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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 -
PLoS Neglected Tropical Diseases Jun 2024The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature....
The geographical range of schistosomiasis is affected by the ecology of schistosome parasites and their obligate host snails, including their response to temperature. Previous models predicted schistosomiasis' thermal optimum at 21.7°C, which is not compatible with the temperature in sub-Saharan Africa (SSA) regions where schistosomiasis is hyperendemic. We performed an extensive literature search for empirical data on the effect of temperature on physiological and epidemiological parameters regulating the free-living stages of S. mansoni and S. haematobium and their obligate host snails, i.e., Biomphalaria spp. and Bulinus spp., respectively. We derived nonlinear thermal responses fitted on these data to parameterize a mechanistic, process-based model of schistosomiasis. We then re-cast the basic reproduction number and the prevalence of schistosome infection as functions of temperature. We found that the thermal optima for transmission of S. mansoni and S. haematobium range between 23.1-27.3°C and 23.6-27.9°C (95% CI) respectively. We also found that the thermal optimum shifts toward higher temperatures as the human water contact rate increases with temperature. Our findings align with an extensive dataset of schistosomiasis prevalence in SSA. The refined nonlinear thermal-response model developed here suggests a more suitable current climate and a greater risk of increased transmission with future warming for more than half of the schistosomiasis suitable regions with mean annual temperature below the thermal optimum.
Topics: Animals; Humans; Temperature; Schistosoma haematobium; Schistosoma mansoni; Africa South of the Sahara; Biomphalaria; Schistosomiasis; Schistosomiasis mansoni; Bulinus; Schistosomiasis haematobia; Prevalence
PubMed: 38857289
DOI: 10.1371/journal.pntd.0011836 -
Parasitology Research Jun 2024Echinococcosis is a worldwide disease endemic to the western region of China. In 2023, echinococcosis was detected in one of 27 wild boars (Sus scrofa) in Yili...
Echinococcosis is a worldwide disease endemic to the western region of China. In 2023, echinococcosis was detected in one of 27 wild boars (Sus scrofa) in Yili Prefecture, Xinjiang, northwestern China. Histopathological staining and full sequence mitochondrial (mt) analysis were used to determine the infection genotype. Echinococcus granulosus was detected in the wild boar liver, and the cystic lesion characteristics indicated the E. granulosus genotype (G1). This case is the first confirmation of wild boar serving as a transmitter for the G1 genotype of E. granulosus within China. These findings suggest that surveillance is needed to assess the risk of E. granulosus sensu lato transmission to humans and wild animals.
Topics: Animals; China; Echinococcus granulosus; Sus scrofa; Genotype; Swine Diseases; Swine; Echinococcosis; Liver; Sequence Analysis, DNA; DNA, Mitochondrial; DNA, Helminth; Phylogeny
PubMed: 38856927
DOI: 10.1007/s00436-024-08249-3 -
BMC Veterinary Research Jun 2024The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the...
BACKGROUND
The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation.
RESULTS
The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles.
CONCLUSIONS
This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.
Topics: Animals; Fasciola; Signal Transduction; Insulin; Helminth Proteins
PubMed: 38851737
DOI: 10.1186/s12917-024-04107-7 -
Endoscopy Dec 2024
Topics: Humans; Clonorchiasis; Clonorchis sinensis; Animals; Male; Endoscopy, Digestive System; Anthelmintics; Cholangiopancreatography, Endoscopic Retrograde
PubMed: 38848763
DOI: 10.1055/a-2333-9258 -
Journal of Medicinal Chemistry Jun 2024The NAD-dependent lysine deacylase sirtuin 2 (Sirt2) is involved in multiple pathological conditions such as cancer. Targeting Sirt2 has thus received an increased...
The NAD-dependent lysine deacylase sirtuin 2 (Sirt2) is involved in multiple pathological conditions such as cancer. Targeting Sirt2 has thus received an increased interest for therapeutic purposes. Furthermore, the orthologue from (Sirt2) has been considered for the potential treatment of the neglected tropical disease schistosomiasis. We previously identified a 1,2,4-oxadiazole-based scaffold from the screening of the "Kinetobox" library as a dual inhibitor of human Sirt2 (hSirt2) and Sirt2. Herein, we describe the structure-activity studies on 1,2,4-oxadiazole-based analogues, which are potent inhibitors of human Sirt2 deacetylation. As proposed by docking studies, a substrate-competitive and cofactor-noncompetitive binding mode of inhibition could be determined binding assays and kinetic analysis and further confirmed by a crystal structure of an oxadiazole inhibitor in complex with hSirt2. Optimized analogues reduced cell viability and inhibited prostate cancer cell migration, in correlation with Sirt2 deacetylase inhibition both and in cells.
Topics: Sirtuin 2; Oxadiazoles; Humans; Structure-Activity Relationship; Molecular Docking Simulation; Animals; Cell Line, Tumor; Cell Survival; Schistosoma mansoni; Cell Movement
PubMed: 38847803
DOI: 10.1021/acs.jmedchem.4c00229 -
Folia Parasitologica May 2024Schistosomiasis is a snail-borne disease that has a considerable impact on human and animal health, particularly in sub-Saharan Africa. The intermediate hosts of the...
Schistosomiasis is a snail-borne disease that has a considerable impact on human and animal health, particularly in sub-Saharan Africa. The intermediate hosts of the schistosome parasites are freshwater snails of the genera Biomphalaria Preston, 1910 and Bulinus Müller, 1781. In order to identify existing gaps in the spread of the disease in the Democratic Republic of Congo (DRC), this study compiled the available knowledge of the distribution, population dynamics and ecology of the intermediate hosts of schistosomiasis. A systematic literature search was conducted in PubMed, Embase and Scopus for all malacological studies on schistosoma intermediate hosts in DRC published between 1927 and October 2022. A total of 55 records were found, of which 31 met the inclusion criteria: these were published field and experimental studies conducted in the DRC and focused on snails as intermediate hosts of schistosomes. The analysis of these studies revealed that more up-to-date data on the distribution of snail intermediate hosts in the DRC are needed. Moreover, ecological factors have been less studied for Bulinus species than for Biomphalaria species. These factors play a crucial role in determining suitable snail habitats, and the lack of comprehensive information poses a challenge in snail control. This review makes it clear that there are no current malacological data in the DRC. There is a clear need for molecular and ecological research to update the exact species status and population dynamics of all potential intermediate host species. This will facilitate targeted snail control measures that complement drug treatment in the control of schistosomiasis in the country.
Topics: Animals; Humans; Biomphalaria; Bulinus; Democratic Republic of the Congo; Schistosoma; Schistosomiasis; Snails
PubMed: 38841845
DOI: 10.14411/fp.2024.010 -
Frontiers in Immunology 2024Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature...
Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1 mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.
Topics: Animals; Receptors, Leukotriene; Mice; Disease Models, Animal; Cyclopropanes; Acetates; Sulfides; Schistosomiasis mansoni; Mice, Knockout; Quinolines; Female; Schistosoma mansoni; Chronic Disease; Leukotriene Antagonists; Liver; Mice, Inbred C57BL; Praziquantel; T-Lymphocytes, Regulatory
PubMed: 38840916
DOI: 10.3389/fimmu.2024.1279043 -
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 -
Parasites, Hosts and Diseases May 2024Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis...
Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-μ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D2 synthases. Recombinant forms of these CsGST-σ and CsGST-μ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H2 (PGS substrate; average Km of 30.7 and 3.0 μm for prostaglandin D2 [PGDS] and E2 synthase [PGES], respectively) than those toward CDNB (GST substrate; average Km of 1,205.1 μm). Furthermore, the catalytic efficiency (Kcat/Km) of the PGDS/PGES activity was higher than that of GST activity (average Kcat/Km of 3.1, 0.7, and 7.0×10-3 s-1μm-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD2 and PGE2 in addition to their roles in general detoxification.
Topics: Glutathione Transferase; Clonorchis sinensis; Animals; Intramolecular Oxidoreductases; Recombinant Proteins; Lipocalins; Escherichia coli; Prostaglandin H2; Kinetics
PubMed: 38835261
DOI: 10.3347/PHD.24004