Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 9
·1841-1851
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IF 5.344
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Jiyu Fang
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints of the body. Although liposomes are a promising drug delivery vehicle, there is still a challenge of using conventional liposomes for the treatment of RA due to their short circulation time and physicochemical instability in blood vessels. Here, we report the formation of polymerized stealth liposomes composed of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG2000) with a thin-film hydration method, in which DC8,9PC molecules are cross-linked in the bilayer of the liposomes by UV irradiation and the PEG chains present at the surface of the liposomes provide a stealth layer. We demonstrate that the polymerized stealth liposomes are stable and show long circulation time in blood vessels. They can be internalized by cells without significant toxicity. After being injected into arthritic rats, the polymerized stealth liposomes with loaded dexamethasone (Dex) show long blood circulation time and accumulate preferentially in inflamed joints, consequently suppressing the level of proinflammatory cytokines (TNF-α and IL-1β) in joint tissues, reducing the swelling of inflamed joints and alleviating the progression of RA. We believe that polymerized stealth liposomes can be used as a promising drug delivery vehicle for various therapeutic applications.
研究领域:
药理学
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药物递送系统
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风湿病学
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纳米技术
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PubMed
高影响因子
Redox Biology
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2025
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IF 11.9
Jianwen Su,Sushuang Ma,Mankai Yang,Jichang Wu,Yijie Chen,Mingchao Jin,Qin Shi,Xianrong Zhang
Bone marrow adipogenic precursors play important roles in bone metabolism in both young and adult mice, but their contributions to early long bone development remains poorly understood. In this study, we elucidate the role of bone marrow adipocyte lineage precursors in modulating bone marrow redox homeostasis through the secretion of fibulin-5 (Fbln5), using a prenatal dexamethasone exposure (PDE) mouse model. Our previous research demonstrates that PDE induces cellular senescence in the bone marrow, resulting in long bone growth retardation in young offspring. Extending these findings, we now reveal that PDE not only induces cellular senescence and impairs bone formation, but also disrupts type H vessels and reduces Adiponectin-expressing ( Adipoq + ) cells. Importantly, genetic ablation of Adipoq + cells recapitulates the phenotypes observed in PDE-exposed offspring, characterized by increased cellular senescence and loss of osteoblasts and osteoprogenitors during the early postnatal period, ultimately resulting in reduced trabecular bone mass in young adult mice. RNA-seq and in vivo data identify that Adipoq + cells are a primary source of Fbln5, and that PDE significantly reduced the number of Adipoq + cells, thereby decreasing Fbln5 expression and elevating ROS stress in bone marrow. Moreover, targeted overexpression of Fbln5 in Adipoq + cells via adeno-associated virus effectively mitigates cellular senescence and ROS accumulation, preserves type H vessels and osteoblasts, and normalizes osteoclasts activity, thereby rescuing the long bone growth retardation caused by PDE. Collectively, these findings uncover a previously unrecognized function of Adipoq + cells in regulating redox homeostasis within the bone marrow microenvironment during the early stages of long bone development.
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高影响因子
Nano Today
·
2024
·
IF 13.2
Hongbing Liu,Muse Ji,Yi Qin,Yin Sun,Hanxun Wang,Peifu Xiao,Jiansong Zhao,Yaxin Deng,Zhen Zhang,Jingxin Gou,Tian Yin,Haibing He,Guoliang Chen,Xing Tang,Yu Zhang
Cytokine storm and pulmonary fibrosis caused by Coronavirus Disease 2019 (COVID-19) are the two major culprits threatening human life and health. Herein, we engineered a novel disulfide-bridged carrier-free prodrug self-assembled nanoparticles (DSSL NPs) composed of Dexamethasone (Dex) and α-linolenic acid (LNA) for synergistic inhibition of cytokine storm and pulmonary fibrosis. DSSL NPs possess the capability to selectively target injured lung tissue and precisely release drugs after intravenous administration. Consequently, a single administration of DSSL NPs effectively mitigated pro-inflammatory cytokines and tissue damage in mice with lipopolysaccharide (LPS)-induced cytokine storm by blocking the TNF, NF-κB, and Toll-like receptor signaling pathways. Moreover, long-term administration of DSSL NPs alleviated the abnormal fibroblast activation and collagen deposition in mice with LPS-induced pulmonary fibrosis by inhibiting the Wnt-PCP signaling pathway without obvious Dex-related side effects. Together, DSSL NPs achieved the effect of ‘killing two birds with one stone’, presenting a safe and reliable strategy for comprehensive treatment for COVID-19-related diseases.
研究领域:
药学
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纳米技术
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免疫学
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肺科学
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病毒学
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高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 5
·1-10
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IF 2.4
Jiaqi Shi,Li Chen,Xu Wang,Xin Ma
Steroid‑induced osteonecrosis of the femoral head (ONFH) is a serious complication caused by long‑term or excessive use of glucocorticoids. The present study aimed to ascertain the effects of tripartite motif‑containing protein 21 (TRIM21) on the process of steroid‑induced ONFH and its hidden action mechanism. TRIM21 expression in dexamethasone (Dex)‑treated mouse MC3T3‑E1 preosteoblast cells was examined using reverse transcription‑quantitative PCR and western blotting. The Cell Counting Kit‑8 (CCK‑8) method and lactate dehydrogenase release assay were used to respectively measure cell viability and injury. Flow cytometry analysis was used to assay cell apoptosis. Caspase 3 activity was evaluated using a specific assay, while alkaline phosphatase and Alizarin red S staining were used to evaluate osteogenesis. 2,7‑dichloro‑dihydrofluorescein diacetate fluorescence probe was used to estimate reactive oxygen species generation. Specific assay kits were used to appraise oxidative stress levels. In addition, the expression of apoptosis‑, osteogenic differentiation‑ and Kelch‑like ECH‑associated protein 1 (Keap1)/nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling‑associated proteins was assessed using western blotting. In Nrf2 inhibitor (ML385)‑pretreated MC3T3‑E1 cells exposed to Dex, cell apoptosis, osteogenesis and oxidative stress were detected again as aforementioned. Results revealed that TRIM21 expression was raised in Dex‑induced MC3T3‑E1 cells and TRIM21 deletion improved the viability and osteogenic differentiation, whereas it hampered the oxidative stress and apoptosis in MC3T3‑E1 cells with Dex induction. In addition, silencing of TRIM21 activated Keap1/Nrf2 signaling. Moreover, ML385 partially abrogated the effects of TRIM21 depletion on the oxidative stress, apoptosis and osteogenic differentiation in MC3T3‑E1 cells exposed to Dex. In conclusion, TRIM21 silencing might activate Keap1/Nrf2 signaling to protect against steroid‑induced ONFH.
研究领域:
骨科
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细胞生物学
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分子生物学
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PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-20
·
IF 7.5
Zhang Bin,Bai Miao,Yang Mengshi,Wang Yumei,Chen Xiyu,Liu Baiyun,Shi Guangzhi
Background Glucocorticoids (GCs) have been widely used in the treatment of severe traumatic brain injury (TBI) to inhibit neuroinflammation and alleviating brain edema and cannot be replaced by other drugs. However, their systemic application still faces many obstacles, such as the poor blood-brain-barrier (BBB) penetration and severe side effects. Therefore, new treatment strategy or compounds are urgently needed in clinic.Methods Herein, an injectable nanocomposite hydrogel is developed as a biofunctionalized delivery platform for intraoperative administration of dexamethasone (DEX) after TBI. By using a mice TBI model, the safety and efficacy of the nanohydrogels in treating BBB disruption, brain edema and nerve injury were evaluated after TBI.Results The hydrogel is composed of polysaccharide matrix (carboxymethyl chitosan and oxidized dextran) and mesoporous polydopamine (MPDA) nanoparticles loaded with DEX (MPDA@DEX@gel) that could realize in situ injection, self-assembly, a high DEX loading rate and sustained release around the lesion. The MPDA@DEX@gel exhibits excellent antibacterial and hemostatic properties, good biocompatibility and antioxidation, and self-healing capability in vitro. These in vitro and in vivo results show that local application of MPDA@DEX@gel not only alleviates brain edema, promotes neuronal survival, and improves neurological function by restoring the integrity of BBB and inhibiting neuroinflammation after TBI, but also effectively avoids the peripheral and central side effects.Conclusion Our study provides a promising treatment strategy for the rational use of GCs in patients with severe TBI.
研究领域:
神经科学
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药剂学
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材料科学
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PubMed
高影响因子
CELL TRANSPLANTATION
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2022
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IF 4.139
Wan Wei,Qiuhong Yang,Jing Hu,Yong Yao,Huayuan Yang
The physicochemical stimulation of acupoints is a widespread treatment strategy for different diseases, such as sciatica. Its efficacy is mainly based on the temporal and spatial modulation of the physicochemical properties of the acupoints. The existing therapies based on the stimulation of acupoints have certain disadvantages. Therefore, in this study, injectable dexamethasone (DXM)- and magnetic Fe3O4 nanoparticles-loaded chitosan/β-glycerophosphate (CS/GP) thermal crosslinking hydrogels were prepared, thereby improving the performance of embedding materials. The sciatica rat models were established to compare the therapeutic effects of hydrogels and catgut. The DXM or Fe3O4-loaded CS/GP hydrogels were compared in terms of their gelation kinetics, release kinetics, magnetic responsiveness in-vitro, and biocompatibility as well as their analgesic effects on the chronic constriction injury of the sciatic nerve (CCI) rats in-vivo. The CS/GP/Fe3O4/DXM hydrogel showed comparable gelation kinetics and good magnetic responsiveness in-vitro. This hydrogel could relieve sciatica by reducing the expression levels of inflammatory factors in serum, inhibiting the p38MAPK (p38, mitogen-activated protein kinase) phosphorylation, and decreasing the expression level of the P2X4 receptor (P2X4R) in the spinal dorsal horn. In conclusion, the DXM or Fe3O4-loaded CS/GP hydrogels can be considered as a treatment option for the physiochemical stimulation therapy of acupoints to improve sciatica.
研究领域:
药理学
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材料科学
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神经科学
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生物医学工程
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中医
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PubMed
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donghao Gu,Le Zhou,Yanming Zhang,Haochun Jin,Wenlong Nie,Minquan Zhang,Yidian Dong
Dexamethasone (Dex) is a primary medication for treating dry eye syndrome, and tobramycin-dexamethasone eye drops are commercially available. However, the eye's complex physiological environment reduces its bioavailability, and repeated use can lead to significant systemic toxicity and side effects. This study introduces a novel conjugate of chitosan (CS) and N -acetylcysteine (NAC), a bioadhesive material, which was grafted onto the surface of a Dex-supported nanostructured lipid carrier (NLC) to develop an innovative nanoparticle lipid ocular drug delivery system (CS-NAC@Dex-NLC). The enhancements afforded by CS-NAC, such as adhesion, osmotic, and targeting properties, address the limitations of traditional eye drops. NMR characterization confirmed the successful synthesis of the copolymer (CS-NAC). Particle size (PS), zeta potential, and transmission electron microscopy (TEM) verified the proper formation of the CS-NAC@Dex-NLC system. Cytotoxicity tests confirmed its excellent biocompatibility and safety. Cellular uptake studies showed that CS-NAC@Dex-NLC achieved the highest efficiency. Pharmacokinetic assessments revealed a significant increase in Dex's bioavailability in tears and aqueous humor. In vitro corneal penetration and in vivo imaging experiments demonstrated effective corneal penetration and retention, enhancing the drug's duration on the ocular surface and overcoming the barrier effect. Pharmacodynamic studies in rabbits with dry eye syndrome indicated that CS-NAC@Dex-NLC effectively alleviates symptoms, repairs corneal damage, and stabilizes the tear film. ELISA results showed a reduction in inflammation caused by dry eye. These findings suggest that CS-NAC@Dex-NLC is a promising vector for dry eye treatment, offering significant clinical relevance.
研究领域:
药剂学
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眼科
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生物材料学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Jingting Luo,Yanyu Li,Xin Zhang,Zhen Wang,Jingjie Wang,Jia Hao,Cheng Ran,Xiaobo Ma,Zhimin Zhou
Combination therapies with two or more drugs administrated by intratympanic (IT) injection represent a promising strategy for the treatment of sensorineural hearing loss (SNHL), an inner ear disease imposing a substantial burden on patients. However, the therapeutic outcomes of conventional liquid formulations have been hindered by poor drug retention in the middle ear cavity. In the present study, a versatile hydrogel (CT Gel) was engineered for co-delivery of dexamethasone and lidocaine with drug-loaded microparticles as both cross-linkers and modular drug reservoirs. Specifically, dexamethasone microcrystals and lidocaine-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were separately prepared and subsequently coated with polydopamine (PDA). The resulting PDA-functionalized microparticles were then employed to crosslink phenylboronic acid-modified hyaluronic acid via dynamic covalent boronate ester bonds, thereby forming the hydrogel. CT Gel exhibited injectable, bioadhesive, antioxidant and sustained-release properties. Moreover, it was shown that, following IT administration in guinea pigs, CT Gel persisted in the middle ear cavity for over 7 days, enhanced drug exposure in the perilymph, and exhibited favorable biocompatibility. We anticipate that such hydrogels, crosslinked using drug-loaded microparticles as modular drug reservoirs, will find broad applications in the combinatorial treatment of inner ear disorders.
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CANCER LETTERS
·
2022
·
IF 9.756
Ying Zhou,Li Guan,Wei Li,Ruinan Jia,Lejiao Jia,Yuanyuan Zhang,Xin Wen,Sibo Meng,Daoxin Ma,Na Zhang,Min Ji,Yongjun Liu,Chunyan Ji
T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy and glucocorticoid resistance is the main recurrent cause for a high relapsed and death rate. Here, we proposed an effective therapeutic regimen of combining gamma-secretase inhibitors (GSIs) with dexamethasone (DEX) to overcome glucocorticoid resistance. Moreover, the bone marrow targeting DT7 peptide-modified lecithin nanoparticles co-loaded with DEX and GSI (TLnp/D&G) were developed to enhance T-ALL cells recognition and endocytosis. In vitro cytotoxicity studies showed that TLnp/D&G significantly inhibited cell survival and promoted apoptosis of T-ALL cells. Mechanically, we found that GSIs promoted DEX-induced cell apoptosis by two main synergetic mechanisms: 1) GSIs significantly upregulated glucocorticoid receptor (GR) expression in T-ALL and restored the glucocorticoid-induced pro-apoptotic response. 2) Both DEX and GSI synergistically inhibited BCL2 and suppressed the survival of T-ALL cells. Furthermore, in vivo studies demonstrated that TLnp/D&G showed high bone marrow accumulation and better antileukemic efficacy both in leukemia bearing models and in systemic Notch1-induced T-ALL models, with excellent biosafety and reduced gastrointestinal toxicity. Overall, our study provides new strategies for the treatment of T-ALL and promising bone marrow targeting systems with high transformation potential.
研究领域:
肿瘤学
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药学
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纳米技术
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血液学
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DOI
PubMed
高影响因子
Food Bioscience
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2025
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IF 5.9
Hongfei Yang,Liangni Qin,Jiaxu Xiao,Xiaoming Pan,Shiyun Han,Linwei Zhang,Jixiang Liang,Yu Si,Hao Wen,Long Li,Xingyu Wang,Xiaojuan Zhang,Dapeng Peng
Dexamethasone, a long-acting glucocorticoid, exhibits considerable structural similarity to other glucocorticoids. To avoid false-positive results in immunoassays due to cross-reactivity of antibodies with structural analogues, the preparation of highly specific antibodies is crucial. In this study, a novel hapten DEX-GA was designed and synthesized, and the monoclonal antibody (mAb) 3D1 was successfully prepared based on the hapten. The mAb 3D1 has the 50 % inhibitory concentration of 0.38 ng/mL for dexamethasone, with cross-reactivity below 7.45 % against twelve glucocorticoids including betamethasone, prednisone, triamcinolone and beclomethasone. Based on this antibody, indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold immunochromatography assay (GICA) were developed for accurate detection of dexamethasone in milk and animal tissues. The limits of detection of ic-ELISA in milk and animal tissues ranged from 0.132 to 0.215 μg/kg, which was a 1-3-fold increase in sensitivity compared with the previously reported ic-ELISA method. The GICA method established in this study had a visual limit of detection of 0.3 μg/L in milk. Notably, this constitutes the first application of GICA in animal tissues, demonstrating a visual detection limit of 0.2 μg/kg. The accuracy and reliability of both ic-ELISA and GICA were validated using liquid chromatography-tandem mass spectrometry.
研究领域:
免疫学
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分析化学
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生物化学
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药理学
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兽医学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2017
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IF 6.216
Jiabing Ran,Hao Zeng,Jing Cai,Pei Jiang,Pan Yan,Lingyue Zheng,Yi Bai,Xinyu Shen,Bin Shi,Hua Tong
Endowing titanium implants with the capability of delivering dexamethasone in a sustained and controlled manner to promote osseointegration and osteogenesis has become an emerging field. However, most of the currently developed dexamethasone/titanium implants are far from satisfactory because of some inherent defects. In this work, we constructed a stable, effective, and sustained dexamethasone delivery platform on titanium disc by immobilizing [email protected] imidazolate framework-8 nanoparticles into the micrometer-scale artificial etch pits on titanium substrate using methanol-induced regenerated silk fibroin membrane encapsulation. In addition, the titanium substrate was aminated and covalent interactions were established between the titanium substrate and the silk fibroin membrane through genipin crosslinking. Briefly, owing to the synergistic barrier effect of the zeolitic imidazolate framework-8 shell and the silk fibroin membrane, the silk fibroin-dexamethasone [email protected] imidazolate framework-8-titanium could release dexamethasone in a controlled manner over 30 days. Moreover, the pit walls together with the silk fibroin membrane protected the nanoparticles from detaching from the titanium substrate in the case of mechanical wear. The covalent interactions between the silk fibroin membrane and the titanium substrate prevented the silk fibroin membrane from self-peeling from the titanium substrate in a moist environment. In vitro cell culture indicated that the as-prepared titanium disc had good cytocompatibility with MC3T3-E1 cells. Furthermore, the cells cultured on the titanium disc demonstrated higher differentiation, calcium deposition, and expression of osteogenic genes than the cells cultured on the silk fibroin-zeolitic imidazolate framework-8-titanium and pristine titanium. In this work, dexamethasone was utilized as a drug model and could be replaced by other osteogenic drugs or growth factors. Thus, we believed that our design philosophy could inspire future research work on the development of Ti implants.
研究领域:
生物材料
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药物递送系统
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组织工程
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骨科
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高影响因子
REPRODUCTION FERTILITY AND DEVELOPMENT
·
2021
·Vol. 33
·期 12
·700-712
·
IF 2.311
Xin Zhan,Yiran Xie,Liping Sun,Qi Si,Hongkai Shang,Xin Zhan,Yiran Xie,Liping Sun,Qi Si,Hongkai Shang
This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.
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高影响因子
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