Discovery of TYRA-300: First Oral Selective FGFR3 Inhibitor for the Treatment of Urothelial Cancers and Achondroplasia.

Activating FGFR3 alterations have been identified in up to 15-20% of muscle-invasive bladder cancer and metastatic urothelial carcinoma (mUC), and as high as 80% in nonmuscle invasive bladder cancers. FGFR3 germline mutations have also been associated with a variety of skeletal dysplasias. Achondroplasia, the most common form of dwarfism in humans, results from a G380R mutation in FGFR3.

WormBase 2024: status and transitioning to Alliance infrastructure.

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable.

Distinct profiles of oxylipid mediators in liver, lung, and placenta after maternal nano-TiO nanoparticle inhalation exposure.

Nano-titanium dioxide (nano-TiO) is a widely used nanomaterial found in several industrial and consumer products, including surface coatings, paints, sunscreens and cosmetics, among others. Studies have linked gestational exposure to nano-TiO with negative maternal and fetal health outcomes. For example, maternal pulmonary exposure to nano-TiO during gestation has been associated not only with maternal, but also fetal microvascular dysfunction in a rat model.

WormBase in 2022-data, processes, and tools for analyzing Caenorhabditis elegans.

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans.

Developing a UV climatology for public health purposes using satellite data.

The effects of solar ultraviolet (UV) radiation on life on Earth differ greatly. While overexposure to UV rays is harmful, small amounts of exposure are necessary for the synthesis of Vitamin D and good health. To optimize individual exposure to solar UV, it is therefore crucial to use UV data sources representative for entire populations and realistically accounting for various influencing factors.

Selection of Potent Inhibitors of Soluble Epoxide Hydrolase for Usage in Veterinary Medicine.

The veterinary pharmacopeia available to treat pain and inflammation is limited in number, target of action and efficacy. Inhibitors of soluble epoxide hydrolase (sEH) are a new class of anti-inflammatory, pro-resolving and analgesic drugs being tested in humans that have demonstrated efficacy in laboratory animals. They block the hydrolysis, and thus, increase endogenous concentrations of analgesic and anti-inflammatory signaling molecules called epoxy-fatty acids.

WormBase: a modern Model Organism Information Resource.

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture.

Epoxyeicosatrienoic acid (EET)-stimulated angiogenesis is mediated by epoxy hydroxyeicosatrienoic acids (EHETs) formed from COX-2.

Epoxyeicosatrienoic acids (EETs) are formed from the metabolism of arachidonic acid by cytochrome P450s. EETs promote angiogenesis linked to tumor growth in various cancer models that is attenuated in vivo by cyclooxygenase 2 (COX-2) inhibitors. This study further defines a role for COX-2 in mediating endothelial EET metabolism promoting angiogenesis.

Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride-Induced Model of Liver Injury.

The cyclooxygenase-2 (COX-2) selective inhibitor celecoxib is widely used in the treatment of pain and inflammation. Celecoxib has been explored as a possible treatment of liver fibrosis with contradictory results, depending on the model. The present study reports the effect of celecoxib in a 5-week carbon tetrachloride (CCl)-induced liver fibrosis mouse model.

Using WormBase: A Genome Biology Resource for Caenorhabditis elegans and Related Nematodes.

WormBase ( www.wormbase.org ) provides the nematode research community with a centralized database for information pertaining to nematode genes and genomes.

Micropublication: incentivizing community curation and placing unpublished data into the public domain.

Unlabelled: Large volumes of data generated by research laboratories coupled with the required effort and cost of curation present a significant barrier to inclusion of these data in authoritative community databases. Further, many publicly funded experimental observations remain invisible to curation simply because they are never published: results often do not fit within the scope of a standard publication; trainee-generated data are forgotten when the experimenter (e.g.

Orally Available Soluble Epoxide Hydrolase/Phosphodiesterase 4 Dual Inhibitor Treats Inflammatory Pain.

Inspired by previously discovered enhanced analgesic efficacy between soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4) inhibitors, we designed, synthesized and characterized 21 novel sEH/PDE4 dual inhibitors. The best of these displayed good efficacy in in vitro assays. Further pharmacokinetic studies of a subset of four selected compounds led to the identification of a bioavailable dual inhibitor N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA).

Effects of adamantane alterations on soluble epoxide hydrolase inhibition potency, physical properties and metabolic stability.

Adamantyl groups are widely used in medicinal chemistry. However, metabolism limits their usage. Herein, we report the first systematic study of adamantyl ureas and diureas bearing substituents in bridgehead positions of adamantane and/or spacers between urea groups and adamantane group, and tested their effects on soluble epoxide hydrolase inhibitor potency and metabolic stability.

Visual Sensor for Sterilization of Polymer Fixtures Using Embedded Mesoporous Silicon Photonic Crystals.

A porous photonic crystal is integrated with a plastic medical fixture (IV connector hub) to provide a visual colorimetric sensor to indicate the presence or absence of alcohol used to sterilize the fixture. The photonic crystal is prepared in porous silicon (pSi) by electrochemical anodization of single crystal silicon, and the porosity and the stop band of the material is engineered such that the integrated device visibly changes color (green to red or blue to green) when infiltrated with alcohol. Two types of self-reporting devices are prepared and their performance compared: the first type involves heat-assisted fusion of a freestanding pSi photonic crystal to the connector end of a preformed polycarbonate hub, forming a composite where the unfilled portion of the pSi film acts as the sensor; the second involves generation of an all-polymer replica of the pSi photonic crystal by complete thermal infiltration of the pSi film and subsequent chemical dissolution of the pSi portion.

WormBase 2017: molting into a new stage.

WormBase (http://www.wormbase.org) is an important knowledge resource for biomedical researchers worldwide.

Occurrence of urea-based soluble epoxide hydrolase inhibitors from the plants in the order Brassicales.

Recently, dibenzylurea-based potent soluble epoxide hydrolase (sEH) inhibitors were identified in Pentadiplandra brazzeana, a plant in the order Brassicales. In an effort to generalize the concept, we hypothesized that plants that produce benzyl glucosinolates and corresponding isothiocyanates also produce these dibenzylurea derivatives. Our overall aim here was to examine the occurrence of urea derivatives in Brassicales, hoping to find biologically active urea derivatives from plants.

Engaging Adolescents Through Participatory and Qualitative Research Methods to Develop a Digital Communication Intervention to Reduce Adolescent Obesity.

Background: The complexity of the childhood obesity epidemic requires the application of community-based participatory research (CBPR) in a manner that can transcend multiple communities of stakeholders, including youth, the broader community, and the community of health care providers.

Aim: To (a) describe participatory processes for engaging youth within context of CBPR and broader community, (b) share youth-engaged research findings related to the use of digital communication and implications for adolescent obesity intervention research, and (c) describe and discuss lessons learned from participatory approaches.

Method: CBPR principles and qualitative methods were synergistically applied in a predominantly African American part of the city that experiences major obesity-related issues.

An ω-3-enriched diet alone does not attenuate CCl-induced hepatic fibrosis.

Exposure to the halogenated hydrocarbon carbon tetrachloride (CCl) leads to hepatic lipid peroxidation, inflammation and fibrosis. Dietary supplementation of ω-3 fatty acids has been increasingly advocated as being generally anti-inflammatory, though its effect in models of liver fibrosis is mixed. This raises the question of whether diets high in ω-3 fatty acids will result in a greater sensitivity or resistance to liver fibrosis as a result of environmental toxicants like CCl.

WormBase 2016: expanding to enable helminth genomic research.

WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes.

1,3-Disubstituted and 1,3,3-trisubstituted adamantyl-ureas with isoxazole as soluble epoxide hydrolase inhibitors.

Adamantyl ureas are good soluble epoxide hydrolase (sEH) inhibitors; however they have limited solubility and rapid metabolism, thus limiting their usefulness in some therapeutic indications. Herein, we test the hypothesis that nodal substitution on the adamantane will help solubilize and stabilize the compounds. A series of compounds containing adamantane derivatives and isoxazole functional groups were developed.

Cross-organism analysis using InterMine.

InterMine is a data integration warehouse and analysis software system developed for large and complex biological data sets. Designed for integrative analysis, it can be accessed through a user-friendly web interface. For bioinformaticians, extensive web services as well as programming interfaces for most common scripting languages support access to all features.

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide.

Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice.

Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl4)-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress.

Identification of potent inhibitors of the chicken soluble epoxide hydrolase.

In vertebrates, soluble epoxide hydrolase (sEH) hydrolyzes natural epoxy-fatty acids (EpFAs), which are chemical mediators modulating inflammation, pain, and angiogenesis. Chick embryos are used to study angiogenesis, particularly its role in cardiovascular biology and pathology. To find potent and bio-stable inhibitors of the chicken sEH (chxEH) a library of human sEH inhibitors was screened.

Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model.

Background: Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart.