查找使用阿拉丁产品的科研文献

PEG-conjugated single-walled carbon nanotubes enhance the cellular uptake of Coenzyme Q10: in vitro evaluation and mechanism study

Yang Shuoye,Niu Yakun,Li Luheng,Liu Jiaxin,Ma Mengjin,Duan Xiaoyu,Zhang Lu,Wang Le,Qu Lingbo

Coenzyme Q10 (CoQ10) has a wide range of physiological functions and therapeutic value. However, its biomedical application as a health product or drug is limited by its insolubility and low bioavailability. Single-walled carbon nanotubes (SWCNTs) have attracted great interest for drug or therapeutic agent delivery due to their unique properties. In this study, the pristine SWCNTs are purified with different oxidizing acid, and the resulting shortened CNTs (CNTs-COOH) are conjugated with poly-(ethylene glycol) (PEG) groups. Afterwards, CoQ10 is loaded by CNTs carriers. CNTs carriers are systematically characterized and evaluated in terms of drug loading, in vitro release, cytotoxicity, and cellular uptake. The results reveal that the sizes (length) of CNTs-COOH and CNTs-PEG are 253.2 and 328.7 nm, respectively, and they have high loading capacity for CoQ10 and low cytotoxicity toward Caco-2 cells. In comparison with CNTs-COOH, CNTs-PEG exhibited better sustained-release property for CoQ10. Also, CNTs-PEG carriers loaded with CoQ10 can be effectively delivered into cells and have enhanced cellular uptake efficiency over time. Further study results of the uptake mechanism illustrate that CNTs-PEG can be internalized into cells through the broader and more efficient entry routes, including direct penetration, clathrin-mediated endocytosis and macropinocytosis pathway. In summary, the PEG-conjugated CNTs may be used as novel nanocarriers, and the findings will contribute to the rational design of multifunctional delivery vehicles for CoQ10. Graphical abstract

Effect of molecular weight on the emulsion properties of microfluidized gelatin hydrolysates

Wenqi Cao,Linfan Shi,Gengxin Hao,Jun Chen,Wuyin Weng

Microfluidized gelatin hydrolysates (MGH) with decreasing molecular weight from MGH-A to MGH-E were prepared, and their emulsion properties were investigated. The molecular weight, particle size, and emulsifying activity of MGH decreased as gelatin degraded by enzymatic hydrolysis with neutral protease increased. Dramatic decreases in the surface hydrophobicity and emulsifying stability of MGH were observed as the content of peptide fractions of 18 and 23 kDa increased. The average droplet sizes of emulsions based on MGH-A, MGH-B, MGH-C, and MGH-D were 622.1, 558.8, 389.7, and 1058.9 nm, respectively, and the MGH-E-based emulsion exhibited creaming. While the flow index of the MGH-A-based emulsion was greater than 1, those of the other emulsions were less than 1. Optical and confocal laser scanning microscopic images showed fine and uniform droplet distributions without flocculation or coalescence in the MGH-A-, MGH-B-, and MGH-C-based emulsions. The encapsulation efficiency (EE) of co-enzyme Q 10 (CoQ 10 ) in the spray-dried encapsulation prepared from MGH-B was 84.3%, and EE generally decreased with increasing or decreasing degradation degree of MGH. No obvious differences were observed among the surface images of encapsulations prepared using MGH-A, MGH-B, and MGH-C, and aggregated distributions were found in the MGH-D- and MGH-E-based encapsulations. The storage stability and in vitro bioaccessibility of CoQ 10 encapsulated by MGH-E were poorer than those of CoQ 10 encapsulated by the other wall materials. The results of the current study indicate that molecular weight and particle size have significant effects on the emulsion and encapsulation properties of MGH.

CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy

Peiwen Zhang,Shen Chen,Huanwen Tang,Wanjun Fang,Ke Chen,Xu Chen

Coenzyme Q10 (CoQ10), which is a key cofactor of the electron transport chain in the mitochondria has shown many beneficial effects on liver diseases. However, the mechanisms of CoQ10 protective role on the acetaminophen (APAP)-induced liver injury are elusive and unclear. In this study, we further investigated the CoQ10 therapeutic effects on APAP-overdose liver injury. C57BL/6 J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 1.5 h after APAP treatment. The results showed that hepatic CoQ10 levels were decreased during the APAP-induced hepatotoxicity and preceded serum ALT elevation. Treatment of CoQ10 significantly improved the liver injury induced by APAP. Moreover, CoQ10 treatment decreased the ROS levels and promoted the antioxidative related gene expression in APAP overdose mice. Importantly, results showed that even though CoQ10 had no effects on the mtDNA copy number and the expression of genes related to mitochondrial biogenesis , it significantly improved the mitochondrial complex I and V activities and promoted the mitophagy in APAP-overdose mice. To further authenticate mitophagy role in CoQ10-mediated improved liver injury in vivo, we administrated APAP-overdose mice with chloroquine 1 h prior to APAP treatment and found that chloroquine treatment functionally abrogated the CoQ10 protective role on APAP overdose mice. To conclude, this study provides evidence that CoQ10 activates mitophagy to protect against APAP-induced liver injury. Therefore, CoQ10 may represent a novel therapeutic option for the prevention and treatment of drug-induced liver injury.

Coenzyme Q10 ameliorates BPA-induced apoptosis by regulating autophagy-related lysosomal pathways

Yuan Liu,Yaxin Yao,Wenjing Tao,Feng Liu,Songbai Yang,Ayong Zhao,Dan Song,Xiangchen Li

Bisphenol A (BPA) is a widely distributed environmental endocrine disruptor. The accumulation of BPA has been proved that produce various toxic effects both on human and animals. However, the strategies to reduce the damage of BPA on the body and related mechanisms remain to be studied. Coenzyme Q10 (CoQ10), as a powerful antioxidant, is ubiquitous in many eukaryotic cells, which can improve the integrity of lysosomal membrane, lysosomal degradation function and promote autophagy. Here, we examined the ability of CoQ10 to alleviate oxidative stress and apoptosis in BPA-induced damages in C2C12 cells, and how to alleviate it. Our results showed that BPA treatment significantly reduced cell viability, increased the number of cell apoptosis and ROS production, decreased mitochondrial membrane potential, and inhibited the gene expression of mitochondria biogenesis. Moreover, we demonstrated that exposure to BPA increased expression levels of autophagy protein (LC3-II, p62), inhibited autophagy flux, and disrupted the acidic pH environment of lysosomes. Importantly, CoQ10 supplementation effectively restored these abnormalities caused by BPA. CoQ10 significantly decreased the apoptotic incidence and ROS levels, improved mitochondrial membrane potential. Moreover, CoQ10 improved lysosome function and enhanced autophagy flux. Taken together, our results indicate that CoQ10 supplementation is a feasible and effective way to promote the level of autophagy by improving lysosomal function, thereby reducing the apoptosis caused by BPA accumulation. This study aims to provide evidence for the role of CoQ10 in repairing BPA-induced cell damage in clinical practice.

Enhancement of denitrification performance with reduction of nitrite accumulation and N2O emission by Shewanella oneidensis MR-1 in microbial denitrifying process

Meng Jiang,Xiong Zheng,Yinguang Chen

Bio-denitrification (i.e., microbial reduction of nitrate to gaseous nitrogen) is usually reported to be affected by operating and environmental parameters, such as carbon source type, pH value, and temperature. In this paper, the enhancement of denitrification performance with the elimination of nitrite accumulation and nitrous oxide emission by Shewanella oneidensis MR-1 were investigated and the mechanisms were explored. It was found that S. oneidensis MR-1 itself had marginal nitrate removal capacity, but its presence in the denitrification system of a well-studied denitrifier (Paracoccus denitrificans ) obviously enhanced nitrate removal efficiency (from 65.3% to 97.8%) and reduced nitrite accumulation (0.67 against none-detectable) and N 2 O generation (from 8.87 μm/mM-TN to none-detectable). The mechanism study showed that S. oneidensis MR-1 promoted electrons transfer activity via the formation of nanotube between cells, which resulted in the increase of denitrification enzymes activity , carbon source metabolism, ATP level and cell viability. As the generation, transfer and consumption of electrons were enhanced by S. oneidensis MR-1, the improvement of denitrification performance with reduction of nitrite accumulation and N 2 O emission was therefore achieved. Finally, the performance of denitrification enhanced by S. oneidensis MR-1 was testified by laboratory groundwater treatment experiment. This study suggested the potential role of S. oneidensis MR-1 in accelerating nitrate bio-transformation in nitrogen geochemical cycle and increasing bio-treatment of nitrate contamination with negligible harmful intermediates (nitrite and N 2 O) accumulation.

Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model

Liu Ze,Li Zonglin,Wu Ya’Nan,Song Shaohui,Yang Huijuan,Cai Wei,Weidong Li,Guoyang Liao

Study of the Interaction Between Coenzyme Q10 and Human Serum Albumin: Spectroscopic Approach

Peng Xin,Sun Yinhe,Qi Wei,Su Rongxin,He Zhimin

UV–vis absorption, fluorescence, circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopic methods were employed to reveal the mechanism of the binding between coenzyme Q 10 (CoQ 10 ) and human serum albumin (HSA) under simulated physiological conditions (pH = 7.4). The binding parameters were calculated by the fluorescence quenching method. The results demonstrate that the fluorescence quenching of HSA by CoQ 10 is mainly static quenching due to the formation of HSA–CoQ 10 complexes, and the number of binding sites ( n ) is equal to 1. The thermodynamic parameters (Δ H 0  = −43.18 kJ·mol −1 , Δ S 0  = −47.05 J·mol −1 ·K −1 , Δ G 0  = −29.15 kJ·mol −1 ) indicate that the enthalpy-driven binding process is favorable, and the main binding forces between CoQ 10 and HSA are hydrogen bonds and van der Waals forces. The competitive experiments using different site markers indicate that subdomain IIA (site I) of HSA is the primary binding site for CoQ 10 . The average binding distance ( r ) between HSA and CoQ 10 is 4.29 nm, which was estimated according to the Förster’s theory of non-radiation energy transfer. In addition, the UV–vis absorption, synchronous fluorescence, three-dimensional fluorescence, 8-anilino-1-naphthalenesulfonic acid fluorescence, CD spectra, and FT-IR spectroscopy data show slight conformational changes of HSA in the presence of CoQ 10 . These findings provide valuable binding information between HSA and CoQ 10 , which may be beneficial to pharmacokinetics research and could be used to design the dosage form of CoQ 10 .

Preparation and quality evaluation of coenzyme Q10 long-circulating liposomes

Huibin Li,Fang Chen

The aim of this work was to prepare coenzyme Q10 (CoQ10) long-circulating liposomes, and establish the quality standard to determine the content and entrapment efficiency. CoQ10 long-circulating liposomes were prepared by the film dispersion method, HPLC assay for the determination of CoQ10 was developed. Free drugs and liposomes were separated using the protamine aggregation method and entrapment efficiency was determined. The liposomes were homogeneous and the mean diameter was 166.0   nm, Zeta potential was −22.2   mV. The content and entrapment efficiency of CoQ10 were 98.2% and 93.2% for three batches of liposomes, respectively. The lyophilized form of liposomes prepared by freeze-drying showed stable quality characteristics during storage. The formulation and preparative method can be used to prepare CoQ10 long-circulating liposomes with high entrapment efficiency and high quality, the determination method of drug content and entrapment efficiency were effective and rapid and can be used for quality evaluation of liposomes.

Combination of coenzyme Q10-loaded liposomes with ultrasound targeted microbubbles destruction (UTMD) for early theranostics of diabetic nephropathy

Ting Yue,He-Lin Xu,Pian-Pian Chen,Lei Zheng,Qun Huang,Wen-Shuang Sheng,Yuan-Di Zhuang,Li-Zhuo Jiao,Ting-Ting Chi,De-Li ZhuGe,Jin-Jin Liu,Ying-Zheng Zhao,Li Lan

Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN. CoQ10-lip exhibited a good round morphology with a diameter of 183   ±   1.7   nm and a negative zeta potential of −25.3   mV, which was capable of prolonging the release of the encapsulated CoQ10. The early DN rat models were induced by streptozotocin (STZ) and confirmed by contrast-enhanced ultrasound (CEUS) and 24-h urinary albumin. After the administration of CoQ10-lip combined with the UTMD technique to rats with early DN, the morphology and function of the kidney were evaluated by ultrasonography, histological and molecular analyses. The renal hemodynamics were significantly improved, moreover, 24-h urinary protein, and oxidative stress indexes were modulated after treatment with CoQ10-lip   +   UTMD indicating recovery of renal function. An elevated level of Nphs2 protein and reduced caspase 3 level indicated the preservation of podocytes and inhibition of cell apoptosis after CoQ10-lip   +   UTMD treatment. The molecular mechanism was associated with the upregulation of Bcl-2 and the downregulation of Bax. Moreover, the combination of CoQ10-lip and ultrasound microbubbles demonstrated a better protective effect on the damaged kidney than the other groups (free CoQ10 or CoQ10-lip+/− UTMD). Conclusively, CoQ10-lip in combination with ultrasound microbubbles might be a potential strategy to reverse the progress of early DN.

Ionic Liquid-Based Grapeseed Oil Emulsion for Enhanced Anti-Wrinkle Treatment

Bo Yang,Xu Zhang,Liguo Zhang,Jinjin Wu,Wei Wang,Qiaomei Huang,Zhenyuan Wang,Jichuan Zhang,Tongjie Xu,Chengyu Wu,Jiaheng Zhang

Objectives: To address the poor efficacy and percutaneous penetration of grape seed oil, ionic liquids and nanotechnology were combined to prepare a grape seed oil emulsion. Methods: A novel Menthol-CoQ10 ionic liquid and ionic liquid based grapeseed oil emulsion were prepared and confirmed. Results: The average size of the grapeseed oil emulsion was 218 nm, and its zeta potential was −33.5 mV. The ionic liquid-based grape seed oil emulsion exhibited a transdermal penetration effect 4.63-fold higher than that of ordinary grape seed oil emulsion. Ionic liquid also displayed enhanced efficiency both in vitro and in vivo. It significantly inhibited the production of DPPH free radicals and tyrosinase, inhibited melanin and matrix metalloproteinase-1 (MMP-1) produced by cells, and promoted type I collagen expression in fibroblasts. After 28 days of continuous use, the grapeseed oil emulsion improved the water content of the stratum corneum and the rate of transepidermal water loss, enhanced the firmness and elasticity of the skin, and significantly improved the total number and length of under-eye lines, tail lines, nasolabial folds, and marionette lines on the face. Conclusions: Menthol-CoQ10 ionic liquid is a promising functional excipient for both transdermal delivery increase and efficient enhancement. Ionic liquid and nanotechnology for grape seed oil facial mask displayed significantly enhanced efficacy and permeability.

One-dimensional confinement-induced MOF-in-COF layer on polymeric substrate for helium separation

Zhou Qu,Yanni Liu,Haoran Wang,Qianxi Yang,Hongwei Fan,Hong Meng

Hetero-structured nanocomposite membranes have great potential in advanced gas separation due to the synergy of hierarchical pores. Herein, we report a MOF (metal–organic framework)-in-COF (covalent organic framework) layer supported on a polyacrylonitrile (PAN) ultrafiltration substrate prepared by a contra-diffusion reaction of MOF inside a one-dimensional (1D) pore-channels of COF layer. Such 1D confinement-induced membrane features a unique ultramicropore-in-nanopore structure, which intensifies the molecular sieving while preserving high-speed transfer pathways. The prepared ZIF-67-in-TAPB-BPDA-PAN membrane exhibited an excellent helium (He) permeance of ∼1500 GPU together with an enhanced separation selectivities of 3.89 for He/N 2 and 5.38 for He/CH 4 , respectively. The overall performance is competitive among the reported He-selective membranes. A continuous gas permeation test for 100 h indicates good stability. This work would bring insights into the engineering and preparation of nanocomposite functional materials applied in various separation fields.

Nrf2/FSP1/CoQ10 axis-mediated ferroptosis is involved in sodium aescinate-induced nephrotoxicity

Haiyan Zhu,Yijing Yang,Yenan Duan,Xin Zheng,Zixiong Lin,Jie Zhou

Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events , particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis ; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability , disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the −1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.