Incidence, risk factor, and prognosis of end-stage renal disease after heart transplantation in Chinese recipients

Background/PurposeEnd-stage renal disease (ESRD) is an important complication arising after heart transplantation. At least 3–10% of recipients reach ESRD within 10 years after transplant. The incidence of ESRD in Chinese recipients has not been reported. Here we sought to assess the incidence, prognosis, and risk factors for ESRD in Chinese recipients.MethodsWe conducted a retrospective analysis of 248 heart recipients who survived >1 year from 1998 through 2007. ESRD was defined as the requirement of maintenance dialysis.ResultsRenal dysfunction was present in 20 patients (8%) prior to transplant. With a follow-up duration of 5.8 ± 3.9 years, 30 patients developed ESRD. The cumulative incidence of ESRD after heart transplantation was 2.1% ± 0.9%, 6.5% ± 1.8%, 16.8% ± 3.3%, and 36.5% ± 9.5% at 2, 5, 10, and 15 years after transplant, respectively. Median onset of ESRD was 6.9 years after transplant. Actuarial survival after dialysis was 74.8% ± 8.3%, 66.6% ± 9.2%, and 43.6% ± 12.6% at 1, 2, and 5 years, respectively. Independent risk factors for ESRD included pretransplant serum creatinine (hazard ratio, 1.84; p = 0.001), presence of diabetes prior to transplant (hazard ratio, 2.51; p = 0.017), and old age at transplant (hazard ratio, 1.05; p = 0.008).ConclusionThere was a high incidence of ESRD in Chinese heart recipients. Patients with ESRD had poor prognosis after dialysis

Drosophila Decapping Protein 1, dDcp1, Is a Component of the oskar mRNP Complex and Directs Its Posterior Localization in the Oocyte

SummaryIn Drosophila, posterior deposition of oskar (osk) mRNA in oocytes is critical for both pole cell and abdomen formation. Exon junction complex components, translational regulation factors, and other proteins form an RNP complex that is essential for directing osk mRNA to the posterior of the oocyte. Until now, it has not been clear whether the mRNA degradation machinery is involved in regulating osk mRNA deposition. Here we show that Drosophila decapping protein 1, dDcp1, is a posterior group gene required for the transport of osk mRNA. In oocytes, dDcp1 is localized posteriorly in an osk mRNA position- and dosage-dependent manner. In nurse cells, dDcp1 colocalizes with dDcp2 and Me31B in discrete foci that may be related to processing bodies (P bodies), which are sites of active mRNA degradation. Thus, as well as being a general factor required for mRNA decay, dDcp1 is an essential component of the osk mRNP localization complex

Theoretical prediction of new noble-gas molecules OBNgF (Ng = Ar, Kr, and Xe)

Abstract High-level electronic structure calculation has been performed on the noble-gas molecules OBArF, OBKrF, and OBXeF. The energetics of the two unimolecular dissociation pathways, (1) OBNgF ! OB + Ng + F, and (2) OBNgF ! OBF + Ng, were also calculated. The B-Ng bonds were calculated to be 1.8-2.2 Å and were found to be covalent in nature. Highly positive charges were assigned to B and Ng atoms and highly negative charges to O and F atoms. Both unimolecular dissociation pathways were found to have high energy barriers (>15 kcal/mol), and thus suggests that OBNgF are dynamically stable species

MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins

Motivation: Molecular recognition features (MoRFs) are short binding regions located within longer intrinsically disordered regions that bind to protein partners via disorder-to-order transitions. MoRFs are implicated in important processes including signaling and regulation. However, only a limited number of experimentally validated MoRFs is known, which motivates development of computational methods that predict MoRFs from protein chains

Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction

<p>Abstract</p> <p>Background</p> <p><it>Ganoderma lucidum </it>has been widely used as a herbal medicine for promoting health and longevity in China and other Asian countries. Polysaccharide extracts from <it>Ganoderma lucidum </it>have been reported to exhibit immuno-modulating and anti-tumor activities. In previous studies, F3, the active component of the polysaccharide extract, was found to activate various cytokines such as IL-1, IL-6, IL-12, and TNF-<it>α</it>. This gave rise to our investigation on how F3 stimulates immuno-modulating or anti-tumor effects in human leukemia THP-1 cells.</p> <p>Results</p> <p>Here, we integrated time-course DNA microarray analysis, quantitative PCR assays, and bioinformatics methods to study the F3-induced effects in THP-1 cells. Significantly disturbed pathways induced by F3 were identified with statistical analysis on microarray data. The apoptosis induction through the DR3 and DR4/5 death receptors was found to be one of the most significant pathways and play a key role in THP-1 cells after F3 treatment. Based on time-course gene expression measurements of the identified pathway, we reconstructed a plausible regulatory network of the involved genes using reverse-engineering computational approach.</p> <p>Conclusion</p> <p>Our results showed that F3 may induce death receptor ligands to initiate signaling via receptor oligomerization, recruitment of specialized adaptor proteins and activation of caspase cascades.</p

Improving protein order-disorder classification using charge-hydropathy plots

BACKGROUND: The earliest whole protein order/disorder predictor (Uversky et al., Proteins, 41: 415-427 (2000)), herein called the charge-hydropathy (C-H) plot, was originally developed using the Kyte-Doolittle (1982) hydropathy scale (Kyte & Doolittle., J. Mol. Biol, 157: 105-132(1982)). Here the goal is to determine whether the performance of the C-H plot in separating structured and disordered proteins can be improved by using an alternative hydropathy scale. RESULTS: Using the performance of the CH-plot as the metric, we compared 19 alternative hydropathy scales, with the finding that the Guy (1985) hydropathy scale (Guy, Biophys. J, 47:61-70(1985)) was the best of the tested hydropathy scales for separating large collections structured proteins and intrinsically disordered proteins (IDPs) on the C-H plot. Next, we developed a new scale, named IDP-Hydropathy, which further improves the discrimination between structured proteins and IDPs. Applying the C-H plot to a dataset containing 109 IDPs and 563 non-homologous fully structured proteins, the Kyte-Doolittle (1982) hydropathy scale, the Guy (1985) hydropathy scale, and the IDP-Hydropathy scale gave balanced two-state classification accuracies of 79%, 84%, and 90%, respectively, indicating a very substantial overall improvement is obtained by using different hydropathy scales. A correlation study shows that IDP-Hydropathy is strongly correlated with other hydropathy scales, thus suggesting that IDP-Hydropathy probably has only minor contributions from amino acid properties other than hydropathy. CONCLUSION: We suggest that IDP-Hydropathy would likely be the best scale to use for any type of algorithm developed to predict protein disorder

Evaluating the Primary Prevention of Ischemic Stroke of Oral Antithrombotic Therapy in Head and Neck Cancer Patients with Radiation Therapy

Although previous studies demonstrated the risk of ischemic stroke (IS) in patients with head and neck cancer (HNC), the impact of oral antithrombotic therapy (OAT) on this risk has not yet been assessed. We aimed to evaluate the effectiveness and safety of OAT in patients with HNC treated with RT. This retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. A total of 37,638 patients diagnosed with HNC included in the study were classified as users and nonusers of OAT. Primary outcome was IS or transient ischemic attack (TIA), and secondary outcomes were death and major bleeding. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). There was no significant difference in the risk of IS or TIA between patients on continuous OAT and nonusers (adjusted HR, 0.812; 95% CI,). The risk of major bleeding was not significantly different between the groups. From a national population database, we did not find an association between OAT and decreasing risk of ischemic stroke/TIA or increasing hazard of major bleeding

Cyclooxygenase-2 enhances α2β1 integrin expression and cell migration via EP1 dependent signaling pathway in human chondrosarcoma cells

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. Interaction of COX-2 with its specific EP receptors on the surface of cancer cells has been reported to induce cancer invasion. However, the effects of COX-2 on migration activity in human chondrosarcoma cells are mostly unknown. In this study, we examined whether COX-2 and EP interaction are involved in metastasis of human chondrosarcoma.</p> <p>Results</p> <p>We found that over-expression of COX-2 or exogenous PGE₂increased the migration of human chondrosarcoma cells. We also found that human chondrosarcoma tissues and chondrosarcoma cell lines had significant expression of the COX-2 which was higher than that in normal cartilage. By using pharmacological inhibitors or activators or genetic inhibition by the EP receptors, we discovered that the EP1 receptor but not other PGE receptors is involved in PGE₂-mediated cell migration and α2β1 integrin expression. Furthermore, we found that human chondrosarcoma tissues expressed a higher level of EP1 receptor than normal cartilage. PGE₂-mediated migration and integrin up-regulation were attenuated by phospholipase C (PLC), protein kinase C (PKC) and c-Src inhibitor. Activation of the PLCβ, PKCα, c-Src and NF-κB signaling pathway after PGE₂treatment was demonstrated, and PGE₂-induced expression of integrin and migration activity were inhibited by the specific inhibitor, siRNA and mutants of PLC, PKC, c-Src and NF-κB cascades.</p> <p>Conclusions</p> <p>Our results indicated that PGE₂enhances the migration of chondrosarcoma cells by increasing α2β1 integrin expression through the EP1/PLC/PKCα/c-Src/NF-κB signal transduction pathway.</p