Publications by authors named "Lihong Diao"

22 Publications

  • Page 1 of 1

UbiBrowser 2.0: a comprehensive resource for proteome-wide known and predicted ubiquitin ligase/deubiquitinase-substrate interactions in eukaryotic species.

Nucleic Acids Res 2021 Oct 20. Epub 2021 Oct 20.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.

As an important post-translational modification, ubiquitination mediates ∼80% of protein degradation in eukaryotes. The degree of protein ubiquitination is tightly determined by the delicate balance between specific ubiquitin ligase (E3)-mediated ubiquitination and deubiquitinase-mediated deubiquitination. In 2017, we developed UbiBrowser 1.0, which is an integrated database for predicted human proteome-wide E3-substrate interactions. Here, to meet the urgent requirement of proteome-wide E3/deubiquitinase-substrate interactions (ESIs/DSIs) in multiple organisms, we updated UbiBrowser to version 2.0 (http://ubibrowser.ncpsb.org.cn). Using an improved protocol, we collected 4068/967 known ESIs/DSIs by manual curation, and we predicted about 2.2 million highly confident ESIs/DSIs in 39 organisms, with >210-fold increase in total data volume. In addition, we made several new features in the updated version: (i) it allows exploring proteins' upstream E3 ligases and deubiquitinases simultaneously; (ii) it has significantly increased species coverage; (iii) it presents a uniform confidence scoring system to rank predicted ESIs/DSIs. To facilitate the usage of UbiBrowser 2.0, we also redesigned the web interface for exploring these known and predicted ESIs/DSIs, and added functions of 'Browse', 'Download' and 'Application Programming Interface'. We believe that UbiBrowser 2.0, as a discovery tool, will contribute to the study of protein ubiquitination and the development of drug targets for complex diseases.
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http://dx.doi.org/10.1093/nar/gkab962DOI Listing
October 2021

CTR-DB, an omnibus for patient-derived gene expression signatures correlated with cancer drug response.

Nucleic Acids Res 2021 Sep 27. Epub 2021 Sep 27.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.

To date, only some cancer patients can benefit from chemotherapy and targeted therapy. Drug resistance continues to be a major and challenging problem facing current cancer research. Rapidly accumulated patient-derived clinical transcriptomic data with cancer drug response bring opportunities for exploring molecular determinants of drug response, but meanwhile pose challenges for data management, integration, and reuse. Here we present the Cancer Treatment Response gene signature DataBase (CTR-DB, http://ctrdb.ncpsb.org.cn/), a unique database for basic and clinical researchers to access, integrate, and reuse clinical transcriptomes with cancer drug response. CTR-DB has collected and uniformly reprocessed 83 patient-derived pre-treatment transcriptomic source datasets with manually curated cancer drug response information, involving 28 histological cancer types, 123 drugs, and 5139 patient samples. These data are browsable, searchable, and downloadable. Moreover, CTR-DB supports single-dataset exploration (including differential gene expression, receiver operating characteristic curve, functional enrichment, sensitizing drug search, and tumor microenvironment analyses), and multiple-dataset combination and comparison, as well as biomarker validation function, which provide insights into the drug resistance mechanism, predictive biomarker discovery and validation, drug combination, and resistance mechanism heterogeneity.
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http://dx.doi.org/10.1093/nar/gkab860DOI Listing
September 2021

RadAtlas 1.0: a knowledgebase focusing on radiation-associated genes.

Int J Radiat Biol 2020 08 12;96(8):980-987. Epub 2020 May 12.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing, China.

Ionizing radiation has very complex biological effects, such as inducing damage to DNA and proteins, ionizing water molecules to produce toxic free radicals, and triggering genetic and somatic effects. Understanding the biomolecular response mechanism of radiation is very important for the prevention and treatment of radiation diseases. However, function information of these radiation-associated genes is hidden in numbers of scientific papers and databases, making it difficult to understand the response mechanism of ionizing radiation. We collected radiation-associated genes by literature and database mining. Literature and database mining was performed on the basis of biomedical literature from PubMed and gene expression datasets from GEO respectively. We built an ionizing radiation related knowledgebase RadAtlas 1.0 (http://biokb.ncpsb.org/radatlas), which contains 598 radiation-associated genes compiled from literature mining, and 611 potential radiation-associated genes collected from gene expression datasets by differential gene expression analysis. We also provide a user-friendly web interface that offers multiple search methods. RadAtlas collected a large amount of information about genes, biological processes, and pathways related to ionizing radiation. It is the first attempt to provide a comprehensive catalog of radiation-associated genes with literature evidence and potential radiation-associated genes with differential expression evidence. We believe that RadAtlas would be a helpful tool to understand the response mechanism to ionizing radiation.
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http://dx.doi.org/10.1080/09553002.2020.1761567DOI Listing
August 2020

Rivaroxaban in Peripheral Artery Disease after Revascularization.

N Engl J Med 2020 05 28;382(21):1994-2004. Epub 2020 Mar 28.

From Colorado Prevention Center (CPC) Clinical Research (M.P.B., M.R.N., W.H.C., L.D., N.J., C.N.H., W.R.H.), the Department of Medicine, Division of Cardiovascular Medicine (M.P.B., C.N.H., W.R.H.), the Department of Surgery, Division of Vascular Surgery (M.R.N.), and the Department of Medicine, Division of Endocrinology (W.H.C.), University of Colorado Anschutz Medical Campus, and the Department of Biostatistics and Informatics, Colorado School of Public Health (J.M.K.) - all in Aurora; the Department of Vascular Medicine, Klinikum Darmstadt, Darmstadt, and Center for Thrombosis and Hemostasis, University of Mainz, Mainz (R.M.B.), the Department of Vascular Medicine, Vascular Surgery-Angiology-Endovascular Therapy, University of Hamburg-Eppendorf, Hamburg (E.S.D.), and Bayer, Wuppertal (A.F.P., E.M.) - all in Germany; the Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada (S.S.A.); Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, NC (M.R.P.); the Vascular and Interventional Radiology Department, Careggi University Hospital, University of Florence, Florence, Italy (F.F.); Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine (I.G.); B-A-Z County University Teaching Hospital, Miskolc, Hungary (L.M.); University of Latvia, Pauls Stradins University Hospital, Riga (D.K.K.); ECLA (Estudios Clínicos Latino América), ICR (Instituto Cardiovascular de Rosario), Rosario, Argentina (R.D.); the Division of Angiology, Medical University Graz, Graz, Austria (M.B.); and Janssen Research and Development, Raritan (L.P.H.), and Thrombosis Group Head, Clinical Development, Bayer U.S., Whippany (S.D.B.) - both in New Jersey.

Background: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain.

Methods: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome.

Results: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007).

Conclusions: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).
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http://dx.doi.org/10.1056/NEJMoa2000052DOI Listing
May 2020

FibroAtlas: A Database for the Exploration of Fibrotic Diseases and Their Genes.

Cardiol Res Pract 2019 30;2019:4237285. Epub 2019 Dec 30.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Background: Fibrosis is a highly dynamic process caused by prolonged injury, deregulation of the normal processes of wound healing, and extensive deposition of extracellular matrix (ECM) proteins. During fibrosis process, multiple genes interact with environmental factors. Over recent decades, tons of fibrosis-related genes have been identified to shed light on the particular clinical manifestations of this complex process. However, the genetics information about fibrosis is dispersed in lots of extensive literature.

Methods: We extracted data from literature abstracts in PubMed by text mining, and manually curated the literature and identified the evidence sentences.

Results: We presented FibroAtlas, which included 1,439 well-annotated fibrosis-associated genes. FibroAtlas 1.0 is the first attempt to build a nonredundant and comprehensive catalog of fibrosis-related genes with supporting evidence derived from curated published literature and allows us to have an overview of human fibrosis-related genes.
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http://dx.doi.org/10.1155/2019/4237285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012261PMC
December 2019

OsteoporosAtlas: a human osteoporosis-related gene database.

PeerJ 2019 26;7:e6778. Epub 2019 Apr 26.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China.

Background: Osteoporosis is a common, complex disease of bone with a strong heritable component, characterized by low bone mineral density, microarchitectural deterioration of bone tissue and an increased risk of fracture. Due to limited drug selection for osteoporosis and increasing morbidity, mortality of osteoporotic fractures, osteoporosis has become a major health burden in aging societies. Current researches for identifying specific loci or genes involved in osteoporosis contribute to a greater understanding of the pathogenesis of osteoporosis and the development of better diagnosis, prevention and treatment strategies. However, little is known about how most causal genes work and interact to influence osteoporosis. Therefore, it is greatly significant to collect and analyze the studies involved in osteoporosis-related genes. Unfortunately, the information about all these osteoporosis-related genes is scattered in a large amount of extensive literature. Currently, there is no specialized database for easily accessing relevant information about osteoporosis-related genes and miRNAs.

Methods: We extracted data from literature abstracts in PubMed by text-mining and manual curation. Moreover, a local MySQL database containing all the data was developed with PHP on a Windows server.

Results: OsteoporosAtlas (http://biokb.ncpsb.org/osteoporosis/), the first specialized database for easily accessing relevant information such as osteoporosis-related genes and miRNAs, was constructed and served for researchers. OsteoporosAtlas enables users to retrieve, browse and download osteoporosis-related genes and miRNAs. Gene ontology and pathway analyses were integrated into OsteoporosAtlas. It currently includes 617 human encoding genes, 131 human non-coding miRNAs, and 128 functional roles. We think that OsteoporosAtlas will be an important bioinformatics resource to facilitate a better understanding of the pathogenesis of osteoporosis and developing better diagnosis, prevention and treatment strategies.
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http://dx.doi.org/10.7717/peerj.6778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487800PMC
April 2019

UVGD 1.0: a gene-centric database bridging ultraviolet radiation and molecular biology effects in organisms.

Int J Radiat Biol 2019 08 13;95(8):1172-1177. Epub 2019 May 13.

a State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences-Beijing (PHOENIX Center), Beijing Institute of Lifeomics , Beijing , China.

Exposing to ultraviolet for a certain time will trigger some significant molecular biology effects in an organism. In the past few decades, varied ultraviolet-associated biological effects as well as their related genes, have been discovered under biologists' efforts. However, information about ultraviolet-related genes is dispersed in thousands of scientific papers, and there is still no study emphasizing on the systematic collection of ultraviolet-related genes. We collected ultraviolet-related genes and built this gene-centric database UVGD based on literature mining and manual curation. Literature mining was based on the ultraviolet-related abstracts downloaded from PubMed, and we obtained sentences in which ultraviolet keywords and genes co-occur at single-sentence level by using bio-entity recognizer. After that, manual curation was implemented in order to identify whether the genes are related to ultraviolet or not. We built the ultraviolet-related knowledge base UVGD 1.0 (URL: http://biokb.ncpsb.org/UVGD/ ), which contains 663 ultraviolet-related genes, together with 17 associated biological processes, 117 associated phenotypes, and 2628 MeSH terms. UVGD is helpful to understand the ultraviolet-related biological processes in organisms and we believe it would be useful for biologists to study the responding mechanisms to ultraviolet.
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http://dx.doi.org/10.1080/09553002.2019.1609127DOI Listing
August 2019

Revealing the metabolic characteristics of human embryonic stem cells by genome-scale metabolic modeling.

FEBS Lett 2018 11 2;592(22):3670-3682. Epub 2018 Nov 2.

School of Life Sciences, Tsinghua University, Beijing, China.

Embryonic stem cells (ESCs) are characterized by a dual capacity, self-renewal and pluripotency, which can be regulated by metabolism. A better understanding of ESC metabolism and regulatory mechanisms is pivotal for research into development, ageing, and cancer treatment. However, a systematic and comprehensive delineation of human ESC metabolism is still lacking. Here, we reconstructed the first genome-scale metabolic model (GEM) of human ESCs (hESCs). By GEM simulation and analyses, hESC global metabolic characteristics including essential metabolites and network motifs were identified. Potential metabolic subsystems responsible for self-renewal and pluripotency were also identified by analyses and experiments. This first GEM of hESCs provides a novel view and resource for stem cell metabolism research and will contribute to the elucidation of their metabolic characteristics.
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http://dx.doi.org/10.1002/1873-3468.13255DOI Listing
November 2018

AllerGAtlas 1.0: a human allergy-related genes database.

Database (Oxford) 2018 01;2018

School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Database Url: http://biokb.ncpsb.org/AlleRGatlas/.
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http://dx.doi.org/10.1093/database/bay010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824776PMC
January 2018

An integrated bioinformatics platform for investigating the human E3 ubiquitin ligase-substrate interaction network.

Nat Commun 2017 08 24;8(1):347. Epub 2017 Aug 24.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (The PHOENIX Center, Beijing), Beijing, 102206, China.

The ubiquitination mediated by ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and ubiquitin ligase (E3) cascade is crucial to protein degradation, transcription regulation, and cell signaling in eukaryotic cells. The high specificity of ubiquitination is regulated by the interaction between E3 ubiquitin ligases and their target substrates. Unfortunately, the landscape of human E3-substrate network has not been systematically uncovered. Therefore, there is an urgent need to develop a high-throughput and efficient strategy to identify the E3-substrate interaction. To address this challenge, we develop a computational model based on multiple types of heterogeneous biological evidence to investigate the human E3-substrate interactions. Furthermore, we provide UbiBrowser as an integrated bioinformatics platform to predict and present the proteome-wide human E3-substrate interaction network ( http://ubibrowser.ncpsb.org ).Protein stability modulation by E3 ubiquitin ligases is an important layer of functional regulation, but screening for E3 ligase-substrate interactions is time-consuming and costly. Here, the authors take an in silico naïve Bayesian classifier approach to integrate multiple lines of evidence for E3-substrate prediction, enabling prediction of the proteome-wide human E3 ligase interaction network.
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http://dx.doi.org/10.1038/s41467-017-00299-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570908PMC
August 2017

Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight.

Front Pharmacol 2017 29;8:315. Epub 2017 May 29.

State Key Laboratory of Space Medicine Fundamentals and Applications, China Astronaut Research and Training CenterBeijing, China.

Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE), which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS), alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.
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http://dx.doi.org/10.3389/fphar.2017.00315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446991PMC
May 2017

HisgAtlas 1.0: a human immunosuppression gene database.

Database (Oxford) 2017 Jan;2017

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.

Immunosuppression is body's state in which the activation or efficacy of immune system is weakened. It is associated with a wide spectrum of human diseases. In the last two decades, tremendous efforts have been made to elucidate the mechanism of hundreds of immunosuppression genes. Immunosuppression genes could be valuable drug targets or biomarkers for the immunotherapeutic treatment of different diseases. However, the information of all previously identified immunosuppression genes is dispersed in thousands of publications. Here, we provide the HisgAtlas database that collects 995 previously identified human immunosuppression genes using text mining and manual curation. We believe HisgAtlas will be a valuable resource to search human immunosuppression genes as well as to investigate their functions in further research. Database URL: http://biokb.ncpsb.org/HisgAtlas/.
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http://dx.doi.org/10.1093/database/bax094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243927PMC
January 2017

BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine.

Sci Rep 2016 Feb 16;6:21146. Epub 2016 Feb 16.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm.
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http://dx.doi.org/10.1038/srep21146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754750PMC
February 2016

CAPER 3.0: A Scalable Cloud-Based System for Data-Intensive Analysis of Chromosome-Centric Human Proteome Project Data Sets.

J Proteome Res 2015 Sep 27;14(9):3720-8. Epub 2015 Mar 27.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine , Beijing 100850, China.

The Chromosome-centric Human Proteome Project (C-HPP) aims to catalog genome-encoded proteins using a chromosome-by-chromosome strategy. As the C-HPP proceeds, the increasing requirement for data-intensive analysis of the MS/MS data poses a challenge to the proteomic community, especially small laboratories lacking computational infrastructure. To address this challenge, we have updated the previous CAPER browser into a higher version, CAPER 3.0, which is a scalable cloud-based system for data-intensive analysis of C-HPP data sets. CAPER 3.0 uses cloud computing technology to facilitate MS/MS-based peptide identification. In particular, it can use both public and private cloud, facilitating the analysis of C-HPP data sets. CAPER 3.0 provides a graphical user interface (GUI) to help users transfer data, configure jobs, track progress, and visualize the results comprehensively. These features enable users without programming expertise to easily conduct data-intensive analysis using CAPER 3.0. Here, we illustrate the usage of CAPER 3.0 with four specific mass spectral data-intensive problems: detecting novel peptides, identifying single amino acid variants (SAVs) derived from known missense mutations, identifying sample-specific SAVs, and identifying exon-skipping events. CAPER 3.0 is available at http://prodigy.bprc.ac.cn/caper3.
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http://dx.doi.org/10.1021/pr501335wDOI Listing
September 2015

Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population.

J Vasc Surg 2014 Sep 10;60(3):686-95.e2. Epub 2014 May 10.

Vascular Medicine Program, Lillehei Heart Institute and Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minn.

Background: Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD) and is the major cause of ischemic amputation in the United States. Risk factors and the associated incidence and prevalence of CLI have not been well described in the general population. This study describes the risk factors for PAD progression to CLI and estimates the annual incidence and prevalence of CLI in a representative United States patient cohort.

Methods: This was a retrospective cohort analysis of adults with commercial, Medicare supplemental, or Medicaid health insurance who had at least one PAD or CLI health care claim from January 1, 2003, through December 31, 2008, and 12 months of continuous coverage. Two subgroups of CLI presentation were identified: primary CLI (patients without any prior PAD or subsequent PAD diagnostic code >30 days after CLI diagnostic code) and secondary CLI (patients with prior PAD or subsequent PAD diagnostic codes ≤30 days of a CLI diagnostic code). Patterns of presentation, annual incidence, and prevalence of CLI were stratified by health care plan. Risk factors for progression to CLI were compared by presentation type.

Results: From 2003 to 2008, the mean annual incidence of PAD was 2.35% (95% confidence interval [CI], 2.34%-2.36%) and the incidence of CLI was 0.35% (95% CI, 0.34%-0.35%) of the eligible study population, with primary and secondary presentations occurring at similar rates. The mean annualized prevalence of PAD was 10.69% (95% CI, 10.67%10.70%) and the mean annualized prevalence of CLI was 1.33% (95% CI, 1.32%-1.34%) of the eligible study population, and two-thirds of the cases presented as secondary CLI. CLI developed in 11.08% (95% CI, 11.30%-11.13%) of patients with PAD. A multivariable model demonstrated that diabetes, heart failure, stroke, and renal failure were stronger predictors of primary rather than secondary CLI presentation.

Conclusions: These data establish new national estimates of the incidence and prevalence of CLI and define key risk factors that contribute to primary or secondary presentations of CLI within a very large contemporary insured population cohort in the United States.
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http://dx.doi.org/10.1016/j.jvs.2014.03.290DOI Listing
September 2014

CAPER 2.0: an interactive, configurable, and extensible workflow-based platform to analyze data sets from the Chromosome-centric Human Proteome Project.

J Proteome Res 2014 Jan 3;13(1):99-106. Epub 2013 Dec 3.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine , 33 Life Science Park Road, Beijing 100850, China.

The Chromosome-centric Human Proteome Project (C-HPP) aims to map and annotate the entire human proteome by the "chromosome-by-chromosome" strategy. As the C-HPP proceeds, the increasing volume of proteomic data sets presents a challenge for customized and reproducible bioinformatics data analyses for mining biological knowledge. To address this challenge, we updated the previous static proteome browser CAPER into a higher version, CAPER 2.0 - an interactive, configurable and extensible workflow-based platform for C-HPP data analyses. In addition to the previous visualization functions of track-view and heatmap-view, CAPER 2.0 presents a powerful toolbox for C-HPP data analyses and also integrates a configurable workflow system that supports the view, construction, edit, run, and share of workflows. These features allow users to easily conduct their own C-HPP proteomic data analyses and visualization by CAPER 2.0. We illustrate the usage of CAPER 2.0 with four specific workflows for finding missing proteins, mapping peptides to chromosomes for genome annotation, integrating peptides with transcription factor binding sites from ENCODE data sets, and functionally annotating proteins. The updated CAPER is available at http://www.bprc.ac.cn/CAPE.
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http://dx.doi.org/10.1021/pr400795cDOI Listing
January 2014

Diphenytoin, riluzole and lidocaine: three sodium channel blockers, with different mechanisms of action, decrease hippocampal epileptiform activity.

Neuropharmacology 2013 Oct 21;73:48-55. Epub 2013 May 21.

University of Colorado Anschutz Medical Campus, Mailstop 8105, PO Box 6511, Aurora, CO 80045, USA.

Epilepsy is a condition affecting 1-2% of the population, characterized by the presence of spontaneous, recurrent seizures. The most common type of acquired epilepsy is temporal lobe epilepsy (TLE). Up to 30% of patients with TLE are refractory to currently available compounds, and there is an urgent need to identify novel targets for therapy. Here, we utilized the in-vitro CA3 burst preparation to examine alterations in network excitability, characterized by changes in interburst interval. Specifically, we show that bath application of three different sodium channel blockers-diphenytoin, riluzole, and lidocaine-slow spontaneous CA3 bursts. This in turn, decreased the epileptiform activity. These compounds work at different sites on voltage-gated sodium channels, but produce a similar network phenotype of decreased excitability. In the case of diphenytoin and riluzole, the change in network activity (i.e., increased interburst intervals) was persistent following drug washout. Lidocaine application, however, only increased the CA3 interburst interval when it was in the bath solution. Thus, its action was not permanent and resulted in returning CA3 bursting to baseline levels. These data demonstrate that the CA3 burst preparation provides a relatively easy and quick platform for identifying compounds that can decrease network excitability, providing the initial screen for further and more complex in-vivo, freely-behaving animal studies.
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http://dx.doi.org/10.1016/j.neuropharm.2013.04.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766392PMC
October 2013

Cyclic water clusters in tape-like and cage-like structures.

Molecules 2011 Apr 4;16(4):2871-83. Epub 2011 Apr 4.

College of Chemistry and Ecological Engineering, Guangxi University for Nationalities, Nanning 530006, China.

Controlling the ratio of 2,2'-bpy to benzene-1,3,5-tricarboxylic acid produces two interesting complexes, namely [Co(2,2'-bpy)₃]·(SO₄)·8.5H₂O (1) and [Cu₂(BTCA) (2,2'-bpy)₄] (OH)·(2,2'-bpy)₀.₅·14H₂O (2) (H₃BTCA = benzene-1,3,5-tricarboxylic acid, 2,2'-bpy = 2,2'-bipyridine). We report the structural evidence in the solid state of discrete lamellar water cluster conformations. These units are found to act as supramolecular glue in the aggregation of cobalt (II) or copper (II) complexes to give three dimensional cage-like networks through hydrogen-bonding. It is interesting that the structure of complex 1 contains a 3D negatively charged cage.
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http://dx.doi.org/10.3390/molecules16042871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260625PMC
April 2011

Housing environments and child health conditions among recent Mexican immigrant families: a population-based study.

J Immigr Minor Health 2010 Oct;12(5):617-25

Department of Environmental & Occupational Health, Colorado School of Public Health, University of Colorado Denver, Denver, CO 80045, USA.

The influx of immigrants to urban areas throughout the United States has raised concerns about accessibility of safe, affordable housing and the health consequences of poor-quality housing, particularly among immigrant children. We conducted a population-based study of home environmental conditions among recently immigrated Mexican families (weighted n = 473), generally of low socioeconomic status, and the health conditions of their children, in an urban industrial area north of Denver, Colorado. The majority of recent immigrants had low socioeconomic status; virtually all had household incomes below the Colorado median ($50,841). Approximately one quarter of homes were overcrowded. Adverse environmental conditions were present across recent immigrant homes. These conditions include dampness or mold (44%), pests (28%), and minimal to no ventilation potential (26%), all of which are associated with asthma and atopic diseases. At least one of these three environmental hazards was found in 67% of homes; multiple hazards were present in 27% of homes. Children of recent immigrant families had active symptoms within the past 12 months suggestive of asthma (4%) and atopic disorders (10%); however, fewer than 2% had been diagnosed with these conditions. The prevalence of asthma and atopic symptoms among Mexican immigrant children, albeit lower than in other low income and minority communities, is partially explained by housing conditions. Many of the conditions identified (e.g., pest infestation, mold resulting from plumbing leaks, and lack of exhaust fans) are amenable to low cost interventions. Solutions to address unhealthy housing conditions among recent immigrants must be multi-faceted and include strategies that target household-level improvements and access to health care.
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http://dx.doi.org/10.1007/s10903-009-9261-8DOI Listing
October 2010

Synaptic GABAergic and glutamatergic mechanisms underlying alcohol sensitivity in mouse hippocampal neurons.

J Physiol 2006 Aug 8;575(Pt 1):145-59. Epub 2006 Jun 8.

VA Eastern Colorado Health Care System, Denver, CO80220, USA.

This study was designed to examine the neuronal mechanisms of ethanol sensitivity by utilizing inbred short sleep (ISS) and inbred long sleep (ILS) mouse strains that display large differences in sensitivity to the behavioural effects of ethanol. Comparisons of whole-cell electrophysiological recordings from CA1 pyramidal neurons in hippocampal slices of ISS and ILS mice indicate that ethanol enhances GABAA receptor-mediated inhibitory postsynaptic currents (GABAA IPSCs) and reduces NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) in a concentration- and strain-dependent manner. In ILS neurons, these receptor systems are significantly more sensitive to ethanol than those in ISS neurons. To further examine the underlying mechanisms of differential ethanol sensitivities in these mice, GABAB activity and presynaptic and postsynaptic actions of ethanol were investigated. Inhibition of GABAB receptor function enhances ethanol-mediated potentiation of distal GABAA IPSCs in ILS but not ISS mice, and this blockade of GABAB receptor function has no effect on the action of ethanol on NMDA EPSCs in either mouse strain. Thus, subregional differences in GABAB activity may contribute to the differential ethanol sensitivity of ISS and ILS mice. Moreover, analysis of the effects of ethanol on paired-pulse stimulation, spontaneous IPSC events, and brief local GABA or glutamate application suggest that postsynaptic rather than presynaptic mechanisms underlie the differential ethanol sensitivity of these mice. Furthermore, these results provide essential information to focus better on appropriate target sites for more effective drug development for the treatment of alcohol abuse.
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http://dx.doi.org/10.1113/jphysiol.2006.112730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819416PMC
August 2006

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly.

Synapse 2005 Jul;57(1):8-16

Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neuroscience, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.

Using mice with a targeted disruption of the adenosine A1 receptor (A1R), we examined the role of A1Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A1 receptor knockout (A1R-/-), heterozygote (A1R+/-), and wildtype (A1R+/+) mice. However, paired pulse facilitation was impaired significantly in A1R-/- slices as compared to A1R+/+ slices. LTD in the CA1 region was unaffected by the genetic manipulation. The three genotypes showed similar memory acquisition patterns when assessed for spatial reference and working memory in the Morris water maze tasks at 9 months of age. However, 10 months later A1R-/- mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine A1R knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model.
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http://dx.doi.org/10.1002/syn.20146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213905PMC
July 2005

Modulation of hippocampal glutamatergic transmission by ATP is dependent on adenosine a(1) receptors.

J Pharmacol Exp Ther 2002 Oct;303(1):356-63

Department of Pharmacology and Program in Neuroscience, University of Colorado Health Sciences Center, Denver 80262, USA.

Excitatory glutamatergic synapses in the hippocampal CA1 region of rats are potently inhibited by purines, including adenosine, ATP, and ATP analogs. Adenosine A(1) receptors are known to mediate at least part of the response to adenine nucleotides, either because adenine nucleotides activate A(1) receptors directly, or activate them secondarily upon the nucleotides' conversion to adenosine. In the present studies, the inhibitory effects of adenosine, ATP, the purportedly stable ATP analog adenosine-5'-O-(3-thio)triphosphate (ATPgammaS), and cyclic AMP were examined in mice with a null mutation in the adenosine A(1) receptor gene. ATPgammaS displaced the binding of A(1)-selective ligands to intact brain sections and brain homogenates from adenosine A(1) receptor wild-type animals. In homogenates, but not in intact brain sections, this displacement was abolished by adenosine deaminase. In hippocampal slices from wild-type mice, purines abolished synaptic responses, but slices from mice lacking functional A(1) receptors showed no synaptic modulation by adenosine, ATP, cAMP, or ATPgammaS. In slices from heterozygous mice the dose-response curve for both adenosine and ATP was shifted to the right. In all cases, inhibition of synaptic responses by purines could be blocked by prior treatment with the competitive adenosine A(1) receptor antagonist 8-cyclopentyltheophylline. Taken together, these results show that even supposedly stable adenine nucleotides are rapidly converted to adenosine at sites close to the A(1) receptor, and that inhibition of synaptic transmission by purine nucleotides is mediated exclusively by A(1) receptors.
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http://dx.doi.org/10.1124/jpet.102.036731DOI Listing
October 2002
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