Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA260906 | ENA |
REPOSITORIES: ENA
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Project description:We have performed a genome wide transcriptional survey of liver biopsies obtained from patients in Hunan China, who have chronic schistosomiasis with and without past viral hepatitis history, compared to patients with no liver disease history or indicators. These results present a comprehensive transcriptional profile of chronic schistosomiasis japonica patients and demonstrate similarities and differences with other hepatic diseases. These unique features of gene expression, in conjunction with previous reports of the cellular composition of granuloma formation and recovery, present an improved understanding of the molecular immunopathology and general physiological status underlying hepatic schistosomiasis.
2014-09-13 | GSE61376 | GEO
Project description:We have performed a genome wide transcriptional survey of liver biopsies obtained from patients in Hunan China, who have chronic schistosomiasis with and without past viral hepatitis history, compared to patients with no liver disease history or indicators. These results present a comprehensive transcriptional profile of chronic schistosomiasis japonica patients and demonstrate similarities and differences with other hepatic diseases. These unique features of gene expression, in conjunction with previous reports of the cellular composition of granuloma formation and recovery, present an improved understanding of the molecular immunopathology and general physiological status underlying hepatic schistosomiasis. The gene expression profile of the human liver was examined for chronic patients with Schistosoma japonicum infections. Microarray analysis was performed on cRNA synthesised from total RNA derived from the liver biopsy tissue from huan China. Three groups were examined based on infections status [C] were without history or indicators of schistosomiasis or viral heapatitis controls ; [S] with a history or active for schistosomiasis but no indicators of viral heapatitis; and [S]
2014-09-13 | E-GEOD-61376 | biostudies-arrayexpress
Project description:Liver fibrosis is a poor outcome of patients with schistosomiasis, impacting the quality of life and even survival. Eggs deposited in the liver were the main pathogenic factors of hepatic fibrosis in Schistosomiasis japonica. However, the mechanism of hepatic fibrosis in schistosomiasis remains not well defined and there is no effective measure to prevent and treat schistosome-induced hepatic fibrosis. In this study, we applied single-cell sequencing to primarily explore the mechanism of hepatic fibrosis in murine schistosomiasis japonica(n=1) and normal mouse was served as control(n=1). A total of 10,403 cells were included in our analysis and grouped into 18 major cell clusters. Th2 cells and NKT cells were obviously increased and there was a close communication between NKT cells and FASLG signaling pathway. Flow cytometry analysis indicated that the expression of Fasl in NKT cells, CD8+ T cell and NK cell were higher in SJ groups. Arg1, Retnla and Chil3, marker genes of alternatively activated macrophages (M2), were mainly expressed in mononuclear phagocyte(1) (MP(1)), suggesting that Kupffer cells might undergo M2-like polarization in fibrotic liver of schistosomiasis. CXCL and CCL signaling pathway analysis with CellChat showed that Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 were the most dominant L−R and there were close interactions between T cells and MPs. Overall, our research profiled a preliminary immunological network of hepatic fibrosis in murine schistosomiasis japonica, which might contribute to a better understanding of the mechanisms of liver fibrosis in schistosomiasis. NKT cells and CXCL and CCL signaling pathway such as Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 might be potential targets to alleviate hepatic fibrosis of schistosomiasis.
2022-12-16 | GSE220286 | GEO
Project description:In schistosomiasis japonica, the egg-induced granulomatous response and the development of extensive hepatic fibrosis is the main pathology. Information regarding the specific mechanisms associated with granuloma regression and the subsequent recovery events in the host liver are still limited. In this study, a murine model of schistosomiasis japonica was used to characterise the multicellular pathways occurring during liver regeneration. Schistosoma japonicum-infected C57BL/6 mice were administered with the drug praziquantel (PZQ), on a daily basis for five consecutive days to eliminate all adult parasites. The pathological changes of PZQ-treated groups after 3, 6 and 7 weeks post PZQ treatment were examined, along with the assessment of cellular infiltration to the liver. PZQ treatment significantly reduced the degree of splenomegaly, granuloma density and the collagen deposition of liver fibrosis. The infiltration of inflammatory cells, including neutrophils, eosinophils and macrophages to the liver were as well significantly decreased. Transcriptomic analysis revealed the significant up-regulation of fatty acid metabolism genes and the identification of peroxisome proliferator-activated receptor alpha (PPAR-α) as the upstream regulator during the process of liver recovery. Aryl hydrocarbon receptor (AhR) signalling pathway that is involved primarily in the regulation of hepatic enzymes responsible for xenobiotic metabolism was as well differentially up-regulated. These findings indicate that schistosome egg-induced fibrogenesis process is reversible, and provide a better understanding of the regression mechanisms associated with hepatic schistosomiasis. These results hold important implications for the future alleviation of this and other fibrotic diseases of clinical significance.
2014-08-31 | GSE59276 | GEO
Project description:In schistosomiasis japonica, the egg-induced granulomatous response and the development of extensive hepatic fibrosis is the main pathology. Information regarding the specific mechanisms associated with granuloma regression and the subsequent recovery events in the host liver are still limited. In this study, a murine model of schistosomiasis japonica was used to characterise the multicellular pathways occurring during liver regeneration. Schistosoma japonicum-infected C57BL/6 mice were administered with the drug praziquantel (PZQ), on a daily basis for five consecutive days to eliminate all adult parasites. The pathological changes of PZQ-treated groups after 3, 6 and 7 weeks post PZQ treatment were examined, along with the assessment of cellular infiltration to the liver. PZQ treatment significantly reduced the degree of splenomegaly, granuloma density and the collagen deposition of liver fibrosis. The infiltration of inflammatory cells, including neutrophils, eosinophils and macrophages to the liver were as well significantly decreased. Transcriptomic analysis revealed the significant up-regulation of fatty acid metabolism genes and the identification of peroxisome proliferator-activated receptor alpha (PPAR-α) as the upstream regulator during the process of liver recovery. Aryl hydrocarbon receptor (AhR) signalling pathway that is involved primarily in the regulation of hepatic enzymes responsible for xenobiotic metabolism was as well differentially up-regulated. These findings indicate that schistosome egg-induced fibrogenesis process is reversible, and provide a better understanding of the regression mechanisms associated with hepatic schistosomiasis. These results hold important implications for the future alleviation of this and other fibrotic diseases of clinical significance. C57BL/6 murine model infected with S. japonicum were treated orally with Praziquantel (PZQ) after 7 weeks post infection to examine the hepatic regression process following drug treatment. These PZQ-treated, non PZQ-treated and uninfected mice were then euthanised at 10, 13, and 14 weeks p.i. Livers were collected from each mice, and subjected to total RNA isolation and gene expression analysis. Microarray analysis of this study was performed using samples derived from 3 individual mice per group/time-point.
2014-08-31 | E-GEOD-59276 | biostudies-arrayexpress
Project description:Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental schistosomiasis is the progressive granuloma and fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanisms that underlie the hepatic pathogenesis induced by schistosomal egg deposition have not yet been well-defined. Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at day 15, 30, and 45 post infection (pi) with that from uninfected mice as controls. Meanwhile, microRNA expression profiles from the same samples were decoded by parallel solexa sequencing. Gene expression alternation associated with liver damage was observed even at early stage of infection (e.g., pi 15), which became more magnificent onset of egg deposition within the liver tissue. Up-regulated genes were dominantly associated with inflammatory infiltration of liver during S. japonicum infection, whereas down-regulated genes primarily led to the hepatic functional disorders. More than 130 miRNAs were differentially expressed during S. japonicum infection, and dynamic miRNA-gene co-expression network has been constructed during the development of hepatic pathology. A four chip study using total RNA recovered from liver tissues of BALB/c mice which were percutaneously infected with 30 ± 2 cercariae of S. japonicum at day 0, 15, 30, and 45 post infection, respectively.
2013-06-12 | E-GEOD-45985 | biostudies-arrayexpress
Project description:Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental schistosomiasis is the progressive granuloma and fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanisms that underlie the hepatic pathogenesis induced by schistosomal egg deposition have not yet been well-defined. Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at day 15, 30, and 45 post infection (pi) with that from uninfected mice as controls. Meanwhile, microRNA expression profiles from the same samples were decoded by parallel solexa sequencing. Gene expression alternation associated with liver damage was observed even at early stage of infection (e.g., pi 15), which became more magnificent onset of egg deposition within the liver tissue. Up-regulated genes were dominantly associated with inflammatory infiltration of liver during S. japonicum infection, whereas down-regulated genes primarily led to the hepatic functional disorders. More than 130 miRNAs were differentially expressed during S. japonicum infection, and dynamic miRNA-gene co-expression network has been constructed during the development of hepatic pathology.
2013-06-12 | GSE45985 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature