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PLoS Neglected Tropical Diseases Feb 2024Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal...
Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease.
Topics: Mice; Humans; Animals; Schistosomiasis mansoni; Schistosomiasis; Schistosoma japonicum; Biomarkers; Early Diagnosis; Disease Progression
PubMed: 38381759
DOI: 10.1371/journal.pntd.0011966 -
Experimental Parasitology Apr 2024Glutathione S-transferases (GSTs) are a family of multifunctional isoenzymes involved in the neutralization of toxic compounds, drug resistance and several other...
Glutathione S-transferases (GSTs) are a family of multifunctional isoenzymes involved in the neutralization of toxic compounds, drug resistance and several other cellular functions. The glutathione S-transferase enzyme of Schistosoma japonicum (SjGST-26) plays a role in human schistosomiasis and is also a frequently used fusion partner in mammalian and bacterial expression and pull-down systems. GSTs seem not to be naturally associated with metal ions. Exceptionally, in vitro, metal binding sites have been previously described in some schistosome GSTs; however, their possible physiological role is unclear. Molecules of several neurotransmitter transporters also contain a regulatory zinc binding site, which affects their transport cycle. Here we show that among several metals, manganese and zinc are able to induce a specific protein interaction of SjGST-26 with the glycine transporter GlyT1 and the GABA transporter GAT3 in vitro. The results suggest that metal-binding sites on SjGST-26 and neurotransmitter transporters might function in metal-coordinated interactions with other metalloproteins. Our results additionally indicate that the presence of metal ions in SjGST-26-based GST protein pull-down assays may lead to a false-positive interaction if the potential interacting target is the metalloprotein.
Topics: Animals; Humans; Schistosoma japonicum; Manganese; Zinc; Glutathione Transferase; Ions; Glutathione; Mammals
PubMed: 38369179
DOI: 10.1016/j.exppara.2024.108721 -
International Journal of Molecular... Jan 2024Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth... (Review)
Review
Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.
Topics: Animals; Female; Cattle; Humans; Schistosomiasis japonica; Schistosoma japonicum; Vaccines; Schistosomiasis; Vaccination; China; Buffaloes
PubMed: 38338980
DOI: 10.3390/ijms25031707 -
Animals : An Open Access Journal From... Feb 2024Fasciolosis is a global zoonotic parasitic disease caused by infection that is particularly harmful to cattle and sheep. A biotin-streptavidin signal amplification...
The Detection of Circulating Antigen Glutathione S-Transferase in Sheep Infected with with Double-Antibody Sandwich Signal Amplification Enzyme-Linked Immunosorbent Assay.
Fasciolosis is a global zoonotic parasitic disease caused by infection that is particularly harmful to cattle and sheep. A biotin-streptavidin signal amplification ELISA (streptavidin-ELISA/SA-ELISA) based on circulating antigens can allow for the early detection of -infected animals and is suitable for batch detection. It is considered to be a better means of detecting infection than traditional detection methods. In this study, using the serum of sheep artificially infected with , the cDNA expression library of was screened, 17 immunodominant antigen genes of were obtained, and glutathione s-transferase (GST) was selected as the candidate detection antigen. Firstly, the GST cDNA sequence was amplified from , followed by the preparation of recombinant protein GST (rFhGST). Then, monoclonal and polyclonal antibodies against rFhGST were prepared using the GST protein. Afterward, the immunolocalization of the target protein in the worm was observed via confocal microscopy, and it was found that the GST protein was localized in the uterus, intestinal tract, and body surface of . Finally, a double-antibody sandwich SA-ELISA based on the detection of circulating antigens was established. There was no cross-reaction with positive sera infected with (), (), (), or (). Forty serum and fecal samples from the same batch of sheep in Nong'an County, Changchun City, Jilin Province, China were analyzed using the established detection method and fecal detection method. The positive rate of the SA-ELISA was 17.5%, and the positive rate of the fecal detection method was 15%. The detection results of this method were 100% consistent with commercial ELISA kits. A total of 152 sheep serum samples were tested in Nong'an County, Changchun City, Jilin Province, and the positive rate was 5.92%. This study laid the foundation for the development of serological detection preparations for infection based on the detection of circulating antigens.
PubMed: 38338149
DOI: 10.3390/ani14030506 -
FASEB Journal : Official Publication of... Feb 2024
PubMed: 38334436
DOI: 10.1096/fj.202400191 -
PLoS Pathogens Jan 2024Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding...
Schistosomes are flatworm parasites that undergo a complex life cycle involving two hosts. The regulation of the parasite's developmental processes relies on both coding RNAs and non-coding RNAs. However, the roles of non-coding RNAs, including long non-coding RNAs (lncRNAs) in schistosomes remain largely unexplored. Here we conduct advanced RNA sequencing on male and female S. japonicum during their pairing and reproductive development, resulting in the identification of nearly 8,000 lncRNAs. This extensive dataset enables us to construct a comprehensive co-expression network of lncRNAs and mRNAs, shedding light on their interactions during the crucial reproductive stages within the mammalian host. Importantly, we have also revealed a specific lncRNA, LNC3385, which appears to play a critical role in the survival and reproduction of the parasite. These findings not only enhance our understanding of the dynamic nature of lncRNAs during the reproductive phase of schistosomes but also highlight LNC3385 as a potential therapeutic target for combating schistosomiasis.
Topics: Animals; Male; Female; Schistosoma japonicum; RNA, Long Noncoding; RNA, Antisense; Schistosomiasis; Parasites; Mammals
PubMed: 38285715
DOI: 10.1371/journal.ppat.1011949 -
Scientific Reports Jan 2024Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life...
Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life cycle. This study aimed to explore the microRNA (miRNA) profiles across these developmental stages to understand their potential functions and evolutionary significance, which have not been studied. Pre-processed sequencing reads of small RNA (sRNA) were obtained, and annotations were performed against the S. japonicum reference miRNA database. Results indicated marked variations in miRNA profiles across different life stages, with notable similarities observed between female and male S. mekongi. Principal Coordinate Analysis (PCoA) and unsupervised clustering revealed distinct miRNA signatures for each stage. Gene ontology (GO) analysis unveiled the potential roles of these miRNAs in various biological processes. The differential expression of specific miRNAs was prominent across stages, suggesting their involvement in crucial developmental processes. Furthermore, orthologous miRNA analysis against various worm species revealed distinct presence-absence patterns, providing insights into the evolutionary relationships of these miRNAs. In conclusion, this comprehensive investigation into the miRNA profiles of S. mekongi offers valuable insights into the functional and evolutionary aspects of miRNAs in schistosome biology.
Topics: Animals; Male; Female; Schistosoma japonicum; MicroRNAs; Life Cycle Stages; RNA, Helminth
PubMed: 38281987
DOI: 10.1038/s41598-024-52835-5 -
Tropical Medicine and Infectious Disease Dec 2023Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in...
From Perpetual Wetness to Soil Chemistry: Enumerating Environmental and Physicochemical Factors Favoring Snail Presence in the Municipality of Gonzaga, Cagayan, Philippines.
Snail control to complement mass drug administration is being promoted by the World Health Organization for schistosomiasis control. , the snail intermediate host of in the Philippines, has a very focal distribution; thus, scrutinizing baseline data and parameters affecting this distribution is very crucial. In this study in Gonzaga, Cagayan, Philippines, snail habitats were surveyed, and the various factors affecting the existence of the snails were determined. Malacological surveys and the mapping of sites of perpetual wetness in five endemic and five neighboring non-endemic barangays were conducted. Environmental and physicochemical factors were also examined. Maps of both snail and non-snail sites were generated. Of the fifty sites surveyed, were found in twelve sites, and two sites yielded snails that were infected with cercariae. Factors such as silty loam soil, proximity to a snail site, water ammonia, and soil attributes (organic matter, iron, and pH) are all significantly associated with the presence of snails. In contrast, types of habitats, temperatures, and soil aggregation have no established association with the existence of snails. Mapping snail sites and determining factors favoring snail presence are vital to eliminating snails. These approaches will significantly maximize control impact and minimize wasted efforts and resources, especially in resource-limited schistosomiasis endemic areas.
PubMed: 38251207
DOI: 10.3390/tropicalmed9010009 -
BMC Immunology Jan 2024Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to...
BACKGROUND
Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum.
METHODS
The production of TLR3 cells in CD4T cells (CD4CD3), CD8T cells (CD8CD3), γδT cells (γδTCRCD3), NKT cells (NK1.1CD3), B cells (CD19CD3), NK (NK1.1CD3) cells, MDSC (CD11bGr1), macrophages (CD11bF4/80), DCs (CD11cCD11b) and neutrophils (CD11b Ly6g) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry.
RESULTS
Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice.
CONCLUSIONS
Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.
Topics: Animals; Mice; Schistosoma japonicum; Toll-Like Receptor 3; Mice, Inbred C57BL; Immunoglobulin G; Immunoglobulin M
PubMed: 38172683
DOI: 10.1186/s12865-023-00586-9 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Nov 2023To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to...
OBJECTIVE
To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to provide insights into creation of a sensitive and highly efficient surveillance and early warning system for schistosomiasis.
METHODS
National and international publications, documents, laws and regulations pertaining to schistosomiasis control were retrieved with keywords including schistosomiasis, surveillance, early warning and control interventions from 2008 to 2022, and a thematic panel discussion was held to preliminarily construct surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin. The index system was then comprehensively scored and screened using the Delphi method, and the weight of each index was determined using analytic hierarchy process and the modified proportional allocation method. In addition, the credibility of the Delphi method was evaluated using positive coefficient, authority coefficient, degree of concentration and degree of coordination of experts.
RESULTS
Following two rounds of expert consultation, a surveillance and early warning index system for schistosomiasis transmission risk in endemic areas along the middle and lower reaches of the Yangtze River basin was preliminarily constructed, including 3 primary indicators, 9 secondary indicators and 41 tertiary indicators. The normalized weights of primary indicators epidemics, natural and social factors and comprehensive control were 0.639 8, 0.145 6 and 0.214 6, respectively, and among all secondary indicators, snail status (0.321 3) and schistosomiasis prevalence (0.318 5) had the highest combined weights, while social factors had the lowest combined weight (0.030 4). Of all tertiary indicators, human egg-positive rate (0.041 9), number of acute schistosomiasis cases (0.041 5), number of stool-positive bovine and sheep (0.041 1), and prevalence of in free-ranging livestock (0.041 1) had the highest combined weights. During two rounds of consultation, the positive coefficient of experts was both 100%, and the authority coefficient was both 0.9 and greater, while the coordination coefficients were 0.338 to 0.441 and 0.426 to 0.565 (χ = 22.875 to 216.524, both values < 0.05).
CONCLUSIONS
The established surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin is of great scientific values and authority, which may provide insights into construction of the sensitive and highly efficient surveillance and early warning system for schistosomiasis in the context of low prevalence and low intensity of infection in China.
Topics: Animals; Cattle; Humans; Sheep; Rivers; Schistosomiasis; Schistosoma japonicum; China; Snails
PubMed: 38148537
DOI: 10.16250/j.32.1374.2023119