International Journal of Nanomedicine
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2023
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IF 8
Jun Li,Yangyang Yang,Xiumin Han,Jing Li,Mengxiao Tian,Wenjing Qi,Huniu An,Chuanchuan Wu,Yao Zhang,Shuai Han,Liping Duan,Weisi Wang,Wenbao Zhang
Background Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment.Methods Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE.Results H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals.Conclusion Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.
研究领域:
药理学
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寄生虫学
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纳米技术
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医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Alifu Nuernisha,Yan Ting,Li Jun,Zhu Lijun,Aini Abudusalamu,Amuti Siyiti,Wu Juan,Qi Wenjing,Guo Gang,Zhang Wenbao,Zhang Xueliang
Hepatic alveolar echinococcosis (HAE) is caused by the metacestode of Echinococcus multilocularis, which shows characteristics of malignant tumors with high mortality. However, traditional diagnostic imaging methods are still not sufficient for the recognition of HAE microlesions in the early stages. Near-infrared-II (900–1700 nm, NIR-II) fluorescence microscopic imaging (NIR-II-FMI) has shown great potential for biomedical detection. A novel type of negative target imaging method based on NIR-II-FMI with the assistance of indocyanine green (ICG) was explored. Then, NIR-II-FMI was applied to the early detection of HAE for the first time. The negative targeting NIR-II fluorescence imaging of HAE-infected mice at different stages with the assistance of ICG under 808 nm of laser irradiation was obtained. Especially, HAE microlesions at the early stage were detected clearly. Moreover, clear intrahepatic angiography was achieved under the same NIR-II-FMI system.
研究领域:
医学影像学
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寄生虫病学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PARASITOLOGY
·
2024
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IF 2.1
Weisi Wang,Jun Li,Wenjing Qi,Ying Chen,Mengxiao Tian,Chuanchuan Wu,Yao Zhang,Yingfang Yu,Shuai Han,Xiumin Han,Liping Duan,Wenbao Zhang
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
研究领域:
药理学
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寄生虫学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2022
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IF 6.064
Gao Haijun,Huo Lele,Mo Xiaojin,Jiang Bin,Luo Yanping,Xu Bin,Li Jingzhong,Ma Xingming,Jing Tao,Feng Zheng,Zhang Ting,Hu Wei
Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.
研究领域:
寄生虫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Infectious Diseases of Poverty
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2021
·Vol. 10
·期 1
·1-12
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IF 4.388
Yang Shi-Jie,Xiao Ning,Li Jing-Zhong,Feng Yu,Ma Jun-Ying,Quzhen Gong-Sang,Yu Qing,Zhang Ting,Yi Shi-Cheng,Zhou Xiao-Nong
Background As a neglected cross-species parasitic disease transmitted between canines and livestock, echinococcosis remains a global public health concern with a heavy disease burden. In China, especially in the epidemic pastoral communities on the Qinghai-Tibet Plateau, the harsh climate, low socio-economic status, poor overall hygiene, and remote and insufficient access to all owned dogs exacerbate the difficulty in implementing the ambitious control programme for echinococcosis. We aimed to design and implement a remote management system (RMS) based on internet of things (IoT) for control and surveillance of echinococcosis by combining deworming devices to realise long-distance smart deworming control, smooth statistical analysis and result display. New methods and tools are urgently needed to increase the deworming coverage and frequency, promote real-time scientific surveillance, and prevent transmission of echinococcosis in remoted transmission areas. Methods From 2016 to 2019, we had cooperated and developed the smart collar and smart feeder with the Central Research Institute of Shanghai Electric Group Co., Ltd. (Shanghai, China) and Shenzhen Jizhi Future Technology Co., Ltd. (Shenzhen, China). From September 2019 to March 2020, We had proposed the RMS based on IoT as a novel tool to control smart deworming devices to deliver efficient praziquantel (PZQ) baits to dogs regularly and automatically and also as a smart digital management platform to monitor, analyse, and display the epidemic trends of echinococcosis dynamically, in real time in Hezuo City, Gannan Tibetan Autonomous Prefecture, Gansu Province, China. Starting from January 2018, The RMS has been maintained and upgraded by Shanghai Yier Information Technology Co., Ltd (Shanghai, China). The database was based on MySQL tools and the Chi-square test was used to probe the difference and changes of variables in different groups. Results The smart collars are fully capable of anti-collision, waterproof, and cold-proof performance, and the battery’s energy is sufficient, the anti-collision rate, water-proof rate, cold-proof rate and voltage normal rate is 99.6% (521/523), 100.0% (523/523), 100.0% (523/523) and 100.0% (523/523), respectively. The RMS can accurately analyse the monitoring data and parameters including positive rates of canine faeces, and the prevalence of echinococcosis in the general population livestock, and children. The data of dogs deworming and surveillance for echinococcosis is able to be controlled using RMS and has expanded gradually in townships to the whole Hezuo region. The automatic delivering PZQ rate, collar positioning rate, deliver PZQ reminding rate, and fault report rate is 91.1% (1914/2102), 92.1% (13 580/14 745), 92.1% (1936/2102) and 84.7% (1287/1519), respectively. After using the RMS from 2019, the missing rate of monitoring data decreased from 32.1% (9/28) to 0 (0/16). A total of 48 administrators (3, 3, 8, 11, 23 at the provincial, municipal, county, township, village levels, respectively) participated in the questionnaire survey, with 93.8% of its overall satisfaction rate. Conclusions The existing difficulties and challenges in the way of prevention and control for echinococcosis can partially be resolved using the innovative, IoT-based technologies and tools. The proposed RMS advance the upgrade of existing manual prevention and control models for echinococcosis, especially in the current ongoing COVID-19 pandemic, as social distance and community blockade continue. Graphic abstract
研究领域:
公共卫生
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兽医学
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远程医疗
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传染病学
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科技与医疗
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DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Chi Zhang,Li Jun,Yuxiang Gao,Le Guo,Jiayi Ding,Lijun Zhu,Zhong Du,Jiabao Xiong,Xueliang Zhang,Wenbao Zhang,Biao Dong,Nuernisha Alifu
Alveolar echinococcosis (AE) is a serious parasitic infectious disease that is highly invasive and destructive to the liver and has a high mortality rate. However, currently, there is no effective targeted imaging and treatment method for the precise detection and therapy of AE. We proposed a new two-step targeting strategy (TSTS) for AE based on poly(lactic-co-glycolic acid) (PLGA). We designed and constructed a novel type of ICG@PLGA@Lips nanoprobe with integrated imaging and treatment properties. First, we used the characteristics of PLGA gluconeogenic raw material to target the liver during blood circulation. Then, we utilized the characteristics of PLGA specifically penetrating the AE shell to achieve specific identification of AE in the liver. Under 808 nm laser excitation, ICG@PLGA@Lips effectively achieved accurate imaging of AE based on near-infrared II (NIR-II, 900–1700 nm) fluorescence imaging methods and achieved AE treatment through PDT effects. PLGA improved the optical properties of ICG, while liposomes further improved the biocompatibility of the nanoprobe. As ICG@PLGA@Lips showed strong NIR-II fluorescence emission and good biocompatibility, ICG@PLGA@Lips showed advantages in the specific fluorescence navigation of AE surgical resection lesions. Thus, with the assistance of ICG@PLGA@Lips, we achieved precise targeted and real-time NIR-II fluorescence imaging of AE for the first time. We successfully obtained in vivo NIR-II fluorescence imaging-guided photodynamic/surgical therapy of AE. This TSTS-based AE imaging and treatment exploration provided a new strategy for accurate imaging and treatment of early AE, which is expected to significantly improve the prognosis of patients.
研究领域:
医学成像
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诊疗学
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纳米技术
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寄生虫学
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外科手术
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光子学
✓ 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）