MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
He Lian,Tianhong Zhang,Jin Sun,Xiaohong Liu,Guolian Ren,Longfa Kou,Youxi Zhang,Xiaopeng Han,Wenya Ding,Xiaoyu Ai,Chunnuan Wu,Lin Li,Yongjun Wang,Yinghua Sun,Siling Wang,Zhonggui He
In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min–1, Papp = 0.059 cm·min–1) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0–t (586.37 ng/mL·h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Yang Chen,Yile Chen,Tian Li,Jiamei Wang,Weimin Zhang
Atmospheric cold plasma (ACP) presents a promising method for the sterilization of coconut milk and exhibits a modifying effect on coconut globulin (CG), the primary allergen in coconut milk. This study investigated the potential role of ACP treatment in mitigating the allergenic properties of coconut milk by examining changes in protein structure. ACP treatment induced structural alterations in CG, disrupting binding sites with immunoglobulin E (IgE). Consequently, this led to a reduction in the affinity between CG and IgE, evidenced by a decrease in K a from 2.17 × 10 4 /M to 0.64 × 10 4 /M, thereby diminishing IgE-mediated allergic reactions. The findings from allergenic and cellular models further corroborated that ACP treatment decreased the allergenicity of CG by 55.18%, while inhibiting degranulation and the release of allergic mediators. This study presents an innovative methodology for producing hypoallergenic coconut milk, thereby expanding the applicability of ACP technology within the food industry.
研究领域:
食品科学
·
过敏研究
·
等离子技术
·
蛋白质化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2023
·
IF 6.1
Jun Li,Fangbo Yuan,Jiayou Teng,Fang Li,Penghui Zhou,Yanlan Bi
The effects of tea polyphenols (TP) on the quality of palm oils (PO) and losses of endogenous vitamin E during batch frying of instant noodles as well as oxidative stability of fried instant noodles were investigated. PO without antioxidant addition was negative control and with tertiary butylhydroquinone (TBHQ) addition positive control. TP and TBHQ addition inhibited the increase of peroxide, p -anisidine, and total oxidation values of PO and reduced tocopherol and tocotrienol losses with 200 mg/kg of TP having the best performance, but didn’t affect acid value and triglyceride composition. 200 mg/kg of TP and 100 mg/kg of TBHQ inhibited unsaturated fatty acid losses. During frying, TBHQ was mainly volatilized but TP transformed. TP more effectively reduced tocopherol and tocotrienol losses than TBHQ, reducing PO deterioration. The extended lifecycles of PO and shelf life of fried instant noodles are attributed to nonvolatility of TP and antioxidative properties of its transformation products.
研究领域:
食品科学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2023
·
IF 5.9
Nouman Ali Shah,Rui Hong,Xue Yang,Shi-Shu Huang,Rizwan M. Gul,Yuwei Liu,Lingli Li,Jia-Zhuang Xu,Ka Li,Zhong-Ming Li
Maintaining reliability remains a great challenge for ultrahigh molecular weight polyethylene (UHMWPE) bearings due to oxidation in biological environments. This work aimed at inspecting the efficacy of the hybrid antioxidant strategy in stabilizing crosslinked UHMWPE under an in vitro clinically relevant accelerated aging condition. The hybrid antioxidant system was composed of vitamin E (VE) and D-sorbitol (DS) as primary and secondary antioxidants, respectively. The already established in vitro clinically relevant accelerated aging was performed via squalene absorption and subsequent thermal oxidation treatment. Compared to the use of VE alone, the combination of VE and DS significantly protracted the oxidation induction time of UHMWPE with no apparent oxidation after aging, showing a notable synergistic effect on the oxidative stability of UHMWPE. The crosslink density was higher for VE/DS/UHMWPE than VE/UHMWPE at each aging period. It revealed that the hybrid antioxidant strategy settled the longstanding contradiction between oxidation stability and crosslinking of UHMWPE. Attributed to improved oxidation stability, there was a positive reversal in the tensile property between VE/DS/UHMWPE and VE/UHMWPE after aging, where comparable ultimate tensile strength and higher elongation at break were observed. These findings underline the high potential of the hybrid antioxidant strategy for developing artificial joint materials with desired ability to resist oxidation and balanced performance.
研究领域:
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Parikshit Banerjee,Tianjiao Geng,Arpan Mahanty,Tiantian Li,Li Zong,Bo Wang
The ‘repurposed drug,’ disulfiram (DSF), is an inexpensive FDA-approved anti-alcoholism drug with multi-target anti-cancer effect. However, the use of DSF in clinical settings remains limited due to its high instability in blood. In the present study, we created nanostructured lipid carriers (NLC) encapsulated DSF modified with d -α-tocopheryl polyethylene glycol 1000 succinate (vitamin E-TPGS). A spherical shape, superior drug encapsulation (80.7%), and decreased crystallinity of DSF were confirmed with results obtained from TEM, XRD, and DSC analysis. Addition of TPGS considerably improved the physicochemical stability profile of NLC-encapsulated DSF under the different conditions tested here. Furthermore, TPGS-DSF-NLCs outperformed unmodified DSF-NLCs and the free DSF solution by having significantly higher cytotoxicity, lower IC50 value (4T1: 263.2 nM and MCF-7: 279.9 nM), and an enhanced cellular uptake in MCF7 and 4T1 cell lines. In vivo anti-tumor analysis in 4T1 murine xenograft model mice revealed a significant (p-value < 0.05) decrease in tumor volume and higher tumor growth inhibition rate (48.24%) with TPGS-DSF-NLC treatment as compared to both the free DSF solution (8.49%) and DSF-NLC formulations (29.2%). Histopathology analysis of tumor tissues further confirmed a noticeably higher anti-tumor activity of TPGS-DSF-NLC through augmented cell necrosis in solid tumors. Hence, the present study established that addition of TPGS can synergize the anti-cancer activity of NLC-encapsulated DSF formulations, and thus, offer a promising anti-cancer delivery system for DSF.
研究领域:
药学
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers of Environmental Science & Engineering
·
2021
·Vol. 15
·期 6
·1-10
·
IF 4.357
Wang Xinyu,Jin Ye,Chen Weirui,Zou Ruini,Xie Jinxin,Tang Yiming,Li Xukai,Li Laisheng
E-peroxone (EP) was one of the most attractive AOPs for removing refractory organic compounds from water, but the high energy consumption for in situ generating H 2 O 2 and its low reaction efficiency for activating O 3 under acidic conditions made the obstacles for its practical application. In this study, cerium oxide was loaded on the surface of graphite felt (GF) by the hydrothermal method to construct the efficient electrode (CeO x /GF) for mineralizing carbamazepine (CBZ) via EP process. CeO x /GF was an efficient cathode, which led to 69.4% TOC removal in CeO x /GF-EP process with current intensity of 10 mA in 60 min. Moreover, CeO x /GF had the flexible application in the pH range from 5.0 to 9.0, TOC removal had no obvious decline with decrease of pH. Comparative characterizations showed that CeO x could enhance surface hydrophilicity and reduce the charge-transfer resistance of GF. About 5.4 mg/L H 2 O 2 generated in CeO x /GF-EP process, which was 2.1 times as that in GF-EP process. The greater ozone utility was also found in CeO x /GF-EP process. More O 3 was activated into hydroxyl radicals, which accounted for the mineralization of CBZ. An interfacial electron transfer process was revealed, which involved the function of oxygen vacancies and Ce 3+ /Ce 4+ redox cycle. CeO x /GF had the good recycling property in fifth times’ use.
研究领域:
环境科学
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水处理
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电化学
·
催化
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2021
·Vol. 298
·期 2
·
IF 5.157
Binxiang Cai,Chunyan Liao,Danxue He,Jingmeng Chen,Jiahuai Han,Jiaying Lu,Kaiqi Qin,Wenxu Liang,Xiaoling Wu,Zuguo Liu,Yalin Wu
The breakdown of all-trans-retinal (atRAL) clearance is closely associated with photoreceptor cell death in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its mechanisms remain elusive. Here, we demonstrate that activation of gasdermin E (GSDME) but not gasdermin D promotes atRAL-induced photoreceptor damage by activating pyroptosis and aggravating apoptosis through a mitochondria-mediated caspase-3-dependent signaling pathway. Activation of c-Jun N-terminal kinase was identified as one of the major causes of mitochondrial membrane rupture in atRAL-loaded photoreceptor cells, resulting in the release of cytochrome c from mitochondria to the cytosol, where it stimulated caspase-3 activation required for cleavage of GSDME. Aggregation of the N-terminal fragment of GSDME in the mitochondria revealed that GSDME was likely to penetrate mitochondrial membranes in photoreceptor cells after atRAL exposure. ABC (subfamily A, member 4) and all-trans-retinol dehydrogenase 8 are two key proteins responsible for clearing atRAL in the retina. Abca4−/−Rdh8−/− mice exhibit serious defects in atRAL clearance upon light exposure and serve as an acute model for dry AMD and STGD1. We found that N-terminal fragment of GSDME was distinctly localized in the photoreceptor outer nuclear layer of light-exposed Abca4−/−Rdh8−/− mice. Of note, degeneration and caspase-3 activation in photoreceptors were significantly alleviated in Abca4−/−Rdh8−/−Gsdme−/− mice after exposure to light. The results of this study indicate that GSDME is a common causative factor of photoreceptor pyroptosis and apoptosis arising from atRAL overload, suggesting that repressing GSDME may represent a potential treatment of photoreceptor atrophy in dry AMD and STGD1.
研究领域:
眼科学
·
分子生物学
·
细胞生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2024
·
IF 3.9
Zhonghua Wang,Wei Song,Wanqing Wei,Hejia Qi,Weiwei Meng,Jia Liu,Xiaomin Li,Cong Gao,Liming Liu,Guipeng Hu,Yiwen Zhou,Jing Wu
Natural chondroitin sulfate (CS), extracted from animal cartilage, is widely used in the pharmaceuticals and foods. However, contamination with animal-derived heteropolysaccharides presents significant challenges, including potential immune responses. To address this, we developed a green and efficient method for synthesizing chondroitin sulfate E (CSE) via enzymatic synthesis, identifying EcCHST15, a sulfotransferase that catalyzes the conversion of chondroitin sulfate A (CSA) to CSE. We investigated the novel catalytic mechanism of CHST15 through quantum mechanical (QM) calculations and experimental validation, confirming its alignment with the SN2 reaction mechanism. Subsequently, we enhanced the catalytic efficiency of CHST15 using protein engineering, improving the catalytic efficiency from 18.1% in the wild type (WT) to 62.5% in the M7 mutant—a 3.5-fold increase. Finally, we constructed a six-enzyme cascade whole-cell catalyst, achieving a 72.2% conversion of 15 g/L CSA to produce CSE within 24 h. These findings offer a promising strategy for the industrial production of CSE.
研究领域:
生物技术
·
制药
·
生物化学
·
蛋白质工程
·
酶学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 10
·5911-5925
·
IF 4.486
Dafeng Yang,Zhousheng Yang,Lei Chen,Dabin Kuang,Yang Zou,Jie Li,Xu Deng,Songyuan Luo,Jianfang Luo,Jun He,Miao Yan,Guixia He,Yang Deng,Rong Li,Qiong Yuan,Yangzhao Zhou,Pei Jiang,Shenglan Tan
Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata , in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient ( Apoe − / − ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe − / − mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe − / − mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.
研究领域:
心血管疾病
·
药理学
·
分子生物学
·
传统中药
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2022
·
IF 4.225
Fan Yang,Xin Ma,Wei Hu,Ziyi Xiong,Meijiang Huang,Yong Wu,Xuanyi Meng,Zhihua Wu,Anshu Yang,Xin Li,Hongbing Chen
ABSTRACT Dairy processing can alter the digestion stability and bioavailability of cow milk proteins in the gastrointestinal tract. However, analysis of stable linear epitopes on cow milk allergens that could enter into intestinal mucosal is limited. Thus, this study aimed to investigate the digestion and transportation properties and residual allergen epitopes entering into gastrointestinal mucosa of 3 commercial dairy products, including pasteurized milk (PM), ultra-heat-treated milk (UHTM), and dried skim milk (DSM). In this work, the digestive stability of the 3 kinds of dairy products has been performed in a standard multistep static digestion model in vitro and characterized by Tricine-SDS-polyacrylamide gel electrophoresis and reversed-phase HPLC. With respect to gastrointestinal digestion in vitro, the main allergens including β-lactoglobulin (β-LG), α-lactalbumin (α-LA), and caseins were degraded gradually, and the resistance peptides remained in the PM with a molecular weight of range from 3.4 to 5.0 kDa. Simultaneously, the potential allergenicity of the cow milk proteins was diminished gradually and is basically consistent after 60 min of gastrointestinal digestion. After gastrointestinal digestion, the remaining peptides were transported via an Ussing chamber and identified by liquid chromatography-MS/MS. By alignment, 10 epitopes peptides were identified from 16 stable peptides, including 5 peptides (AA 92–100, 125–135, 125–138, and 149–162) in β-LG, 2 peptides in α-LA (AA 80–93 and 63–79), 2 peptides in α S1 -casein (AA 84–90 and 125–132), and 1 peptide (AA 25–32) in α S2 -casein were identified by dot-blotting mainly exist in UHTM and PM. This study demonstrates dairy processing can affect the digestion and transport characteristics of milk proteins and in turn alter epitope peptides release.
研究领域:
食品科学
·
过敏原学
·
蛋白质组学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 23
·5871-5878
·
IF 3.307
Wang Yu,Cui Min,Jiao Mingxia,Luo Xiliang
Accurate detection of protein biomarkers in complex media remains a challenge due to severe nonspecific adsorption and biofouling, and sensing interfaces that combine the high sensitivity and antifouling ability are highly desirable. Herein, an antifouling sensing interface capable of sensitively assaying immunoglobulin E (IgE) in biological samples was constructed. The sensing interface was fabricated through the self-assembly of a zwitterionic peptide and the IgE aptamer onto a macroporous Au substrate, which was electrochemically fabricated with the aid of multilayer polystyrene nanospheres self-assembled on glassy carbon electrode. Due to the huge surface area arising from porous morphology and high specificity of aptamer, the developed electrochemical biosensor exhibits ultrahigh sensitivity and selectivity towards IgE, with the linear range of 0.1–10 pg mL −1 , and a very low limit of detection down to 42 fg mL −1 . Interestingly, owing to the presence of the zwitterionic peptide, the biosensing interface can satisfyingly reduce the nonspecific adsorption and fouling effect. Consequently, the biosensor was successfully applied to detect IgE in complex biological samples, indicating great promise of this peptide-based sensing interface for antifouling assays.
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研究领域:
分析化学
·
生物传感器
·
电化学
·
生物分析科学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 24
·3984
·
IF 4.7
Zhenbao Shi,Wenzhe Li,Ziqiang Chen,Zhengcong Peng,Mingtao Ma,Jinglong Zhang,Dianhui Wu,Guangfa Xie,Jian Lu
Greengage alcoholic beverage (GAB) is gaining popularity for its distinctive fruity aroma and nutritional benefits. TheSaccharomyces cerevisiaestrain applied for fermentation significantly influences the metabolic production of aroma compounds, making the selection ofS. cerevisiaestrains to be critical for enhancing the unique flavor profile of the GAB in commercial production. In this study, the effects of two common commercialS. cerevisiaestrains (SY, EC-1118) and two laboratory-derived strains (ET008-c54, NM-8) on the flavor profile of the GAB were investigated. Volatile organic compounds (VOCs) of the GAB samples were analyzed using GC-E-Nose, HS-SPME-GC-MS, and HS-GC-IMS. Results showed significant differences in the flavor compound content of the GAB fermented by different strains. Nine VOCs were identified as potential markers by partial least squares–discriminant analysis (PLS-DA) combined with variable importance in projection (VIP), with ethyl esters playing a key role in distinguishing the aroma characteristics of different groups. Consequently, 13 aromatic compounds were selected and considered to be the typical VOCs of the GAB. Notably, β-ionone and ethyl octanoate emerged as representative aroma compounds, both showing the highest concentrations in the SY sample. These findings will provide valuable insights into the aroma differences of the GAB fermented by different strains and offer theoretical guidance for selecting suitable strains in the industrial production of the GAB.
研究领域:
食品科学
·
微生物学
✓ 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）