Journal of Ginseng Research
·
2019
·
IF 4.029
Dongxia Gou,Xuejing Pei,Jiao Wang,Yue Wang,Chenxing Hu,Chengcheng Song,Sisi Cui,Yifa Zhou
Background Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride–induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca 2+ /calmodulin-dependent protein kinase II. Conclusion Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.
研究领域:
药理学
·
心脏病学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Zhenjie Wang,Xinxin Lin,Dongxu Chi,Zhaochu Xu,Guimei Lin,Hongzhuo Liu,Jin Sun,Zhonggui He,Yongjun Wang
Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B 0,+ (ATB 0,+ ) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro , the largest amount of tumor site accumulation and the best antitumor effect in vivo , compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhan Huang,Xing Huang,Yanfei Zhang,Meng Chen,Shaoqiang Wen,Zhou Zhang,Zong Dai,Xiaoyong Zou,Si-Yang Liu
DNAzyme-based gene silencing is a promising cancer therapy technology, while its efficiency and safety issues still need to be addressed. In this study, we developed a chirality/microRNA dual-gating theranostic nanomachine for messenger RNA (mRNA) gene silencing therapy with enhanced targeting towards human cervical cancer (HeLa) cells. The chiral nanoparticle, an emerging material with unique chirality-induced properties, e.g. chirality-dependent cellular uptake, has been widely applied in biomedical fields. The L-type gold nanoparticles (L-AuNPs) are used as the nanocarrier with the first “chirality-gating”. L-AuNPs showed 2.4-fold uptake efficiency for HeLa cells comparing to normal cell, as well as 2.2-fold uptake efficiency in cancer cell comparing to D-type gold nanoparticles (D-AuNPs), which exhibited no cancer cell targeting effect. Moreover, an entropy-driven-DNAzyme (EDz) circuit that can release numerous DNAzyme and fluorescence probes with the trigger of single microRNA (miRNA) conducted the theranostic role of both miRNA imaging and gene silencing, constituting the second “miRNA gating”. Ascribing to the prominent targeting nanocarrier L-AuNPs, the miRNA imaging sensitivity and gene silencing therapy efficiency were improved by 2.6- and 5.0-fold, respectively, comparing to those by D-AuNPs. In general, this dual-gating nanomachine, designed with a powerful yet simple strategy, has showed great prospects in optimizing delivery specificity and avoiding off-target toxicities.
研究领域:
癌症治疗
·
纳米技术
·
分子生物学
·
生物医学工程
·
基因治疗
✓ 已验证
产品关联
DOI
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Xiuhuan Chen,Cui Zhang,Yan Guo,Xin Liu,Tianxin Ye,Yuhong Fo,Chuan Qu,Jinjun Liang,Shaobo Shi,Bo Yang
Aim The purpose of the study was to investigate what effects the sigma-1 receptor (S1R) could exert on the cardiac myocyte ion channels in a rodent model of depression and to explore the underlying mechanisms since depression is an independent risk factor for cardiovascular diseases including ventricular arrhythmias (VAs). Materials and methods To establish the depression model in rats, chronic mild unpredictable stress (CMUS) for 28 days was used. The S1R agonist fluvoxamine was injected intraperitoneally from the second week to the last week for 21 days in total, and the effects were evaluated by patch clamp, western blot analysis, and Masson staining. Key findings We demonstrated that depression was improved after treatment with fluvoxamine. In addition, the prolongation of the corrected QT (QTc) interval under CMUS that increased vulnerability to VAs was significantly attenuated by stimulation of S1R due to the decreased amplitude of L-type calcium current (I Ca-L ) and the restoration of reduced transient outward potassium current (I to ) resulting from CMUS induction. The S1R also decelerated I to inactivation and accelerated I to recovery by activating Ca 2+ /calmodulin-dependent kinase II. Moreover, the stimulation of S1R ameliorated the structural remodeling as the substrate for maintenance of VAs. All these effects were abolished by the administration of S1R antagonist BD1047, which verified the roles for S1R. Significance Activation of S1R could decrease the vulnerability to VAs by inhibiting I Ca-L and restoring I to , in addition to ameliorating the CMUS-induced depressive symptoms and structural remodeling.
研究领域:
药理学
·
心脏病学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-21
·
IF 9.429
Qian ZhiZhi,Wang QianYi,Qiu ZhaoShun,Li DanYang,Zhang ChenCheng,Xiong XiYu,Zheng ZiHui,Ruan QinLi,Guo YiChen,Guo Jun
Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury. Graphical Abstract
研究领域:
肺病学
·
药理学
·
细胞生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMINO ACIDS
·
2021
·Vol. 53
·期 2
·195-204
·
IF 3.52
Yang Jiangxia,Li Xiaoqi,Du Yingxiang,Ma Mingxuan,Zhang Liu,Zhang Jian,Li Peipei
In this work, we prepared gold nanoparticles (AuNPs) by employing gluconic acid (GlcA) as reducing-cum-stabilizing agent. The proposed GlcA-AuNPs successfully worked as a colorimetric sensor for visual chiral recognition of aromatic amino acid enantiomers, namely tyrosine ( d/l -Tyr), phenylalanine ( d/l -Phe), and tryptophan ( d/l -Trp). After adding L-types to GlcA-AuNPs solution, the color of the mixture changed from red to purple (or gray), while no obvious color change occurred on the addition of D-types. The effect can be detected by naked eyes. The particles have been characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, zeta potential, the dynamic light scattering analysis as well as UV–Vis spectroscopy. This assay can be used to determine the enantiomeric excess of l -Trp in the range from 0 to + 100%. The method has advantages in simplicity, sensitivity, fast response, and low cost.
研究领域:
纳米技术
·
分析化学
·
材料科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）