BACKGROUND: Schistosoma japonicum (S. japonicum) is the main species of Schistosoma prevalent in China. Myeloid-derived suppressor cells (MDSCs) are important immunoregulatory cells and generally expand in parasite infection, but there is little research relating to MDSCs in Schistosoma infection.
METHODS: Fifty-six S. japonicum-infected patients were included in this study. MDSCs and percentages and absolute cell numbers of lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells and natural killer (NK) cells were detected using flow cytometry. The degree of liver fibrosis was determined using color Doppler ultrasound.
RESULTS: Patients infected with S. japonicum had a much higher percentage of MDSCs among peripheral blood mononuclear cells (PBMCs) than the healthy control. Regarding subpopulations of MDSCs, the percentage of granulocytic myeloid-derived suppressor cells (G-MDSCs) was clearly increased. Correlation analysis showed that the absolute cell counts of T-cell subsets correlated negatively with the percentages of MDSCs and G-MDSCs among PBMCs. The percentage of G-MDSCs in PBMCs was also significantly higher in patients with liver fibrosis diagnosed by color doppler ultrasound (grade > 0), and the percentage of G-MDSCs in PBMCs and liver fibrosis grading based on ultrasound showed a positive correlation.
CONCLUSIONS: S. japonicum infection contributes to an increase in MDSCs, especially G-MDSCs, whose proliferation may inhibit the number of CD4+ T cells in peripheral blood. Meanwhile, there is a close relationship between proliferation of G-MDSCs and liver fibrosis in S. japonicum-infected patients.
UNASSIGNED: La prolifération des MDSC peut indiquer une réponse immunitaire des lymphocytes T CD4+ plus faible dans la schistosomiase japonica.
UNASSIGNED: Contexte : Schistosoma japonicum est la principale espèce de Schistosoma répandue en Chine. Les cellules myéloïdes suppressives (MDSC) sont des cellules immunorégulatrices importantes et se développent généralement lors d’une infection parasitaire, mais il existe peu de recherches sur les MDSC dans l’infection à Schistosoma. Méthodes : Cinquante-six patients infectés par S. japonicum ont été inclus dans cette étude. Les MDSC, les pourcentages et les nombres absolus des sous-ensembles de lymphocytes, notamment les lymphocytes T CD3+, les lymphocytes T CD4+, les lymphocytes T CD8+, les lymphocytes B et les cellules tueuses naturelles (NK) ont été détectés par cytométrie en flux. Le degré de fibrose hépatique a été déterminé par échographie Doppler couleur. Résultats : Les patients infectés par S. japonicum présentaient un pourcentage beaucoup plus élevé de MDSC parmi les cellules mononucléées du sang périphérique (CMSP) que les patients sains. En ce qui concerne les sous-populations de MDSC, le pourcentage de cellules suppressives granulocytaires dérivées de myéloïdes (G-MDSC) était augmenté de manière évidente. L’analyse de corrélation a montré que le nombre absolu des cellules des sous-ensembles de lymphocytes T était en corrélation négative avec les pourcentages de MDSC et de G-MDSC parmi les CMSP. Le pourcentage de G-MDSC dans les CMSP était également significativement plus élevé chez les patients présentant une fibrose hépatique diagnostiquée par échographie Doppler couleur (grade > 0), et le pourcentage de G-MDSC dans les CMSP et le classement de la fibrose hépatique basé sur l’échographie ont montré une corrélation positive. Conclusion : L’infection à S. japonicum contribue à une augmentation des MDSC, notamment des G-MDSC, dont la prolifération pourrait inhiber le nombre de lymphocytes T CD4+ dans le sang périphérique. Parallèlement, il existe une relation étroite entre la prolifération des G-MDSC et la fibrose hépatique chez les patients infectés par S. japonicum.

BACKGROUND: Schistosomiasis is still one of the most serious parasitic diseases. Evidence showed that the metabolite profile in serum can potentially act as a marker for parasitic disease diagnosis and evaluate disease progression and prognosis. However, the serum metabolome in patients with Schistosoma japonicum infection is not well defined. In this study, we investigated the metabolite profiles of patients with chronic and with advanced S. japonicum infection.
METHODS: The sera of 33 chronic S. japonicum patients, 15 patients with advanced schistosomiasis and 17 healthy volunteers were collected. Samples were extracted for metabolites and analyzed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).
RESULTS: We observed significant differences in metabolite profiles in positive and negative ion modes between patients with advanced and chronic S. japonicum infection. In patients with chronic S. japonicum infection, 199 metabolites were significantly upregulated while 207 metabolites were downregulated in advanced infection. These differential metabolites were mainly concentrated in steroid hormone biosynthesis, cholesterol metabolism and bile secretion pathways. We also found that certain bile acid levels were significantly upregulated in the progression from chronic to advanced S. japonicum infection. In receiver operator characteristic (ROC) analysis, we identified three metabolites with area under the curve (AUC) > 0.8, including glycocholic (GCA), glycochenodeoxycholate (GCDCA) and taurochenodeoxycholic acid (TCDCA) concentrated in cholesterol metabolism, biliary secretion and primary bile acid biosynthesis.
CONCLUSIONS: This study provides evidence that GCA, GCDCA and TCDCA can potentially act as novel metabolite biomarkers to distinguish patients in different stages of S. japonicum infection. This study will contribute to the understanding of the metabolite mechanisms of the transition from chronic to advanced S. japonicum infection, although more studies are needed to validate this potential role and explore the underlying mechanisms.

BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART.
METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment.
RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms\' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART.
CONCLUSIONS: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.

UNASSIGNED: Schistosomiasis is a zoonotic parasitic disorder induced by the infestation of schistosomes, a genus of trematodes. MicroRNAs (miRNAs) in egg-derived exosomes are crucial for modulating the host\'s immune responses and orchestrating the pathophysiological mechanisms. Although the exosomes secreted by S. japonicum contain abundant miRNAs, the specific roles of these miRNAs in the pathogenesis of schistosomiasis-induced hepatic fibrosis are yet to be comprehensively elucidated. The egg exosomes of S. japonicum secrete miRNA-30, a novel miRNA.
UNASSIGNED: In vitro, the effect of miRNA-30 was evaluated by transfecting HSCs with miRNA mimics. The target gene biosignature for miRNA-30 was predicted using the miRDB software. The effect of miRNA-30 in hepatic fibrosis was evaluated by either elevating its expression in healthy mice or by inhibiting its activity in infected mice by administration of recombinant adeno-associated virus serotype eight vectors expressing miRNA-30 or miRNA sponges.
UNASSIGNED: This novel miRNA can activate hepatic stellate cells (HSCs), the prinary effector cells of hepatic fibrosis, in vitro, i.e., it significantly increases the fibrogenic factors Col1(α1), Col3(α1), and α-SMA at both mRNA and protein levels. In addition, miRNA-30 may activate HSCs by targeting the host RORA gene. In addition, in vivo experiments were conducted by administering a recombinant adeno-associated viral vector to modulate the expression levels of miRNA-30. The overexpression of miRNA-30 in healthy mice significantly elevated the expression of Col1(α1), Col3(α1), and α-SMA at both the transcriptomic and proteomic scales. This overexpression was coupled with a pronounced augmentation in the hepatic hydroxyproline content. Conversely, the in vivo silencing of miRNA-30 in infected mice induced a considerable reduction in the size of hepatic granulomas and areas of collagen deposition. Hence, in vivo, modulation of miRNA-30 expression may play a pivotal role in ameliorating the severity of hepatic fibrosis in mice afflicted with S. japonica.
UNASSIGNED: The study results suggest that miRNA-30 may augment schistosomiasis-induced hepatic fibrosis through a probable interaction with the host RORA. Our study may improve the current theoretical framework regarding cross-species regulation by miRNAs of hepatic fibrosis in schistosomiasis.

BACKGROUND: The primary pathogenic mechanism of schistosomiasis-associated liver fibrosis involves the deposition of schistosome eggs, leading to the formation of liver egg granulomas and subsequent liver fibrosis. Hepatic stellate cells are abnormally activated, resulting in excessive collagen deposition and fibrosis development. While specific long non-coding RNAs (lncRNAs) have been associated with fibrotic processes, their roles in schistosomiasis-associated liver fibrosis remain unclear.
METHODS: Our previous research indicated that downregulating the ICOSL/ICOS could partially alleviate liver fibrosis. In this study, we established a schistosomiasis infection model in C57BL/6 and ICOSL knockout (KO) mice, and the liver pathology changes were observed at various weeks postinfection (wpi) using hematoxylin and eosin and Masson\'s trichrome staining. Within the first 4 wpi, no significant liver abnormalities were observed. However, mice exhibited evident egg granulomas and fibrosis in their livers at 7 wpi. Notably, ICOSL-KO mice had significantly smaller pathological variations compared with simultaneously infected C57BL/6 mice. To investigate the impact of lncRNAs on schistosomiasis-associated liver fibrosis, quantitative real-time polymerase chain reaction (RT-qPCR) was used to monitor the dynamic changes of lncRNAs in hepatic stellate cells of infected mice.
RESULTS: The results demonstrated that lncRNA-H19, -MALAT1, -PVT1, -P21 and -GAS5 all participated in liver fibrosis formation after schistosome infection. In addition, ICOSL-KO mice exhibited significantly inhibited expression of lncRNA-H19, -MALAT1 and -PVT1 after 7 wpi. In contrast, they showed enhanced expression of lncRNA-P21 and -GAS5 compared with C57BL/6 mice, influencing liver fibrosis development. Furthermore, small interfering RNA transfection (siRNA) in JS-1 cells in vitro confirmed that lncRNA-H19, -MALAT1, and -PVT1 promoted liver fibrosis, whereas lncRNA-P21 and -GAS5 had the opposite effect on key fibrotic molecules, including α- smooth muscle actin and collagen I expression.
CONCLUSIONS: This study uncovers that ICOSL/ICOS may play a role in activating hepatic stellate cells and promoting liver fibrosis in mice infected with Schistosoma japonicum by dynamically regulating the expression of specific lncRNAs. These findings offer potential therapeutic targets for schistosomiasis-associated liver fibrosis.

Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX-2 cell activation, we performed RNA-seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum-induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA-494-3p, a microRNA associated with anti-liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA-494-3p in LX-2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α-SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum.

BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River.
METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density.
RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west.
CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.

BACKGROUND: Schistosomiasis japonica represents a significant public health concern in South Asia. There is an urgent need to optimize existing schistosomiasis diagnostic techniques. This study aims to develop models for the different stages of liver fibrosis caused by Schistosoma infection utilizing ultrasound radiomics and machine learning techniques.
METHODS: From 2018 to 2022, we retrospectively collected data on 1,531 patients and 5,671 B-mode ultrasound images from the Second People\'s Hospital of Duchang City, Jiangxi Province, China. The datasets were screened based on inclusion and exclusion criteria suitable for radiomics models. Liver fibrosis due to Schistosoma infection (LFSI) was categorized into four stages: grade 0, grade 1, grade 2, and grade 3. The data were divided into six binary classification problems, such as group 1 (grade 0 vs. grade 1) and group 2 (grade 0 vs. grade 2). Key radiomic features were extracted using Pyradiomics, the Mann-Whitney U test, and the Least Absolute Shrinkage and Selection Operator (LASSO). Machine learning models were constructed using Support Vector Machine (SVM), and the contribution of different features in the model was described by applying Shapley Additive Explanations (SHAP).
RESULTS: This study ultimately included 1,388 patients and their corresponding images. A total of 851 radiomics features were extracted for each binary classification problems. Following feature selection, 18 to 76 features were retained from each groups. The area under the receiver operating characteristic curve (AUC) for the validation cohorts was 0.834 (95% CI: 0.779-0.885) for the LFSI grade 0 vs. LFSI grade 1, 0.771 (95% CI: 0.713-0.835) for LFSI grade 1 vs. LFSI grade 2, and 0.830 (95% CI: 0.762-0.885) for LFSI grade 2 vs. LFSI grade 3.
CONCLUSIONS: Machine learning models based on ultrasound radiomics are feasible for classifying different stages of liver fibrosis caused by Schistosoma infection.

Schistosoma species are the causative agent of schistosomiasis and shows worldwide distribution. There is a great need to develop a sensitive diagnostic approach for controlling the disease. Previously, we identified large numbers of Extracellular Vesicle (EV) proteins from Schistosoma japonicum (S. japonicum), but rarely these proteins have been evaluated for their diagnostic potential. In the present study, we performed bioinformatic analyses of S. japonicum identified EV-associated proteins from the previous study and then identified Schistosoma-specific proteins with potentially secreted capability. Among them, we selected SJCHGC02838 protein, SJCHGC05593 protein, SJCHGC05668 protein and a hypothetical protein (SJHYP) to evaluate their diagnostic potential for detecting S. japonicum infection. First, we determined the expression of these four proteins at the transcript levels using qRT-PCR and revealed that all these genes showed higher expression in adult stage. Then, we cloned the full-length cDNA for each protein into a prokaryotic expression vector and successfully generated the recombinant proteins. Upon the purification of recombinant proteins, we developed an indirect ELISA method to evaluate the diagnostic potential of these purified recombinant proteins. The results showed high sensitivity for detecting Schistosoma infection. Additionally, these proteins also displayed a good potential for detecting Schistosoma infection, especially SJCHGC05668 protein at an early stage. The diagnostic potentials of these recombinant proteins were further evaluated by Western blot and comparatively analyzed by our previously developed cfDNA methods.

BACKGROUND: Schistosoma japonicum eggs lodge in the liver and induce a fibrotic granulomatous immune response in the liver of host. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs. However, the pathology and molecular mechanisms promoting hepatic granuloma formation remain poorly understood.
METHODS: To investigate the effect of blocking galectin-receptor interactions by α-lactose on liver immunopathology in mice with S. japonicum infection, C57BL/6 mice were infected with S. japonicum and alpha (α)-lactose was intraperitoneally injected to block the interactions of galectins and their receptors.
RESULTS: Compared with S. japonicum-infected mice, there were significantly decreased Gal-3 mRNA and protein expression levels, decreased intensity of Gal-3 fluorescence in the liver, decreased serum ALT and AST levels, decreased egg numbers of S. japonicum in the liver section, attenuated hepatic and spleen pathology, and alleviated liver fibrosis accompanied with decreased protein expression levels of fibrosis markers [α-smooth muscle actin (α-SMA), collagen I, and collagen IV] in the liver of S. japonicum-infected mice blocked galectin-receptor interactions with hematoxylin-eosin staining, Masson\'s trichrome staining, immunohistochemistry, or Western blot analysis. Compared with S. japonicum-infected mice, blocking galectin-receptor interactions led to increased eosinophil infiltration and higher eosinophil cationic protein (ECP) expression in the liver, accompanied by increased mRNA levels of eosinophil granule proteins [ECP and eosinophil peroxidase (EPO)], IL-5, CCL11, and CCR3 in the liver and decreased mRNA levels of Gal-3 and M2 macrophage cytokines (TGF-β, IL-10, and IL-4) in the liver and spleen by using quantitative real-time reverse transcription-polymerase chain reaction. In addition, there were increased Beclin1 protein expression and protein expression ratio of LC3B-II/LC3B-I and decreased p62 protein expression and protein expression ratios of phospho-mTOR/mTOR and phospho-AKT/AKT by Western blot; increased double-labeled F4/80+/LC3B+ cells by immunofluorescence staining; increased M1 macrophage polarization in the liver of S. japonicum-infected mice blocked galectin-receptor interactions by flow cytometric analysis and immunofluorescence staining.
CONCLUSIONS: Our data found that blockage of galectin-receptor interactions downregulated Gal-3, which in turn led to reduced liver functional damage, elevated liver eosinophil recruitment, promoted macrophage autophagy through the Akt/mTOR signaling pathway, and alleviated liver pathology and fibrosis. Therefore, Gal-3 plays a pivotal role during S. japonicum infection and could be a target of pharmacologic potential for liver fibrosis induced by S. japonicum infection.