<i>Echinococcus multilocularis</i>
            protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway

Zhang, Tao; Zhang, Yuegang; Yang, Zihan; Jiang, Yuan; Sun, Li; Huang, Dengliang; Tian, Meiyuan; Shen, Yinhong; Deng, Jun; Hou, Jing; Ma, Yanyan

doi:10.1080/20477724.2022.2104055

Cited by 3 publications

(3 citation statements)

References 39 publications

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“…The PI3k-Akt signaling pathway orchestrates a spectrum of biological processes (e.g., cell proliferation, apoptosis, invasion, metastasis, and angiogenesis) and holds significant relevance to tumorigenesis [40]. E. multilocularis infection induces alterations in glucose metabolism, macrophage polarization, and the PI3K/Akt/mTOR signaling cascade [41]. Previous investigations have delineated how E. multilocularis microcyst fluid can stimulate fibroblast MMP2 and MMP9 expression within lesions via PI3K/Akt signaling pathway activation [42].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model

Lu,

Wang,

Liu

et al. 2024

TropicalMed

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Alveolar echinococcosis (AE) stands as a perilous zoonotic affliction caused by the larvae of Echinococcus multilocularis. There is an imperative need to explore novel therapeutic agents or lead compounds for the treatment of AE. Asparagusic acid, characterized by its low toxicity and possessing antimicrobial, antioxidant, and anti-parasitic attributes, emerges as a promising candidate. The aim of this study was to investigate the in vivo and in vitro efficacy of asparagusic acid against E. multilocularis. Morphological observations, scanning electron microscopy, ROS assays, mitochondrial membrane potential assays, and Western blot were used to evaluate the in vitro effects of asparagusic acid on protoscoleces. The effects of asparagusic acid on vesicles were assessed via PGI release, γ-GGT release, and transmission electron microscopy observations. CellTiter-Glo assays, Caspase3 activity assays, flow cytometry, and Western blot were used for an evaluation of the effect of asparaginic acid on the proliferation and apoptosis of germinal cells. The in vivo efficacy of asparagusic acid was evaluated in a murine AE model. Asparagusic acid exhibited a pronounced killing effect on the protoscoleces post-treatment. Following an intervention with asparagusic acid, there was an increase in ROS levels and a decline in mitochondrial membrane potential in the protoscolex. Moreover, asparagusic acid treatment resulted in the upregulation of PGI and γ-GGT release in metacestode vesicles, concomitant with the inhibition of germinal cell viability. Furthermore, asparagusic acid led to an enhanced relative expression of Caspase3 in the culture supernatant of both the protoscoleces and germinal cells, accompanied by an increase in the proportion of apoptotic germinal cells. Notably, asparagusic acid induced an augmentation in Bax and Caspase3 protein expression while reducing Bcl2 protein expression in both the protoscoleces and germinal cells. In vitro cytotoxicity assessments demonstrated the low toxicity of asparagusic acid towards normal human hepatocytes and HFF cells. Additionally, in vivo experiments revealed that asparagusic acid administration at doses of 10 mg/kg and 40 mg/kg significantly reduced metacestode wet weight. A histopathological analysis displayed the disruption of the germinal layer structure within lesions post-asparagusic acid treatment, alongside the preservation of laminated layer structures. Transmission electron microscopy further revealed mitochondrial swelling and heightened cell necrosis subsequent to the asparagusic acid treatment. Furthermore, asparagusic acid promoted Caspase3 and Bax protein expression while decreasing Bcl2 protein expression in perilesional tissues. Subsequently, it inhibited the expression of Ki67, MMP2, and MMP9 proteins in the perilesional tissues and curbed the activation of the PI3K/Akt signaling pathway within the lesion-host microenvironmental tissues. Asparagusic acid demonstrated a pronounced killing effect on E. multilocularis, suggesting its potential as a promising therapeutic agent for the management of AE.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model

Lu,

Wang,

Liu

et al. 2024

TropicalMed

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“…51 Conversely, in Alveolar Echinococcosis, Echinococcus multilocularis protoscoleces promote M2 polarization of macrophages, thereby contributing to the genesis of hepatic cysts by activating the PI3K/Akt/ mTOR signaling pathway. 52 However, the phenotypic manifestation of macrophages is not rigid; under suitable external stimuli, diverse phenotypes can interconvert. Infections, signals indicative of acute damage, and implanted biomaterials can impact this process by triggering many signaling pathways.…”

Section: Macrophagesmentioning

confidence: 99%

“…For instance, in the context of osteoarthritis, synovial macrophages transform into the M1 phenotype, governed by signaling pathways encompassing the mammalian target of rapamycin (mTOR), nuclear factor‐kappa B (NF‐κB), c‐Jun N‐terminal kinase, and phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt) 51 . Conversely, in Alveolar Echinococcosis, Echinococcus multilocularis protoscoleces promote M2 polarization of macrophages, thereby contributing to the genesis of hepatic cysts by activating the PI3K/Akt/mTOR signaling pathway 52 …”

Section: Electrospun Fiber‐based Strategies To Regulate Immune Cellsmentioning

confidence: 99%

Electrospun fiber‐based immune engineering in regenerative medicine

Xu,

Saiding,

Zhou

et al. 2024

Smart Medicine

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Immune engineering, a burgeoning field within regenerative medicine, involves a spectrum of strategies to optimize the intricate interplay between tissue regenerative biomaterials and the host tissue. These strategies are applied across different types of biomaterials and various disease models, which encompasses finely modulating the immune response at the levels of immune cells and factors, aiming to mitigate adverse effects like fibrosis and persistent inflammation that may arise at the injury site and consequently promote tissue regeneration. With the continuous progress in electrospinning technology, the immunoregulatory capabilities of electrospun fibers have gained substantial attention over the years. Electrospun fibers, with their extracellular matrix‐like characteristics, high surface‐area‐to‐volume ratio, and reliable pharmaceutical compound capacity, have emerged as key players among tissue engineering materials. This review specifically focuses on the role of electrospun fiber‐based immune engineering, emphasizing their unique design strategies. Notably, electrospinning actively engages in immune engineering by modulating immune responses through four essential strategies: (i) surface modification, (ii) drug loading, (iii) physicochemical parameters, and (iv) biological grafting. This review presents a comprehensive overview of the intricate mechanisms of the immune system in injured tissues while unveiling the key strategies adopted by electrospun fibers to orchestrate immune regulation. Furthermore, the review explores the current developmental trends and limitations concerning the immunoregulatory function of electrospun fibers, aiming to drive the advancements in electrospun fiber‐based immune engineering to its full potential.

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Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis

Bai

Yan

et al. 2023

Acta Tropica

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Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway

Cited by 3 publications

References 39 publications

Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model

Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model

Electrospun fiber‐based immune engineering in regenerative medicine

Metabolomic profiling of early inactive hepatic alveolar and cystic echinococcosis

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