Antibacterial activity and physicochemical properties of a sealer containing copaiba oil.

This study aimed to evaluate the antimicrobial activity and physicochemical properties of a novel dual-cure endodontic sealer containing copaiba oil. The copaiba oil was obtained and characterized by gas chromatography (GC), and the minimum inhibitory concentration (MIC) was performed. The experimental sealers were formulated with copaiba oil concentrations of 0, 0.5, 1, and 2%, and the RealSeal™ (Sybron endo, Orange, USA) and AH Plus (Dentsply De Trey Gmbh, Konstanz, Germany) were used as the commercial references. The antimicrobial activity of the sealers was evaluated by the direct contact test for 1h and 24h. To evaluate the physicochemical properties of the sealers, the degree of conversion, setting time, film thickness, dimensional stability, and radiopacity tests were performed. The data were statistically analyzed by one-way ANOVA and Tukey's test (α = 0.05). Concerning the results, the sealers containing copaiba oil showed antimicrobial activity without harming the physicochemical properties.

Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma.

SUMOylation is a post-translational modification of proteins that regulates these proteins' localization, turnover or function. Aberrant SUMOylation is frequently found in cancers but its origin remains elusive. Using a genome-wide transposon mutagenesis screen in a MYC-driven B-cell lymphoma model, we here identify the SUMO isopeptidase (or deconjugase) SENP6 as a tumor suppressor that links unrestricted SUMOylation to tumor development and progression. Notably, SENP6 is recurrently deleted in human lymphomas and SENP6 deficiency results in unrestricted SUMOylation. Mechanistically, SENP6 loss triggers release of DNA repair- and genome maintenance-associated protein complexes from chromatin thereby impairing DNA repair in response to DNA damages and ultimately promoting genomic instability. In line with this hypothesis, SENP6 deficiency drives synthetic lethality to Poly-ADP-Ribose-Polymerase (PARP) inhibition. Together, our results link SENP6 loss to defective genome maintenance and reveal the potential therapeutic application of PARP inhibitors in B-cell lymphoma.

GeneTrail: A Framework for the Analysis of High-Throughput Profiles.

Experimental high-throughput techniques, like next-generation sequencing or microarrays, are nowadays routinely applied to create detailed molecular profiles of cells. In general, these platforms generate high-dimensional and noisy data sets. For their analysis, powerful bioinformatics tools are required to gain novel insights into the biological processes under investigation. Here, we present an overview of the GeneTrail tool suite that offers rich functionality for the analysis and visualization of (epi-)genomic, transcriptomic, miRNomic, and proteomic profiles. Our framework enables the analysis of standard bulk, time-series, and single-cell measurements and includes various state-of-the-art methods to identify potentially deregulated biological processes and to detect driving factors within those deregulated processes. We highlight the capabilities of our web service with an analysis of a single-cell COVID-19 data set that demonstrates its potential for uncovering complex molecular mechanisms. GeneTrail can be accessed freely and without login requirements at http://genetrail.bioinf.uni-sb.de.

A pragmatic randomised controlled trial referring to a Personalised Self-management SUPport Programme (P-SUP) for persons enrolled in a disease management programme for type 2 diabetes mellitus and/or for coronary heart disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) are two chronic diseases that cause a tremendous burden. To reduce this burden, several programmes for optimising the care for these diseases have been developed. In Germany, so-called disease management programmes (DMPs), which combine components of Disease Management and the Chronic Care Model, are applied. These DMPs have proven effective. Nevertheless, there are opportunities for improvement. Current DMPs rarely address self-management of the disease, make no use of peer support, and provide no special assistance for persons with low health literacy and/or low patient activation. The study protocol presented here is for the evaluation of a programme that addresses these possible shortcomings and can be combined with current German DMPs for T2DM and CHD. This programme consists of four components: 1) Meetings of peer support groups 2) Personalised telephone-based health coaching for patients with low literacy and/or low patient activation 3) Personalised patient feedback 4) A browser-based web portal METHODS: Study participants will be adults enrolled in a DMP for T2DM and/or CHD and living in North Rhine-Westphalia, a state of the Federal Republic of Germany. Study participants will be recruited with the assistance of their general practitioners by the end of June 2021. Evaluation will be performed as a pragmatic randomised controlled trial with one intervention group and one waiting control group. The intervention group will receive the intervention for 18 months. During this time, the waiting control group will continue with usual care and the usual measures of their DMPs. After 18 months, the waiting control group will also receive a shortened intervention. The primary outcome is number of hospital days. In addition, the effects on self-reported health-state, physical activity, nutrition, and eight different psychological variables will be investigated. Differences between values at month 18 and at the beginning will be compared to judge the effectiveness of the intervention. DISCUSSION: If the intervention proves effective, it may be included into the DMPs for T2DM and CHD. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) in early 2019 under the number 00020592. This registry has been affiliated with the WHO Clinical Trials Network ( https://www.drks.de/drks_web/setLocale_EN.do ) since 2008. It is based on the WHO template, but contains some additional categories for which information has to be given ( https://www.drks.de/drks_web/navigate.do?navigationId=entryfields&messageDE=Beschreibung%20der%20Eingabefelder&messageEN=Description%20of%20entry%20fields ). A release and subsequent number assignment only take place when information for all categories has been given.

MERIDA: a novel Boolean logic-based integer linear program for personalized cancer therapy.

MOTIVATION: A major goal of personalized medicine in oncology is the optimization of treatment strategies given measurements of the genetic and molecular profiles of cancer cells. To further our knowledge on drug sensitivity, machine learning techniques are commonly applied to cancer cell line panels. RESULTS: We present a novel integer linear programming formulation, called MEthod for Rule Identification with multi-omics DAta (MERIDA), for predicting the drug sensitivity of cancer cells. The method represents a modified version of the LOBICO method and yields easily interpretable models amenable to a Boolean logic-based interpretation. Since the proposed altered logical rules lead to an enormous acceleration of the running times of MERIDA compared to LOBICO, we cannot only consider larger input feature sets integrated from genetic and molecular omics data but also build more comprehensive models that mirror the complexity of cancer initiation and progression. Moreover, we enable the inclusion of a priori knowledge that can either stem from biomarker databases or can also be newly acquired knowledge gathered iteratively by previous runs of MERIDA. Our results show that this approach does not only lead to an improved predictive performance but also identifies a variety of putative sensitivity and resistance biomarkers. We also compare our approach to state-of-the-art machine learning methods and demonstrate the superior performance of our method. Hence, MERIDA has great potential to deepen our understanding of the molecular mechanisms causing drug sensitivity or resistance. AVAILABILITY AND IMPLEMENTATION: The corresponding code is available on github (https://github.com/unisb-bioinf/MERIDA.git). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Antimicrobial and physical properties of experimental endodontic sealers containing vegetable extracts.

To assess the antimicrobial activity and the physical properties of resin-based experimental endodontic sealers with the incorporation of vegetable extracts obtained from Bixa orellana, Mentha piperita, and Tagetes minuta species. The extracts were obtained and characterized by gas chromatography-mass spectrometry (GC-MS), and minimum inhibitory concentration (MIC) against Streptococcus mutans, Enterococcus faecalis, and Candida albicans. The extracts were individually incorporated into a dual-cure experimental sealer at a mass concentration of 0.5%. A commercial reference RealSeal was used. The sealers were evaluated by measuring the setting time, degree of conversion, dimensional stability, radiopacity, flow, and film thickness of these materials, also and its antimicrobial effect was evaluated using the direct contact test. Data were statistically analyzed by analysis of variance and Tukey's post-hoc test at α = 0.05 significance level. The physical properties were not influenced by the addition of the vegetable extracts (p > 0.05). For S. mutans, only T. minuta and B. orellana groups presented antibacterial activity after 24 h of contact (p < 0.05). All extracts evidenced an antibacterial effect against E. faecalis (p < 0.05). The experimental sealers hold promise as a novel vegetable sealer with great antimicrobial activity and also great physical-mechanical properties. Nonetheless, more studies are needed.

SUMO pathway inhibition targets an aggressive pancreatic cancer subtype.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies. DESIGN: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC. RESULTS: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition. CONCLUSION: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype.

Strategies and Challenges in Recruiting Pregnant Women with Elevated Body Mass Index for a Behavioral Lifestyle Intervention.

Purpose: Pregnant women with elevated body mass index (BMI) are difficult to recruit into lifestyle studies. This article (1) summarized strategies to recruit pregnant women into a randomized trial, and (2) reported recruitment statistics and their correlates. Materials and Methods: African American and white women with BMI ≥25 and gestational age <16 weeks were recruited primarily through obstetric clinics into the Health in Pregnancy and Postpartum study. Women completed a brief screening form, and if initially eligible, a phone screening. We compared characteristics of those randomized versus not randomized. Results: Initially eligible pregnant women (N = 1578) were identified through direct recruitment by research staff, indirect recruitment by clinic staff at obstetric clinics, and self-referrals through advertisements. Of these women, 54.0% (850) were reached for further screening, and 43.5% (685) were fully eligible. Among eligible women, 58.8% (403) were scheduled for a baseline visit, and 33.3% (228) were randomized. The overall recruitment yield was 14.4%. Recruited participants were diverse (44% African Americans) and averaged 12.6 weeks gestation at baseline. Randomized (vs. nonrandomized) women were more likely to own a cell phone, have access to a computer with internet at home or work, and have downloaded a podcast. Conclusions: Although this study did not reach the recruitment goal, a relatively large and diverse sample of pregnant women were recruited early in pregnancy. Recruiting women with elevated BMI for a behavioral lifestyle intervention is challenging, particularly among women with characteristics, including less phone and internet access and limited experience in using podcasts. This study is registered at Clinicaltrials.gov: NCT02260518.

Dietary sodium, potassium, and blood pressure in normotensive pregnant women: the National Health and Nutrition Examination Survey.

Dietary sodium, potassium, and sodium-to-potassium ratio are linearly associated with blood pressure in nonpregnant adults. Earlier investigations suggested null or inverse associations of blood pressure and sodium during normotensive pregnancy; findings have not been confirmed in race/ethnically diverse women or while accounting for potassium. Our purpose was to evaluate associations of blood pressure with sodium and potassium and sodium-to-potassium ratio in race/ethnically diverse normotensive pregnant women. We used cross-sectional blood pressure and dietary data from 984 women in multiple cycles of the National Health and Nutrition Examination Survey (mean age = 27.6 ± 0.2 years). We tested for differences in blood pressure across quartiles of sodium intake using Kruskal-Wallis tests and linear regression to evaluate associations of sodium, potassium, and the sodium-to-potassium ratio with systolic (SBP) and diastolic (DBP) blood pressures. We adjusted for potential confounding variables: age, race/ethnicity, education, marital status, body mass index, smoking, and month of pregnancy. SBP and DBP were similar across quartiles of sodium intake: quartile 1 (lowest sodium intake): 107/59; quartile 2: 106/59; quartile 3: 108/60; quartile 4 (highest sodium intake): 108/58 mm Hg, p > 0.60 for all. Sodium (ß = 0.16, 95% confidence interval (CI): -0.20 to 0.52) and potassium (ß = 0.18, 95% CI: -0.24 to 0.60) and the sodium-to-potassium ratio (ß = -0.54, 95% CI: -1.55 to 0.47) were not associated with SBP or DBP. Results were similar in stratified analyses. Novelty Blood pressure was similar among quartiles of sodium or potassium intake, even in analyses stratified by race/ethnicity and trimester of pregnancy. There was no association of sodium or potassium with blood pressure. Blood pressure may be insensitive to dietary sodium and potassium during normotensive pregnancy.

ClinOmicsTrailbc: a visual analytics tool for breast cancer treatment stratification.

MOTIVATION: Breast cancer is the second leading cause of cancer death among women. Tumors, even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process. RESULTS: Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates for drug repositioning and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the tumor's main driver mutations, the tumor mutational burden, activity patterns of core cancer-relevant pathways, drug-specific biomarkers, the status of molecular drug targets and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbc's rich functionality, we present three case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best possible treatment options for their breast cancer patients based on actionable, evidence-based results. AVAILABILITY AND IMPLEMENTATION: ClinOmicsTrailbc can be freely accessed at https://clinomicstrail.bioinf.uni-sb.de. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Use of rice husk in waste cooking oil pretreatment.

Since industrial wastes are increasing, the development of studies to find ways for their use is urgent. Waste cooking oil is an important source for the production of biodiesel, one of the main biofuels in Brazil. However, during cooking, the oil undergoes conditions that change its properties and decrease its quality, such as its acidity value. Current research treats waste cooking oil by the adsorption process using rice husk, an agro-industrial waste, and activated carbon to compare results. The potential of the adsorbents to remove free fatty acids in waste cooking oil has been investigated by the batch technique, evaluating different operating conditions of temperature, adsorbent mass and agitation. Adsorbents were characterized by nitrogen physisorption, scanning electron microscope, energy-dispersive spectroscopy and X-ray diffraction. The maximum result obtained for activated carbon at acidity reduction was 63%, using 22.4°C, 169.64 rpm and 3.39 g of adsorbent mass. Already, using the rice husk the percentage of removal was the same, 63% using 22.4°C, 80.36 rpm and 1.61 g of adsorbent, however in shorter times. The results prove that the application of the rice husk for this purpose is advantageous, for being a low-cost material, available on a large scale and that provide results similar to activated carbon.

Evaluation of different adsorbents for acidity reduction in residual oils.

This work aims to evaluate the adsorption potential of bentonite and sugarcane bagasse clay for the reduction of free fatty acids in cooking oil through batch technique, experimental planning with different operating conditions (temperature, adsorbent mass and agitation). After were carried out kinetic studies and thermodynamic studies. Thus, both adsorbents were characterized by nitrogen dispersion, scanning electron microscopy with coupled energy dispersion spectroscopy. The sugarcane bagasse provided higher reductions compared to the bentonite clay, 58 and 50%, respectively. In the kinetic studies, it was observed that the pseudo-secunda model for both materials. Among the isotherms studied, the Langmuir model was better adjusted for sugarcane bagasse and Freundlich for bentonite clay. Thermodynamic parameters indicated spontaneous and endothermic adsorption at temperatures of 18°C, 20°C and 25°C. Both materials showed an advantageous result with the reduction to the adsorption of free fatty acids in the residual oil, considering that they are low-cost materials, their pre-treatment is simple from the operational point of view and their physical and chemical characteristics are favorable to the adsorption process, sugarcane bagasse contains about 42% hemicellulose, which is a hydroxyl-rich material that attracts the H+ ions from the medium.

Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP.

BACKGROUND: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. METHODS: Data from the population-based, case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. RESULTS: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). CONCLUSIONS: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.

The role of TCF3 as potential master regulator in blastemal Wilms tumors.

Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.

REGGAE: a novel approach for the identification of key transcriptional regulators.

Motivation: Transcriptional regulators play a major role in most biological processes. Alterations in their activities are associated with a variety of diseases and in particular with tumor development and progression. Hence, it is important to assess the effects of deregulated regulators on pathological processes. Results: Here, we present REGulator-Gene Association Enrichment (REGGAE), a novel method for the identification of key transcriptional regulators that have a significant effect on the expression of a given set of genes, e.g. genes that are differentially expressed between two sample groups. REGGAE uses a Kolmogorov-Smirnov-like test statistic that implicitly combines associations between regulators and their target genes with an enrichment approach to prioritize the influence of transcriptional regulators. We evaluated our method in two different application scenarios, which demonstrate that REGGAE is well suited for uncovering the influence of transcriptional regulators and is a valuable tool for the elucidation of complex regulatory mechanisms. Availability and implementation: REGGAE is freely available at https://regulatortrail.bioinf.uni-sb.de. Supplementary information: Supplementary data are available at Bioinformatics online.

A randomized controlled trial to prevent excessive gestational weight gain and promote postpartum weight loss in overweight and obese women: Health In Pregnancy and Postpartum (HIPP).

BACKGROUND: Interventions to prevent excessive gestational weight gain and promote postpartum weight loss have yielded modest results, particularly in overweight and obese women. OBJECTIVES: To examine the impact of a theory-based lifestyle intervention on gestational weight gain, postpartum weight loss, and related maternal and child outcomes and to examine race differences in these outcomes. DESIGN: A randomized controlled trial (target N=400; 200 intervention, 200 standard care; 200 African American, 200 white). METHODS: Overweight and obese African American and white women ≤16weeks gestation are recruited from obstetrics and gynecology clinics in South Carolina. Intervention participants receive two in-depth counseling sessions (early pregnancy and postpartum), telephone counseling, behavioral podcasts, and social media support that target weight self-monitoring and increasing physical activity and healthy dietary behavior practices, guided by Social Cognitive Theory. Standard care participants receive monthly mailings and a matched number of podcasts on non-weight related topics. All intervention activities last from ≤18weeks gestation to 6months after delivery. Gestational weight gain is the primary outcome. Secondary outcomes are meeting gestational weight gain guidelines (inadequate, adequate, excessive), weekly rate of gestational weight gain, postpartum weight retention, physical activity and dietary behaviors, health-related quality of life, and offspring adiposity. Participants are assessed at baseline (≤16weeks gestation), 32weeks gestation, and 6 and 12months postpartum, and offspring are assessed at 6 and 12months. SUMMARY: HIPP is an innovative study that addresses significant gaps in the literature. Primary outcome results are expected in 2019.

The Phytochemistry and Pharmacology of Butia sp.: A Systematic Review and an Overview of the Technological Monitoring Process.

The Butia sp. are native South America trees, whose fruits are consumed in natura and have significant biological properties; however, trees of this genus plant are in danger of extinction. A systematic review of the literature and a technological overview were carried out to summarize the available evidence on the therapeutic uses and the phytochemical compounds of Butia sp. The following electronic databases were researched: MedLine (PubMed), Web of Science, Scopus, Scielo, and the gray literature. Furthermore, the online system such as the US Patent and Trademark Office, Espacenet, National Institute of Industrial Property, and Google Patents were accessed to obtain patent data. The inclusion criteria were articles that describe either the therapeutic uses of Butia sp. (antimicrobial activity, antioxidant activity, anti-inflammatory activity, antineoplastic activity) or studies describing phytochemical compounds of Butia sp. A limited amount of manual search was also undertaken. Reference lists were scanned to identify other relevant studies, and requests for unpublished data were conducted to people working in the field. Among 12 papers and 14 patents, 9 complete texts of scientific articles and 1 patent were scrutinised by two reviewers. We concluded that Butia has shown some antioxidant, anti-inflammatory, and antimicrobial activity, and its use could have important implications for future therapeutic uses. Although there is evidence of pharmacological potential from in vitro studies, clinical studies must be conducted to confirm the effectiveness of Butia sp. The evidence of its therapeutic uses has not been extensively studied yet, and the available evidence still needs further confirmation. Copyright © 2017 John Wiley & Sons, Ltd.

Systematic review and technological overview of the antimicrobial activity of Tagetes minuta and future perspectives.

ETHNOPHARMACOLOGICAL RELEVANCE: The antimicrobial potential of Tagetes minuta was correlated with its traditional use as antibacterial, insecticidal, biocide, disinfectant, anthelminthic, antifungal, and antiseptic agent as well as its use in urinary tract infections. AIM OF THE STUDY: This study aimed to systematically review articles and patents regarding the antimicrobial activity of T. minuta and give rise to perspectives on this plant as a potential antimicrobial agent. MATERIALS AND METHODS: A literature search of studies published between 1997 and 2015 was conducted over five databases: MedLine (PubMed), Web of Science, Scopus, Google Scholar, Portal de Periódicos Capes and SciFinder, grey literature was explored using the System for Information on Dissertations database, and theses were searched using the ProQuest Dissertations and Theses Full text database and the Periódicos Capes Theses database. Additionally, the following databases for patents were analysed: United States Patent and Trademark Office (USPTO), Google Patents, National Institute of Industrial Property (INPI) and Espacenet patent search (EPO). The data were tabulated and analysed using Microsoft Office Excel 2010. RESULTS: After title screening, 51 studies remained and this number decreased to 26 after careful examinations of the abstracts. The full texts of these 26 studies were assessed to check if they were eligible. Among them, 3 were excluded for not having full text access, and 11 were excluded because they did not fit the inclusion criteria, which left 10 articles for this systematic review. The same process was conducted for the patent search, resulting in 4 patents being included in this study. CONCLUSION: Recent advances highlighted by this review may shed light on future directions of studies concerning T. minuta as a novel antimicrobial agent, which should be repeatedly proven in future animal and clinical studies. Although more evidence on its specificity and clinical efficacy are necessary to support its clinical use, T. minuta is expected to be a highly effective, safe and affordable treatment for infectious diseases.

RegulatorTrail: a web service for the identification of key transcriptional regulators.

Transcriptional regulators such as transcription factors and chromatin modifiers play a central role in most biological processes. Alterations in their activities have been observed in many diseases, e.g. cancer. Hence, it is of utmost importance to evaluate and assess the effects of transcriptional regulators on natural and pathogenic processes. Here, we present RegulatorTrail, a web service that provides rich functionality for the identification and prioritization of key transcriptional regulators that have a strong impact on, e.g. pathological processes. RegulatorTrail offers eight methods that use regulator binding information in combination with transcriptomic or epigenomic data to infer the most influential regulators. Our web service not only provides an intuitive web interface, but also a well-documented RESTful API that allows for a straightforward integration into third-party workflows. The presented case studies highlight the capabilities of our web service and demonstrate its potential for the identification of influential regulators: we successfully identified regulators that might explain the increased malignancy in metastatic melanoma compared to primary tumors, as well as important regulators in macrophages. RegulatorTrail is freely accessible at: https://regulatortrail.bioinf.uni-sb.de/.

miRPathDB: a new dictionary on microRNAs and target pathways.

In the last decade, miRNAs and their regulatory mechanisms have been intensively studied and many tools for the analysis of miRNAs and their targets have been developed. We previously presented a dictionary on single miRNAs and their putative target pathways. Since then, the number of miRNAs has tripled and the knowledge on miRNAs and targets has grown substantially. This, along with changes in pathway resources such as KEGG, leads to an improved understanding of miRNAs, their target genes and related pathways. Here, we introduce the miRNA Pathway Dictionary Database (miRPathDB), freely accessible at https://mpd.bioinf.uni-sb.de/ With the database we aim to complement available target pathway web-servers by providing researchers easy access to the information which pathways are regulated by a miRNA, which miRNAs target a pathway and how specific these regulations are. The database contains a large number of miRNAs (2595 human miRNAs), different miRNA target sets (14 773 experimentally validated target genes as well as 19 281 predicted targets genes) and a broad selection of functional biochemical categories (KEGG-, WikiPathways-, BioCarta-, SMPDB-, PID-, Reactome pathways, functional categories from gene ontology (GO), protein families from Pfam and chromosomal locations totaling 12 875 categories). In addition to Homo sapiens, also Mus musculus data are stored and can be compared to human target pathways.