Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo

Muhedier, Muzhabaier; Li, Jintian; Liu, Hui; Ma, Guizhi; Amahong, Kuerbannisha; Lin, Renyong; Lü, Guodong

doi:10.1016/j.actatropica.2020.105708

Cited by 11 publications

(5 citation statements)

References 68 publications

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“…As examples, 3-bromopyruvate which blocks glucose entry into the glycolysis pathway by inhibiting hexokinase (HK) ( Ko et al., 2001 ) has been shown to inhibit Echinococcus spp. viability in vitro and in vivo ( Xin et al., 2019 ); tacrolimus, a rapamycin-target protein inhibitor, exerts anti-CE effects in vivo and in vitro and affects the glucose metabolism of cysts in vivo ( Muhedier et al., 2020 ); and metformin can reduce the larval viability of E. granulosus s.l. by inhibiting its glucose metabolism pathway ( Loos and Cumino, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Amahong

Yan

et al. 2021

Front. Cell. Infect. Microbiol.

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Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae of Echinococcus granulosus sensu lato (s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, the role of GLUT1 in E. granulosus s.l. (EgGLUT1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) from E. granulosus sensu stricto (s.s.) and found EgGLUT1-ss was crucial for glucose uptake and viability by the protoscoleces of E. granulosus s.s. WZB117, a GLUT1 inhibitor, inhibited glucose uptake by E. granulosus s.s. and the viability of the metacestode in vitro. In addition, WZB117 showed significant therapeutic activity in E. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts (P < 0.05) as efficiently as the reference drug, albendazole. Our results demonstrate that EgGLUT1-ss is crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 has a therapeutic effect on CE.

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Section: Discussionmentioning

confidence: 99%

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

Amahong

Yan

et al. 2021

Front. Cell. Infect. Microbiol.

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“…To naturally eliminate fragments of the brood capsule from the protoscoleces sediment, it was digested with 1% pepsin (BioFroxx) and then rinsed three times with sterile PBS containing 100 U/mL penicillin‐streptomycin solution (Gibco). The sediment was stained with 0.5% eosin (BKMAMLAB) for 5 min, and the number of active protoscoleces (>90%) was counted microscopically and diluted to 10,000 protoplasts/mL in suspension with sterile PBS containing penicillin‐streptomycin solution and kept on standby 11 …”

Section: Methodsmentioning

confidence: 99%

“…The sediment was stained with 0.5% eosin (BKMAMLAB) for 5 min, and the number of active protoscoleces (>90%) was counted microscopically and diluted to 10,000 protoplasts/mL in suspension with sterile PBS containing penicillin‐streptomycin solution and kept on standby. 11 …”

Section: Methodsmentioning

confidence: 99%

The role of memory T cells in Echinococcus granulosus‐induced sensitization

Zhou,

Du,

Abulajiang

et al. 2023

Immunity Inflam & Disease

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ObjectiveTo investigate the changes in memory T cells and the related factors in mice by the establishment of a BALB/c mouse model of Echinococcus granulosus‐induced sensitization.MethodsA sensitized BALB/c mouse model was established by intraperitoneal injection of E. granulosus. A control group (CTRL), a nonsensitized group infected with E. granulosus (CE), and a sensitized group infected with E. granulosus (ANPC) were set up. The pathological changes in lung tissue in mice, the change in memory T cells (CD4 Tm), and the change in peripheral blood nucleated interleukin‐23 (IL‐23) were detected using HE staining, flow cytometry, and liquid‐phase multiple protein quantification techniques, respectively.ResultsThe individual percentage of mouse memory T cells was 9.14 ± 0.45, 25.23 ± 0.17, and 13.29 ± 0.32 in the CTRL, CE, and ANPC groups, respectively. The percentage of memory T cells in the ANPC group was higher than that in the CTRL group (t = 18.410, p < .001) but lower than that in the CE group (t = −80.147, p < .001). The levels of IL‐23 in peripheral blood of mice in the CTRL, CE, and ANPC groups were 225.76 ± 27.16, 359.21 ± 28.67, and 215.69 ± 22.69, respectively. The level of IL‐23 in peripheral blood of mice in the ANPC group was lower than that in the CE group (t = 9.609, p < .001), and there was no statistical difference with the CTRL group (t = 0.697, p = .502).ConclusionIn the BALB/c mouse model of E. granulosus‐induced sensitization, the expression of IL‐23 in peripheral blood increased, and the memory T cell proliferated and became activated; there was a decrease in the content of IL‐23 in peripheral blood and number of activated memory T cells in the sensitization group infected with E. granulosus. The E. granulosus‐induced allergic reaction was related to IL‐23 and the activation of memory T cells.

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“…U0126 and BIBW2992 exhibited efficacy against E. multilocularis (Cheng et al 2020). Among the seven mTOR inhibitors, the tacrolimus (TAC) was found to be more effective than other inhibitors against hydatid cyst in vitro and also there was an effective reduction in weight and number of the parasitic cyst at a concentration of 4 mg/kg/day in vivo (Muhedier et al 2020). Chen et al (2020) studied the effect of hMASP-2 DNA-nanolipoplexes against Cystic Echinococcosis and reported that they induced degradation of germinal layer cells and up-regulated Tcell immunity in mice, therefore, could be used as an alternate for Cystic Echinococcosis treatment.…”

Section: Other Optionsmentioning

confidence: 99%

Introduction To Echinococcosis and A Review of Treatment Panels

2021

Int J Vet Sci

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Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo

Cited by 11 publications

References 68 publications

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

The role of memory T cells in Echinococcus granulosus‐induced sensitization

Introduction To Echinococcosis and A Review of Treatment Panels

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