ABSTRACT
Background: Cystic echinococcosis, caused by the larval stage of Echinococcus granulosus, remains a global health challenge. Mesenchymal stem cells (MSCs) are renowned for their regenerative and immunomodulatory properties. Given the parasite's mode of establishment, we postulate that MSCs likely play a pivotal role in the interaction between the parasite and the host. This study aims to explore the response of MSCs to antigens derived from Echinococcus granulosus, the etiological agent of hydatid disease, with the hypothesis that exposure to these antigens may alter MSC function and impact the host's immune response to the parasite. Methods: MSCs were isolated from mouse bone marrow and co-cultured with ESPs, HCF, or pLL antigens. We conducted high-throughput sequencing to examine changes in the MSCs' mRNA expression profile. Additionally, cell cycle, migration, and secretory functions were assessed using various assays, including CCK8, flow cytometry, real-time PCR, Western blot, and ELISA. Results: Our analysis revealed that hydatid antigens significantly modulate the mRNA expression of genes related to cytokine and chemokine activity, impacting MSC proliferation, migration, and cytokine secretion. Specifically, there was a downregulation of chemokines (MCP-1, CXCL1) and pro-inflammatory cytokines (IL-6, NOS2/NO), alongside an upregulation of anti-inflammatory mediators (COX2/PGE2). Furthermore, all antigens reduced MSC migration, and significant alterations in cellular metabolism-related pathways were observed. Conclusion: Hydatid disease antigens induce a distinct immunomodulatory response in MSCs, characterized by a shift towards an anti-inflammatory phenotype and reduced cell migration. These changes may contribute to the parasite's ability to evade host defenses and persist within the host, highlighting the complex interplay between MSCs and hydatid disease antigens. This study provides valuable insights into the pathophysiology of hydatid disease and may inform the development of novel therapeutic strategies.
ABSTRACT
Background: Hydatid disease is caused by Echinococcus parasites and can affect various tissues and organs in the body. The disease is characterized by the presence of hydatid cysts, which contain specific antigens that interact with the host's immune system. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can regulate immunity through the secretion of extracellular vesicles (EVs) containing microRNAs (miRNAs). Methods: In this study, hydatid antigens were isolated from sheep livers and mice peritoneal cavities. MSCs derived from mouse bone marrow were treated with different hydatid antigens, and EVs were isolated and characterized from the conditioned medium of MSCs. Small RNA library construction, miRNA target prediction, and differential expression analysis were conducted to identify differentially expressed miRNAs. Functional enrichment and network construction were performed to explore the biological functions of the target genes. Real-time PCR and Western blotting were used for miRNA and gene expression verification, while ELISA assays quantified TNF, IL-1, IL-6, IL-4, and IL-10 levels in cell supernatants. Results: The study successfully isolated hydatid antigens and characterized MSC-derived EVs, demonstrating the impact of antigen concentration on MSC viability. Key differentially expressed miRNAs, such as miR-146a and miR-9-5p, were identified, with functional analyses revealing significant pathways like Endocytosis and MAPK signaling associated with these miRNAs' target genes. The miRNA-HUB gene regulatory network identified crucial miRNAs and HUB genes, such as Traf1 and Tnf, indicating roles in immune modulation and osteogenic differentiation. Protein-protein interaction (PPI) network analysis highlighted central HUB genes like Akt1 and Bcl2. ALP activity assays confirmed the influence of antigens on osteogenic differentiation, with reduced ALP activity observed. Expression analysis validated altered miRNA and chemokine expression post-antigen stimulation, with ELISA analysis showing a significant reduction in CXCL1 expression in response to antigen exposure. Conclusion: This study provides insights into the role of MSC-derived EVs in regulating parasite immunity. The findings suggest that hydatid antigens can modulate the expression of miRNAs in MSC-derived EVs, leading to changes in chemokine expression and osteogenic capacity. These findings contribute to a better understanding of the immunomodulatory mechanisms involved in hydatid disease and provide potential therapeutic targets for the development of new treatment strategies.
ABSTRACT
Osteoporosis is a common systemic skeletal disease and a predominant underlying factor in the increased occurrence of fractures. The structure of isoflavones resembles that of estrogen and can confer similar but weaker effects. This study investigated the potential inhibitory effects of isoflavones from chickpea sprouts (ICS) on ovariectomy (OVX)-induced osteoporosis in vitro and in vivo. Notably, we found that ICS treatment could attenuate bone loss and improve trabecular microarchitecture and biomechanical properties of the fourth lumbar vertebra in OVX-induced osteoporotic rats and could also inhibit the development of a hyperosteometabolic state in this model. The osteogenic differentiation of bone marrow stem cells (BMSCs) was significantly enhanced by ICS intervention in vitro, and we confirmed that estrogen receptor α signaling was required for this increased osteogenic differentiation. Additionally, ICS has been shown to inhibit bone resorption via ERa modulation of the OPG/RANKL pathway. RANKL-induced osteoclastogenesis was reduced under ICS treatment, supporting that NF-κB signaling was inhibited by ICS. Thus, ICS attenuates osteoporosis progression by promoting osteogenic differentiation and inhibiting osteoclastic resorption. These results support the further exploration and development of ICS as a pharmacological agent for the treatment and prevention of osteoporosis.
