The efficacy of an alternative mebendazole formulation in mice infected with Echinococcus multilocularis

Liu, Congshan; Han, Xiumin; Wen, Lei; Yin, Jiong; Wu, Shile; Zhang, Haobing

doi:10.1016/j.actatropica.2019.05.009

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…Through RNA sequencing technology, a previous study identified a multitude of differentially expressed genes in the peripheral blood of patients afflicted with HE, thereby presenting novel targets for pharmacological intervention 59 . The combination of albendazole with novel materials (such as solid dispersion 60 , liposomes 61 , nanoparticles 62 , 63 , microspheres 50 , and self-microemulsion 64 , 65 ) has been reported to enhance hepatic drug concentrations, thereby facilitating disease control; however, certain limitations still exist 66 . Moreover, during investigation on the correlation between HE and immune sites, we notably revealed that the downregulation of PD-1/PD-L1 in the liver can effectively impede the pathophysiological progression caused by parasites through modulation of natural killer T (NKT) cells and regulatory T cells (Tregs), as evidenced by in vivo animal studies 67 , 68 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of research trends and prospects on hepatic echinococcosis over the past forty years: a bibliometric analysis

Li,

Su,

Wang

et al. 2024

International Journal of Surgery

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Background: The distribution of hepatic echinococcosis (HE) is extensive, significantly impacting public health and economic development. Therefore, analyzing global collaboration networks and tracking developmental trends over the past four decades are crucial. This study aimed to demonstrate collaboration in the field of HE and explore key topics and future directions. Materials and Methods: Bibliometric analyses were conducted using CiteSpace, Bibliometrix package of R, and VOSviewer software on HE-related studies from the Web of Science Core Collection published before August 1, 2023. Results: This study identified 2,605 records published in 196 journals by 9,860 authors from 2,607 institutes in 90 countries. Publications significantly notably increased in 2021. Developing countries like Turkey and China made notable contributions, while developed countries like the USA had higher average citation rates. The largest nodes in every cluster of the collaboration network were Hacettepe University, Tehran University, Xinjiang Medical University, Salford University, and the University of Pavia, and the top-producing authors were Wen H, Vuitton DA, Gottstein B, and Craig PS. Keyword co-occurrence analysis suggested that surgical techniques and novel drugs targeting combined immune checkpoints are the main therapeutic approaches in the future. Conclusion: Although developing countries had significantly contributed to publications on HE, the citation rate for individual articles from developed countries was significantly higher. Additionally, advancements in surgical techniques and novel drugs targeting combined immune checkpoints may emerge as the next research focus and developmental direction.

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Section: Discussionmentioning

confidence: 99%

Characterization of research trends and prospects on hepatic echinococcosis over the past forty years: a bibliometric analysis

Li,

Su,

Wang

et al. 2024

International Journal of Surgery

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“…The remaining 8 mice in each group were challenged with 2000 PSCs by intraperitoneal injection in total volume of 100 µL. All challenged mice were sacrificed 14 weeks after infection and the total metacestode vesicles developed in the abdominal cavity were collected to measure the parasite weight [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Immunization with EmCRT-Induced Protective Immunity against Echinococcus multilocularis Infection in BALB/c Mice

et al. 2022

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Alveolar echinococcosis (AE) is a severe parasitic zoonosis caused by the larval stage of Echinococcus multilocularis. The identification of the antigens eliciting acquired immunity during infection is important for vaccine development against Echinococcus infection. Here, we identified that E. multilocularis calreticulin (EmCRT), a ubiquitous protein with a Ca2+-binding ability, could be recognized by the sera of mice infected with E. multilocularis. The native EmCRT was expressed on the surface of E. multilocularis larvae as well as in the secreted products of metacestode vesicles and protoscoleces (PSCs). The coding DNA for EmCRT was cloned from the mRNA of the E. multilocularis metacestode vesicles and a recombinant EmCRT protein (rEmCRT) was expressed in E. coli. Mice immunized with soluble rEmCRT formulated with Freund’s adjuvant (FA) produced a 43.16% larval vesicle weight reduction against the challenge of E. multilocularis PSCs compared to those that received the PBS control associated with a high titer of IgG, IgG1 and IgG2a antibody responses as well as high levels of Th1 cytokines (IFN-γ and IL-2) and Th2 cytokines (IL-4, IL-5 and IL-10), produced by splenocytes. Our results suggest that EmCRT is an immunodominant protein secreted by E. multilocularis larvae and a vaccine candidate that induces partial protective immunity in vaccinated mice against Echinococcus infection.

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“…multilocularis-infected animals [BALB/c mice (SLAC Laboratory Animal Center)] were maintained by serial i.p. transplantation passages through for 6 months, the details can be found in our published paper (Liu et al, 2019). Eighty infected BALB/c mice were prepared for in vivo treatment experiments.…”

Section: Parasites and Animalsmentioning

confidence: 99%

Pharmacophore-Based Virtual Screening Toward the Discovery of Novel Anti-echinococcal Compounds

Liu

Yin

Yao

et al. 2020

Front. Cell. Infect. Microbiol.

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Echinococcosis is a serious helminthic zoonosis with a great impact on human health and livestock husbandry. However, the clinically used drugs (benzimidazoles) have a low cure rate, so alternative drugs are urgently needed. Currently, drug screenings for echinococcosis are mainly phenotype-based, and the efficiency of identifying active compounds is very low. With a pharmacophore model generated from the structures of active amino alcohols, we performed a virtual screening to discover novel compounds with anti-echinococcal activity. Sixty-two compounds from the virtual screening were tested on Echinococcus multilocularis protoscoleces, and 10 of these compounds were found to be active. After further evaluation of their cytotoxicity, S6 was selected along with two active amino alcohols for in vivo pharmacodynamic and pharmacokinetic studies. At the two tested doses (50 and 25 mg/kg), S6 inhibited the growth of E. multilocularis in mice (14.43 and 9.53%), but no significant difference between the treatment groups and control group was observed. Treatment with BTB4 and HT3 was shown to be ineffective. During the 28 days of treatment, the death of mice in the mebendazole, HT3, and BTB4 groups indicated their toxicity. The plasma concentration of S6 administered by both methods was very low, with the C max being only 1 ng/ml after oral administration and below the detection limit after intramuscular administration. In addition, the plasma concentrations of BTB4 and HT3 in vitro did not reach high enough levels to kill the parasites. The toxicities of these two amino alcohols indicated that they are not suitable for further development as anti-echinococcal drugs. However, further attempts should be made to increase the bioavailability of S6 and modify its structure. In this study, we demonstrate that pharmacophore-based virtual screenings with high drug identification efficiency could be used to find novel drugs for treating echinococcosis.

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The efficacy of an alternative mebendazole formulation in mice infected with Echinococcus multilocularis

Cited by 7 publications

References 17 publications

Characterization of research trends and prospects on hepatic echinococcosis over the past forty years: a bibliometric analysis

Characterization of research trends and prospects on hepatic echinococcosis over the past forty years: a bibliometric analysis

Immunization with EmCRT-Induced Protective Immunity against Echinococcus multilocularis Infection in BALB/c Mice

Pharmacophore-Based Virtual Screening Toward the Discovery of Novel Anti-echinococcal Compounds

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