Frontiers in Pharmacology
·
2020
·
IF 4.225
Li Qianqian,Zhou Jia,Zhang Dingyi,Zhang Xiafeng,Xu Zhenghao,Wu Dehong
Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, etc.), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.
研究领域:
免疫学
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药理学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2013
·
IF 2.206
Yan-Ling Luo,Li-Li Chen,Yan Miao,Feng Xu
Novel AB4-type polyurethane (PU) micelle-like amphiphilic block copolymers consisting of hydroxyl-functionalized carboxyl-terminated poly(butadiene-co-acrylonitrile) (f-CTBN) as the hydrophobic cores and methoxy poly(ethylene glycol) (MPEG) as the hydrophilic branched blocks were synthesized via esterification, followed by coupling reaction. Their chemical structure and molecular weight were characterized by FTIR, NMR, and SEC measurements. The block copolymers could easily self-assemble to form core–shell micelle nanoparticles in various media. The micelles bear a critical micelle concentration (CMC) in a range from 0.740 to 6.310 mg L–1 and were very stable even in PBS solutions. The TEM and DLS findings revealed that the micelles were almost spherical and narrow-size-distribution, with TEM mean diameters from 13 to 24 nm, and average hydrodynamic diameter about 124–151 nm. All these depended on chain lengths and compositional ratios of hydrophilic MPEG blocks. The drug loading and in vitro release indicated that the self-assembled micelle nanoparticles could effectively load hydrophobic prednisone, with encapsulation capacity of about 27–30%, and the drug release from the nanoparticles was dependent on MPEG chain lengths and the molar ratios of f-CTBN to MPEG. Cytotoxicity assays disclosed that the as-prepared block copolymer micelle nanoparticles exhibit good biocompatibility and could be employed as potential drug controlled release carriers.
研究领域:
生物材料
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药物递送
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纳米医学
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高分子化学
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药剂学
✓ 已验证
DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2024
·
IF 2
Xiaofang Luo,Yuntian Xiao,Linlin Shi,Lingli Hou,Yongkang Liu,Ling Zhou,Qiuxiang Yin
Prednisolone (PDL), a corticosteroid extensively used in the treatment of allergic and autoimmune inflammatory diseases, faces limitations in clinical application due to its poor water solubility. Consequently, grasping the solid–liquid equilibrium behavior across diverse solvents is imperative for advancing the development of solid formulations with improved bioavailability. This study measured the solubility of PDL Form I in 13 pure solvents using gravimetric analysis and employed molecular dynamics, including molecular electrostatic potential surface analysis, Hirshfeld surface analysis, the independent gradient model based on Hirshfeld partitioning, radial distribution function, and solute–solvent interaction energy calculations, to explore the solid–liquid equilibrium behavior. The solubility of PDL Form I across various solvents exhibited a temperature-dependent increase, showing the largest variation in acetone. Radial distribution function analysis indicated multiple hydrogen-bonding interactions between the PDL molecule and the solvents tested. The calculations of solute–solvent interaction energy revealed that ethanol had the highest interaction energy with PDL, correlating with its the highest solubility. The validity of the solid–liquid equilibrium data was confirmed by fitting to the Apelblat equation, λh model, van’t Hoff equation, and NRTL equation, with an average relative deviation below 2.5, indicating good correlation.
研究领域:
药学
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生物物理学
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化学工程
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产品关联
DOI
高影响因子
MethodsX
·
2022
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IF 0
Tongtong Zhu,Mengyang Jiang,Mingran Zhang,Liguo Cui,Xiaoyu Yang,Xukai Wang,Guangyao Liu,Jianxun Ding,Xuesi Chen
Osteonecrosis is a common orthopedic disease in clinic, resulting in joint collapse if appropriate treatment is not given in time. The clinical usage of high-dose steroid is one of the common causes of osteonecrosis. In several studies, the intravenous injection of steroid with or without lipopolysaccharide is the most commonly used strategy to construct osteonecrosis animal model. However, the injection dose, frequency, and interval of steroid and validation of successful model construction lack generally accepted protocol, and the survival and model formation rates are unsatisfactory. We have optimized the construction protocol of osteonecrosis animal model based on the previously reported ones and established a mature animal model of osteonecrosis for future studies. • A rabbit model of osteonecrosis was constructed by multiple injections of high-dose methylprednisolone. • The multidisciplinary biomedical examinations demonstrated the successful construction of osteonecrosis model in the rabbit.
研究领域:
骨科
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药理学
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动物模型
✓ 已验证
产品关联
DOI
PubMed
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
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2013
·
IF 2.207
Feng Xu,Ting-Ting Yan,Yan-Ling Luo
Novel amphiphilic block copolymers consisting of hydrophobic poly(D,L-lactide) segments and hydrophilic poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide) blocks were designed and synthesized through a simple free radical copolymerization route based on a bifunctional initiator, followed by the ring-opening polymerization of D,L-lactide. The copolymers self-assembled into thermosensitive spherical-nanosized core–shell micelles in aqueous solution in the presence or the absence of the model drug prednisone. The chemical and physical characterizations of drug-loaded and unloaded micelles revealed a lower critical solution temperature of 40°C–47°C, and a critical micelle concentration less than 7.20 mg L−1, a transmission electron microscope mean particle size from 50 to 75 nm, and a narrow dynamic light scattering diameter below 180 nm. The prepared blank and drug-loaded micellar nanoparticles were thermodynamically stabile and employed in targeted drug delivery by responding to the higher temperature of the local microenvironment. Based on prednisone release kinetic studies, structural changes of the self-assembled micelles as well as temperature- or environment-induced diffusion controlled drug release and improved bioavailability. The copolymer micelles exhibited good biocompatibility as established by the MTT cytotoxicity assay. Therefore, an effective target therapy against lesion tissues is feasible using these polymeric micelles.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子
Orthopaedic Surgery
·
2022
·Vol. 14
·期 10
·2669-2681
·
IF 2.279
Bo-yong Jang,Shi-bing Guo,Rui Bai,Wan-lin Liu,Yu-lin Gong,Zhen-qun Zhao
Objective To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid-induced avascular necrosis of the femoral head (SANFH). Methods In cell experiment, VEC were isolated and cultured from the femoral head of Sprague–Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR-shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT-PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6-keto-PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. Results In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups ( P < 0.05). The mRNA expression levels of PI3K, Akt and mTOR in the MP group were significantly higher than in the Ctrl group, while the MP+ shmTOR group presented intermediate levels between these groups (average gray value were 3837.90, 2996.30, 3005.60, F = 428.64, P < 0.05). MRNA expression levels of Beclin1 and MAP1LC3 in the MP group were significantly lower than that in Ctrl group ( P < 0.05). The content of 6-keto-PGF1α in the MP + shmTOR group was higher than in the Ctrl group and lower than in the MP group at the evaluated time intervals (average absorbance value were 104.98, 206.83, 145.91, F = 352.83, P < 0.01). In vivo experiment, the content of 6-Keto-PGF1α in the hormone group increased as time went on; the mTOR-si group was higher than that in control group, but lower than that in the hormone group ( P < 0.01). The mRNA expressions of Beclin1 and MAP1LC3 in the control group were higher than those in the hormone group, while the mRNA expressions of PI3K, Akt and mTOR were lower than those in the mTOR-si group ( P < 0.05). Conclusion The steroid inhibited the physiological protective effect of autophagy on SANFH by increasing the expression of PI3K/Akt/mTOR signaling pathway related factors and decreasing the expression of Beclin1 and MAP1LC3 in the femoral head VEC.
研究领域:
药理学
·
细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Hoang Nguyen Tien,Fredrick M. Mwazighe
In this work, a novel La-doped βPbO 2 (Ti/SnO 2 –Sb/La-βPbO 2 ) was prepared using electrodeposition method and applied to the degradation of prednisolone (PRD), 8-Hydroxyquinoline (8-HQ), and other typical organic pollutants. Compared with the conventional electrode Ti/SnO 2 –Sb/βPbO 2 , La 2 O 3 doping enhanced oxygen evolution potential (OEP), reactive surface area, stability and repeatability of the electrode. The 10 g L −1 of La 2 O 3 doping exhibited the highest electrochemical oxidation capability of the electrode with [•OH]ss being determined at 5.6 × 10 −13 M. The quenching experiments were conducted to confirm the main oxidizing species (here: •OH) in the electrochemical process. The study showed that the pollutants were removed in the electrochemical (EC) process with different degradation rates and indicated that the second-order rate constant of organic pollutants towards •OH ( k OP,•OH ) has a linear relationship with the degradation rate of organic pollutants ( k OP ) in the electrochemical process. Another new finding in this work is that a regression line of k OP,•OH and k OP can be used to estimate k OP,•OH of an organic chemical, which cannot be determined using the competition method. k PRD,•OH and k 8-HQ,•OH were determined to be 7.4 × 10 9 M −1 s −1 and (4.6–5.5) × 10 9 M −1 s −1 , respectively. Compared with conventional supporting electrolyte (like SO 4 2− ), H 2 PO 4 − and HPO 4 2− improved k PRD and k 8-HQ by 1.3–1.6-fold, while SO 3 2− and HCO 3 − inhibited k PRD and k 8-HQ significantly, down to 80%. Additionally, the degradation pathway of 8-HQ was proposed based on the detection of intermediates from GC-MS.
研究领域:
环境科学
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电化学工程
·
污染控制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
·
2018
·
IF 3.394
Deng Shuang,Zhou Jian-Lin,Fang Hong-Song,Nie Zhi-Gang,Chen Sen,Peng Hao
Glucocorticoids intake has become the most common pathogenic factor for osteonecrosis of the femoral head (ONFH). Annually, tens of millions of patients suffer from pain related to ONFH. Researchers have proposed several underlying mechanisms of ONFH, including osteocyte apoptosis, cell differentiation disorder, and angiogenesis hindrance. Sesamin, isolated from Sesamum indicum seeds, was reported could affect osteocyte inflammation and differentiation in osteoarthritis and osteoporosis. We investigated the underlying influence of sesamin on ONFH rat model. Fifteen male Sprague-Dawley rats were randomly divided into three groups. The ONFH model group only received the methylprednisolone (MPS) and lipopolysaccharide (LPS) injection to promote the development of ONFH. The sesamin treatment group was injected with sesamin, MPS, and LPS. The control group was untreated. Rats from above groups were sacrificed 4 weeks later. The effect of sesamin on ONFH rats was validated by H&E staining. TUNEL staining showed that femoral head necrosis was attenuated by sesamin. Furthermore, the phosphorylation of Akt was increased and the downstream cellular apoptosis signal pathway was inhibited. Intracellular ROS level was decreased after sesamin treatment. In conclusion, our findings suggest that sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis.
研究领域:
药理学
·
骨科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2013
·
IF 2.108
Yan-Ling Luo,Rui-Juan Huang,Li-Li Zhang,Feng Xu,Ya-Shao Chen
A thermo- and pH-stimuli-responsive brush-shaped graft copolymer based on macromonomers acrylate terminated PMAA–CH=CH 2 and PNIPAAm–CH=CH 2 was synthesized, which is composed of poly(methacrylic acid) (PMAA) and poly( N -ispropylacrylamide) (PNIPAAm) as graft brushes, named PMAA- b -PNIPAAm. The copolymers can self-assemble to form spherically-shaped core-shell nanostrucrued micelles in different media, with the critical micelle concentration (CMC) in aqueous solution from 9.24 to 32.81 mg L −1 , and the hydrodynamic diameters varying with pH and temperature, from 120 to 195 nm. The resultant nanoscale copolymer micelles exhibited pH-triggered thermoresponsive behavior, with low critical solution temperature (LCST) about 38.2–47.5 °C. The polymer micelle nanoparticles were observed to be stable under simulated physiological conditions. The cytotoxicity studies by MTT assay and in vitro prednisone drug release demonstrated that the PMAA- b -PNIPAAm copolymer micelles were not directly toxic to L929 mouse embryonic fibroblasts and the in vitro release behavior under various physiological environments depended upon pH and temperature change. Therefore the as-prepared brush-shaped graft copolymer micelle nanoparticles may serve as a promising “intelligent” drug delivery carrier.
研究领域:
材料科学与工程
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
MATERIALS TECHNOLOGY
·
2023
·
IF 3.1
Quan Chen,Huiyan Deng,Bihua Liang,Runxiang Li,Huaping Li,Yanan Ke,Huilan Zhu
Recurrent eczematous lesions and acute itching describe chronic actinic dermatitis (CAD). Continuous use of corticosteroids might result in a dermal adverse effect. Chitosan (CS)-coated PLGA nanoparticles encapsulated prednisolone (PDS) and co-encapsulated to poloxamer hydrogel to enhance anti-inflammatory action and reduce side effects. The PDS@NPs were synthesized using the solvent-emulsification evaporation method, and their physical and chemical properties were analysed. Ex vivo drug absorption experiment was conducted utilizing the Franz diffusion cells in vitro. Toxic effects on human fibroblasts and keratinocytes were not observed in the nanoparticle formulations. Nanoparticles and hydrogels altered PDS’s release kinetics, but not by the non-encapsulated PDS (NE@PDS). Nanoparticles could not penetrate the stratum corneum of removed the skin, which shows the nano-encapsulation of PDS improved skin absorptions. Pseudoplastic and non-Newtonian behaviour was seen in all hydrogels. The nanoformulations appear to be a promising option for glucocorticoid delivery to individuals with chronic actinic dermatitis (CAD).
研究领域:
药剂学
·
纳米技术
·
皮肤病学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2024
·
IF 13
Taoyang Yuan,Weijie Liu,Tianyou Wang,Feng Ye,Jianhua Zhang,Zhipeng Gu,Jianguo Xu,Yiwen Li
The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.
研究领域:
药理学
·
神经科学
·
材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2019
·Vol. 12
·期 3
·659-667
·
IF 8.515
Xu Xin,Yang Weijing,Liang Qiujun,Shi Yanan,Zhang Wenxin,Wang Xiao,Meng Fenghua,Zhong Zhiyuan,Yin Lichen
Co-delivery of anti-inflammatory siRNA and hydrophilic drug provides a promising approach for the treatment of ulcerative colitis (UC). However, lack of a suitable and efficient co-delivery carrier poses critical challenge against their utilization. We herein developed macrophage-targeting, reversibly crosslinked polymersomes (TKPR-RCP) based on the TKPR-modified, poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate)-b-polyethylenimine (PEG-P(TMC-DTC)-PEI) triblock copolymer, which could efficiently encapsulate TNF-α siRNA and dexamethasone sodium phosphate (DSP) in their hydrophilic core. The cationic PEI segments provided additional electrostatic interactions with cargo molecules to promote the encapsulation, and disulfide crosslinking of the polymersome membrane endowed the TKPR-RCP with high colloidal stability. Because the cationic PEI was embedded in the hydrophilic core, the polymersomes displayed neutral surface charge and thus possessed high serum stability. The TKPR-RCP co-encapsulating TNF-α siRNA and DSP could be efficiently internalized by macrophages (∼ 98%) and undergo redox-responsive membrane de-crosslinking to accelerate cargo release in the cytoplasm, thus inducing efficient gene silencing and anti-inflammatory effect. Intravenous injection of the co-delivery TKPR-RCP mediated potent and cooperative anti-inflammatory effect in inflamed colons of UC mice, and significantly prevented animals from colonic injury. This study therefore provides a promising approach for the co-delivery of hydrophilic drug/siRNA toward the treatment of inflammatory bowel diseases.
研究领域:
药学
·
生物医学工程
·
炎症性肠病
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）