumulation of complex I and arrested mitochondria formation, which arrested the seed development. The failed assembly of complex I triggers significant upregulation of Aox expression in emp602 mutants. Transcriptome analysis showed that the expression of mitochondrial-related genes, e.g. the genes associated with mitochondrial inner membrane presequence translocase complex and electron carrier activity, were extensively upregulated in emp602 mutant. These results demonstrate that EMP602 functions in the splicing of Nad4 intron 1 and intron 3, and the loss of function of Emp602 arrested maize seed development by disrupting the mitochondria complex I assembly. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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33. Synthesis, characterization, molecular docking, RNA-sequence and anticancer efficacy evaluation in vitro of ruthenium(II) complexes on B16 cells.
- Author
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Huang, Chunxia, Zhang, Huiwen, Yang, Yan, Liu, Haimei, Chen, Jing, Wang, Yi, Liang, Lijuan, Hu, Huiyan, and Liu, Yunjun
- Subjects
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BCL-2 proteins , *MOLECULAR docking , *LIGANDS (Biochemistry) , *RUTHENIUM , *ANTINEOPLASTIC agents , *RUTHENIUM compounds , *INHIBITION of cellular proliferation - Abstract
In recent years, the studies of the ruthenium(II) complexes on anticancer activity have been paid great attention, many Ru(II) complexes possess high anticancer efficiency. In this paper, three ligands CPIP (2-(4-chlorophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline), DCPIP (2-(3,4-dichlorophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline), TCPIP (2-(2,3,5-trichlorophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline) and their three ruthenium (II) complexes [Ru(dip) 2 (CPIP)](PF 6) 2 (1 , dip = 4,7-diphenyl-1,10-phenanthroline), [Ru(dip) 2 (DCPIP)](PF 6) 2 (2) and [Ru(dip) 2 (TCPIP)](PF 6) 2 (3) were synthesized and characterized. 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assay was used to investigate in vitro cytotoxicity of complexes against various cancer cells. The results showed that complexes 1 – 3 exhibited pronounced cytotoxic effect on B16 cells with low IC 50 values of 7.2 ± 0.1, 11.7 ± 0.6 and 1.2 ± 0.2 μM, respectively. The 3D model demonstrated that the complexes can validly prevent the cell proliferation. Apoptosis determined using Annexin V-FITC/PI double staining revealed that complexes 1 – 3 can effectively induce apoptosis in B16 cells. The intracellular localization of 1 – 3 in the mitochondria, the levels of intracellular reactive oxygen species (ROS), the opening of mitochondrial permeability transition pore as well as the decline of mitochondrial membrane potential were investigated, which demonstrated that the complexes 1 – 3 led to apoptosis via a ROS-mediated mitochondrial dysfunction pathway. The RNA-sequence indicated that the complexes upregulate the expression of 74 genes and downregulate the expression of 81 genes. The molecular docking showed that the complexes interact with the proteins through hydrogen bond, π-cation and π-π interaction. The results show that ruthenium(II) complexes 1 , 2 and 3 can block tumor cell growth and induce cell death through autophagy and ROS-mediated mitochondrial dysfunction pathways. Three new Ru(II) complexes were synthesized and characterized. The anticancer activity in vitro of the complexes against B16 cells were investigated. [Display omitted] • Three new iridium(III) complexes were synthesized and characterized. • The complexes can induce apoptosis and inhibit the cell proliferation at the S phase. • RNA-sequence demonstrate that complexes induce cell death via autophagy. • Molecular docking shows that complexes interact on protein by hydrogen bond, π-cation. • The complexes can regulate the expression of B-cell lymphoma-2 proteins. [ABSTRACT FROM AUTHOR]
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- 2023
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34. Significant increase of anticancer efficacy in vitro and in vivo of liposome entrapped ruthenium(II) polypyridyl complexes.
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Chen, Yichuan, Li, Wenlong, Yang, Yan, Zhong, Ruitong, Hu, Huiyan, Huang, Chunxia, Chen, Jing, Liang, Lijuan, and Liu, Yunjun
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LIPOSOMES , *CELL cycle , *ANTINEOPLASTIC agents , *CANCER cell proliferation , *WESTERN immunoblotting , *RUTHENIUM - Abstract
Two polypyridyl ruthenium(II) complexes [Ru(DIP) 2 (BIP)](PF 6) 2 (DIP = 4,7-diphenyl-1,10-phenanthrolie, BIP = 2-(1,1′-biphenyl-4-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline, Ru1) and [Ru(DIP) 2 (CBIP)](PF 6) 2 (CBIP = 2-(4′-chloro-1,1′-biphenyl-4-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline, Ru2) were synthesized. The cytotoxic activities in vitro of Ru1, Ru2 toward B16, A549, HepG2, SGC-7901, HeLa, BEL-7402, non-cancer LO2 were investigated using MTT method (3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide). Unexpectedly, Ru1, Ru2 can't prevent these cancer cells proliferation. To improve the anti-cancer effect, we used liposomes to entrap the complexes Ru1, Ru2 to form Ru1lipo, Ru2lipo. As expectation, Ru1lipo and Ru2lipo exhibit high anti-cancer efficacy, especially, Ru1lipo (IC 50 3.4 ± 0.1 μM), Ru2lipo (IC 50 3.5 ± 0.1 μM) display strong ability to block the cell proliferation in SGC-7901. The cell colony, wound healing, and cell cycle distribution show that the complexes can validly inhibit the cell growth at G2/M phase. Apoptotic studied with Annex V/PI doubling method showed that Ru1lipo and Ru2lipo can effectively induce apoptosis. Reactive oxygen species (ROS), malondialdehyde, glutathione and GPX4 demonstrate that Ru1lipo and Ru2lipo improve ROS and malondialdehyde levels, inhibit generation of glutathione, and finally result in a ferroptosis. Ru1lipo and Ru2lipo interact on the lysosomes and mitochondria and damage mitochondrial dysfunction. Additionally, Ru1lipo and Ru2lipo increase intracellular Ca2+ concentration and induce autophagy. The RNA-sequence and molecular docking were performed, the expression of Bcl-2 family was investigated by Western blot analysis. Antitumor in vivo experiments confirm that 1.23 mg/kg, 2.46 mg/kg of Ru1lipo possesses a high inhibitory rate of 53.53% and 72.90% to prevent tumor growth, hematoxylin-eosin (H&E) results show that Ru1lipo doesn't cause chronic organ damage and strongly promotes the necrosis of solid tumor. Taken together, we conclude that Ru1lipo and Ru2lipo cause cell death through the following pathways: autophagy, ferroptosis, ROS-regulated mitochondrial dysfunction, and blocking the PI3K/AKT/mTOR. Two new Ru(II) polypyridyl complexes [Ru(dip) 2 (BIP)](PF 6) 2 (dip = 4,7-diphenyl-1,10-phenanthrolie, BIP = 2-(1,1′-biphenyl-4-yl)-1 H -imidazo[4,5-f] [1,10]phenanthroline, Ru1) and [Ru(dip) 2 (CBIP)](PF 6) 2 (CBIP = 2-(4′-chloro-1,1′-biphenyl-4-yl)-1 H -imidazo[4,5-f] [1,10]phenanthroline, Ru2) and complexes-loaded liposomes Ru1lipo and Ru2lipo were synthesized and characterized. The cytotoxicity of the complexes Ru1, Ru2, Ru1lipo and Ru2lipo against B16, BEL-7402, A549, HepG2, SGC-7901 cancer cells and non-cancer cell LO2 was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The high inhibitory rate in vivo of Ru1lipo inhibiting SGC-7901 tumor growth reaches 72.90%. [Display omitted] • Two new Ru(II) polypyridyl complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes and liposomes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were performed. • RNA-sequence assay was investigated. • The antitumor activity in vivo was investigated. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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35. QTG-Seq Accelerates QTL Fine Mapping through QTL Partitioning and Whole-Genome Sequencing of Bulked Segregant Samples.
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Zhang, Hongwei, Wang, Xi, Pan, Qingchun, Li, Pei, Liu, Yunjun, Lu, Xiaoduo, Zhong, Wanshun, Li, Minqi, Han, Linqian, Li, Juan, Wang, Pingxi, Li, Dongdong, Liu, Yan, Li, Qing, Yang, Fang, Zhang, Yuan-Ming, Wang, Guoying, and Li, Lin
- Abstract
Abstract Deciphering the genetic mechanisms underlying agronomic traits is of great importance for crop improvement. Most of these traits are controlled by multiple quantitative trait loci (QTLs), and identifying the underlying genes by conventional QTL fine-mapping is time-consuming and labor-intensive. Here, we devised a new method, named quantitative trait gene sequencing (QTG-seq), to accelerate QTL fine-mapping. QTG-seq combines QTL partitioning to convert a quantitative trait into a near-qualitative trait, sequencing of bulked segregant pools from a large segregating population, and the use of a robust new algorithm for identifying candidate genes. Using QTG-seq, we fine-mapped a plant-height QTL in maize (Zea mays L.), qPH7 , to a 300-kb genomic interval and verified that a gene encoding an NF-YC transcription factor was the functional gene. Functional analysis suggested that qPH7 -encoding protein might influence plant height by interacting with a CO-like protein and an AP2 domain-containing protein. Selection footprint analysis indicated that qPH7 was subject to strong selection during maize improvement. In summary, QTG-seq provides an efficient method for QTL fine-mapping in the era of "big data". QTG-seq was devised for rapid fine-mapping of QTL in plants. As a proof of concept, the robustness of QTG-seq was proved by successfully identifying the causal gene underlying a plant-height QTL, qPH7 , in maize. Furthermore, simulation analyses suggested that QTG-seq can be widely adopted for QTL fine-mapping in plants. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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36. Pyramiding of nine transgenes in maize generates high-level resistance against necrotrophic maize pathogens.
- Author
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Zhu, Xiang, Zhao, Jinfeng, Abbas, Hafiz Muhammad Khalid, Liu, Yunjun, Cheng, Menglan, Huang, Jue, Cheng, Wenjuan, Wang, Beibei, Bai, Cuiying, Wang, Guoying, and Dong, Wubei
- Subjects
- *
RHIZOCTONIA solani , *PLANT defenses , *TRANSGENIC plants , *BLIGHT diseases (Botany) , *PATHOGENIC microorganisms - Abstract
Abstract: Key message Nine transgenes from different categories, viz. plant defense response genes and anti-apoptosis genes, played combined roles in maize to inhibit the necrotrophic pathogensRhizoctonia solani andBipolaris maydis.Abstract: Maize sheath blight and southern corn leaf blight are major global threats to maize production. The management of these necrotrophic pathogens has encountered limited success due to the characteristics of their lifestyle. Here, we presented a transgenic pyramiding breeding strategy to achieve nine different resistance genes integrated in one transgenic maize line to combat different aspects of necrotrophic pathogens. These nine genes, selected from two different categories, plant defense response genes (Chi, Glu, Ace-AMP1, Tlp, Rs-AFP2, ZmPROPEP1 and Pti4), and anti-apoptosis genes (Iap and p35), were successfully transferred into maize and further implicated in resistance against the necrotrophic pathogens Rhizoctonia solani and Bipolaris maydis. Furthermore, the transgenic maize line 910, with high expression levels of the nine integrated genes, was selected from 49 lines. Under greenhouse and field trial conditions, line 910 showed significant resistance against maize sheath blight and southern corn leaf blight diseases. Higher-level resistance was obtained after the pyramiding of more resistance transgenes from different categories that function via different mechanisms. The present study provides a successful strategy for the management of necrotrophic pathogens. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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37. Synthesis, RNA-sequence and evaluation of anticancer efficacy of ruthenium(II) polypyridyl complexes toward HepG2 cells.
- Author
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Hu, Huiyan, Zhang, Huiwen, Zhong, Ruitong, Yang, Yan, Huang, Chunxia, Chen, Jing, Liang, Lijuan, Chen, Yichuan, and Liu, Yunjun
- Subjects
- *
RUTHENIUM compounds , *BCL-2 proteins , *LIGANDS (Biochemistry) , *ANTINEOPLASTIC agents , *CELL cycle , *RUTHENIUM , *CELL death - Abstract
In this article, four new Ru(II) complexes [Ru(dmbpy) 2 (TFBIP)](PF 6) 2 (dmbpy = 4,4′-dimethyl-2,2′-bipyridine, TFPIP = 2-(4′-trifluoromethyl)-[1,1′-biphenyl]-4-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline) (Ru1), [Ru(bpy) 2 (TFBIP)](PF 6) 2 (bpy = 2,2′-bipyridine) (Ru2), [Ru(phen) 2 (TFBIP)](PF 6) 2 (phen = 1,10-phenanthroline) (Ru3) and [Ru(dmp) 2 (TFBIP)](PF 6) 2 (dmp = 2,9-dimethyl-1,10-phenanthroline) (Ru4) were synthesized and characterized by elemental analysis, HRMS, IR, 1H NMR, 13C NMR and 19F NMR. The in vitro anticancer effect of the complexes on HepG2, A549, B16, HeLa, BEL-7402 and non-cancer LO2 cells was screened using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results illustrate that the complexes display moderate anticancer activity. Apoptotic assay with Annexin V/PI double staining method indicated that complexes induce apoptosis in HepG2 cells. Also, the complexes interfere with the mitochondrial functions, accompanied by the production of intracellular ROS as well as a reduction of mitochondrial membrane potential. The results obtained from the western blot demonstrated that the complexes upregulate pro-apoptotic Bax and downregulate anti-apoptotic Bcl-2, which further activates caspase 3 and promotes the cleavage of PARP. RNA-sequence showed that the complexes upregulate the expression of 40 genes and downregulate 66 genes. Antitumour in vivo demonstrated that Ru1 inhibits the tumor growth with a high inhibitory rate of 51.19%. Taken together, these results revealed that complexes Ru1 , Ru2 , Ru3 and Ru4 induce cell death in HepG2 cells via autophagy and a ROS-mediated mitochondrial apoptotic pathway. Four new Ru(II) complexes were synthesized and characterized. The anticancer activity of the complexes against HepG2 cells were investigated, the complexes display high antitumour efficacy in vivo. [Display omitted] • Four new Ru(II) complex were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were detected. • The RNA-sequence was determined. • The expression of B-cell lymphoma-2 family proteins was examined. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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38. Iridium(III) complexes inhibit the proliferation and migration of BEL-7402 cells through the PI3K/AKT/mTOR signaling pathway.
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Chen, Jing, Liu, Haimei, Chen, Yichuan, Hu, Huiyan, Huang, Chunxia, Wang, Yi, Liang, Lijuan, and Liu, Yunjun
- Subjects
- *
BCL-2 proteins , *CELL migration , *IRIDIUM , *PROTEIN kinase B , *CELLULAR signal transduction , *RAPAMYCIN , *LIGANDS (Biochemistry) - Abstract
Iridium(III) complexes are largely studied as anti-cancer complexes due to their excellent anti-cancer activity. In this article, two new iridium(III) complexes [Ir(piq) 2 (THPIP)]PF 6 (THPIP = 2,4-di-tert-butyl-6-(1 H -imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol, piq = deprotonated 1-phenylisoquinoline) (Ir1) and [Ir(bzq) 2 (THPIP)]PF 6 (bzq = deprotonated benzo[ h ]quinolone) (Ir2) were synthesized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that complex Ir1 exhibits moderate activity (IC 50 = 29.9 ± 4.6 μM) and Ir2 shows high cytotoxicity (IC 50 = 9.8 ± 1.8 μM) against BEL-7402 cells. Further studies on the mechanism showed that Ir1 and Ir2 induced apoptosis by changing the mitochondrial membrane potential, Ca2+ release, ROS accumulation, and cell cycle arrest at the S phase. The complexes can effectively inhibit cell colony formation and migration. The expression of B-cell lymphoma-2 (Bcl-2) family proteins, PI3K (phosphatidylinositol 3-kinase), AKT (protein kinase B), mTOR (mammalian target of rapamycin), and p-mTOR was studied by immunoblotting. Complexes Ir1 and Ir2 downregulated the expression of anti-apoptotic protein Bcl-2 and increased the expression of autophagy-related proteins of Beclin-1 and LC3-II. Further experiments showed that the complexes inhibited the production of glutathione (GSH) and increased the amounts of malondialdehyde (MDA). Fluorescence of HMGB1 was significantly increased. We also investigated the effect of the complexes on the expression of genes using RNA-sequence analysis, we further calculated the lowest binding energies between the complexes and proteins using molecular docking. Taken together, the above results indicated that complexes Ir1 and Ir2 induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondrial dysfunction and inhibition of the PI3K/AKT/mTOR signaling pathway. Two new iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes against BEL-7402 cells were studied, the complexes display high anticancer activity toward BEL-7402 cells. [Display omitted] • Two new iridium(III) complex was synthesized and characterized. • The cytotoxicity in vitro of the complexes was studied. • Apoptosis, reactive oxygen species and cell cycle arrest were carried out. • The RNA-sequence was assayed. • The expression of B-cell lymphoma-2 family proteins was examined. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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39. Design, synthesis and biological evaluation of liposome entrapped iridium(III) complexes toward SGC-7901 cells.
- Author
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Chen, Yichuan, Gu, Yiying, Hu, Huiyan, Liu, Haimei, Li, Wenlong, Huang, Chunxia, Chen, Jing, Liang, Lijuan, and Liu, Yunjun
- Subjects
- *
BIOSYNTHESIS , *BCL-2 proteins , *LIPOSOMES , *HEAT shock proteins , *POLY(ADP-ribose) polymerase , *IRIDIUM , *CYTOCHROME c - Abstract
In this study, two new iridium(III) polypyridyl complexes [Ir(bzq) 2 (DIPH)](PF 6) (bzq = deprotonated benzo[ h ]quinoline, DIPH = 4-(2,5-dibromo-4-(1 H -imidazo[4,5-f][1,10]phenanthrolim-2-yl)-4-hydroxybutan-2-one) (Ir1) and [Ir(piq) 2 (DIPH)](PF 6) (piq = deprotonated 1-phenylisoquinoline) (Ir2) were synthesized and characterized by elemental analysis, HRMS, 1H and 13C NMR. The cytotoxic activity of Ir1 , Ir2 , Ir1lipo and Ir2lipo against cancer cells SGC-7901, HepG2, A549, HeLa, B16 and normal NIH3T3 cells in vitro was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir1 and Ir2 showed no cytotoxic activity, but their liposome-entrapped Ir1 (Ir1lipo) and Ir2 (Ir2lipo) showed significant cellular activity, especially sensitive to SGC-7901 with IC 50 values of 4.7 ± 0.2 and 12.4 ± 0.5 μM, respectively. The cellular uptake, endoplasmic reticulum (ER) localization, autophagy, tubulin polymerization, glutathione (GSH), malondialdehyde (MDA) and release of cytochrome c were investigated to explore the mechanisms of apoptosis. The calreticulin (CRT), heat shock protein 70 (HSP70), high mobility group box 1 (HMGB1) were also explored. Western blotting showed that Ir1lipo and Ir2lipo inhibited PI3K (phosphoinositide-3 kinase), AKT (protein kinase B), p-AKT and activated Bcl-2 (B-cell lymphoma-2) protein and apoptosis-regulated factor caspase 3 (cysteinyl aspartate specific proteinase-3) and cleaving PARP (poly ADP-ribose polymerase). The results demonstrated that Ir1lipo and Ir2lipo induce cell apoptosis through targeting the endoplasmic reticulum (ER), cause oxidative stress damage, inhibiting PI3K/AKT signaling pathway, immunogenic cell death (ICD) and inhibit the cell growth at G2/M phase. Two new iridium(III) complexes were synthesized and characterized. The anticancer activity of the liposome-entrapped complexes against SGC-7901 cells were investigated, the liposome-entrapped complexes exhibit high anticancer activity toward SGC-7901 cells. [Display omitted] • Two iridium(III) complexes and liposomes was synthesized and characterized. • The cytotoxicity of the complexes and their liposomes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were carried out. • The immunogenic cell death and molecular docking were performed. • The expression of B-cell lymphoma-2 family proteins was examined. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
40. Synthesis, biological evaluation of novel iridium(III) complexes targeting mitochondria toward melanoma B16 cells.
- Author
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Yuan, Yuhan, Zhang, Yuanyuan, Chen, Jing, Huang, Chunxia, Liu, Haimei, Li, Wenlong, Liang, Lijuan, Wang, Yi, and Liu, Yunjun
- Subjects
- *
IRIDIUM , *MELANOGENESIS , *MITOCHONDRIA , *CELL cycle , *REACTIVE oxygen species , *MITOCHONDRIAL membranes - Abstract
A new ligand 2-(1 E ,3 E ,5 E ,7 E)-2,6-dimethyl-8-(2,6,6-trimethylcyclohex-1-yl)octa-1,2,5,7-tetraen-1-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline (DTOIP) was synthesized and combined with [Ir(ppy) 2 Cl] 2 ·2H 2 O (ppy = deprotonated Hppy: 2-phenylpyridine), [Ir(piq) 2 Cl] 2 ·2H 2 O (piq = deprotonated Hpiq: 1-phenylisoquinoline) and [Ir(bzq) 2 Cl] 2 ·2H 2 O (bzq = deprotonated Hbzq: benzo[h]quinolone) to form [Ir(ppy) 2 (DTOIP)](PF 6) (Ir1), [Ir(piq) 2 (DTOIP)](PF 6) (Ir2), and [Ir(bzq) 2 (DTOIP)](PF 6) (Ir3), respectively. The complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRMS), 1H NMR and 13C NMR. The antiproliferative activity of the complexes toward B16, BEL-7402, Eca-109 and normal LO2 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Complexes Ir1 , Ir2 and Ir3 showed high antiproliferative activity against B16 cells with a low IC 50 values of 0.4 ± 0.1, 2.0 ± 0.1 and 1.4 ± 0.09 μM, respectively. Three-dimensional (3D) in vitro cell models also demonstrated that the iridium(III) complexes have a remarkable cytotoxicity to B16 cells. The experiments of cellular uptake, mitochondrial localization, and intracellular distribution of the drugs proved that the three iridium(III) complexes can enter the mitochondria, leading to the loss of mitochondrial membrane potential (MMP), decreased glutathione (GSH) levels, causing an increase of intracellular ROS content, and DNA damage, finally inducing apoptosis. RNA-sequence and bioinformatics analyses were used to analyze the differentially expressed genes and enriched biology processes. Antitumor in vivo demonstrated that complex Ir1 (5 mg/kg) exhibits a high efficacy to inhibit the tumor growth with an inhibitory rate of 71.67%. These results show that the complexes may be potent anticancer candidate drugs. Three new iridium(III) complexes [Ir(ppy) 2 (DTOIP)](PF 6) (Ir1) (DTOIP = 2-(1 E ,3 E ,5 E ,7 E)-2,6-dimethyl-8-(2,6,6-trimethylcyclohex-1-yl)octa-1,2,5,7-tetraen-1-yl)-1 H -imidazo[4,5-f][1,10]phenanthroline, ppy = deprotonated 2-phenylpyridine), [Ir(piq) 2 (DTOIP)](PF 6) (Ir2) (piq = deprotonated 1-phenylisoquinoline) and [Ir(bzq) 2 (DTOIP)](PF 6) (Ir3) (bzq = deprotonated benzo[h]quinolone) were synthesized. The cytotoxicity of the complexes against B16, BEL-7402, A549, Eca-109 cancer cells and normal LO2 was evaluated using 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The inhibitory rate in vivo reaches 71.67% for Ir1. [Display omitted] • Three new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was investigated. • Apoptosis, reactive oxygen species and cell cycle arrest were carried out. • The distribution of the complexes in the cytoplasm, mitochondria and nuclei were explored. • The antitumor efficacy in vivo was investigated. [ABSTRACT FROM AUTHOR]
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- 2023
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41. Characterization of maize male sterile 2 mutant by phenotypic and RNA sequencing analyses.
- Author
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Kang, Dan, Wang, Cuiyun, Xu, Qilong, Wang, Guoying, Liu, Yunjun, and Lübberstedt, T.
- Subjects
- *
MALE sterility in plants , *HYBRID corn , *RNA sequencing , *PLANT genes ,CORN genetics - Abstract
Male sterility plays an important role in the hybrid seed production. Elucidation of the mechanism of male sterility will provide useful information for the usage of male sterility. In this study, we performed detailed phenotypic analysis of ms2 mutant, and the results showed that ms2 anthers are defects in synthesis and transportation of lipophilic molecules. To investigate the defects of transcriptome of ms2 anthers, 1.5, 2.5 and 3.5 mm anthers were sampled, respectively. Among the 23 037 expressed transcripts at 1.5 mm stage, only 15 genes were differentially expressed between fertile siblings and ms2 mutant. Compared to the fewer detected differentially expressed genes (DEGs) at 1.5 mm stage, 950 DEGs and 2212 DEGs between the fertile siblings and ms2 anthers were detected at 2.5 mm and 3.5 mm stages. These differentially expressed genes (DEGs) were mainly enriched in the secondary metabolism and lipid metabolism pathways. A series of genes related to the long-chain fatty acids metabolism process were changed in ms2 mutant compared with the fertile siblings. The results in this study provide useful information on the mechanism of male sterility in ms2 mutant. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
42. Mutations in the maize zeta-carotene desaturase gene lead to viviparous kernel.
- Author
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Chen, Yan, Li, Jiankun, Fan, Kaijian, Du, Yicong, Ren, Zhenjing, Xu, Jing, Zheng, Jun, Liu, Yunjun, Fu, Junjie, Ren, Dongtao, and Wang, Guoying
- Subjects
- *
CORN quality , *GENETIC mutation , *DESATURASES , *CAROTENES , *CORN yields - Abstract
Preharvest sprouting reduces the maize quality and causes a significant yield loss in maize production. vp-wl2 is a Mutator (Mu)-induced viviparous mutant in maize, causing white or pale yellow kernels, dramatically reduced carotenoid and ABA content, and a high level of zeta-carotene accumulation. Here, we reported the cloning of the vp-wl2 gene using a modified digestion-ligation-amplification method (DLA). The results showed that an insertion of Mu9 in the first intron of the zeta-carotene desaturase (ZDS) gene results in the vp-wl2 mutation. Previous studies have suggested that ZDS is likely the structural gene of the viviparous9 (vp9) locus. Therefore, we performed an allelic test using vp-wl2 and three vp9 mutants. The results showed that vp-wl2 is a novel allele of the vp9 locus. In addition, the sequences of ZDS gene were identified in these three vp9 alleles. The vp-wl2 mutant gene was subsequently introgressed into four maize inbred lines, and a viviparous phenotype was observed with yield losses from 7.69% to 13.33%. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
43. The U6 Biogenesis-Like 1 Plays an Important Role in Maize Kernel and Seedling Development by Affecting the 3′ End Processing of U6 snRNA.
- Author
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Li, Jiankun, Fu, Junjie, Chen, Yan, Fan, Kaijian, He, Cheng, Zhang, Zhiqiang, Li, Li, Liu, Yunjun, Zheng, Jun, Ren, Dongtao, and Wang, Guoying
- Abstract
Regulation of gene expression at the post-transcriptional level is of crucial importance in the development of an organism. Here we present the characterization of a maize gene, U6 biogenesis-like 1 ( UBL1 ), which plays an important role in kernel and seedling development by influencing pre-mRNA splicing. The ubl1 mutant, exhibiting small kernel and weak seedling, was isolated from a Mutator -tagged population. Transgenic complementation and three independent mutant alleles confirmed that UBL1 , which encodes a putative RNA exonuclease belonging to the 2H phosphodiesterase superfamily, is responsible for the phenotype of ubl1 . We demonstrated that UBL1 possess the RNA exonuclease activity in vitro and found that loss of UBL1 function in ubl1 causes decreased level and abnormal 3′ end constitution of snRNA U6, resulting in splicing defect of mRNAs. Through the in vitro and in vivo studies replacing two histidines with alanines in the H-X-T/S-X (X is a hydrophobic residue) motifs we demonstrated that these two motifs are essential for the normal function of UBL1. We further showed that the function of UBL1 may be conserved across a wide phylogenetic distance as the heterologous expression of maize UBL1 could complement the Arabidopsis ubl1 mutant. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
44. Anticancer effect evaluation of iridium(III) complexes targeting mitochondria and endoplasmic reticulum.
- Author
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Wang, Yi, Li, Yizhen, Chen, Ju, Liu, Haimei, Zhou, Yi, Huang, Chunxia, Liang, Lijuan, Liu, Yunjun, and Wang, Xiuzhen
- Subjects
- *
ENDOPLASMIC reticulum , *ANTIBODY-dependent cell cytotoxicity , *BCL-2 proteins , *IRIDIUM , *ANTINEOPLASTIC agents , *CELL cycle , *WOUND healing , *CELL death - Abstract
Ligand HMSPIP (2-(4-(methylsulfonyl)phenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline) and its iridium(III) complexes [Ir(ppy) 2 (HMSPIP)]PF 6 (ppy = 2-phenylpyridine, Ir1) and [Ir(bzq) 2 (HMSPIP)]PF 6 (bzq = benzo[ h ]quinoline, Ir2) were synthesized. The complexes were characterized by 1H NMR, 13C NMR, and UV/Vis spectra. The cytotoxicity of the complexes toward cancer cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, the scratch wound healing and colony-forming were also investigated. MTT assay certificated that the complexes show high toxic effect on the HeLa cells. The cell cycle assay illustrated that the complexes blocked cell growth at G 0 /G 1 phase in HeLa cells. A series of subsequent experiments showed that the complexes first enter the endoplasmic reticulum (ER) and then enter the mitochondria, leading to an increase in intracellular Ca2+ and reactive oxygen species (ROS) content, depolarizing mitochondrial membrane potential (MMP), and ultimately resulting in apoptosis. In addition, the experimental results revealed that the complexes not only increase the level of ROS but also inhibit the production of GSH and eventually produce large amounts of MDA and further leading to cell death. Taken together, we consider that the complexes can be used as potential candidate drugs for HeLa cancer treatment. [Display omitted] • Two new iridium(III) complex was synthesized and characterized. • The cytotoxicity in vitro of the complexes was studied. • Apoptosis, reactive oxygen species and cell cycle arrest were carried out. • The location and mitochondrial membrane potential were investigated. • The expression of B-cell lymphoma-2 family proteins was examined. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
45. Development of monoclonal antibody-based sensitive ELISA for the determination of Cry1Ie protein in transgenic plant.
- Author
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Zhang, Yuwen, Zhang, Wei, Liu, Yan, Wang, Jianhua, Wang, Guoying, and Liu, Yunjun
- Subjects
- *
BACILLUS thuringiensis , *TRANSGENIC plants , *ENZYME-linked immunosorbent assay , *BIOLOGICAL assay , *OSTRINIA furnacalis - Abstract
Cry1Ie is a kind of Bacillus thuringiensis (Bt) toxin protein which has a different action model than the Cry1Ab and Cry1Ac protein. The transgenic maize expressing Cry1Ie might be commercially used in the near future and it is urgent to develop a method to detect Cry1Ie protein in transgenic plants and their products. To develop an ELISA method, Cry1Ie protein was expressed in Escherichia coli strain Transetta DE3, purified with the Ni-NTA spin columns, and then validated by sequencing. Bioassay results showed that the purified Cry1Ie protein was highly toxic to the Asian corn borer. The polyclonal antibody (pAb) and the specific monoclonal antibody (mAb) 1G2D were generated from rabbit and mice which were immunized with Cry1Ie protein, respectively. Western blotting of crude Cry1Ie protein extracts was established by employing mAb 1G2D, whereas the mAb 1G2D negligibly recognized other Bt proteins. Sandwich ELISA against Cry1Ie protein was established by coating with pAb and detecting with mAb 1G2D. The limit of detection (LOD), the limit of quantification (LOQ), and the quantification range of the assay in different matrices of maize plant were determined as 0.27-0.51, 0.29-0.78, and 0.45-15.71 ng/mL, respectively. Recoveries of Cry1Ie protein spiked in different maize tissues ranged from 75.1 to 99.5 %. The established sandwich ELISA was verified using transgenic maize overexpressing Cry1Ie. The results in this study suggested that the established ELISA method is effective for detecting Cry1Ie protein in transgenic plants. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
46. Polyhydric Corrole and Its Gallium Complex: Synthesis, DNA-binding Properties and Photodynamic Activities.
- Author
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Liang, Zhenhua, Liu, Haiyang, Jiang, Guangbin, Wen, Jinyan, Liu, Yunjun, and Xiao, Xinyan
- Subjects
- *
HYDROPHILIC compounds , *GALLIUM , *MOLECULAR structure of DNA-binding proteins , *PHOTODYNAMIC therapy , *TUMORS , *PHOTOSENSITIZERS , *ANTINEOPLASTIC agents - Abstract
A new hydrophilic polyhydric corrole ( 1) and its Ga(III) complex ( 1-Ga) were synthesized and characterized. Corroles 1 and 1-Ga bind to calf thymus DNA externally and exhibit remarkable photonuclease-like activity. Singlet oxygen (1O2) was identified as the reactive oxygen species involved. These corroles also exhibit significant photocytotoxicity against HeLa, A549, BEL-7402 and HepG2 tumor cell lines. They mainly accumulated in the nuclei of tumor cells. ROS-mediated mitochondrial damage and intracellular DNA disintegration contributed to the observed photodynamic activity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
47. Astragaloside IV alleviates E. coli-caused peritonitis via upregulation of neutrophil influx to the site of infection.
- Author
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Huang, Ping, Lu, Xiaoyan, Yuan, Baohong, Liu, Tao, Dai, Liangcheng, Liu, Yunjun, and Yin, Hui
- Subjects
- *
PERITONITIS , *NEUTROPHIL immunology , *TOLL-like receptors , *G protein coupled receptors , *SAPONINS , *ANTIBACTERIAL agents , *GENE expression , *THERAPEUTICS - Abstract
Astragaloside IV (AS-IV), an active saponin purified from Astragali Radix, has been identified with broad biological and pharmacological activities. In the present study, we continue to explore the potential effect of AS-IV on antibacterial response using an acute E. coli peritoneal infection model. Our findings implied that administration of AS-IV decreases mortality in mice challenged by lethal E. coli infection. The protection of AS-IV was related to promotion of neutrophil extravasation into the peritoneum and bacterial clearance. Toll-like receptor (TLR) activation in neutrophils has been reported to reduce CXCR2 expression and subsequent neutrophil migration. Our data indicated that AS-IV prevented the reduction of CXCR2 expression and neutrophil migration induced by LPS, the activator for TLR4. Moreover, we found that AS-IV blocks LPS-induced suppression of CXCR2 on neutrophils by inhibiting the expression of G protein-coupled receptor kinase-2 (GRK2), an agonist that regulates desensitization and internalization of chemokine receptors. Taken together, these data propose that AS-IV, through modulating GRK2-CXCR2 signal in neutrophils, offers an essential efficacy on host antibacterial immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
48. Light activation of iridium(III) complexes driving ROS production and DNA damage enhances anticancer activity in A549 cells.
- Author
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Li, Wenlong, Shi, Chuanling, Wu, Xiaoyun, Zhang, Yuanyuan, Liu, Haimei, Wang, Xiuzhen, Huang, Chunxia, Liang, Lijuan, and Liu, Yunjun
- Subjects
- *
BCL-2 proteins , *DNA damage , *IRIDIUM , *HEAT shock proteins , *CELL death , *CELL cycle , *ENDOPLASMIC reticulum - Abstract
The work aimed to synthesize and characterize two iridium(III) complexes [Ir(ppy) 2 (IPPH)](PF 6) (Ir1 , IPPH = (2 S ,3 R ,5 S ,6 R)-2-(2-(1 H -imidazo[4,5- f ][1,10]phenanthrolin-2-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2 H -pyran-3,4,5-triol, ppy = 2-phenylpyridine), [Ir(piq) 2 (IPPH)](PF 6) (Ir2 , piq = 1-phenylisoquinoline). The cytotoxicity of the complexes against BEL-7402, A549, HCT-116, B16 cancer cells and normal LO2 was evaluated through 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. The complexes show no cytotoxic activity (IC 50 > 100 μM) against these cancer cells, while their cytotoxicity can significantly be elevated upon illumination. The IC 50 values range from 0.2 ± 0.05 to 35.5 ± 3.5 μM. The cellular uptake, endoplasmic reticulum and mitochondria localization, reactive oxygen species, the change of mitochondrial membrane potential, γ-H2AX levels, cycle arrest, apoptosis and the expression of B-cell lymphoma-2 were investigated. The calreticulin (CRT), heat shock protein 70 (HSP70), high mobility group box 1 (HMGB1) were explored. This study demonstrates that photoactivatable complexes induce cell death in A549 through ROS-mediated endoplasmic reticulum stress-mitochondrial pathway, DNA damage pathways, immunogenic cell death (ICD), activation of PI3K/AKT signaling pathway and inhibit the cell growth at S phase. Two new iridium(III) complexes [Ir(ppy) 2 (IPPH)](PF 6) (IPPH = (2 S ,3 R ,5 S ,6 R)-2-(2-(1 H -imidazo[4,5- f ][1,10]phenanthrolin-2-yl)phenoxy)-6-(hydroxymethyl)tetrahydro-2 H -pyran-3,4,5-triol, ppy = 2-phenylpyridine), [Ir(piq) 2 (IPPH)](PF 6) (piq = 1-phenylisoquinoline) were synthesized. The cytotoxicity of the complexes against BEL-7402, A549, HCT-116, B16 cancer cells and normal LO2 was evaluated through 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method in the absence and presence of white irradiation. [Display omitted] • Two new iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro of the complexes toward A549 cells was studied. • The apoptosis and cell cycle arrest were performed. • Location of complexes at the endoplasm reticulum and mitochondria was investigated. • The expression of B-cell lymphoma-2 family proteins was explored. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. Synthesis and characterization of polypyridine ruthenium(II) complexes and anticancer efficacy studies in vivo and in vitro.
- Author
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Liang, Lijuan, Wu, Xiaoyun, Shi, Chuanling, Wen, Haoyu, Wu, Shouhai, Chen, Jing, Huang, Chunxia, Wang, Yi, and Liu, Yunjun
- Subjects
- *
RUTHENIUM compounds , *BCL-2 proteins , *ADP-ribosylation , *ANTINEOPLASTIC agents , *CELL migration , *RUTHENIUM , *CELL cycle - Abstract
In this article, ligand IPP (IPP = 4-(1 H -imidazo[4,5-f][1,10]phenanthrolin-2-yl)- N , N -diphenylaniline) and its three Ru(II) complexes: [Ru(bpy) 2 (IPP)](ClO 4) 2 (1) (bpy = 2,2′-bipyridine), [Ru(dmbpy) 2 (IPP)](ClO 4) 2 (2) (dmbpy = 4,4′-dimethyl-2,2′-bipyridine), and [Ru(phen) 2 (IPP)](ClO 4) 2 (3) (phen = 1,10-phenanthroline) were synthesized and characterized. The anticancer activity in vitro of the complexes was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The scratching and colony-forming experiments confirmed the complexes 1 , 2 , 3 interfered with the proliferation and migration ability of cells. The accumulation of the complexes in cells was researched and we found that these complexes directly accumulated in mitochondria, then the complexes cause a decline of the mitochondrial membrane potential and induce an increase of intracellular reactive oxygen species (ROS) levels. The growth of B16 cells were inhibited by 1 , 2 and 3 at G0/G1 phase. Apoptosis was induced through mitochondrial pathway and the expression of apoptosis-related factors was regulated. In addition, the complexes promoted the transition of poly(ADP-ribose)polymerase (PARP) into the cleaved form (Cleaved PARP), downregulated the anti-apoptotic proteins, and upregulated the pro-apoptotic proteins. Consequently, complexes 1 , 2 and 3 exerted their anticancer activity by regulating B-cell lymphoma-2 (Bcl-2) family proteins. Complex 2 showed excellent antitumor effects with a high inhibitory rate of 65.95% in vivo. Taken together, the complexes cause apoptosis in B16 cells through a ROS-mediated mitochondrial dysfunction pathway. Three new Ru(II) complexes [Ru(N-N) 2 (IPP)](ClO 4) 2 (N-N: bpy = 2,2'-bipyridine 1 , dmbpy = 4,4'-dimethyl-2,2'-bipyridine 2 , phen = 1,10-phenanthroline 3 , IPP = 4-(1 H -imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline) were synthesized and characterized. The antitumor in vivo shows that the complex 2 can effectively inhibit the tumor growth with an inhibitory rate of 65.95%. [Display omitted] • Three new Ru(II) complexes were synthesized and characterized. • The cytotoxicity in vitro and in vivo of the complexes was investigated. • Apoptosis, reactive oxygen species, autophagy and cell cycle arrest were performed. • The location and mitochondrial membrane potential were assayed. • The expression of B-cell lymphoma-2 family proteins was explored. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
50. Iridium (III) complexes induce cervical carcinoma apoptosis via disturbing cellular redox homeostasis disorder and inhibiting PI3K/AKT/mTOR pathway.
- Author
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Hao, Jing, Liu, Haimei, Wang, Jiawen, Wang, Xiuzhen, Huang, Chunxia, Liang, Lijuan, Chen, Jing, Wang, Yi, and Liu, Yunjun
- Subjects
- *
BCL-2 proteins , *HELA cells , *IRIDIUM , *PROTEIN kinase B , *PHOSPHATIDYLINOSITOL 3-kinases , *ANTIBODY-dependent cell cytotoxicity ,ANTINEOPLASTIC agent development - Abstract
Improvement of antineoplastic activity and selectivity is a main goal in the development of antineoplastic agents. Herein, we synthesized three new iridium (III) complexes: [Ir(ppy) 2 (FTTP)](PF 6) (Ir1 , ppy = 2-phenylpyridine, FTTP = 2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene), [Ir(bzq) 2 (FTTP)](PF 6) (Ir2 , bzq = benzo[ h ]quinolone), [Ir(piq) 2 (FTTP)](PF 6) (Ir3 , piq = 1-phenylisoquinoline). Ir1-3 exhibit excellent cytotoxicity against various cancer cells particularly towards human cervical carcinoma HeLa cells while remaining non-toxic to normal cell lines. Assays on 2D cell colony formation and 3D multicellular tumor spheroid model confirm that Ir1-3 can effectively inhibit the colony-forming and penetrate deeply into HeLa 3D multicellular tumor spheroid model exhibiting a notable cytotoxic effect, which was consistent with the results from the viability assays. Meanwhile, confocal microscopy shows a rapid uptake of Ir1-3 and co-localization experiments with subcellular markers reveal that Ir1-3 locate mainly at the mitochondria. Further investigation of the mechanism indicated the complexes Ir1-3 promote the excessive generation of ROS, inhibit glutathione and thioredoxin reductase that effectively interferes with the intracellular redox balance, induce oxidative stress and result in caspase-dependent apoptosis. Moreover, the ROS-mediated inactivation of the PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) pathway, DNA damage combing with suppression of the cyclin D1/CDK4/6 activity arrested cell cycle in the G0/G1 phase are involved in complexes-induced cell apoptosis. Finally, assays on xenografted cervical carcinoma mouse model confirm the excellent biocompatibility and antineoplastic efficiency of Ir3 in vivo. Collectively, this work offers building blocks for developing iridium (III) complexes as clinical application potential. Three new iridium(III) complexes were synthesized and characterized. The anticancer activity of the complexes was investigated. Complex [Ir(piq) 2 (FTTP)](PF 6) (FTTP = 2-(3-fluoronaphthalen-2-yloxy)-1,4,8,9-tetraazatriphenylene, piq = 1-phenylisoquinoline) can effectively inhibit the tumor growth with an inhibitory rate of 54.8%. [Display omitted] • Three new iridium(III) complexes were synthesized and cytotoxicity in vitro and in vivo was studied. • Apoptosis, reactive oxygen species, colony formation, cell cycle arrest were studied. • The location and mitochondrial membrane potential were explored. • The intracellular glutathione, malondialdehyde and thioredoxin reductase were performed. • The expression of B-cell lymphoma-2 family proteins was assayed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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