Intestinal schistosomiasis, caused by infection with Schistosoma japonicum, remains a zoonotic neglected tropical disease (NTD) of significant public health importance in parts of China, the Philippines, and Indonesia. Ongoing schistosomiasis control programmes in these areas have achieved significant reductions in disease prevalence, transmission, and morbidity associated with infection; however, they have also presented new challenges, particularly in detecting and monitoring low-intensity and low-prevalence S. japonicum infections. Highly sensitive and highly specific diagnostic assays are therefore needed for effective disease diagnosis and transmission monitoring in low-endemicity areas, and the development of such assays has been recommended by the World Health Organisation. We first aimed to determine whether a Schistosoma spp. genus-specific real-time PCR assay routinely used to diagnose infections with African schistosome species (namely Schistosoma mansoni and Schistosoma haematobium), as well as two more recently developed S. japonicum species-specific real-time PCR assays, can accurately diagnose low-intensity S. japonicum infections. We also sought to optimise one of the S. japonicum species-specific real-time PCR assays by adding the same DNA extraction and PCR internal positive control target commonly used with the Schistosoma spp. genus-specific real-time PCR assay. This was done using in silico analyses and endpoint PCR with Sanger sequencing and real-time PCR using genomic DNA isolated from Schistosoma spp. adult worms, H2O spiked with individual S. japonicum ova, and naïve human faecal material also spiked with individual S. japonicum ova. We demonstrate that the Schistosoma spp. genus-specific real-time PCR assay and one of the S. japonicum species-specific real-time PCR assays described here are likely incapable of reliably diagnosing low-intensity S. japonicum infections. We also demonstrate that the other S. japonicum species-specific real-time PCR assay can be performed using an additional DNA extraction and PCR internal positive control target and may reliably diagnose low-intensity S. japonicum infections. Whilst clinical assessment of the optimised S. japonicum species-specific real-time PCR assay described here is needed, it is our hope that this assay will become a standard and routinely used method to diagnose low-intensity S. japonicum infections and will be used support future S. japonicum transmission surveillance and elimination programmes.

A rapid and specific strategy for detecting Orientobilharzia turkestanicum, a water-associated schistosome of veterinary and environmental concern.

Eosinophilic inflammation is a feature of allergic asthma, with eosinophil depletion shown to alleviate symptoms. Elevated levels of eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid (BALF) correlate with asthma severity. Sj16 is a protein from Schistosoma japonicum with known immunoregulatory properties. Exosomes, with their protective phospholipid bilayer, serve as efficient drug carriers. We extracted exosomes secreted by Escherichia coli Nissle 1917 engineered to express Sj16 (EcN-Sj16-Exo), and sought to investigate the role of EcN-Sj16-Exo in asthma. In an ovalbumin-induced experimental asthma model in mice, EET levels were elevated. The experimental asthma model was treated with EcN-Sj16-Exo. EET formation was assessed using immunofluorescence and scanning electron microscopy. Lung function, airway remodelling and inflammation were evaluated. Wiskott-Aldrich syndrome-like (WASL) knockout mice and recombinant adeno-associated virus (rAAV)-expressing neural Wiskott-Aldrich syndrome protein (N-WASP) were used to investigate the potential mechanisms of EcN-Sj16-Exo. EET formation is increased in sputum and BALF from patients with asthma. We demonstrate that Sj16 inhibits EET formation in vitro and localises primarily in exosomes when secreted by EcN-Sj16. In the experimental asthma model, EcN-Sj16-Exo significantly reduced EET formation. Moreover, EcN-Sj16-Exo significantly attenuated airway hyperreactivity and airway remodelling, as evidenced by reduced lung resistance, improved dynamic compliance and diminished inflammatory cell infiltration, fibrosis and mucus hypersecretion. Furthermore, EcN-Sj16-Exo decreased eosinophil and neutrophil counts, IgE levels and type 2 cytokine levels in BALF while increasing T-regulatory cells in the spleen. Mechanistically, EcN-Sj16-Exo inhibited EET formation by upregulating N-WASP. WASL-knockout mice and AAV6-WASL-mediated N-WASP expression confirmed that EcN-Sj16-Exo alleviates experimental asthma by upregulating N-WASP to inhibit EET formation. Our findings suggest that EcN-Sj16-Exo represents a promising therapeutic approach in asthma, highlighting the potential of targeting EETs and N-WASP in asthma therapy.

Integrating network pharmacology and experimental validation to uncover the therapeutic mechanisms of Chaigui decoction in Schistosoma japonicum-induced liver fibrosis.

Although schistosome eggs are widely recognized as the principal drivers of hepatic granulomatous inflammation and fibrosis, the independent effects of adult worms may be masked by strong egg antigen-mediated responses. This study aimed to investigate whether adult Schistosoma japonicum worms alter the miRNA expression profile of hepatic stellate cells and to explore the potential relevance of these changes to liver fibrosis and hepatocellular carcinoma-related processes. A non-contact Transwell co-culture system was established using paired Schistosoma japonicum worms or male worms and hepatic stellate cells. Male worms were additionally included to further assess worm-derived effects independent of egg production-related influences. Untreated hepatic stellate cells served as controls. Total RNA was extracted for miRNA sequencing, and differentially expressed miRNAs were identified. Target gene prediction, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and validation using The Cancer Genome Atlas database were subsequently performed. Both paired worms and male worms significantly altered the miRNA expression profile of hepatic stellate cells. Several differentially expressed miRNAs were identified, among which hsa-miR-103a-3p showed relatively stable changes. Pathway enrichment analysis suggested that the potential target genes of hsa-miR-103a-3p were mainly enriched in AMP-activated protein kinase, mechanistic target of rapamycin, tumor necrosis factor, insulin signaling, and cellular senescence pathways. Further analysis using The Cancer Genome Atlas database showed that hsa-miR-103a-3p had diagnostic value in hepatocellular carcinoma and was associated with alpha-fetoprotein level, albumin level, Ishak fibrosis score, pathological stage, histological type, and tumor status. These findings suggest that adult S. japonicum worms may alter the miRNA expression profile of hepatic stellate cells, and that hsa-miR-103a-3p may be associated with fibrogenic responses and may have potential relevance to hepatocellular carcinoma-related processes. However, this inference is based on correlative TCGA data and does not imply a causal role in schistosomiasis-associated hepatocarcinogenesis.

Structural variation drives praziquantel response and host adaptation in Schistosoma japonicum

Schistosomiasis, a zoonotic parasitic disease caused by schistosome infection, remains a serious public health concern. However, diagnostic methods with both high sensitivity and specificity or early diagnosis for detecting schistosome infection are still lacking. This study aimed to evaluate the diagnostic potential of parasite-derived exosomes miRNAs in Schistosoma japonicum (S. japonicum) infection. Exosomes were isolated and purified from adult worms and eggs of S. japonicum using ultracentrifugation. Nine highly abundant miRNAs were identified in these exosomes through small RNA sequencing. TaqMan probe-based reverse transcription real-time PCR (RT-qPCR) revealed that serum levels of all nine parasite-derived miRNAs were significantly elevated in infected mice at different time points post-infection. Compared with healthy controls, infected patients exhibited significantly elevated serum levels of sja-miR-61 and sja-miR-7-5p. Receiver operating characteristic (ROC) analysis indicated that the area under the curve (AUC) values for serum sja-miR-61 and sja-miR-7-5p were 0.8750 and 0.8375, respectively, surpassing those of the other miRNAs examined in human serum. The sensitivity and specificity for detecting these miRNAs in human serum were 85.00% and 85.00% for sja-miR-61, and 70.00% and 80.00% for sja-miR-7-5p. When both miRNAs were detected in combination, sensitivity increased to 95.00% with a specificity of 75.00%. In mice, the sensitivity and specificity for detecting sja-miR-7-5p at 2 weeks post-infection were 73.33% and 86.67%, improving to 93.33% and 93.33% at 6 weeks. For sja-miR-61, sensitivity and specificity were 93.33% and 80.00% at 2 weeks, reaching 100.00% and 100.00% at 6 weeks. Serum levels of sja-miR-61 and sja-miR-7-5p dropped to undetectable levels two weeks after praziquantel treatment, underscoring their utility in monitoring treatment response. Furthermore, measurement of sja-miR-61 and sja-miR-7-5p in mice with varying infection intensities showed rising serum levels corresponding to increased worm burdens, with a minimum detection threshold equivalent to an infection with 5 cercariae, highlighting the high sensitivity of this approach for detecting low-level infections in mice. Collectively, the detection of these miRNAs in patient or mouse serum using TaqMan RT-qPCR exhibits good sensitivity and specificity, along with considerable value for early diagnosis and treatment monitoring. sja-miR-61 and sja-miR-7-5p represent promising biomarkers for the diagnosis of schistosomiasis japonica.

To establish a fluorescent recombinase-aided amplification (RAA) assay for detection of Strongyloides stercoralis nucleic acid and to preliminarily evaluate its performance. Six sets of specific primers targeting S. stercoralis 18S ribosomal RNA (18S rRNA) gene and one fluorescent probe were designed and synthesized. The optimal primer-probe set was determined through systematic screening and optimization to establish the fluorescent RAA assay. The assay was evaluated using S. stercoralis genomic DNA at concentrations of 100, 10, and 1 pg/μL, and 100, 10, and 1 fg/μL, as well as recombinant pUC57 plasmids containing the target gene fragments at 1 × 105, 1 × 104, 1 × 103, 1 × 102, 1 × 101, 1 × 100 copies/reaction, to determine the analytical sensitivity. Genomic DNA from Ascaris lumbricoides, Ancylostoma duodenale, Enterobius vermicularis, Angiostrongylus cantonensis, Trichinella spiralis, Clonorchis sinensis, Schistosoma japonicum, and Taenia saginata was used to assess assay specificity. A total of 25 stool samples from patients suspected of S. stercoralis infection were tested by the modified Baermann funnel technique, PCR, and the established fluorescent RAA assay. The sensitivity, specificity, concordance rate and their 95% confidence intervals (CI) of these three techniques were estimated, and agreement between methods was evaluated using the Kappa coefficient. Exo-4 was identified as the optimal primer set screened from the six primer sets, and the best amplification performance was achieved when the final concentrations of the forward and reverse primers were 0.44 μmol/L and a probe concentration was 0.20 μmol/L. The limit of detection of the fluorescent RAA assay was 100 fg/μL for genomic DNA of S. stercoralis and 1 × 100 copies/reaction for recombinant plasmids. Specific fluorescence signals were detected within 5 min, with no cross-reactivity observed with A. lumbricoides, A. duodenale, E. vermicularis, A. cantonensis, T. spiralis, C. sinensis, S. japonicum, or T. saginata. Among the 25 clinical stool samples from patients suspected of S. stercoralis infections, the modified Baermann funnel technique and fluorescent RAA assay detected 19 positives and 6 negatives, whereas PCR detected 18 positives and 7 negatives. The fluorescent RAA assay showed a sensitivity of 100.00% [95% CI: (82.35%, 100.00%)], specificity of 100.00% [95% CI: (54.07%, 100.00%)], concordance rate of 100.00% [95% CI: (86.28%, 100.00%)], and a Kappa coefficient of 1.00 [95% CI: (1.00, 1.00)] (P < 0.001) relative to the modified Baermann funnel technique, and a sensitivity of 100.00% [95% CI: (81.47%, 100.00%)], specificity of 85.71% [95% CI: (42.13%, 99.64%)], concordance rate of 96.00% [95% CI: (79.65%, 99.90%)], and a Kappa coefficient of 0.90 [95% CI: (0.70, 1.00)] (P < 0.001). Positive amplification products emitted green fluorescence under a portable blue-light device, enabling visual interpretation of results. The fluorescent RAA assay established in this study is rapid, highly sensitive, and highly specific. It enables detection of S. stercoralis nucleic acid under isothermal conditions and allows visual interpretation of results, providing a novel tool for rapid clinical diagnosis and field screening of S. stercoralis infections.

This paper examines the research output and impact of Veterinary Research Institutes (VRIs) of the Chinese Academy of Agricultural Sciences (CAAS), namely Shanghai Veterinary Research Institute (SHVRI), Harbin Veterinary Research Institute (HVRI), and Lanzhou Veterinary Research Institute (LVRI), to answer research questions. The study explores publication count, citation structure, h-index, most-cited articles, keyword trends, trend topics, co-authorship, thematic maps, and bibliographic coupling. The data is extracted from Scopus, covering publications from 2009 to 2023. Utilizing Excel, R (Biblioshiny), and VOSviewer (version 1.6.20, Leiden University, Netherlands), we found that VRIs of the CAAS demonstrated a steady upward trend in their research output, with SHVRI leading in top-cited articles, HVRI in citations and h-index, and LVRI in publications. Key journals include Veterinary Microbiology and Parasites and Vectors. Leading authors are Chan Ding (SHVRI), Xiaomei Wang (HVRI), and Xing-Quan Zhu (LVRI). Key research focus is on parasitology, virology, immunology, and molecular biology. SHVRI and HVRI's demonstrated focus is on virology, while LVRI's interest is in genetic analyses of the pathogens. Bibliographic coupling highlights core themes: SHVRI on Newcastle disease, Schistosoma japonicum, Toxoplasma gondii, and Porcine reproductive and respiratory syndrome virus; HVRI on African swine fever virus, Influenza viruses, and Porcine epidemic diarrhea virus; and LVRI on Toxoplasma gondii, the parasitic mitochondrial genome, and Foot and Mouth disease virus. Findings reflect CAAS's commitment to addressing critical animal diseases for China's development and food security.

Dynamic DNA methylation landscapes underpin host adaptation and sexual dimorphism in Schistosoma japonicum.

Core-xylosylated N-glycans represent a ubiquitous class of N-glycans widely distributed across nature. Recently, core-xylosylated N-glycans have attracted considerable attention in the medical field, as they could elicit strong immune responses. Notably, antibodies targeting core-xylosylated N-glycans could kill Schistosoma in vitro, and thus process potentials for protecting host from Schistosoma infections. However, the structural complexity has posed significant challenges to access structure-defined core-xylosylated N-glycans. Here, a powerful synthetic platform enabling the efficient preparation of core-xylosylated N-glycans is described. The strategy is based on de novo biosynthetic pathways to efficiently generate a sufficient quantity of N-glycan core precursors, coupled with the use of a robust β1,2-Xylosyltransferase to install core xylose in a stereoselective and regioselective manner. This approach further leverages diversity-oriented synthesis to systematically construct a comprehensive core-xylosylated N-glycan library, encompassing a broad range of structurally diverse N-glycans through enzymatic extension strategy. With the glycan array made from this glycan library, we investigated the binding activities of the antibodies against Schistosoma japonicum, which has caused widespread infections in Asia. In addition to the synthetic breakthroughs, this work also provides an insightful understanding of the structure-function relationships of core-xylosylated N-glycans, which will advance the rational design of carbohydrate-based vaccine against Schistosoma infections.

Despite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection. We evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis. Our findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown. We identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.

BackgroundHepatic fibrosis induced by Schistosoma japonicum (S. japonicum) infection is a major global public health concern. Centrosomal protein 72 (CEP72), a key regulator involved in maintaining cellular architecture and integrity, is significantly upregulated during the progression of hepatic fibrosis; however, its specific biological function in this pathological process remains largely elusive. This study was designed to elucidate the novel biological role of CEP72 in liver fibrosis, with a particular focus on the pathogenesis of S. japonicum-induced hepatic fibrosis.MethodsPublicly available transcriptomic datasets of human hepatic fibrosis were analyzed, and the key findings were validated in two murine models of liver fibrosis (S. japonicum infection and carbon tetrachloride (CCl4) injection). To investigate the functional role of CEP72 in hepatic fibrogenesis, Cep72 knockout (Cep72−/−) mice were employed. Histological staining was performed to evaluate liver pathological changes, fibrotic area, and granuloma size. Transcriptomic profiling, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and western blot analyses were performed to assess the fibrogenic and inflammatory responses in liver tissues.ResultsCEP72 expression was significantly elevated in both human fibrotic liver samples and murine models of hepatic fibrosis. Notably, CEP72 deficiency markedly exacerbated liver fibrosis, as evidenced by significantly increased granuloma size and enhanced collagen deposition in both S. japonicum-infected and CCl4-treated mice. Transcriptomic analysis revealed a global upregulation of pro-fibrotic and pro-inflammatory genes in the livers of Cep72−/− mice compared with wild-type controls. These findings were further confirmed by qRT-PCR, IHC, and western blot analyses, which showed increased expression of fibrogenic markers, including α-smooth muscle actin and Collagen I. Mechanistically, loss of CEP72 promoted hepatic fibrogenesis by enhancing the expression of the transcription factor early growth response 1 (EGR1), which in turn upregulated tumor necrosis factor-α (TNF-α) transcription.ConclusionsCollectively, our findings demonstrate that CEP72 functions as a key negative regulator of inflammation-driven hepatic fibrosis. CEP72 deficiency accelerates the progression of liver fibrosis through the EGR1–TNF-α signaling pathway. This study identifies a previously unrecognized protective role of CEP72 in hepatic fibrosis and highlights its potential as a novel therapeutic target for the treatment of S. japonicum-induced and other types of inflammation-associated liver fibrosis.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s13071-026-07372-7.

Schistosomiasis is a neglected zoonotic disease, and the liver fibrosis induced by Schistosoma japonicum infection poses a significant threat to human health. Traditionally, liver fibrosis in schistosomiasis has been attributed to eggs deposited in the liver, which trigger hepatic inflammation and fibrosis. However, our study reveals that schistosomula migration to the liver induces epithelial-to-mesenchymal transition (EMT) in liver sinusoidal endothelial cell (LSEC), thereby contributing to the progression of liver fibrosis. In the early stage of S. japonicum infection, mice exhibited a reduction in the proportion of LSEC and impairment of their function. RNA-sequencing revealed significant alterations in β-Klotho (KLB) expression in injured LSEC. Although KLB is known to exert anti-inflammatory functions as a co-receptor for fibroblast growth factor (FGF) in the liver, its role in LSEC EMT and schistosomiasis-induced liver fibrosis was unclear. Using SK-Hep1 cells, we found that KLB knockdown exacerbated EMT, whereas KLBover-expressionattenuated EMT and decreased TGFβ1 secretion from LSEC, thereby suppressing LX-2 activation. In mice infected with S. japonicum, treatment with recombinant KLB protein or AAV8-KLB increased the LSEC population, mitigated EMT in both LSEC and liver tissues, ameliorated hepatic fibrosis, and inhibited TGFβ1 pathway activation. Our study reveals that KLB suppresses LSEC EMT induced by liver-stage schistosomula and TGFβ1 secretion, thereby inhibiting HSC activation and reducing liver fibrosis. Our findings highlight KLB as a promising therapeutic target for hepatic fibrosis in schistosomiasis.

Progressive IL-13 signaling is closely associated with liver fibrosis. Among fibrotic diseases, liver fibrosis induced by Schistosoma japonicum in advanced schistosomiasis is the primary driver of portal hypertension, which is the leading cause of mortality in affected patients. RNA sequencing analysis of human hepatic stellate cells revealed that IL-13RA2 was markedly upregulated in activated hepatic stellate cells and enriched in the cytokine-receptor interaction pathways, suggesting a potential role for IL-13RA2 in hepatic stellate cell activation and fibrosis progression. Based on these findings, we aimed to investigate whether IL-13RA2 also contributes to liver fibrosis during Schistosoma japonicum infection. In this study, we established a murine model of Schistosoma japonicum infection. Compared with IL-13RA1, IL-13RA2 expression was significantly increased at week 9 post-infection in mice. IL-13RA2 was enriched within fibrotic regions and increased in parallel with collagen accumulation and stellate cell activation. The phosphorylation levels of MEK and ERK changed in parallel with IL-13RA2 abundance. Furthermore, overexpression of IL-13RA2 markedly accelerated hepatic fibrogenesis, while knockdown of IL-13RA2 attenuated liver fibrosis induced by schistosomiasis via the MEK/ERK pathway. Hence, IL-13RA2 may represent an effective and promising therapeutic target for the attenuation of liver fibrosis.

Praziquantel (PZQ) is currently the only agent for treating schistosomiasis, but it is plagued by suboptimal efficacy to juvenile parasites, looming drug resistance, and inability to prevent reinfection. Thioredoxin glutathione reductase (TGR) is regarded as a promising therapeutic target due to its essential role in maintaining schistosome redox homeostasis. Herein, the crystal structures of Schistosoma japonicum TGR (SjTGR) in multiple redox states and in complex with NADPH, GSH, and the anti-helminthic agent Auranofin were elucidated. Structural analyses identified the hook-shaped conformation at the C-terminal redox center, which DTNB assays further confirmed enhances electron transfer efficiency. Structural and ITC data indicated that R317 was critical for NADPH binding via hydrogen-bond interactions. The analysis also indicated that the structure basis of Auranofin's potency was its tripartite interaction at the redox-active sites. In addition, we investigated the substrate specificity of SjTrx1i and SjTRP14, downstream proteins regulated by SjTGR, and elucidated the structural basis for this specificity by determining their oxidized/reduced structures. Furthermore, in vivo RNAi indicated knockdown of SjTGR or SjTRP14 blocked the survival and oviposition of schistosomes, thus ameliorating egg-induced granulomatous pathology in mice. This work provided a framework for knowledge-based design of novel anti-schistosomals targeting parasite-specific redox vulnerabilities.

Schistosomiasis affects approximately 250 million people globally. Eggs deposited in the colon are the main culprits causing pathological damage, with soluble egg antigen (SEA) being the most significant pathogenic factor in schistosomiasis. Colorectal cancer (CRC) is the most common type of gastrointestinal carcinoma. The colorectum is a common organ affected by both CRC and schistosomiasis. Clinical reports have demonstrated a correlation between the onset and poor prognosis of CRC and Schistosoma japonicum infection. However, there is still a lack of experimental evidence regarding the effect of schistosomiasis japonica on CRC. In this study, we found that S. japonicum SEA promoted the proliferation of CRC cells in a dose-dependent manner and upregulated the expression of Ki67. Moreover, SEA enhanced the migration and epithelial-mesenchymal transition of CRC cells. RNA sequencing analysis revealed that SEA activated the MAPK and PI3K-AKT signaling pathways while inhibiting autophagy in HCT116 cells, findings that were subsequently validated by Western blotting. In the murine xenograft model, SEA promoted tumor growth, increased the expression of Ki67 and Vimentin, and activated the MAPK and PI3K-AKT signaling pathways in tumor tissues. Overall, our findings demonstrate that S. japonicum SEA accelerates the malignant development of CRC both in vitro and in vivo, which is linked to the suppression of autophagy and the activation of MAPK and PI3K-AKT signaling. This is the first demonstration that the S. japonicum SEA participates in the induction of CRC-related signaling pathways, thus providing experimental evidence for the impact of schistosomiasis in endemic areas on CRC.IMPORTANCEThis research provides crucial experimental evidence bridging clinical observations and molecular mechanisms in schistosomiasis-associated colorectal cancer (CRC). For the first time, we demonstrate that S. japonicum soluble egg antigen (SEA) accelerates CRC malignancy both in vitro and in vivo. Mechanistically, SEA activates the key oncogenic MAPK and PI3K-AKT signaling pathways while inhibiting autophagy. These findings establish a functional link between a specific parasitic factor and host cancer-driving pathways. This work strongly suggests that chronic exposure to SEA in endemic areas constitutes a defined biological risk factor for CRC. Ultimately, this study provides experimental evidence for elucidating the impact of S. japonicum infection on CRC and further deepens our understanding of the role of SEA in promoting tumor progression. Our study highlights the importance of schistosomiasis control as a potential strategy for CRC prevention in endemic regions.

Schistosomiasis Japonica in Patient from Philippines.

Hidden drivers of schistosomiasis: a role for hyperparasitism.

A case of colorectal lateral spreading tumor associated with Schistosoma japonicum infection.