Schistosomiasis is caused by Schistosoma infection and affects more than 200 million people worldwide. A large number of eggs produced by adult Schistosoma play central the role in host pathology and subsequent disease dissemination. However, the underlying mechanisms of egg production in Schistosoma still need to be further elucidated. Previously, we found that miR-31 was highly enriched in the female reproductive organs of Schistosoma japonicum (S. japonicum), which was shown to be associated with ovarian development. In the present study, we analyzed the potential targets of miR-31 including mRNA and long noncoding RNAs (lncRNAs) in S. japonicum by RNA seq combined with bioinformatics. Then, six putative targets of miR-31 including three mRNAs such as EWB00_000918, EWB00_004242, and EWB00_009323 and three lncRNAs such as LncSJG_010465, LncSJG_015374 and LncSJG_013128 were further analyzed their expressions in the parasites treated with miR-31 inhibitor by qPCR to confirm their potential regulations. Whole mount in suit hybridization (WISH) analysis of some miR-31 targets were carried out to determine their colocalizations with miR-31. Furthermore, we selected EWB00_009323, which is an eggshell synthetic protein and also a target of miR-31, to inhibit its functions by small interfering RNA. The results indicated that inhibition of EB00_009323 led to decreased oviposition and defective ovarian morphology. Overall, the potential targets of miR-31 including mRNA and lncRNAs were identified in female S. japonicum and the results indicated that miR-31 coordinates with its targets, at least EWB00_009323, play an important role in ovarian development and egg production.

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: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis.
UNASSIGNED: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms.
CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

To research the role of the NLRP3 inflammasome in Schistosoma japonicum-induced granuloma formation and liver fibrosis. In in vivo tests, BALB/c mice were used. shNLRP3 plasmid based on adeno-associated virus serotype 8 (AAV8-shNLRP3) was injected to block NLRP3 inflammasome via tail vein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected to assess liver injury. H&E staining was used for routine histopathological assessment; Masson\'s trichrome staining was used to detect fibrous tissues and collagen fibers. Hepatic expression of NLRP3, procaspase-1, bioactive caspase-1, collagen-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot. Serum levels of IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The inflammatory cell infiltration and hepatic expression of IL-1β around the granuloma were detected by immunohistochemistry staining. Treatment of S. japonicum infected mice with AAV8-shNLRP3 significantly reduced the hepatic levels of bioactive caspase-1 and IL-1β, as well as circulating IL-1β concentrations, while reducing the amounts of myeloperoxidase (MPO) and F4/80 positive cells around the granuloma. Moreover, collagen deposition, TIMP-1, and α-SMA, which are markers of hepatic stellate cell (HSC) activation, were reduced around the liver granuloma. These findings highlight a therapeutic potential of AAV8-shNLRP3 in schistosomiasis cirrhosis.

Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum. We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.

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.

Schistosomiasis caused by Schistosoma japonicum (S. japonicum) is a major public health problem in the Philippines, China and Indonesia. In this study, the immunopotentiator CpG-ODN was encapsulated within chitosan nanoparticles (Chi NPs) to create a combination adjuvant (Chi-CpG NP). This approach was employed to enhance the immunogenicity of 26 kDa glutathione S-transferase (Sj26GST) from S. japonicum through intranasal immunization. The results demonstrated higher levels of specific anti-Sj26GST antibodies and Sj26GST-specific splenocyte proliferation compared to mice that were immunized with Sj26GST + Chi-CpG NP. Cytokine analysis of splenocytes revealed that the Sj26GST + Chi-CpG NP induced a slight Th1-biased immune response, with increased production of IFN-γ by CD4+ T-cells in the spleen. Subsequently, mice were intradermally inoculated with 1 × 107 organisms in the Coeliac cavity. The bacterial organ burden detected in the liver of immunized mice suggested that Sj26GST + Chi-CpG NP enhances protective immunity to inhibit S. japonicum colonization. Therefore, Sj26GST + Chi-CpG NP vaccination enhances Sj26GST-specific immunogenicity and provides protection against S. japonicum.

Infection with Schistosoma japonicum (S. japonicum) is an important zoonotic parasitic disease that causes liver fibrosis in both human and domestic animals. The activation of hepatic stellate cells (HSCs) is a crucial phase in the development of liver fibrosis, and inhibiting their activation can alleviate this progression. Total flavonoids of litchi seed (TFL) is a naturally extracted drug, and modern pharmacological studies have shown its anti-fibrotic and liver-protective effects. However, the role of TFL in schistosomiasis liver fibrosis is still unclear. This study investigated the therapeutic effects of TFL on liver fibrosis in S. japonicum infected mice and explored its potential mechanisms. Animal study results showed that TFL significantly reduced the levels of Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), Interleukin-4 (IL-4), and Interleukin-6 (IL-6) in the serum of S. japonicum infected mice. TFL reduced the spleen index of mice and markedly improved the pathological changes in liver tissues induced by S. japonicum infection, decreasing the expression of alpha-smooth muscle actin (α-SMA), Collagen I and Collagen III protein in liver tissues. In vitro studies indicated that TFL also inhibited the activation of HCSs induced by Transforming Growth Factor-β1 (TGF-β1) and reduced the levels of α-SMA. Gut microbes metagenomics study revealed that the composition, abundance, and functions of the mice gut microbiomes changed significantly after S. japonicum infection, and TLF treatment reversed these changes. Therefore, our study indicated that TFL alleviated granulomatous lesions and improved S. japonicum induced liver fibrosis in mice by inhibiting the activation of HSCs and by improving the gut microbiomes.