International Journal of Nanomedicine
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2023
·
IF 8
Dinghu Zhang,Yanhong Chu,Hanqing Qian,Lingyu Qian,Jie Shao,Qiuping Xu,Lixia Yu,Rutian Li,Quanan Zhang,Fenglei Wu,Baorui Liu,Qin Liu
Introduction Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity.Methods The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size.Results The thermo-sensitive properties of hydrogels were characterized by 3–4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased.Discussion The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Dengke Yin,Ye Yang,Hanxu Cai,Fei Wang,Daiyin Peng,Liqing He
This study aims to assess the targeted effect and antitumor efficacy of Gambogic-acid-loaded particles (GA-Ps). GA-Ps with uniform particle sizes of 69.8 ± 17.8 nm (GA-P1), 185.6 ± 33.8 nm (GA-P2), 357.8 ± 81.5 nm (GA-P3), and 7.56 ± 0.95 μm (GA-P4) were prepared using an electrospray technique and exhibited extremely high entrapment efficiency. As the particle size increased from the nano- to microscale, the in vitro GA release rate sharply decreased. After tail-vein injection in mice, GA-P samples GA-P1, GA-P2, GA-P3, and GA-P4 improved the uptake of GA 1.67-times in the liver, 1.78-times in the liver, 2.18-times in the spleen, and 2.35-times in the lung, respectively, compared with GA solution (GA-S). The antitumor efficacy of GA-P2, with an 82.51% targeting efficiency (Te) for the liver, was examined in hepatocellular carcinoma (HCC) model mice. After 2 weeks of administration, HCC mice in the GA-P2 group exhibited a lower degree of tumor invasion and cell lesions in hepatic tissue, recovered liver function, and significantly prolonged survival time, compared with mice in the model, GA-S, and normal saline (NS) groups. Pharmacokinetic studies indicated that the superior antitumor efficacy of GA-P2 was attributed not only to tissue targeting but also to low clearance, extended retention, high bioavailability in plasma, and increased GA stability.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Toxics
·
2023
·Vol. 11
·期 4
·328
·
IF 4.6
Xiangqin Zheng,Yuexin Wei,Jiadong Chen,Xia Wang,Dinggang Li,Chengjun Yu,Yifan Hong,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu
Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.Keywords:difenoconazole;reproductive toxicity;testis;retinoic acid signaling;GC-2 cell;apoptosis
研究领域:
毒理学
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生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
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2016
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IF 2.233
Jinpu Peng,Lianju Shen,Jinjun Chen,Xining Cao,Yue Zhou,Huali Weng,Chunlan Long,Deying Zhang,Shengfen Tu,Yan Zhang,Dawei He,Tao Lin,Guanghui Wei
This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group ( n = 10) and normal control group ( n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.
研究领域:
生殖生物学
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内分泌学
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组织病理学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2023
·Vol. 13
·期 5
·3364-3370
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IF 3.9
Yuying Jiang,Yifeng E,Pengyan Wei,Jia Wang,Peng Chen,Lei Wang,Thomas F. Krenzel,Kun Qian,Xiyuan Tong
An electrochemical method based on a Linde Type-A zeolite-modified glass carbon electrode (LTA/GCE) was introduced for the determination of retinoic acid (RA). LTA zeolite could be synthesized through a hydrothermal method and served as a commercial electrochemical sensor with high stability and sensitivity in electrochemical progress. The as-synthesized product was characterized by scanning electron microscopy (SEM), differential thermal analysis (DTA), X-ray powder diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Under optimal conditions, a detection limit of 0.8 μM was obtained for RA with a linear range of 0.8–20.1 μM. This electrochemical method for determining RA was simpler and cheaper than previously reported methods. Furthermore, the modified electrode could be applied to the detection of RA in tap water, achieving a linear range of 1.4–15.0 μM with a detection limit of 1.4 μM and good recovery. The modified electrode designed by this method provided good selectivity, stability, and reproducibility for RA determination and reliable application for the analysis of RA in environmental water.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
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2013
·Vol. 51
·期 18
·3932-3940
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IF 3.543
Wei Lu,Meng-Ling Lu,Qing-Peng Zhang,Yong-Qing Tian,Zhi-Xiang Zhang,Han-Hong Xu
Environment-friendly and controlled release formulation is highly promising for reducing environmental pollution and achieving the most effective utilization of pesticides. As a novel “green” nanocarrier of pesticides, amphiphilic self-assembled nanoparticles were prepared by chemical conjugation of octahydrogenated retinoic acid (OR) to the backbone of glycol chitosan (GC). In aqueous media, the synthesized OR-GC conjugates formed nanosized particles with a diameter of 257 nm. Hydrophobic azadirachtin (AZA) was efficiently loaded into the OR-GC nanoparticles at a feed weight ratio of up to 1:4 using a simple dialysis method, the maximum drug-loading efficiency of which was 74%. AZA-OR-GC (25 wt %) nanoparticles also showed sustained release of the incorporated AZA (65% of the loaded dose was released in 7 days at 27 °C in phosphate-buffered saline; pH 7.2). Cytotoxicity tests and cell cycle arrest assays confirmed that OR-GC exhibits good biocompatibility; AZA-OR-GC (25 wt %) nanoparticles also showed favorable inhibition of cell proliferation in Sl-1 cells compared with free AZA in organic solvents. Overall, controlled release AZA-OR-GC may be a promising environment-friendly formulation for integrated pest management. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51 , 3932–3940
研究领域:
农药科学
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生物材料
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环境科学
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产品关联
DOI
高影响因子
Polymers
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2017
·Vol. 9
·期 4
·135
·
IF 3.364
Wenxia Cheng,Fengfeng Fan,Ying Zhang,Zhichao Pei,Wenji Wang,Yuxin Pei
By taking advantage of the self-polymerization of dopamine on the surface of magnetic nanospheres in weak alkaline Tris-HCl buffer solution, a facile approach was established to fabricate core-shell magnetic molecularly imprinted nanospheres towards hypericin (Fe3O4@PDA/Hyp NSs), via a surface molecular imprinting technique. The Fe3O4@PDA/Hyp NSs were characterized by FTIR, TEM, DLS, and BET methods, respectively. The reaction conditions for adsorption capacity and selectivity towards hypericin were optimized, and the Fe3O4@PDA/Hyp NSs synthesized under the optimized conditions showed a high adsorption capacity (Q= 18.28 mg/g) towards hypericin. The selectivity factors of Fe3O4@PDA/Hyp NSs were about 1.92 and 3.55 towards protohypericin and emodin, respectively. In addition, the approach established in this work showed good reproducibility for fabrication of Fe3O4@PDA/Hyp.Keywords:surface molecular imprinting;hypericin;magnetic nanospheres;dopamine;core-shell
研究领域:
材料科学
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药物化学
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产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
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2017
·Vol. 28
·期 1
·48-68
·
IF 15.606
Xu Xingxing,Li Chuanyin,Gao Xiaobo,Xia Kun,Guo Hui,Li Yali,Hao Zijian,Zhang Lei,Gao Daming,Xu Chenfan,Xu Huatai,Xiong Zhi-Qi,Qiu Zilong,Mei Ling,Xie Xiaoduo,Ruan Kangcheng,Hu Ronggui
The autism spectrum disorders (ASDs) are a collection of human neurological disorders with heterogeneous etiologies. Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner. Excessive UBE3A dosage was found to impair RA-mediated neuronal homeostatic synaptic plasticity. ASD-like symptoms were recapitulated in mice by overexpressing UBE3A in the prefrontal cortex or by administration of an ALDH1A antagonist, whereas RA supplements significantly alleviated excessive UBE3A dosage-induced ASD-like phenotypes. By identifying reduced RA signaling as an underlying mechanism in ASD phenotypes linked to UBE3A hyperactivities, our findings introduce a new vista of ASD etiology and facilitate a mode of therapeutic development against this increasingly prevalent disease.
研究领域:
神经科学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Ying Zou,Chaoxian Chi,Fangling Wu,Chuan-Fan Ding
Retinoic acid (RA) regulates cell proliferation, differentiation, and apoptosis and exists in three primary isomers: all-trans-RA (ATRA), 9-cis-RA (9cRA), and 13-cis-RA (13cRA). RA derivatives, such as bexarotene (BT) and arotinoid acid (TTNPB), are used to treat cutaneous T-cell lymphoma and induce cellular pluripotency. Due to their distinct biological activities, accurate identification and analysis of these isomers are crucial. This study developed a rapid and efficient method for analyzing RA isomers and their derivatives using ion mobility mass spectrometry (IM-MS) and theoretical calculations. RA isomers and derivatives exhibit overlapping mobilities and cannot be separated by direct IM-MS. By forming ternary complexes with β-cyclodextrin (β-CD) and metal ions, baseline separation was achieved with a peak resolution (R p-p ) of up to 3.42. Tandem MS and theoretical calculations revealed distinct differences in interactions, spatial structures, and binding energies, enabling mobility-based separation. Photostability tests showed rapid photoisomerization of 13cRA into 9cRA and ATRA within seconds. Analysis of 13cRA soft capsules from four brands demonstrated good stability, with measured content aligning closely with labeled values. This method offers a new approach for accurate RA isomer analysis, with potential applications in pharmaceuticals and food industries.
研究领域:
生物化学
·
药物化学
·
分析化学
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DOI
PubMed
高影响因子
NATURE GENETICS
·
2016
·Vol. 49
·期 1
·119-124
·
IF 31.616
Shao Changwei,Bao Baolong,Xie Zhiyuan,Chen Xinye,Li Bo,Jia Xiaodong,Yao Qiulin,Ortí Guillermo,Li Wenhui,Li Xihong,Hamre Kristin,Xu Juan,Wang Lei,Chen Fangyuan,Tian Yongsheng,Schreiber Alex M,Wang Na,Wei Fen,Zhang Jilin,Dong Zhongdian,Gao Lei,Gai Junwei,Sakamoto Takashi,Mo Sudong,Chen Wenjun,Shi Qiong,Li Hui,Xiu Yunji,Li Yangzhen,Xu Wenteng,Shi Zhiyi,Zhang Guojie,Power Deborah M,Wang Qingyin,Schartl Manfred,Chen Songlin
Flatfish have the most extreme asymmetric body morphology of vertebrates. During metamorphosis, one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of lopsided body pigmentation1,2,3,4,5. The evolution of this developmental and physiological innovation remains enigmatic. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. We demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration. The unexpected expression of the visual opsins from the phototransduction pathway in the skin translates illumination differences and generates retinoic acid gradients that underlie the generation of asymmetry. Identifying the genetic underpinning of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, but it also provides insight into the mechanisms that control body shape in vertebrates.
研究领域:
遗传学
·
发育生物学
·
比较基因组学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Xue Yang,Hui Liu,Fuyi Han,Shuai Jiang,Lifang Liu,Zhaopeng Xia
Cellulose nanocrystal (CNC) was extracted from Carex meyeriana Kunth (CMK) by a combination of TEMPO oxidation and mechanical homogenization method, and used to remove methylene blue (MB) from aqueous solution. After alkali-oxygen treatment, the aqueous biphasic system (polyethylene glycol/inorganic salt) was applied to further remove lignin from CMK. The characteriazation of CNC, and the effects of H 2 O 2 dosage, CNC dosage, adsorption time, and initial MB concentration on the MB removal capacity of CNC were investigated. The results showed that the removal percentage of MB by CNC was raised with the increase of H 2 O 2 and CNC dosage. The adsorption kinetics of prepared CNC followed the pseudo-second-order model, and the adsorption isotherms fitted well to the Langmuir model with a calculated maximum adsoption capacity of 217.4 mg/g, which was higher than those of CNC extracted by acid hydrolysis method, indicating CNC extracted from CMK had promising potentials in the field of MB adsorption.
研究领域:
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Tingting Luo,Jingtian Han,Feng Zhao,Xiaohong Pan,Baocheng Tian,Xiujuan Ding,Jing Zhang
Novel chitosan-cystamine-retinoic acid conjugate (CS-SS-RA) was synthesized and could self-assemble into redox-sensitive micelles in aqueous environment with low critical micelle concentration value. CS-SS-RA micelles were characterized with spherical shape, desirable particle size, negative zeta potential, high paclitaxel (PTX) loading and encapsulation efficiency and redox-sensitivity. Hemolysis and cytotoxicity studies proved the safety of CS-SS-RA micelles for intravenous administration. Cytotoxicity study against HepG2 cells and the growth inhibition study on three-dimensional multicellular tumor spheroids (MCTSs) revealed that PTX-loaded CS-SS-RA micelles exhibited higher antitumor activity than free PTX. The in vitro cellular uptake profiles of FITC-labeled CS-SS-RA micelles evaluated via confocal laser scanning microscopy and flow cytometry indicated that CS-SS-RA micelles could enhance cellular uptake efficiency of PTX, and their internalization by HepG2 cells were mediated by clathrin-mediated endocytosis and macropinocytosis. These results demonstrated that CS-SS-RA micelles could be developed as a promising platform for intracellular delivery of hydrophobic antitumor agents.
研究领域:
药剂学
·
肿瘤学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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