Frontiers in Immunology
·
2025
·
IF 5.9
Xinhang Meng,Minfeng Shi,Jinfeng Qian,Yujie Luo,Liyuan Cui,Dajin Li,Songcun Wang
The establishment of placentation and maternal-fetal tolerance are important determinants of a successful pregnancy. Tacrolimus, also known as FK506, is a calcineurin inhibitor that has often been used for pregnant women after solid organ transplantation. Previous therapeutic interventions have shown the benefits of using the immuno-suppressive agent FK506 in improving clinical pregnancy and live birth rates and reducing the risk of spontaneous miscarriage. However, the mechanism(s) by which FK506 is involved in these processes have not been fully elucidated. To further characterize its function in early pregnancy, we explored the effect of FK506 on the human-derived first trimester extravillous trophoblast cells (HTR8/SVneo cells) and found that FK506 promoted invasion, tube formation and proliferation, but inhibited apoptosis of HTR8/SVneo cells. Based on the integrated metabolomics and transcriptomics analyses, the present study provided the cellular and molecular cues evidently showing that FK506 had positive effects on the placentation and maternal-fetal tolerance through modulating FASN-CEACAM1 pathway. The spontaneous-abortion-prone model gave further evidence that FK506 exerted a protective effect on pregnancy by regulating the FASN-CEACAM1 axis. These findings might provide a new fundamental mechanism and promising potential of low-dose FK506 in preventing pregnancy loss.
研究领域:
妇产科学
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免疫学
·
生殖生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2024
·
IF 5.7
Guo Zhixin,Song Yutong,Liu Zhihong,Dai Jiansheng,Chen Zhenzhen,Feng Xianquan,Gao Wenhao,Zeng Lingjun,Song Hongtao
Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy. FK506 M-CNS had a particle size of 87.69 ± 1.05 nm and zeta potential of 22.06 ± 1.01 mV. Results of histological evaluation through H&E staining and in vitro cytotoxicity of human corneal epithelial cells consistently revealed the excellent biocompatibility of FK506 M-CNS. FK506 M-CNS exhibited superior ocular retention compared to the market product Talymus ® . FK506 M-CNS significantly alleviated the symptoms of DED and promoted the recovery of corneal epithelia. FK506 M-CNS group had the lowest expression levels of inflammatory factors associated with DED. These superiorities might be due to the electrostatic interaction between cationic niosomes and negatively charged mucin in the eye, and the covalent binding of maleimide with the thiol group in the mucin. The maleimide group improved the ocular retention and efficacy of FK506, but did not increase the toxicity. Results indicated that FK506 M-CNS had great potential as a nanopharmaceutical in the treatment of ocular diseases, and M-CNS could be a promising drug carrier for ophthalmic drug delivery systems. Graphical
研究领域:
药学
·
眼科学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Dongmei Wang,Mengmeng Luo,Baoshan Huang,Wa Gao,Yan Jiang,Qing Li,Kaihui Nan,Sen Lin
Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.
研究领域:
神经科学
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 5
·765-778
·
IF 7.571
Maolei Sun,Yun Liu,Kun Jiao,Wenyuan Jia,Kongzhao Jiang,Zhiqiang Cheng,Guomin Liu,Yungang Luo
Guided tissue regeneration (GTR) strategies are an effective approach to repair periodontal defects by using GTR membranes. However, commercial GTR membranes still have limitations in periodontal tissue regeneration owing to lack of antibacterial and osteogenic properties. The development of novel Janus nanofibers with biphasic release characteristics based on the therapeutic needs of GTR is essential to tackle this issue. Here, we developed a multifunctional Janus nanofiber via uniaxial electrospinning, with zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP) loading in the hydrophilic polyvinylpyrrolidone (PVP) part and FK506 embedding in the hydrophobic polycaprolactone (PCL) part. The release of Zn2+ conformed to the Ritger–Peppas kinetics which could effectively prevent bacterial infection, and the release profile of FK506 was fitted to a first-order equation which could provide persistent osteogenic stimulation for osteogenesis. The periodontal tissue regeneration data from a rat periodontitis model revealed that the multifunctional electrospun Janus nanofibers could be used as an effective bioplatform to restore alveolar bone impairment, compared with the control group. In summary, the Janus nanofibers with biphasic release characteristics quickly exert antibacterial function as well as continuously provide a microenvironment beneficial to the osteogenesis process, demonstrating its great potential for GTR treatment in dental clinic applications.
研究领域:
牙科材料
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组织工程
·
生物材料
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牙周病学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Jiani Qiu,Yishu Song,Mengrong He,Nan Cui,Cheng Deng,Ying Bai,Shukun He,Yingxin Li,Tianshu Liu,Wenqian Wu,Li Zhang,Yali Yang,Tang Gao,Mingxing Xie,Qiaofeng Jin,Jing Wang
Significant efforts have been made to deliver immunosuppressants-loaded nanoparticles (NPs) to lymph nodes (LNs) to mitigate transplant rejection. However, conventional administration techniques encounter challenges in enhancing the retention of NPs in the LNs. Attributing the strong affinity of tannic acid (TA) molecules to the elastin of LN conduits, we developed a novel formulation of NPs encapsulating Tacrolimus (FK506), and subsequently modified with TA to produce TA-FNP with a final diameter of approximately 86.07 ± 2.78 nm. These particles could traverse the the intercellular gaps in the lymphatic endothelial cells layers, enter the paracortex through LN capsule-associated conduits, and releases FK506 to inhibit the activation and proliferation of allogeneic T cells. Our finding demonstrated that TA-FNP could accumulate in LNs, significantly increasing the local concentration of FK506 from 69.06 ± 21.96 ng/g to 1041.28 ± 343.59 ng/g compared to the free FK506 treatment group. Subsequently, the therapeutic efficacy of TA-FNP was assessed in heart transplantation model, where treatment with TA-FNP resulted in decreased T cells infiltration within the grafts, reduced rejection grades, and a significant extension of graft survival time. In contrast, FNP without TA showed relatively poor therapeutic outcomes. Consequently, this study reveals a promising strategy utilizing TA to enhance the prolonged retention of FK506 within LNs, underscoring its potential therapeutic application in preventing heart transplant rejection.
研究领域:
药剂学
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免疫学
·
移植医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Xueqin He,Xiaorong Wang,Lianyi Yang,Zhihang Yang,Wenqi Yu,Yazhen Wang,Rui Liu,Meiwan Chen,Huile Gao
The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu& [email protected] ), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain. Meanwhile, these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS. As a result, the cognition of AD mice was significantly improved and the quantity of A β plaques was decreased. Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons. Besides, the neuroinflammation dominated by NF- κ B pathway was significantly inhibited with decreased NF- κ B and IL-1 β in the brain. Overall, Ibu& [email protected] can efficiently and successively target diseased BBB and astrocytes in AD lesion. Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.
研究领域:
神经科学
·
药学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2022
·
IF 9.618
Xiaoyue Zheng,Jiazhou Ye,Weiwei Chen,Xiaoyuan Wang,Jianhua Li,Fengmei Su,Caiping Ding,Youju Huang
Tacrolimus (FK506) is widely used in the prevention of organ transplant rejection and the treatment of autoimmune diseases, but it is difficult to detect within the low and narrow concentration range in practical clinical fields. A magnetic plasmonic superstructure-targets-plasmonic superstructure-based sandwich-type SERS biosensor is presented here to ultrasensitively detect FK506 in the blood of organ transplant patients. The spiky Fe3O4@SiO2@Ag flower magnetic superstructure and hollow Ag@Au superstructure enhanced the SERS signals by providing rich sharp tips, cavities, and abundant hot spot gaps. And the magnetic feature makes it easy to concentrate and separate the biological target. Using the designed sandwich-type SERS biosensor, FK506 could be detected within a range of 0.5–20 ng/mL with a detection limit of 0.33 ng/mL. All results indicated that the sandwich-type SERS biosensor has good stability, sensitivity, and anti-interference properties. It is noteworthy that this allowed us to successfully analyze FK506 in the blood of transplant patients, which is in strong agreement with the clinical results. Consequently, the attractive sandwich-type SERS biosensor can be used for the detection of FK506 in real samples, which is promising for clinical diagnosis.
研究领域:
分析化学
·
生物医学工程
·
纳米技术
·
临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Medicine-JIM
·
2020
·
IF 2.446
Tian Fang,Ze-sheng Xue,Jia-xuan Li,Jia-kuan Liu,Di Wu,Mei-qian Li,Yu-ting Song,Shi-feng Yun,Jun Yan
Objective Herbal medicine is an important therapeutic option for benign prostatic hyperplasia (BPH), a common disease in older men that can seriously affect their quality of life. Currently, it is crucial to develop agents with strong efficacy and few side effects. Herein we investigated the effects of the extract of Rauwolfia vomitoria , a shrub grown in West Africa, on BPH. Methods Rats with testosterone-induced BPH were treated with R. vomitoria . Prostates were histologically analyzed by Hematoxylin and eosin staining. Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting. Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction. The sperm count and body weight of rats were also measured. Results The oral administration of R. vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats, supported by the decreased thickness of the prostate epithelial layer and increased lumen size. Similar effects were observed in the BPH rats treated with the reference drug, finasteride. R. vomitoria extract significantly reduced the testosterone-induced proliferation markers, including proliferating cell nuclear antigen and cyclin D1 , in the prostate glands of BPH rats; it also reduced levels of androgen receptor, its associated protein steroid 5α-reductase 1 and its downstream target genes ( FK506-binding protein 5 and matrix metalloproteinase 2 ). Notably, compared with the finasteride group, R. vomitoria extract did not significantly reduce sperm count. Conclusion R. vomitoria suppresses testosterone-induced BPH development. Due to its milder side effects, R. vomitoria could be a promising therapeutic agent for BPH.
研究领域:
药理学
·
泌尿学
·
草药医学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2019
·
IF 5.667
Yixian Zhang,Haolan Zhang,Zhengwei Mao,Changyou Gao
Although the negative impacts of particulate matter (PM2.5) on human health have been well recognized, very few efforts have been paid to find new strategies to suppress the toxicity of PM2.5 both in vitro and in vivo. In this study, reactive oxygen species (ROS)-responsive nanoparticles made of poly(1,4-phenleneacetonedimethylene thioketal) (PPADT) were used to load immunosuppressant drug tacrolimus (FK506) with a drug loading efficiency of around 44%. The PPADT particles showed very good ROS-responsiveness and were degraded in an oxidation environment. By exhausting intracellular ROS, they could effectively suppress the toxicity of A549 lung epithelial cells and RAW264.7 macrophages induced by the PM2.5 particulates collected from three different regions in China. Moreover, the inflammatory response of PM2.5 could also be significantly suppressed, showing much better performance than the free FK506 drugs both in vitro and in vivo. This concept-proving research demonstrates the promising application for the ROS-sensitive drug release particles in dispelling the toxicity and suppressing the inflammation of PM2.5 pollutes, shedding a new light in the design and applications of stimuli-responsive systems in the bionanotechnology and healthcare fields.
研究领域:
纳米技术
·
生物医学工程
·
环境科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2015
·
IF 2.711
Shaopeng Li
The label-free and sensitive detection of small molecule drugs on SPRi is still a challenging task, mainly due to the limited surface immobilization capacity of the sensor. In this research, a dextran hydrogel-coated gold sensor chip for SPRi was successfully fabricated via photo-cross-linking for enhanced surface immobilization capacity. The density of the dextran hydrogel was optimized for protein immobilization and sensitive small molecule detection. The protein immobilization capacity of the hydrogel was 10 times greater than a bare gold surface, and 20 times greater than an 11-mercaptoundecanoic acid (MUA) surface. Such a drastic improvement in immobilization capacity allowed the SPRi sensor to detect adequate response signals when probing small molecule binding events. The binding signal of 4 nM liquid-phase biotin to streptavidin immobilized on the dextran surface reached 435 RU, while no response was observed on bare gold or MUA surfaces. The dextran hydrogel-coated SPRi sensor was also applied in a kinetic study of the binding between an immunosuppressive drug (FK506) and its target protein (FKBP12) in a high-throughput microarray format. The measured binding affinity was shown to be consistent with reported literature values, and a detection limit of 0.5 nM was achieved.
研究领域:
分析化学
·
生物传感器
·
药物发现
·
生物物理学
✓ 已验证
产品关联
DOI
高影响因子
APPLIED SURFACE SCIENCE
·
2018
·
IF 4.439
Wenfei Zhou,Mo Yang,Shaopeng Li,Jinsong Zhu
Systematic and rapid profiling of the interactions between small molecule drugs (or candidates) and target proteins is vital in studying drug promiscuity and drug discovery. However, a label-free and high-throughput method for the detection of small molecules binding on protein microarray is still lacking. In this research, we introduced surface plasmon resonance imaging (SPRi) technology combined with protein microarray on 3D-dextran hydrogel chip surface to realize the detection of small molecule drugs. With the development and optimization of this method, we obtained the ideal binding signals of small molecular drugs versus their target proteins, with good quality and uniformity (CV = 10.3%, n = 48). Then we demonstrated three applications, including in situ mimicking and detecting the formation of FK506-mediated trimer complex (FKBP12-FK506-calcineurin), rapid validation of FK506-FKBP12 recognition via FKBP12 mutant microarray (1 vs n mode), and 3 × 4 orthogonal studying the drug binding specificity on protein microarray (m vs n mode). Fortunately, these trials enable the label-free and kinetic study of drug-protein interactions on SPRi in a high-throughput manner, which could be a promising solution in screening/forecasting side effect of drugs (or candidates), drug repositioning or repurposing, target identification of natural products and personalized medicine, etc.
研究领域:
药学
·
生物化学
·
生物技术
·
药物发现
·
蛋白质组学
✓ 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）