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Parasites & Vectors Sep 2023Interruption of parasite reproduction by targeting migrating schistosomula is a promising strategy for managing schistosomiasis. Hepatic schistosomula proteins...
BACKGROUND
Interruption of parasite reproduction by targeting migrating schistosomula is a promising strategy for managing schistosomiasis. Hepatic schistosomula proteins previously identified based on second-generation schistosome DNA sequencing were found to hold excellent potential for schistosomiasis japonica diagnosis and as vaccine candidates. However, there are still many unknown schistosomula proteins that warrant further investigations. Herein, a novel schistosomula protein, the Schistosoma japonicum erythroid Krüppel-like factor (SjEKLF/KLF1), was explored.
METHODS
Sequence alignment was carried out to detect the amino acid sequence characteristics of SjEKLF. The expression profile of SjEKLF was determined by western blot and immunofluorescence analysis. Enzyme-linked immunosorbent assay was used to determine the antigenicity of SjEKLF in hosts. Mice immunised with recombinant SjEKLF were challenged to test the potential value of the protein as an immunoprotective target.
RESULTS
SjEKLF is defined as EKLF/KLF1 for its C-terminal DNA-binding domain. SjEKLF is mainly expressed in hepatic schistosomula and male adults and located within the intestinal intima of the parasites. Notably, high levels of SjEKLF-specific antibodies were detected in host sera and SjEKLF exhibited outstanding sensitivity and specificity for schistosomiasis japonica immunodiagnosis but failed to distinguish between ongoing infection and previous exposure. In addition, SjEKLF immunisation reduced the infection in vivo, resulting in decreased worm and egg counts, and alleviated body weight loss and hepatomegaly in infected mice.
CONCLUSIONS
Overall, these findings demonstrate that SjEKLF is critical for the infection of S. japonicum and may be a potential target to help control S. japonicum infection and transmission.
Topics: Animals; Male; Mice; Kruppel-Like Transcription Factors; Schistosoma japonicum; Schistosomiasis; Schistosomiasis japonica; Helminth Proteins
PubMed: 37742024
DOI: 10.1186/s13071-023-05947-2 -
Frontiers in Cellular and Infection... 2022Schistosomiasis is a tropical parasitic disease that seriously endangers humans and animals. In this study, two snails, () and (), were infected with () cercariae...
Schistosomiasis is a tropical parasitic disease that seriously endangers humans and animals. In this study, two snails, () and (), were infected with () cercariae during the early period, and ICR mice were subsequently infected with two kinds of miracidia that developed in male and female adult worms. In this study, isobaric tags for relative and absolute quantification (iTRAQ) were used to identify four channels: 113, 115, 117, and 119. A total of 2364 adult schistosome proteins were identified, and 1901 proteins were quantitative. Our results revealed 68 differentially expressed proteins (DEPs) in female adult worms, including 24 upregulated proteins and 44 downregulated proteins, and 55 DEPs in male adult worms, including 25 upregulated proteins and 30 downregulated proteins. LC-MS/MS and bioinformatics analysis indicated that these DEPs are mainly concentrated in cellular composition, molecular function, biological function and catabolism pathways. In summary, this proteomics analysis of adult schistosomes that hatched in two intermediate hosts helps to improve our understanding of the growth and developmental mechanisms of .
Topics: Humans; Animals; Mice; Male; Female; Schistosoma japonicum; Chromatography, Liquid; Proteomics; Mice, Inbred ICR; Tandem Mass Spectrometry; Snails
PubMed: 36710964
DOI: 10.3389/fcimb.2022.959766 -
Acta Tropica May 2023Praziquantel (PZQ) is the first line drug for the treatment of schistosomiasis. Several studies have confirmed that PZQ regulates host immunity, and we have recently...
Praziquantel (PZQ) is the first line drug for the treatment of schistosomiasis. Several studies have confirmed that PZQ regulates host immunity, and we have recently found that pretreatment with PZQ enhances resistance against Schistosoma japonicum infection in buffaloes. We speculate that PZQ induces physiological changes in mice that prevent S. japonicum infection. To test this hypothesis and provide a practical measure to prevent S. japonicum infection, we determined the effective dose (the minimum dose), protection period and onset time of protection by comparing the worm burden, female worm burden and egg burden in PZQ-pretreated mice and blank control mice. Morphological differences between parasites were observed by measuring the total worm length, oral sucker, ventral sucker and ovary. The levels of cytokines, nitrogen monoxide (NO), 5-hydroxytryptamine (5-HT) and specific antibodies were measured using kits or soluble worm antigens. Hematological indicators on day 0 were analyzed in mice that received PZQ on days -15, -18, -19, -20, -21 and -22. The PZQ concentrations in plasma and blood cells were monitored using high performance liquid chromatography (HPLC). The effective dose was found to be two oral administrations (interval of 24 h) at 300 mg/kg body weight (BW) or one injection at 200 mg/kg BW, and the protection period of PZQ injection was 18 days. The optimal preventive effect was observed at two days post-administration, with a >92% worm reduction rate and significant worm reduction until 21 days after administration. Adult worms from PZQ-pretreated mice were runtish showing a shorter length, smaller organs and fewer eggs in the uteri of females. Detection of cytokines, NO, 5-HT and hematological indicators showed that PZQ induced immune-physiological changes, including higher levels of NO, IFN-γ and IL-2, and a lower level of TGF-β. No significant difference in the anti-S. japonicum specific antibody levels was observed. The PZQ concentrations in plasma and blood cells 8 and 15 days post-administration were lower than the detection limit. Our results confirmed that pretreatment with PZQ promotes the protection of mice against S. japonicum infection within 18 days. Although we observed some immune-physiological changes in the PZQ-pretreated mice, the exact mechanisms involved in the preventive effect require further study.
Topics: Female; Animals; Mice; Praziquantel; Schistosomiasis japonica; Schistosoma japonicum; Serotonin; Administration, Oral; Antibodies; Schistosoma mansoni; Anthelmintics
PubMed: 36863502
DOI: 10.1016/j.actatropica.2023.106874 -
Acta Parasitologica Sep 2021For the evolution of schistosomiasis in China, a systematic review was provided about the history of the disease and its public health impacts. We aimed to depict the... (Review)
Review
PURPOSE
For the evolution of schistosomiasis in China, a systematic review was provided about the history of the disease and its public health impacts. We aimed to depict the journey from disease discovery to elimination and the experience and lessons learned during the process.
METHODS
We systematically reviewed the Chinese history of schistosomiasis and its public health impacts and collected data on the disease by searching relevant books and articles.
RESULTS
An important milestone for the disease discovery is that Schistosoma japonicum eggs were identified in the two Chinese corpses dating back to around 2180 years ago. The earliest Chinese ancient book documented symptoms resembling schistosomiasis that could date back to about 4700 years ago. The first nationwide survey on the disease in the mid-1950s revealed that schistosomiasis was endemic in 433 counties or cities of 12 provinces and affected about 11.6 million people in China. The Chinese government has provided continuous investment in schistosoiasis control, and the national multifaceted, integrated control programs have been uninterruptedly implemented since 1955. Schistosomiasis control in China can be divided into six stages, and various schistosomiasis control strategies have been developed and adjusted. The number of schistosomiasis cases decreased from 11.6 million in 1950s to 38,000 in 2017 and the number of acute cases decreased from 13,191 in 1989 to only 1 in 2017.
CONCLUSIONS
Schistosomiasis transmission has been under control in all parts of China since 2017. An elimination of schistosomiasis can be achieved in the foreseeable future in China.
Topics: Animals; China; Cities; Humans; Schistosoma japonicum; Schistosomiasis; Snails
PubMed: 33713275
DOI: 10.1007/s11686-021-00357-9 -
Frontiers in Oncology 2023Only a few studies have focused on the association between and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall...
BACKGROUND
Only a few studies have focused on the association between and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of patients with human malignancy.
METHODS
From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups.
RESULTS
Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between and non- patients with/without digestive system tumor (p < 0.001). The odds ratio of patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9).
CONCLUSION
contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.
PubMed: 38125940
DOI: 10.3389/fonc.2023.1288197 -
BMC Veterinary Research Oct 2021N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity.
BACKGROUND
N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity.
RESULTS
In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro.
CONCLUSIONS
Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.
Topics: Acetyltransferases; Animals; Cloning, Molecular; DNA, Complementary; Female; Gene Expression Regulation, Enzymologic; Gene Silencing; Helminth Proteins; Male; Mice; Mice, Inbred BALB C; RNA, Messenger; Random Allocation; Schistosoma japonicum; Schistosomiasis japonica; Vaccines
PubMed: 34686208
DOI: 10.1186/s12917-021-03045-y -
Journal of Immunology Research 2021The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated...
The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with , we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21FOXP3 (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21FOXP3 mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.
Topics: Animals; Cytokines; Disease Susceptibility; Female; Forkhead Transcription Factors; Genetic Predisposition to Disease; Immunophenotyping; Liver; Mice; Mice, Knockout; Neglected Diseases; Schistosomiasis japonica; Spleen; T-Lymphocytes, Regulatory; Ubiquitin Thiolesterase
PubMed: 33628844
DOI: 10.1155/2021/6613162 -
PloS One 2019In recent years, the prevalence and infection intensity of Schistosoma japonicum in endemic areas of the Philippines have significantly decreased due to yearly...
Detection of Schistosoma japonicum and Oncomelania hupensis quadrasi environmental DNA and its potential utility to schistosomiasis japonica surveillance in the Philippines.
In recent years, the prevalence and infection intensity of Schistosoma japonicum in endemic areas of the Philippines have significantly decreased due to yearly population-based treatment strategies, yet transmission rates remain high and uninterrupted. An important indicator of active disease transmission is the presence of Schistosoma japonicum and its snail intermediate host Oncomelania hupensis quadrasi in freshwater habitats. In this study, we sought to apply a species-specific real-time PCR (qPCR) assay for the detection of S. japonicum and O. hupensis quadrasi in freshwater samples using environmental DNA approach that can complement the commonly utilized malacological survey in determining potential transmission foci in order to have a more effective snail surveillance strategy for schistosomiasis japonica in endemic areas. The newly developed assay was specific to S. japonicum and O. hupensis quadrasi with no amplification detected against non-target trematode Fasciola spp. and snails such as Lymnaea spp., Pomacea canaliculata, and Melanoides spp. that typically co-exist in the same environment. The assay effectiveness was determined using 19 environmental water samples collected from Northern Samar (N = 5 sites), Leyte (N = 11 sites) and Compostela Valley (N = 3 sites) and compared to malacological survey for determining O. hupensis quadrasi snail colonies and snail crushing to visualize S. japonicum cercariae. TaqMan qPCR targeting a short fragment of the cytochrome c oxidase subunit 1 (cox1) gene was positive for S. japonicum in 9 sites, for O. hupensis quadrasi in 9 sites, and for both S. japonicum and O. hupensis quadrasi in 5 sampling sites. Moreover, it was able to detect O. hupensis quadrasi in 3 out of 12 sites found negative and 6 out of 7 sites found positive through malacological survey, and in 4 of the 5 snail sites positive for snails with cercariae. Overall, this method can complement malacological surveys for monitoring of schistosomes in endemic areas of the Philippines, especially those with high risk of human infection.
Topics: Animals; Cercaria; DNA, Environmental; Disease Vectors; Epidemiological Monitoring; Humans; Philippines; Schistosoma japonicum; Schistosomiasis japonica; Snails; Species Specificity
PubMed: 31747401
DOI: 10.1371/journal.pone.0224617 -
PLoS Neglected Tropical Diseases Mar 2021Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most of national schistosomiasis elimination programmes in Asia are relying on stool examination, particularly Kato Katz stool examination technique for regular transmission monitoring. However, the Kato-Katz technique has shown low sensitivity for the detection of light-intensity infections, and therefore highly sensitive diagnostic tools are urgently required to monitor prevalence of infection in low transmission settings. The objective of this systematic review was to evaluate and synthesize the performance of diagnostic tests for detecting Schistosoma japonicum and S. mekongi infection in people living in endemic areas.
METHODOLOGY/PRINCIPAL FINDINGS
We comprehensively searched these nine electronic databases and other resources until July 2019, with no language or publication limits: PubMed, EMBASE, MEDLINE, Web of Science, BIOSIS Citation Index, HTA, CINAHL PLUS, The Cochrane Library, and PsycINFO. We included original studies that assessed diagnostic performance using antibody, antigen, and molecular tests with stool examination test as a reference standard. Two reviewers independently extracted a standard set of data and assessed study quality. We estimated the pooled estimates of sensitivity and specificity for each index test. We used diagnostic odds ratio to determine the overall accuracy and hierarchical summary receiver operating characteristics (HSROC) curve to assess the index tests performance. Fifteen studies (S. japonicum [n = 13] and S. mekongi [n = 2]) testing 15,303 participants were included in the review. Five studies reported performance of enzyme-linked immunosorbent assay (ELISA), seven studies reported indirect hemagglutination assay (IHA), and four studies reported polymerase chain reaction (PCR) for detecting S. japonicum. The pooled sensitivity and specificity were 0.93 (95% CI: 0.84-0.98) and 0.40 (95% CI: 0.29-0.53) for ELISA, 0.97 (95% CI: 0.90-0.99) and 0.66 (95% CI: 0.58-0.73) for IHA, and 0.89 (95% CI: 0.71-0.96) and 0.49 (95% CI: 0.29-0.69) for PCR respectively. A global summary indicated the best performance for IHA, closely followed by ELISA. We were unable to perform meta-analysis for S. mekongi due to insufficient number of studies.
CONCLUSIONS/SIGNIFICANCE
IHA showed the highest detection accuracy for S. japonicum. Further studies are needed to determine the suitable diagnostic methods to verify the absence of transmission of S. mekongi and also to compare detection accuracy against more sensitive reference standards such as PCR.
Topics: Animals; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Polymerase Chain Reaction; Schistosoma; Schistosoma japonicum
PubMed: 33730048
DOI: 10.1371/journal.pntd.0009244 -
PLoS Neglected Tropical Diseases Jan 2022Schistosoma japonicum is prevalent in Asia with a wide mammalian host range, which leads to highly harmful zoonotic parasitic diseases. Most previous transcriptomic...
Schistosoma japonicum is prevalent in Asia with a wide mammalian host range, which leads to highly harmful zoonotic parasitic diseases. Most previous transcriptomic studies have been performed on this parasite, but mainly focus on stages inside the mammalian host. Moreover, few larval transcriptomic data are available in public databases. Here we mapped the detailed transcriptome profiles of four S. japonicum larval stages including eggs, miracidia, sporocysts and cercariae, providing a comprehensive development picture outside of the mammalian host. By analyzing the stage-specific/enriched genes, we identified functional genes associated with the biological characteristic at each stage: e.g. we observed enrichment of genes necessary for DNA replication only in sporocysts, while those involved in proteolysis were upregulated in sporocysts and/or cercariae. This data indicated that miracidia might use leishmanolysin and neprilysin to penetrate the snail, while elastase (SjCE2b) and leishmanolysin might contribute to the cercariae invasion. The expression profile of stem cell markers revealed potential germinal cell conversion during larval development. Additionally, our analysis indicated that tandem duplications had driven the expansion of the papain family in S. japonicum. Notably, all the duplicated cathepsin B-like proteases were highly expressed in cercariae. Utilizing our 3rd version of S. japonicum genome, we further characterized the alternative splicing profiles throughout these four stages. Taken together, the present study provides compressive gene expression profiles of S. japonicum larval stages and identifies a set of genes that might be involved in intermediate and definitive host invasion.
Topics: Animals; Gene Expression Regulation, Developmental; Helminth Proteins; Host-Parasite Interactions; Humans; Larva; Schistosoma japonicum; Transcriptome
PubMed: 35025881
DOI: 10.1371/journal.pntd.0009889