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Journal of Ethnopharmacology Jun 2024Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health.... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2,000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice.
AIM OF THE STUDY
To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis.
MATERIALS AND METHODS
In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China.
RESULTS
In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy.
CONCLUSION
Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.
PubMed: 38944361
DOI: 10.1016/j.jep.2024.118501 -
The Journal of Infectious Diseases Jun 2024Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune...
Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.
PubMed: 38942608
DOI: 10.1093/infdis/jiae330 -
Ecotoxicology and Environmental Safety Jun 2024Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS)...
BACKGROUND
Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated.
METHODS
PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-β were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury.
RESULT
We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-β from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway.
CONCLUSIONS
Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.
PubMed: 38905933
DOI: 10.1016/j.ecoenv.2024.116615 -
PLoS Neglected Tropical Diseases Jun 2024Schistosomiasis japonica represents a significant public health concern in South Asia. There is an urgent need to optimize existing schistosomiasis diagnostic...
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.
CONCLUSION
Machine learning models based on ultrasound radiomics are feasible for classifying different stages of liver fibrosis caused by Schistosoma infection.
Topics: Humans; Schistosomiasis japonica; Ultrasonography; Male; Liver Cirrhosis; Female; Retrospective Studies; Middle Aged; Adult; Schistosoma japonicum; China; Feasibility Studies; Animals; Machine Learning; Support Vector Machine; Aged; Young Adult; Adolescent; Liver; Radiomics
PubMed: 38870200
DOI: 10.1371/journal.pntd.0012235 -
QJM : Monthly Journal of the... Jun 2024
PubMed: 38867695
DOI: 10.1093/qjmed/hcae116 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Apr 2024To investigate the changes in distribution of snails in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023, so as to provide insights into...
OBJECTIVE
To investigate the changes in distribution of snails in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023, so as to provide insights into formulation of snail surveillance programs.
METHODS
The reports on snail surveillance in Songjiang District, Shanghai Municipality from 2009 to 2023 were collected, and the snail surveillance data in forestlands were extracted. The trends in the proportion of areas with snails in forestlands in total areas with snails, occurrence of frames with living snails and density of living snails were evaluated using a Joinpoint regression model in Songjiang District from 2009 to 2023, and the annual percent change (APC) and average annual percent change (AAPC).
RESULTS
A total of 40 sites with snails were found in forestlands in 14 administrative villages of 4 townships, Songjiang District, Shanghai Municipality from 2009 to 2023. A total of 39 065 frames were surveyed for snails in settings covering an area of 609 600 m, and there were 6 084 frames with snails, covering 151 250 m snail habitats. A total of 22 210 snails were captured, with the highest density of 260.00 snails/0.1 m, and 6 262 snails were dissected, with no infection identified in snails. The proportion of areas with snails in forestlands in total areas with snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality from 2009 to 2023 (APC = AAPC = 24.9%, > 0.05); however, there were no turning points in the trend curve, with the highest proportion seen in 2009 (53.81%), the lowest in 2011 and 2023 (both 0) and a mean proportion of 24.81%. The occurrence of frames with living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 41.5%, > 0.05); however, there were no turning points in the trend curve, with the highest occurrence in 2009 (53.81%), the lowest in 2011 and 2013 (both 0), and the mean occurrence of 15.57%. In addition, the density of living snails appeared a tendency towards a rise from 2009 to 2023 (APC = AAPC = 55.0%, > 0.05); however, there were no turning points in the trend curve, with the highest density in 2023 (0.96 snails/0.1 m), the lowest in 2011 and 2013 (both 0), and a mean density of 0.57 snails/0.1 m.
CONCLUSIONS
The difficulty in snail control and risk of imported snails appeared a tendency towards a rise in forestlands in Songjiang District, Shanghai Municipality over years from 2009 to 2023. Supervision and assessment prior to seedling transplantation and intensified surveillance post-transplantation are recommended to reduce the risk of snail importation and spread.
Topics: Animals; China; Snails; Forests
PubMed: 38857960
DOI: 10.16250/j.32.1374.2023174 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Apr 2024To analyze the trends in distribution in Wuhan City, Hubei Province from 2003 to 2022, so as to provide insights into precision schistosomiasis control.
OBJECTIVE
To analyze the trends in distribution in Wuhan City, Hubei Province from 2003 to 2022, so as to provide insights into precision schistosomiasis control.
METHODS
Data pertaining to snail survey in Wuhan City from 2003 to 2022 were collected. The trends in the proportion of areas with snail habitats, actual area with snail habitats, mean density of living snails and prevalence of infection in snails were evaluated in schistosomiasis-endemic areas of Wuhan City from 2003 to 2022 with the slope of trend curve (β), annual percent change (APC) and average annual percent change (AAPC) using a Joinpoint regression model.
RESULTS
During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in Wuhan City in 2005 and 2015, with a rise during the period from 2003 to 2005 (β = 5.93, = 1.280, > 0.05), a decline from 2005 to 2015 (β = -0.88, = -2.074, > 0.05) and a rise from 2015 to 2022 (β = 1.46, = -2.356, < 0.05). During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in islet endemic areas of Wuhan City in 2006 and 2015, with no significant differences in the trends from 2003 to 2006 (β = 4.64, = 1.888, > 0.05) or from 2006 to 2015 (β = -1.45, = -2.143, > 0.05), and with a tendency towards a rise from 2015 to 2022 (β = 2.04, = -3.100, < 0.05). During the period from 2003 through 2022, there were two turning points for the proportion of areas with snail habitats in inner embankment endemic areas of Wuhan City in 2012 and 2020, with a tendency towards a decline from 2003 to 2012 (β = -0.39, = -4.608, < 0.05) and with no significant differences in the trends from 2012 to 2020 (β = 0.03, = 0.245, > 0.05) and from 2020 to 2022 (β = 1.38, = 1.479, > 0.05). During the period from 2003 to 2022, the actual area with snail habitats all appeared a tendency towards a decline in Wuhan City, and in islet and inner embankment endemic areas of Wuhan City from 2003 to 2022 (AAPC = -2.39%, -5.75% and -2.35%, all values < 0.05). The mean density of living snails reduced from 0.087 snails/0.1 m in 2003 to 0.027 snails/0.1 m in 2022 in Wuhan City, with a significant difference in the tendency towards the decline (APC = AAPC = -11.47%, < 0.05). The annual mean decline rate of the mean density of living snails was 17.36% in outside embankment endemic areas of Wuhan City from 2003 to 2022 (APC = AAPC = -17.36%, < 0.05), and there was no significant difference in the trends in the mean density of living snails in islet endemic areas of Wuhan City from 2003 to 2022 (APC = AAPC = -0.97%, > 0.05). In addition, the prevalence of infection in snails appeared a tendency towards a decline in Wuhan City from 2003 to 2022 (APC = AAPC = -12.45%, < 0.05).
CONCLUSIONS
The proportion of areas with snail habitats, actual area with snail habitats, mean density of living snails and prevalence of infection in snails all appeared a tendency towards a decline in Wuhan City from 2003 to 2022. Intensified snail control, modification of snail habitats, shrinking of areas with snails and implementation of grazing prohibition in snail-infested settings are required, in order to facilitate the progress towards schistosomiasis elimination in Wuhan City.
Topics: China; Animals; Snails; Schistosomiasis; Regression Analysis; Humans; Disease Reservoirs
PubMed: 38857959
DOI: 10.16250/j.32.1374.2023149 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... May 2024To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with during the chronic pathogenic stage and identify their functions,...
OBJECTIVE
To screen differentially expressed long non-coding RNAs (lncRNAs) in the liver of mice infected with during the chronic pathogenic stage and identify their functions, so as to provide insights into unravelling the role of lncRNAs in infection-induced liver disorders.
METHODS
Twenty 6-week-old C57BL/6 mice were randomly divided into two groups, of 10 animals each group. Each mouse in the experimental group was infected with (15 ± 2) cercariae via the abdomen for modeling chronic infection in mice, and distilled water served as controls. All mice were sacrificed 70 days post-infection, and mouse liver specimens were sampled for RNA extraction and library construction. All libraries were sequenced on the Illumina NovaSeq 6000 sequencing platform. Data cleaning was performed using the fastp software, and reference genome alignment and gene expression (FPKM) calculation were performed using the HISAT2 software. Potential lncRNA sequences were predicted using the software CNIC, CPC, Pfam, and PLEK, and potential lncRNAs were screened. Differentially expressed lncRNAs were screened with the DESeq2 software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify biological processes and metabolic pathways involved in target genes of differentially expressed lncRNAs.
RESULTS
A total of 333 potential lncRNAs were screened, and 67 were identified as differentially expressed lncRNAs, including 49 up-regulated and 18 down-regulated lncRNAs. A total of 53 target genes were predicted for differentially expressed lncRNAs. GO enrichment analysis showed that these target genes were mainly enriched in biological process and molecular function, among which , , and genes may be hub target genes for positive regulation of extracellular regulated protein kinase 1 (ERK1) and ERK2 cascades and may participate in the regulation of collagen expression. KEGG enrichment analysis showed that the target genes of differentially expressed lncRNAs were mainly enriched in cytokine-cytokine receptor interaction, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear factor kappa-B (NF-κB) signaling pathway.
CONCLUSIONS
This study identifies differentially expressed lncRNAs and functional enrichment of their target genes in the liver of mice during the chronic pathogenic stage of infection. Up-regulated lncRNAs may affect biological processes of ERK1/2 cascades and chemokine signaling pathways via target genes , , and , thereby affecting collagen expression and inflammatory signal pathways, ultimately affecting the development of liver disorders.
Topics: Animals; Schistosomiasis japonica; RNA, Long Noncoding; Mice; Schistosoma japonicum; Liver; Mice, Inbred C57BL; Gene Expression Profiling; Chronic Disease; Female
PubMed: 38857956
DOI: 10.16250/j.32.1374.2024076 -
Scientific Reports Jun 2024Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts...
Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.
Topics: Animals; Humans; Proteomics; Schistosoma; Schistosomiasis; Transcriptome; Molecular Docking Simulation; Focal Adhesion Protein-Tyrosine Kinases; Helminth Proteins; Gene Expression Profiling; Protein Kinase Inhibitors; Proteome
PubMed: 38839835
DOI: 10.1038/s41598-024-63869-0 -
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