JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 25
·期 2
·1140-1150
·
IF 4.486
Jie Xu,Dazhi Chen,Lanling Jin,Zhengkang Chen,Yulu Tu,Xiaozhe Huang,Feiben Xue,Jialu Xu,Mingzhuan Chen,Xiaodong Wang,Yongping Chen
Inflammation and fibrosis are major consequences of autoimmune hepatitis, however, the therapeutic mechanism remains to be investigated. USP4 is a deubiquitinating enzyme and plays an important role in tissue fibrosis and immune disease. Vialinin A is an extract from mushroom and is a specific USP4 inhibitor. However, there is lack of evidences that Vialinin A plays a role in autoimmune hepatitis. By employing S100-induced autoimmune hepatitis in mice and AML12 cell line, therapeutic mechanism of Vialinin A was examined. Inflammation was documented by liver histological staining and inflammatory cytokines. Fibrosis was demonstrated by Masson, Sirius red staining and fibrotic cytokines with western blot and real-time RT-PCR. In experimental animal, there were increases in inflammation and fibrosis as well as USP4, and which were reduced after treatment of Vialinin A. Vialinin A also reduced Rheb and phosphorylated mTOR. Moreover, in LPS-treated AML12 cells, LPS-induced USP4, inflammatory and fibrotic cytokines, phosphorylated mTOR and Rheb. Specific inhibitory siRNA of USP4 reduced USP4 level and the parameters mentioned above. In conclusion, USP4 was significantly elevated in autoimmune hepatitis mice and Vialinin A reduced USP4 level and attenuate inflammation and fibrosis in the liver. The mechanism may be related to regulation of Rheb/mTOR signalling.
研究领域:
药理学
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免疫学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Huizhen Tian,Qigang Pan,Jianfeng Wu,Juanjuan Liao,Yuwei Wan,Ke Pei,Qiong Liu,Lingbing Zeng,Yanli Cao,Qiaofa shi,Nanzhen Kuang,LiJuan Sun,Xiaomin Yu,Xiaotian Huang
Background Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis and is currently lacking specific pharmacological treatments, highlighting the critical need for therapeutic development. Icariin (ICA), a prenylated flavonol glycoside, was previously found to exhibit several pharmacological effects, but its potential to combat CVB3 remains uninvestigated. Purpose This study aimed to elucidate the anti-CVB3 efficacy of ICA and elucidate its molecular mechanisms. Methods CVB3-infected HeLa cells, H9C2 cells and neonate rat ventricular cardiomyocytes (NRVCs) were selected as in vitro models, and were treated with ICA at 1 and 10 μM. Additionally, BALB/c mice that were infected with CVB3 via intraperitoneal injection were chosen as in vivo model and were treated with ICA or ribavirin over 3 days. The effect of ICA against CVB3 was determined by Cell Counting Kit-8 (CCK-8) assay, western blot, real-time fluorescence quantitative PCR (RT–qPCR), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and flow cytometry. Results In this study, it was found that ICA is capable of reducing CVB3 viral load both in vitro and in vivo . Mechanistic studies suggested that ICA prevents cardiomyocyte apoptosis by attenuating the S100 calcium binding protein A6 (S100A6)/β-catenin/c-Myc signaling pathway. Additionally, ICA inhibits the secretion of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and CXC motif chemokine ligand 2 (CXCL2) in heart tissue, thereby mitigating CVB3-induced myocarditis. Moreover, ICA also regulates the immune response of CD4 + T, CD8 + T and Treg cells by changing the cells numbers in spleen tissue. Lastly, ICA can reduce the load of other enteroviruses (such as CVA6, CVA16 and EV71) in rhabdomyosarcoma (RD) cells as well. Conclusion Our findings indicate that ICA provides significant protection against CVB3 infection by modulating the S100A6/β-catenin/c-Myc signaling pathway, suggesting its potential use as a novel drug against CVB3 infection in clinical application.
研究领域:
药理学
·
病毒学
·
心脏病学
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免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Anqi Wang,Yuanyuan Liu,Wugui Xiong,Wei Li,Jin Li,Zhiqiang Yang,Zhongtao Zou,Yinjia Luo,Zhoujiang Chen,Hanmei Li,Chi Teng Vong,Liang Zou
Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis , and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Meixia Xu,Minjie Sun,Hongzhi Qiao,Qineng Ping,Eltayeb Suliman Elamin
Oral modified-release delivery systems, such as bio-adhesive one, enable drug delivery to affected regions and minimize the side effects by reducing the systemic absorption. Our aim was to develop colon adhesive pellets of 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis . The core of the pellet was formulated from bioadhesive agents, Carbomer 940 and hydroxypropyl cellulose (HPC), by extrusion/spheronization method and coated with Surelease ® as inner layer for waterproof and with Eudragit ® S100 as outer layer for pH control. The rat model of ulcerative colitis was used to evaluate the efficiency of our loaded pellets as a drug carrier. Microcrystalline cellulose 101 (PH 301) was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as (1:1) to achieve high bioadhesion. When the amount of Surelease ® was from 16% to 20% and of Eudragit ® S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in the artificial gastric fluid (pH 1.0) within 2 h and less than 10% was released in phosphate buffer (pH 6.0) within 2 h whereas complete dissolution was observed in colonic fluid of pH 7.4 for 20 h. The animal experiment showed that 5-ASA loaded colon adhesive pellets had optimal therapeutic effect. We showed a novel approach to prepare effective bioadhesive pellets as colon targeted drug delivery system .
研究领域:
药剂学
·
消化病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
U. Eranka Illangakoon,Deng-Guang Yu,Bilal S. Ahmad,Nicholas P. Chatterton,Gareth R. Williams
A series of 5-fluorouracil (5-FU) loaded core/shell electrospun fibers is reported. The fibers have shells made of Eudragit S100 (ES-100), and drug-loaded cores comprising poly(vinylpyrrolidone), ethyl cellulose , ES-100, or drug alone. Monolithic 5-FU loaded ES-100 fibers were also prepared for comparison. Electron microscopy showed all the fibers to have smooth cylindrical shapes, and clear core–shell structures were visible for all samples except the monolithic fibers. 5-FU was present in the amorphous physical form in all the materials prepared. Dissolution studies showed that the ES-100 shell was not able to prevent drug release at pH 1.0, even though the polymer is completely insoluble at this pH: around 30–80% of the maximum drug release was reached after 2 h immersion at pH 1.0. These observations are ascribed to the low molecular weight of 5-FU permitting it to diffuse through pores in the ES-100 coating, and the relatively high acid solubility of the drug providing a thermodynamic impetus for this to happen. In addition, the fibers were observed to be broken or merged following 2 h at pH 1.0, giving additional escape routes for the 5-FU.
研究领域:
药学
·
材料科学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 6
·3143-3150
·
IF 2.936
Ying Wang,Peng Zhao,Leilei Mao,Yajun Hou,Dawei Li
The development of rapid, highly sensitive detection methods for neuron-specific enolase (NSE) and S100-β protein is very important as the levels of NSE and S100-β protein in the blood are closely related to brain injury. Therefore, we can use NSE and S100-β protein concentration detection to realize the preliminary judgment of brain injury. In this paper, we report that a simple label-free three dimensional hierarchical plasmonic nano-architecture has been designed for the sensitive surface-enhanced Raman scattering immunosensor detection of NSE and S100-β. Owing to the active group of the hollow gold nanospheres (HAuNPs), the redox molecules 4-mercaptobenzoic acid (4-MBA) and Nile blue A (NBA) absorb antibodies and provide signal generation. The prepared HAuNPs@4-MBA and HAuNPs@NBA are used as probes to easily construct a surface-enhanced Raman scattering immunosensor. When protein biomarkers are present, the sandwich nanoparticles are captured over the substrate, forming a confined plasmonic field, leading to an enhanced electromagnetic field in intensity and in space. As a result, the Raman reporter molecules are exposed to a high density of “hot spots”, which remarkably amplify the Raman signal, improving the sensitivity of the surface-enhanced Raman scattering immunosensor. Under the optimized conditions, the linear range of the proposed immunosensor is from 0.2 to 22 ng mL−1 for both NSE and S100-β. The lowest detectable concentration is 0.1 and 0.06 ng mL−1 for NSE and S100-β, respectively. The assay results for serum samples with the proposed method were in a good agreement with the standard enzyme-linked immunosorbent assay method. The proposed immunosensor is promising in clinical diagnosis. This method, which utilizes the surface-enhanced Raman scattering of HAuNPs, has great potential in the detection of biomarkers, which are vital in medical diagnoses and disease monitoring.
研究领域:
医学诊断
·
生物化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Yinmei Tian,Qian Hu,Zhengjun Sun,Yulin Yu,Xiaonan Li,Tianyi Tian,Xinying Bi,Yang Li,Boning Niu,Zhiping Zhang
Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid–liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity. Herein, in this study, a biocompatible diethylaminoethyl-dextran hydrochloride/sodium polyphenylene sulfonate coacervates, coated with eudragit S100 to improve the stability and colon targeting ability, named EU-Coac, is developed. Emodin, an active ingredient in traditional Chinese herbs proven to alleviate UC symptoms, is loaded in EU-Coac (EMO@EU-Coac) showing good stability in gastric acid and pepsin and pH-responsive release behavior. After oral administration, EMO@EU-Coac can effectively target and retain in the colon, displaying good therapeutic effects on UC treatment through attenuating inflammation and oxidative stress response, repairing colonic epithelia, as well as regulating intestinal flora balance. In short, this study provides a novel and facile coacervate microdroplet delivery system for UC treatment.
研究领域:
药学
·
生物医学工程
·
胃肠病学
·
药物递送系统
·
炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 34
·13381-13387
·
IF 3.069
Jingyi Sun,Yi Zhao,Yajun Hou,Hanxia Li,Mingfeng Yang,Ying Wang,Baoliang Sun
In this work, a real-time assay for a highly sensitive, label-free, multiplexed electrochemical and surface-enhanced Raman spectroscopic (SERS) detection of stroke biomarkers by neuron-specific enolase (NSE) and S100-β protein was developed using lateral flow devices. We found two kinds of Raman dye (Nile blue A (NBA) and 4-mercaptobenzoic acid (4-MBA))-decorated Au@AgNPs, which show both strong SERS signals and electrochemical redox characteristic peaks. The lateral flow assays are performed by a two-biomarker method for the first time. A sandwich structure contains the Raman dye-labeled Au@AgNPs with the first antibody, the second antibody immobilized on the lateral flow assay biosensor, and the target antigens. Thus, in the presence of the target antigens, the Raman dye-labeled Au@AgNPs could be bonded to the modified lateral flow device surface by antibody–antigen–antibody interactions. As a result, a simultaneous immunoassay for NSE and S100-β based on multiple labels is developed using electrochemical and SERS immunoassays. The prepared immunoassay biosensor for the detection of NSE and S100-β shows high sensitivity, selectivity, low detection limit and long-term stability. Compared with different Raman signals and electrochemical characteristic peaks, this has the lowest detectable concentration for NSE and S100-β at a signal to noise ratio of 3. The proposed immunosensor can be applied to determine NSE and S100-β in human blood serum. In addition, the electrochemical and SERS immunosensor has potential applications in the diagnosis and treatment of strokes in the field of clinical research.
研究领域:
医学诊断
·
生物传感
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Zhenhua Chen,Teng Zhao,Liangliang Zhou,Jinjin Kang,Yongmei Guan,Ming Yang,Shilin Yang,Hongning Liu
Based on the anti-ulcerative colitis (UC) effect of total saponins of Pulsatilla (PTS), a pH dependent colonic targeting particle design powder of PTS was prepared. The core-shell composite particle design powder of PTS was prepared with pH sensitive polymer material Eudragit S100 superfine powder as shell and the drug as core. The release of PTS composite particle design powder was increased in the artificial colon fluid and decreased in the artificial stomach and small intestine fluid. In this paper, the release performance of Pulsatilla saponin D in PTS and the ulcerative colitis model induced by TNBS in rats were used to evaluate the targeting of PTS composite particle design powder in colon. The results showed that the content of Pulsatilla saponin D in colon tissue was significantly higher than that of the original drug group after oral administration of PTS composite particle design powder. The solubility of Pulsatilla saponin D in colon tissue was also higher than that in the stomach and small intestine. The peak time and retention time in vivo were prolonged, and the maximum blood concentration was decreased (C max ). The effect of colonic targeting powder of PTS (50 mg/kg)on anti-ulcerative colitis induced by TNBS in SD rats was better than the original drug (200 mg/kg). Therefore, it is a great significance to make the PTS into colon targeted preparation for improving bioavailability, efficacy and reducing gastrointestinal stimulation.
研究领域:
药剂学
·
药物递送
·
药理学
·
结直肠疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Jie-Zhou,Tian-Le Li,Bo-Wei,Yue-Feng Ruan,Ye-Qin Wang,Jiao-Yan Liu,Meng-Meng Song,Yu-Xian Shen
Midbrain astrocyte-derived neurotrophic factor (MANF) is a secreted protein induced by endoplasmic reticulum stress. Previous studies have indicated that intravenous administration of 1 mg/kg/day recombinant human MANF protein with His tag (His-MANF) for 3 days can ameliorate acute ulcerative colitis in mice. However, long-term intravenous therapy has many disadvantages. In this paper, His-MANF protein was successfully encapsulated into alginate and hyaluronic acid hybrid hydrogel microcapsules in one step using the gas shear method and then coated by Eudragit S100 to construct an oral colon-targeted delivery system (MSH@E). The MSH@E microcapsules exhibited controlled and sustained release behavior and colon-targeting properties. Both fluorescent imaging and immunohistochemistry staining results showed that His-MANF protein could accumulate in the colitis colon for a longer residence time after oral delivery. In vivo studies demonstrated that oral administration of MSH@E microcapsules could alleviate DSS-induced colitis in mice without systemic toxicity. Importantly, even if the oral His-MANF dose was half of the intravenous His-MANF dose, oral delivery was still much more effective than intravenous injection, suggesting the development of the oral colon-targeted delivery system (MSH@E) has great significance and makes a breakthrough from intravenous to oral administration for His-MANF treatment of ulcerative colitis (UC).
研究领域:
药剂学
·
胃肠病学
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Qing Zhou,Guanghui Li,Kaiyang Chen,Hong Yang,Mengran Yang,Yuye Zhang,Yakun Wan,Yanfei Shen,Yuanjian Zhang
Due to exceptional electron-accepting ability, light-absorption, and a delocalized conjugated structure, buckminsterfullerene (C60) has attracted fascinating interest in the field of organic solar cells. However, poor delocalization and accumulation of electrons for pristine C60 in physiological aqueous solution and difficulties in conjugation with biomolecules limit its extended photovoltaic applications in bioassay. Herein, we reported the noncovalent coupling of C60 to an electronically complementary porphyrin-derived metal–organic framework (PCN-224) with carboxyl-group terminals. Such assembly not only offered a friendly interface for bioconjugation but also resulted in a long-range ordering C60@PCN-224 donor–acceptor system that demonstrated an unprecedented photocurrent enhancement up to 10 times with respect to each component. As an example, by further cooperating with Nanobodies, the as-prepared C60@PCN-224 was applied to a photoelectrochemical (PEC) immunosensor for S100 calcium-binding protein B with by far the most promising detection activities. This work may open a new venue to unlock the great potential of C60 in PEC biosensing with excellent performances.
研究领域:
材料科学
·
生物化学
·
分析化学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2023
·
IF 5
Ying Xu,Chenguang Hu,Jiayu liu,Haoran Guo,Jingkai Gao,Chi Wang,Chengbin Wang
Background and Aims Synovial fluid lactoferrin (LTF) and S100 calcium-binding protein A8 (S100A8) have been considered as potential biomarkers for the diagnosis of periprosthetic joint infection (PJI) through our previous research. However, the detection methods of these two proteins are still immature, so a rapid, accurate and cost-effective testing method is warranted. Materials and Methods We developed chemiluminescent immunoassays (CLIA) for the automated detection of synovial fluid LTF and S100A8 and assessed the analytical performance for these two methods. In addition, we recruited 86 patients who were suspected of PJI after total joint replacement (TJA) and examined their synovial fluid using CLIA to explore the clinical application value of these methods and the diagnostic efficiency of synovial fluid LTF and S100A8 for PJI. Results Our established CLIA methods have a wide linear range of 20–10,000 ng/mL for LTF detection system and 5–5000 ng/mL for S100A8 detection system. Performance parameters such as precision, specificity, and recovery rate can meet the industry standards. Then, the established methods were used to detect LTF and S100A8 in synovial fluid samples, which showed excellent diagnostic efficiency for PJI, and the areas under ROC curve (AUC) were 0.954 (95 % CI : 0.909–0.999) and 0.958 (95 % CI : 0.918–0.997), respectively. Conclusion Our established CLIA methods have the advantages of automation, high throughput, low price, and is expected to be widely popularized in clinical applications. Synovial fluid LTF and S100A8 detected through CLIA had efficient diagnostic potentiality for predicting and diagnosing PJI.
研究领域:
临床诊断
·
骨科
·
免疫学
·
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）