Monitoring serum IL-18 levels is useful for treatment of a patient with systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome

Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease characterized by arthritis, spiking fever and a skin rash that is frequently complicated by macrophage activation syndrome (MAS), a life-threatening disorder. We report a 22-month-old girl with sJIA who developed severe MAS but was successfully treated with corticosteroids, cyclosporin A, and non-steroidal anti-inflammatory drugs by monitoring serum IL-18 levels. IL-18 is an extremely useful cytokine for monitoring the activity of sJIA and MAS, and serum IL-18 can be used as an indicator for the effectiveness of treatment and the decision to discontinue therapy.ArticlePEDIATRIC RHEUMATOLOGY. 9:15 (2011)journal articl

Review of Evidence Suggesting That the Fascia Network Could Be the Anatomical Basis for Acupoints and Meridians in the Human Body

The anatomical basis for the concept of meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the evidence supporting a relationship between acupuncture points/meridians and fascia. The reviewed evidence supports the view that the human body's fascia network may be the physical substrate represented by the meridians of TCM. Specifically, this hypothesis is supported by anatomical observations of body scan data demonstrating that the fascia network resembles the theoretical meridian system in salient ways, as well as physiological, histological, and clinical observations. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Epigenetic crosstalk between DNA demethylation and histone acetylation

Abnormal methylation patterns such as regional hypermethylation and genomic hypomethylation often result in transcriptional changes of critical genes that are central to the progression of human cancers. It is therefore important to identify the mechanisms that are responsible for the alterations in order to identify proper pharmacological targets. This thesis examines whether specific cellular factors are involved in establishing the state of DNA hypomethylation in cancer cells and whether changes in chromatin structure could affect DNA methylation. MBD2 is a protein that has been previously characterized to possess distinct transcription activities; it can either function as a methylation-dependent transcription repressor, a methylation-independent transcription activator, as well as an inducer of DNA demethylation. Chapters 3 and 4 demonstrate that MBD2 induces gene-specific DNA demethylation in pancreatic and bladder cancer cells by recruiting transcriptional activator AP-2, Sp1 and the histone acetyltransferase CBP to the associated promoters. These results substantiate the idea that demethylation induced by MBD2 might facilitate the recruitment of transcription factors to the gene to activate its expression. Histone deacetylase (HDAC) inhibitors are drugs designed to target chromatin modification. In chapter 5, we showed that increasing histone acetylation by HDAC inhibitor TSA was associated with a significant decrease in global methylation. TSA also induces histone acetylation, DNA demethylation and expression of specific methylated tumor suppressor genes, such as E-CADHERIN and RARβ2 in different human cancer cell lines. Our findings provide evidence for aUn patron de méthylation anormal, tel que l'hyperméthylation régionale ou l'hypométhylation génomique, modifie la transcription de gènes critiques jouant ainsi un rôle central dans la progression de nombreux cancers chez l'humain. Il est donc devenu essentiel d'identifier les mécanismes responsables de ces altérations afin de développer des traitements pharmacologiques ciblés. Le but principal de cette thèse est d'examiner si certains facteurs cellulaires sont impliqués dans l'établissement de l'ADN hypométhylé des cellules cancéreuses, ainsi que l'effet des changements dans la structure de la chromatine sur la méthylation de l'ADN. Il a été préalablement démontré que la protéine MBD2 possède plusieurs rôles distincts lors de la transcription, elle peut agir à la fois comme un répresseur de la transcription dépendant de la méthylation, comme un inducteur de la déméthylation ainsi qu'un activateur de la transcription indépendant de la méthylation. Les chapitres 3 et 4 présentés dans cet ouvrage démontrent que MBD2 induit la déméthylation de gènes spécifiques dans les cellules cancéreuses pancréatiques et urinaires grâce au recrutement des activateurs transcriptionnels AP-2, Sp1 ainsi que de l'histone acétyltransférase CBP au promoteur impliqué. Ces résultats supportent l'hypothèse selon laquelle la déméthylation induite par MBD2 faciliterait le recrutement de facteurs de transcription au sein du gène afin d'activer son expression. Les inhibiteurs de l'Histone déacétylase (HDAC) sont des drogues pharmaceutiques développées afin de cibler les modifications de la chromatine. Nous sommes parvenus à démontrer, dans l

Characteristic analysis of skin keratinocytes in patients with type 2 diabetes based on the single-cell levels

Abstract. Background:. Keratinocytes play an important role in wound healing; however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions. Methods:. We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody™ Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes. Results:. In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons’ diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum. Conclusions:. This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways