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101.
Franck Desmoulin Michel Galinier Charlotte Trouillet Matthieu Berry Clément Delmas Annie Turkieh Pierre Massabuau Heinrich Taegtmeyer Fatima Smih Philippe Rouet 《PloS one》2013,8(4)
Objective
Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value.Methods
We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for 1H NMR – based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings.Results
Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort.Conclusion
This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care. 相似文献102.
103.
104.
Christophe Blanchetot Dennis Verzijl Azra Muji?-Deli? Leontien Bosch Louise Rem Rob Leurs C. Theo Verrips Michael Saunders Hans de Haard Martine J. Smit 《The Journal of biological chemistry》2013,288(35):25173-25182
Chemokine receptors and their ligands play a prominent role in immune regulation but many have also been implicated in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, allograft rejection after transplantation, and also in cancer metastasis. Most approaches to therapeutically target the chemokine system involve targeting of chemokine receptors with low molecular weight antagonists. Here we describe the selection and characterization of an unprecedented large and diverse panel of neutralizing Nanobodies (single domain camelid antibodies fragment) directed against several chemokines. We show that the Nanobodies directed against CCL2 (MCP-1), CCL5 (RANTES), CXCL11 (I-TAC), and CXCL12 (SDF-1α) bind the chemokines with high affinity (at nanomolar concentration), thereby blocking receptor binding, inhibiting chemokine-induced receptor activation as well as chemotaxis. Together, we show that neutralizing Nanobodies can be selected efficiently for effective and specific therapeutic treatment against a wide range of immune and inflammatory diseases. 相似文献
105.
Katherine Reiter Debaditya Mukhopadhyay Hong Zhang Lauren E. Boucher Nirbhay Kumar Jürgen Bosch Michael J. Matunis 《The Journal of biological chemistry》2013,288(39):27724-27736
Small ubiquitin-related modifiers (SUMOs) are post-translationally conjugated to other proteins and are thereby essential regulators of a wide range of cellular processes. Sumoylation, and enzymes of the sumoylation pathway, are conserved in the malaria causing parasite, Plasmodium falciparum. However, the specific functions of sumoylation in P. falciparum, and the degree of functional conservation between enzymes of the human and P. falciparum sumoylation pathways, have not been characterized. Here, we demonstrate that sumoylation levels peak during midstages of the intra-erythrocyte developmental cycle, concomitant with hemoglobin consumption and elevated oxidative stress. In vitro studies revealed that P. falciparum E1- and E2-conjugating enzymes interact effectively to recognize and modify RanGAP1, a model mammalian SUMO substrate. However, in heterologous reactions, P. falciparum E1 and E2 enzymes failed to interact with cognate human E2 and E1 partners, respectively, to modify RanGAP1. Structural analysis, binding studies, and functional assays revealed divergent amino acid residues within the E1-E2 binding interface that define organism-specific enzyme interactions. Our studies identify sumoylation as a potentially important regulator of oxidative stress response during the P. falciparum intra-erythrocyte developmental cycle, and define E1 and E2 interactions as a promising target for development of parasite-specific inhibitors of sumoylation and parasite replication. 相似文献
106.
Rasheeda Bashir Ayesha Imtiaz Amara Fatima Afzaal Alam Sadaf Naz 《Biochemical genetics》2013,51(5-6):350-357
The DFNB79 locus harbors TPRN mutations in which have been reported in a few families with deafness. Four frameshift mutations in TPRN have been described to cause severe or severe-to-profound hearing loss in Moroccan and Pakistani families, and a single frameshift mutation was associated with progressive hearing loss in deaf individuals in a Dutch family. We identified a Pakistani family in which the affected individuals were homozygous for a pathogenic mutation, c.42_52del11, in TPRN (p.G15Afs150X). In contrast to the previously reported individuals affected by the same mutation, hearing loss is likely to be progressive in this family. Thus the same mutation of TPRN can be associated with different thresholds of hearing as well as differences in the stability of the phenotype. 相似文献
107.
Peptides of the corticotropin-releasing hormone/Urocortin (CRH/Ucn) family are known to suppress appetite primarily via CRH2 receptors. In the rat hypothalamic supraoptic nucleus (SON), synthesis of both Ucn1 and CRH2 receptors has been reported, yet little is known about the effects of Ucn1 in the SON on feeding behaviour. We first established the dose-related effects of Ucn1 injected into the SON on the feeding response in both freely fed and 24-h food-deprived rats. A conditioned taste avoidance paradigm was performed to investigate possible generalised effects of local Ucn1 treatment. Administration of Ucn1 into the SON at doses equal to or higher than 0.5 μg significantly decreased food intake in both freely fed and food-deprived rats. The Ucn1-mediated suppression of food intake was delayed in freely fed as compared to food-deprived animals. Conditioning for taste aversion to saccharine appeared at 0.5 and 1 μg of Ucn1. Both the early and the delayed onset of anorexia observed after intra-SON injection of Ucn1 under fasting and fed conditions, respectively, suggest the possible involvement of different CRH receptor subtypes in the two conditions, while the conditioned taste aversion seems to be responsible for the initial latency to eat the first meal in these animals. 相似文献
108.
J. G. M. Houdijk R. Hartemink M. W. A. Verstegen Marlou Bosch 《Archives of animal nutrition》2013,67(4):297-307
Fructooligosaccharides (FOS) and transgalactooligosaccharides (TOS), which are non-digestible oligosaccharides (NDO), were included at 10 and 40g/kg in an NDO-free control diet at the expense of purified cellulose. Each of the 5 diets was fed to 4 weaner pigs and microbial characteristics of their ileal chyme and faeces were assessed. The NDO-pigs had lower ileal pH than the control pigs. Dietary NDO did not affect the ileal volatile fatty acid concentration, though FOS-pigs had a higher concentration of lactic acid and relatively more iso-valeric acid and less acetic acid than TOS-pigs. The NDO-pigs had lower ileal aerobic bacterial counts than the control pigs, whilst the FOS-pigs had a larger ileal anaerobic bacterial counts than the TOS-pigs. The NDO-pigs had an higher faecal pH and their faecal volatile fatty acid pool contained relatively more iso-butyric acid and iso-valeric acid than the control pigs. The TOS-pigs tended to have higher faecal anaerobic bacterial counts and had a smaller concentration of faecal volatile fatty acid than the FOS-pigs. We concluded that whilst effects at the faecal level may have been partly due to a reduced intake of cellulose, dietary NDO can exert precaecal prebiotic effects in weaner pigs. 相似文献
109.
S?ren Franzenburg Sebastian Fraune Philipp M Altrock Sven Künzel John F Baines Arne Traulsen Thomas CG Bosch 《The ISME journal》2013,7(4):781-790
Animals are colonized by complex bacterial communities. The processes controlling community membership and influencing the establishment of the microbial ecosystem during development are poorly understood. Here we aimed to explore the assembly of bacterial communities in Hydra with the broader goal of elucidating the general rules that determine the temporal progression of bacterial colonization of animal epithelia. We profiled the microbial communities in polyps at various time points after hatching in four replicates. The composition and temporal patterns of the bacterial communities were strikingly similar in all replicates. Distinct features included high diversity of community profiles in the first week, a remarkable but transient adult-like profile 2 weeks after hatching, followed by progressive emergence of a stable adult-like pattern characterized by low species diversity and the preponderance of the Betaproteobacterium Curvibacter. Intriguingly, this process displayed important parallels to the assembly of human fecal communities after birth. In addition, a mathematical modeling approach was used to uncover the organizational principles of this colonization process, suggesting that both, local environmental or host-derived factor(s) modulating the colonization rate, as well as frequency-dependent interactions of individual bacterial community members are important aspects in the emergence of a stable bacterial community at the end of development. 相似文献
110.
Daria Grafodatskaya Barian HY Chung Darci T Butcher Andrei L Turinsky Sarah J Goodman Sana Choufani Yi-An Chen Youliang Lou Chunhua Zhao Rageen Rajendram Fatima E Abidi Cindy Skinner James Stavropoulos Carolyn A Bondy Jill Hamilton Shoshana Wodak Stephen W Scherer Charles E Schwartz Rosanna Weksberg 《BMC medical genomics》2013,6(1):1-18