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Greiciane MS Florim Heloisa C Caldas Julio CR de Melo Maria Alice SF Baptista Ida MM Fernandes Marcela Savoldi-Barbosa Gustavo H Goldman Mario Abbud-Filho 《Arthritis research & therapy》2015,17(1)
IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users. 相似文献137.
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Jonathan W. Kotula Jinpeng Sun Margie Li Elizabeth D. Pratico Mark P. Fereshteh Douglas P. Ahrens Bruce A. Sullenger Jeffrey J. Kovacs 《PloS one》2014,9(4)
β-arrestins, ubiquitous cellular scaffolding proteins that act as signaling mediators of numerous critical cellular pathways, are attractive therapeutic targets because they promote tumorigenesis in several tumor models. However, targeting scaffolding proteins with traditional small molecule drugs has been challenging. Inhibition of β-arrestin 2 with a novel aptamer impedes multiple oncogenic signaling pathways simultaneously. Additionally, delivery of the β-arrestin 2-targeting aptamer into leukemia cells through coupling to a recently described cancer cell-specific delivery aptamer, inhibits multiple β-arrestin-mediated signaling pathways known to be required for chronic myelogenous leukemia (CML) disease progression, and impairs tumorigenic growth in CML patient samples. The ability to target scaffolding proteins such as β-arrestin 2 with RNA aptamers may prove beneficial as a therapeutic strategy.
Highlights
- An RNA aptamer inhibits β-arrestin 2 activity.
- Inhibiting β-arrestin 2 impedes multiple tumorigenic pathways simultaneously.
- The therapeutic aptamer is delivered to cancer cells using a cell-specific DNA aptamer.
- Targeting β-arrestin 2 inhibits tumor progression in CML models and patient samples.
139.
Stephan Fuchs Martin Kucklick Erik Lehmann Alexander Beckmann Maya Wilkens Baban Kolte Ayten Mustafayeva Tobias Ludwig Maurice Diwo Josef Wissing Lothar Jnsch Christian H. Ahrens Zoya Ignatova Susanne Engelmann 《PLoS genetics》2021,17(6)
Small proteins play essential roles in bacterial physiology and virulence, however, automated algorithms for genome annotation are often not yet able to accurately predict the corresponding genes. The accuracy and reliability of genome annotations, particularly for small open reading frames (sORFs), can be significantly improved by integrating protein evidence from experimental approaches. Here we present a highly optimized and flexible bioinformatics workflow for bacterial proteogenomics covering all steps from (i) generation of protein databases, (ii) database searches and (iii) peptide-to-genome mapping to (iv) visualization of results. We used the workflow to identify high quality peptide spectrum matches (PSMs) for small proteins (≤ 100 aa, SP100) in Staphylococcus aureus Newman. Protein extracts from S. aureus were subjected to different experimental workflows for protein digestion and prefractionation and measured with highly sensitive mass spectrometers. In total, 175 proteins with up to 100 aa (SP100) were identified. Out of these 24 (ranging from 9 to 99 aa) were novel and not contained in the used genome annotation.144 SP100 are highly conserved and were found in at least 50% of the publicly available S. aureus genomes, while 127 are additionally conserved in other staphylococci. Almost half of the identified SP100 were basic, suggesting a role in binding to more acidic molecules such as nucleic acids or phospholipids. 相似文献
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McKay JD Truong T Gaborieau V Chabrier A Chuang SC Byrnes G Zaridze D Shangina O Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Holcatova I Janout V Foretova L Lagiou P Trichopoulos D Benhamou S Bouchardy C Ahrens W Merletti F Richiardi L Talamini R Barzan L Kjaerheim K Macfarlane GJ Macfarlane TV Simonato L Canova C Agudo A Castellsagué X Lowry R Conway DI McKinney PA Healy CM Toner ME Znaor A Curado MP Koifman S Menezes A Wünsch-Filho V Neto JE Garrote LF Boccia S 《PLoS genetics》2011,7(3):e1001333
Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility. 相似文献