ABSTRACT
Echinococcosis, caused by Echinococcus spp., often affects the lungs and liver, and spinal involvement is rare. Echinococcus multilocularis is prevalent in Japan, particularly in Hokkaido. We herein report a rare case of spinal echinococcosis in a 31-year-old woman who was diagnosed in Tokyo. Spinal echinococcosis is uncommon and often leads to misdiagnoses. The patient likely contracted the disease via contaminated fresh produce transported from an endemic region. This study emphasizes the diagnostic challenges of spinal echinococcosis in non-endemic regions and highlights the public health concerns related to the spread of infections in non-endemic areas.
ABSTRACT
Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.
Subject(s)
Echinococcosis , Xanthones , Humans , Glutamine/therapeutic use , Echinococcosis/drug therapy , Xanthones/pharmacology , ProteinsABSTRACT
Currently, there is a lack of clinically safe and effective treatment for spinal cystic echinococcosis (CE). Recent studies have shown that albendazole chitosan microspheres (ABZ-CS-MPs) and irradiation have certain anti-abdominal echinococcosis ability, so this study aims to compare the in vitro and in vivo therapeutic effects of ABZ-CS-MPs, intensity-modulated radiation therapy (IMRT), and combination therapy on spinal echinococcosis. First, protoscoleces were processed by different treatments to evaluate their respective antiechinococcosis effects by monitoring the viability change of protoscoleces. Then, the apoptotic status of protoscoleces was evaluated by detecting the changes of mitochondrial membrane potential, the expression of apoptosis proteins, and the ultrastructural alterations of protoscoleces. After that, we constructed a gerbil model of spinal CE and further applied B-ultrasound and magnetic resonance imaging (MRI) technology to assess the size of hydatid in vivo. Finally, the cysts were obtained and weighed to compare the inhibition rate in different groups. The combined therapy increased protoscoleces mortality to over 90% after 18 days, which showed the highest scolicidal effect. Moreover, confocal imaging, expression of apoptotic proteins, and ultrastructural changes of protoscoleces showed the highest apoptotic rate in this group. In vivo, the combination treatment also exhibited the highest cyst inhibition rate (61.4%). In conclusion, our results showed that ABZ-CS-MPs combined with IMRT could be a new treatment option for spinal CE. We also provided a method to evaluate the growth and metastasis of hydatid in animals with B-ultrasound and MRI technologies.