MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
Background: Epidemiological knowledge is very poor in regards to anorectal disorders. The patients do not often discuss perianal symptoms leading to late diagnosis and treatment. There is a need of doing systematic questioning and clinical evaluation of the population to assess the prevalence of anorectal disorders.
Aim and objectives: The aim of this study is to assess the prevalence of anorectal disorders among the residents of Kirtipur municipality in Nepal.
Methods: The first section was the cross-sectional survey to assess the demographic and lifestyle characteristics of the study population. The second section was the observation study to assess the prevalence of anorectal symptoms. 1483 patients were recruited from 10 wards of Kirtipur municipality. We analyzed the comparison of diagnostic approach between patients with perianal symptoms spontaneously visited and those revealed after targeted questioning. We further analyzed the reason for not performing perianal examination by both patients and general practitioners. Factors associated with referral to a proctologist and diagnosis rate were also evaluated.
Results: The study showed that the prevalence of anorectal symptoms increased from 9.4% to 21.2% after systematic targeted questioning by general practitioners. Spice intake was the only covariate associated with decrease risk of proctological symptoms. Haemorrhoids (31.2%) and anal fissure (28.7%) were the most prevalent anorectal disorders. However, physicians have diagnosed anorectal disorders in 20.2% of patients without performing any perianal examination. Diagnosis of haemorrhoids and fistula in ano were significantly associated with referral to a proctologist.
Conclusion: This study may contribute to epidemiological knowledge about the prevalence of anorectal disorders among Nepalese population.
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
The feed-forward loop (FFL) is an important and basic network motif to understand specific biological functions. Cyclic-AMP (cAMP) receptor protein (CRP), a transcription factor (TF), mediates catabolite repression and regulates more than 400 genes in response to changes in intracellular concentrations of cAMP in Escherichia coli. CRP participates in some FFLs like araBAD and araFGH operons and adapt to fluctuating environmental nutrients thus enhancing the survivability of E. coli. Although computational simulations have been used to explore the potential functionality of FFLs, a comprehensive study of the functions of all structural types based on in vivo data is lacking. Also, the regulatory role of CRP-mediated feed-forward loops (CRP-FFLs) remain unclear to date. Using EcoCyc and RegulonDB, we identified 393 CRP-FFLs in the E. coli. Dose-response genomic microarray of E. coli revealed dynamic gene expression of each target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types of FFLs were present in CRP regulon with various expression patterns of each CRP-FFL, that were further divided into five functional groups. Microarray and reported regulatory relationships identified 202 CRP-FFLs which were directly regulated by CRP in these eight types of FFLs. Interestingly, 30% (147/482) of genes were directly regulated by CRP and CRP-regulated TFs, indicating that these CRP-regulated genes were also regulated by other CRP-regulated TFs responding to environmental signals through CRP-FFLs. Furthermore, we applied gene ontology annotation to reveal the biological functions of CRP-FFLs.
Introduction: In the United States and Europe, endometrial endometrioid carcinoma (EEC) is the most prevalent gynecologic malignancy. Lymph node metastasis (LNM) is the key determinant of the prognosis and treatment of EEC. A biomarker that predicts LNM in patients with EEC would be beneficial, enabling individualized treatment. Current preoperative assessment of LNM in EEC is not sufficiently accurate to predict LNM and prevent overtreatment. This pilot study established a biomarker signature for the prediction of LNM in early stage EEC. Methods: We performed RNA sequencing in 24 clinically early stage (T1) EEC tumors (lymph nodes positive and negative in 6 and 18, respectively) from Cathay General Hospital and analyzed the RNA sequencing data of 289 patients with EEC from The Cancer Genome Atlas (lymph node positive and negative in 33 and 256, respectively). We analyzed clinical data including tumor grade, depth of tumor invasion, and age to construct a sequencing-based prediction model using machine learning. For validation, we used another independent cohort of early stage EEC samples (n = 72) and performed quantitative real-time polymerase chain reaction (qRT-PCR). Finally, a PCR-based prediction model and risk score formula were established. Results: Eight genes (ASRGL1, ESR1, EYA2, MSX1, RHEX, SCGB2A1, SOX17, and STX18) plus one clinical parameter (depth of myometrial invasion) were identified for use in a sequencing-based prediction model. After qRT-PCR validation, five genes (ASRGL1, RHEX, SCGB2A1, SOX17, and STX18) were identified as predictive biomarkers. Receiver operating characteristic curve analysis revealed that these five genes can predict LNM. Combined use of these five genes resulted in higher diagnostic accuracy than use of any single gene, with an area under the curve of 0.898, sensitivity of 88.9%, and specificity of 84.1%. The accuracy, negative, and positive predictive values were 84.7%, 98.1%, and 44.4%, respectively. Conclusion: We developed a five-gene biomarker panel associated with LNM in early stage EEC. These five genes may represent novel targets for further mechanistic study. Our results, after corroboration by a prospective study, may have useful clinical implications and prevent unnecessary elective lymph node dissection while not adversely affecting the outcome of treatment for early stage EEC.
Background: Kayachikitsa is one of the most important specialized departments in an Ayurvedic hospital. A number of patients get effective, affordable and safe Ayurvedic services from Out Patient Department (OPD). Objective: the major objective of this study was to find out the treated disease pattern, frequency of patients who got benefits from treatments and services provided in the OPD of Kayachikitsa department. Methods: The study was analytical retrospective in nature where analysis of registered patients’ case record of Kaya Chikitsa OPD during the period of May 15 to November 15 of year 2018 AD. Results: Despite of good number of patients visiting in the OPD of Kayachikitsa department, patients of different diseases visited and treated with Ayurvedic medications, due to lack of good publicity and awareness in general population about wide range of treatments available for various diseases in Kayachikitsa department. The follow up cases were also good. Conclusions: The study showed the Kayachikitsa department provided services to various diseases, health services to senior citizens. The follow up cases were also better suggestive of good quality services. Hence improving the services and conducting awareness program can provide better Ayurvedic health services to many needy people.
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