microRNA-125b-5p is a promising novel plasma biomarker for alveolar echinococcosis in patients from the southern province of Qinghai

Cao, Deping; Jiang, Bofan; Yaogang, Zhang; Pang, Mingquan

doi:10.1186/s12879-021-05940-z

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…An increase of miR-1839-5p and miR-146a-5p in the primary as well as in the secondary infection mouse models suggests that these two miRs may represent potential biomarkers of AE; however, for this purpose they will need to be robustly detected and quantified in blood samples. In this respect, a recent study showed elevated miR-125b-5p levels in plasma of patients with AE [ 56 ], supporting the potential use of miRs as biomarkers of AE. Furthermore, Luis et al .…”

Section: Discussionmentioning

confidence: 91%

“…The miRs, isolated from human specimen, including urine, saliva, serum and tissues, are considered as biomarkers of several immune pathologies such as cancer, autoimmune diseases and viral or bacterial infections [49][50][51][52][53][54][55]. A recent study revealed miR-125b-5p to be elevated in the plasma of AE patients [56]. Furthermore, recent investigations provided evidence for a role of some miRs in the regulation of UPR signaling, with miR-181a-5p and miR-199a-5p shown to suppress the UPR master regulator GRP78 [48,57,58].…”

Section: Introductionmentioning

confidence: 99%

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Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

et al. 2022

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Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. Results E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. Conclusions and significance AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

et al. 2022

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“…It is worth pondering that the DLK1/Notch1 axis does not affect the activation and proliferation of naive CD4 + T cells, suggesting that there are other mechanisms affecting activation and proliferation after miR-126a-5p action. It has been found that hsa-miR-125b-5p may be a promising biomarker for early non-invasive diagnosis of alveolar echinococcosis (58). Similarly, miR-126-5p may also serve as a biomarker for early CE infection and as an auxiliary detection molecule for late imaging confirmation.…”

Section: Discussionmentioning

confidence: 99%

“…It has been found that hsa-miR-125b-5p may be a promising biomarker for early non-invasive diagnosis of alveolar echinococcosis ( 58 ). Similarly, miR-126-5p may also serve as a biomarker for early CE infection and as an auxiliary detection molecule for late imaging confirmation.…”

Section: Discussionmentioning

confidence: 99%

The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Zhu

Zhang

et al. 2022

Front. Immunol.

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Cystic echinococcosis (CE) is a zoonotic parasitic disease spread worldwide caused by Echinococcus granulosus (Eg), which sometimes causes serious damage; however, in many cases, people are not aware that they are infected. A number of recombinant vaccines based on Eg are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant Eg.P29 (rEg.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4+ T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using rEg.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4+ T cells into Th1/Th2 under rEg.P29 immunization and determined the mechanisms associated with delta-like 1 homolog (DLK1) and Notch1 signaling pathway. One week after P29 immunization of mice, we found that miR-126a-5p was significantly increased and DLK1 expression was decreased, while Notch1 pathway activation was enhanced and Th1 response was significantly stronger. The identical conclusion was obtained by overexpression of mmu-miR-126a-5p in primary naive CD4+ T cells in mice. Intriguingly, mmu-miR-126a-5p was significantly raised in serum from mice infected with protoscolex in the early stages of infection and markedly declined in the late stages of infection, while has-miR-126-5p expression was dramatically reduced in serum from CE patients. Taken together, we show that miR-126a-5p functions as a positive regulator of Notch1-mediated differentiation of CD4+ T cells into Th1 through downregulating DLK1 in vivo and in vitro. Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.

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“…Previous research has shown that hydatidosis can be diagnosed early and monitored through the biomarker of serum-derived egr-miR-71 [24]. The expression of hsa-miR-125b-5p was stably upregulated in the plasma and liver tissue samples from patients with alveolar echinococcosis (AE), which suggested that hsa-miR-125b-5p may be a promising biomarker for early non-invasive diagnosis of AE [45]. Serum aca-miR-146a was found to be expressed significantly higher in mice infected by Angiostrongylus cantonensis and its receiver operating characteristic (ROC) curve analysis showed that aca-miR-146a was an effective biomarker for discriminating the infected from uninfected cases with an area under the ROC curve (AUC) of 0.90.…”

Section: Discussionmentioning

confidence: 99%

Identification and Expression Profiling of Circulating MicroRNAs in Serum of Cysticercus pisiformis-Infected Rabbits

Chen

Wang

Liu

et al. 2021

Genes

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Cysticercus pisiformis (C. pisiformis), the larval form of Taenia pisiformis, parasitize mainly the liver, omentum and mesentery of rabbits and cause huge economic losses in the rabbit breeding industry. MicroRNA (miRNA), a short non-coding RNA, is widely and stably distributed in the plasma and serum. Numerous data demonstrates that, after parasitic infection, miRNAs become the key regulatory factor for controlling host biological processes. However, the roles of serum miRNAs in C. Pisiformis-infected rabbits have not been elucidated. In this study, we compared miRNA expression profiles between the C. pisiformis-infected and healthy rabbit serum using RNA-seq. A total of 192 miRNAs were differentially expressed (fold change ≥ 2 and P < 0.05), including 79 up- and 113 downregulated miRNAs. These data were verified by qRT-PCR (real time quantitative polymerase chain reaction) analysis. Additionally, GO analysis showed that the target genes of these dysregulated miRNAs were most enriched in cellular, single-organism and metabolic processes. KEGG pathway analysis showed that these miRNAs target genes were involved in PI3K-Akt, viral carcinogenesis and B cell receptor signaling pathways. Interestingly, after aligning clean reads to the T. pisiformis genome, four (miR-124-3p_3, miR-124-3p_4, miR-124a and novel-miR1) T. pisiformis-derived miRNAs were found. Of these, novel-miR1was upregulated in different periods after C. pisiformis infection, which was verified qRT-PCR, and pre- novel-miR-1 was amplified from the cysticerci by RT-PCR, implying novel-miR-1 was derived from C. pisiformis and has great potential for the diagnosis of Cysticercosis pisiformis infection. This is the first investigation of miRNA expression profile and function in the serum of rabbits infected by C. pisiformis, providing fundamental data for developing diagnostic targets for Cysticercosis pisiformis.

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microRNA-125b-5p is a promising novel plasma biomarker for alveolar echinococcosis in patients from the southern province of Qinghai

Cited by 8 publications

References 34 publications

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Identification and Expression Profiling of Circulating MicroRNAs in Serum of Cysticercus pisiformis-Infected Rabbits

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