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FASEB Journal : Official Publication of... Jun 2024Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host...
Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.
Topics: Animals; Gastrointestinal Microbiome; Colitis, Ulcerative; Mice; Schistosoma japonicum; Dextran Sulfate; Female; Disease Models, Animal; Immunization; Ovum; Mice, Inbred C57BL
PubMed: 38822662
DOI: 10.1096/fj.202302576RR -
Frontiers in Cellular and Infection... 2024species are the causative agent of schistosomiasis and shows worldwide distribution. There is a great need to develop a sensitive diagnostic approach for controlling...
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 (), but rarely these proteins have been evaluated for their diagnostic potential. In the present study, we performed bioinformatic analyses of identified EV-associated proteins from the previous study and then identified -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 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 infection. Additionally, these proteins also displayed a good potential for detecting 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.
Topics: Schistosoma japonicum; Animals; Extracellular Vesicles; Schistosomiasis japonica; Helminth Proteins; Biomarkers; Enzyme-Linked Immunosorbent Assay; Recombinant Proteins; Computational Biology; Sensitivity and Specificity; Mice; Humans; Female; Cloning, Molecular
PubMed: 38817446
DOI: 10.3389/fcimb.2024.1391168 -
Parasites & Vectors May 2024Schistosoma 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...
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.
Topics: Animals; Schistosomiasis japonica; Liver Cirrhosis; Schistosoma japonicum; Mice, Inbred C57BL; Mice; Galectin 3; Liver; Female; Lactose; Galectins
PubMed: 38769548
DOI: 10.1186/s13071-024-06314-5 -
Scientific Reports May 2024This study intends to use the basic information and blood routine of schistosomiasis patients to establish a machine learning model for predicting liver fibrosis. We...
This study intends to use the basic information and blood routine of schistosomiasis patients to establish a machine learning model for predicting liver fibrosis. We collected medical records of Schistosoma japonicum patients admitted to a hospital in China from June 2019 to June 2022. The method was to screen out the key variables and six different machine learning algorithms were used to establish prediction models. Finally, the optimal model was compared based on AUC, specificity, sensitivity and other indicators for further modeling. The interpretation of the model was shown by using the SHAP package. A total of 1049 patients' medical records were collected, and 10 key variables were screened for modeling using lasso method, including red cell distribution width-standard deviation (RDW-SD), Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), hematocrit (HCT), Red blood cells, Eosinophils, Monocytes, Lymphocytes, Neutrophils, Age. Among the 6 different machine learning algorithms, LightGBM performed the best, and its AUCs in the training set and validation set were 1 and 0.818, respectively. This study established a machine learning model for predicting liver fibrosis in patients with Schistosoma japonicum. The model could help improve the early diagnosis and provide early intervention for schistosomiasis patients with liver fibrosis.
Topics: Humans; Machine Learning; Liver Cirrhosis; Schistosomiasis japonica; Male; Female; Schistosoma japonicum; Middle Aged; Adult; Animals; China; Erythrocyte Indices; Algorithms; Aged
PubMed: 38769391
DOI: 10.1038/s41598-024-62521-1 -
Frontiers of Medicine Jun 2024Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been...
Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.
Topics: Animals; MicroRNAs; Liver Cirrhosis; Mice; Autophagy; Humans; Exosomes; Stem Cells; Hepatic Stellate Cells; Schistosomiasis japonica; Male; Schistosoma japonicum; Female; Disease Models, Animal; Mice, Inbred C57BL; Schistosomiasis; Liver
PubMed: 38769281
DOI: 10.1007/s11684-024-1079-1 -
Infection and Immunity Jun 2024Schistosomiasis is a serious public health problem, and previous studies found that liver function and hepatic cells are damaged. To evaluate the serum parameters of...
Schistosomiasis is a serious public health problem, and previous studies found that liver function and hepatic cells are damaged. To evaluate the serum parameters of liver function and fibrosis in schistosomiasis patients infected with (.) and analyze the correlations between liver function and serum fibrosis markers in patients infected with ., this retrospective study enrolled 133 patients. The study population was divided into four groups: healthy people control group ( = 20), chronic schistosomiasis without liver cirrhosis (CS) group ( = 21), schistosomiasis cirrhosis without hypoalbuminemia (SC-HA) group ( = 68), and schistosomiasis cirrhosis with hypoalbuminemia (SC +HA) group ( = 24). Clinical and laboratory data were collected for analysis. In the multiple comparison of abnormal rates of aspartate aminotransferase (AST) and total bilirubin (TBIL), the abnormal rate of the SC +HA group was significantly higher than that of the other three groups ( < 0.05), and the abnormal rate of γ-GT in the SC +HA group was significantly higher than that in the control group ( < 0.05). Multiple comparison results of serum levels of fibrosis markers showed that the SC group had a significantly higher level of indexes than other groups ( < 0.05). The levels of TGF-β1 in the CS group, SC-HA group and SC +HA group were significantly higher than those in the control group ( < 0.001). Our study demonstrated that the liver function and hepatic cells were damaged with the progression of liver disease in patients infected with , and they played an important role in the occurrence and development of liver fibrosis.
Topics: Humans; Liver Cirrhosis; Schistosomiasis japonica; Male; Female; Middle Aged; Animals; Schistosoma japonicum; Adult; Retrospective Studies; Hepatocytes; Biomarkers; Aged; Liver; Liver Function Tests
PubMed: 38767360
DOI: 10.1128/iai.00026-24 -
Experimental Parasitology Jul 2024Timely and accurate diagnosis of Schistosoma infection is important to adopt effective strategies for schistosomiasis control. Previously, we demonstrated that...
Timely and accurate diagnosis of Schistosoma infection is important to adopt effective strategies for schistosomiasis control. Previously, we demonstrated that Schistosoma japonicum can secret extracellular vesicles and their cargos may serve as a novel type of biomarkers for diagnosing schistosomiasis. Here, we developed a Gaussia luciferase immunoprecipitation assay combined with S. japonicum extracellular vesicle (SjEV) protein to evaluate its potential for diagnosing schistosomiasis. A saposin-like protein (SjSLP) identified from SjEVs was fused to the Gaussia luciferase as the diagnostic antigen. The developed method showed good capability for detecting S. japonicum infection in mice and human patients. We also observed that the method could detect Schistosoma infection in mice as early as 7 days of post-infection, which showed better sensitivity than that of indirect ELISA method. Overall, the developed method showed a good potential for detecting Schistosoma infection particularly for early stage, which may provide an alternative strategy for identify Schistosoma infection for disease control.
Topics: Animals; Schistosomiasis japonica; Schistosoma japonicum; Mice; Humans; Immunoprecipitation; Luciferases; Female; Sensitivity and Specificity; Mice, Inbred BALB C; Enzyme-Linked Immunosorbent Assay; Extracellular Vesicles; Antigens, Helminth; Male
PubMed: 38750807
DOI: 10.1016/j.exppara.2024.108776 -
Parasites & Vectors May 2024Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems....
BACKGROUND
Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected.
METHODS
We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, F, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes.
RESULTS
Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host.
CONCLUSIONS
Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.
Topics: Animals; Schistosoma japonicum; Genetic Variation; Host-Parasite Interactions; Evolution, Molecular; Polymorphism, Single Nucleotide; Sex Chromosomes; Selection, Genetic; Schistosoma haematobium; Schistosoma mansoni; Biological Evolution; Schistosomiasis japonica
PubMed: 38720339
DOI: 10.1186/s13071-024-06250-4 -
Infectious Diseases of Poverty May 2024The three most important genera of snails for the transmission of schistosomes are Bulinus, Biomphalaria and Oncomelania. Each of these genera, found in two distantly...
The three most important genera of snails for the transmission of schistosomes are Bulinus, Biomphalaria and Oncomelania. Each of these genera, found in two distantly related families, includes species that act as the intermediate host for one of the three most widespread schistosome species infecting humans, Schistosoma haematobium, S. mansoni and S. japonicum, respectively. An important step in the fight against schistosomiasis in Asia has been taken with the publication of the article "Chromosome-level genome assembly of Oncomelania hupensis: the intermediate snail host of Schistosoma japonicum", which means that genomes for all three major genera, including species across three continents, are now available in the public domain. This includes the first genomes of African snail vectors, namely Biomphalaria sudanica, Bi. pfeifferi and Bulinus truncatus, as well as high-quality chromosome level assemblies for South American Bi. glabrata. Most importantly, the wealth of new genomic and transcriptomic data is helping to establish the specific molecular mechanisms that underly compatibility between snails and their schistosomes, which although diverse and complex, may help to identify potential targets dictating host parasite interactions that can be utilised in future transmission control strategies. This new work on Oncomelania hupensis and indeed studies on other snail vectors, which provide deep insights into the genome, will stimulate research that may well lead to new and much needed control interventions.
Topics: Animals; Humans; Disease Vectors; Genomics; Host-Parasite Interactions; Schistosomiasis; Snails
PubMed: 38711151
DOI: 10.1186/s40249-024-01199-z -
Pathogens (Basel, Switzerland) Mar 2024Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of...
Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway.
PubMed: 38668242
DOI: 10.3390/pathogens13040287