Infection with Echinococcus spp. causes fibrosis in various vital organs, including the liver and lungs. Hepatic fibrosis is a pathological feature of Echinococcus infection that destroys normal liver tissue, leading to jaundice, cholecystitis, portal hypertension, etc. Severe Echinococcus multilocularis infections lead to liver failure and hepatic encephalopathy. The formation of peripheral fiberboards around the metacestode is a major reason as to why antiparasitic drugs fail to be effectively transported to the lesion site. Studies on the mechanism of hepatic fibrosis caused by Echinococcus are important for treatment in patients. Recent studies have focused on miRNA and TGF-β. More recent findings have focused on the generation of collagen fibers around the metacestode. In this review paper we focus on the mechanism by which the Echinococcus parasite induces fibrosis in liver and some other organs in intermediate hosts—animals as well as human beings.
Echinococcus multilocularis is a small parasite that causes alveolar echinococcosis. It primarily induces liver disorder, such as liver fibrosis and even liver cancer, which severely endangers human lives. This study aims to explore the efficacy of Echinococcus multilocularis soluble antigen in preventing and alleviating alveolar echinococcosis-induced liver fibrosis and determine the underlying mechanism. We first identified the optimal dose and time of Echinococcus multilocularis soluble antigen. The protein levels of key genes in the RhoA-MAPK signaling pathway were remarkably upregulated in RAW264.7 and Ana-1 cells induced with 80 μg/mL Echinococcus multilocularis soluble antigen for 8 h. Interestingly, the upregulated expression levels were remarkably reversed by the RhoA, JNK, ERK, or p38 inhibitor, confirming the significance of the RhoA-MAPK signaling pathway. In addition, the relative contents of M2 polarization markers IL-10 and Arg-1 in macrophages induced with 80 μg/mL Echinococcus multilocularis soluble antigen for 8 h increased, whereas those of M1 polarization markers IL-12 and NOS-2 decreased. Mouse hepatic stellate cells were the key components of the hepatocellular carcinoma tumor microenvironment. Hepatic stellate cells were activated by Echinococcus multilocularis soluble antigen and transformed into the morphology of myofibroblasts in response to liver disorders. By detecting the marker of myofibroblast formation, RhoA inhibitor remarkably reduced the positive expression of α-SMA in mouse hepatic stellate cells induced with Echinococcus multilocularis soluble antigen. Therefore, Echinococcus multilocularis soluble antigen remarkably activated the RhoA-MAPK pathways in macrophages, further inducing the polarization of macrophages and ultimately causing liver fibrosis. Hypothesis: We hypothesize that infection with Echinococcus multilocularis activates the RhoA-MAPK signaling pathway and subsequently induces macrophage polarization to promote hepatic stellate cells activation leading to liver fibrosis. Aims: To investigate the mechanism by which soluble antigen of Echinococcus multilocularis affects liver fibrosis through the RhoA-MAPK pathway driving polarization of macrophages. Goals: To identify new pathways of intervention and drug targets for the regulation of macrophage polarity phenotype switching and the attenuation or inhibition of the development and treatment of liver fibrosis caused by Echinococcus multilocularis infection.
Few major advances in fighting parasitic diseases have been made in China since the development of new methods for prevention, control, and elimination. However, the proportion of immunocompromised individuals has increased due to the growth of chronic diseases, population aging, and more frequent cases of patients with AIDS and cancer. All these problems can promote development of parasitic infections, which is commonly associated with manipulation of host signaling pathways and the innate immune system. Mitogen-activated protein kinase (MAPK) signaling pathways are evolutionarily conserved in metazoan organisms, which play critical roles in the cell cycle, gene expression, growth, differentiation, apoptosis, and parasite–host interactions. Recent discoveries of the MAPK components involved in activation, regulation, and signal transduction appeared to be promising for the diagnosis, prevention, and treatment of parasitic diseases in the future. This review summarizes the involvement and critical role of the MAPK family in parasitic disease development and maintenance in the host. Moreover, it highlights recent studies concerning the mechanisms and novel drug development for inhibition and regulation of MAPK pathways in order to prevent parasitic disease. In addition, we discuss some antigenic proteins as prospective inhibitory molecules or vaccines for the regulation and control of MAPK signaling involved in parasite physiological activity.
Background: Heavy ion radiation has more advantages than traditional radiation therapy in the treatment of cancer, mainly because of its superior biological effects. However, there is currently no reliable evidence that heavy ion radiation can induce cell death in hydatid cysts at the cellular and molecular level. In addition, we believe heavy ion therapy could be a potential alternative approach for the treatment of hydatid cysts. Methodology/Principal Finding: The hydatid cysts and protoscolices were obtained from an experimentally infected KunMing mice. LD50 was used to evaluate the death of the protoscolex. The cellular and ultrastructure of the parasites were observed under light and electron microscopes, the damage and copy numbers of mitochondrial DNA (mtDNA) were decided by QPCR. The apoptosis was evaluated by the expression and activity of caspase3. Dose-dependent ionizing radiation induced damage to the initial mtDNA. Echinococcosis cyst after ionizing radiation showed sparse cytoplasm, disorganized and clumped organelles, huge vacuoles, and villus deletions. The kinetic of DNA repair activity after X-ray irradiation was faster than those after carbon-ion irradiation. High doses of carbon ion radiation caused irreversible attenuation of mitochondrial DNA. Cysts showed obvious reduction in size after radiation. Carbon ion radiation was more effective than X-ray radiation in inhibiting hydatid cysts. Conclusions: These studies provide evidence that heavy-ion radiation can cause the extinction of hydatid cysts in vitro. The carbon-ion radiation is more advantageous than X-ray radiation in suppress hydatid cyst.
The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. japonicum mouse models treated with HSP47 shRNA in vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors. HSP47-shRNA could markedly down-regulate the expression of collagen (Col1a1 and Col3a1). The expressions of HSP47, endothelin receptor A (ETAR) and endothelin receptor B (ETBR) significantly increased in the liver tissue of infected mice. However, the expressions of ETAR and HSP47 and ETBR remarkably decreased after the administration of HSP47 shRNA in vitro and in vivo. ETAR and ETBR levels were found to be positively correlated with HSP47 expression. HSP47 might exert influence on liver fibrosis via the regulation of ETAR and ETBR.
Objectives In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in Leishmania major‐infected human dendritic cells (DCs). Methods Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in L. major‐infected human DCs. Results CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in L. major‐infected human DCs. During the L. major infection, total number of L. major‐infected human DCs were increased, as well as the relative expression levels of CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression. Conclusion L. major infection‐induced activation of CCR7, as well as JAK2 and STAT1, might well upregulate the expression of BAX yet suppress the expression of both Bcl2 and c‐Jun to affect leishmaniasis progression.
The abstract must include the following separate sections: Background: Hydatid disease, which is caused by larvae of Echinococcus multilocularis. Is common in husbandry area. It's serious disease to human that has a significantly high fatality rate. However, as a non-echinococcous endemic area, Guangxi has not reported on hydatid disease, and this first primary patient may provide new possible routes of infection and diagnostic ideas. Case presentation: A brief description of the patient's clinical and demographic details, the diagnosis, any interventions and the outcomes. The patient suffered from hypertension for 6 years and hypo tensors were used to control the blood pressure. In 2014, he was confirmed to have hepatic cyst. In December 2016, he had been hospitalized in the Department of Encephalopathy because of intracerebral haemorrhage, which led his left limb activities impaired. This patient reported a hepatic cyst detected by B-mode ultrasound during the physical examination 1 year ago. He did not pay close attention to it and did not receive any re-examination. Recently, B-mode ultrasound in another physical examination showed hepatic cyst (176 × 158 mm). No obvious abnormality was found in the gallbladder, pancreas, spleen and both kidneys. Computed tomography scan can be applied to examine all organs in human body and is an important diagnostic examination for echinococcosis. Conclusions: A brief summary of the clinical impact or potential implications of the case report. This patient finally diagnosis as Cystic echinococcosis in the right liver lobe (Simplex cyst), hypertensive disease, hemorrhage sequel and arrhythmia-atrial premature beat. According to the diagnosis, we plan the treatment as using laparoscopic surgery for echinococcosis. This case will help us to find out possible causes of the incidence of echinococcosis in Guangxi and the potential transmission risks, and thus put forward the measures for the prevention and treatment of echinococcosis in Guangxi.
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