Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgically resected specimens, consisting of tumor and adjacent non-neoplastic liver tissue, were obtained from 40 patients with primary liver cancer at Zhong Shan Hospital, Shanghai Medical University, the People's Republic of China, between March 1983 and July 1984. All were hepatocellular carcinomas (HCC), one being admixed with cholangiocarcinoma. The relationship of hepatitis B virus (HBV) markers with iron and ferritin was evaluated in liver tissues from patients with primary liver cancers. The serum HBsAg (Hepatitis B surface antigen) positive rate was 80.0% (32/40). Cirrhosis was observed in 97.5% (39/40). HBsAg was identified in 82.5% (33/40) of uninvolved liver, and 35.0% (14/40) of HCC tissues (P less than 0.001). HBcAg (hepatitis B core antigen) was detected in 25.0% (10/40) of liver, and 7.5% (3/40) of HCC tissues (P less than 0.05). Stainable iron was found in 65.0% (26/40) of unaffected livers, and 10.0% (4/40) of HCC tissues (P less than 0.001). Ferritin was demonstrated in 75% (30/40) of non-neoplastic liver, and 40% (16/40) of HCC tissues (P less than 0.001). Twenty-two of 33 HCC patients (66.7%) with HBsAg positive cells in their livers also showed stainable iron. Of 16 patients positive for ferritin in HCC cells, iron was found in only two. Iron was found in nine of ten patients with HBcAg in non-neoplastic hepatocytes (P = 0.056); a finding compatible with the hypothesis that iron accumulates in cells replicating HBV. The other results indicate that: immunohistologic ferritin in HCC is not due to increased stainable iron; tumor cells may produce ferritin; polyclonal antibodies to human liver ferritin react better with non-neoplastic hepatocytes than with HCC cells; the high prevalence of HBsAg and cirrhosis in HCC suggests that HBV plays a major etiologic role in hepatocarcinogenesis in China; and one case of HCC is attributed to Schistosoma japonicum infestation via cirrhosis.
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PMID:Iron, ferritin, hepatitis B surface and core antigens in the livers of Chinese patients with hepatocellular carcinoma. 302 1

Our previous work showed that immunization of mice with Schistosoma japonicum (Sj) immature eggs induced significant immunity against fecundity and embryonation of the parasite. The Sj adult cDNA library was screened by sera from rabbits against Sj immature egg antigen (RASjIEA). The genes encoding molecules which may induce immunity against fecundity/embryonation were chosen for further cloning and expression. First of all, RASjIEA was absorbed with E. coli lysate to remove cross reactive antibodies. The cDNA library was then immunoscreened using the routine method. The resulted positive plaques were rescreened till individual clones were confirmed. Phagemids were obtained using in vivo excision. The positive clones were amplified using PCR. The sizes of the genes were determined by agarose gel electrophoresis. After DNA sequencing of the genes cloned, Gene bank was searched and six different genes were identified from a total of 102 positive clones. One of six identified genes, Sj ferritin (SjFer) was chosen to subclone into pGMC vector. According to DNA sequences of Sj Fer and MCS (multiple cloning site) of the vector, forward primer (Fer/GMC1) and reverse primer (Fer/GMC2) were designed and used to amplify Sj Fer by PCR. The Sj Fer cDNA and expression vector pGMC were digested with BamHI and XhoI. The digested cDNA and pGMC were ligased by T4 DNA ligase to construct a recombinant which was then used to transform E. coli strain ER2566. The fusion protein GMCSF-Sj Ferritin was expressed in insoluble form, the inclusion body. Pellets were harvested and resolved in Tris-HCl buffer containing 8M urea. GMCSF-Sj Ferritin was purified by affinity chromatography using Ni-NTA resin. The molecular weight was determined by SDS-PAGE. This study first reports the gene encoding S. japonicum ferritin as a new candidate for schistosome vaccine.
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PMID:[Schistosoma japonicum ferritin: cloning, nucleotide sequencing, expression, and purification]. 1068 50

In an attempt to isolate and identify the antigenic epitopes on ferritin of Schistosoma japonicum (SjFer) and to test their protective potentiality against Schistosoma japonicum (S.j), polyclonal antisera against SjFer was prepared to screen a 12-mer random peptide library. Three rounds of biopanning were performed and resulted in an enrichment. Six peptides selected randomly from the third elute were all found to be positive by evaluating the binding to anti-SjFer sera by ELISA and Western blotting. Three amino acid sequences were deduced from the six phage clones by sequencing. When they were used to vaccinate mice, the three peptides could induce significant reduction in adult worms (26.7%, 20.4%, and 25.9%) as well as in liver eggs per gram (LEPG) (40.0%, 38.2%, and 40.8%). This result showed that three mimotopes on SjFer were obtained and they could induce significant protective efficacy against S.j.
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PMID:Schistosoma japonicum: isolation and identification of peptides mimicking ferritin epitopes from phage display library. 1520 5

Pubertal development and associated downmodulation of proinflammatory cytokines may predict improved nutritional status, independent of chronic parasite infections, in developing countries. We enrolled 731 individuals, aged 7-30 y, from Leyte, the Philippines, where helminth infections and nutritional morbidity are highly prevalent. The following data were collected: venous blood hemoglobin and serum concentrations of ferritin, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein and proinflammatory cytokines (IL-1, IL-6, TNF-alpha, and soluble TNF receptor I); anthropometric measurements to calculate upper arm muscle area Z-score and sum of triceps and subscapular skinfolds Z-score; stool samples to determine Schistosoma japonicum and geohelminth egg counts; and responses to questionnaires assessing socio-economic status. In cross-sectional multilevel linear and logistic regression analyses adjusted for confounders, relations were assessed between 1) DHEAS and nutritional status, 2) DHEAS and proinflammatory cytokines, and 3) nutritional status and proinflammatory cytokines. Independent of age, socio-economic status, and helminth infections, increased levels of DHEAS were associated with improved nutritional status and decreased prevalence of non-iron deficiency anemia in both males and females. DHEAS showed dose-dependent inverse associations with C-reactive protein (P=0.08) and the production of IL-6 (P<0.0001). These inflammatory markers, in turn, were consistently associated with undernutrition and anemia. The results suggest that the puberty-associated rise in DHEAS downmodulates proinflammatory immune responses and thereby reduces undernutrition and anemia in a population experiencing a high burden of chronic helminth infections. This novel regulatory mechanism of inflammation-related nutritional morbidity emphasizes the importance of treating prepubescent children for helminth infections.
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PMID:Higher serum concentrations of DHEAS predict improved nutritional status in helminth-infected children, adolescents, and young adults in Leyte, the Philippines. 1723 23

Iron (Fe) is an important trace element found in nearly all organisms, and is used as a cofactor in many biological reactions. One role for Fe in some invertebrates is in stabilization of extracellular matrices. The human blood fluke, Schistosoma japonicum, is responsible for significant human disease in developing and tropical nations. Disease in humans arises from host immunological reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for development in their hosts, and store abundant Fe in vitelline (eggshell-forming) cells of the female system. The understanding of Fe metabolism and functionality are aspects of its biology that may be exploited in future therapeutics. The biology of Fe stores in vitelline cells of S. japonicum was investigated to illuminate possible functions of this element in early development of these parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females and is also expressed at low levels in egg-stages and adult males. Laser microdissection microscopy, coupled with reverse transcriptase- and real time-PCR amplification of schistosome ferritin sequences, confirmed that the vitelline cells are the likely progenitor cells of yolk ferritin. Assessment of Fe concentrations in whole male and whole female adult worms, eggs and purified eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels of Fe in the female parasite, but also high levels of the element in whole parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix of which is composed of heavily cross-linked eggshell precursor proteins. Thus, vitelline stores of Fe are implicated in eggshell cross-linking in platyhelminths. These observations emphasise the importance of Fe in schistosome metabolism and egg formation and suggest new avenues for disruption of egg formation in these pathogenic parasites.
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PMID:Tracking the fate of iron in early development of human blood flukes. 1755 9

Hemozoin (Hz) is considered a disposal product during the digestion of red blood cells by some blood-feeding parasites, such as Plasmodium, Schistosome, and Rhodnius. The only function of Hz that has been reported is to detoxify the free heme (Fe((III))-protoporphyrin-IX) in worms. Here we report a new role for Hz in iron transport in Schistosoma japonicum. Using transmission electron microscopy (TEM), we observed that S. japonicum hemozoin (sjHz) granules were a group of electron-dense, globe-, and comma-shaped granules. At the anterior end of female worm gut, these dark brown granules were found to be mixed with biconcave disc-shaped erythrocytes, in the middle portion of the gut these granules attached to destroyed erythrocytes and in the posterior portion of the gut no intact erythrocytes were observed except free sjHz granules. By energy dispersive spectroscopy (EDS) and Prussian blue iron staining, we found that these iron-containing sjHz granules are degraded near the microvilli adjacent to vitelline glands, resulting in the accumulation of a large amount of iron in the vitelline cells and eggs of developed S. japonicum. The accumulation of iron in vitelline glands was synchronized with the increase of sjHz granules in the gut. When S. japonicum just contained a little amount of sjHz granules in gut, hardly any accumulation of iron was detected in vitelline glands. However, when the lumen of gut filled full with sjHz granules, large amounts of iron was detected in vitelline glands. Solexa sequencing revealed that expression of iron store protein, ferritin-1 (CAX77379.1), is just significantly up-regulated in worms that contained a large amount of sjHz in gut. In contrast to the idea that sjHz granules are simply by-product of heme detoxification, we found that formation and degradation of sjHz granules in vivo likely serve for the iron transport. Our findings provide new insights into the biological significance of Hz formation.
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PMID:Beyond heme detoxification: a role for hemozoin in iron transport in S. japonicum. 2373 33

Pairing of Schistosoma japonicum initiates female development, leads to female sexual maturation, and maintains this mature state. To understand the mechanism involved in these processes, we studied parasites isolated from single- and double-sex cercariae-infected mice using deep-sequencing analysis, Solexa, to uncover pair-regulated transcriptional profiles. In this study, we report the results of high-throughput tag-sequencing (Tag-seq) analysis of the transcriptome of female worms 18 and 23 days postsingle- and double-sex infections. We sequenced over 3 million tags, obtained a total of 14,034, 27,251, 22,755, and 22,555 distinct tags corresponding to 5,773, 9,794, 8,885, and 8,870 tag-mapped genes for 23-day-old female schistosomula from double-sex infections (23DSI), 23-day-old female schistosomula from single-sex infections (23SSI), 18-day-old female schistosomula from double-sex infections (18DSI), and 18-day-old female schistosomula from single-sex infections (18SSI), respectively. Analyses of differentially expressed genes revealed similarities in the gene expression profiles between 18SSI and 18DSI as well as rational differential gene expression between 18SSI and 23SSI. However, fewer upregulated genes were found in 23DSI compared with 18DSI. Of the 3,446 differentially expressed genes between 23DSI and 23SSI, 2,913 genes were upregulated in 23SSI, whereas only 533 genes were upregulated in 23DSI. In these upregulated genes in 23DSI, phosphoglycerate mutase, superoxide dismutase, egg antigen, ribosomal proteins, ferritin-1 heavy chain, and eukaryotic translation initiation factor 2 were detected. Detection of these genes suggests that gene expression in 23DSI is specialized for functions such as promotion and maintenance of female sexual maturation and egg production. Quantitative real-time (RT)-PCR analysis confirmed the Solexa results, thereby supporting the reliability of the system. Our results offer new insights into the biological significance of pairing, which directs the expression of genes specific for sexual maturation and egg production.
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PMID:Transcriptome profilings of female Schistosoma japonicum reveal significant differential expression of genes after pairing. 2429 95